<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02190604</url>
  </required_header>
  <id_info>
    <org_study_id>CQBW251X2101</org_study_id>
    <secondary_id>2011-005085-37</secondary_id>
    <nct_id>NCT02190604</nct_id>
  </id_info>
  <brief_title>Safety, Tolerability, Pharmacokinetics, and Preliminary Pharmacodynamics of QBW251 in Healthy Subjects and Cystic Fibrosis Patients</brief_title>
  <official_title>A Randomized, Double Blind Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Pharmacodynamics of Single and Multiple Ascending Doses of QBW251 in Healthy Subjects and Multiple Doses in Cystic Fibrosis Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is designed to assess the safety, tolerability, pharmacokinetics and preliminary&#xD;
      pharmacodynamics (proof of concept) of QBW251 in healthy subjects and cystic fibrosis&#xD;
      patients following single and multiple doses. This first-in-human and proof of concept study&#xD;
      will consist of 4 parts, with Parts 1 and 2 in healthy volunteers and Parts 3 and 4 in cystic&#xD;
      fibrosis patients.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <start_date type="Actual">July 31, 2012</start_date>
  <completion_date type="Actual">November 30, 2015</completion_date>
  <primary_completion_date type="Actual">November 30, 2015</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Part 1 and 2:Number of Participants (Healthy Volunteers) With Reported Adverse Events Receiving QBW251</measure>
    <time_frame>Day 1 to Day 36</time_frame>
    <description>All adverse events (in healthy volunteers) reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 3: Change in Lung Clearance Index (LCI) From Baseline to Day 15</measure>
    <time_frame>Baseline and Day 15</time_frame>
    <description>Change in Lung Clearance Index (LCI) will be conducted according to international standards in cystic fibrosis patients. Lung clearance index (LCI) is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test, A reduction in mean change from baseline for LCI2.5 indicates improvement.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 3: Number of Participants (Patients) With Reported Adverse Events Receiving QBW251</measure>
    <time_frame>Day 1 to Day 56</time_frame>
    <description>All adverse events and serious adverse events (in patients) reported.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Part 3:Change in Forced Expiratory Volume in 1 Second (FEV1) at Day 15</measure>
    <time_frame>Baseline and Day 15</time_frame>
    <description>Forced Expiratory Volume in 1 second (FEV1) will be measured via spirometer according to international standards. Forced Expiratory Volume in 1 second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 3: Change in Cystic Fibrosis Questionnaire-Revised Reported Outcomes</measure>
    <time_frame>Baseline and Day 14</time_frame>
    <description>Change in Cystic Fibrosis Questionnaire data will be obtained from patient reported outcomes (CFQ-R PRO). Respiratory Domain, cores range from 0 to 100, with higher scores indicating better health, a change of 4 is considered clinically relevant</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1: AUC0-t in Healthy Volunteers</measure>
    <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 2-5)</time_frame>
    <description>Pharmacokinetics of QBW251 in plasma: area under the plasma concentration versus time curve from time zero to time of last measurable concentration (AUC0-t). In part one of the study a single dose was administered and samples were collected up to 5 days. As a result the AUC0-t goes from Day 1 to Day 5 (for some lower doses QBW251 concentrations were not measured up to Day 5 as the concentrations were low due to the low dose administered)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1: Maximum Concentration (Cmax) in Healthy Volunteers</measure>
    <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 1 - 5)</time_frame>
    <description>Pharmacokinetics of QBW251 in plasma: observed maximum plasma concentration following administration of QBW251. In this analysis Cmax will be reported using blood samples taken on Days 1- 5 are from healthy volunteers</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1: Time to Maximum Concentration (Tmax) in Healthy Volunteers</measure>
    <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 1 - 5)</time_frame>
    <description>Pharmacokinetics of QBW251 in plasma: time to reach the maximum concentration after administration of QBW251. In this analysis Tmax will be reported using blood samples taken on Days 1 - 5 from healthy volunteers. In this part of the study a single dose was administered and samples were collected up to 5 days. As a result the Tmax is one value as the concentration-time curve goes to Day 5 (for some lower does QBW251 concentrations were not measured up to Day 5 as the concentrations were low due to the low dose administered).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1: T1/2 in Healthy Volunteers</measure>
    <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 1 - 5)</time_frame>
    <description>Pharmacokinetics of QBW251 in plasma: terminal elimination half-life. In this analysis T1/2 will be reported using blood samples taken on Days 1 - 5 from healthy volunteers. In part one of the study a single dose was administered and samples were collected up to 5 days. As a result the T1/2 goes from Day 1 to Day 5 (for some lower doses QBW251 concentrations were not measured up to Day 5 as the concentrations were low due to the low dose administered).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1: AUCinf in Healthy Volunteers</measure>
    <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 1 - 5)</time_frame>
    <description>Pharmacokinetics of QBW251 in plasma: area under the plasma concentration time curve from time zero to infinity. In this analysis AUCinf will be reported using blood samples taken on Days 1 - 5 from healthy volunteers. In part one of the study a single dose was administered and samples were collected up to 5 days. As a result the AUCinf goes from Day 1 to Day 5 (for some lower doses QBW251 concentrations were not measured up to Day 5 as the concentrations were low due to the low dose administered)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1: CL/F in Healthy Volunteers</measure>
    <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 1 - 5)</time_frame>
    <description>Pharmacokinetics of QBW251 in plasma: apparent systemic clearance from plasma following extravascular administration. In this analysis CL/F will be reported using blood samples taken on Days 1 - 5 from healthy volunteers. In part one of the study a single dose was administered and samples were collected up to 5 days. As a result the CL/F goes from Day 1 to Day 5 (for some lower doses QBW251 concentrations were not measured up to Day 5 as the concentrations were low due to the low dose administered)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1: Vz/F in Healthy Volunteers</measure>
    <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 1 - 5)</time_frame>
    <description>Pharmacokinetics of QBW251 in plasma: apparent volume of distribution during the terminal elimination phase following extravascular administration. In this analysis Vz/F will be reported using blood samples taken on Days 1 - 5 from healthy volunteers.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: AUCtau in Healthy Volunteers</measure>
    <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1 and 14; ( If B ID dosing, 12 hours samples will be pre-dosed)</time_frame>
    <description>Pharmacokinetics of QBW251 in plasma after multiple doses: the area under the plasma concentration-time curve from time zero to end of the dosing interval tau. In this analysis AUCtau will be reported. Samples taken on Days 1 and 14 from healthy volunteers</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: Maximum Concentration (Cmax) in Healthy Volunteers</measure>
    <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1 and 14; ( If B ID dosing, 12 hours samples will be pre-dosed)</time_frame>
    <description>Pharmacokinetics of QBW251 in plasma after multiple doses: observed maximum plasma concentration following QBW251 at steady state. In this analysis Cmax will be reported using blood samples taken on Days 1 and 14 from healthy volunteers.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: Time to Maximum Concentration (Tmax) in Healthy Volunteers</measure>
    <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1 and 14; ( If B ID dosing, 12 hours samples will be pre-dosed)</time_frame>
    <description>Pharmacokinetics of QBW251 in plasma after multiple doses: time to reach the maximum concentration after administration of QBW251. In this analysis Tmax will be reported using blood samples taken on Days 1 and 14 from healthy volunteers.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: AUC0-t</measure>
    <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 14; ( If B ID dosing, 12 hours samples will be pre-dosed)</time_frame>
    <description>Pharmacokinetics of QBW251 in plasma: area under the plasma concentration versus time curve from time zero to time of last measurable concentration. In this analysis AUC0-t will be reported using blood samples taken on Day 14 are from healthy volunteers.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: Cav in Healthy Volunteers</measure>
    <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1 and 14; ( If B ID dosing, 12 hours samples will be pre-dosed)</time_frame>
    <description>The average drug concentration in plasma during multiple dosing. In this analysis Cav will be reported using blood samples taken on Days 1 and 14 are from healthy volunteers.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: CL/F in Healthy Volunteers</measure>
    <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 14; ( If B ID dosing, 12 hours samples will be pre-dosed)</time_frame>
    <description>apparent systemic clearance from plasma following extravascular administration. In this analysis CL/F will be reported using blood samples taken on Day 14 from healthy volunteers.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: Vz/F in Healthy Volunteers</measure>
    <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 14; ( If B ID dosing, 12 hours samples will be pre-dosed)</time_frame>
    <description>Apparent volume of distribution during the terminal elimination phase following extravascular administration. In this analysis Vz/F will be reported using blood samples taken on Day 14 from healthy volunteers.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: Racc in Healthy Volunteers</measure>
    <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1 - 14; ( If B ID dosing, 12 hours samples will be pre-dosed)</time_frame>
    <description>Accumulation ratio (Racc). In this analysis Racc will be reported using blood samples taken on Days 1 - 14 from healthy volunteers.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: T1/2 in Healthy Volunteers</measure>
    <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 14; ( If B ID dosing, 12 hours samples will be pre-dosed)</time_frame>
    <description>terminal elimination half-life (T1/2). In this analysis T1/2 will be reported using blood samples taken on Day 14 from healthy volunteers.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 3: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of QBW251 in CF Patients</measure>
    <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day 14</time_frame>
    <description>Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 3: Plasma Concentration at the Last Quantifiable Time Point (Clast) of QBW251 in CF Patients</measure>
    <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day2</time_frame>
    <description>Blood samples were collected at timepoints prespecified in the study protocol. Tlast of QBW251 was the last time point when blood sample collected was quantifiable</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 3: Maximum Concentration (Cmax) in CF Patients</measure>
    <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day 14</time_frame>
    <description>Observed maximum plasma concentration following administration of QBW251. In this analysis Cmax will be reported using blood samples taken on Day 1and day 14 from patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 3: Tlast in CF Patients</measure>
    <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day 14</time_frame>
    <description>Blood samples were collected at timepoints prespecified in the study protocol. Tlast of QBW251 was the last time point when blood sample collected was quantifiable day 1 and day 14</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 3: Time to Maximum Concentration (Tmax)</measure>
    <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day 14</time_frame>
    <description>Pharmacokinetics of QBW251 in plasma after multiple doses: time to reach the maximum concentration after administration of QBW251. In this analysis Tmax will be reported using blood samples taken on Days 1 and 14 in patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: Ae0-t in Healthy Volunteers</measure>
    <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1</time_frame>
    <description>Pharmacokinetics of QBW251 in urine: amount of drug excreted in urine from time zero until last measurable concentration. In this analysis Ae0-t will be reported using urine samples taken on Day 1 from healthy volunteers.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: CLr in Healthy Volunteers</measure>
    <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1; Day 14 was calculated as urine was only collected up to 12 hours on Day 1 thus CLr cannot be calculated.</time_frame>
    <description>Pharmacokinetics of QBW251 in urine: renal clearance following drug administration. In this analysis CLr will be reported using urine samples taken on Day 1 from healthy volunteers.</description>
  </secondary_outcome>
  <number_of_arms>20</number_of_arms>
  <enrollment type="Actual">153</enrollment>
  <condition>Cystic Fibrosis</condition>
  <arm_group>
    <arm_group_label>Part 1 Cohort 1: QBW251</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of QBW251 10 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1 Cohort 2: QBW251</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of QBW251 25 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1 Cohort 3: QBW251</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of QBW251 75 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1 Cohort 4: QBW251</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of QBW251 150 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1 Cohort 5: QBW251</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of QBW251 300 mg in healthy volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1 Cohort 6: QBW251</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of QBW251 500 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1 Cohort 6: QBW251(fed)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of QBW251 500 mg (fed). single dose with food for a preliminary assessment of the effect of food on the absorption of QBW251 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1 Cohort 7: QBW251</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of QBW251 750 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1 Cohort 8: QBW251</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of QBW251 1000 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1 Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo to QBW251 in all cohorts of part 1 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2 Cohort 1: QBW251</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2 Cohort 2: QBW251</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2 Cohort 3: QBW251</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2 Cohort 4: QBW251</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2 Cohort 5: QBW251</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2 Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo to QBW251 in all cohorts of part 2 in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 3 Cohort 1: QBW251</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>150 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 3 Cohort 2: QBW251</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>450 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 3 Cohort 3: QBW251</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>450 mg b.i.d. Multiple doses. Patients who are homozygous for the F508del mutation in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 3 Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo to QBW251 in all cohorts of part 3 in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Capsule- oral dose</description>
    <arm_group_label>Part 1 Placebo</arm_group_label>
    <arm_group_label>Part 2 Placebo</arm_group_label>
    <arm_group_label>Part 3 Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>QBW251</intervention_name>
    <description>Capsule - oral dose</description>
    <arm_group_label>Part 1 Cohort 1: QBW251</arm_group_label>
    <arm_group_label>Part 1 Cohort 2: QBW251</arm_group_label>
    <arm_group_label>Part 1 Cohort 3: QBW251</arm_group_label>
    <arm_group_label>Part 1 Cohort 4: QBW251</arm_group_label>
    <arm_group_label>Part 1 Cohort 5: QBW251</arm_group_label>
    <arm_group_label>Part 1 Cohort 6: QBW251</arm_group_label>
    <arm_group_label>Part 1 Cohort 6: QBW251(fed)</arm_group_label>
    <arm_group_label>Part 1 Cohort 7: QBW251</arm_group_label>
    <arm_group_label>Part 1 Cohort 8: QBW251</arm_group_label>
    <arm_group_label>Part 2 Cohort 1: QBW251</arm_group_label>
    <arm_group_label>Part 2 Cohort 2: QBW251</arm_group_label>
    <arm_group_label>Part 2 Cohort 3: QBW251</arm_group_label>
    <arm_group_label>Part 2 Cohort 4: QBW251</arm_group_label>
    <arm_group_label>Part 2 Cohort 5: QBW251</arm_group_label>
    <arm_group_label>Part 3 Cohort 1: QBW251</arm_group_label>
    <arm_group_label>Part 3 Cohort 2: QBW251</arm_group_label>
    <arm_group_label>Part 3 Cohort 3: QBW251</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key inclusion criteria (Parts 1 and 2)&#xD;
&#xD;
          -  Healthy female (of non-childbearing potential) and male subjects of 18 to 55 years of&#xD;
             age (inclusive)&#xD;
&#xD;
          -  Body mass index (BMI) must be within the range of 15 to 30 kg/m2&#xD;
&#xD;
          -  Oxygen saturation (O2) at screening must be ≥ 96% on room air.&#xD;
&#xD;
        Key exclusion criteria (Parts 1 and 2)&#xD;
&#xD;
          -  Use of any prescription drugs or herbal supplements within four (4) weeks prior to&#xD;
             dosing or within 5 half-lives of the drug, whichever is longer&#xD;
&#xD;
          -  Over-the-counter (OTC) medication (including vitamins, dietary supplements) within two&#xD;
             (2) weeks prior to dosing&#xD;
&#xD;
          -  Use of other investigational drugs at the time of enrollment, or within 30 days or 5&#xD;
             half-lives of enrollment, whichever is longer&#xD;
&#xD;
          -  Unwilling to avoid direct sun exposure by covering exposed skin, using topical sun&#xD;
             block and wearing sunglasses from the first dose of study drug to the end of&#xD;
             participation in the study&#xD;
&#xD;
          -  Pregnant or nursing (lactating) women.&#xD;
&#xD;
        Key inclusion criteria (Parts 3 and 4):&#xD;
&#xD;
          -  Male and female patients of 18 to 65 years of age (inclusive) with a confirmed&#xD;
             diagnosis of cystic fibrosis as per the Cystic Fibrosis Foundation (CFF) consensus&#xD;
             guidelines&#xD;
&#xD;
          -  Heterozygous with one allele represented as any CFTR mutation and the other allele&#xD;
             must represent a class III, IV, V, VI CFTR mutation (Note: since the CFTR mutation,&#xD;
             F508del, can be considered either a class II or III mutation, heterozygous CF patients&#xD;
             that have one allele that contains F508del, must have the other allele contain a class&#xD;
             III (i.e., not F508del), IV, V, or VI mutation). Patients with F508del/F508del&#xD;
             mutation should only be included in Part 3 Cohort 3.&#xD;
&#xD;
          -  Body mass index (BMI) must be within the range of 15-35 kg/m2&#xD;
&#xD;
          -  FEV1 at Screening must be 40 to 100% predicted (inclusive) by NHANES/Hankinson&#xD;
             standards&#xD;
&#xD;
          -  Oxygen saturation (O2) at screening must be &gt; 90% on room air.&#xD;
&#xD;
        Key exclusion criteria (Parts 3 and 4)&#xD;
&#xD;
          -  Use of herbal supplements within four (4) weeks prior to dosing or within 5 half-lives&#xD;
             of the supplement, whichever is longer&#xD;
&#xD;
          -  Use of other investigational drugs at the time of enrollment, or within 30 days or 5&#xD;
             half-lives of enrollment, whichever is longer&#xD;
&#xD;
          -  Unwilling to avoid direct sun exposure by covering exposed skin, using topical sun&#xD;
             block and wearing sunglasses from the first dose of study drug to the end of&#xD;
             participation in the study&#xD;
&#xD;
          -  Pregnant or nursing (lactating) women&#xD;
&#xD;
          -  Women of child-bearing potential, UNLESS they are using highly effective contraception&#xD;
&#xD;
          -  Any changes in concomitant medications for 14 days prior to screening&#xD;
&#xD;
          -  History or clinical evidence of pancreatic injury or pancreatitis; clinical evidence&#xD;
             of liver disease or liver injury as indicated by clinically significant abnormal liver&#xD;
             function tests as judged by the investigator such as SGOT, SGPT, GGT, alkaline&#xD;
             phosphatase, or serum bilirubin&#xD;
&#xD;
          -  History or presence of impaired renal function as indicated by abnormal creatinine or&#xD;
             BUN values or abnormal urinary constituents (e.g., albuminuria)&#xD;
&#xD;
          -  History of Burkholderia cepacia respiratory tract infection (must have at least two&#xD;
             negative cultures and no positive cultures in the past 18 months prior to screening to&#xD;
             be eligible for enrollment)&#xD;
&#xD;
          -  Sexually active males unless they use a condom during intercourse while taking drug&#xD;
             and for condom is required to be used also by vasectomized men in order to prevent&#xD;
             delivery of drug via seminal fluid.&#xD;
&#xD;
          -  Patient is currently receiving (or has received within 4 weeks of baseline visit)&#xD;
             VX-770/Ivacaftor.&#xD;
&#xD;
          -  History of lung transplant&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Novartis Pharmaceuticals</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294-0006</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27514</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Brussel</city>
        <zip>1090</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Gent</city>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Montpellier</city>
        <zip>34059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Paris</city>
        <zip>75014</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>PIERRE BENITE Cedex</city>
        <zip>69495</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Koeln</city>
        <state>Nordrhein-Westfalen</state>
        <zip>50937</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Berlin</city>
        <zip>10098</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Dublin 4</city>
        <zip>4</zip>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bucuresti</city>
        <zip>050159</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Livingston</city>
        <state>West Lothian</state>
        <zip>EH54 6PP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Belfast</city>
        <zip>BT9 7AB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>London</city>
        <zip>SW 6NP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Manchester</city>
        <zip>M23 9QZ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Mid Glamorgan</city>
        <zip>CF484DR</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>France</country>
    <country>Germany</country>
    <country>Ireland</country>
    <country>Romania</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Netherlands</country>
  </removed_countries>
  <link>
    <url>https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=127</url>
    <description>A Plain Language Trial Summary is available on novartisclinicaltrials.com</description>
  </link>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>July 11, 2014</study_first_submitted>
  <study_first_submitted_qc>July 14, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 15, 2014</study_first_posted>
  <results_first_submitted>November 23, 2016</results_first_submitted>
  <results_first_submitted_qc>July 18, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">July 19, 2017</results_first_posted>
  <last_update_submitted>December 9, 2020</last_update_submitted>
  <last_update_submitted_qc>December 9, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 30, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>FEV1- Forced Expiratory volume</keyword>
  <keyword>LCI - Lung Clearance Index</keyword>
  <keyword>CFTR - cystic fibrosis transmembrane conductance regulator</keyword>
  <keyword>cystic fibrosis</keyword>
  <keyword>allergic bronchopulmonary aspergillosis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cystic Fibrosis</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>For Cohort 6 continuing into the food effect part of the study the subjects remained on the same treatment assignment that was required during the fed state. Therefore no randomization f the subject occurred during the food effect arm. Only 5 of the 6 subjects went into the fed cohort.</recruitment_details>
      <pre_assignment_details>In parts 1 and 2, participants (Healthy Volunteers) were randomized 3:1 to receive QBW251X or placebo. In part 3, participants (cystic fibrosis (CF) patients) were randomized 3:1 to receive QBW251X or placebo.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Part 1 Cohort 1: QBW251</title>
          <description>Single dose of QBW251 10 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
        </group>
        <group group_id="P2">
          <title>Part 1 Cohort 2: QBW251</title>
          <description>Single dose of QBW251 25 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
        </group>
        <group group_id="P3">
          <title>Part 1 Cohort 3: QBW251</title>
          <description>Single dose of QBW251 75 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
        </group>
        <group group_id="P4">
          <title>Part 1 Cohort 4: QBW251</title>
          <description>Single dose of QBW251 150 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
        </group>
        <group group_id="P5">
          <title>Part 1 Cohort 5: QBW251</title>
          <description>Single dose of QBW251 300 mg in healthy volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
        </group>
        <group group_id="P6">
          <title>Part 1 Cohort 6: QBW251 (Fasting/Fed), Same Subjects</title>
          <description>Single dose of QBW251 500 mg (fed). single dose with food for a preliminary assessment of the effect of food on the absorption of QBW251 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
        </group>
        <group group_id="P7">
          <title>Part 1 Cohort 7: QBW251</title>
          <description>Single dose of QBW251 750 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
        </group>
        <group group_id="P8">
          <title>Part 1 Cohort 8: QBW251</title>
          <description>Single dose of QBW251 1000 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
        </group>
        <group group_id="P9">
          <title>Part 1 Placebo</title>
          <description>Placebo to QBW251 in all cohorts of part 1 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
        </group>
        <group group_id="P10">
          <title>Part 2 Cohort 1: QBW251</title>
          <description>Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
        </group>
        <group group_id="P11">
          <title>Part 2 Cohort 2: QBW251</title>
          <description>Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
        </group>
        <group group_id="P12">
          <title>Part 2 Cohort 3: QBW251</title>
          <description>Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
        </group>
        <group group_id="P13">
          <title>Part 2 Cohort 4: QBW251</title>
          <description>Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
        </group>
        <group group_id="P14">
          <title>Part 2 Cohort 5: QBW251</title>
          <description>Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
        </group>
        <group group_id="P15">
          <title>Part 2 Placebo</title>
          <description>Placebo to QBW251 in all cohorts of part 2 in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
        </group>
        <group group_id="P16">
          <title>Part 3 Cohort 1: QBW251</title>
          <description>150 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
        </group>
        <group group_id="P17">
          <title>Part 3 Cohort 2: QBW251</title>
          <description>450 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
        </group>
        <group group_id="P18">
          <title>Part 3 Cohort 3: QBW251</title>
          <description>450 mg b.i.d. Multiple doses. Patients who are homozygous for the F508del mutation in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
        </group>
        <group group_id="P19">
          <title>Part 3 Placebo</title>
          <description>Placebo to QBW251 in all cohorts of part 3 in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Part 1 and 2 (Healthy Volunteers)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="6"/>
                <participants group_id="P5" count="6"/>
                <participants group_id="P6" count="6"/>
                <participants group_id="P7" count="6"/>
                <participants group_id="P8" count="6"/>
                <participants group_id="P9" count="16"/>
                <participants group_id="P10" count="6"/>
                <participants group_id="P11" count="6"/>
                <participants group_id="P12" count="6"/>
                <participants group_id="P13" count="6"/>
                <participants group_id="P14" count="6"/>
                <participants group_id="P15" count="10"/>
                <participants group_id="P16" count="0"/>
                <participants group_id="P17" count="0"/>
                <participants group_id="P18" count="0"/>
                <participants group_id="P19" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="6"/>
                <participants group_id="P5" count="6"/>
                <participants group_id="P6" count="6"/>
                <participants group_id="P7" count="6"/>
                <participants group_id="P8" count="6"/>
                <participants group_id="P9" count="16"/>
                <participants group_id="P10" count="6"/>
                <participants group_id="P11" count="6"/>
                <participants group_id="P12" count="6"/>
                <participants group_id="P13" count="6"/>
                <participants group_id="P14" count="5"/>
                <participants group_id="P15" count="8"/>
                <participants group_id="P16" count="0"/>
                <participants group_id="P17" count="0"/>
                <participants group_id="P18" count="0"/>
                <participants group_id="P19" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
                <participants group_id="P12" count="0"/>
                <participants group_id="P13" count="0"/>
                <participants group_id="P14" count="1"/>
                <participants group_id="P15" count="2"/>
                <participants group_id="P16" count="0"/>
                <participants group_id="P17" count="0"/>
                <participants group_id="P18" count="0"/>
                <participants group_id="P19" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
                <participants group_id="P12" count="0"/>
                <participants group_id="P13" count="0"/>
                <participants group_id="P14" count="0"/>
                <participants group_id="P15" count="2"/>
                <participants group_id="P16" count="0"/>
                <participants group_id="P17" count="0"/>
                <participants group_id="P18" count="0"/>
                <participants group_id="P19" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
                <participants group_id="P12" count="0"/>
                <participants group_id="P13" count="0"/>
                <participants group_id="P14" count="1"/>
                <participants group_id="P15" count="0"/>
                <participants group_id="P16" count="0"/>
                <participants group_id="P17" count="0"/>
                <participants group_id="P18" count="0"/>
                <participants group_id="P19" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Part 3 (Patients)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
                <participants group_id="P12" count="0"/>
                <participants group_id="P13" count="0"/>
                <participants group_id="P14" count="0"/>
                <participants group_id="P15" count="0"/>
                <participants group_id="P16" count="6"/>
                <participants group_id="P17" count="12"/>
                <participants group_id="P18" count="19"/>
                <participants group_id="P19" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
                <participants group_id="P12" count="0"/>
                <participants group_id="P13" count="0"/>
                <participants group_id="P14" count="0"/>
                <participants group_id="P15" count="0"/>
                <participants group_id="P16" count="6"/>
                <participants group_id="P17" count="12"/>
                <participants group_id="P18" count="19"/>
                <participants group_id="P19" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
                <participants group_id="P12" count="0"/>
                <participants group_id="P13" count="0"/>
                <participants group_id="P14" count="0"/>
                <participants group_id="P15" count="0"/>
                <participants group_id="P16" count="0"/>
                <participants group_id="P17" count="0"/>
                <participants group_id="P18" count="0"/>
                <participants group_id="P19" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Part 1 Cohort 1: QBW251</title>
          <description>Single dose of QBW251 10 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
        </group>
        <group group_id="B2">
          <title>Part 1 Cohort 2: QBW251</title>
          <description>Single dose of QBW251 25 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
        </group>
        <group group_id="B3">
          <title>Part 1 Cohort 3: QBW251</title>
          <description>Single dose of QBW251 75 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
        </group>
        <group group_id="B4">
          <title>Part 1 Cohort 4: QBW251</title>
          <description>Single dose of QBW251 150 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
        </group>
        <group group_id="B5">
          <title>Part 1 Cohort 6: QBW251</title>
          <description>Single dose of QBW251 500 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
        </group>
        <group group_id="B6">
          <title>Part 1 Cohort 6: QBW251 (Fastin / Fed), Same Subjects</title>
          <description>Single dose of QBW251 500 mg (fed). single dose with food for a preliminary assessment of the effect of food on the absorption of QBW251 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
        </group>
        <group group_id="B7">
          <title>Part 1 Cohort 7: QBW251</title>
          <description>Single dose of QBW251 750 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
        </group>
        <group group_id="B8">
          <title>Part 1 Cohort 8: QBW251</title>
          <description>Single dose of QBW251 1000 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
        </group>
        <group group_id="B9">
          <title>Part 1 Placebo</title>
          <description>Placebo to QBW251 in all cohorts of part 1 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
        </group>
        <group group_id="B10">
          <title>Part 2 Cohort 1: QBW251</title>
          <description>Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
        </group>
        <group group_id="B11">
          <title>Part 2 Cohort 2: QBW251</title>
          <description>Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
        </group>
        <group group_id="B12">
          <title>Part 2 Cohort 3: QBW251</title>
          <description>Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
        </group>
        <group group_id="B13">
          <title>Part 2 Cohort 4: QBW251</title>
          <description>Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
        </group>
        <group group_id="B14">
          <title>Part 2 Cohort 5: QBW251</title>
          <description>Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
        </group>
        <group group_id="B15">
          <title>Part 2 Placebo</title>
          <description>Placebo to QBW251 in all cohorts of part 2 in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
        </group>
        <group group_id="B16">
          <title>Part 3 Cohort 1: QBW251</title>
          <description>150 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
        </group>
        <group group_id="B17">
          <title>Part 3 Cohort 2: QBW251</title>
          <description>450 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
        </group>
        <group group_id="B18">
          <title>Part 3 Cohort 3: QBW251</title>
          <description>450 mg b.i.d. Multiple doses. Patients who are homozygous for the F508del mutation in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
        </group>
        <group group_id="B19">
          <title>Part 3 Placebo</title>
          <description>Placebo to QBW251 in all cohorts of part 3 in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
        </group>
        <group group_id="B20">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="6"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="6"/>
            <count group_id="B4" value="6"/>
            <count group_id="B5" value="6"/>
            <count group_id="B6" value="6"/>
            <count group_id="B7" value="6"/>
            <count group_id="B8" value="6"/>
            <count group_id="B9" value="16"/>
            <count group_id="B10" value="6"/>
            <count group_id="B11" value="6"/>
            <count group_id="B12" value="6"/>
            <count group_id="B13" value="6"/>
            <count group_id="B14" value="6"/>
            <count group_id="B15" value="10"/>
            <count group_id="B16" value="6"/>
            <count group_id="B17" value="12"/>
            <count group_id="B18" value="19"/>
            <count group_id="B19" value="12"/>
            <count group_id="B20" value="153"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <title>Part 1, HV (n= 64)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="36.3" spread="8.69"/>
                    <measurement group_id="B2" value="35" spread="14.25"/>
                    <measurement group_id="B3" value="43.5" spread="3.39"/>
                    <measurement group_id="B4" value="33.3" spread="9.61"/>
                    <measurement group_id="B5" value="44.2" spread="8.23"/>
                    <measurement group_id="B6" value="43.6" spread="9.07"/>
                    <measurement group_id="B7" value="28.2" spread="9.28"/>
                    <measurement group_id="B8" value="33.2" spread="9.47"/>
                    <measurement group_id="B9" value="30.3" spread="9.18"/>
                    <measurement group_id="B10" value="NA" spread="NA">This row is for Part 1 HV</measurement>
                    <measurement group_id="B11" value="NA" spread="NA">This row is for Part 1 HV</measurement>
                    <measurement group_id="B12" value="NA" spread="NA">This row is for Part 1 HV</measurement>
                    <measurement group_id="B13" value="NA" spread="NA">This row is for Part 1 HV</measurement>
                    <measurement group_id="B14" value="NA" spread="NA">This row is for Part 1 HV</measurement>
                    <measurement group_id="B15" value="NA" spread="NA">This row is for Part 1 HV</measurement>
                    <measurement group_id="B16" value="NA" spread="NA">This row is for Part 1 HV</measurement>
                    <measurement group_id="B17" value="NA" spread="NA">This row is for Part 1 HV</measurement>
                    <measurement group_id="B18" value="NA" spread="NA">This row is for Part 1 HV</measurement>
                    <measurement group_id="B19" value="NA" spread="NA">This row is for Part 1 HV</measurement>
                    <measurement group_id="B20" value="34.4" spread="9.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part 2, HV (n=40)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="NA" spread="NA">This row is for Part 2 HV</measurement>
                    <measurement group_id="B2" value="NA" spread="NA">This row is for Part 2 HV</measurement>
                    <measurement group_id="B3" value="NA" spread="NA">This row is for Part 2 HV</measurement>
                    <measurement group_id="B4" value="NA" spread="NA">This row is for Part 2 HV</measurement>
                    <measurement group_id="B5" value="NA" spread="NA">This row is for Part 2 HV</measurement>
                    <measurement group_id="B6" value="NA" spread="NA">This row is for Part 2 HV</measurement>
                    <measurement group_id="B7" value="NA" spread="NA">This row is for Part 2 HV</measurement>
                    <measurement group_id="B8" value="NA" spread="NA">This row is for Part 2 HV</measurement>
                    <measurement group_id="B9" value="NA" spread="NA">This row is for Part 2 HV</measurement>
                    <measurement group_id="B10" value="30.3" spread="5.13"/>
                    <measurement group_id="B11" value="30.5" spread="5.89"/>
                    <measurement group_id="B12" value="29.2" spread="11.62"/>
                    <measurement group_id="B13" value="31.7" spread="13.22"/>
                    <measurement group_id="B14" value="27.8" spread="5"/>
                    <measurement group_id="B15" value="29" spread="6.22"/>
                    <measurement group_id="B16" value="NA" spread="NA">This row is for Part 2 HV</measurement>
                    <measurement group_id="B17" value="NA" spread="NA">This row is for Part 2 HV</measurement>
                    <measurement group_id="B18" value="NA" spread="NA">This row is for Part 2 HV</measurement>
                    <measurement group_id="B19" value="NA" spread="NA">This row is for Part 2 HV</measurement>
                    <measurement group_id="B20" value="29.7" spread="7.82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part 3, CF patients (n=49)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="NA" spread="NA">This row is for Part 3 HV</measurement>
                    <measurement group_id="B2" value="NA" spread="NA">This row is for Part 3 HV</measurement>
                    <measurement group_id="B3" value="NA" spread="NA">This row is for Part 3 HV</measurement>
                    <measurement group_id="B4" value="NA" spread="NA">This row is for Part 3 HV</measurement>
                    <measurement group_id="B5" value="NA" spread="NA">This row is for Part 3 HV</measurement>
                    <measurement group_id="B6" value="NA" spread="NA">This row is for Part 3 HV</measurement>
                    <measurement group_id="B7" value="NA" spread="NA">This row is for Part 3 HV</measurement>
                    <measurement group_id="B8" value="NA" spread="NA">This row is for Part 3 HV</measurement>
                    <measurement group_id="B9" value="NA" spread="NA">This row is for Part 3 HV</measurement>
                    <measurement group_id="B10" value="NA" spread="NA">This row is for Part 3 HV</measurement>
                    <measurement group_id="B11" value="NA" spread="NA">This row is for Part 3 HV</measurement>
                    <measurement group_id="B12" value="NA" spread="NA">This row is for Part 3 HV</measurement>
                    <measurement group_id="B13" value="NA" spread="NA">This row is for Part 3 HV</measurement>
                    <measurement group_id="B14" value="NA" spread="NA">This row is for Part 3 HV</measurement>
                    <measurement group_id="B15" value="NA" spread="NA">This row is for Part 3 HV</measurement>
                    <measurement group_id="B16" value="39.3" spread="5.47"/>
                    <measurement group_id="B17" value="32.7" spread="13.77"/>
                    <measurement group_id="B18" value="27" spread="5.44"/>
                    <measurement group_id="B19" value="27.9" spread="6.37"/>
                    <measurement group_id="B20" value="30.1" spread="9.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="0"/>
                    <measurement group_id="B10" value="0"/>
                    <measurement group_id="B11" value="0"/>
                    <measurement group_id="B12" value="0"/>
                    <measurement group_id="B13" value="0"/>
                    <measurement group_id="B14" value="0"/>
                    <measurement group_id="B15" value="0"/>
                    <measurement group_id="B16" value="1"/>
                    <measurement group_id="B17" value="5"/>
                    <measurement group_id="B18" value="9"/>
                    <measurement group_id="B19" value="4"/>
                    <measurement group_id="B20" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="6"/>
                    <measurement group_id="B6" value="6"/>
                    <measurement group_id="B7" value="6"/>
                    <measurement group_id="B8" value="6"/>
                    <measurement group_id="B9" value="16"/>
                    <measurement group_id="B10" value="6"/>
                    <measurement group_id="B11" value="6"/>
                    <measurement group_id="B12" value="6"/>
                    <measurement group_id="B13" value="6"/>
                    <measurement group_id="B14" value="6"/>
                    <measurement group_id="B15" value="10"/>
                    <measurement group_id="B16" value="5"/>
                    <measurement group_id="B17" value="7"/>
                    <measurement group_id="B18" value="10"/>
                    <measurement group_id="B19" value="8"/>
                    <measurement group_id="B20" value="134"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Part 1 and 2:Number of Participants (Healthy Volunteers) With Reported Adverse Events Receiving QBW251</title>
        <description>All adverse events (in healthy volunteers) reported.</description>
        <time_frame>Day 1 to Day 36</time_frame>
        <population>All treated subjects were included in the data analysis. Subjects were analyzed according to the study treatment(s) received.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1 Cohort 4: QBW251</title>
            <description>Single dose of QBW251 150 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O2">
            <title>Part 1 Cohort 5: QBW251</title>
            <description>Single dose of QBW251 300 mg in healthy volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O3">
            <title>Part 1 Cohort 6: QBW251</title>
            <description>Single dose of QBW251 500 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O4">
            <title>Part 1 Cohort 6: QBW251(Fed)</title>
            <description>Single dose of QBW251 500 mg (fed). single dose with food for a preliminary assessment of the effect of food on the absorption of QBW251 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O5">
            <title>Part 1 Cohort 7: QBW251</title>
            <description>Single dose of QBW251 750 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O6">
            <title>Part 1 Cohort 8: QBW251</title>
            <description>Single dose of QBW251 1000 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O7">
            <title>Part 1 Placebo</title>
            <description>Placebo to QBW251 in all cohorts of part 1 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O8">
            <title>Part 2 Cohort 1: QBW251</title>
            <description>Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O9">
            <title>Part 2 Cohort 2: QBW251</title>
            <description>Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O10">
            <title>Part 2 Cohort 3: QBW251</title>
            <description>Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O11">
            <title>Part 2 Cohort 4: QBW251</title>
            <description>Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O12">
            <title>Part 2 Cohort 5: QBW251</title>
            <description>Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O13">
            <title>Part 2 Placebo</title>
            <description>Placebo to QBW251 in all cohorts of part 2 in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O14">
            <title>Part 1 Cohort 1: QBW251</title>
            <description>Single dose of QBW251 10 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15</description>
          </group>
          <group group_id="O15">
            <title>Part 1 Cohort 2: QBW251</title>
            <description>Single dose of QBW251 25 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O16">
            <title>Part 1 Cohort 3: QBW251</title>
            <description>Single dose of QBW251 75 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
        </group_list>
        <measure>
          <title>Part 1 and 2:Number of Participants (Healthy Volunteers) With Reported Adverse Events Receiving QBW251</title>
          <description>All adverse events (in healthy volunteers) reported.</description>
          <population>All treated subjects were included in the data analysis. Subjects were analyzed according to the study treatment(s) received.</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="5"/>
                <count group_id="O5" value="6"/>
                <count group_id="O6" value="6"/>
                <count group_id="O7" value="16"/>
                <count group_id="O8" value="6"/>
                <count group_id="O9" value="6"/>
                <count group_id="O10" value="6"/>
                <count group_id="O11" value="6"/>
                <count group_id="O12" value="6"/>
                <count group_id="O13" value="10"/>
                <count group_id="O14" value="6"/>
                <count group_id="O15" value="6"/>
                <count group_id="O16" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Adverse events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="1"/>
                    <measurement group_id="O5" value="1"/>
                    <measurement group_id="O6" value="4"/>
                    <measurement group_id="O7" value="8"/>
                    <measurement group_id="O8" value="3"/>
                    <measurement group_id="O9" value="6"/>
                    <measurement group_id="O10" value="3"/>
                    <measurement group_id="O11" value="6"/>
                    <measurement group_id="O12" value="4"/>
                    <measurement group_id="O13" value="7"/>
                    <measurement group_id="O14" value="3"/>
                    <measurement group_id="O15" value="2"/>
                    <measurement group_id="O16" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious adverse events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                    <measurement group_id="O7" value="0"/>
                    <measurement group_id="O8" value="0"/>
                    <measurement group_id="O9" value="0"/>
                    <measurement group_id="O10" value="0"/>
                    <measurement group_id="O11" value="0"/>
                    <measurement group_id="O12" value="0"/>
                    <measurement group_id="O13" value="0"/>
                    <measurement group_id="O14" value="0"/>
                    <measurement group_id="O15" value="0"/>
                    <measurement group_id="O16" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Death</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                    <measurement group_id="O7" value="0"/>
                    <measurement group_id="O8" value="0"/>
                    <measurement group_id="O9" value="0"/>
                    <measurement group_id="O10" value="0"/>
                    <measurement group_id="O11" value="0"/>
                    <measurement group_id="O12" value="0"/>
                    <measurement group_id="O13" value="0"/>
                    <measurement group_id="O14" value="0"/>
                    <measurement group_id="O15" value="0"/>
                    <measurement group_id="O16" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Part 3: Change in Lung Clearance Index (LCI) From Baseline to Day 15</title>
        <description>Change in Lung Clearance Index (LCI) will be conducted according to international standards in cystic fibrosis patients. Lung clearance index (LCI) is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test, A reduction in mean change from baseline for LCI2.5 indicates improvement.</description>
        <time_frame>Baseline and Day 15</time_frame>
        <population>Pharmacodynamics (PD) analysis set: All randomized patients were included in the PD analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Part 3 Cohort 1: QBW251</title>
            <description>150 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
          </group>
          <group group_id="O2">
            <title>Part 3 Cohort 2: QBW251</title>
            <description>450 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
          </group>
          <group group_id="O3">
            <title>Part 3 Cohort 3: QBW251</title>
            <description>450 mg b.i.d. Multiple doses. Patients who are homozygous for the F508del mutation in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
          </group>
          <group group_id="O4">
            <title>Part 3 Placebo</title>
            <description>Placebo to QBW251 in all cohorts of part 3 in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
          </group>
        </group_list>
        <measure>
          <title>Part 3: Change in Lung Clearance Index (LCI) From Baseline to Day 15</title>
          <description>Change in Lung Clearance Index (LCI) will be conducted according to international standards in cystic fibrosis patients. Lung clearance index (LCI) is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test, A reduction in mean change from baseline for LCI2.5 indicates improvement.</description>
          <population>Pharmacodynamics (PD) analysis set: All randomized patients were included in the PD analysis</population>
          <units>Ratio</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="11"/>
                <count group_id="O3" value="17"/>
                <count group_id="O4" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.27" spread="0.769"/>
                    <measurement group_id="O2" value="-0.85" spread="1.798"/>
                    <measurement group_id="O3" value="-0.13" spread="2.276"/>
                    <measurement group_id="O4" value="0.28" spread="1.959"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Part 3: Number of Participants (Patients) With Reported Adverse Events Receiving QBW251</title>
        <description>All adverse events and serious adverse events (in patients) reported.</description>
        <time_frame>Day 1 to Day 56</time_frame>
        <population>Safety analysis set: All randomized patients were included in the safety analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Part 3 Cohort 1: QBW251</title>
            <description>150 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
          </group>
          <group group_id="O2">
            <title>Part 3 Cohort 2: QBW251</title>
            <description>450 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
          </group>
          <group group_id="O3">
            <title>Part 3 Cohort 3: QBW251</title>
            <description>450 mg b.i.d. Multiple doses. Patients who are homozygous for the F508del mutation in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
          </group>
          <group group_id="O4">
            <title>Part 3 Placebo</title>
            <description>Placebo to QBW251 in all cohorts of part 3 in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
          </group>
        </group_list>
        <measure>
          <title>Part 3: Number of Participants (Patients) With Reported Adverse Events Receiving QBW251</title>
          <description>All adverse events and serious adverse events (in patients) reported.</description>
          <population>Safety analysis set: All randomized patients were included in the safety analysis</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="19"/>
                <count group_id="O4" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Adverse Events (AE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="8"/>
                    <measurement group_id="O3" value="18"/>
                    <measurement group_id="O4" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious Adverse Events (SAE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 3:Change in Forced Expiratory Volume in 1 Second (FEV1) at Day 15</title>
        <description>Forced Expiratory Volume in 1 second (FEV1) will be measured via spirometer according to international standards. Forced Expiratory Volume in 1 second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation</description>
        <time_frame>Baseline and Day 15</time_frame>
        <population>Pharmacodynamics (PD) analysis set: All randomized patients were included in the PD analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Part 3 Cohort 1: QBW251</title>
            <description>150 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
          </group>
          <group group_id="O2">
            <title>Part 3 Cohort 2: QBW251</title>
            <description>450 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
          </group>
          <group group_id="O3">
            <title>Part 3 Cohort 3: QBW251</title>
            <description>450 mg b.i.d. Multiple doses. Patients who are homozygous for the F508del mutation in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
          </group>
          <group group_id="O4">
            <title>Part 3 Placebo</title>
            <description>Placebo to QBW251 in all cohorts of part 3 in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
          </group>
        </group_list>
        <measure>
          <title>Part 3:Change in Forced Expiratory Volume in 1 Second (FEV1) at Day 15</title>
          <description>Forced Expiratory Volume in 1 second (FEV1) will be measured via spirometer according to international standards. Forced Expiratory Volume in 1 second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation</description>
          <population>Pharmacodynamics (PD) analysis set: All randomized patients were included in the PD analysis</population>
          <units>Liters</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="11"/>
                <count group_id="O3" value="16"/>
                <count group_id="O4" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.58" spread="2.476"/>
                    <measurement group_id="O2" value="5.99" spread="1.648"/>
                    <measurement group_id="O3" value="-1.16" spread="1.059"/>
                    <measurement group_id="O4" value="-1.46" spread="1.229"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 3: Change in Cystic Fibrosis Questionnaire-Revised Reported Outcomes</title>
        <description>Change in Cystic Fibrosis Questionnaire data will be obtained from patient reported outcomes (CFQ-R PRO). Respiratory Domain, cores range from 0 to 100, with higher scores indicating better health, a change of 4 is considered clinically relevant</description>
        <time_frame>Baseline and Day 14</time_frame>
        <population>Pharmacodynamics (PD) analysis set: All randomized patients were included in the PD analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Part 3 Cohort 1: QBW251</title>
            <description>150 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
          </group>
          <group group_id="O2">
            <title>Part 3 Cohort 2: QBW251</title>
            <description>450 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
          </group>
          <group group_id="O3">
            <title>Part 3 Cohort 3: QBW251</title>
            <description>450 mg b.i.d. Multiple doses. Patients who are homozygous for the F508del mutation in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
          </group>
          <group group_id="O4">
            <title>Part 3 Placebo</title>
            <description>Placebo to QBW251 in all cohorts of part 3 in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
          </group>
        </group_list>
        <measure>
          <title>Part 3: Change in Cystic Fibrosis Questionnaire-Revised Reported Outcomes</title>
          <description>Change in Cystic Fibrosis Questionnaire data will be obtained from patient reported outcomes (CFQ-R PRO). Respiratory Domain, cores range from 0 to 100, with higher scores indicating better health, a change of 4 is considered clinically relevant</description>
          <population>Pharmacodynamics (PD) analysis set: All randomized patients were included in the PD analysis</population>
          <units>Units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="11"/>
                <count group_id="O3" value="19"/>
                <count group_id="O4" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.06" spread="6.872"/>
                    <measurement group_id="O2" value="5.04" spread="4.617"/>
                    <measurement group_id="O3" value="-2.62" spread="2.853"/>
                    <measurement group_id="O4" value="-2.06" spread="4.415"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 1: AUC0-t in Healthy Volunteers</title>
        <description>Pharmacokinetics of QBW251 in plasma: area under the plasma concentration versus time curve from time zero to time of last measurable concentration (AUC0-t). In part one of the study a single dose was administered and samples were collected up to 5 days. As a result the AUC0-t goes from Day 1 to Day 5 (for some lower doses QBW251 concentrations were not measured up to Day 5 as the concentrations were low due to the low dose administered)</description>
        <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 2-5)</time_frame>
        <population>All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1 Cohort 1: QBW251</title>
            <description>Single dose of QBW251 10 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O2">
            <title>Part 1 Cohort 2: QBW251</title>
            <description>Single dose of QBW251 25 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O3">
            <title>Part 1 Cohort 3: QBW251</title>
            <description>Single dose of QBW251 75 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O4">
            <title>Part 1 Cohort 4: QBW251</title>
            <description>Single dose of QBW251 150 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O5">
            <title>Part 1 Cohort 5: QBW251</title>
            <description>Single dose of QBW251 300 mg in healthy volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O6">
            <title>Part 1 Cohort 6: QBW251</title>
            <description>Single dose of QBW251 500 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O7">
            <title>Part 1 Cohort 6: QBW251(Fed)</title>
            <description>Single dose of QBW251 500 mg (fed). single dose with food for a preliminary assessment of the effect of food on the absorption of QBW251 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O8">
            <title>Part 1 Cohort 7: QBW251</title>
            <description>Single dose of QBW251 750 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O9">
            <title>Part 1 Cohort 8: QBW251</title>
            <description>Single dose of QBW251 1000 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O10">
            <title>Part 1 Placebo</title>
            <description>Placebo to QBW251 in all cohorts of part 1 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
        </group_list>
        <measure>
          <title>Part 1: AUC0-t in Healthy Volunteers</title>
          <description>Pharmacokinetics of QBW251 in plasma: area under the plasma concentration versus time curve from time zero to time of last measurable concentration (AUC0-t). In part one of the study a single dose was administered and samples were collected up to 5 days. As a result the AUC0-t goes from Day 1 to Day 5 (for some lower doses QBW251 concentrations were not measured up to Day 5 as the concentrations were low due to the low dose administered)</description>
          <population>All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis.</population>
          <units>hr*ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="6"/>
                <count group_id="O6" value="6"/>
                <count group_id="O7" value="5"/>
                <count group_id="O8" value="6"/>
                <count group_id="O9" value="6"/>
                <count group_id="O10" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="52.5" spread="28.1"/>
                    <measurement group_id="O2" value="73.7" spread="51.8"/>
                    <measurement group_id="O3" value="692" spread="389"/>
                    <measurement group_id="O4" value="1650" spread="907"/>
                    <measurement group_id="O5" value="5470" spread="1070"/>
                    <measurement group_id="O6" value="9450" spread="1740"/>
                    <measurement group_id="O7" value="7470" spread="2190"/>
                    <measurement group_id="O8" value="20200" spread="11500"/>
                    <measurement group_id="O9" value="35900" spread="9100"/>
                    <measurement group_id="O10" value="NA" spread="NA">Not calculated</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 1: Maximum Concentration (Cmax) in Healthy Volunteers</title>
        <description>Pharmacokinetics of QBW251 in plasma: observed maximum plasma concentration following administration of QBW251. In this analysis Cmax will be reported using blood samples taken on Days 1- 5 are from healthy volunteers</description>
        <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 1 - 5)</time_frame>
        <population>All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1 Cohort 1: QBW251</title>
            <description>Single dose of QBW251 10 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O2">
            <title>Part 1 Cohort 2: QBW251</title>
            <description>Single dose of QBW251 25 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O3">
            <title>Part 1 Cohort 3: QBW251</title>
            <description>Single dose of QBW251 75 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O4">
            <title>Part 1 Cohort 4: QBW251</title>
            <description>Single dose of QBW251 150 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O5">
            <title>Part 1 Cohort 5: QBW251</title>
            <description>Single dose of QBW251 300 mg in healthy volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O6">
            <title>Part 1 Cohort 6: QBW251</title>
            <description>Single dose of QBW251 500 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O7">
            <title>Part 1 Cohort 6: QBW251(Fed)</title>
            <description>Single dose of QBW251 500 mg (fed). single dose with food for a preliminary assessment of the effect of food on the absorption of QBW251 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O8">
            <title>Part 1 Cohort 7: QBW251</title>
            <description>Single dose of QBW251 750 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O9">
            <title>Part 1 Cohort 8: QBW251</title>
            <description>Single dose of QBW251 1000 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
        </group_list>
        <measure>
          <title>Part 1: Maximum Concentration (Cmax) in Healthy Volunteers</title>
          <description>Pharmacokinetics of QBW251 in plasma: observed maximum plasma concentration following administration of QBW251. In this analysis Cmax will be reported using blood samples taken on Days 1- 5 are from healthy volunteers</description>
          <population>All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
          <units>ug/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="6"/>
                <count group_id="O6" value="6"/>
                <count group_id="O7" value="5"/>
                <count group_id="O8" value="6"/>
                <count group_id="O9" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21.1" spread="11.9"/>
                    <measurement group_id="O2" value="24.7" spread="15.9"/>
                    <measurement group_id="O3" value="186" spread="82.3"/>
                    <measurement group_id="O4" value="459" spread="267"/>
                    <measurement group_id="O5" value="1110" spread="330"/>
                    <measurement group_id="O6" value="1910" spread="413"/>
                    <measurement group_id="O7" value="1090" spread="449"/>
                    <measurement group_id="O8" value="2680" spread="1000"/>
                    <measurement group_id="O9" value="4540" spread="930"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 1: Time to Maximum Concentration (Tmax) in Healthy Volunteers</title>
        <description>Pharmacokinetics of QBW251 in plasma: time to reach the maximum concentration after administration of QBW251. In this analysis Tmax will be reported using blood samples taken on Days 1 - 5 from healthy volunteers. In this part of the study a single dose was administered and samples were collected up to 5 days. As a result the Tmax is one value as the concentration-time curve goes to Day 5 (for some lower does QBW251 concentrations were not measured up to Day 5 as the concentrations were low due to the low dose administered).</description>
        <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 1 - 5)</time_frame>
        <population>All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1 Cohort 1: QBW251</title>
            <description>Single dose of QBW251 10 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O2">
            <title>Part 1 Cohort 2: QBW251</title>
            <description>Single dose of QBW251 25 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O3">
            <title>Part 1 Cohort 3: QBW251</title>
            <description>Single dose of QBW251 75 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O4">
            <title>Part 1 Cohort 4: QBW251</title>
            <description>Single dose of QBW251 150 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O5">
            <title>Part 1 Cohort 5: QBW251</title>
            <description>Single dose of QBW251 300 mg in healthy volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O6">
            <title>Part 1 Cohort 6: QBW251</title>
            <description>Single dose of QBW251 500 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O7">
            <title>Part 1 Cohort 6: QBW251(Fed)</title>
            <description>Single dose of QBW251 500 mg (fed). single dose with food for a preliminary assessment of the effect of food on the absorption of QBW251 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O8">
            <title>Part 1 Cohort 7: QBW251</title>
            <description>Single dose of QBW251 750 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O9">
            <title>Part 1 Cohort 8: QBW251</title>
            <description>Single dose of QBW251 1000 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
        </group_list>
        <measure>
          <title>Part 1: Time to Maximum Concentration (Tmax) in Healthy Volunteers</title>
          <description>Pharmacokinetics of QBW251 in plasma: time to reach the maximum concentration after administration of QBW251. In this analysis Tmax will be reported using blood samples taken on Days 1 - 5 from healthy volunteers. In this part of the study a single dose was administered and samples were collected up to 5 days. As a result the Tmax is one value as the concentration-time curve goes to Day 5 (for some lower does QBW251 concentrations were not measured up to Day 5 as the concentrations were low due to the low dose administered).</description>
          <population>All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
          <units>hr</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="6"/>
                <count group_id="O6" value="6"/>
                <count group_id="O7" value="5"/>
                <count group_id="O8" value="6"/>
                <count group_id="O9" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.756" spread="0.268"/>
                    <measurement group_id="O2" value="1.25" spread="0.612"/>
                    <measurement group_id="O3" value="1.33" spread="0.516"/>
                    <measurement group_id="O4" value="1.50" spread="0.548"/>
                    <measurement group_id="O5" value="1.50" spread="0.837"/>
                    <measurement group_id="O6" value="2.17" spread="1.17"/>
                    <measurement group_id="O7" value="3.40" spread="0.894"/>
                    <measurement group_id="O8" value="2.52" spread="0.850"/>
                    <measurement group_id="O9" value="1.83" spread="0.753"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 1: T1/2 in Healthy Volunteers</title>
        <description>Pharmacokinetics of QBW251 in plasma: terminal elimination half-life. In this analysis T1/2 will be reported using blood samples taken on Days 1 - 5 from healthy volunteers. In part one of the study a single dose was administered and samples were collected up to 5 days. As a result the T1/2 goes from Day 1 to Day 5 (for some lower doses QBW251 concentrations were not measured up to Day 5 as the concentrations were low due to the low dose administered).</description>
        <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 1 - 5)</time_frame>
        <population>All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1 Cohort 1: QBW251</title>
            <description>Single dose of QBW251 10 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O2">
            <title>Part 1 Cohort 2: QBW251</title>
            <description>Single dose of QBW251 25 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O3">
            <title>Part 1 Cohort 3: QBW251</title>
            <description>Single dose of QBW251 75 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O4">
            <title>Part 1 Cohort 4: QBW251</title>
            <description>Single dose of QBW251 150 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O5">
            <title>Part 1 Cohort 5: QBW251</title>
            <description>Single dose of QBW251 300 mg in healthy volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O6">
            <title>Part 1 Cohort 6: QBW251</title>
            <description>Single dose of QBW251 500 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O7">
            <title>Part 1 Cohort 6: QBW251(Fed)</title>
            <description>Single dose of QBW251 500 mg (fed). single dose with food for a preliminary assessment of the effect of food on the absorption of QBW251 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O8">
            <title>Part 1 Cohort 7: QBW251</title>
            <description>Single dose of QBW251 750 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O9">
            <title>Part 1 Cohort 8: QBW251</title>
            <description>Single dose of QBW251 1000 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
        </group_list>
        <measure>
          <title>Part 1: T1/2 in Healthy Volunteers</title>
          <description>Pharmacokinetics of QBW251 in plasma: terminal elimination half-life. In this analysis T1/2 will be reported using blood samples taken on Days 1 - 5 from healthy volunteers. In part one of the study a single dose was administered and samples were collected up to 5 days. As a result the T1/2 goes from Day 1 to Day 5 (for some lower doses QBW251 concentrations were not measured up to Day 5 as the concentrations were low due to the low dose administered).</description>
          <population>All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
          <units>hr</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="6"/>
                <count group_id="O6" value="6"/>
                <count group_id="O7" value="5"/>
                <count group_id="O8" value="6"/>
                <count group_id="O9" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">There were not enough time points to calculated the T1/2</measurement>
                    <measurement group_id="O2" value="NA" spread="NA">There were not enough time points to calculated the T1/2</measurement>
                    <measurement group_id="O3" value="10.3" spread="4.24"/>
                    <measurement group_id="O4" value="10.1" spread="3.35"/>
                    <measurement group_id="O5" value="12.0" spread="2.26"/>
                    <measurement group_id="O6" value="12.7" spread="1.99"/>
                    <measurement group_id="O7" value="15.6" spread="5.03"/>
                    <measurement group_id="O8" value="12.8" spread="3.85"/>
                    <measurement group_id="O9" value="10.7" spread="2.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 1: AUCinf in Healthy Volunteers</title>
        <description>Pharmacokinetics of QBW251 in plasma: area under the plasma concentration time curve from time zero to infinity. In this analysis AUCinf will be reported using blood samples taken on Days 1 - 5 from healthy volunteers. In part one of the study a single dose was administered and samples were collected up to 5 days. As a result the AUCinf goes from Day 1 to Day 5 (for some lower doses QBW251 concentrations were not measured up to Day 5 as the concentrations were low due to the low dose administered)</description>
        <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 1 - 5)</time_frame>
        <population>All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1 Cohort 1: QBW251</title>
            <description>Single dose of QBW251 10 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O2">
            <title>Part 1 Cohort 2: QBW251</title>
            <description>Single dose of QBW251 25 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O3">
            <title>Part 1 Cohort 3: QBW251</title>
            <description>Single dose of QBW251 75 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O4">
            <title>Part 1 Cohort 4: QBW251</title>
            <description>Single dose of QBW251 150 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O5">
            <title>Part 1 Cohort 5: QBW251</title>
            <description>Single dose of QBW251 300 mg in healthy volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O6">
            <title>Part 1 Cohort 6: QBW251</title>
            <description>Single dose of QBW251 500 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O7">
            <title>Part 1 Cohort 6: QBW251(Fed)</title>
            <description>Single dose of QBW251 500 mg (fed). single dose with food for a preliminary assessment of the effect of food on the absorption of QBW251 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O8">
            <title>Part 1 Cohort 7: QBW251</title>
            <description>Single dose of QBW251 750 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O9">
            <title>Part 1 Cohort 8: QBW251</title>
            <description>Single dose of QBW251 1000 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
        </group_list>
        <measure>
          <title>Part 1: AUCinf in Healthy Volunteers</title>
          <description>Pharmacokinetics of QBW251 in plasma: area under the plasma concentration time curve from time zero to infinity. In this analysis AUCinf will be reported using blood samples taken on Days 1 - 5 from healthy volunteers. In part one of the study a single dose was administered and samples were collected up to 5 days. As a result the AUCinf goes from Day 1 to Day 5 (for some lower doses QBW251 concentrations were not measured up to Day 5 as the concentrations were low due to the low dose administered)</description>
          <population>All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
          <units>hr*ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="6"/>
                <count group_id="O6" value="6"/>
                <count group_id="O7" value="5"/>
                <count group_id="O8" value="6"/>
                <count group_id="O9" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not calculated due to insufficient data</measurement>
                    <measurement group_id="O2" value="NA" spread="NA">Not calculated due to insufficient data</measurement>
                    <measurement group_id="O3" value="731" spread="387"/>
                    <measurement group_id="O4" value="1680" spread="903"/>
                    <measurement group_id="O5" value="5510" spread="1080"/>
                    <measurement group_id="O6" value="9480" spread="1740"/>
                    <measurement group_id="O7" value="7540" spread="2220"/>
                    <measurement group_id="O8" value="20300" spread="11500"/>
                    <measurement group_id="O9" value="36000" spread="9120"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 1: CL/F in Healthy Volunteers</title>
        <description>Pharmacokinetics of QBW251 in plasma: apparent systemic clearance from plasma following extravascular administration. In this analysis CL/F will be reported using blood samples taken on Days 1 - 5 from healthy volunteers. In part one of the study a single dose was administered and samples were collected up to 5 days. As a result the CL/F goes from Day 1 to Day 5 (for some lower doses QBW251 concentrations were not measured up to Day 5 as the concentrations were low due to the low dose administered)</description>
        <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 1 - 5)</time_frame>
        <population>All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1 Cohort 1: QBW251</title>
            <description>Single dose of QBW251 10 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O2">
            <title>Part 1 Cohort 2: QBW251</title>
            <description>Single dose of QBW251 25 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O3">
            <title>Part 1 Cohort 3: QBW251</title>
            <description>Single dose of QBW251 75 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O4">
            <title>Part 1 Cohort 4: QBW251</title>
            <description>Single dose of QBW251 150 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O5">
            <title>Part 1 Cohort 5: QBW251</title>
            <description>Single dose of QBW251 300 mg in healthy volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O6">
            <title>Part 1 Cohort 6: QBW251</title>
            <description>Single dose of QBW251 500 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O7">
            <title>Part 1 Cohort 6: QBW251(Fed)</title>
            <description>Single dose of QBW251 500 mg (fed). single dose with food for a preliminary assessment of the effect of food on the absorption of QBW251 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O8">
            <title>Part 1 Cohort 7: QBW251</title>
            <description>Single dose of QBW251 750 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O9">
            <title>Part 1 Cohort 8: QBW251</title>
            <description>Single dose of QBW251 1000 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
        </group_list>
        <measure>
          <title>Part 1: CL/F in Healthy Volunteers</title>
          <description>Pharmacokinetics of QBW251 in plasma: apparent systemic clearance from plasma following extravascular administration. In this analysis CL/F will be reported using blood samples taken on Days 1 - 5 from healthy volunteers. In part one of the study a single dose was administered and samples were collected up to 5 days. As a result the CL/F goes from Day 1 to Day 5 (for some lower doses QBW251 concentrations were not measured up to Day 5 as the concentrations were low due to the low dose administered)</description>
          <population>All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
          <units>L/hr</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="6"/>
                <count group_id="O6" value="6"/>
                <count group_id="O7" value="5"/>
                <count group_id="O8" value="6"/>
                <count group_id="O9" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not calculated due to insufficient data</measurement>
                    <measurement group_id="O2" value="NA" spread="NA">Not calculated due to insufficient data</measurement>
                    <measurement group_id="O3" value="123" spread="49.0"/>
                    <measurement group_id="O4" value="114" spread="63.9"/>
                    <measurement group_id="O5" value="56.2" spread="11.0"/>
                    <measurement group_id="O6" value="54.5" spread="11.9"/>
                    <measurement group_id="O7" value="71.6" spread="22.6"/>
                    <measurement group_id="O8" value="45.9" spread="19.9"/>
                    <measurement group_id="O9" value="29.7" spread="9.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 1: Vz/F in Healthy Volunteers</title>
        <description>Pharmacokinetics of QBW251 in plasma: apparent volume of distribution during the terminal elimination phase following extravascular administration. In this analysis Vz/F will be reported using blood samples taken on Days 1 - 5 from healthy volunteers.</description>
        <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 1 - 5)</time_frame>
        <population>All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1 Cohort 1: QBW251</title>
            <description>Single dose of QBW251 10 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O2">
            <title>Part 1 Cohort 2: QBW251</title>
            <description>Single dose of QBW251 25 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O3">
            <title>Part 1 Cohort 3: QBW251</title>
            <description>Single dose of QBW251 75 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O4">
            <title>Part 1 Cohort 4: QBW251</title>
            <description>Single dose of QBW251 150 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O5">
            <title>Part 1 Cohort 5: QBW251</title>
            <description>Single dose of QBW251 300 mg in healthy volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O6">
            <title>Part 1 Cohort 6: QBW251</title>
            <description>Single dose of QBW251 500 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O7">
            <title>Part 1 Cohort 6: QBW251(Fed)</title>
            <description>Single dose of QBW251 500 mg (fed). single dose with food for a preliminary assessment of the effect of food on the absorption of QBW251 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O8">
            <title>Part 1 Cohort 7: QBW251</title>
            <description>Single dose of QBW251 750 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
          <group group_id="O9">
            <title>Part 1 Cohort 8: QBW251</title>
            <description>Single dose of QBW251 1000 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).</description>
          </group>
        </group_list>
        <measure>
          <title>Part 1: Vz/F in Healthy Volunteers</title>
          <description>Pharmacokinetics of QBW251 in plasma: apparent volume of distribution during the terminal elimination phase following extravascular administration. In this analysis Vz/F will be reported using blood samples taken on Days 1 - 5 from healthy volunteers.</description>
          <population>All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
          <units>Liters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="6"/>
                <count group_id="O6" value="6"/>
                <count group_id="O7" value="5"/>
                <count group_id="O8" value="6"/>
                <count group_id="O9" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not calculated due to insufficient data</measurement>
                    <measurement group_id="O2" value="NA" spread="NA">Not calculated due to insufficient data</measurement>
                    <measurement group_id="O3" value="1700" spread="772"/>
                    <measurement group_id="O4" value="1490" spread="622"/>
                    <measurement group_id="O5" value="957" spread="151"/>
                    <measurement group_id="O6" value="995" spread="235"/>
                    <measurement group_id="O7" value="1580" spread="587"/>
                    <measurement group_id="O8" value="827" spread="375"/>
                    <measurement group_id="O9" value="447" spread="112"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 2: AUCtau in Healthy Volunteers</title>
        <description>Pharmacokinetics of QBW251 in plasma after multiple doses: the area under the plasma concentration-time curve from time zero to end of the dosing interval tau. In this analysis AUCtau will be reported. Samples taken on Days 1 and 14 from healthy volunteers</description>
        <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1 and 14; ( If B ID dosing, 12 hours samples will be pre-dosed)</time_frame>
        <population>Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Part 2 Cohort 1: QBW251</title>
            <description>Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O2">
            <title>Part 2 Cohort 2: QBW251</title>
            <description>Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O3">
            <title>Part 2 Cohort 3: QBW251</title>
            <description>Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O4">
            <title>Part 2 Cohort 4: QBW251</title>
            <description>Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O5">
            <title>Part 2 Cohort 5: QBW251</title>
            <description>Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
        </group_list>
        <measure>
          <title>Part 2: AUCtau in Healthy Volunteers</title>
          <description>Pharmacokinetics of QBW251 in plasma after multiple doses: the area under the plasma concentration-time curve from time zero to end of the dosing interval tau. In this analysis AUCtau will be reported. Samples taken on Days 1 and 14 from healthy volunteers</description>
          <population>Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
          <units>hr*ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1800" spread="794"/>
                    <measurement group_id="O2" value="6170" spread="1250"/>
                    <measurement group_id="O3" value="16100" spread="8170"/>
                    <measurement group_id="O4" value="7160" spread="1960"/>
                    <measurement group_id="O5" value="18800" spread="6360"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2060" spread="708"/>
                    <measurement group_id="O2" value="7620" spread="1470"/>
                    <measurement group_id="O3" value="28300" spread="5570"/>
                    <measurement group_id="O4" value="12100" spread="4930"/>
                    <measurement group_id="O5" value="80300" spread="56300"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 2: Maximum Concentration (Cmax) in Healthy Volunteers</title>
        <description>Pharmacokinetics of QBW251 in plasma after multiple doses: observed maximum plasma concentration following QBW251 at steady state. In this analysis Cmax will be reported using blood samples taken on Days 1 and 14 from healthy volunteers.</description>
        <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1 and 14; ( If B ID dosing, 12 hours samples will be pre-dosed)</time_frame>
        <population>Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Part 2 Cohort 1: QBW251</title>
            <description>Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O2">
            <title>Part 2 Cohort 2: QBW251</title>
            <description>Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O3">
            <title>Part 2 Cohort 3: QBW251</title>
            <description>Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O4">
            <title>Part 2 Cohort 4: QBW251</title>
            <description>Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O5">
            <title>Part 2 Cohort 5: QBW251</title>
            <description>Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
        </group_list>
        <measure>
          <title>Part 2: Maximum Concentration (Cmax) in Healthy Volunteers</title>
          <description>Pharmacokinetics of QBW251 in plasma after multiple doses: observed maximum plasma concentration following QBW251 at steady state. In this analysis Cmax will be reported using blood samples taken on Days 1 and 14 from healthy volunteers.</description>
          <population>Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
          <units>ug/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="541" spread="338"/>
                    <measurement group_id="O2" value="1650" spread="343"/>
                    <measurement group_id="O3" value="2790" spread="1040"/>
                    <measurement group_id="O4" value="1650" spread="188"/>
                    <measurement group_id="O5" value="3720" spread="1530"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="430" spread="145"/>
                    <measurement group_id="O2" value="1500" spread="442"/>
                    <measurement group_id="O3" value="3840" spread="868"/>
                    <measurement group_id="O4" value="2190" spread="769"/>
                    <measurement group_id="O5" value="9420" spread="4330"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 2: Time to Maximum Concentration (Tmax) in Healthy Volunteers</title>
        <description>Pharmacokinetics of QBW251 in plasma after multiple doses: time to reach the maximum concentration after administration of QBW251. In this analysis Tmax will be reported using blood samples taken on Days 1 and 14 from healthy volunteers.</description>
        <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1 and 14; ( If B ID dosing, 12 hours samples will be pre-dosed)</time_frame>
        <population>Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Part 2 Cohort 1: QBW251</title>
            <description>Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O2">
            <title>Part 2 Cohort 2: QBW251</title>
            <description>Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O3">
            <title>Part 2 Cohort 3: QBW251</title>
            <description>Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O4">
            <title>Part 2 Cohort 4: QBW251</title>
            <description>Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O5">
            <title>Part 2 Cohort 5: QBW251</title>
            <description>Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
        </group_list>
        <measure>
          <title>Part 2: Time to Maximum Concentration (Tmax) in Healthy Volunteers</title>
          <description>Pharmacokinetics of QBW251 in plasma after multiple doses: time to reach the maximum concentration after administration of QBW251. In this analysis Tmax will be reported using blood samples taken on Days 1 and 14 from healthy volunteers.</description>
          <population>Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
          <units>hr</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.67" spread="0.816"/>
                    <measurement group_id="O2" value="1.17" spread="0.408"/>
                    <measurement group_id="O3" value="2.33" spread="1.21"/>
                    <measurement group_id="O4" value="2.68" spread="0.813"/>
                    <measurement group_id="O5" value="3.67" spread="0.516"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.17" spread="1.17"/>
                    <measurement group_id="O2" value="2.17" spread="0.408"/>
                    <measurement group_id="O3" value="2.33" spread="1.03"/>
                    <measurement group_id="O4" value="3.25" spread="1.41"/>
                    <measurement group_id="O5" value="3.80" spread="0.447"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 2: AUC0-t</title>
        <description>Pharmacokinetics of QBW251 in plasma: area under the plasma concentration versus time curve from time zero to time of last measurable concentration. In this analysis AUC0-t will be reported using blood samples taken on Day 14 are from healthy volunteers.</description>
        <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 14; ( If B ID dosing, 12 hours samples will be pre-dosed)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Part 2 Cohort 1: QBW251</title>
            <description>Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O2">
            <title>Part 2 Cohort 2: QBW251</title>
            <description>Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O3">
            <title>Part 2 Cohort 3: QBW251</title>
            <description>Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O4">
            <title>Part 2 Cohort 4: QBW251</title>
            <description>Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O5">
            <title>Part 2 Cohort 5: QBW251</title>
            <description>Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O6">
            <title>Part 2 Placebo</title>
            <description>Placebo to QBW251 in all cohorts of part 2 in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
        </group_list>
        <measure>
          <title>Part 2: AUC0-t</title>
          <description>Pharmacokinetics of QBW251 in plasma: area under the plasma concentration versus time curve from time zero to time of last measurable concentration. In this analysis AUC0-t will be reported using blood samples taken on Day 14 are from healthy volunteers.</description>
          <units>hr*ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="5"/>
                <count group_id="O6" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2060" spread="708"/>
                    <measurement group_id="O2" value="7620" spread="1470"/>
                    <measurement group_id="O3" value="28300" spread="5570"/>
                    <measurement group_id="O4" value="12100" spread="4930"/>
                    <measurement group_id="O5" value="80300" spread="56300"/>
                    <measurement group_id="O6" value="NA" spread="NA">Not calculated</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 2: Cav in Healthy Volunteers</title>
        <description>The average drug concentration in plasma during multiple dosing. In this analysis Cav will be reported using blood samples taken on Days 1 and 14 are from healthy volunteers.</description>
        <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1 and 14; ( If B ID dosing, 12 hours samples will be pre-dosed)</time_frame>
        <population>Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Part 2 Cohort 1: QBW251</title>
            <description>Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O2">
            <title>Part 2 Cohort 2: QBW251</title>
            <description>Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O3">
            <title>Part 2 Cohort 3: QBW251</title>
            <description>Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O4">
            <title>Part 2 Cohort 4: QBW251</title>
            <description>Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O5">
            <title>Part 2 Cohort 5: QBW251</title>
            <description>Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
        </group_list>
        <measure>
          <title>Part 2: Cav in Healthy Volunteers</title>
          <description>The average drug concentration in plasma during multiple dosing. In this analysis Cav will be reported using blood samples taken on Days 1 and 14 are from healthy volunteers.</description>
          <population>Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
          <units>ug/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="85.8" spread="29.5"/>
                    <measurement group_id="O2" value="318" spread="61.1"/>
                    <measurement group_id="O3" value="1180" spread="232"/>
                    <measurement group_id="O4" value="NA" spread="NA">Not calculated due to insufficient data</measurement>
                    <measurement group_id="O5" value="NA" spread="NA">Not calculated due to insufficient data</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 2: CL/F in Healthy Volunteers</title>
        <description>apparent systemic clearance from plasma following extravascular administration. In this analysis CL/F will be reported using blood samples taken on Day 14 from healthy volunteers.</description>
        <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 14; ( If B ID dosing, 12 hours samples will be pre-dosed)</time_frame>
        <population>Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Part 2 Cohort 1: QBW251</title>
            <description>Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O2">
            <title>Part 2 Cohort 2: QBW251</title>
            <description>Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O3">
            <title>Part 2 Cohort 3: QBW251</title>
            <description>Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O4">
            <title>Part 2 Cohort 4: QBW251</title>
            <description>Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O5">
            <title>Part 2 Cohort 5: QBW251</title>
            <description>Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
        </group_list>
        <measure>
          <title>Part 2: CL/F in Healthy Volunteers</title>
          <description>apparent systemic clearance from plasma following extravascular administration. In this analysis CL/F will be reported using blood samples taken on Day 14 from healthy volunteers.</description>
          <population>Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
          <units>L/hr</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="80.8" spread="29.7"/>
                    <measurement group_id="O2" value="54.0" spread="9.40"/>
                    <measurement group_id="O3" value="27.5" spread="5.98"/>
                    <measurement group_id="O4" value="NA" spread="NA">Not calculated due to insufficient data</measurement>
                    <measurement group_id="O5" value="NA" spread="NA">Not calculated due to insufficient data</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 2: Vz/F in Healthy Volunteers</title>
        <description>Apparent volume of distribution during the terminal elimination phase following extravascular administration. In this analysis Vz/F will be reported using blood samples taken on Day 14 from healthy volunteers.</description>
        <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 14; ( If B ID dosing, 12 hours samples will be pre-dosed)</time_frame>
        <population>Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Part 2 Cohort 1: QBW251</title>
            <description>Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O2">
            <title>Part 2 Cohort 2: QBW251</title>
            <description>Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O3">
            <title>Part 2 Cohort 3: QBW251</title>
            <description>Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O4">
            <title>Part 2 Cohort 4: QBW251</title>
            <description>Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O5">
            <title>Part 2 Cohort 5: QBW251</title>
            <description>Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
        </group_list>
        <measure>
          <title>Part 2: Vz/F in Healthy Volunteers</title>
          <description>Apparent volume of distribution during the terminal elimination phase following extravascular administration. In this analysis Vz/F will be reported using blood samples taken on Day 14 from healthy volunteers.</description>
          <population>Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
          <units>Liters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1330" spread="550"/>
                    <measurement group_id="O2" value="1120" spread="395"/>
                    <measurement group_id="O3" value="608" spread="255"/>
                    <measurement group_id="O4" value="NA" spread="NA">Not calculated due to insufficient data</measurement>
                    <measurement group_id="O5" value="NA" spread="NA">Not calculated due to insufficient data</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 2: Racc in Healthy Volunteers</title>
        <description>Accumulation ratio (Racc). In this analysis Racc will be reported using blood samples taken on Days 1 - 14 from healthy volunteers.</description>
        <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1 - 14; ( If B ID dosing, 12 hours samples will be pre-dosed)</time_frame>
        <population>Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Part 2 Cohort 1: QBW251</title>
            <description>Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O2">
            <title>Part 2 Cohort 2: QBW251</title>
            <description>Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O3">
            <title>Part 2 Cohort 3: QBW251</title>
            <description>Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O4">
            <title>Part 2 Cohort 4: QBW251</title>
            <description>Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O5">
            <title>Part 2 Cohort 5: QBW251</title>
            <description>Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
        </group_list>
        <measure>
          <title>Part 2: Racc in Healthy Volunteers</title>
          <description>Accumulation ratio (Racc). In this analysis Racc will be reported using blood samples taken on Days 1 - 14 from healthy volunteers.</description>
          <population>Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
          <units>Ratio</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.27" spread="0.425"/>
                    <measurement group_id="O2" value="1.25" spread="0.199"/>
                    <measurement group_id="O3" value="2.08" spread="0.913"/>
                    <measurement group_id="O4" value="1.66" spread="0.386"/>
                    <measurement group_id="O5" value="3.88" spread="2.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 2: T1/2 in Healthy Volunteers</title>
        <description>terminal elimination half-life (T1/2). In this analysis T1/2 will be reported using blood samples taken on Day 14 from healthy volunteers.</description>
        <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 14; ( If B ID dosing, 12 hours samples will be pre-dosed)</time_frame>
        <population>Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Part 2 Cohort 1: QBW251</title>
            <description>Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O2">
            <title>Part 2 Cohort 2: QBW251</title>
            <description>Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O3">
            <title>Part 2 Cohort 3: QBW251</title>
            <description>Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O4">
            <title>Part 2 Cohort 4: QBW251</title>
            <description>Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O5">
            <title>Part 2 Cohort 5: QBW251</title>
            <description>Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
        </group_list>
        <measure>
          <title>Part 2: T1/2 in Healthy Volunteers</title>
          <description>terminal elimination half-life (T1/2). In this analysis T1/2 will be reported using blood samples taken on Day 14 from healthy volunteers.</description>
          <population>Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
          <units>hr</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.3" spread="1.44"/>
                    <measurement group_id="O2" value="14.1" spread="3.80"/>
                    <measurement group_id="O3" value="15.1" spread="4.40"/>
                    <measurement group_id="O4" value="NA" spread="NA">Not calculated due to insufficient data</measurement>
                    <measurement group_id="O5" value="NA" spread="NA">Not calculated due to insufficient data</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 3: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of QBW251 in CF Patients</title>
        <description>Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)</description>
        <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day 14</time_frame>
        <population>Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Part 3 Cohort 1: QBW251</title>
            <description>150 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
          </group>
          <group group_id="O2">
            <title>Part 3 Cohort 2: QBW251</title>
            <description>450 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
          </group>
          <group group_id="O3">
            <title>Part 3 Cohort 3: QBW251</title>
            <description>450 mg b.i.d. Multiple doses. Patients who are homozygous for the F508del mutation in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
          </group>
        </group_list>
        <measure>
          <title>Part 3: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of QBW251 in CF Patients</title>
          <description>Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)</description>
          <population>Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
          <units>ng × hr /mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1110" spread="709"/>
                    <measurement group_id="O2" value="7530" spread="2480"/>
                    <measurement group_id="O3" value="6020" spread="2960"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1760" spread="943"/>
                    <measurement group_id="O2" value="18900" spread="6850"/>
                    <measurement group_id="O3" value="NA" spread="NA">PK parameters were not calculated for Day 14 as blood samples were collected up to 2 hours post-dose.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 3: Plasma Concentration at the Last Quantifiable Time Point (Clast) of QBW251 in CF Patients</title>
        <description>Blood samples were collected at timepoints prespecified in the study protocol. Tlast of QBW251 was the last time point when blood sample collected was quantifiable</description>
        <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day2</time_frame>
        <population>Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Part 3 Cohort 1: QBW251</title>
            <description>150 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
          </group>
          <group group_id="O2">
            <title>Part 3 Cohort 2: QBW251</title>
            <description>450 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
          </group>
          <group group_id="O3">
            <title>Part 3 Cohort 3: QBW251</title>
            <description>450 mg b.i.d. Multiple doses. Patients who are homozygous for the F508del mutation in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
          </group>
        </group_list>
        <measure>
          <title>Part 3: Plasma Concentration at the Last Quantifiable Time Point (Clast) of QBW251 in CF Patients</title>
          <description>Blood samples were collected at timepoints prespecified in the study protocol. Tlast of QBW251 was the last time point when blood sample collected was quantifiable</description>
          <population>Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42.3" spread="14.1"/>
                    <measurement group_id="O2" value="423" spread="275"/>
                    <measurement group_id="O3" value="653" spread="318"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="86.4" spread="16.3"/>
                    <measurement group_id="O2" value="1570" spread="813"/>
                    <measurement group_id="O3" value="NA" spread="NA">PK parameters were not calculated for Day 14 as blood samples were collected up to 2 hours post-dose</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 3: Maximum Concentration (Cmax) in CF Patients</title>
        <description>Observed maximum plasma concentration following administration of QBW251. In this analysis Cmax will be reported using blood samples taken on Day 1and day 14 from patients</description>
        <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day 14</time_frame>
        <population>Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Part 3 Cohort 1: QBW251</title>
            <description>150 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
          </group>
          <group group_id="O2">
            <title>Part 3 Cohort 2: QBW251</title>
            <description>450 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
          </group>
          <group group_id="O3">
            <title>Part 3 Cohort 3: QBW251</title>
            <description>450 mg b.i.d. Multiple doses. Patients who are homozygous for the F508del mutation in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
          </group>
        </group_list>
        <measure>
          <title>Part 3: Maximum Concentration (Cmax) in CF Patients</title>
          <description>Observed maximum plasma concentration following administration of QBW251. In this analysis Cmax will be reported using blood samples taken on Day 1and day 14 from patients</description>
          <population>Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="419" spread="316"/>
                    <measurement group_id="O2" value="1950" spread="715"/>
                    <measurement group_id="O3" value="2380" spread="1240"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="632" spread="438"/>
                    <measurement group_id="O2" value="4080" spread="1780"/>
                    <measurement group_id="O3" value="NA" spread="NA">PK parameters were not calculated for Day 14 as blood samples were collected up to 2 hours post-dose</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 3: Tlast in CF Patients</title>
        <description>Blood samples were collected at timepoints prespecified in the study protocol. Tlast of QBW251 was the last time point when blood sample collected was quantifiable day 1 and day 14</description>
        <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day 14</time_frame>
        <population>Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Part 3 Cohort 1: QBW251</title>
            <description>150 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
          </group>
          <group group_id="O2">
            <title>Part 3 Cohort 2: QBW251</title>
            <description>450 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
          </group>
          <group group_id="O3">
            <title>Part 3 Cohort 3: QBW251</title>
            <description>450 mg b.i.d. Multiple doses. Patients who are homozygous for the F508del mutation in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
          </group>
        </group_list>
        <measure>
          <title>Part 3: Tlast in CF Patients</title>
          <description>Blood samples were collected at timepoints prespecified in the study protocol. Tlast of QBW251 was the last time point when blood sample collected was quantifiable day 1 and day 14</description>
          <population>Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
          <units>hr</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.99" spread="0.0136"/>
                    <measurement group_id="O2" value="7.95" spread="0.149"/>
                    <measurement group_id="O3" value="5.80" spread="0.639"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.97" spread="0.0667"/>
                    <measurement group_id="O2" value="7.96" spread="0.0554"/>
                    <measurement group_id="O3" value="NA" spread="NA">PK parameters were not calculated for Day 14 as blood samples were collected up to 2 hours post-dose</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 3: Time to Maximum Concentration (Tmax)</title>
        <description>Pharmacokinetics of QBW251 in plasma after multiple doses: time to reach the maximum concentration after administration of QBW251. In this analysis Tmax will be reported using blood samples taken on Days 1 and 14 in patients</description>
        <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day 14</time_frame>
        <population>Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Part 3 Cohort 1: QBW251</title>
            <description>150 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
          </group>
          <group group_id="O2">
            <title>Part 3 Cohort 2: QBW251</title>
            <description>450 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
          </group>
          <group group_id="O3">
            <title>Part 3 Cohort 3: QBW251</title>
            <description>450 mg b.i.d. Multiple doses. Patients who are homozygous for the F508del mutation in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.</description>
          </group>
        </group_list>
        <measure>
          <title>Part 3: Time to Maximum Concentration (Tmax)</title>
          <description>Pharmacokinetics of QBW251 in plasma after multiple doses: time to reach the maximum concentration after administration of QBW251. In this analysis Tmax will be reported using blood samples taken on Days 1 and 14 in patients</description>
          <population>Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
          <units>hr</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.17" spread="2.47"/>
                    <measurement group_id="O2" value="3.08" spread="1.68"/>
                    <measurement group_id="O3" value="3.18" spread="0.838"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.82" spread="0.750"/>
                    <measurement group_id="O2" value="2.39" spread="0.973"/>
                    <measurement group_id="O3" value="NA" spread="NA">PK parameters were not calculated for Day 14 as blood samples were collected up to 2 hours post-dose</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 2: Ae0-t in Healthy Volunteers</title>
        <description>Pharmacokinetics of QBW251 in urine: amount of drug excreted in urine from time zero until last measurable concentration. In this analysis Ae0-t will be reported using urine samples taken on Day 1 from healthy volunteers.</description>
        <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1</time_frame>
        <population>All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Part 2 Cohort 1: QBW251</title>
            <description>Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O2">
            <title>Part 2 Cohort 2: QBW251</title>
            <description>Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O3">
            <title>Part 2 Cohort 3: QBW251</title>
            <description>Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O4">
            <title>Part 2 Cohort 4: QBW251</title>
            <description>Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O5">
            <title>Part 2 Cohort 5: QBW251</title>
            <description>Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O6">
            <title>Part 2 Placebo</title>
            <description>Placebo to QBW251 in all cohorts of part 2 in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
        </group_list>
        <measure>
          <title>Part 2: Ae0-t in Healthy Volunteers</title>
          <description>Pharmacokinetics of QBW251 in urine: amount of drug excreted in urine from time zero until last measurable concentration. In this analysis Ae0-t will be reported using urine samples taken on Day 1 from healthy volunteers.</description>
          <population>All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
          <units>L/hr</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="5"/>
                <count group_id="O5" value="5"/>
                <count group_id="O6" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.36" spread="1.84"/>
                    <measurement group_id="O2" value="2.20" spread="1.26"/>
                    <measurement group_id="O3" value="1.21" spread="0.697"/>
                    <measurement group_id="O4" value="0.419" spread="0.271"/>
                    <measurement group_id="O5" value="0.140" spread="0.0936"/>
                    <measurement group_id="O6" value="NA" spread="NA">Not calculated</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 2: CLr in Healthy Volunteers</title>
        <description>Pharmacokinetics of QBW251 in urine: renal clearance following drug administration. In this analysis CLr will be reported using urine samples taken on Day 1 from healthy volunteers.</description>
        <time_frame>Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1; Day 14 was calculated as urine was only collected up to 12 hours on Day 1 thus CLr cannot be calculated.</time_frame>
        <population>Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Part 2 Cohort 1: QBW251</title>
            <description>Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O2">
            <title>Part 2 Cohort 2: QBW251</title>
            <description>Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O3">
            <title>Part 2 Cohort 3: QBW251</title>
            <description>Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O4">
            <title>Part 2 Cohort 4: QBW251</title>
            <description>Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
          <group group_id="O5">
            <title>Part 2 Cohort 5: QBW251</title>
            <description>Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).</description>
          </group>
        </group_list>
        <measure>
          <title>Part 2: CLr in Healthy Volunteers</title>
          <description>Pharmacokinetics of QBW251 in urine: renal clearance following drug administration. In this analysis CLr will be reported using urine samples taken on Day 1 from healthy volunteers.</description>
          <population>Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis</population>
          <units>L/hr</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.36" spread="1.84"/>
                    <measurement group_id="O2" value="2.20" spread="1.26"/>
                    <measurement group_id="O3" value="1.21" spread="0.697"/>
                    <measurement group_id="O4" value="0.419" spread="0.271"/>
                    <measurement group_id="O5" value="0.140" spread="0.0936"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Part 1 Placebo</title>
          <description>Part 1 Placebo</description>
        </group>
        <group group_id="E2">
          <title>Part 1 QBW251 10mg</title>
          <description>Part 1 QBW251 10mg</description>
        </group>
        <group group_id="E3">
          <title>Part 1 QBW251 25mg</title>
          <description>Part 1 QBW251 25mg</description>
        </group>
        <group group_id="E4">
          <title>Part 1 QBW251 150mg</title>
          <description>Part 1 QBW251 150mg</description>
        </group>
        <group group_id="E5">
          <title>Part 1 QBW251 300mg</title>
          <description>Part 1 QBW251 300mg</description>
        </group>
        <group group_id="E6">
          <title>Part 1 QBW251 500mg</title>
          <description>Part 1 QBW251 500mg</description>
        </group>
        <group group_id="E7">
          <title>Part 1 QBW251 500mg (Fed)</title>
          <description>Part 1 QBW251 500mg (fed)</description>
        </group>
        <group group_id="E8">
          <title>Part 1 QBW251 750mg</title>
          <description>Part 1 QBW251 750mg</description>
        </group>
        <group group_id="E9">
          <title>Part 1 QBW251 1000mg</title>
          <description>Part 1 QBW251 1000mg</description>
        </group>
        <group group_id="E10">
          <title>Part 2 Placebo</title>
          <description>Part 2 Placebo</description>
        </group>
        <group group_id="E11">
          <title>Part 2 QBW251 150mg</title>
          <description>Part 2 QBW251 150mg</description>
        </group>
        <group group_id="E12">
          <title>Part 2 QBW251 400mg</title>
          <description>Part 2 QBW251 400mg</description>
        </group>
        <group group_id="E13">
          <title>Part 2 QBW251 750mg</title>
          <description>Part 2 QBW251 750mg</description>
        </group>
        <group group_id="E14">
          <title>Part 2 QBW251 450mg BID</title>
          <description>Part 2 QBW251 450mg BID</description>
        </group>
        <group group_id="E15">
          <title>Part 2 QBW251 750mg BID</title>
          <description>Part 2 QBW251 750mg BID</description>
        </group>
        <group group_id="E16">
          <title>Part 3 Placebo C1/C2/C3</title>
          <description>Part 3 Placebo C1/C2/C3</description>
        </group>
        <group group_id="E17">
          <title>Part 3 QBW251 150mg BID C1</title>
          <description>Part 3 QBW251 150mg BID C1</description>
        </group>
        <group group_id="E18">
          <title>Part 3 QBW251 450mg BID C2</title>
          <description>Part 3 QBW251 450mg BID C2</description>
        </group>
        <group group_id="E19">
          <title>Part 3 QBW251 450mg BID C3</title>
          <description>Part 3 QBW251 450mg BID C3</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>INFECTIVE PULMONARY EXACERBATION OF CYSTIC FIBROSIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>SINUSITIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="7" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="8" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="8" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="18" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>PALPITATIONS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Congenital, familial and genetic disorders</title>
            <event_list>
              <event>
                <sub_title>ICHTHYOSIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>EAR DISCOMFORT</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>EAR PAIN</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>TINNITUS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>ABDOMINAL DISCOMFORT</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>ABDOMINAL DISTENSION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>ABDOMINAL PAIN</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>ABDOMINAL PAIN LOWER</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>APHTHOUS STOMATITIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>DIARRHOEA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="2" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>FAECES DISCOLOURED</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>FLATULENCE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>GASTROOESOPHAGEAL REFLUX DISEASE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>GINGIVAL DISORDER</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>NAUSEA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="4" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="2" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>SALIVA ALTERED</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>SALIVARY GLAND PAIN</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>VOMITING</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="2" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>ASTHENIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>CHEST DISCOMFORT</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>CHEST PAIN</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>FATIGUE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="2" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>INFLUENZA LIKE ILLNESS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>PAIN</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>PERIPHERAL SWELLING</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>PYREXIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>SENSATION OF FOREIGN BODY</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>THIRST</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>VESSEL PUNCTURE SITE BRUISE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>BRONCHITIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>BRONCHOPULMONARY ASPERGILLOSIS ALLERGIC</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>FOLLICULITIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>FUNGAL INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>GASTROENTERITIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>INFECTIVE PULMONARY EXACERBATION OF CYSTIC FIBROSIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="2" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>NASOPHARYNGITIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>ORAL HERPES</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>PHARYNGITIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>SINUSITIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>UPPER RESPIRATORY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>VIRAL UPPER RESPIRATORY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>ARTHROPOD BITE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>LIGAMENT SPRAIN</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>SKIN WOUND</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>ADENOVIRUS TEST POSITIVE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>BLOOD ALKALINE PHOSPHATASE INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>BLOOD POTASSIUM DECREASED</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>BREATH SOUNDS ABNORMAL</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>CORONAVIRUS TEST POSITIVE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>DECREASED APPETITE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>HYPOGLYCAEMIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>VITAMIN D DEFICIENCY</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>BACK PAIN</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>JOINT SWELLING</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>MUSCLE SPASMS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>MUSCULOSKELETAL CHEST PAIN</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>MUSCULOSKELETAL PAIN</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>MUSCULOSKELETAL STIFFNESS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>NECK PAIN</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>PAIN IN EXTREMITY</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>BALANCE DISORDER</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>DIZZINESS</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>HEADACHE</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="4" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="4" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>HYPERAESTHESIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>PRESYNCOPE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>SCIATICA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>SYNCOPE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>TREMOR</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>AGITATION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>DEPRESSION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>INSOMNIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>STRESS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>CHROMATURIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>GLYCOSURIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>PROTEINURIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>BRONCHIAL OBSTRUCTION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>COUGH</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="4" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>DYSPNOEA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>EPISTAXIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>HAEMOPTYSIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="2" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>NASAL CONGESTION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="2" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>NASAL DISCOMFORT</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>OROPHARYNGEAL PAIN</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>PAINFUL RESPIRATION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>PRODUCTIVE COUGH</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>PULMONARY CONGESTION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>RHINORRHOEA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="2" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>SINUS CONGESTION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>SNEEZING</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>SPUTUM INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="5" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>THROAT IRRITATION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>TONSILLAR DISORDER</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>ERYTHEMA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>HEAT RASH</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>NIGHT SWEATS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>PHOTOSENSITIVITY REACTION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>PRURITUS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="2" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>PRURITUS GENERALISED</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>RASH</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>RASH ERYTHEMATOUS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>RASH PRURITIC</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>URTICARIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>HOT FLUSH</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Study Director</name_or_title>
      <organization>Novartis</organization>
      <phone>862-778-8300</phone>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02190604
org study id: CQBW251X2101
secondary id: 2011-005085-37
nct id: NCT02190604
lead sponsor: 
has dmc: Yes
This study is designed to assess the safety, tolerability, pharmacokinetics and preliminary
      pharmacodynamics (proof of concept) of QBW251 in healthy subjects and cystic fibrosis
      patients following single and multiple doses. This first-in-human and proof of concept study
      will consist of 4 parts, with Parts 1 and 2 in healthy volunteers and Parts 3 and 4 in cystic
      fibrosis patients.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Part 1 and 2:Number of Participants (Healthy Volunteers) With Reported Adverse Events Receiving QBW251
time frame: Day 1 to Day 36
description: All adverse events (in healthy volunteers) reported.
measure: Part 3: Change in Lung Clearance Index (LCI) From Baseline to Day 15
time frame: Baseline and Day 15
description: Change in Lung Clearance Index (LCI) will be conducted according to international standards in cystic fibrosis patients. Lung clearance index (LCI) is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test, A reduction in mean change from baseline for LCI2.5 indicates improvement.
measure: Part 3: Number of Participants (Patients) With Reported Adverse Events Receiving QBW251
time frame: Day 1 to Day 56
description: All adverse events and serious adverse events (in patients) reported.
measure: Part 3:Change in Forced Expiratory Volume in 1 Second (FEV1) at Day 15
time frame: Baseline and Day 15
description: Forced Expiratory Volume in 1 second (FEV1) will be measured via spirometer according to international standards. Forced Expiratory Volume in 1 second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation
measure: Part 3: Change in Cystic Fibrosis Questionnaire-Revised Reported Outcomes
time frame: Baseline and Day 14
description: Change in Cystic Fibrosis Questionnaire data will be obtained from patient reported outcomes (CFQ-R PRO). Respiratory Domain, cores range from 0 to 100, with higher scores indicating better health, a change of 4 is considered clinically relevant
measure: Part 1: AUC0-t in Healthy Volunteers
time frame: Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 2-5)
description: Pharmacokinetics of QBW251 in plasma: area under the plasma concentration versus time curve from time zero to time of last measurable concentration (AUC0-t). In part one of the study a single dose was administered and samples were collected up to 5 days. As a result the AUC0-t goes from Day 1 to Day 5 (for some lower doses QBW251 concentrations were not measured up to Day 5 as the concentrations were low due to the low dose administered)
measure: Part 1: Maximum Concentration (Cmax) in Healthy Volunteers
time frame: Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 1 - 5)
description: Pharmacokinetics of QBW251 in plasma: observed maximum plasma concentration following administration of QBW251. In this analysis Cmax will be reported using blood samples taken on Days 1- 5 are from healthy volunteers
measure: Part 1: Time to Maximum Concentration (Tmax) in Healthy Volunteers
time frame: Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 1 - 5)
description: Pharmacokinetics of QBW251 in plasma: time to reach the maximum concentration after administration of QBW251. In this analysis Tmax will be reported using blood samples taken on Days 1 - 5 from healthy volunteers. In this part of the study a single dose was administered and samples were collected up to 5 days. As a result the Tmax is one value as the concentration-time curve goes to Day 5 (for some lower does QBW251 concentrations were not measured up to Day 5 as the concentrations were low due to the low dose administered).
measure: Part 1: T1/2 in Healthy Volunteers
time frame: Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 1 - 5)
description: Pharmacokinetics of QBW251 in plasma: terminal elimination half-life. In this analysis T1/2 will be reported using blood samples taken on Days 1 - 5 from healthy volunteers. In part one of the study a single dose was administered and samples were collected up to 5 days. As a result the T1/2 goes from Day 1 to Day 5 (for some lower doses QBW251 concentrations were not measured up to Day 5 as the concentrations were low due to the low dose administered).
measure: Part 1: AUCinf in Healthy Volunteers
time frame: Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 1 - 5)
description: Pharmacokinetics of QBW251 in plasma: area under the plasma concentration time curve from time zero to infinity. In this analysis AUCinf will be reported using blood samples taken on Days 1 - 5 from healthy volunteers. In part one of the study a single dose was administered and samples were collected up to 5 days. As a result the AUCinf goes from Day 1 to Day 5 (for some lower doses QBW251 concentrations were not measured up to Day 5 as the concentrations were low due to the low dose administered)
measure: Part 1: CL/F in Healthy Volunteers
time frame: Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 1 - 5)
description: Pharmacokinetics of QBW251 in plasma: apparent systemic clearance from plasma following extravascular administration. In this analysis CL/F will be reported using blood samples taken on Days 1 - 5 from healthy volunteers. In part one of the study a single dose was administered and samples were collected up to 5 days. As a result the CL/F goes from Day 1 to Day 5 (for some lower doses QBW251 concentrations were not measured up to Day 5 as the concentrations were low due to the low dose administered)
measure: Part 1: Vz/F in Healthy Volunteers
time frame: Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 1 - 5)
description: Pharmacokinetics of QBW251 in plasma: apparent volume of distribution during the terminal elimination phase following extravascular administration. In this analysis Vz/F will be reported using blood samples taken on Days 1 - 5 from healthy volunteers.
measure: Part 2: AUCtau in Healthy Volunteers
time frame: Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1 and 14; ( If B ID dosing, 12 hours samples will be pre-dosed)
description: Pharmacokinetics of QBW251 in plasma after multiple doses: the area under the plasma concentration-time curve from time zero to end of the dosing interval tau. In this analysis AUCtau will be reported. Samples taken on Days 1 and 14 from healthy volunteers
measure: Part 2: Maximum Concentration (Cmax) in Healthy Volunteers
time frame: Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1 and 14; ( If B ID dosing, 12 hours samples will be pre-dosed)
description: Pharmacokinetics of QBW251 in plasma after multiple doses: observed maximum plasma concentration following QBW251 at steady state. In this analysis Cmax will be reported using blood samples taken on Days 1 and 14 from healthy volunteers.
measure: Part 2: Time to Maximum Concentration (Tmax) in Healthy Volunteers
time frame: Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1 and 14; ( If B ID dosing, 12 hours samples will be pre-dosed)
description: Pharmacokinetics of QBW251 in plasma after multiple doses: time to reach the maximum concentration after administration of QBW251. In this analysis Tmax will be reported using blood samples taken on Days 1 and 14 from healthy volunteers.
measure: Part 2: AUC0-t
time frame: Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 14; ( If B ID dosing, 12 hours samples will be pre-dosed)
description: Pharmacokinetics of QBW251 in plasma: area under the plasma concentration versus time curve from time zero to time of last measurable concentration. In this analysis AUC0-t will be reported using blood samples taken on Day 14 are from healthy volunteers.
measure: Part 2: Cav in Healthy Volunteers
time frame: Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1 and 14; ( If B ID dosing, 12 hours samples will be pre-dosed)
description: The average drug concentration in plasma during multiple dosing. In this analysis Cav will be reported using blood samples taken on Days 1 and 14 are from healthy volunteers.
measure: Part 2: CL/F in Healthy Volunteers
time frame: Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 14; ( If B ID dosing, 12 hours samples will be pre-dosed)
description: apparent systemic clearance from plasma following extravascular administration. In this analysis CL/F will be reported using blood samples taken on Day 14 from healthy volunteers.
measure: Part 2: Vz/F in Healthy Volunteers
time frame: Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 14; ( If B ID dosing, 12 hours samples will be pre-dosed)
description: Apparent volume of distribution during the terminal elimination phase following extravascular administration. In this analysis Vz/F will be reported using blood samples taken on Day 14 from healthy volunteers.
measure: Part 2: Racc in Healthy Volunteers
time frame: Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1 - 14; ( If B ID dosing, 12 hours samples will be pre-dosed)
description: Accumulation ratio (Racc). In this analysis Racc will be reported using blood samples taken on Days 1 - 14 from healthy volunteers.
measure: Part 2: T1/2 in Healthy Volunteers
time frame: Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 14; ( If B ID dosing, 12 hours samples will be pre-dosed)
description: terminal elimination half-life (T1/2). In this analysis T1/2 will be reported using blood samples taken on Day 14 from healthy volunteers.
measure: Part 3: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of QBW251 in CF Patients
time frame: Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day 14
description: Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
measure: Part 3: Plasma Concentration at the Last Quantifiable Time Point (Clast) of QBW251 in CF Patients
time frame: Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day2
description: Blood samples were collected at timepoints prespecified in the study protocol. Tlast of QBW251 was the last time point when blood sample collected was quantifiable
measure: Part 3: Maximum Concentration (Cmax) in CF Patients
time frame: Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day 14
description: Observed maximum plasma concentration following administration of QBW251. In this analysis Cmax will be reported using blood samples taken on Day 1and day 14 from patients
measure: Part 3: Tlast in CF Patients
time frame: Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day 14
description: Blood samples were collected at timepoints prespecified in the study protocol. Tlast of QBW251 was the last time point when blood sample collected was quantifiable day 1 and day 14
measure: Part 3: Time to Maximum Concentration (Tmax)
time frame: Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day 14
description: Pharmacokinetics of QBW251 in plasma after multiple doses: time to reach the maximum concentration after administration of QBW251. In this analysis Tmax will be reported using blood samples taken on Days 1 and 14 in patients
measure: Part 2: Ae0-t in Healthy Volunteers
time frame: Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1
description: Pharmacokinetics of QBW251 in urine: amount of drug excreted in urine from time zero until last measurable concentration. In this analysis Ae0-t will be reported using urine samples taken on Day 1 from healthy volunteers.
measure: Part 2: CLr in Healthy Volunteers
time frame: Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1; Day 14 was calculated as urine was only collected up to 12 hours on Day 1 thus CLr cannot be calculated.
description: Pharmacokinetics of QBW251 in urine: renal clearance following drug administration. In this analysis CLr will be reported using urine samples taken on Day 1 from healthy volunteers.
arm group label: Part 1 Cohort 1: QBW251
arm group type: Experimental
description: Single dose of QBW251 10 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
arm group label: Part 1 Cohort 2: QBW251
arm group type: Experimental
description: Single dose of QBW251 25 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
arm group label: Part 1 Cohort 3: QBW251
arm group type: Experimental
description: Single dose of QBW251 75 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
arm group label: Part 1 Cohort 4: QBW251
arm group type: Experimental
description: Single dose of QBW251 150 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
arm group label: Part 1 Cohort 5: QBW251
arm group type: Experimental
description: Single dose of QBW251 300 mg in healthy volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
arm group label: Part 1 Cohort 6: QBW251
arm group type: Experimental
description: Single dose of QBW251 500 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
arm group label: Part 1 Cohort 6: QBW251(fed)
arm group type: Experimental
description: Single dose of QBW251 500 mg (fed). single dose with food for a preliminary assessment of the effect of food on the absorption of QBW251 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
arm group label: Part 1 Cohort 7: QBW251
arm group type: Experimental
description: Single dose of QBW251 750 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
arm group label: Part 1 Cohort 8: QBW251
arm group type: Experimental
description: Single dose of QBW251 1000 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
arm group label: Part 1 Placebo
arm group type: Placebo Comparator
description: Placebo to QBW251 in all cohorts of part 1 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
arm group label: Part 2 Cohort 1: QBW251
arm group type: Experimental
description: Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
arm group label: Part 2 Cohort 2: QBW251
arm group type: Experimental
description: Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
arm group label: Part 2 Cohort 3: QBW251
arm group type: Experimental
description: Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
arm group label: Part 2 Cohort 4: QBW251
arm group type: Experimental
description: Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
arm group label: Part 2 Cohort 5: QBW251
arm group type: Experimental
description: Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
arm group label: Part 2 Placebo
arm group type: Placebo Comparator
description: Placebo to QBW251 in all cohorts of part 2 in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
arm group label: Part 3 Cohort 1: QBW251
arm group type: Experimental
description: 150 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
arm group label: Part 3 Cohort 2: QBW251
arm group type: Experimental
description: 450 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
arm group label: Part 3 Cohort 3: QBW251
arm group type: Experimental
description: 450 mg b.i.d. Multiple doses. Patients who are homozygous for the F508del mutation in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
arm group label: Part 3 Placebo
arm group type: Placebo Comparator
description: Placebo to QBW251 in all cohorts of part 3 in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
intervention type: Drug
intervention name: Placebo
description: Capsule- oral dose
arm group label: Part 1 Placebo
arm group label: Part 2 Placebo
arm group label: Part 3 Placebo
intervention type: Drug
intervention name: QBW251
description: Capsule - oral dose
arm group label: Part 1 Cohort 1: QBW251
arm group label: Part 1 Cohort 2: QBW251
arm group label: Part 1 Cohort 3: QBW251
arm group label: Part 1 Cohort 4: QBW251
arm group label: Part 1 Cohort 5: QBW251
arm group label: Part 1 Cohort 6: QBW251
arm group label: Part 1 Cohort 6: QBW251(fed)
arm group label: Part 1 Cohort 7: QBW251
arm group label: Part 1 Cohort 8: QBW251
arm group label: Part 2 Cohort 1: QBW251
arm group label: Part 2 Cohort 2: QBW251
arm group label: Part 2 Cohort 3: QBW251
arm group label: Part 2 Cohort 4: QBW251
arm group label: Part 2 Cohort 5: QBW251
arm group label: Part 3 Cohort 1: QBW251
arm group label: Part 3 Cohort 2: QBW251
arm group label: Part 3 Cohort 3: QBW251
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Novartis Pharmaceuticals
role: Study Director
affiliation: Novartis Pharmaceuticals
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country: Belgium
country: France
country: Germany
country: Ireland
country: Romania
country: United Kingdom
country: United States
country: Netherlands
url: https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=127
description: A Plain Language Trial Summary is available on novartisclinicaltrials.com
responsible party type: Sponsor
mesh term: Cystic Fibrosis
mesh term: Fibrosis
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