<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/NCT01685801</url>
  </required_header>
  <id_info>
    <org_study_id>VX12-770-113</org_study_id>
    <nct_id>NCT01685801</nct_id>
  </id_info>
  <brief_title>Pilot Study Testing the Effect of Ivacaftor on Lung Function in Subjects With Cystic Fibrosis and Residual CFTR Function</brief_title>
  <official_title>A Pilot Study Testing the Effect of Ivacaftor on Lung Function in Subjects With Cystic Fibrosis, Residual CFTR Function, and FEV1 ≥40% Predicted</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vertex Pharmaceuticals Incorporated</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Vertex Pharmaceuticals Incorporated</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is a multiple within participant crossover study to evaluate the effect of&#xD;
      ivacaftor on lung function in participants aged 12 years and older with cystic fibrosis (CF)&#xD;
      who have phenotypic or molecular evidence of residual CF transmembrane conductance regulator&#xD;
      (CFTR) function.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      CFTR Mutations associated with residual function or defective messenger ribonucleic acid&#xD;
      (mRNA) splicing include the following:&#xD;
&#xD;
      R117H, E56K, P67L, D110E, D110H, R117C, R347H, R352Q, A455E, D579G, S945L, L206W, R1070W,&#xD;
      F1074L, D1152H, S1235R, D1270N, 2789+5G-&gt;A, 3849+10kbC-&gt;T, 3272-26A-&gt;G, 711+5G-&gt;A, 3120G-&gt;A,&#xD;
      1811+1.6kbA-&gt;G, 711+3A-&gt;G, 1898+3A-&gt;G, 1898+1G-&gt;A, 1717-1G-&gt;A, 1717-8G-&gt;A, 1342-2A-&gt;C,&#xD;
      405+3A-&gt;C, 1716G/A 1811+1G-&gt;C, 1898+5G-&gt;T, 3850-3T-&gt;G, IVS14b+5G-&gt;A, 1898+1G-&gt;T, 4005+2T-&gt;C,&#xD;
      621+3A-&gt;G, 621+1G-&gt;T.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">April 2014</completion_date>
  <primary_completion_date type="Actual">April 2014</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) After 2 Weeks of Treatment</measure>
    <time_frame>Cycle 1 baseline, Cycle 1 Day 15 (for Cycle 1 reporting arms); Cycle 2 baseline, Cycle 2 Day 15 (for Cycle 2 reporting arms)</time_frame>
    <description>FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment, for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Lung Clearance Index (LCI) After 2 Weeks of Treatment</measure>
    <time_frame>Cycle 1 baseline, Cycle 1 Day 15 (for Cycle 1 reporting arms); Cycle 2 baseline, Cycle 2 Day 15 (for Cycle 2 reporting arms)</time_frame>
    <description>LCI is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test. The LCI was calculated as the number of lung volume turnovers (cumulative expired volume divided by the functional residual capacity [FRC]) required to reduce end-tidal concentration of an inert gas to 1/40th of the starting value. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment, for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Open-label Period: Absolute Change From Open-label Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) at Day 57</measure>
    <time_frame>Open-label Baseline, Open-label Day 57</time_frame>
    <description>FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Open-label Period: Absolute Change From Open-label Baseline In Lung Clearance Index (LCI) at Day 57</measure>
    <time_frame>Open-label Baseline, Open-label Day 57</time_frame>
    <description>LCI is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test. The LCI was calculated as the number of lung volume turnovers (cumulative expired volume divided by the functional residual capacity [FRC]) required to reduce end-tidal concentration of an inert gas to 1/40th of the starting value. Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Open-label Period: Absolute Change From Study Baseline In Sweat Chloride at Day 57</measure>
    <time_frame>Study Baseline, Open-label Day 57</time_frame>
    <description>Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of greater than or equal to (&gt;=) 15 microliter was required for determination of sweat chloride. Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Open-label Period: Absolute Change From Open-label Baseline In Weight at Day 57</measure>
    <time_frame>Open-label Baseline, Open-label Day 57</time_frame>
    <description>Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)</measure>
    <time_frame>From first dose of study drug through completion of follow-up visit (up to 26 weeks)</time_frame>
    <description>Adverse events (AEs) that started (or increased in severity) from first dose of study drug through completion of Follow-up were considered TEAEs, with exception that if an AE started during a Washout Period and was beyond 14 days from last dose date of preceding cycle, AE was considered as a &quot;Washout Period&quot; AE, and hence not TEAE. A TEAE was attributed to treatment in which it started or to the treatment in second cycling period of previous Crossover Period if it started during a Washout Period. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Data was to be reported by drug treatment for double-blind crossover period (Cycle 1 up to Washout Period 2) and open-label period.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Cystic Fibrosis</condition>
  <arm_group>
    <arm_group_label>Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ivacaftor</intervention_name>
    <description>150 milligram (mg) tablet orally every 12 hours up to 12 weeks.</description>
    <arm_group_label>Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP)</arm_group_label>
    <arm_group_label>Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI)</arm_group_label>
    <arm_group_label>Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP)</arm_group_label>
    <arm_group_label>Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI)</arm_group_label>
    <other_name>Kalydeco, VX-770</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo-matched-to-ivacaftor tablet</intervention_name>
    <description>Orally every 12 hours up to 4 weeks.</description>
    <arm_group_label>Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP)</arm_group_label>
    <arm_group_label>Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI)</arm_group_label>
    <arm_group_label>Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP)</arm_group_label>
    <arm_group_label>Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female participants with confirmed diagnosis of CF&#xD;
&#xD;
          -  Clinical evidence of residual CFTR function based on any 1 of the following: 1)&#xD;
             Clinically documented residual exocrine pancreatic function, 2) Sweat chloride value&#xD;
             less than equal to (&lt;=) 80 millimole per liter (mmol/L) at screening, or 3) Age of&#xD;
             diagnosis greater than equal to (&gt;=) 12 years and at least 1 copy of a CFTR mutation&#xD;
             associated with residual CFTR function or defective mRNA splicing&#xD;
&#xD;
          -  FEV1 &gt;= 40 percent (%)&#xD;
&#xD;
          -  12 years of age or older&#xD;
&#xD;
          -  Willing to agree to meet the contraception requirements&#xD;
&#xD;
          -  Able to swallow tablets&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  A copy of any of the following CFTR mutations: G551D, G178R, S549N, S549R, G551S,&#xD;
             G970R, G1244E, S1251N, S1255P, or G1349D&#xD;
&#xD;
          -  Unable to perform spirometry&#xD;
&#xD;
          -  An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in&#xD;
             therapy (including antibiotics) for pulmonary disease within 4 weeks before Day 1&#xD;
&#xD;
          -  Ongoing participation in another therapeutic clinical study or prior participation in&#xD;
             an investigational drug study within the 30 days prior to screening&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jerry Nick, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Jewish Health</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2015</verification_date>
  <study_first_submitted>September 6, 2012</study_first_submitted>
  <study_first_submitted_qc>September 11, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 14, 2012</study_first_posted>
  <results_first_submitted>April 30, 2015</results_first_submitted>
  <results_first_submitted_qc>April 30, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">May 19, 2015</results_first_posted>
  <last_update_submitted>April 30, 2015</last_update_submitted>
  <last_update_submitted_qc>April 30, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 19, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ivacaftor</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP)</title>
          <description>During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.</description>
        </group>
        <group group_id="P2">
          <title>Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI)</title>
          <description>During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.</description>
        </group>
        <group group_id="P3">
          <title>Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP)</title>
          <description>During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.</description>
        </group>
        <group group_id="P4">
          <title>Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI)</title>
          <description>During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Cycle 1 Period 1 (2 Weeks)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="7"/>
                <participants group_id="P4" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="7"/>
                <participants group_id="P4" count="6"/>
              </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_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Cycle 1 Period 2 (2 Weeks)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="7"/>
                <participants group_id="P4" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="7"/>
                <participants group_id="P4" count="5"/>
              </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="1"/>
              </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="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Washout Period 1 (4 Weeks)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="7"/>
                <participants group_id="P4" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="7"/>
                <participants group_id="P4" count="5"/>
              </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_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Cycle 2 Period 1 (2 Weeks)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="7"/>
                <participants group_id="P4" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="7"/>
                <participants group_id="P4" count="5"/>
              </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_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Cycle 2 Period 2 (2 Weeks)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="7"/>
                <participants group_id="P4" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="7"/>
                <participants group_id="P4" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Non-compliance with Study Drug</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Washout Period 2 (4 Weeks)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="7"/>
                <participants group_id="P4" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="7"/>
                <participants group_id="P4" count="4"/>
              </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_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Open-label Period (8 Weeks)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="7"/>
                <participants group_id="P4" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="7"/>
                <participants group_id="P4" count="4"/>
              </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_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Full Analysis Set (FAS) included all randomized participants who received at least 1 dose of study drug (ivacaftor or placebo).</population>
      <group_list>
        <group group_id="B1">
          <title>IPIP</title>
          <description>Detailed reporting group description is provided in Participant Flow module.</description>
        </group>
        <group group_id="B2">
          <title>IPPI</title>
          <description>Detailed reporting group description is provided in Participant Flow module.</description>
        </group>
        <group group_id="B3">
          <title>PIIP</title>
          <description>Detailed reporting group description is provided in Participant Flow module.</description>
        </group>
        <group group_id="B4">
          <title>PIPI</title>
          <description>Detailed reporting group description is provided in Participant Flow module.</description>
        </group>
        <group group_id="B5">
          <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="5"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="7"/>
            <count group_id="B4" value="6"/>
            <count group_id="B5" value="24"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="44.8" spread="8.04"/>
                    <measurement group_id="B2" value="29.7" spread="11.66"/>
                    <measurement group_id="B3" value="41.4" spread="13.96"/>
                    <measurement group_id="B4" value="33.8" spread="17.26"/>
                    <measurement group_id="B5" value="37.3" spread="13.86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>less than (&lt;) 20 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>20 - 40 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>greater than (&gt;) 40 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="11"/>
                  </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="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Genotype</title>
          <description>All participants were tested for cystic fibrosis transmembrane conductance regulator (CFTR) genotype. Participants with a documented medical history of either a residual function or a messenger ribonucleic acid (mRNA) splice site (Class V) CFTR mutation were reported.</description>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>mRNA Splice Site (Class V) Mutations</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Residual Function Mutations</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) After 2 Weeks of Treatment</title>
        <description>FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment, for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).</description>
        <time_frame>Cycle 1 baseline, Cycle 1 Day 15 (for Cycle 1 reporting arms); Cycle 2 baseline, Cycle 2 Day 15 (for Cycle 2 reporting arms)</time_frame>
        <population>Full analysis set (FAS) population. Here, number of participants analyzed signifies participant evaluable for this outcome measure and &quot;n&quot; signifies participants who were evaluable for the specified category in each arm, respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>Cycle 1: Placebo</title>
            <description>Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 1.</description>
          </group>
          <group group_id="O2">
            <title>Cycle 1: Ivacaftor</title>
            <description>Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 1.</description>
          </group>
          <group group_id="O3">
            <title>Cycle 2: Placebo</title>
            <description>Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 2.</description>
          </group>
          <group group_id="O4">
            <title>Cycle 2: Ivacaftor</title>
            <description>Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) After 2 Weeks of Treatment</title>
          <description>FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment, for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).</description>
          <population>Full analysis set (FAS) population. Here, number of participants analyzed signifies participant evaluable for this outcome measure and &quot;n&quot; signifies participants who were evaluable for the specified category in each arm, respectively.</population>
          <units>Percent predicted of FEV1</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="24"/>
                <count group_id="O3" value="23"/>
                <count group_id="O4" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Overall (n=24, 24, 23, 23)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.5828" spread="3.67326"/>
                    <measurement group_id="O2" value="2.0898" spread="4.63833"/>
                    <measurement group_id="O3" value="0.8495" spread="4.20641"/>
                    <measurement group_id="O4" value="3.6868" spread="6.13466"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>mRNA Splice Site(ClassV)Mutations (n=10, 10, 9, 9)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.5710" spread="3.39739"/>
                    <measurement group_id="O2" value="0.8196" spread="5.09161"/>
                    <measurement group_id="O3" value="1.7132" spread="3.80933"/>
                    <measurement group_id="O4" value="2.0640" spread="3.55493"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Residual Function Mutations (n=14, 14, 14, 14)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.4069" spread="3.75842"/>
                    <measurement group_id="O2" value="2.9971" spread="4.24124"/>
                    <measurement group_id="O3" value="0.2942" spread="4.49056"/>
                    <measurement group_id="O4" value="4.7300" spread="7.27436"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>This statistical analysis is for &quot;Overall&quot; category.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Posterior Mean</param_type>
            <param_value>2.251</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>0.961</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.383</ci_lower_limit>
            <ci_upper_limit>4.144</ci_upper_limit>
            <estimate_desc>The posterior distribution of overall treatment difference was obtained using the Bayesian hierarchical model and 95% credible interval of the treatment effect (posterior mean) was calculated.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Lung Clearance Index (LCI) After 2 Weeks of Treatment</title>
        <description>LCI is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test. The LCI was calculated as the number of lung volume turnovers (cumulative expired volume divided by the functional residual capacity [FRC]) required to reduce end-tidal concentration of an inert gas to 1/40th of the starting value. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment, for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).</description>
        <time_frame>Cycle 1 baseline, Cycle 1 Day 15 (for Cycle 1 reporting arms); Cycle 2 baseline, Cycle 2 Day 15 (for Cycle 2 reporting arms)</time_frame>
        <population>FAS population. Here, number of participants analyzed signifies participant evaluable for this outcome measure and &quot;n&quot; signifies participants who were evaluable for the specified category in each arm, respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>Cycle 1: Placebo</title>
            <description>Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 1.</description>
          </group>
          <group group_id="O2">
            <title>Cycle 1: Ivacaftor</title>
            <description>Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of cycle 1.</description>
          </group>
          <group group_id="O3">
            <title>Cycle 2: Placebo</title>
            <description>Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 2.</description>
          </group>
          <group group_id="O4">
            <title>Cycle 2: Ivacaftor</title>
            <description>Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of cycle 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Lung Clearance Index (LCI) After 2 Weeks of Treatment</title>
          <description>LCI is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test. The LCI was calculated as the number of lung volume turnovers (cumulative expired volume divided by the functional residual capacity [FRC]) required to reduce end-tidal concentration of an inert gas to 1/40th of the starting value. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment, for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).</description>
          <population>FAS population. Here, number of participants analyzed signifies participant evaluable for this outcome measure and &quot;n&quot; signifies participants who were evaluable for the specified category in each arm, respectively.</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="23"/>
                <count group_id="O2" value="24"/>
                <count group_id="O3" value="23"/>
                <count group_id="O4" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Overall (n=23, 24, 23, 22)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.4596" spread="1.97774"/>
                    <measurement group_id="O2" value="0.2822" spread="3.54741"/>
                    <measurement group_id="O3" value="0.4111" spread="2.39920"/>
                    <measurement group_id="O4" value="0.0770" spread="1.98188"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>mRNA Splice Site(ClassV)Mutations (n=10, 10, 9, 9)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.4321" spread="1.97140"/>
                    <measurement group_id="O2" value="-0.5306" spread="1.91374"/>
                    <measurement group_id="O3" value="1.0568" spread="2.12093"/>
                    <measurement group_id="O4" value="-0.3136" spread="1.89562"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Residual Function Mutations (n=13, 14, 14, 13)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.4808" spread="2.06279"/>
                    <measurement group_id="O2" value="0.8628" spread="4.34252"/>
                    <measurement group_id="O3" value="-0.0039" spread="2.54929"/>
                    <measurement group_id="O4" value="0.3475" spread="2.06990"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Open-label Period: Absolute Change From Open-label Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) at Day 57</title>
        <description>FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).</description>
        <time_frame>Open-label Baseline, Open-label Day 57</time_frame>
        <population>FAS population. Here, number of participants analyzed signifies participant evaluable for this outcome measure and &quot;n&quot; signifies participants who were evaluable for the specified category.</population>
        <group_list>
          <group group_id="O1">
            <title>Open-Label Period: Ivacaftor</title>
            <description>Ivacaftor 150 mg tablet orally every 12 hours for 8 weeks during the open-label period after washout period 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Open-label Period: Absolute Change From Open-label Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) at Day 57</title>
          <description>FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).</description>
          <population>FAS population. Here, number of participants analyzed signifies participant evaluable for this outcome measure and &quot;n&quot; signifies participants who were evaluable for the specified category.</population>
          <units>Percent predicted of FEV1</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Overall (n=21)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.6815" spread="4.17934"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>mRNA Splice Site(ClassV)Mutations (n=9)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.3072" spread="2.93624"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Residual Function Mutations (n=12)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.9622" spread="5.02864"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Open-label Period: Absolute Change From Open-label Baseline In Lung Clearance Index (LCI) at Day 57</title>
        <description>LCI is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test. The LCI was calculated as the number of lung volume turnovers (cumulative expired volume divided by the functional residual capacity [FRC]) required to reduce end-tidal concentration of an inert gas to 1/40th of the starting value. Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).</description>
        <time_frame>Open-label Baseline, Open-label Day 57</time_frame>
        <population>FAS population. Here, number of participants analyzed signifies participant evaluable for this outcome measure and &quot;n&quot; signifies participants who were evaluable for the specified category.</population>
        <group_list>
          <group group_id="O1">
            <title>Open-label Period: Ivacaftor</title>
            <description>Ivacaftor 150 mg tablet orally every 12 hours in open-label period (8 weeks) after washout period 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Open-label Period: Absolute Change From Open-label Baseline In Lung Clearance Index (LCI) at Day 57</title>
          <description>LCI is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test. The LCI was calculated as the number of lung volume turnovers (cumulative expired volume divided by the functional residual capacity [FRC]) required to reduce end-tidal concentration of an inert gas to 1/40th of the starting value. Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).</description>
          <population>FAS population. Here, number of participants analyzed signifies participant evaluable for this outcome measure and &quot;n&quot; signifies participants who were evaluable for the specified category.</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="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Overall (n=21)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.5687" spread="2.27137"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>mRNA Splice Site(ClassV)Mutations (n=9)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.3459" spread="2.88447"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Residual Function Mutations (n=12)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.7358" spread="1.80502"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Open-label Period: Absolute Change From Study Baseline In Sweat Chloride at Day 57</title>
        <description>Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of greater than or equal to (&gt;=) 15 microliter was required for determination of sweat chloride. Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).</description>
        <time_frame>Study Baseline, Open-label Day 57</time_frame>
        <population>FAS population. Here, number of participants analyzed signifies participant evaluable for this outcome measure and &quot;n&quot; signifies participants who were evaluable for the specified category.</population>
        <group_list>
          <group group_id="O1">
            <title>Open-label Period: Ivacaftor</title>
            <description>Ivacaftor 150 mg tablet orally every 12 hours for 8 weeks during the open-label period after washout period 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Open-label Period: Absolute Change From Study Baseline In Sweat Chloride at Day 57</title>
          <description>Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of greater than or equal to (&gt;=) 15 microliter was required for determination of sweat chloride. Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).</description>
          <population>FAS population. Here, number of participants analyzed signifies participant evaluable for this outcome measure and &quot;n&quot; signifies participants who were evaluable for the specified category.</population>
          <units>millimole per liter (mmol/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="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Overall (n=19)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-15.74" spread="14.781"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>mRNA Splice Site(ClassV)Mutations (n=8)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-14.13" spread="8.254"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Residual Function Mutations (n=11)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-16.91" spread="18.493"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Open-label Period: Absolute Change From Open-label Baseline In Weight at Day 57</title>
        <description>Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).</description>
        <time_frame>Open-label Baseline, Open-label Day 57</time_frame>
        <population>FAS population. Here, number of participants analyzed signifies participant evaluable for this outcome measure and &quot;n&quot; signifies participants who were evaluable for the specified category.</population>
        <group_list>
          <group group_id="O1">
            <title>Open-label Period: Ivacaftor</title>
            <description>Ivacaftor 150 mg tablet orally every 12 hours for 8 weeks during the open-label period after washout period 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Open-label Period: Absolute Change From Open-label Baseline In Weight at Day 57</title>
          <description>Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).</description>
          <population>FAS population. Here, number of participants analyzed signifies participant evaluable for this outcome measure and &quot;n&quot; signifies participants who were evaluable for the specified category.</population>
          <units>kilograms (kg)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Overall (n=21)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.77" spread="1.906"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>mRNA Splice Site(ClassV)Mutations (n=9)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.32" spread="2.111"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Residual Function Mutations (n=12)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.35" spread="1.710"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)</title>
        <description>Adverse events (AEs) that started (or increased in severity) from first dose of study drug through completion of Follow-up were considered TEAEs, with exception that if an AE started during a Washout Period and was beyond 14 days from last dose date of preceding cycle, AE was considered as a &quot;Washout Period&quot; AE, and hence not TEAE. A TEAE was attributed to treatment in which it started or to the treatment in second cycling period of previous Crossover Period if it started during a Washout Period. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Data was to be reported by drug treatment for double-blind crossover period (Cycle 1 up to Washout Period 2) and open-label period.</description>
        <time_frame>From first dose of study drug through completion of follow-up visit (up to 26 weeks)</time_frame>
        <population>Safety set included all participants who received at least 1 dose of study drug. Here, number of participants analyzed signifies participant evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Crossover Double-blind Period: Placebo</title>
            <description>Placebo matched to ivacaftor tablet orally every 12 hours for 2 weeks either during the double blind period 1 or 2 of cycle 1 and cycle 2.</description>
          </group>
          <group group_id="O2">
            <title>Crossover Double-blind Period: Ivacaftor</title>
            <description>Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks either during the double blind period 1 or 2 of cycle 1 and cycle 2.</description>
          </group>
          <group group_id="O3">
            <title>Open-label Period: Ivacaftor</title>
            <description>Ivacaftor 150 mg tablet orally every 12 hours for 8 weeks during the open-label period after washout period 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)</title>
          <description>Adverse events (AEs) that started (or increased in severity) from first dose of study drug through completion of Follow-up were considered TEAEs, with exception that if an AE started during a Washout Period and was beyond 14 days from last dose date of preceding cycle, AE was considered as a &quot;Washout Period&quot; AE, and hence not TEAE. A TEAE was attributed to treatment in which it started or to the treatment in second cycling period of previous Crossover Period if it started during a Washout Period. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Data was to be reported by drug treatment for double-blind crossover period (Cycle 1 up to Washout Period 2) and open-label period.</description>
          <population>Safety set included all participants who received at least 1 dose of study drug. Here, number of participants analyzed signifies participant evaluable for this outcome measure.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="24"/>
                <count group_id="O3" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                    <measurement group_id="O2" value="18"/>
                    <measurement group_id="O3" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From first dose of study drug through completion of follow-up visit (up to 26 weeks)</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Crossover Double-blind Period: Placebo</title>
          <description>Placebo matched to ivacaftor tablet orally every 12 hours for 2 weeks either during the double blind period 1 or 2 of cycle 1 and cycle 2.</description>
        </group>
        <group group_id="E2">
          <title>Crossover Double-blind Period: Ivacaftor</title>
          <description>Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks either during the double blind period 1 or 2 of cycle 1 and cycle 2.</description>
        </group>
        <group group_id="E3">
          <title>Open-label Period: Ivacaftor</title>
          <description>Ivacaftor 150 mg tablet orally every 12 hours for 8 weeks during the open-label period after washout period 2.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 15.0</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="24"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
              </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="24"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 15.0</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="17" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="20" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac flutter</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Lacrimation increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Ocular hyperaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Chest discomfort</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Hypersensitivity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Infective pulmonary exacerbation of cystic fibrosis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Acute sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Incision site infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Laryngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Oral viral infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection viral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Viral upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Oral candidiasis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Pharyngitis streptococcal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Viral infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Excoriation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Wrist fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Liver function test abnormal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
              </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="24"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Intervertebral disc protrusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Joint swelling</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Musculoskeletal discomfort</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Osteopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Sinus headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Postmenopausal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Haemoptysis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Paranasal sinus hypersecretion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Sputum increased</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Respiration abnormal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Sinus congestion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Sneezing</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Throat irritation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Wheezing</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Pleuritic pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Respiratory tract congestion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Upper-airway cough syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Dysphonia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Dyspnoea exertional</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Respiratory tract irritation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Heat rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
              </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>PI is free to publish results of the study after (1) the first multi-center publication, (2) if the sponsor elects not to publish the results, or (3) 18 months after close of the study, whichever occurs first. Proposed publications are to be submitted to the sponsor for review and comment for a period of at least 45 days (which may be extended under certain circumstances related to protection of intellectual property); the sponsor cannot require changes to the proposed publications.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Medical Monitor</name_or_title>
      <organization>Vertex Pharmaceuticals Incorporated</organization>
      <phone>617-341-6777</phone>
      <email>medicalinfo@vrtx.com</email>
    </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/NCT01685801
org study id: VX12-770-113
nct id: NCT01685801
lead sponsor: 
has dmc: No
This study is a multiple within participant crossover study to evaluate the effect of
      ivacaftor on lung function in participants aged 12 years and older with cystic fibrosis (CF)
      who have phenotypic or molecular evidence of residual CF transmembrane conductance regulator
      (CFTR) function.
CFTR Mutations associated with residual function or defective messenger ribonucleic acid
      (mRNA) splicing include the following:

      R117H, E56K, P67L, D110E, D110H, R117C, R347H, R352Q, A455E, D579G, S945L, L206W, R1070W,
      F1074L, D1152H, S1235R, D1270N, 2789+5G->A, 3849+10kbC->T, 3272-26A->G, 711+5G->A, 3120G->A,
      1811+1.6kbA->G, 711+3A->G, 1898+3A->G, 1898+1G->A, 1717-1G->A, 1717-8G->A, 1342-2A->C,
      405+3A->C, 1716G/A 1811+1G->C, 1898+5G->T, 3850-3T->G, IVS14b+5G->A, 1898+1G->T, 4005+2T->C,
      621+3A->G, 621+1G->T.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Care Provider)
measure: Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) After 2 Weeks of Treatment
time frame: Cycle 1 baseline, Cycle 1 Day 15 (for Cycle 1 reporting arms); Cycle 2 baseline, Cycle 2 Day 15 (for Cycle 2 reporting arms)
description: FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment, for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).
measure: Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Lung Clearance Index (LCI) After 2 Weeks of Treatment
time frame: Cycle 1 baseline, Cycle 1 Day 15 (for Cycle 1 reporting arms); Cycle 2 baseline, Cycle 2 Day 15 (for Cycle 2 reporting arms)
description: LCI is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test. The LCI was calculated as the number of lung volume turnovers (cumulative expired volume divided by the functional residual capacity [FRC]) required to reduce end-tidal concentration of an inert gas to 1/40th of the starting value. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment, for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).
measure: Open-label Period: Absolute Change From Open-label Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) at Day 57
time frame: Open-label Baseline, Open-label Day 57
description: FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).
measure: Open-label Period: Absolute Change From Open-label Baseline In Lung Clearance Index (LCI) at Day 57
time frame: Open-label Baseline, Open-label Day 57
description: LCI is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test. The LCI was calculated as the number of lung volume turnovers (cumulative expired volume divided by the functional residual capacity [FRC]) required to reduce end-tidal concentration of an inert gas to 1/40th of the starting value. Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).
measure: Open-label Period: Absolute Change From Study Baseline In Sweat Chloride at Day 57
time frame: Study Baseline, Open-label Day 57
description: Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of greater than or equal to (>=) 15 microliter was required for determination of sweat chloride. Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).
measure: Open-label Period: Absolute Change From Open-label Baseline In Weight at Day 57
time frame: Open-label Baseline, Open-label Day 57
description: Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
time frame: From first dose of study drug through completion of follow-up visit (up to 26 weeks)
description: Adverse events (AEs) that started (or increased in severity) from first dose of study drug through completion of Follow-up were considered TEAEs, with exception that if an AE started during a Washout Period and was beyond 14 days from last dose date of preceding cycle, AE was considered as a "Washout Period" AE, and hence not TEAE. A TEAE was attributed to treatment in which it started or to the treatment in second cycling period of previous Crossover Period if it started during a Washout Period. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Data was to be reported by drug treatment for double-blind crossover period (Cycle 1 up to Washout Period 2) and open-label period.
arm group label: Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP)
arm group type: Experimental
description: During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.
arm group label: Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI)
arm group type: Experimental
description: During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.
arm group label: Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP)
arm group type: Experimental
description: During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.
arm group label: Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI)
arm group type: Experimental
description: During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.
intervention type: Drug
intervention name: Ivacaftor
description: 150 milligram (mg) tablet orally every 12 hours up to 12 weeks.
arm group label: Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP)
arm group label: Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI)
arm group label: Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP)
arm group label: Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI)
other name: Kalydeco, VX-770
intervention type: Drug
intervention name: Placebo-matched-to-ivacaftor tablet
description: Orally every 12 hours up to 4 weeks.
arm group label: Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP)
arm group label: Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI)
arm group label: Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP)
arm group label: Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI)
criteria: 
gender: All
minimum age: 12 Years
maximum age: N/A
healthy volunteers: No
last name: Jerry Nick, MD
role: Principal Investigator
affiliation: National Jewish Health
facility: 
country: United States
responsible party type: Sponsor
mesh term: Cystic Fibrosis
mesh term: Fibrosis
mesh term: Ivacaftor
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 