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    Clinical Trial Results:
    A Phase 3, 2-Part, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Pharmacokinetics, Efficacy and Safety of VX-770 in Subjects Aged 6 to 11 Years with Cystic Fibrosis and the G551D Mutation

    Due to a system error, the data reported in v1 is not correct and has been removed from public view.
    Summary
    EudraCT number
    2008-007479-26
    Trial protocol
    IE   GB   DE   FR  
    Global end of trial date
    28 Apr 2011

    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
    Address EudraCT system related issues through full data set Quality check and review prior to final release for publication

    Trial information

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    Trial identification
    Sponsor protocol code
    VX08-770-103
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT00909727
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Vertex Pharmaceuticals Incorporated
    Sponsor organisation address
    50 Northern Avenue, Boston, Massachusetts, United States, 02210-1862
    Public contact
    Medical Monitor, Vertex Pharmaceuticals Incorporated, +1 617-444-6777, medicalinfo@vrtx.com
    Scientific contact
    Medical Monitor, Vertex Pharmaceuticals Incorporated, +1 617-444-6777, 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
    03 Oct 2011
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Apr 2011
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Part A: To evaluate the pharmacokinetics (PK) of a single dose of orally-administered VX-770 treatment in subjects 6 to 11 years of age with cystic fibrosis (CF) who have the G551D-cystic fibrosis transmembrane conductance regulator protein (CFTR) mutation on at least 1 allele. Part B: To evaluate the efficacy of VX-770 after 24 weeks of treatment in subjects 6 to 11 years of age with CF who have the G551D CFTR mutation on at least 1 allele.
    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
    05 Aug 2009
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety
    Long term follow-up duration
    2 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 3
    Country: Number of subjects enrolled
    France: 4
    Country: Number of subjects enrolled
    Germany: 2
    Country: Number of subjects enrolled
    Ireland: 2
    Country: Number of subjects enrolled
    United States: 25
    Country: Number of subjects enrolled
    Canada: 2
    Country: Number of subjects enrolled
    Australia: 14
    Worldwide total number of subjects
    52
    EEA total number of subjects
    11
    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)
    48
    Adolescents (12-17 years)
    4
    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
    Part A started on 05 August 2009 (signing of first informed consent). Screening evaluations were completed during Day -28 to Day -2. All subjects completing Part A were offered the opportunity to participate in Part B, which started on 12 March 2010. Screening evaluations were completed during Day -35 to Day -15 before the first dose of study drug.

    Pre-assignment
    Screening details
    Nine subjects were dosed and included in Part A. In Part B, 52 subjects were enrolled and all were randomized to ivacaftor (26 subjects) or placebo (26 subjects). A 2-week run-in period was included to establish the baseline assessments on Day 1 after ensuring that subjects were properly taking their cystic fibrosis (CF) medication regimens.

    Period 1
    Period 1 title
    Overall study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Placebo
    Arm description
    Oral tablet every 12 hours (q12h) for up to 48 weeks.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Oral tablet q12h for up to 48 weeks.

    Arm title
    150 mg Ivacaftor q12h
    Arm description
    Oral tablet of 150 milligram (mg) of ivacaftor q12h for up to 48 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    Ivacaftor
    Investigational medicinal product code
    VX-770
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Oral tablet of 150 mg of ivacaftor q12h for up to 48 weeks.

    Number of subjects in period 1
    Placebo 150 mg Ivacaftor q12h
    Started
    26
    26
    Completed Treatment Period, Week 24
    23
    26
    Completed
    22
    26
    Not completed
    4
    0
         Prohibited Medication
    1
    -
         Withdrawal of Consent
    1
    -
         Adverse event
    1
    -
         Wrong Genotype
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Oral tablet every 12 hours (q12h) for up to 48 weeks.

    Reporting group title
    150 mg Ivacaftor q12h
    Reporting group description
    Oral tablet of 150 milligram (mg) of ivacaftor q12h for up to 48 weeks.

    Reporting group values
    Placebo 150 mg Ivacaftor q12h Total
    Number of subjects
    26 26 52
    Age categorical
    Units: Subjects
        6 to 8 Years
    13 12 25
        9 to 11 Years
    12 11 23
        > 11 Years
    1 3 4
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    8.9 ± 1.86 8.9 ± 2 -
    Gender categorical
    Units: Subjects
        Female
    10 17 27
        Male
    16 9 25
    Race/Ethnicity, Customized
    Units: Subjects
        Hispanic or Latino
    0 1 1
        Not Hispanic or Latino
    24 23 47
        Not Allowed to Ask Per Local Regulations
    2 2 4
    Region of Enrollment
    Units: Subjects
        North America
    15 12 27
        Europe
    5 6 11
        Australia
    6 8 14
    Percent Predicted Forced Expiratory Volume in 1 Second (FEV1)
    Percent predicted for age, gender, and height.
    Units: Subjects
        < 70%
    8 4 12
        ≥ 70% to ≤ 90%
    6 12 18
        > 90%
    12 10 22
    Percent Predicted Forced Expiratory Volume in 1 Second (FEV1)
    Percent predicted for age, gender, and height.
    Units: percentage
        arithmetic mean (standard deviation)
    83.7 ± 20.37 84.7 ± 15.83 -
    Weight
    Units: kilograms
        arithmetic mean (standard deviation)
    30 ± 7.16 31.8 ± 9.95 -
    Body Mass Index
    Units: kilograms per square meter
        arithmetic mean (standard deviation)
    16.8 ± 1.75 17.1 ± 2.61 -
    Sweat Chloride
    Units: millimoles per liter
        arithmetic mean (standard deviation)
    104.8 ± 8.87 104.3 ± 14.54 -

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Oral tablet every 12 hours (q12h) for up to 48 weeks.

    Reporting group title
    150 mg Ivacaftor q12h
    Reporting group description
    Oral tablet of 150 milligram (mg) of ivacaftor q12h for up to 48 weeks.

    Primary: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 24

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    End point title
    Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 24
    End point description
    Spirometry (as measured by FEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies. All randomized subjects who received at least 1 dose of study drug (ivacaftor or placebo)and had available assessments during the time frame.
    End point type
    Primary
    End point timeframe
    Baseline through 24 weeks
    End point values
    Placebo 150 mg Ivacaftor q12h
    Number of subjects analysed
    25
    26
    Units: percent of predicted volume (L)
        least squares mean (standard error)
    0.1 ± 2.1
    12.6 ± 2.1
    Statistical analysis title
    FEV1 Through Week 24
    Statistical analysis description
    Primary analysis for primary efficacy variable was based on MMRM. Model included absolute change from baseline in percent predicted FEV1 as dependent variable, treatment (ivacaftor versus placebo) and visit (Day 15, Week 8, Week 16, and Week 24) as fixed effects, and subject as a random effect, with adjustment for the continuous baseline value of percent predicted FEV1. Denominator degrees of freedom were estimated using the Kenward-Roger approximation. No imputation of missing data was done.
    Comparison groups
    Placebo v 150 mg Ivacaftor q12h
    Number of subjects included in analysis
    51
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [1]
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    12.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    6.6
         upper limit
    18.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.9
    Notes
    [1] - The primary endpoint and key secondary endpoints were tested in sequence. test 1: primary (α=0.05); test 2: using Hochberg's step-up procedure on weight (Wk 24) and sweat chloride (Wk 24)(α=0.05); test 3: CFQ-R respiratory domain score (Wk 24).

    Secondary: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 48

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    End point title
    Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 48
    End point description
    Spirometry (as measured by FEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies. All randomized subjects who received at least 1 dose of study drug (ivacaftor or placebo) and had available assessments during the time frame.
    End point type
    Secondary
    End point timeframe
    Baseline through 48 weeks
    End point values
    Placebo 150 mg Ivacaftor q12h
    Number of subjects analysed
    25
    26
    Units: percent of predicted volume (L)
        least squares mean (standard error)
    0.7 ± 2
    10.7 ± 1.9
    Statistical analysis title
    FEV1 Through Week 48
    Statistical analysis description
    Analysis for this variable was similar to that of the primary analysis of the primary efficacy endpoint, MMRM. Estimates were obtained from MMRM with dependent variable absolute change from baseline, fixed effects for categorical visit & treatment group, & adjustment for the continuous baseline value of percent predicted FEV1, using unstructured covariance matrix. Denominator degrees of freedom were estimated using the Kenward-Roger approximation. No imputation of missing data was done.
    Comparison groups
    Placebo v 150 mg Ivacaftor q12h
    Number of subjects included in analysis
    51
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0006 [2]
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    10
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    4.5
         upper limit
    15.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.7
    Notes
    [2] - There was no adjustment for multiple comparisons.

    Secondary: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Through Week 24 and Week 48 (Respiratory Domain Score, Children)

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    End point title
    Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Through Week 24 and Week 48 (Respiratory Domain Score, Children)
    End point description
    The CFQ-R is a health-related quality of life measure for subjects with cystic fibrosis. Each domain is scored from 0 (worst) to 100 (best). A difference of at least 4 points in the respiratory domain score of the CFQ-R is considered a minimal clinically important difference (MCID). All randomized subjects who received at least 1 dose of study drug (ivacaftor or placebo) and had available assessments during the time frame.
    End point type
    Secondary
    End point timeframe
    Baseline through 24 weeks and 48 weeks
    End point values
    Placebo 150 mg Ivacaftor q12h
    Number of subjects analysed
    25
    26
    Units: score on a scale
    least squares mean (standard error)
        Change from Baseline Through Week 24
    0.3 ± 2.6
    6.3 ± 2.5
        Change from Baseline Through Week 48
    1 ± 2.3
    6.1 ± 2.2
    Statistical analysis title
    CFQ-R Through Week 24
    Statistical analysis description
    Through Week 24: Analysis for this variable was similar to that of the primary analysis of the primary efficacy endpoint, a Mixed-Effects Model for Repeated Measures (MMRM), with the addition of the baseline domain score as a covariate.
    Comparison groups
    Placebo v 150 mg Ivacaftor q12h
    Number of subjects included in analysis
    51
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1092 [3]
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    6.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.4
         upper limit
    13.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.7
    Notes
    [3] - The primary endpoint and key secondary endpoints were tested in sequence. test 1: primary (α=0.05); test 2: using Hochberg's step-up procedure on weight (Wk 24) and sweat chloride (Wk 24)(α=0.05); test 3: CFQ-R respiratory domain score (Wk 24).
    Statistical analysis title
    CFQ-R Through Week 48
    Statistical analysis description
    Through Week 48: Analysis for this variable was similar to that of the primary analysis of the primary efficacy endpoint, a Mixed-Effects Model for Repeated Measures (MMRM), with the addition of the baseline domain score as a covariate.
    Comparison groups
    Placebo v 150 mg Ivacaftor q12h
    Number of subjects included in analysis
    51
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1354 [4]
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    5.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.6
         upper limit
    11.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.3
    Notes
    [4] - There was no adjustment for multiple comparisons.

    Secondary: Absolute Change From Baseline in Sweat Chloride Concentration Through Week 24 and Week 48

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    End point title
    Absolute Change From Baseline in Sweat Chloride Concentration Through Week 24 and Week 48
    End point description
    The sweat chloride (quantitative pilocarpine iontophoresis) test is a standard diagnostic tool for CF, serving as an indicator of cystic fibrosis transmembrane conductance regulator (CFTR) activity. All randomized subjects who received at least 1 dose of study drug (ivacaftor or placebo) and had available assessments during the time frame.
    End point type
    Secondary
    End point timeframe
    Baseline through 24 weeks and 48 weeks
    End point values
    Placebo 150 mg Ivacaftor q12h
    Number of subjects analysed
    23
    23
    Units: millimoles per liter
    least squares mean (standard error)
        Change from Baseline Through Week 24
    -1.2 ± 2.6
    -55.5 ± 2.6
        Change from Baseline Through Week 48
    -2.6 ± 2.6
    -56 ± 2.5
    Statistical analysis title
    Sweat Chloride Concentration Through Week 24
    Statistical analysis description
    Through Week 24: Analysis for this variable was similar to that of the primary analysis of the primary efficacy endpoint. Estimates were from Mixed-Effects Model for Repeated Measures (MMRM) with dependent variable absolute change from baseline, fixed effects for categorical visit and treatment group, and adjustment for continuous baseline value for sweat chloride and percent predicted forced expiratory volume in 1 second (FEV1), using unstructured covariance matrix.
    Comparison groups
    Placebo v 150 mg Ivacaftor q12h
    Number of subjects included in analysis
    46
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [5]
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -54.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -61.8
         upper limit
    -46.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.7
    Notes
    [5] - The primary endpoint and key secondary endpoints were tested in sequence. test 1: primary (α=0.05); test 2: using Hochberg's step-up procedure on weight (Wk 24) and sweat chloride (Wk 24)(α=0.05); test 3: CFQ-R respiratory domain score (Wk 24).
    Statistical analysis title
    Sweat Chloride Concentration Through Week 48
    Statistical analysis description
    Through Week 48: Analysis for this variable was similar to that of the primary analysis of the primary efficacy endpoint. Estimates were from Mixed-Effects Model for Repeated Measures (MMRM) with dependent variable absolute change from baseline, fixed effects for categorical visit and treatment group, and adjustment for continuous baseline value for sweat chloride and percent predicted forced expiratory volume in 1 second (FEV1), using unstructured covariance matrix.
    Comparison groups
    Placebo v 150 mg Ivacaftor q12h
    Number of subjects included in analysis
    46
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [6]
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -53.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -60.9
         upper limit
    -46
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.7
    Notes
    [6] - There was no adjustment for multiple comparisons.

    Secondary: Absolute Change From Baseline in Weight at Week 24 and Week 48

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    End point title
    Absolute Change From Baseline in Weight at Week 24 and Week 48
    End point description
    As malnutrition is common in subjects with CF because of increased energy expenditures due to lung disease and fat malabsorption, body weight is an important clinical measure of nutritional status. All randomized subjects who received at least 1 dose of study drug (ivacaftor or placebo) and had available assessments during the time frame.
    End point type
    Secondary
    End point timeframe
    Baseline to 24 weeks and 48 weeks
    End point values
    Placebo 150 mg Ivacaftor q12h
    Number of subjects analysed
    26
    26
    Units: kilograms
    least squares mean (standard error)
        At Week 24
    1.8 ± 0.4
    3.7 ± 0.4
        At Week 48
    3.1 ± 0.5
    5.9 ± 0.5
    Statistical analysis title
    Weight at Week 24
    Statistical analysis description
    At Week 24: Analysis for this variable was based on a Linear Mixed Effect (LME) model with dependent variable weight; treatment as a fixed effect; and intercept, visit, and treatment by visit interaction as random effects, with adjustment for baseline percent predicted forced expiratory volume in 1 second (FEV1) severity.
    Comparison groups
    Placebo v 150 mg Ivacaftor q12h
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0004 [7]
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    1.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.9
         upper limit
    2.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.5
    Notes
    [7] - The primary endpoint and key secondary endpoints were tested in sequence. test 1: primary (α=0.05); test 2: using Hochberg's step-up procedure on weight (Wk 24) and sweat chloride (Wk 24)(α=0.05); test 3: CFQ-R respiratory domain score (Wk 24).
    Statistical analysis title
    Weight at Week 48
    Statistical analysis description
    At Week 48: Analysis for this variable was based on a Linear Mixed Effect (LME) model with random intercept and random slope, treatment as a fixed effect, and visit (days on study) and treatment by visit interaction as random effects, with adjustment for categorical baseline percent predicted forced expiratory volume in 1 second (FEV1) severity.
    Comparison groups
    Placebo v 150 mg Ivacaftor q12h
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0002 [8]
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    2.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.3
         upper limit
    4.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.7
    Notes
    [8] - P-value is for the treatment effect at Week 48 (obtained as a linear contrast of treatment at Day 336). There was no adjustment for multiple comparisons.

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    For enrolled subjects, adverse events (AEs) were collected through the follow-up visit in each study part. For subjects who completed 48 weeks of treatment and enrolled in the open-label extension study, AEs were only collected through the Week 48 visit.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    12.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Oral tablet every 12 hours (q12h) for up to 48 weeks.

    Reporting group title
    150 mg Ivacaftor q12h
    Reporting group description
    Oral tablet of 150 mg of ivacaftor q12h for up to 48 weeks.

    Serious adverse events
    Placebo 150 mg Ivacaftor q12h
    Total subjects affected by serious adverse events
         subjects affected / exposed
    6 / 26 (23.08%)
    5 / 26 (19.23%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    Injury, poisoning and procedural complications
    Muscle strain
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary function test decreased
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Cystic fibrosis lung
         subjects affected / exposed
    3 / 26 (11.54%)
    2 / 26 (7.69%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Pseudomonas infection
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Productive cough
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung consolidation
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Adjustment disorder
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Affective disorder
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anxiety
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Conversion disorder
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    Placebo 150 mg Ivacaftor q12h
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    25 / 26 (96.15%)
    26 / 26 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Skin papilloma
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Immune system disorders
    Seasonal allergy
         subjects affected / exposed
    2 / 26 (7.69%)
    1 / 26 (3.85%)
         occurrences all number
    2
    1
    Allergy to animal
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    7 / 26 (26.92%)
    6 / 26 (23.08%)
         occurrences all number
    16
    6
    Fatigue
         subjects affected / exposed
    2 / 26 (7.69%)
    1 / 26 (3.85%)
         occurrences all number
    2
    1
    Malaise
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 26 (3.85%)
         occurrences all number
    1
    1
    Application site rash
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Chest pain
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Pain
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    Anger
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Anxiety
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Personality change
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Injury, poisoning and procedural complications
    Excoriation
         subjects affected / exposed
    2 / 26 (7.69%)
    1 / 26 (3.85%)
         occurrences all number
    3
    2
    Skin Laceration
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 26 (3.85%)
         occurrences all number
    1
    1
    Arthropod sting
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    2
    Contusion
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Foreign body in eye
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Joint Sprain
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Limb injury
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Lower limb fracture
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Medical device complication
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Post-traumatic pain
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Procedural pain
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Skeletal injury
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Sunburn
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Tooth fracture
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Wrong drug administered
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    3 / 26 (11.54%)
    2 / 26 (7.69%)
         occurrences all number
    6
    2
    Aspartate aminotransferase increased
         subjects affected / exposed
    2 / 26 (7.69%)
    3 / 26 (11.54%)
         occurrences all number
    3
    3
    Bacteria Sputum Identified
         subjects affected / exposed
    3 / 26 (11.54%)
    2 / 26 (7.69%)
         occurrences all number
    3
    2
    Eosinophil count increased
         subjects affected / exposed
    1 / 26 (3.85%)
    3 / 26 (11.54%)
         occurrences all number
    1
    5
    Culture throat positive
         subjects affected / exposed
    1 / 26 (3.85%)
    2 / 26 (7.69%)
         occurrences all number
    1
    2
    Breath sounds abnormal
         subjects affected / exposed
    2 / 26 (7.69%)
    0 / 26 (0.00%)
         occurrences all number
    3
    0
    Forced expiratory volume decreased
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    2
    Neutrophil count decreased
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    3
    White blood cell count decreased
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    3
    Activated partial thromboplastin time prolonged
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Blood pressure increased
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Chest X-ray abnormal
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Coagulation test abnormal
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Haematocrit increased
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    International normalised ratio increased
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Intraocular pressure increased
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Liver palpable subcostal
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Lymphocyte count increased
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Neutrophil count increased
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Neutrophil percentage decreased
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Platelet count decreased
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    2
    Prothrombin time prolonged
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Sputum abnormal
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Sputum culture positive
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Urine ketone body present
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Virus Serology Test Positive
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    White blood cell count increased
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    PULMONARY FUNCTION TEST DECREASED
         subjects affected / exposed
    3 / 26 (11.54%)
    2 / 26 (7.69%)
         occurrences all number
    4
    2
    Congenital, familial and genetic disorders
    Cystic fibrosis lung
         subjects affected / exposed
    6 / 26 (23.08%)
    7 / 26 (26.92%)
         occurrences all number
    8
    9
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    19 / 26 (73.08%)
    13 / 26 (50.00%)
         occurrences all number
    40
    21
    Oropharyngeal pain
         subjects affected / exposed
    4 / 26 (15.38%)
    7 / 26 (26.92%)
         occurrences all number
    9
    10
    Nasal congestion
         subjects affected / exposed
    4 / 26 (15.38%)
    5 / 26 (19.23%)
         occurrences all number
    7
    7
    Rhinorrhoea
         subjects affected / exposed
    4 / 26 (15.38%)
    3 / 26 (11.54%)
         occurrences all number
    8
    3
    Wheezing
         subjects affected / exposed
    4 / 26 (15.38%)
    3 / 26 (11.54%)
         occurrences all number
    4
    4
    Productive cough
         subjects affected / exposed
    4 / 26 (15.38%)
    2 / 26 (7.69%)
         occurrences all number
    5
    2
    Rales
         subjects affected / exposed
    4 / 26 (15.38%)
    2 / 26 (7.69%)
         occurrences all number
    5
    2
    Dysphonia
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 26 (3.85%)
         occurrences all number
    1
    1
    Epistaxis
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 26 (3.85%)
         occurrences all number
    1
    1
    Nasal inflammation
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 26 (3.85%)
         occurrences all number
    1
    1
    Pharyngeal erythema
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    2
    Respiratory tract congestion
         subjects affected / exposed
    2 / 26 (7.69%)
    0 / 26 (0.00%)
         occurrences all number
    3
    0
    Rhinitis allergic
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    2
    Asthma
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    2
    Asthma exercise induced
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Lung hyperinflation
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Nasal mucosal disorder
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Nasal ulcer
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    PostNasal Drip
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Prolonged expiration
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Rhonchi
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Sinus congestion
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Sneezing
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Throat irritation
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Tonsillar hypertrophy
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Tonsillar inflammation
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Blood and lymphatic system disorders
    Lymphadenopathy
         subjects affected / exposed
    2 / 26 (7.69%)
    1 / 26 (3.85%)
         occurrences all number
    2
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    4 / 26 (15.38%)
    7 / 26 (26.92%)
         occurrences all number
    8
    15
    Lethargy
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Eye disorders
    Astigmatism
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Conjunctivitis
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Hypermetropia
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 26 (3.85%)
         occurrences all number
    1
    2
    Tympanic membrane hyperaemia
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    5 / 26 (19.23%)
    6 / 26 (23.08%)
         occurrences all number
    5
    9
    Vomiting
         subjects affected / exposed
    7 / 26 (26.92%)
    2 / 26 (7.69%)
         occurrences all number
    11
    3
    Abdominal pain
         subjects affected / exposed
    3 / 26 (11.54%)
    3 / 26 (11.54%)
         occurrences all number
    5
    4
    Constipation
         subjects affected / exposed
    2 / 26 (7.69%)
    2 / 26 (7.69%)
         occurrences all number
    2
    2
    Diarrhoea
         subjects affected / exposed
    0 / 26 (0.00%)
    3 / 26 (11.54%)
         occurrences all number
    0
    3
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    2
    Nausea
         subjects affected / exposed
    2 / 26 (7.69%)
    0 / 26 (0.00%)
         occurrences all number
    2
    0
    Abdominal discomfort
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Dysphagia
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Eosinophilic oesophagitis
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Gingival bleeding
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Lip blister
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Loose tooth
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Post-tussive vomiting
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Steatorrhoea
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Tooth disorder
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    3 / 26 (11.54%)
    2 / 26 (7.69%)
         occurrences all number
    3
    3
    Dermatitis contact
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    2
    0
    Drug eruption
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Ecchymosis
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Nail discolouration
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Onychoclasis
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Pruritus
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Rash maculo-papular
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Rash vesicular
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Swelling face
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Urticaria
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 26 (3.85%)
         occurrences all number
    1
    1
    Myalgia
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    4
    Neck pain
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    2
    Pain in extremity
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 26 (3.85%)
         occurrences all number
    1
    1
    Joint swelling
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Muscle spasms
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal pain
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal stiffness
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Diabetes mellitus
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Weight gain poor
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    2 / 26 (7.69%)
    6 / 26 (23.08%)
         occurrences all number
    3
    8
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 26 (7.69%)
    6 / 26 (23.08%)
         occurrences all number
    2
    9
    Bronchitis
         subjects affected / exposed
    2 / 26 (7.69%)
    3 / 26 (11.54%)
         occurrences all number
    2
    4
    Otitis media
         subjects affected / exposed
    1 / 26 (3.85%)
    4 / 26 (15.38%)
         occurrences all number
    2
    7
    Sinusitis
         subjects affected / exposed
    3 / 26 (11.54%)
    2 / 26 (7.69%)
         occurrences all number
    4
    3
    Ear infection
         subjects affected / exposed
    2 / 26 (7.69%)
    0 / 26 (0.00%)
         occurrences all number
    2
    0
    Pharyngitis streptococcal
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    2
    Rhinitis
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    3
    Bacterial disease carrier
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Bronchopulmonary aspergillosis allergic
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Coxsackie viral infection
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Eye infection
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Febrile infection
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Gastroenteritis
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Laryngitis
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Molluscum contagiosum
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Oral candidiasis
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Otitis externa
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Pharyngitis
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Pseudomonas Infection
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Respiratory tract infection
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Respiratory tract infection viral
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Sinobronchitis
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    2
    Urinary tract infection
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    24 Apr 2009
    Added a 24-week Extension Period in Part B for a total treatment duration of 48 weeks to obtain further safety data of VX-770. Changed the Part B secondary objective to evaluate the safety of VX-770 after both 24 weeks (original objective) and 48 weeks (newly added) of treatment. Added a Part B secondary objective “To evaluate the efficacy of VX-770 after 48 weeks of treatment in subjects 6 to 11 years of age with CF who have the G551DCFTR mutation on at least 1 allele”. Added a Part B secondary efficacy endpoint of “Absolute change from baseline in percent predicted FEV1 through Week 48”. Added the analysis of Part B secondary and tertiary efficacy endpoints at Week 48. Added the option for subjects who complete 48 weeks of treatment in Part B to enroll in an open-label safety study of VX-770. Removed exclusion criterion regarding change in antibiotic therapy for pulmonary exacerbation in Part B.
    31 Aug 2009
    Increased the upper limit of eligible FEV1 to 105 percent (%) predicted value. Allowed the scheduling of the Day -14 Visit after a subject without verification of the screening clinical laboratory and ECG results to accommodate those subjects who wish to undergo screening on Day -15 and enter the Run-in Period the next day (Day -14). Updated study restrictions, the emergency unblinding process, and clarified the criteria for withdrawal of subjects from the study.
    05 Feb 2010
    Based on preliminary results from Part A, changed the dose to be administered from 100 mg to 150 mg in Part B. Updated the description of the number of Part B subjects in the Overall Study Design and Plan to indicate that “at least 20 of the 30 subjects with less than equal to (<=) 90% predicted FEV1” will be included in Part B.
    12 Apr 2010
    Changes in study procedures regarding liver function testing and considerations for study drug interruption and discontinuation to ensure the continued safety of subjects in this study. A PK sample collection was added to the Early Termination Visit to assess any potential association between study drug exposure and the reason for discontinuation.
    09 Jul 2010
    FEV1 value to be used to stratify randomization in Part B was inadvertently changed from the Screening Visit to the Day -14 Visit to align the stratification on a visit common to all subjects participating in Part B. Changed the definition of treatment emergent adverse events (TEAEs) for clarity and consistency with the adverse event definition.
    13 Nov 2010
    Changed the secondary endpoint “Rate of change in weight through Weeks 24 and 48” to “Change from baseline in weight at Weeks 24 and 48”.

    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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