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    Clinical Trial Results:
    A Phase 3, Two-Part, Randomized, Double-Blind, Placebo-Controlled, Crossover Study With an Open-Label Period to Evaluate the Efficacy and Safety of Ivacaftor in Subjects With Cystic Fibrosis Who Have a Non-G551D CFTR Gating Mutation

    Summary
    EudraCT number
    		 2012-000388-26
    Trial protocol
    		 BE  
    Global end of trial date
    14 Oct 2013

    Results information
    Results version number
    		 v1(current)
    This version publication date
    28 Jun 2016
    First version publication date
    07 Aug 2015
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    VX12-770-111
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01614470
    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 877634 8789, medicalinfo@vrtx.com
    Scientific contact
    Medical Monitor, Vertex Pharmaceuticals Incorporated, 1 877634 8789, 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
    02 Dec 2013
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    14 Oct 2013
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the efficacy of ivacaftor in subjects with cystic fibrosis (CF) who have a non-G551D CF transmembrane conductance regulator (CFTR) gating mutation.
    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
    11 Jul 2012
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    France: 8
    Country: Number of subjects enrolled
    Belgium: 9
    Country: Number of subjects enrolled
    United States: 22
    Worldwide total number of subjects
    39
    EEA total number of subjects
    17
    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)
    8
    Adolescents (12-17 years)
    11
    Adults (18-64 years)
    20
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 The study included a Screening Period (Day -35 to Day -15 relative to the first dose of study drug). A total of 42 subjects were screened, of which 39 subjects were randomized.

    Period 1
    Period 1 title
    Part 1: Treatment Period 1 (8 Weeks)
    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
    		 Sequence 1: Ivacaftor First, Then Placebo
    Arm description
    		 Ivacaftor 150 milligram (mg) tablet orally twice daily for 8 weeks in treatment period 1 followed by placebo matched to ivacaftor tablet orally twice daily for 8 weeks in treatment period 2. Washout out period of 4 to 8 weeks was maintained between each treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ivacaftor
    Investigational medicinal product code
    VX-770
    Other name
    Kalydeco
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ivacaftor 150 mg tablet orally twice daily for 8 weeks.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo matched to ivacaftor tablet orally twice daily for 8 weeks.

    Arm title
    		 Sequence 2: Placebo First, Then Ivacaftor
    Arm description
    		 Placebo matched to ivacaftor tablet orally twice daily for 8 weeks in treatment period 1 followed by ivacaftor 150 mg tablet orally twice daily for 8 weeks in treatment period 2. Washout out period of 4 to 8 weeks was maintained between each treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo matched to ivacaftor tablet orally twice daily for 8 weeks.

    Investigational medicinal product name
    Ivacaftor
    Investigational medicinal product code
    VX-770
    Other name
    Kalydeco
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ivacaftor 150 mg tablet orally twice daily for 8 weeks.

    Number of subjects in period 1
    		Sequence 1: Ivacaftor First, Then Placebo Sequence 2: Placebo First, Then Ivacaftor
    Started
    20
    19
    Completed
    18
    18
    Not completed
    2
    1
         Lost to follow-up
    1
    -
         Need to extend washout period
    1
    1
    Period 2
    Period 2 title
    Part 1: Treatment Period 2 (8 Weeks)
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Sequence 1: Ivacaftor First, Then Placebo
    Arm description
    		 Ivacaftor 150 milligram (mg) tablet orally twice daily for 8 weeks in treatment period 1 followed by placebo matched to ivacaftor tablet orally twice daily for 8 weeks in treatment period 2. Washout out period of 4 to 8 weeks was maintained between each treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ivacaftor
    Investigational medicinal product code
    VX-770
    Other name
    Kalydeco
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ivacaftor 150 mg tablet orally twice daily for 8 weeks.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo matched to ivacaftor tablet orally twice daily for 8 weeks.

    Arm title
    		 Sequence 2: Placebo First, Then Ivacaftor
    Arm description
    		 Placebo matched to ivacaftor tablet orally twice daily for 8 weeks in treatment period 1 followed by ivacaftor 150 mg tablet orally twice daily for 8 weeks in treatment period 2. Washout out period of 4 to 8 weeks was maintained between each treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo matched to ivacaftor tablet orally twice daily for 8 weeks.

    Investigational medicinal product name
    Ivacaftor
    Investigational medicinal product code
    VX-770
    Other name
    Kalydeco
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ivacaftor 150 mg tablet orally twice daily for 8 weeks.

    Number of subjects in period 2
    		Sequence 1: Ivacaftor First, Then Placebo Sequence 2: Placebo First, Then Ivacaftor
    Started
    18
    18
    Completed
    18
    18
    Period 3
    Period 3 title
    Part 2: Open-label Extension (16 Weeks)
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Open-label Extension (OLE) Ivacaftor
    Arm description
    		 Ivacaftor 150 mg tablet orally twice daily for 16 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ivacaftor
    Investigational medicinal product code
    VX-770
    Other name
    Kalydeco
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ivacaftor 150 mg tablet orally twice daily for 16 weeks.

    Number of subjects in period 3
    		Open-label Extension (OLE) Ivacaftor
    Started
    36
    Completed
    36

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Sequence 1: Ivacaftor First, Then Placebo
    Reporting group description
    		 Ivacaftor 150 milligram (mg) tablet orally twice daily for 8 weeks in treatment period 1 followed by placebo matched to ivacaftor tablet orally twice daily for 8 weeks in treatment period 2. Washout out period of 4 to 8 weeks was maintained between each treatment period.

    Reporting group title
    Sequence 2: Placebo First, Then Ivacaftor
    Reporting group description
    		 Placebo matched to ivacaftor tablet orally twice daily for 8 weeks in treatment period 1 followed by ivacaftor 150 mg tablet orally twice daily for 8 weeks in treatment period 2. Washout out period of 4 to 8 weeks was maintained between each treatment period.

    Reporting group values
    		 Sequence 1: Ivacaftor First, Then Placebo Sequence 2: Placebo First, Then Ivacaftor Total
    Number of subjects
    		 20 19 39
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 23.8 ± 13.25 21.7 ± 12.92 -
    Gender categorical
    Units: Subjects
        Female
    		 7 10 17
        Male
    		 13 9 22

    End points

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    End points reporting groups
    Reporting group title
    Sequence 1: Ivacaftor First, Then Placebo
    Reporting group description
    		 Ivacaftor 150 milligram (mg) tablet orally twice daily for 8 weeks in treatment period 1 followed by placebo matched to ivacaftor tablet orally twice daily for 8 weeks in treatment period 2. Washout out period of 4 to 8 weeks was maintained between each treatment period.

    Reporting group title
    Sequence 2: Placebo First, Then Ivacaftor
    Reporting group description
    		 Placebo matched to ivacaftor tablet orally twice daily for 8 weeks in treatment period 1 followed by ivacaftor 150 mg tablet orally twice daily for 8 weeks in treatment period 2. Washout out period of 4 to 8 weeks was maintained between each treatment period.
    Reporting group title
    Sequence 1: Ivacaftor First, Then Placebo
    Reporting group description
    		 Ivacaftor 150 milligram (mg) tablet orally twice daily for 8 weeks in treatment period 1 followed by placebo matched to ivacaftor tablet orally twice daily for 8 weeks in treatment period 2. Washout out period of 4 to 8 weeks was maintained between each treatment period.

    Reporting group title
    Sequence 2: Placebo First, Then Ivacaftor
    Reporting group description
    		 Placebo matched to ivacaftor tablet orally twice daily for 8 weeks in treatment period 1 followed by ivacaftor 150 mg tablet orally twice daily for 8 weeks in treatment period 2. Washout out period of 4 to 8 weeks was maintained between each treatment period.
    Reporting group title
    Open-label Extension (OLE) Ivacaftor
    Reporting group description
    		 Ivacaftor 150 mg tablet orally twice daily for 16 weeks.

    Subject analysis set title
    Part 1 Treatment Period 2: Ivacaftor, Part 2: OLE Ivacaftor
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Ivacaftor 150 mg tablet orally twice daily for 24 weeks (8 weeks in Part 1: Treatment Period 2 and 16 weeks in Part 2).

    Subject analysis set title
    Part 1: Placebo
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Placebo matched to ivacaftor tablet orally twice daily for 8 weeks in any either Sequence 1 or Sequence 2.

    Subject analysis set title
    Part 1: Ivacaftor
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Ivacaftor 150 mg tablet orally twice daily for 8 weeks in either Sequence 1 or Sequence 2.

    Primary: Part 1: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 8

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    End point title
    		 Part 1: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 8 [1]
    End point description
    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate ppFEV1 (for age, gender, and height). The Hankinson standard was used for male subjects 18 years and older and female subjects 16 years and older. The Wang standard was used for male subjects aged 6 to 17 years and for female subjects aged 6 to 15 years. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during study Part 1. Analysis was performed on Full Analysis Set (FAS) for Part 1 defined as all randomized subjects who received at least 1 dose of study drug (ivacaftor or placebo).
    End point type
    Primary
    End point timeframe
    Part 1: Baseline through Week 8
    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: Statistical Analysis is provided in the attachment.
    End point values
    		 Part 1: Ivacaftor Part 1: Placebo
    Number of subjects analysed
    38
    37
    Units: percent predicted of FEV1
        least squares mean (standard error)
    7.4868 ± 1.2292
    -3.1912 ± 1.2459
    Attachments
    		 Statistical Analysis
    No statistical analyses for this end point

    Primary: Part 2: Absolute Change From Baseline in ppFEV1 at 24 Weeks of Treatment (Week 36 Visit)

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    End point title
    		 Part 2: Absolute Change From Baseline in ppFEV1 at 24 Weeks of Treatment (Week 36 Visit) [2]
    End point description
    FEV1 and ppFEV1 are defined in primary endpoint. Absolute change in ppFEV1 at 24 weeks of ivacaftor treatment (from Week 12 [Part 1: Treatment Period 2] at Week 36 [Part 2]) was reported for subjects who received ivacaftor in Part 1: Treatment Period 2, as per planned analysis. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during Part 1: Treatment Period 2. Analysis was performed on FAS for Part 2 defined as all randomized subjects who received at least 1 dose of study drug (ivacaftor).
    End point type
    Primary
    End point timeframe
    Baseline (pre-dose Week 12), Week 36
    Notes
    [2] - 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 Part 2.
    End point values
    		 Part 1 Treatment Period 2: Ivacaftor, Part 2: OLE Ivacaftor
    Number of subjects analysed
    18
    Units: percent predicted of FEV1
    arithmetic mean (standard deviation)
        Baseline
    74.8375 ± 19.36754
        Change at Week 36
    13.5307 ± 10.18174
    No statistical analyses for this end point

    Secondary: Part 1: Absolute Change From Baseline in Body Mass Index (BMI) Through Week 8

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    End point title
    		 Part 1: Absolute Change From Baseline in Body Mass Index (BMI) Through Week 8
    End point description
    BMI was defined as weight in kilogram (kg) divided by height in meters^2 (m^2). Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during study Part 1. Analysis was performed on FAS for Part 1.
    End point type
    Secondary
    End point timeframe
    Part 1: Baseline through Week 8
    End point values
    		 Part 1: Ivacaftor Part 1: Placebo
    Number of subjects analysed
    38
    37
    Units: kg/m^2
        least squares mean (standard error)
    0.6787 ± 0.4948
    0.0163 ± 0.4954
    Attachments
    		 Statistical Analysis
    No statistical analyses for this end point

    Secondary: Part 2: Absolute Change From Baseline in BMI at 24 Weeks of Treatment (Week 36 Visit)

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    End point title
    		 Part 2: Absolute Change From Baseline in BMI at 24 Weeks of Treatment (Week 36 Visit)
    End point description
    Absolute change in BMI at 24 weeks of ivacaftor treatment (from Week 12 [Part 1: Treatment Period 2] at Week 36 [Part 2]) was reported for subjects who received ivacaftor in Part 1: Treatment Period 2 as per planned analysis. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during Part 1: Treatment Period 2. Analysis was performed on FAS for Part 2.
    End point type
    Secondary
    End point timeframe
    Baseline (pre-dose Week 12), Week 36
    End point values
    		 Part 1 Treatment Period 2: Ivacaftor, Part 2: OLE Ivacaftor
    Number of subjects analysed
    18
    Units: kg/m^2
    arithmetic mean (standard deviation)
        Baseline
    22.222 ± 6.2919
        Change at Week 36
    1.263 ± 0.7588
    No statistical analyses for this end point

    Secondary: Part 1: Absolute Change From Baseline in Sweat Chloride Through Week 8

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    End point title
    		 Part 1: Absolute Change From Baseline in Sweat Chloride Through Week 8
    End point description
    Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during study Part 1. Analysis was performed on FAS for Part 1.
    End point type
    Secondary
    End point timeframe
    Part 1: Baseline through Week 8
    End point values
    		 Part 1: Ivacaftor Part 1: Placebo
    Number of subjects analysed
    37
    37
    Units: millimole per liter (mmol/L)
        least squares mean (standard error)
    -52.2801 ± 2.721
    -3.1134 ± 2.7172
    Attachments
    		 Statistical Analysis
    No statistical analyses for this end point

    Secondary: Part 2: Absolute Change From Baseline in Sweat Chloride at 24 Weeks of Treatment (Week 36 Visit)

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    End point title
    		 Part 2: Absolute Change From Baseline in Sweat Chloride at 24 Weeks of Treatment (Week 36 Visit)
    End point description
    Absolute change in sweat chloride at 24 weeks of ivacaftor treatment (from Week 12 [Part 1: Treatment Period 2] at Week 36 [Part 2]) was reported for subjects who received ivacaftor in Part 1: Treatment Period 2 as per planned analysis. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during Part 1: Treatment Period 2. Analysis was performed on FAS for Part 2. Here, "n" signifies those subjects who were evaluable for this endpoint at specified time-point.
    End point type
    Secondary
    End point timeframe
    Baseline (pre-dose Week 12), Week 36
    End point values
    		 Part 1 Treatment Period 2: Ivacaftor, Part 2: OLE Ivacaftor
    Number of subjects analysed
    18
    Units: mmol/L
    arithmetic mean (standard deviation)
        Baseline (n=18)
    92.03 ± 11.468
        Change at Week 36 (n=17)
    -59.24 ± 32.566
    No statistical analyses for this end point

    Secondary: Part 1: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 8

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    End point title
    		 Part 1: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 8
    End point description
    The CFQ-R is a validated subject-reported outcome measuring health-related quality of life for subjects with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during study Part 1. Analysis was performed on FAS for Part 1.
    End point type
    Secondary
    End point timeframe
    Part 1: Baseline through Week 8
    End point values
    		 Part 1: Ivacaftor Part 1: Placebo
    Number of subjects analysed
    38
    37
    Units: units on a scale
        least squares mean (standard error)
    8.9385 ± 1.8178
    -0.672 ± 1.8475
    Attachments
    		 Statistical Analysis
    No statistical analyses for this end point

    Secondary: Part 2: Absolute Change From Baseline in CFQ-R Respiratory Domain Score at 24 Weeks of Treatment (Week 36 Visit)

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    End point title
    		 Part 2: Absolute Change From Baseline in CFQ-R Respiratory Domain Score at 24 Weeks of Treatment (Week 36 Visit)
    End point description
    The CFQ-R and CFQ-R respiratory domain are defined in Part 1 endpoint. Absolute change in CFQ-R respiratory domain score at 24 weeks of ivacaftor treatment (from Week 12 [Part 1: Treatment Period 2] at Week 36 [Part 2]) was reported for subjects who received ivacaftor in Part 1: Treatment Period 2 as per planned analysis. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during Part 1: Treatment Period 2. Analysis was performed on FAS for Part 2.
    End point type
    Secondary
    End point timeframe
    Baseline (pre-dose Week 12), Week 36
    End point values
    		 Part 1 Treatment Period 2: Ivacaftor, Part 2: OLE Ivacaftor
    Number of subjects analysed
    18
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline
    71.3 ± 19.526
        Change at Week 36
    11.42 ± 13.604
    No statistical analyses for this end point

    Secondary: Part 1: Number of subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)

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    End point title
    		 Part 1: Number of subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)
    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. Safety Set for Part 1 included all subjects who received at least 1 dose of study drug (ivacaftor or placebo).
    End point type
    Secondary
    End point timeframe
    Part 1: From signing of informed consent up to Week 20
    End point values
    		 Part 1: Ivacaftor Part 1: Placebo
    Number of subjects analysed
    38
    37
    Units: subjects
    number (not applicable)
        AEs
    28
    31
        SAEs
    4
    7
    No statistical analyses for this end point

    Secondary: Part 2: Number ofsubjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)

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    End point title
    		 Part 2: Number ofsubjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)
    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. Safety Set for Part 2 included all subjects who received at least 1 dose of study drug (ivacaftor).
    End point type
    Secondary
    End point timeframe
    Part 2: Week 20 up to Week 40
    End point values
    		 Open-label Extension (OLE) Ivacaftor
    Number of subjects analysed
    36
    Units: subjects
    number (not applicable)
        AEs
    30
        SAEs
    3
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Part 1: From signing of informed consent up to Week 20; Part 2: Week 20 up to Week 40
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    15.1
    Reporting groups
    Reporting group title
    Part 1: Placebo
    Reporting group description
    		 Placebo matched to ivacaftor tablet orally twice daily for 8 weeks in either Sequence 1 or Sequence 2.

    Reporting group title
    Part 1: Ivacaftor
    Reporting group description
    		 Ivacaftor 150 mg tablet orally twice daily for 8 weeks in either Sequence 1 or Sequence 2.

    Reporting group title
    Part 2: OLE Ivacaftor
    Reporting group description
    		 Ivacaftor 150 mg tablet orally twice daily for 16 weeks.

    Serious adverse events
    		 Part 1: Placebo Part 1: Ivacaftor Part 2: OLE Ivacaftor
    Total subjects affected by serious adverse events
         subjects affected / exposed
    7 / 37 (18.92%)
    4 / 38 (10.53%)
    3 / 36 (8.33%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    Nervous system disorders
    Convulsion
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Distal ileal obstruction syndrome
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 38 (2.63%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Appendiceal mucocoele
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 38 (0.00%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intussusception
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 38 (0.00%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Distal intestinal obstruction syndrome
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Paranasal cyst
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 38 (0.00%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 38 (0.00%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 38 (2.63%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Infective pulmonary exacerbation of cystic fibrosis
         subjects affected / exposed
    6 / 37 (16.22%)
    2 / 38 (5.26%)
    2 / 36 (5.56%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Part 1: Placebo Part 1: Ivacaftor Part 2: OLE Ivacaftor
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    30 / 37 (81.08%)
    27 / 38 (71.05%)
    30 / 36 (83.33%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Oral papilloma
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 38 (2.63%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    Malignant melanoma
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    Vascular disorders
    Orthostatic hypotension
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 38 (2.63%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    Hypertension
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    1 / 37 (2.70%)
    3 / 38 (7.89%)
    2 / 36 (5.56%)
         occurrences all number
    1
    3
    2
    Exercise tolerance decreased
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 38 (2.63%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    Fatigue
         subjects affected / exposed
    0 / 37 (0.00%)
    2 / 38 (5.26%)
    1 / 36 (2.78%)
         occurrences all number
    0
    2
    1
    Chest pain
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 38 (2.63%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    Malaise
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 38 (2.63%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    Oedema peripheral
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    1
    0
    1
    Medical device site reaction
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 38 (2.63%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    Infusion site thrombosis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    Injection site pain
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    Immune system disorders
    Seasonal allergy
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    Hypersensitivity
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    Reproductive system and breast disorders
    Metrorrhagia
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 38 (2.63%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    Vulvovaginal discomfort
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 38 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Sputum increased
         subjects affected / exposed
    3 / 37 (8.11%)
    3 / 38 (7.89%)
    2 / 36 (5.56%)
         occurrences all number
    3
    3
    2
    Cough
         subjects affected / exposed
    7 / 37 (18.92%)
    6 / 38 (15.79%)
    5 / 36 (13.89%)
         occurrences all number
    10
    6
    7
    Dysphonia
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 38 (2.63%)
    1 / 36 (2.78%)
         occurrences all number
    0
    1
    1
    Epistaxis
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 38 (2.63%)
    1 / 36 (2.78%)
         occurrences all number
    0
    1
    1
    Haemoptysis
         subjects affected / exposed
    2 / 37 (5.41%)
    1 / 38 (2.63%)
    1 / 36 (2.78%)
         occurrences all number
    2
    1
    1
    Lung hyperinflation
         subjects affected / exposed
    1 / 37 (2.70%)
    1 / 38 (2.63%)
    1 / 36 (2.78%)
         occurrences all number
    1
    1
    1
    Nasal congestion
         subjects affected / exposed
    1 / 37 (2.70%)
    1 / 38 (2.63%)
    0 / 36 (0.00%)
         occurrences all number
    1
    1
    0
    Oropharyngeal pain
         subjects affected / exposed
    3 / 37 (8.11%)
    1 / 38 (2.63%)
    3 / 36 (8.33%)
         occurrences all number
    4
    1
    3
    Rales
         subjects affected / exposed
    3 / 37 (8.11%)
    1 / 38 (2.63%)
    1 / 36 (2.78%)
         occurrences all number
    3
    1
    1
    Rhinorrhoea
         subjects affected / exposed
    2 / 37 (5.41%)
    1 / 38 (2.63%)
    0 / 36 (0.00%)
         occurrences all number
    2
    1
    0
    Respiration abnormal
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 38 (2.63%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    Wheezing
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 38 (2.63%)
    2 / 36 (5.56%)
         occurrences all number
    0
    1
    2
    Asthma
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 38 (0.00%)
    3 / 36 (8.33%)
         occurrences all number
    1
    0
    4
    Bronchospasm
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 38 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    Nasal mucosal disorder
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 38 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    Paranasal sinus hypersecretion
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    1
    0
    1
    Productive cough
         subjects affected / exposed
    2 / 37 (5.41%)
    0 / 38 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    2
    0
    0
    Pulmonary congestion
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    1
    0
    1
    Sputum discoloured
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 38 (0.00%)
    2 / 36 (5.56%)
         occurrences all number
    1
    0
    2
    Respiratory tract congestion
         subjects affected / exposed
    2 / 37 (5.41%)
    0 / 38 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    3
    0
    0
    Sinus congestion
         subjects affected / exposed
    2 / 37 (5.41%)
    0 / 38 (0.00%)
    2 / 36 (5.56%)
         occurrences all number
    3
    0
    2
    Nasal polyps
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    Nasal turbinate hypertrophy
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    Vocal cord inflammation
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    Pneumonitis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 38 (2.63%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 38 (2.63%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    Blood creatinine increased
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 38 (2.63%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    C-reactive protein increased
         subjects affected / exposed
    1 / 37 (2.70%)
    1 / 38 (2.63%)
    0 / 36 (0.00%)
         occurrences all number
    2
    1
    0
    Neutrophil count increased
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 38 (2.63%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    Respiratory rate increased
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 38 (2.63%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    Hepatic enzyme increased
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 38 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    White blood cell count increased
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 38 (2.63%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    Breath sounds abnormal
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    Pulmonary function test decreased
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    1
    0
    2
    Weight decreased
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 38 (2.63%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    Ligament sprain
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    1
    0
    1
    Arthropod bite
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    Sunburn
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    Vaccination complication
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    Nervous system disorders
    Dysgeusia
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 38 (2.63%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    Headache
         subjects affected / exposed
    5 / 37 (13.51%)
    3 / 38 (7.89%)
    4 / 36 (11.11%)
         occurrences all number
    6
    5
    8
    Lethargy
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    1
    0
    1
    Sinus headache
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 38 (2.63%)
    0 / 36 (0.00%)
         occurrences all number
    0
    2
    0
    Benign intracranial hypertension
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 38 (2.63%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    Ear and labyrinth disorders
    Hyperacusis
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 38 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    Cerumen impaction
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    Hypoacusis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    Eye disorders
    Conjunctivitis allergic
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    1 / 37 (2.70%)
    2 / 38 (5.26%)
    2 / 36 (5.56%)
         occurrences all number
    1
    2
    2
    Abdominal pain
         subjects affected / exposed
    4 / 37 (10.81%)
    1 / 38 (2.63%)
    3 / 36 (8.33%)
         occurrences all number
    4
    1
    3
    Distal ileal obstruction syndrome
         subjects affected / exposed
    1 / 37 (2.70%)
    1 / 38 (2.63%)
    0 / 36 (0.00%)
         occurrences all number
    1
    1
    0
    Abdominal pain upper
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 38 (2.63%)
    2 / 36 (5.56%)
         occurrences all number
    0
    1
    2
    Vomiting
         subjects affected / exposed
    1 / 37 (2.70%)
    1 / 38 (2.63%)
    0 / 36 (0.00%)
         occurrences all number
    1
    1
    0
    Toothache
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 38 (2.63%)
    1 / 36 (2.78%)
         occurrences all number
    0
    1
    1
    Nausea
         subjects affected / exposed
    4 / 37 (10.81%)
    1 / 38 (2.63%)
    1 / 36 (2.78%)
         occurrences all number
    4
    1
    1
    Cheilitis
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 38 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    Diarrhoea
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    1
    0
    1
    Distal intestinal obstruction syndrome
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 38 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    Flatulence
         subjects affected / exposed
    2 / 37 (5.41%)
    0 / 38 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    2
    0
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    2 / 37 (5.41%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    2
    0
    1
    Abdominal distension
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    Anal fissure
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    Food poisoning
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    Haemorrhoids
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    Gastritis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    Pancreatitis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    Hepatobiliary disorders
    Biliary colic
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    1
    0
    1
    Rash
         subjects affected / exposed
    2 / 37 (5.41%)
    1 / 38 (2.63%)
    1 / 36 (2.78%)
         occurrences all number
    2
    2
    1
    Dermatitis contact
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 38 (2.63%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    Dry skin
         subjects affected / exposed
    1 / 37 (2.70%)
    1 / 38 (2.63%)
    0 / 36 (0.00%)
         occurrences all number
    1
    1
    0
    Pruritus
         subjects affected / exposed
    1 / 37 (2.70%)
    1 / 38 (2.63%)
    0 / 36 (0.00%)
         occurrences all number
    1
    2
    0
    Rash papular
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 38 (2.63%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    Urticaria
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 38 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    Endocrine disorders
    Thyroid disorder
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 38 (2.63%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 37 (0.00%)
    2 / 38 (5.26%)
    1 / 36 (2.78%)
         occurrences all number
    0
    2
    1
    Back pain
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 38 (2.63%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    Torticollis
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 38 (2.63%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    Osteochondrosis
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 38 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    Pain in jaw
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    Tendonitis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    Infections and infestations
    Infective pulmonary exacerbation of cystic fibrosis
         subjects affected / exposed
    6 / 37 (16.22%)
    7 / 38 (18.42%)
    4 / 36 (11.11%)
         occurrences all number
    8
    8
    4
    Rhinitis
         subjects affected / exposed
    2 / 37 (5.41%)
    3 / 38 (7.89%)
    0 / 36 (0.00%)
         occurrences all number
    2
    3
    0
    Conjunctivitis infective
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 38 (2.63%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    Influenza
         subjects affected / exposed
    2 / 37 (5.41%)
    2 / 38 (5.26%)
    0 / 36 (0.00%)
         occurrences all number
    2
    2
    0
    Sinusitis
         subjects affected / exposed
    2 / 37 (5.41%)
    1 / 38 (2.63%)
    2 / 36 (5.56%)
         occurrences all number
    2
    1
    2
    Respiratory tract infection viral
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 38 (2.63%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 37 (5.41%)
    1 / 38 (2.63%)
    3 / 36 (8.33%)
         occurrences all number
    2
    2
    3
    Bronchitis
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 38 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    Urinary tract infection
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 38 (2.63%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    Bacterial disease carrier
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 38 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    Gastroenteritis
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    1
    0
    1
    Tonsillitis
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 38 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    Vulvovaginal mycotic infection
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    1
    0
    1
    Gastrointestinal viral infection
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    Impetigo
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    Pharyngitis streptococcal
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    Metabolism and nutrition disorders
    Hypoglycaemia
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    1
    0
    1
    Decreased appetite
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 38 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    17 Feb 2012
    The ppFEV1 inclusion criterion updated.
    21 Mar 2012
    Study assessments and exclusion criteria updated, Part 2 statistical methodology clarified.
    07 Sep 2012
    Observational arm eligibility criteria, screening assessments and study assessments updated.
    05 Dec 2012
    Study assessments clarified.

    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.
    Statistical analysis is provided in attachment for individual endpoint of Part 1.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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