<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/NCT01707290</url>
  </required_header>
  <id_info>
    <org_study_id>VX12-770-112</org_study_id>
    <secondary_id>2012-000389-39</secondary_id>
    <nct_id>NCT01707290</nct_id>
  </id_info>
  <brief_title>Rollover Study of Ivacaftor in Subjects With Cystic Fibrosis and a Non G551D CFTR Mutation</brief_title>
  <acronym>KONTINUE</acronym>
  <official_title>A Phase 3, Two-Arm, Rollover Study to Evaluate the Safety of Long Term Ivacaftor Treatment in Subjects 6 Years of Age and Older With Cystic Fibrosis and a Non-G551D CFTR Mutation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vertex Pharmaceuticals Incorporated</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Cystic Fibrosis Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Vertex Pharmaceuticals Incorporated</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the safety of long-term ivacaftor treatment in&#xD;
      participants with cystic fibrosis (CF) from Studies 110 (NCT01614457), 111 (NCT01614470), and&#xD;
      113 (NCT01685801).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Ivacaftor is the first Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulator&#xD;
      to show an improvement in CFTR function and clinical benefit in participants with CF. Results&#xD;
      from Phase 3 studies (NCT00909532 [Study 102] and NCT00909727 [Study 103]) showed that&#xD;
      ivacaftor is effective in the treatment of participants with CF who have the G551D-CFTR&#xD;
      mutation, as evidenced by sustained improvements in CFTR channel function (measured by&#xD;
      reduction in sweat chloride concentration) and corresponding substantial, durable&#xD;
      improvements in lung function, pulmonary exacerbations, respiratory symptoms, and weight&#xD;
      gain. Ivacaftor was also well tolerated, as evidenced by the rates and reasons for premature&#xD;
      discontinuation and results of safety assessments.&#xD;
&#xD;
      Ivacaftor (Trade Name Kalydeco; 150 mg tablets) was initially approved in the United States&#xD;
      for the treatment of CF in participants 6 years of age and older who have a G551D mutation in&#xD;
      the CFTR gene.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>February 2013</start_date>
  <completion_date type="Actual">April 2016</completion_date>
  <primary_completion_date type="Actual">April 2016</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Treatment Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) in Ivacaftor Arm</measure>
    <time_frame>Day 1 up to Week 108 (Study 112)</time_frame>
    <description>AE: any untoward medical occurrence in a participants during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after informed consent form is signed. AE includes serious as well as non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the 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. TEAEs were defined as adverse events with start date or increased severity on and after the first dose of study drug through Week 108.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Week 2, 12, 24, 36, 48, 60, 72, 84, 96, and 104</measure>
    <time_frame>Baseline, Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104 (Study 112)</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 6 to 17 years and for female participants aged 6 to 15 years. Baseline was defined as the most recent measurement before intake of the first dose of study drug (Ivacaftor) in Study 112. Results were planned to be reported for Ivacaftor arm and were stratified by parent study 110, 111 and 113.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute Change From Baseline in Body Mass Index (BMI) at Week 2,12, 24, 36, 48, 60, 72, 84, 96 and 104</measure>
    <time_frame>Baseline, Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104 (Study 112)</time_frame>
    <description>BMI was defined as weight in kg divided by height in m^2. Baseline was defined as the most recent measurement before intake of the first dose of study drug (Ivacaftor) in Study 112. Results were planned to be reported for Ivacaftor arm and were stratified by parent study 110, 111 and 113.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute Change From Baseline in Sweat Chloride at Week 2, 24, 48 and 104</measure>
    <time_frame>Baseline, Week 2, 24, 48 and 104 (Study 112)</time_frame>
    <description>Sweat samples were collected using an approved collection device. Baseline was defined as the most recent measurement before intake of the first dose of study drug (Ivacaftor) in Study 112. Results were planned to be reported for Ivacaftor arm and were stratified by parent study 110, 111 and 113.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute Change From Baseline in Respiratory Domain of the Cystic Fibrosis Questionnaire Revised (CFQ-R) at Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104</measure>
    <time_frame>Baseline, Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104 (Study 112)</time_frame>
    <description>The CFQ-R is a validated participant reported outcome measuring health related quality of life for participants with CF. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health related quality of life. Baseline was defined as the most recent measurement before intake of the first dose of study drug (ivacaftor) in Study 112. Results were planned to be reported for Ivacaftor arm and were stratified by parent study 110, 111 and 113.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Pulmonary Exacerbations Events</measure>
    <time_frame>Through Week 104 (Study 112)</time_frame>
    <description>Pulmonary exacerbation events include those events which require treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms. The number of events were reported. Results were planned to be reported for Ivacaftor arm and were stratified by parent study 110, 111 and 113.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Serious Adverse Events (SAEs) in Observational Arm</measure>
    <time_frame>up to 2 years (Study 112)</time_frame>
    <description>SAE was defined as a medical event or condition, which falls into any of the following categories, regardless of its relationship to the 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.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">125</enrollment>
  <condition>Cystic Fibrosis</condition>
  <arm_group>
    <arm_group_label>Ivacaftor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants who received Ivacaftor 150 milligram (mg) tablet and/or Placebo matched to Ivacaftor tablet orally, every 12 hours (q12h) in the previous study VX11-770-110 (Study 110; NCT01614457), VX12-770-111 (Study 111; NCT01614470) or VX12-770-113 (Study 113; NCT01685801); received Ivacaftor 150 mg tablet q12h in this VX12-770-112 (Study 112; NCT01707290) up to 104 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Observational</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet, orally, q12h in the previous Study 110 (NCT01614457) or Study 111 (NCT01614470), were observed (did not receive study drug) in this Study 112 (NCT01707290) for up to 2 years.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ivacaftor</intervention_name>
    <description>150 mg tablet, oral use, every 12 hours (q12h)</description>
    <arm_group_label>Ivacaftor</arm_group_label>
    <other_name>Kalydeco</other_name>
    <other_name>VX-770</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants from Study 110 or Study 111 entering the ivacaftor arm must have&#xD;
             completed the assigned study drug treatment duration in the previous study.&#xD;
&#xD;
          -  Participants from Study 113 entering the ivacaftor arm must have completed all study&#xD;
             related treatments through the Follow-up Visit and met the Study 113 responder&#xD;
             criteria during the previous study.&#xD;
&#xD;
          -  Participants entering the observational arm must have completed at least 4 weeks of&#xD;
             study drug treatment in their previous study (Study 110 or Study 111), must have&#xD;
             completed the previous study but do not wish to enroll in the ivacaftor arm, or must&#xD;
             have completed the previous study but do not meet the inclusion criteria of the&#xD;
             ivacaftor arm.&#xD;
&#xD;
          -  Participants of childbearing potential entering the ivacaftor arm must not be&#xD;
             pregnant.&#xD;
&#xD;
          -  Participants entering the ivacaftor arm must be willing to comply with contraception&#xD;
             requirements.&#xD;
&#xD;
        Exclusion Criteria (Ivacaftor Arm Only):&#xD;
&#xD;
          -  History of any illness or condition that might confound the results of the study or&#xD;
             pose an additional risk in administering ivacaftor to the Participant.&#xD;
&#xD;
          -  Use of moderate or strong inhibitors or inducers of cytochrome P450 (CYP) 3A.&#xD;
&#xD;
          -  Evidence of cataract or lens opacity at or before the Day 1 Visit.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joseph Pilewski, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pittsburgh</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Hartford</city>
        <state>Connecticut</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Grand Rapids</city>
        <state>Michigan</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>St. Louis</city>
        <state>Missouri</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>New York</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Syracuse</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Valhalla</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Fort Worth</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Morgantown</city>
        <state>West Virginia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Leuven</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Montpellier</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Belfast</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Edinburgh</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>France</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Ireland</country>
  </removed_countries>
  <verification_date>April 2017</verification_date>
  <study_first_submitted>October 9, 2012</study_first_submitted>
  <study_first_submitted_qc>October 15, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 16, 2012</study_first_posted>
  <results_first_submitted>April 3, 2017</results_first_submitted>
  <results_first_submitted_qc>April 3, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">May 12, 2017</results_first_posted>
  <last_update_submitted>April 3, 2017</last_update_submitted>
  <last_update_submitted_qc>April 3, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 12, 2017</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>
      <pre_assignment_details>The study consisted of 2 arms: Ivacaftor arm and Observational arm. The Ivacaftor arm enrolled subjects from Study VX11-770-110 (NCT01614457), Study VX12-770-111 (NCT01614470) and Study VX12-770-113 (NCT01685801). The Observational arm enrolled subjects from Study VX11-770-110 (NCT01614457) and Study VX12-770-111 (NCT01614470).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Ivacaftor Arm</title>
          <description>Participants who received Ivacaftor 150 milligram (mg) tablet and/or Placebo matched to Ivacaftor tablet, every 12 hours (q12h) in the previous study VX11-770-110 (Study 110; NCT01614457), VX12-770-111 (Study 111; NCT01614470) or VX12-770-113 (Study 113; NCT01685801); received Ivacaftor 150 mg tablet orally q12h in this VX12-770-112 (Study 112; NCT01707290) up to 104 weeks.</description>
        </group>
        <group group_id="P2">
          <title>Observational Arm</title>
          <description>Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet q12h in the previous Study 110 (NCT01614457) or Study 111 (NCT01614470), were observed (did not receive study drug) in this Study 112 (NCT01707290) for up to 2 years.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="121"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="35"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="86"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse event (AE)</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal of Consent (Not Due to AE)</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Commercial drug available</title>
              <participants_list>
                <participants group_id="P1" count="60"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other unspecified</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Ivacaftor Arm</title>
          <description>Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet, q12h in the previous study VX11-770-110 (Study 110; NCT01614457), VX12-770-111 (Study 111; NCT01614470) or VX12-770-113 (Study 113; NCT01685801); received Ivacaftor 150 mg tablet orally q12h in this VX12-770-112 (Study 112; NCT01707290) up to 104 weeks.</description>
        </group>
        <group group_id="B2">
          <title>Observational Arm</title>
          <description>Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet q12h in the previous Study 110 (NCT01614457) or Study 111 (NCT01614470), were observed (did not receive study drug) in this Study 112 (NCT01707290) for up to 2 years.</description>
        </group>
        <group group_id="B3">
          <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="121"/>
            <count group_id="B2" value="4"/>
            <count group_id="B3" value="125"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>6 to 11 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 to 17 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>18 years and over</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="89"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="91"/>
                  </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="61"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="64"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="60"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Treatment Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) in Ivacaftor Arm</title>
        <description>AE: any untoward medical occurrence in a participants during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after informed consent form is signed. AE includes serious as well as non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the 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. TEAEs were defined as adverse events with start date or increased severity on and after the first dose of study drug through Week 108.</description>
        <time_frame>Day 1 up to Week 108 (Study 112)</time_frame>
        <population>Safety Set included all participants who received at least 1 dose of study drug (Ivacaftor).</population>
        <group_list>
          <group group_id="O1">
            <title>Ivacaftor Arm</title>
            <description>Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet q12h in the previous study VX11-770-110 (Study 110; NCT01614457), VX12-770-111 (Study 111; NCT01614470) or VX12-770-113 (Study 113; NCT01685801); received Ivacaftor 150 mg tablet orally q12h in this VX12-770-112 (Study 112; NCT01707290) up to 104 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) in Ivacaftor Arm</title>
          <description>AE: any untoward medical occurrence in a participants during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after informed consent form is signed. AE includes serious as well as non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the 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. TEAEs were defined as adverse events with start date or increased severity on and after the first dose of study drug through Week 108.</description>
          <population>Safety Set included all participants who received at least 1 dose of study drug (Ivacaftor).</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="121"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Participants with TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="117"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with SAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Week 2, 12, 24, 36, 48, 60, 72, 84, 96, and 104</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 6 to 17 years and for female participants aged 6 to 15 years. Baseline was defined as the most recent measurement before intake of the first dose of study drug (Ivacaftor) in Study 112. Results were planned to be reported for Ivacaftor arm and were stratified by parent study 110, 111 and 113.</description>
        <time_frame>Baseline, Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104 (Study 112)</time_frame>
        <population>Full Analysis Set (FAS) included all participants who received at least 1 dose of study drug (Ivacaftor). Here, &quot;Number Analyzed&quot; signifies those participants who were evaluable for this measure at the specified time point for each arm, respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>Ivacaftor Arm: Study 110</title>
            <description>Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet orally, q12h in the previous Study 110; received Ivacaftor 150 mg tablet q12h in this Study 112 up to 104 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Ivacaftor Arm: Study 111</title>
            <description>Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet orally, q12h in the previous Study 111; received Ivacaftor 150 mg tablet q12h in this Study 112 up to 104 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Ivacaftor Arm: Study 113</title>
            <description>Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet orally, q12h in the previous Study 113; received Ivacaftor 150 mg tablet q12h in this Study 112 up to 104 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Week 2, 12, 24, 36, 48, 60, 72, 84, 96, and 104</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 6 to 17 years and for female participants aged 6 to 15 years. Baseline was defined as the most recent measurement before intake of the first dose of study drug (Ivacaftor) in Study 112. Results were planned to be reported for Ivacaftor arm and were stratified by parent study 110, 111 and 113.</description>
          <population>Full Analysis Set (FAS) included all participants who received at least 1 dose of study drug (Ivacaftor). Here, &quot;Number Analyzed&quot; signifies those participants who were evaluable for this measure at the specified time point for 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="65"/>
                <count group_id="O2" value="35"/>
                <count group_id="O3" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="65"/>
                    <count group_id="O2" value="35"/>
                    <count group_id="O3" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="71.8" spread="20.4"/>
                    <measurement group_id="O2" value="78.3" spread="21.1"/>
                    <measurement group_id="O3" value="62.8" spread="22.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="65"/>
                    <count group_id="O2" value="35"/>
                    <count group_id="O3" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.8" spread="8"/>
                    <measurement group_id="O2" value="4.4" spread="7.7"/>
                    <measurement group_id="O3" value="4" spread="7.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="63"/>
                    <count group_id="O2" value="33"/>
                    <count group_id="O3" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.4" spread="8.9"/>
                    <measurement group_id="O2" value="5.5" spread="8.3"/>
                    <measurement group_id="O3" value="4.9" spread="6.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="62"/>
                    <count group_id="O2" value="34"/>
                    <count group_id="O3" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.5" spread="8.4"/>
                    <measurement group_id="O2" value="7.1" spread="8.3"/>
                    <measurement group_id="O3" value="4.6" spread="8.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 36</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="60"/>
                    <count group_id="O2" value="29"/>
                    <count group_id="O3" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.4" spread="7.1"/>
                    <measurement group_id="O2" value="7.5" spread="8.2"/>
                    <measurement group_id="O3" value="4.9" spread="8.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 48</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="58"/>
                    <count group_id="O2" value="19"/>
                    <count group_id="O3" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.4" spread="7.5"/>
                    <measurement group_id="O2" value="6.4" spread="10.7"/>
                    <measurement group_id="O3" value="4.9" spread="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 60</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="58"/>
                    <count group_id="O2" value="16"/>
                    <count group_id="O3" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.5" spread="8.4"/>
                    <measurement group_id="O2" value="8.2" spread="8.3"/>
                    <measurement group_id="O3" value="4.5" spread="8.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 72</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="50"/>
                    <count group_id="O2" value="13"/>
                    <count group_id="O3" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.6" spread="8.9"/>
                    <measurement group_id="O2" value="7.8" spread="9.2"/>
                    <measurement group_id="O3" value="5.9" spread="9.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 84</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="40"/>
                    <count group_id="O2" value="11"/>
                    <count group_id="O3" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.4" spread="13.5"/>
                    <measurement group_id="O2" value="7.7" spread="7.6"/>
                    <measurement group_id="O3" value="4.8" spread="7.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 96</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="28"/>
                    <count group_id="O2" value="9"/>
                    <count group_id="O3" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.1" spread="14.6"/>
                    <measurement group_id="O2" value="9.9" spread="6.4"/>
                    <measurement group_id="O3" value="5.9" spread="8.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 104</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                    <count group_id="O2" value="9"/>
                    <count group_id="O3" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.6" spread="13.2"/>
                    <measurement group_id="O2" value="4.9" spread="5.8"/>
                    <measurement group_id="O3" value="6.3" spread="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Absolute Change From Baseline in Body Mass Index (BMI) at Week 2,12, 24, 36, 48, 60, 72, 84, 96 and 104</title>
        <description>BMI was defined as weight in kg divided by height in m^2. Baseline was defined as the most recent measurement before intake of the first dose of study drug (Ivacaftor) in Study 112. Results were planned to be reported for Ivacaftor arm and were stratified by parent study 110, 111 and 113.</description>
        <time_frame>Baseline, Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104 (Study 112)</time_frame>
        <population>FAS included all participants who received at least 1 dose of study drug (Ivacaftor). Here, &quot;Number analyzed&quot; signifies those participants who were evaluable for this measure at the specified time point for each arm, respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>Ivacaftor Arm: Study 110</title>
            <description>Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet orally, q12h in the previous Study 110; received Ivacaftor 150 mg tablet q12h in this Study 112 up to 104 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Ivacaftor Arm: Study 111</title>
            <description>Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet orally, q12h in the previous Study 111; received Ivacaftor 150 mg tablet q12h in this Study 112 up to 104 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Ivacaftor Arm: Study 113</title>
            <description>Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet orally, q12h in the previous Study 113; received Ivacaftor 150 mg tablet q12h in this Study 112 up to 104 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Absolute Change From Baseline in Body Mass Index (BMI) at Week 2,12, 24, 36, 48, 60, 72, 84, 96 and 104</title>
          <description>BMI was defined as weight in kg divided by height in m^2. Baseline was defined as the most recent measurement before intake of the first dose of study drug (Ivacaftor) in Study 112. Results were planned to be reported for Ivacaftor arm and were stratified by parent study 110, 111 and 113.</description>
          <population>FAS included all participants who received at least 1 dose of study drug (Ivacaftor). Here, &quot;Number analyzed&quot; signifies those participants who were evaluable for this measure at the specified time point for each arm, respectively.</population>
          <units>kilogram per square meter (kg/m^2)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="65"/>
                <count group_id="O2" value="35"/>
                <count group_id="O3" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="65"/>
                    <count group_id="O2" value="35"/>
                    <count group_id="O3" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.75" spread="5.63"/>
                    <measurement group_id="O2" value="23.15" spread="5.28"/>
                    <measurement group_id="O3" value="24.81" spread="5.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="65"/>
                    <count group_id="O2" value="35"/>
                    <count group_id="O3" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.06" spread="0.43"/>
                    <measurement group_id="O2" value="0.16" spread="0.47"/>
                    <measurement group_id="O3" value="0.07" spread="0.43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="64"/>
                    <count group_id="O2" value="35"/>
                    <count group_id="O3" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.32" spread="0.59"/>
                    <measurement group_id="O2" value="0.39" spread="0.62"/>
                    <measurement group_id="O3" value="0.22" spread="0.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="62"/>
                    <count group_id="O2" value="35"/>
                    <count group_id="O3" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.43" spread="0.92"/>
                    <measurement group_id="O2" value="0.65" spread="0.96"/>
                    <measurement group_id="O3" value="0.17" spread="0.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 36</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="60"/>
                    <count group_id="O2" value="29"/>
                    <count group_id="O3" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.62" spread="1.04"/>
                    <measurement group_id="O2" value="0.64" spread="1.07"/>
                    <measurement group_id="O3" value="0.02" spread="1.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 48</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="59"/>
                    <count group_id="O2" value="19"/>
                    <count group_id="O3" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.54" spread="1.39"/>
                    <measurement group_id="O2" value="0.58" spread="1.22"/>
                    <measurement group_id="O3" value="0.28" spread="1.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 60</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="58"/>
                    <count group_id="O2" value="16"/>
                    <count group_id="O3" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.72" spread="1.32"/>
                    <measurement group_id="O2" value="0.25" spread="1.09"/>
                    <measurement group_id="O3" value="0.38" spread="1.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 72</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="13"/>
                    <count group_id="O3" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.05" spread="1.73"/>
                    <measurement group_id="O2" value="0.45" spread="1.34"/>
                    <measurement group_id="O3" value="0.22" spread="1.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 84</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="40"/>
                    <count group_id="O2" value="11"/>
                    <count group_id="O3" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.72" spread="1.51"/>
                    <measurement group_id="O2" value="0.33" spread="1.42"/>
                    <measurement group_id="O3" value="0.23" spread="0.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 96</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="28"/>
                    <count group_id="O2" value="9"/>
                    <count group_id="O3" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.49" spread="1.44"/>
                    <measurement group_id="O2" value="0.1" spread="1.49"/>
                    <measurement group_id="O3" value="0.52" spread="1.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 104</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                    <count group_id="O2" value="9"/>
                    <count group_id="O3" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.42" spread="1.49"/>
                    <measurement group_id="O2" value="0.16" spread="1.37"/>
                    <measurement group_id="O3" value="0.88" spread="1.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Absolute Change From Baseline in Sweat Chloride at Week 2, 24, 48 and 104</title>
        <description>Sweat samples were collected using an approved collection device. Baseline was defined as the most recent measurement before intake of the first dose of study drug (Ivacaftor) in Study 112. Results were planned to be reported for Ivacaftor arm and were stratified by parent study 110, 111 and 113.</description>
        <time_frame>Baseline, Week 2, 24, 48 and 104 (Study 112)</time_frame>
        <population>FAS included all participants who received at least 1 dose of study drug (Ivacaftor). Here, &quot;Number of participants analyzed&quot; signifies those participants who were evaluable for this outcome and &quot;Number Analyzed&quot; signifies those participants who were evaluable for this measure at the specified time point for each arm respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>Ivacaftor Arm: Study 110</title>
            <description>Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet orally, q12h in the previous Study 110; received Ivacaftor 150 mg tablet q12h in this Study 112 up to 104 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Ivacaftor Arm: Study 111</title>
            <description>Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet orally, q12h in the previous Study 111; received Ivacaftor 150 mg tablet q12h in this Study 112 up to 104 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Ivacaftor Arm: Study 113</title>
            <description>Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet orally, q12h in the previous Study 113; received Ivacaftor 150 mg tablet q12h in this Study 112 up to 104 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Absolute Change From Baseline in Sweat Chloride at Week 2, 24, 48 and 104</title>
          <description>Sweat samples were collected using an approved collection device. Baseline was defined as the most recent measurement before intake of the first dose of study drug (Ivacaftor) in Study 112. Results were planned to be reported for Ivacaftor arm and were stratified by parent study 110, 111 and 113.</description>
          <population>FAS included all participants who received at least 1 dose of study drug (Ivacaftor). Here, &quot;Number of participants analyzed&quot; signifies those participants who were evaluable for this outcome and &quot;Number Analyzed&quot; signifies those participants who were evaluable for this measure at the specified time point for each arm respectively.</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="59"/>
                <count group_id="O2" value="33"/>
                <count group_id="O3" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="59"/>
                    <count group_id="O2" value="33"/>
                    <count group_id="O3" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="60.9" spread="19.4"/>
                    <measurement group_id="O2" value="80.2" spread="22.8"/>
                    <measurement group_id="O3" value="55.7" spread="22.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="59"/>
                    <count group_id="O2" value="31"/>
                    <count group_id="O3" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-19.3" spread="10.7"/>
                    <measurement group_id="O2" value="-38.4" spread="27.5"/>
                    <measurement group_id="O3" value="-4.5" spread="10.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="56"/>
                    <count group_id="O2" value="33"/>
                    <count group_id="O3" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-13" spread="18.4"/>
                    <measurement group_id="O2" value="-39.2" spread="27"/>
                    <measurement group_id="O3" value="1.1" spread="15.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 48</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="50"/>
                    <count group_id="O2" value="19"/>
                    <count group_id="O3" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-13.5" spread="16.2"/>
                    <measurement group_id="O2" value="-40.6" spread="26.1"/>
                    <measurement group_id="O3" value="-1.9" spread="17.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 104</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                    <count group_id="O2" value="9"/>
                    <count group_id="O3" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-13.7" spread="22.9"/>
                    <measurement group_id="O2" value="-32.9" spread="26.8"/>
                    <measurement group_id="O3" value="5.4" spread="18.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Absolute Change From Baseline in Respiratory Domain of the Cystic Fibrosis Questionnaire Revised (CFQ-R) at Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104</title>
        <description>The CFQ-R is a validated participant reported outcome measuring health related quality of life for participants with CF. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health related quality of life. Baseline was defined as the most recent measurement before intake of the first dose of study drug (ivacaftor) in Study 112. Results were planned to be reported for Ivacaftor arm and were stratified by parent study 110, 111 and 113.</description>
        <time_frame>Baseline, Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104 (Study 112)</time_frame>
        <population>FAS included all participants who received at least 1 dose of study drug (ivacaftor). Here, &quot;Number Analyzed&quot; signifies those participants who were evaluable for this measure at the specified time point for each arm respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>Ivacaftor Arm: Study 110</title>
            <description>Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet orally, q12h in the previous Study 110; received Ivacaftor 150 mg tablet q12h in this Study 112 up to 104 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Ivacaftor Arm: Study 111</title>
            <description>Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet orally, q12h in the previous Study 111; received Ivacaftor 150 mg tablet q12h in this Study 112 up to 104 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Ivacaftor Arm: Study 113</title>
            <description>Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet orally, q12h in the previous Study 113; received Ivacaftor 150 mg tablet q12h in this Study 112 up to 104 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Absolute Change From Baseline in Respiratory Domain of the Cystic Fibrosis Questionnaire Revised (CFQ-R) at Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104</title>
          <description>The CFQ-R is a validated participant reported outcome measuring health related quality of life for participants with CF. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health related quality of life. Baseline was defined as the most recent measurement before intake of the first dose of study drug (ivacaftor) in Study 112. Results were planned to be reported for Ivacaftor arm and were stratified by parent study 110, 111 and 113.</description>
          <population>FAS included all participants who received at least 1 dose of study drug (ivacaftor). Here, &quot;Number Analyzed&quot; signifies those participants who were evaluable for this measure at the specified time point for each arm respectively.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="65"/>
                <count group_id="O2" value="35"/>
                <count group_id="O3" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="65"/>
                    <count group_id="O2" value="35"/>
                    <count group_id="O3" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="68.6" spread="21.6"/>
                    <measurement group_id="O2" value="72.4" spread="20.3"/>
                    <measurement group_id="O3" value="65.9" spread="18.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="65"/>
                    <count group_id="O2" value="35"/>
                    <count group_id="O3" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.5" spread="17.9"/>
                    <measurement group_id="O2" value="4.5" spread="17.5"/>
                    <measurement group_id="O3" value="13.2" spread="16.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="64"/>
                    <count group_id="O2" value="35"/>
                    <count group_id="O3" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.6" spread="18"/>
                    <measurement group_id="O2" value="5.7" spread="18.5"/>
                    <measurement group_id="O3" value="13.5" spread="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="62"/>
                    <count group_id="O2" value="35"/>
                    <count group_id="O3" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.7" spread="19"/>
                    <measurement group_id="O2" value="3.4" spread="18.7"/>
                    <measurement group_id="O3" value="8.5" spread="14.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 36</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="60"/>
                    <count group_id="O2" value="29"/>
                    <count group_id="O3" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.1" spread="19.3"/>
                    <measurement group_id="O2" value="5.7" spread="13.8"/>
                    <measurement group_id="O3" value="7.9" spread="20.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 48</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="59"/>
                    <count group_id="O2" value="19"/>
                    <count group_id="O3" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.5" spread="17.6"/>
                    <measurement group_id="O2" value="4.4" spread="13.2"/>
                    <measurement group_id="O3" value="11.4" spread="15.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 60</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="57"/>
                    <count group_id="O2" value="15"/>
                    <count group_id="O3" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.1" spread="18.6"/>
                    <measurement group_id="O2" value="4.4" spread="10.9"/>
                    <measurement group_id="O3" value="8.6" spread="19.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 72</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="13"/>
                    <count group_id="O3" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.4" spread="22.2"/>
                    <measurement group_id="O2" value="5.6" spread="11.8"/>
                    <measurement group_id="O3" value="8.6" spread="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 84</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="40"/>
                    <count group_id="O2" value="11"/>
                    <count group_id="O3" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.5" spread="19.5"/>
                    <measurement group_id="O2" value="8.8" spread="14.1"/>
                    <measurement group_id="O3" value="4.9" spread="14.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 96</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="28"/>
                    <count group_id="O2" value="9"/>
                    <count group_id="O3" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.8" spread="21.1"/>
                    <measurement group_id="O2" value="0" spread="9.5"/>
                    <measurement group_id="O3" value="9.4" spread="14.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 104</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                    <count group_id="O2" value="9"/>
                    <count group_id="O3" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.2" spread="14"/>
                    <measurement group_id="O2" value="1.9" spread="8.8"/>
                    <measurement group_id="O3" value="19.9" spread="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Pulmonary Exacerbations Events</title>
        <description>Pulmonary exacerbation events include those events which require treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms. The number of events were reported. Results were planned to be reported for Ivacaftor arm and were stratified by parent study 110, 111 and 113.</description>
        <time_frame>Through Week 104 (Study 112)</time_frame>
        <population>FAS included all participants who received at least 1 dose of study drug (Ivacaftor).</population>
        <group_list>
          <group group_id="O1">
            <title>Ivacaftor Arm: Study 110</title>
            <description>Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet orally, q12h in the previous Study 110; received Ivacaftor 150 mg tablet q12h in this Study 112 up to 104 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Ivacaftor Arm: Study 111</title>
            <description>Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet orally, q12h in the previous Study 111; received Ivacaftor 150 mg tablet q12h in this Study 112 up to 104 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Ivacaftor Arm: Study 113</title>
            <description>Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet orally, q12h in the previous Study 113; received Ivacaftor 150 mg tablet q12h in this Study 112 up to 104 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Pulmonary Exacerbations Events</title>
          <description>Pulmonary exacerbation events include those events which require treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms. The number of events were reported. Results were planned to be reported for Ivacaftor arm and were stratified by parent study 110, 111 and 113.</description>
          <population>FAS included all participants who received at least 1 dose of study drug (Ivacaftor).</population>
          <units>pulmonary exacerbation events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="65"/>
                <count group_id="O2" value="35"/>
                <count group_id="O3" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47"/>
                    <measurement group_id="O2" value="30"/>
                    <measurement group_id="O3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Serious Adverse Events (SAEs) in Observational Arm</title>
        <description>SAE was defined as a medical event or condition, which falls into any of the following categories, regardless of its relationship to the 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.</description>
        <time_frame>up to 2 years (Study 112)</time_frame>
        <population>Analysis population included all participants who were included in the observational arm.</population>
        <group_list>
          <group group_id="O1">
            <title>Observational Arm</title>
            <description>Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet, orally, q12h in the previous Study 110 (NCT01614457) or Study 111 (NCT01614470), were observed (did not receive study drug) in this Study 112 (NCT01707290) for up to 2 years.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Serious Adverse Events (SAEs) in Observational Arm</title>
          <description>SAE was defined as a medical event or condition, which falls into any of the following categories, regardless of its relationship to the 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.</description>
          <population>Analysis population included all participants who were included in the observational arm.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Day 1 up to Week 108 for Ivacaftor arm; up to 2 years for Observational arm (Study 112)</time_frame>
      <desc>Non-SAEs were not collected for Observational arm. Only SAEs were planned to be collected for the Observational arm.</desc>
      <group_list>
        <group group_id="E1">
          <title>Ivacaftor Arm</title>
          <description>Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet q12h in the previous study VX11-770-110 (Study 110; NCT01614457), VX12-770-111 (Study 111; NCT01614470) or VX12-770-113 (Study 113; NCT01685801); received Ivacaftor 150 mg tablet orally q12h in this VX12-770-112 (Study 112; NCT01707290) up to 104 weeks.</description>
        </group>
        <group group_id="E2">
          <title>Observational Arm</title>
          <description>Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet q12h in the previous Study 110 (NCT01614457) or Study 111 (NCT01614470), were observed (did not receive study drug) in this Study 112 (NCT01707290) for up to 2 years.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 15.1</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="27" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiomyopathy acute</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Crohn's disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Pancreatitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
              </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="21" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Pharyngitis bacterial</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Gastroenteritis viral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Influenza A virus test positive</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal failure acute</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Haemoptysis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Angioedema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 15.1</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="117" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Iron deficiency anaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Middle ear effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Otorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Cushingoid</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blepharospasm</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Conjunctivitis allergic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Conjunctival haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Photophobia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Eye swelling</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Visual impairment</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Vitreous floaters</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Tooth impacted</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Abdominal discomfort</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Dental caries</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Steatorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Abdominal pain lower</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Barrett's oesophagus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Defaecation urgency</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Dental discomfort</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Frequent bowel movements</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Palatal disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Pancreatitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Proctitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Rectal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Rectal polyp</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Tooth loss</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Food poisoning</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Feeling of body temperature change</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Device leakage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Implant site rash</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Local swelling</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Vaccination site pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholelithiasis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Bile duct stone</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Seasonal allergy</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Allergy to arthropod bite</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </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="49" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Viral upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Gastroenteritis viral</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Oral candidiasis</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Acute sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Vulvovaginal mycotic infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Bacterial disease carrier</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection bacterial</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Pharyngitis streptococcal</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection viral</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection bacterial</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Tonsillitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Bronchopulmonary aspergillosis allergic</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Otitis externa</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Laryngitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Viral infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Pharyngitis bacterial</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Chronic sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Clostridium difficile colitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Croup infectious</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Diarrhoea infectious</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Folliculitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Ear lobe infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Haemophilus infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Furuncle</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Herpes zoster</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Infected dermal cyst</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Laryngitis viral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Molluscum contagiosum</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Myringitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Oral herpes</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Oesophagitis bacterial</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection bacterial</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Otitis media</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Staphylococcal skin infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Staphylococcal infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Tooth infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Tooth abscess</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Vaginitis bacterial</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Viral pharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Vulvovaginal candidiasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Nasal abscess</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Procedural pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Hand fracture</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Laceration</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Muscle strain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Arthropod sting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Arthropod bite</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Epicondylitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Concussion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Humerus fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Ligament rupture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Joint dislocation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Skeletal injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Snake bite</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Ligament sprain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Soft tissue injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Tooth fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Bacterial test positive</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Forced expiratory volume decreased</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>C-reactive protein increased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Haemophilus test positive</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Liver function test abnormal</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Atypical mycobacterium test positive</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Blood pressure increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Hepatic enzyme increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Body temperature increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Pseudomonas test positive</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Vitamin D decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Weight increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Blood calcium decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Blood urea increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Blood glucose increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Crystal urine present</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Electrocardiogram abnormal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Electrocardiogram QT prolonged</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Flavobacterium test positive</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Influenza A virus test positive</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Streptococcus test positive</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Klebsiella test positive</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Urinary sediment present</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Ultrasound biliary tract abnormal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Urine analysis abnormal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Vitamin A decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>White blood cells urine positive</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Pulmonary function test decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </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="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Vitamin D deficiency</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Diabetes mellitus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Dyslipidaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Fluid retention</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Impaired fasting glucose</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Increased appetite</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Vitamin A deficiency</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Type 2 diabetes mellitus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Osteopenia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Arthritis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Intervertebral disc protrusion</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Clubbing</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Joint swelling</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Monarthritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Metatarsalgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Pain in jaw</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Tendonitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Rotator cuff syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Skin papilloma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Seborrhoeic keratosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Thyroid neoplasm</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </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="9" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Migraine</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Burning sensation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Carpal tunnel syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Hypersomnia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Hyperaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Abnormal dreams</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Panic attack</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Tobacco abuse</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Drug dependence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Nephrolithiasis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Dysuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Amenorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Dysmenorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Breast pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Testicular torsion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Menorrhagia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Vulvovaginal discomfort</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Vulvovaginal pruritus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </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="41" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Sinus congestion</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Sputum increased</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Haemoptysis</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Respiratory tract congestion</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Wheezing</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Rales</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Paranasal sinus hypersecretion</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Pleuritic pain</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Respiration abnormal</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Nasal polyps</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Throat irritation</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Dysphonia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Nasal mucosal disorder</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Upper-airway cough syndrome</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Asthma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Dyspnoea exertional</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Increased viscosity of bronchial secretion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Lung hyperinflation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Nasal oedema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Nasal inflammation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Pleurisy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Painful respiration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Prolonged expiration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Respiratory tract irritation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Rhinitis allergic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Sinus polyp</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Throat tightness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Sneezing</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Sputum discoloured</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Eczema</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Dermatitis contact</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Rash erythematous</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Eczema nummular</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Ingrowing nail</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Night sweats</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Psoriasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Rash generalised</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Rosacea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Skin lesion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Rash pruritic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Subcutaneous nodule</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Acne</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hot flush</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Orthostatic hypotension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Pallor</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </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/NCT01707290
org study id: VX12-770-112
secondary id: 2012-000389-39
nct id: NCT01707290
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this study is to evaluate the safety of long-term ivacaftor treatment in
      participants with cystic fibrosis (CF) from Studies 110 (NCT01614457), 111 (NCT01614470), and
      113 (NCT01685801).
Ivacaftor is the first Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulator
      to show an improvement in CFTR function and clinical benefit in participants with CF. Results
      from Phase 3 studies (NCT00909532 [Study 102] and NCT00909727 [Study 103]) showed that
      ivacaftor is effective in the treatment of participants with CF who have the G551D-CFTR
      mutation, as evidenced by sustained improvements in CFTR channel function (measured by
      reduction in sweat chloride concentration) and corresponding substantial, durable
      improvements in lung function, pulmonary exacerbations, respiratory symptoms, and weight
      gain. Ivacaftor was also well tolerated, as evidenced by the rates and reasons for premature
      discontinuation and results of safety assessments.

      Ivacaftor (Trade Name Kalydeco; 150 mg tablets) was initially approved in the United States
      for the treatment of CF in participants 6 years of age and older who have a G551D mutation in
      the CFTR gene.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) in Ivacaftor Arm
time frame: Day 1 up to Week 108 (Study 112)
description: AE: any untoward medical occurrence in a participants during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after informed consent form is signed. AE includes serious as well as non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the 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. TEAEs were defined as adverse events with start date or increased severity on and after the first dose of study drug through Week 108.
measure: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Week 2, 12, 24, 36, 48, 60, 72, 84, 96, and 104
time frame: Baseline, Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104 (Study 112)
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 6 to 17 years and for female participants aged 6 to 15 years. Baseline was defined as the most recent measurement before intake of the first dose of study drug (Ivacaftor) in Study 112. Results were planned to be reported for Ivacaftor arm and were stratified by parent study 110, 111 and 113.
measure: Absolute Change From Baseline in Body Mass Index (BMI) at Week 2,12, 24, 36, 48, 60, 72, 84, 96 and 104
time frame: Baseline, Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104 (Study 112)
description: BMI was defined as weight in kg divided by height in m^2. Baseline was defined as the most recent measurement before intake of the first dose of study drug (Ivacaftor) in Study 112. Results were planned to be reported for Ivacaftor arm and were stratified by parent study 110, 111 and 113.
measure: Absolute Change From Baseline in Sweat Chloride at Week 2, 24, 48 and 104
time frame: Baseline, Week 2, 24, 48 and 104 (Study 112)
description: Sweat samples were collected using an approved collection device. Baseline was defined as the most recent measurement before intake of the first dose of study drug (Ivacaftor) in Study 112. Results were planned to be reported for Ivacaftor arm and were stratified by parent study 110, 111 and 113.
measure: Absolute Change From Baseline in Respiratory Domain of the Cystic Fibrosis Questionnaire Revised (CFQ-R) at Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104
time frame: Baseline, Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104 (Study 112)
description: The CFQ-R is a validated participant reported outcome measuring health related quality of life for participants with CF. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health related quality of life. Baseline was defined as the most recent measurement before intake of the first dose of study drug (ivacaftor) in Study 112. Results were planned to be reported for Ivacaftor arm and were stratified by parent study 110, 111 and 113.
measure: Number of Pulmonary Exacerbations Events
time frame: Through Week 104 (Study 112)
description: Pulmonary exacerbation events include those events which require treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms. The number of events were reported. Results were planned to be reported for Ivacaftor arm and were stratified by parent study 110, 111 and 113.
measure: Number of Participants With Serious Adverse Events (SAEs) in Observational Arm
time frame: up to 2 years (Study 112)
description: SAE was defined as a medical event or condition, which falls into any of the following categories, regardless of its relationship to the 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.
arm group label: Ivacaftor
arm group type: Experimental
description: Participants who received Ivacaftor 150 milligram (mg) tablet and/or Placebo matched to Ivacaftor tablet orally, every 12 hours (q12h) in the previous study VX11-770-110 (Study 110; NCT01614457), VX12-770-111 (Study 111; NCT01614470) or VX12-770-113 (Study 113; NCT01685801); received Ivacaftor 150 mg tablet q12h in this VX12-770-112 (Study 112; NCT01707290) up to 104 weeks.
arm group label: Observational
arm group type: No Intervention
description: Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet, orally, q12h in the previous Study 110 (NCT01614457) or Study 111 (NCT01614470), were observed (did not receive study drug) in this Study 112 (NCT01707290) for up to 2 years.
intervention type: Drug
intervention name: Ivacaftor
description: 150 mg tablet, oral use, every 12 hours (q12h)
arm group label: Ivacaftor
other name: Kalydeco
other name: VX-770
criteria: 
gender: All
minimum age: 6 Years
maximum age: N/A
healthy volunteers: No
last name: Joseph Pilewski, MD
role: Principal Investigator
affiliation: University of Pittsburgh
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country: Belgium
country: France
country: United Kingdom
country: United States
country: Ireland
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: 