<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/NCT01705145</url>
  </required_header>
  <id_info>
    <org_study_id>VX11-770-108</org_study_id>
    <secondary_id>KIWI</secondary_id>
    <nct_id>NCT01705145</nct_id>
  </id_info>
  <brief_title>Study of Ivacaftor in Cystic Fibrosis Subjects 2 Through 5 Years of Age With a CFTR Gating Mutation</brief_title>
  <official_title>A Phase 3, 2-Part, Open-Label Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of Ivacaftor in Subjects With Cystic Fibrosis Who Are 2 Through 5 Years of Age and Have a CFTR Gating 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>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the safety, pharmacokinetics (PK), and&#xD;
      pharmacodynamics (PD), of ivacaftor in children with cystic fibrosis (CF) who are 2 through 5&#xD;
      years of age and have a CF Transmembrane Conductance Regulator (CFTR) gating mutation in at&#xD;
      least 1 allele.&#xD;
&#xD;
      Part A is designed to evaluate the safety and PK of multiple-dose administration of ivacaftor&#xD;
      in participants 2 through 5 years of age and to confirm the doses for Part B. Part B is&#xD;
      designed to evaluate the safety, PK, PD, and efficacy of ivacaftor in participants 2 through&#xD;
      5 years of age.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>January 2013</start_date>
  <completion_date type="Actual">March 2014</completion_date>
  <primary_completion_date type="Actual">March 2014</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Part A: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs</measure>
    <time_frame>Part A: Up to 93 Days</time_frame>
    <description>AE: any adverse change from participant's baseline (pre-treatment) condition, including any adverse experience, abnormal recording/clinical laboratory assessment which occurs during course of study, whether it is considered related to study drug or not. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event.&#xD;
Related AEs includes all AEs for which the causality was either related to study drug or possibly related to study drug. Data was reported as per the dose received and for overall participants.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs</measure>
    <time_frame>Part B: Up to 28 Weeks</time_frame>
    <description>AE: any adverse change from participant's baseline (pre-treatment) condition, including any adverse experience, abnormal recording/clinical laboratory assessment which occurs during course of study, whether it is considered related to study drug or not. AE includes both serious and non-serious AE. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event.&#xD;
Related AEs includes all AEs for which the causality was either related to study drug or possibly related to study drug. Data was reported as per the dose received.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part A: Plasma Concentration of Ivacaftor and Its Metabolites</measure>
    <time_frame>Part A: up to 24 hours post-dose on Day 4</time_frame>
    <description>Plasma concentration was reported for ivacaftor and its metabolites (hydroxymethyl ivacaftor [M1] and ivacaftor carboxylate [M6]) up to 24 hours post-dose on Day 4 (Hour 0 [pre-dose] on Day 1 and Day 4; 2, 3, 6, 24 hours post-dose on Day 4). Data was planned to be reported for overall participants in the period.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Part B: Plasma Concentration of Ivacaftor and Its Metabolites</measure>
    <time_frame>Part B: up to 24 hours post-dose on Day 168</time_frame>
    <description>Plasma concentration was reported for ivacaftor and its metabolites (M1 and M6) up to 24 hours post-dose on Day 168 (Hour 0 [predose] on Day 1, 14, 56, 112, and 168; 2, 3, 6 hours post-dose on Day 14; 1 hour post-dose on Day 56; 4, 6 hours post-dose on Day 112; 24 hours post-dose on Day 168). Data was planned to be reported for overall participants in the period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Absolute Change From Baseline in Sweat Chloride at Week 24</measure>
    <time_frame>Part B: Baseline, Week 24</time_frame>
    <description>Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of greater than or equal to (&gt;=) 15 microliter was required for determination of sweat chloride. Data was reported as per the dose received and for overall participants.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Absolute Change From Baseline in Weight at Week 24</measure>
    <time_frame>Part B: Baseline, Week 24</time_frame>
    <description>Data was reported as per the dose received and for overall participants.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Absolute Change From Baseline in Stature at Week 24</measure>
    <time_frame>Part B: Baseline, Week 24</time_frame>
    <description>Stature was measured as height if children could stand unassisted and follow directions; otherwise, stature was measured as length. Data was reported as per the dose received and for overall participants.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24</measure>
    <time_frame>Baseline, Week 24</time_frame>
    <description>BMI = (Weight [in kg]) divided by (Stature [in meters])^2. Data was reported as per the dose received and for overall participants.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">35</enrollment>
  <condition>Cystic Fibrosis</condition>
  <arm_group>
    <arm_group_label>Ivacaftor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part A: Ivacaftor 50 milligram (mg) (for participants weighing less than [&lt;] 14 kilograms [kg]) or 75 mg (for participants weighing greater than or equal to [&gt;=] 14 kg) every 12 hours (q12h) from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study..&#xD;
Part B: Ivacaftor 50 mg (for participants weighing &lt;14 kg) or 75 mg (for participants weighing &gt;=14 kg) q12h for 24 weeks during Part B of the study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ivacaftor</intervention_name>
    <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;
          -  Male or female with confirmed diagnosis of CF&#xD;
&#xD;
          -  Must have a CFTR gating mutation in at least 1 allele&#xD;
&#xD;
          -  Aged 2 through 5 years at screening and Day 1&#xD;
&#xD;
          -  Weight &gt;= 8 kg at screening and Day 1&#xD;
&#xD;
          -  Hematology, serum chemistry, coagulation, and vital signs results at screening with no&#xD;
             clinically significant abnormalities that would interfere with the study assessments,&#xD;
             as judged by the investigator&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of any illness or condition that, in the opinion of the investigator, might&#xD;
             confound the results of the study or pose an additional risk in administering study&#xD;
             drug to the participant&#xD;
&#xD;
          -  An acute upper or lower respiratory infection, or pulmonary exacerbation, or changes&#xD;
             in therapy for pulmonary disease within 4 weeks before Day 1&#xD;
&#xD;
          -  Abnormal liver function, at screening&#xD;
&#xD;
          -  History of solid organ or hematological transplantation&#xD;
&#xD;
          -  Use of any moderate or strong inducers or inhibitors of cytochrome P450 (CYP) 3A&#xD;
             within 2 weeks before Day 1&#xD;
&#xD;
          -  Participation in a clinical study involving administration of either an&#xD;
             investigational or a marketed drug within 30 days or 5 terminal half-lives before&#xD;
             screening&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>5 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Margaret Rosenfeld, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Seattle Children's Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jane Davies, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Imperial College London</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Aurora</city>
        <state>Colorado</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>Indianapolis</city>
        <state>Indiana</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>Boston</city>
        <state>Massachusetts</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>Kansas City</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>Pittsburgh</city>
        <state>Pennsylvania</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>Charlottesville</city>
        <state>Virginia</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>Vancouver</city>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Edinburgh</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Liverpool</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2016</verification_date>
  <study_first_submitted>October 8, 2012</study_first_submitted>
  <study_first_submitted_qc>October 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 12, 2012</study_first_posted>
  <results_first_submitted>April 2, 2015</results_first_submitted>
  <results_first_submitted_qc>April 23, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">April 24, 2015</results_first_posted>
  <last_update_submitted>March 9, 2016</last_update_submitted>
  <last_update_submitted_qc>March 9, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 5, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cystic Fibrosis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cystic Fibrosis</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ivacaftor</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Ivacaftor</title>
          <description>Part A: Ivacaftor 50 milligram (mg) (for participants weighing less than [&lt;] 14 kilograms [kg]) or 75 mg (for participants weighing greater than or equal to [&gt;=] 14 kg) every 12 hours (q12h) from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study.&#xD;
Part B: Ivacaftor 50 mg (for participants weighing &lt;14 kg) or 75 mg (for participants weighing &gt;=14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Part A</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Part B</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="34">Eight participants from Part A continued in Part B of the study.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="33"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety set included all participants who received at least 1 dose of study drug.</population>
      <group_list>
        <group group_id="B1">
          <title>Ivacaftor</title>
          <description>Part A: Ivacaftor 50 mg (for participants weighing &lt;14 kg) or 75 mg (for participants weighing &gt;=14 kg) q12h from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study.&#xD;
Part B: Ivacaftor 50 mg (for participants weighing &lt;14 kg) or 75 mg (for participants weighing &gt;=14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="35"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <description>Data was planned to be reported separately for Part A and Part B of the study. Here &quot;n&quot; signifies participants who were evaluable for specified part of the study.</description>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <title>Part A (n = 9)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3.1" spread="1.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part B (n = 34)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3.2" spread="0.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex/Gender, Customized</title>
          <description>Data was planned to be reported separately for Part A and Part B of the study. Here &quot;n&quot; signifies participants who were evaluable for specified part of the study.</description>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Part A (n = 9): Female</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part A (n = 9): Male</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part B (n = 34): Female</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part B (n = 34): Male</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Part A: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs</title>
        <description>AE: any adverse change from participant's baseline (pre-treatment) condition, including any adverse experience, abnormal recording/clinical laboratory assessment which occurs during course of study, whether it is considered related to study drug or not. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event.&#xD;
Related AEs includes all AEs for which the causality was either related to study drug or possibly related to study drug. Data was reported as per the dose received and for overall participants.</description>
        <time_frame>Part A: Up to 93 Days</time_frame>
        <population>Part A Safety set included all participants who received at least 1 dose of study drug in part A.</population>
        <group_list>
          <group group_id="O1">
            <title>Part A: Ivacaftor 50 mg</title>
            <description>Ivacaftor 50 mg (for participants weighing &lt;14 kg) q12h from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study.</description>
          </group>
          <group group_id="O2">
            <title>Part A: Ivacaftor 75 mg</title>
            <description>Ivacaftor 75 mg (for participants weighing &gt;=14 kg) q12h from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study.</description>
          </group>
          <group group_id="O3">
            <title>Part A: Overall Ivacaftor</title>
            <description>Ivacaftor 50 mg (for participants weighing &lt;14 kg) or 75 mg (for participants weighing &gt;=14 kg) q12h from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Part A: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs</title>
          <description>AE: any adverse change from participant's baseline (pre-treatment) condition, including any adverse experience, abnormal recording/clinical laboratory assessment which occurs during course of study, whether it is considered related to study drug or not. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event.&#xD;
Related AEs includes all AEs for which the causality was either related to study drug or possibly related to study drug. Data was reported as per the dose received and for overall participants.</description>
          <population>Part A Safety set included all participants who received at least 1 dose of study drug in part A.</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 group_id="O2" value="5"/>
                <count group_id="O3" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="5"/>
                    <measurement group_id="O3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Related AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs</title>
        <description>AE: any adverse change from participant's baseline (pre-treatment) condition, including any adverse experience, abnormal recording/clinical laboratory assessment which occurs during course of study, whether it is considered related to study drug or not. AE includes both serious and non-serious AE. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event.&#xD;
Related AEs includes all AEs for which the causality was either related to study drug or possibly related to study drug. Data was reported as per the dose received.</description>
        <time_frame>Part B: Up to 28 Weeks</time_frame>
        <population>Part B Safety set included all participants who received at least 1 dose of study drug in part B.</population>
        <group_list>
          <group group_id="O1">
            <title>Part B: Ivacaftor 50 mg</title>
            <description>Ivacaftor 50 mg (for participants weighing &lt;14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.</description>
          </group>
          <group group_id="O2">
            <title>Part B: Ivacaftor 75 mg</title>
            <description>Ivacaftor 75 mg (for participants weighing &gt;=14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.</description>
          </group>
          <group group_id="O3">
            <title>Part B: Overall Ivacaftor</title>
            <description>Ivacaftor 50 mg (for participants weighing &lt;14 kg) or 75 mg (for participants weighing &gt;=14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.</description>
          </group>
        </group_list>
        <measure>
          <title>Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs</title>
          <description>AE: any adverse change from participant's baseline (pre-treatment) condition, including any adverse experience, abnormal recording/clinical laboratory assessment which occurs during course of study, whether it is considered related to study drug or not. AE includes both serious and non-serious AE. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event.&#xD;
Related AEs includes all AEs for which the causality was either related to study drug or possibly related to study drug. Data was reported as per the dose received.</description>
          <population>Part B Safety set included all participants who received at least 1 dose of study drug in part B.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="24"/>
                <count group_id="O3" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="23"/>
                    <measurement group_id="O3" value="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Related AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="8"/>
                    <measurement group_id="O3" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part B: Plasma Concentration of Ivacaftor and Its Metabolites</title>
        <description>Plasma concentration was reported for ivacaftor and its metabolites (M1 and M6) up to 24 hours post-dose on Day 168 (Hour 0 [predose] on Day 1, 14, 56, 112, and 168; 2, 3, 6 hours post-dose on Day 14; 1 hour post-dose on Day 56; 4, 6 hours post-dose on Day 112; 24 hours post-dose on Day 168). Data was planned to be reported for overall participants in the period.</description>
        <time_frame>Part B: up to 24 hours post-dose on Day 168</time_frame>
        <population>Part B Safety set included all participants who received at least 1 dose of study drug in part B.</population>
        <group_list>
          <group group_id="O1">
            <title>Part B: Overall Ivacaftor</title>
            <description>Ivacaftor 50 mg (for participants weighing &lt;14 kg) or 75 mg (for participants weighing &gt;=14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.</description>
          </group>
        </group_list>
        <measure>
          <title>Part B: Plasma Concentration of Ivacaftor and Its Metabolites</title>
          <description>Plasma concentration was reported for ivacaftor and its metabolites (M1 and M6) up to 24 hours post-dose on Day 168 (Hour 0 [predose] on Day 1, 14, 56, 112, and 168; 2, 3, 6 hours post-dose on Day 14; 1 hour post-dose on Day 56; 4, 6 hours post-dose on Day 112; 24 hours post-dose on Day 168). Data was planned to be reported for overall participants in the period.</description>
          <population>Part B Safety set included all participants who received at least 1 dose of study drug in part B.</population>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Ivacaftor: Hour 0 on Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" spread="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ivacaftor: Hour 0 on Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="614" spread="590"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ivacaftor: 2 Hours Post-Dose on Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="932" spread="541"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ivacaftor: 3 Hours Post-Dose on Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1080" spread="587"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ivacaftor: 6 Hours Post-Dose on Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1140" spread="627"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ivacaftor: Hour 0 on Day 56</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="448" spread="455"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ivacaftor: 1 Hour Post-Dose on Day 56</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="514" spread="421"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ivacaftor: Hour 0 on Day 112</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="596" spread="747"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ivacaftor: 4 Hours Post-Dose on Day 112</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1080" spread="835"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ivacaftor: 6 Hours Post-Dose on Day 112</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1010" spread="885"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ivacaftor: Hour 0 on Day 168</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="500" spread="545"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ivacaftor: 24 Hours Post-Dose on Day 168</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="207" spread="372"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M1: Hour 0 on Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" spread="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M1: Hour 0 on Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1580" spread="1030"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M1: 2 Hours Post-Dose on Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1870" spread="924"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M1: 3 Hours Post-Dose on Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2280" spread="1140"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M1: 6 Hours Post-Dose on Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2670" spread="1080"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M1: Hour 0 on Day 56</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1340" spread="880"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M1: 1 Hour Post-Dose on Day 56</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1170" spread="698"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M1: Hour 0 on Day 112</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1680" spread="1360"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M1: 4 Hours Post-Dose on Day 112</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2450" spread="1510"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M1: 6 Hours Post-Dose on Day 112</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2500" spread="1520"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M1: Hour 0 on Day 168</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1460" spread="1200"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M1: 24 Hours Post-Dose on Day 168</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="602" spread="647"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M6: Hour 0 on Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" spread="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M6: Hour 0 on Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1520" spread="1130"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M6: 2 Hours Post-Dose on Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1430" spread="989"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M6: 3 Hours Post-Dose on Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1630" spread="1130"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M6: 6 Hours Post-Dose on Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2090" spread="1350"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M6: Hour 0 on Day 56</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1510" spread="1080"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M6: 1 Hour Post-Dose on Day 56</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1310" spread="974"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M6: Hour 0 on Day 112</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1660" spread="1130"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M6: 4 Hours Post-Dose on Day 112</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1810" spread="1230"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M6: 6 Hours Post-Dose on Day 112</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2130" spread="1380"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M6: Hour 0 on Day 168</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1520" spread="1130"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M6: 24 Hours Post-Dose on Day 168</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="632" spread="465"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part B: Absolute Change From Baseline in Sweat Chloride at Week 24</title>
        <description>Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of greater than or equal to (&gt;=) 15 microliter was required for determination of sweat chloride. Data was reported as per the dose received and for overall participants.</description>
        <time_frame>Part B: Baseline, Week 24</time_frame>
        <population>Part B Safety set included all participants who received at least 1 dose of study drug in part B. Number of participants analyzed is for participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Part B: Ivacaftor 50 mg</title>
            <description>Ivacaftor 50 mg (for participants weighing &lt;14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.</description>
          </group>
          <group group_id="O2">
            <title>Part B: Ivacaftor 75 mg</title>
            <description>Ivacaftor 75 mg (for participants weighing &gt;=14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.</description>
          </group>
          <group group_id="O3">
            <title>Part B: Overall Ivacaftor</title>
            <description>Ivacaftor 50 mg (for participants weighing &lt;14 kg) or 75 mg (for participants weighing &gt;=14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.</description>
          </group>
        </group_list>
        <measure>
          <title>Part B: Absolute Change From Baseline in Sweat Chloride at Week 24</title>
          <description>Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of greater than or equal to (&gt;=) 15 microliter was required for determination of sweat chloride. Data was reported as per the dose received and for overall participants.</description>
          <population>Part B Safety set included all participants who received at least 1 dose of study drug in part B. Number of participants analyzed is for participants who were evaluable for this outcome measure.</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="7"/>
                <count group_id="O2" value="18"/>
                <count group_id="O3" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-47.07" spread="24.256"/>
                    <measurement group_id="O2" value="-46.78" spread="27.584"/>
                    <measurement group_id="O3" value="-46.86" spread="26.193"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part B: Absolute Change From Baseline in Weight at Week 24</title>
        <description>Data was reported as per the dose received and for overall participants.</description>
        <time_frame>Part B: Baseline, Week 24</time_frame>
        <population>Part B Safety set included all participants who received at least 1 dose of study drug in part B. Number of participants analyzed is for participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Part B: Ivacaftor 50 mg</title>
            <description>Ivacaftor 50 mg (for participants weighing &lt;14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.</description>
          </group>
          <group group_id="O2">
            <title>Part B: Ivacaftor 75 mg</title>
            <description>Ivacaftor 75 mg (for participants weighing &gt;=14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.</description>
          </group>
          <group group_id="O3">
            <title>Part B: Overall Ivacaftor</title>
            <description>Ivacaftor 50 mg (for participants weighing &lt;14 kg) or 75 mg (for participants weighing &gt;=14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.</description>
          </group>
        </group_list>
        <measure>
          <title>Part B: Absolute Change From Baseline in Weight at Week 24</title>
          <description>Data was reported as per the dose received and for overall participants.</description>
          <population>Part B Safety set included all participants who received at least 1 dose of study drug in part B. Number of participants analyzed is for participants who were evaluable for this outcome measure.</population>
          <units>kilograms (kg)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="24"/>
                <count group_id="O3" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.00" spread="0.418"/>
                    <measurement group_id="O2" value="1.50" spread="0.552"/>
                    <measurement group_id="O3" value="1.36" spread="0.561"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part B: Absolute Change From Baseline in Stature at Week 24</title>
        <description>Stature was measured as height if children could stand unassisted and follow directions; otherwise, stature was measured as length. Data was reported as per the dose received and for overall participants.</description>
        <time_frame>Part B: Baseline, Week 24</time_frame>
        <population>Part B Safety set included all participants who received at least 1 dose of study drug in part B. Number of participants analyzed is for participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Part B: Ivacaftor 50 mg</title>
            <description>Ivacaftor 50 mg (for participants weighing &lt;14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.</description>
          </group>
          <group group_id="O2">
            <title>Part B: Ivacaftor 75 mg</title>
            <description>Ivacaftor 75 mg (for participants weighing &gt;=14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.</description>
          </group>
          <group group_id="O3">
            <title>Part B: Overall Ivacaftor</title>
            <description>Ivacaftor 50 mg (for participants weighing &lt;14 kg) or 75 mg (for participants weighing &gt;=14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.</description>
          </group>
        </group_list>
        <measure>
          <title>Part B: Absolute Change From Baseline in Stature at Week 24</title>
          <description>Stature was measured as height if children could stand unassisted and follow directions; otherwise, stature was measured as length. Data was reported as per the dose received and for overall participants.</description>
          <population>Part B Safety set included all participants who received at least 1 dose of study drug in part B. Number of participants analyzed is for participants who were evaluable for this outcome measure.</population>
          <units>centimeters (cm)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="23"/>
                <count group_id="O3" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.5" spread="1.45"/>
                    <measurement group_id="O2" value="3.5" spread="0.93"/>
                    <measurement group_id="O3" value="3.3" spread="1.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Part A: Plasma Concentration of Ivacaftor and Its Metabolites</title>
        <description>Plasma concentration was reported for ivacaftor and its metabolites (hydroxymethyl ivacaftor [M1] and ivacaftor carboxylate [M6]) up to 24 hours post-dose on Day 4 (Hour 0 [pre-dose] on Day 1 and Day 4; 2, 3, 6, 24 hours post-dose on Day 4). Data was planned to be reported for overall participants in the period.</description>
        <time_frame>Part A: up to 24 hours post-dose on Day 4</time_frame>
        <population>Part A Safety set included all participants who received at least 1 dose of study drug in part A.</population>
        <group_list>
          <group group_id="O1">
            <title>Part A: Overall Ivacaftor</title>
            <description>Ivacaftor 50 mg (for participants weighing &lt;14 kg) or 75 mg (for participants weighing &gt;=14 kg) q12h from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Part A: Plasma Concentration of Ivacaftor and Its Metabolites</title>
          <description>Plasma concentration was reported for ivacaftor and its metabolites (hydroxymethyl ivacaftor [M1] and ivacaftor carboxylate [M6]) up to 24 hours post-dose on Day 4 (Hour 0 [pre-dose] on Day 1 and Day 4; 2, 3, 6, 24 hours post-dose on Day 4). Data was planned to be reported for overall participants in the period.</description>
          <population>Part A Safety set included all participants who received at least 1 dose of study drug in part A.</population>
          <units>nanogram per milliliter (ng/mL)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Ivacaftor: Hour 0 on Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" spread="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ivacaftor: Hour 0 on Day 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="396" spread="337"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ivacaftor: 2 Hours Post-Dose on Day 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="726" spread="284"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ivacaftor: 3 Hours Post-Dose on Day 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="957" spread="283"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ivacaftor: 6 Hours Post-Dose on Day 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="542" spread="241"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ivacaftor: 24 Hours Post-Dose on Day 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="124" spread="149"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M1: Hour 0 on Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" spread="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M1: Hour 0 on Day 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1240" spread="723"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M1: 2 Hours Post-Dose on Day 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1540" spread="578"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M1: 3 Hours Post-Dose on Day 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2310" spread="820"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M1: 6 Hours Post-Dose on Day 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1580" spread="622"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M1: 24 Hours Post-Dose on Day 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="389" spread="336"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M6: Hour 0 on Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" spread="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M6: Hour 0 on Day 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1150" spread="709"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M6: 2 Hours Post-Dose on Day 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1050" spread="606"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M6: 3 Hours Post-Dose on Day 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1300" spread="614"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M6: 6 Hours Post-Dose on Day 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1390" spread="532"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M6: 24 Hours Post-Dose on Day 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="439" spread="355"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24</title>
        <description>BMI = (Weight [in kg]) divided by (Stature [in meters])^2. Data was reported as per the dose received and for overall participants.</description>
        <time_frame>Baseline, Week 24</time_frame>
        <population>Part B Safety set included all participants who received at least 1 dose of study drug in part B. Number of participants analyzed is for participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Part B: Ivacaftor 50 mg</title>
            <description>Ivacaftor 50 mg (for participants weighing &lt;14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.</description>
          </group>
          <group group_id="O2">
            <title>Part B: Ivacaftor 75 mg</title>
            <description>Ivacaftor 75 mg (for participants weighing &gt;=14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.</description>
          </group>
          <group group_id="O3">
            <title>Part B: Overall Ivacaftor</title>
            <description>Ivacaftor 50 mg (for participants weighing &lt;14 kg) or 75 mg (for participants weighing &gt;=14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.</description>
          </group>
        </group_list>
        <measure>
          <title>Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24</title>
          <description>BMI = (Weight [in kg]) divided by (Stature [in meters])^2. Data was reported as per the dose received and for overall participants.</description>
          <population>Part B Safety set included all participants who received at least 1 dose of study drug in part B. Number of participants analyzed is for participants who were evaluable for this outcome measure.</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="9"/>
                <count group_id="O2" value="23"/>
                <count group_id="O3" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.332" spread="0.5393"/>
                    <measurement group_id="O2" value="0.314" spread="0.5492"/>
                    <measurement group_id="O3" value="0.319" spread="0.5378"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Part A: up to 93 days; Part B: up to 28 weeks</time_frame>
      <desc>Adverse events were reported separately for each part and as per the dose received and for overall participants in each part.</desc>
      <group_list>
        <group group_id="E1">
          <title>Part A: Ivacaftor 50 mg</title>
          <description>Ivacaftor 50 mg (for participants weighing &lt;14 kg) q12h from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study.</description>
        </group>
        <group group_id="E2">
          <title>Part A: Ivacaftor 75 mg</title>
          <description>Ivacaftor 75 mg (for participants weighing &gt;=14 kg) q12h from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study.</description>
        </group>
        <group group_id="E3">
          <title>Part A: Overall Ivacaftor</title>
          <description>Ivacaftor 50 mg (for participants weighing &lt;14 kg) or 75 mg (for participants weighing &gt;=14 kg) q12h from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study.</description>
        </group>
        <group group_id="E4">
          <title>Part B: Ivacaftor 50 mg</title>
          <description>Ivacaftor 50 mg (for participants weighing &lt;14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.</description>
        </group>
        <group group_id="E5">
          <title>Part B: Ivacaftor 75 mg</title>
          <description>Ivacaftor 75 mg (for participants weighing &gt;=14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.</description>
        </group>
        <group group_id="E6">
          <title>Part B: Overall Ivacaftor</title>
          <description>Ivacaftor 50 mg (for participants weighing &lt;14 kg) or 75 mg (for participants weighing &gt;=14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.</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="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="6" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title vocab="MedDRA (15.1)">Infective pulmonary exacerbation of cystic fibrosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Device related sepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title vocab="MedDRA (15.1)">Pseudomonas test positive</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Transaminases increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Convulsion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </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="3" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="9" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="23" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="32" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Lymphadenopathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title vocab="MedDRA (15.1)">Amblyopia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Anisometropia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Eye inflammation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="6" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="9" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="4" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Eructation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Lip blister</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Oral mucosal erythema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Retching</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Teething</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="6" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Application site rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Product taste abnormal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="7" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="8" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Croup infectious</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="3" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Infective pulmonary exacerbation of cystic fibrosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="3" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Otitis media</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="3" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="3" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Gastroentritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Bacterial disease carrier</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Genital candidiasis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Hand-foot-and-mouth disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Infectious mononucleosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Pharyngitis streptococcal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title vocab="MedDRA (15.1)">Respiratory tract infection viral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Viral rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Viral upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Bronchitis viral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Face injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Mouth injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Open wound</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Traumatic haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Upper limb fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title vocab="MedDRA (15.1)">Bacterial test positive</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="3" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Haemophilus test positive</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="3" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Hepatic enzyme increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Activated partial thromboplastin time prolonged</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Antibiotic resistant Staphylococcus test positive</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Blood creatine increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Liver function test abnormal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Lymphocyte count increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Respiratory rate increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Pancreatic enzyme increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Staphylococcus test positive</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>White blood cell count increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Weight gain poor</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Drooling</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Sinus headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Chromaturia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Pollakiuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title vocab="MedDRA (15.1)">Cough</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="15" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="19" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="9" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="7" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="3" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Dysponea exertional</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Nasal inflamation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Snoring</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Tonsillar hypertrophy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Upper respiratory track congestion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="4" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Acne</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Dermatitis contact</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Petechiae</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Skin irritation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Ecchymosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Rash macular</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="34"/>
              </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/NCT01705145
org study id: VX11-770-108
secondary id: KIWI
nct id: NCT01705145
lead sponsor: 
collaborator: 
has dmc: Yes
The purpose of this study is to evaluate the safety, pharmacokinetics (PK), and
      pharmacodynamics (PD), of ivacaftor in children with cystic fibrosis (CF) who are 2 through 5
      years of age and have a CF Transmembrane Conductance Regulator (CFTR) gating mutation in at
      least 1 allele.

      Part A is designed to evaluate the safety and PK of multiple-dose administration of ivacaftor
      in participants 2 through 5 years of age and to confirm the doses for Part B. Part B is
      designed to evaluate the safety, PK, PD, and efficacy of ivacaftor in participants 2 through
      5 years of age.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Part A: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs
time frame: Part A: Up to 93 Days
description: AE: any adverse change from participant's baseline (pre-treatment) condition, including any adverse experience, abnormal recording/clinical laboratory assessment which occurs during course of study, whether it is considered related to study drug or not. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event.
Related AEs includes all AEs for which the causality was either related to study drug or possibly related to study drug. Data was reported as per the dose received and for overall participants.
measure: Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs
time frame: Part B: Up to 28 Weeks
description: AE: any adverse change from participant's baseline (pre-treatment) condition, including any adverse experience, abnormal recording/clinical laboratory assessment which occurs during course of study, whether it is considered related to study drug or not. AE includes both serious and non-serious AE. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event.
Related AEs includes all AEs for which the causality was either related to study drug or possibly related to study drug. Data was reported as per the dose received.
measure: Part A: Plasma Concentration of Ivacaftor and Its Metabolites
time frame: Part A: up to 24 hours post-dose on Day 4
description: Plasma concentration was reported for ivacaftor and its metabolites (hydroxymethyl ivacaftor [M1] and ivacaftor carboxylate [M6]) up to 24 hours post-dose on Day 4 (Hour 0 [pre-dose] on Day 1 and Day 4; 2, 3, 6, 24 hours post-dose on Day 4). Data was planned to be reported for overall participants in the period.
measure: Part B: Plasma Concentration of Ivacaftor and Its Metabolites
time frame: Part B: up to 24 hours post-dose on Day 168
description: Plasma concentration was reported for ivacaftor and its metabolites (M1 and M6) up to 24 hours post-dose on Day 168 (Hour 0 [predose] on Day 1, 14, 56, 112, and 168; 2, 3, 6 hours post-dose on Day 14; 1 hour post-dose on Day 56; 4, 6 hours post-dose on Day 112; 24 hours post-dose on Day 168). Data was planned to be reported for overall participants in the period.
measure: Part B: Absolute Change From Baseline in Sweat Chloride at Week 24
time frame: Part B: Baseline, Week 24
description: Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of greater than or equal to (>=) 15 microliter was required for determination of sweat chloride. Data was reported as per the dose received and for overall participants.
measure: Part B: Absolute Change From Baseline in Weight at Week 24
time frame: Part B: Baseline, Week 24
description: Data was reported as per the dose received and for overall participants.
measure: Part B: Absolute Change From Baseline in Stature at Week 24
time frame: Part B: Baseline, Week 24
description: Stature was measured as height if children could stand unassisted and follow directions; otherwise, stature was measured as length. Data was reported as per the dose received and for overall participants.
measure: Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24
time frame: Baseline, Week 24
description: BMI = (Weight [in kg]) divided by (Stature [in meters])^2. Data was reported as per the dose received and for overall participants.
arm group label: Ivacaftor
arm group type: Experimental
description: Part A: Ivacaftor 50 milligram (mg) (for participants weighing less than [<] 14 kilograms [kg]) or 75 mg (for participants weighing greater than or equal to [>=] 14 kg) every 12 hours (q12h) from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study..
Part B: Ivacaftor 50 mg (for participants weighing <14 kg) or 75 mg (for participants weighing >=14 kg) q12h for 24 weeks during Part B of the study.
intervention type: Drug
intervention name: Ivacaftor
arm group label: Ivacaftor
other name: Kalydeco
other name: VX-770
criteria: 
gender: All
minimum age: 2 Years
maximum age: 5 Years
healthy volunteers: No
last name: Margaret Rosenfeld, MD
role: Principal Investigator
affiliation: Seattle Children's Hospital
last name: Jane Davies, MD
role: Principal Investigator
affiliation: Imperial College London
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country: Canada
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Cystic Fibrosis
mesh term: Fibrosis
mesh term: Ivacaftor
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