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    Clinical Trial Results:
    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

    Due to a system error, the data reported in v1 is not correct and has been removed from public view.
    Summary
    EudraCT number
    		 2012-000204-15
    Trial protocol
    		 GB  
    Global end of trial date
    18 Mar 2014

    Results information
    Results version number
    		 v2(current)
    This version publication date
    13 Jul 2016
    First version publication date
    07 Aug 2015
    Other versions
    		 v1 (removed from public view)
    Version creation reason
    • Correction of full data set
    Edit to address EudraCT bug related issues & also data errors

    Trial information

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    Trial identification
    Sponsor protocol code
    VX11-770-108
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01705145
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Vertex Pharmaceuticals Incorporated
    Sponsor organisation address
    50 Northern Avenue, Boston, MA, United States, 02210-1862
    Public contact
    Medical Monitor, Vertex Pharmaceuticals Incorporated, 1 617-341-6777, medicalinfo@vrtx.com
    Scientific contact
    Medical Monitor, Vertex Pharmaceuticals Incorporated, 1 617-341-6777, medicalinfo@vrtx.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-000335-PIP01-08
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    26 Jun 2014
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    18 Mar 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    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 subjects 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 subjects 2 through 5 years of age.
    Protection of trial subjects
    The study was conducted in accordance with the ethical principles stated in the Declaration of Helsinki and the International Conference on Harmonization (ICH) Guideline for Good Clinical Practice (GCP).
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    08 Jan 2013
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    Long term follow-up duration
    		 20 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 8
    Country: Number of subjects enrolled
    Canada: 3
    Country: Number of subjects enrolled
    United States: 24
    Worldwide total number of subjects
    35
    EEA total number of subjects
    8
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    35
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 For Part A: a total of 11 subjects were screened, of whom 9 subjects were enrolled. For Part B: a total of 37 subjects were screened, of whom 34 subjects were enrolled (eight of the 9 subjects who participated in Part A were enrolled in Part B).

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 Part A: Ivacaftor 50 mg
    Arm description
    		 Ivacaftor 50 milligram (mg) (for subjects weighing less than [<] 14 kilograms [kg]) every 12 hours (q12h) from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ivacaftor
    Investigational medicinal product code
    VX-770
    Other name
    Kalydeco
    Pharmaceutical forms
    Granules
    Routes of administration
    Oral use
    Dosage and administration details
    Ivacaftor 50 mg (for subjects weighing <14 kg) q12h from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study.

    Arm title
    		 Part A: Ivacaftor 75 mg
    Arm description
    		 Ivacaftor 75 mg (for subjects weighing >=14 kg) q12h from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ivacaftor
    Investigational medicinal product code
    VX-770
    Other name
    Kalydeco
    Pharmaceutical forms
    Granules
    Routes of administration
    Oral use
    Dosage and administration details
    Ivacaftor 75 mg (for subjects weighing >=14 kg) q12h from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study.

    Arm title
    		 Part B: Ivacaftor 50 mg
    Arm description
    		 Ivacaftor 50 mg (for subjects weighing <14 kg) q12h for 24 weeks during Part B of the study. Part B included subjects from Part A and newly enrolled subjects.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ivacaftor
    Investigational medicinal product code
    VX-770
    Other name
    Kalydeco
    Pharmaceutical forms
    Granules
    Routes of administration
    Oral use
    Dosage and administration details
    Ivacaftor 50 mg (for subjects weighing <14 kg) q12h for 24 weeks during Part B of the study. Part B included subjects from Part A and newly enrolled subjects.

    Arm title
    		 Part B: Ivacaftor 75 mg
    Arm description
    		 Ivacaftor 75 mg (for subjects weighing >=14 kg) q12h for 24 weeks during Part B of the study. Part B included subjects from Part A and newly enrolled subjects.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ivacaftor
    Investigational medicinal product code
    VX-770
    Other name
    Kalydeco
    Pharmaceutical forms
    Granules
    Routes of administration
    Oral use
    Dosage and administration details
    Ivacaftor 75 mg (fo subjects weighing >=14 kg) q12h for 24 weeks during Part B of the study. Part B included subjects from Part A and newly enrolled subjects.

    Number of subjects in period 1
    		Part A: Ivacaftor 50 mg Part A: Ivacaftor 75 mg Part B: Ivacaftor 50 mg Part B: Ivacaftor 75 mg
    Started
    4
    5
    10
    24
    Completed
    4
    5
    9
    24
    Not completed
    0
    0
    1
    0
         Adverse Event
    -
    -
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Part A: Ivacaftor 50 mg
    Reporting group description
    		 Ivacaftor 50 milligram (mg) (for subjects weighing less than [<] 14 kilograms [kg]) every 12 hours (q12h) from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study.

    Reporting group title
    Part A: Ivacaftor 75 mg
    Reporting group description
    		 Ivacaftor 75 mg (for subjects weighing >=14 kg) q12h from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study.

    Reporting group title
    Part B: Ivacaftor 50 mg
    Reporting group description
    		 Ivacaftor 50 mg (for subjects weighing <14 kg) q12h for 24 weeks during Part B of the study. Part B included subjects from Part A and newly enrolled subjects.

    Reporting group title
    Part B: Ivacaftor 75 mg
    Reporting group description
    		 Ivacaftor 75 mg (for subjects weighing >=14 kg) q12h for 24 weeks during Part B of the study. Part B included subjects from Part A and newly enrolled subjects.

    Reporting group values
    		 Part A: Ivacaftor 50 mg Part A: Ivacaftor 75 mg Part B: Ivacaftor 50 mg Part B: Ivacaftor 75 mg Total
    Number of subjects
    		 4 5 10 24 35
    Age categorical
    Units: Subjects
        Children (2-11 years)
    		 4 5 10 24 35
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 2.3 ( 0.5 ) 3.8 ( 1.1 ) 2.3 ( 0.48 ) 3.6 ( 0.82 ) -
    Gender categorical
    Units: Subjects
        Female
    		 2 1 4 2 7
        Male
    		 2 4 6 22 28

    End points

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    End points reporting groups
    Reporting group title
    Part A: Ivacaftor 50 mg
    Reporting group description
    		 Ivacaftor 50 milligram (mg) (for subjects weighing less than [<] 14 kilograms [kg]) every 12 hours (q12h) from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study.

    Reporting group title
    Part A: Ivacaftor 75 mg
    Reporting group description
    		 Ivacaftor 75 mg (for subjects weighing >=14 kg) q12h from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study.

    Reporting group title
    Part B: Ivacaftor 50 mg
    Reporting group description
    		 Ivacaftor 50 mg (for subjects weighing <14 kg) q12h for 24 weeks during Part B of the study. Part B included subjects from Part A and newly enrolled subjects.

    Reporting group title
    Part B: Ivacaftor 75 mg
    Reporting group description
    		 Ivacaftor 75 mg (for subjects weighing >=14 kg) q12h for 24 weeks during Part B of the study. Part B included subjects from Part A and newly enrolled subjects.

    Subject analysis set title
    Part B: Overall Ivacaftor
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Ivacaftor 50 mg (for subjects weighing <14 kg) or 75 mg (for subjects weighing >=14 kg) q12h for 24 weeks during Part B of the study. Part B included subjects from Part A and newly enrolled subjects.

    Subject analysis set title
    Part A: Overall Ivacaftor
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Ivacaftor 50 mg (for subjects weighing <14 kg) or 75 mg (for subjects weighing >=14 kg) q12h from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study.

    Primary: Part A: Number of subjects With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs

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    End point title
    		 Part A: Number of subjects With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs [1] [2]
    End point description
    AE: any adverse change from subject'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. Part A Safety set included all subjects who received at least 1 dose of study drug in part A.
    End point type
    Primary
    End point timeframe
    Part A: Up to 93 Days
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis was planned for this endpoint.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is not reporting the data for all arms because Part A and Part B endpoints are reported separately and hence, this endpoint includes only those arms which are applicable for the Part specified in endpoint title.
    End point values
    		 Part A: Ivacaftor 50 mg Part A: Ivacaftor 75 mg Part A: Overall Ivacaftor
    Number of subjects analysed
    4
    5
    9
    Units: subjects
    number (not applicable)
        AEs
    3
    5
    8
        SAEs
    0
    0
    0
        Related AEs
    1
    3
    4
    No statistical analyses for this end point

    Primary: Part B: Number of subjects With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs

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    End point title
    		 Part B: Number of subjects With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs [3] [4]
    End point description
    AE: any adverse change from subject'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. Part B Safety set included all subjects who received at least 1 dose of study drug in part B.
    End point type
    Primary
    End point timeframe
    Part B: Up to 28 Weeks
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis was planned for this endpoint.
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is not reporting the data for all arms because Part A and Part B endpoints are reported separately and hence, this endpoint includes only those arms which are applicable for the Part specified in endpoint title.
    End point values
    		 Part B: Ivacaftor 50 mg Part B: Ivacaftor 75 mg Part B: Overall Ivacaftor
    Number of subjects analysed
    10
    24
    34
    Units: subjects
    number (not applicable)
        AEs
    10
    23
    33
        SAEs
    3
    3
    6
        Related AEs
    3
    8
    11
    No statistical analyses for this end point

    Primary: Part A: Plasma Concentration of Ivacaftor and its Metabolites

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    End point title
    		 Part A: Plasma Concentration of Ivacaftor and its Metabolites [5]
    End point 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 subjects in the period. Part A Safety set included all subjects who received at least 1 dose of study drug in part A.
    End point type
    Primary
    End point timeframe
    Part A: up to 24 hours post-dose on Day 4
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis was planned for this endpoint.
    End point values
    		 Part A: Overall Ivacaftor
    Number of subjects analysed
    9
    Units: nanogram per milliliter (ng/mL)
    arithmetic mean (standard deviation)
        Ivacaftor: Hour 0 on Day 1
    0 ( 0 )
        Ivacaftor: Hour 0 on Day 4
    396 ( 337 )
        Ivacaftor: 2 Hours Post-Dose on Day 4
    726 ( 284 )
        Ivacaftor: 3 Hours Post-Dose on Day 4
    957 ( 283 )
        Ivacaftor: 6 Hours Post-Dose on Day 4
    542 ( 241 )
        Ivacaftor: 24 Hours Post-Dose on Day 4
    124 ( 149 )
        M1: Hour 0 on Day 1
    0 ( 0 )
        M1: Hour 0 on Day 4
    1240 ( 723 )
        M1: 2 Hours Post-Dose on Day 4
    1540 ( 578 )
        M1: 3 Hours Post-Dose on Day 4
    2310 ( 820 )
        M1: 6 Hours Post-Dose on Day 4
    1580 ( 622 )
        M1: 24 Hours Post-Dose on Day 4
    389 ( 336 )
        M6: Hour 0 on Day 1
    0 ( 0 )
        M6: Hour 0 on Day 4
    1150 ( 709 )
        M6: 2 Hours Post-Dose on Day 4
    1050 ( 606 )
        M6: 3 Hours Post-Dose on Day 4
    1300 ( 614 )
        M6: 6 Hours Post-Dose on Day 4
    1390 ( 532 )
        M6: 24 Hours Post-Dose on Day 4
    439 ( 355 )
    No statistical analyses for this end point

    Secondary: Part B: Plasma Concentration of Ivacaftor and its Metabolites

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    End point title
    		 Part B: Plasma Concentration of Ivacaftor and its Metabolites
    End point 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 subjects in the period. Part B Safety set included all subjects who received at least 1 dose of study drug in part B.
    End point type
    Secondary
    End point timeframe
    Part B: up to 24 hours post-dose on Day 168
    End point values
    		 Part B: Overall Ivacaftor
    Number of subjects analysed
    34
    Units: ng/mL
    arithmetic mean (standard deviation)
        Ivacaftor: Hour 0 on Day 1
    0 ( 0 )
        Ivacaftor: Hour 0 on Day 14
    614 ( 590 )
        Ivacaftor: 2 Hours Post-Dose on Day 14
    932 ( 541 )
        Ivacaftor: 3 Hours Post-Dose on Day 14
    1080 ( 587 )
        Ivacaftor: 6 Hours Post-Dose on Day 14
    1140 ( 627 )
        Ivacaftor: Hour 0 on Day 56
    448 ( 455 )
        Ivacaftor: 1 Hour Post-Dose on Day 56
    514 ( 421 )
        Ivacaftor: Hour 0 on Day 112
    596 ( 747 )
        Ivacaftor: 4 Hours Post-Dose on Day 112
    1080 ( 835 )
        Ivacaftor: 6 Hours Post-Dose on Day 112
    1010 ( 885 )
        Ivacaftor: Hour 0 on Day 168
    500 ( 545 )
        Ivacaftor: 24 Hours Post-Dose on Day 168
    207 ( 372 )
        M1: Hour 0 on Day 1
    0 ( 0 )
        M1: Hour 0 on Day 14
    1580 ( 1030 )
        M1: 2 Hours Post-Dose on Day 14
    1870 ( 924 )
        M1: 3 Hours Post-Dose on Day 14
    2280 ( 1140 )
        M1: 6 Hours Post-Dose on Day 14
    2670 ( 1080 )
        M1: Hour 0 on Day 56
    1340 ( 880 )
        M1: 1 Hour Post-Dose on Day 56
    1170 ( 698 )
        M1: Hour 0 on Day 112
    1680 ( 1360 )
        M1: 4 Hours Post-Dose on Day 112
    2450 ( 1510 )
        M1: 6 Hours Post-Dose on Day 112
    2500 ( 1520 )
        M1: Hour 0 on Day 168
    1460 ( 1200 )
        M1: 24 Hours Post-Dose on Day 168
    602 ( 647 )
        M6: Hour 0 on Day 1
    0 ( 0 )
        M6: Hour 0 on Day 14
    1520 ( 1130 )
        M6: 2 Hours Post-Dose on Day 14
    1430 ( 989 )
        M6: 3 Hours Post-Dose on Day 14
    1630 ( 1130 )
        M6: 6 Hours Post-Dose on Day 14
    2090 ( 1350 )
        M6: Hour 0 on Day 56
    1510 ( 1080 )
        M6: 1 Hour Post-Dose on Day 56
    1310 ( 974 )
        M6: Hour 0 on Day 112
    1660 ( 1130 )
        M6: 4 Hours Post-Dose on Day 112
    1810 ( 1230 )
        M6: 6 Hours Post-Dose on Day 112
    2130 ( 1380 )
        M6: Hour 0 on Day 168
    1520 ( 1130 )
        M6: 24 Hours Post-Dose on Day 168
    632 ( 465 )
    No statistical analyses for this end point

    Secondary: Part B: Absolute Change from Baseline in Sweat Chloride at Week 24

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    End point title
    		 Part B: Absolute Change from Baseline in Sweat Chloride at Week 24 [6]
    End point 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 subjects. Part B Safety set included all subjects who received at least 1 dose of study drug in part B. Number of subjects analyzed is for subjects who were evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Part B: Baseline, Week 24
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is not reporting the data for all arms because Part A and Part B endpoints are reported separately and hence, this endpoint includes only those arms which are applicable for the Part specified in endpoint title.
    End point values
    		 Part B: Ivacaftor 50 mg Part B: Ivacaftor 75 mg Part B: Overall Ivacaftor
    Number of subjects analysed
    7
    18
    25
    Units: millimole per liter (mmol/L)
        arithmetic mean (standard deviation)
    -47.07 ( 24.256 )
    -46.78 ( 27.584 )
    -46.86 ( 26.193 )
    No statistical analyses for this end point

    Secondary: Part B: Absolute Change from Baseline in Weight at Week 24

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    End point title
    		 Part B: Absolute Change from Baseline in Weight at Week 24 [7]
    End point description
    Data was reported as per the dose received and for overall subjects. Part B Safety set included all subjects who received at least 1 dose of study drug in part B. Number of subjects analyzed is for subjects who were evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Part B: Baseline, Week 24
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is not reporting the data for all arms because Part A and Part B endpoints are reported separately and hence, this endpoint includes only those arms which are applicable for the Part specified in endpoint title.
    End point values
    		 Part B: Ivacaftor 50 mg Part B: Ivacaftor 75 mg Part B: Overall Ivacaftor
    Number of subjects analysed
    9
    24
    33
    Units: kilograms (kg)
        arithmetic mean (standard deviation)
    1 ( 0.418 )
    1.5 ( 0.552 )
    1.36 ( 0.561 )
    No statistical analyses for this end point

    Secondary: Part B: Absolute Change from Baseline in Stature at Week 24

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    End point title
    		 Part B: Absolute Change from Baseline in Stature at Week 24 [8]
    End point 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 subjects. Part B Safety set included all subjects who received at least 1 dose of study drug in part B. Number of subjects analyzed is for subjects who were evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Part B: Baseline, Week 24
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is not reporting the data for all arms because Part A and Part B endpoints are reported separately and hence, this endpoint includes only those arms which are applicable for the Part specified in endpoint title.
    End point values
    		 Part B: Ivacaftor 50 mg Part B: Ivacaftor 75 mg Part B: Overall Ivacaftor
    Number of subjects analysed
    9
    23
    32
    Units: centimeters (cm)
        arithmetic mean (standard deviation)
    2.5 ( 1.45 )
    3.5 ( 0.93 )
    3.3 ( 1.17 )
    No statistical analyses for this end point

    Secondary: Part B: Absolute Change from Baseline in Body Mass Index (BMI) at Week 24

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    End point title
    		 Part B: Absolute Change from Baseline in Body Mass Index (BMI) at Week 24 [9]
    End point description
    BMI = (Weight [in kg]) divided by (Stature [in meters])^2. Data was reported as per the dose received and for overall subjects. Part B Safety set included all subjects who received at least 1 dose of study drug in part B. Number of subjects analyzed is for subjects who were evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is not reporting the data for all arms because Part A and Part B endpoints are reported separately and hence, this endpoint includes only those arms which are applicable for the Part specified in endpoint title.
    End point values
    		 Part B: Ivacaftor 50 mg Part B: Ivacaftor 75 mg Part B: Overall Ivacaftor
    Number of subjects analysed
    9
    23
    32
    Units: kilogram per square meter (kg/m^2)
        arithmetic mean (standard deviation)
    0.332 ( 0.5393 )
    0.314 ( 0.5492 )
    0.319 ( 0.5378 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Part A: up to 93 days; Part B: up to 28 weeks
    Adverse event reporting additional description
    Adverse events were reported separately for each part and as per the dose received and for overall subjects in each part.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    15.1
    Reporting groups
    Reporting group title
    Part A: Ivacaftor 50 mg
    Reporting group description
    		 Ivacaftor 50 mg (for subjects weighing <14 kg) q12h from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study.

    Reporting group title
    Part A: Ivacaftor 75 mg
    Reporting group description
    		 Ivacaftor 75 mg (for subjects weighing >=14 kg) q12h from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study.

    Reporting group title
    Part A: Overall Ivacaftor
    Reporting group description
    		 Ivacaftor 50 mg (for subjects weighing <14 kg) or 75 mg (for subjects weighing >=14 kg) q12h from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study.

    Reporting group title
    Part B: Ivacaftor 50 mg
    Reporting group description
    		 Ivacaftor 50 mg (for subjects weighing <14 kg) q12h for 24 weeks during Part B of the study. Part B included subjects from Part A and newly enrolled subjects.

    Reporting group title
    Part B: Ivacaftor 75 mg
    Reporting group description
    		 Ivacaftor 75 mg (for subjects weighing >=14 kg) q12h for 24 weeks during Part B of the study. Part B included subjects from Part A and newly enrolled subjects.

    Reporting group title
    Part B: Overall Ivacaftor
    Reporting group description
    		 Ivacaftor 50 mg (for subjects weighing <14 kg) or 75 mg (for subjects weighing >=14 kg) q12h for 24 weeks during Part B of the study. Part B included subjects from Part A and newly enrolled subjects.

    Serious adverse events
    		 Part A: Ivacaftor 50 mg Part A: Ivacaftor 75 mg Part A: Overall Ivacaftor Part B: Ivacaftor 50 mg Part B: Ivacaftor 75 mg Part B: Overall Ivacaftor
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    3 / 10 (30.00%)
    3 / 24 (12.50%)
    6 / 34 (17.65%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Investigations
    Pseudomonas test positive
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 24 (0.00%)
    1 / 34 (2.94%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transaminases increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 24 (0.00%)
    1 / 34 (2.94%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Convulsion
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Device related sepsis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 24 (0.00%)
    1 / 34 (2.94%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infective pulmonary exacerbation of cystic fibrosis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    1 / 24 (4.17%)
    2 / 34 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Part A: Ivacaftor 50 mg Part A: Ivacaftor 75 mg Part A: Overall Ivacaftor Part B: Ivacaftor 50 mg Part B: Ivacaftor 75 mg Part B: Overall Ivacaftor
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    3 / 4 (75.00%)
    5 / 5 (100.00%)
    8 / 9 (88.89%)
    9 / 10 (90.00%)
    23 / 24 (95.83%)
    32 / 34 (94.12%)
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    2 / 4 (50.00%)
    2 / 5 (40.00%)
    4 / 9 (44.44%)
    4 / 10 (40.00%)
    2 / 24 (8.33%)
    6 / 34 (17.65%)
         occurrences all number
    2
    2
    4
    5
    3
    8
    Application site rash
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Fatigue
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 24 (0.00%)
    0 / 34 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Product taste abnormal
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 24 (0.00%)
    0 / 34 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Rhinorrhoea
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 5 (40.00%)
    2 / 9 (22.22%)
    2 / 10 (20.00%)
    5 / 24 (20.83%)
    7 / 34 (20.59%)
         occurrences all number
    0
    2
    2
    2
    7
    9
    Cough
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    4 / 10 (40.00%)
    15 / 24 (62.50%)
    19 / 34 (55.88%)
         occurrences all number
    0
    1
    1
    8
    29
    37
    Upper respiratory tract congestion
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    1
    1
    0
    2
    2
    Nasal congestion
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    4 / 10 (40.00%)
    5 / 24 (20.83%)
    9 / 34 (26.47%)
         occurrences all number
    0
    0
    0
    6
    5
    11
    Productive cough
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    3 / 24 (12.50%)
    3 / 34 (8.82%)
         occurrences all number
    0
    0
    0
    0
    3
    3
    Dyspnoea exertional
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 24 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    Epistaxis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Nasal inflammation
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Oropharyngeal pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Snoring
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Tonsillar hypertrophy
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 24 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    1
    1
    0
    2
    2
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    1
    1
    0
    2
    2
    Pancreatic enzymes increased
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 24 (0.00%)
    0 / 34 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Bacterial test positive
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    3 / 24 (12.50%)
    3 / 34 (8.82%)
         occurrences all number
    0
    0
    0
    0
    3
    3
    Haemophilus test positive
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    3 / 24 (12.50%)
    3 / 34 (8.82%)
         occurrences all number
    0
    0
    0
    0
    4
    4
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    2 / 10 (20.00%)
    0 / 24 (0.00%)
    2 / 34 (5.88%)
         occurrences all number
    0
    0
    0
    4
    0
    4
    Activated partial thromboplastin time prolonged
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 24 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    Antibiotic resistant Staphylococcus test positive
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 24 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    Blood creatine increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Blood creatinine increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Liver function test abnormal
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Lymphocyte count increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    2
    2
    Respiratory rate increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 24 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    2
    0
    2
    Staphylococcus test positive
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    2
    2
    White blood cell count increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    2 / 24 (8.33%)
    2 / 34 (5.88%)
         occurrences all number
    0
    0
    0
    0
    2
    2
    Face injury
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Fall
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Mouth injury
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Open wound
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Traumatic haemorrhage
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Upper limb fracture
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    2 / 24 (8.33%)
    2 / 34 (5.88%)
         occurrences all number
    0
    1
    1
    0
    2
    2
    Drooling
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Sinus headache
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    2
    2
    Blood and lymphatic system disorders
    Lymphadenopathy
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 24 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    Eye disorders
    Amblyopia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Anisometropia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Eye inflammation
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 5 (40.00%)
    2 / 9 (22.22%)
    3 / 10 (30.00%)
    6 / 24 (25.00%)
    9 / 34 (26.47%)
         occurrences all number
    0
    2
    2
    3
    6
    9
    Abdominal distension
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    1 / 10 (10.00%)
    0 / 24 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    1
    1
    1
    0
    1
    Abdominal pain
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    1
    1
    0
    1
    1
    Constipation
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    4 / 24 (16.67%)
    4 / 34 (11.76%)
         occurrences all number
    0
    1
    1
    0
    4
    4
    Diarrhoea
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 24 (0.00%)
    0 / 34 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Eructation
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Lip blister
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Nausea
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Oral mucosal erythema
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Retching
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Teething
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 24 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    3
    0
    3
    Skin and subcutaneous tissue disorders
    Ecchymosis
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 5 (40.00%)
    2 / 9 (22.22%)
    0 / 10 (0.00%)
    0 / 24 (0.00%)
    0 / 34 (0.00%)
         occurrences all number
    0
    3
    3
    0
    0
    0
    Rash macular
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 24 (0.00%)
    0 / 34 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Rash
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    2 / 10 (20.00%)
    2 / 24 (8.33%)
    4 / 34 (11.76%)
         occurrences all number
    0
    0
    0
    2
    4
    6
    Acne
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Dermatitis contact
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 24 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    Petechiae
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Skin irritation
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 24 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    Urticaria
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 24 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    Renal and urinary disorders
    Chromaturia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 24 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    Pollakiuria
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Pain in extremity
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Infections and infestations
    Bronchitis viral
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 24 (0.00%)
    0 / 34 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    7 / 24 (29.17%)
    8 / 34 (23.53%)
         occurrences all number
    0
    0
    0
    1
    12
    13
    Croup infectious
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    2 / 10 (20.00%)
    1 / 24 (4.17%)
    3 / 34 (8.82%)
         occurrences all number
    0
    0
    0
    2
    1
    3
    Infective pulmonary exacerbation of cystic fibrosis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    3 / 24 (12.50%)
    3 / 34 (8.82%)
         occurrences all number
    0
    0
    0
    0
    4
    4
    Otitis media
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    2 / 10 (20.00%)
    1 / 24 (4.17%)
    3 / 34 (8.82%)
         occurrences all number
    0
    0
    0
    2
    1
    3
    Sinusitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    2 / 10 (20.00%)
    1 / 24 (4.17%)
    3 / 34 (8.82%)
         occurrences all number
    0
    0
    0
    2
    1
    3
    Gastroenteritis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    2 / 24 (8.33%)
    2 / 34 (5.88%)
         occurrences all number
    0
    0
    0
    0
    2
    2
    Rhinitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    2 / 24 (8.33%)
    2 / 34 (5.88%)
         occurrences all number
    0
    0
    0
    0
    2
    2
    Bacterial disease carrier
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Genital candidiasis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 24 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    Hand-foot-and-mouth disease
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Infectious mononucleosis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 24 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    Lung infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Nasopharyngitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Pharyngitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Pharyngitis streptococcal
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 24 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    2
    0
    2
    Respiratory tract infection viral
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Viral rash
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 24 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    1 / 24 (4.17%)
    2 / 34 (5.88%)
         occurrences all number
    0
    0
    0
    1
    1
    2
    Weight gain poor
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 24 (4.17%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    07 Aug 2012
    Changed inclusion criterion to allow subjects older than 5 years of age at entry in Part B to enter Part B from Part A. Added ophthalmologic examinations. Study design was modified to state that all subjects in Part B were to be enrolled in VX11-770-109 (Study 109). Modified secondary endpoints for analysis of PK parameters (remove duration of treatment) and of weight, stature, and BMI to be “through 24 weeks”.
    02 Nov 2012
    Changed required components of ophthalmologic examinations. Aligned requirement for all subjects who prematurely discontinue treatment in Part B to enroll in the observational arm of VX11-770-109 (Study 109). Aligned food requirement for study drug administration to more closely align with approved product labeling.
    09 Nov 2012
    The reference evaluation scale was changed to the Lens Opacities Classification System III (LOCS III) grading scale.
    08 May 2013
    Removed upper limit on the number of subjects in Part B. Added text to specify that the data monitoring committee (DMC), should be notified if a lens opacity or cataract is identified. Modified prohibited medications to restrict only moderate and strong inhibitors and inducers of cytochrome P4503A (CYP3A). Added urinalysis screening assessment to the Part B Schedule of Assessments.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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