Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44339   clinical trials with a EudraCT protocol, of which   7369   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Pilot Study Testing the Effect of Ivacaftor on Lung Function in Subjects With Cystic Fibrosis, Residual CFTR Function, and FEV1 ≥40% Predicted

    Summary
    EudraCT number
    		 2017-000673-37
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    03 Apr 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    08 Jun 2017
    First version publication date
    08 Jun 2017
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    VX12-770-113
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01685801
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Vertex Pharmaceuticals Incorporated
    Sponsor organisation address
    50 Northern Avenue, Boston, Massachusetts, United States, 022101862
    Public contact
    Medical Monitor, Vertex Pharmaceuticals Incorporated, 1 617-341-6777, medicalinfo@vrtx.com
    Scientific contact
    Medical Monitor, Vertex Pharmaceuticals Incorporated, 1 617-341-6777, medicalinfo@vrtx.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    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
    24 Apr 2014
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    03 Apr 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the effect of ivacaftor on lung function in subjects aged 12 years and older with cystic fibrosis (CF) who have phenotypic or molecular evidence of residual cystic fibrosis transmembrane conductance regulator (CFTR) function.
    Protection of trial subjects
    The study was conducted in accordance with the ethical principles stated in the Declaration of Helsinki and the International Council on Harmonization (ICH) Guideline for Good Clinical Practice (GCP).
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    11 Sep 2012
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 24
    Worldwide total number of subjects
    24
    EEA total number of subjects
    0
    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)
    0
    Adolescents (12-17 years)
    1
    Adults (18-64 years)
    23
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A total of 24 subjects were enrolled at a single site in United States.

    Period 1
    Period 1 title
    Cycle 1 Period 1 (2 Weeks)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) - Intervention 1
    Arm description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Ivacaftor during first intervention period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ivacaftor
    Investigational medicinal product code
    VX-770
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during Cycle 1 Period 1.

    Arm title
    		 Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) - Intervention 1
    Arm description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Ivacaftor during first intervention period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ivacaftor
    Investigational medicinal product code
    VX-770
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during Cycle 1 Period 1.

    Arm title
    		 Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) - Intervention 1
    Arm description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Placebo matched to Ivacaftor during first intervention period.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo-matched-to-ivacaftor
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during Cycle 1 Period 1.

    Arm title
    		 Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI) - Intervention 1
    Arm description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Placebo matched to Ivacaftor during first intervention period.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo-matched-to-ivacaftor
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during Cycle 1 Period 1.

    Number of subjects in period 1
    		Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) - Intervention 1 Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) - Intervention 1 Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) - Intervention 1 Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI) - Intervention 1
    Started
    5
    6
    7
    6
    Completed
    5
    6
    7
    6
    Period 2
    Period 2 title
    Cycle 1 Period 2 (2 Weeks)
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) - Intervention 2
    Arm description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Placebo matched to Ivacaftor during second intervention period.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo-matched-to-ivacaftor
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during Cycle 1 Period 2.

    Arm title
    		 Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) - Intervention 2
    Arm description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Placebo matched to Ivacaftor during second intervention period.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo-matched-to-ivacaftor
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during Cycle 1 Period 2.

    Arm title
    		 Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) - Intervention 2
    Arm description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Ivacaftor during second intervention period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ivacaftor
    Investigational medicinal product code
    VX-770
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during Cycle 1 Period 2.

    Arm title
    		 Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI) - Intervention 2
    Arm description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Ivacaftor during second intervention period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ivacaftor
    Investigational medicinal product code
    VX-770
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during Cycle 1 Period 2.

    Number of subjects in period 2
    		Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) - Intervention 2 Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) - Intervention 2 Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) - Intervention 2 Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI) - Intervention 2
    Started
    5
    6
    7
    6
    Completed
    5
    6
    7
    5
    Not completed
    0
    0
    0
    1
         Adverse Event
    -
    -
    -
    1
    Period 3
    Period 3 title
    Washout Period 1 (4 Weeks)
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) - Washout Period
    Arm description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor.
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    		 Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) - Washout Period
    Arm description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor.
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    		 Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) - Washout Period
    Arm description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor.
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    		 Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI) - Washout Period
    Arm description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor.
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 3
    		Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) - Washout Period Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) - Washout Period Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) - Washout Period Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI) - Washout Period
    Started
    5
    6
    7
    5
    Completed
    5
    6
    7
    5
    Period 4
    Period 4 title
    Cycle 2 Period 1 (2 Weeks)
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) - Intervention 3
    Arm description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Ivacaftor during third intervention period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ivacaftor
    Investigational medicinal product code
    VX-770
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during Cycle 2 Period 1.

    Arm title
    		 Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) - Intervention 3
    Arm description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Placebo matched to Ivacaftor during third intervention period.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo-matched-to-ivacaftor
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during Cycle 2 Period 1.

    Arm title
    		 Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) - Intervention 3
    Arm description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received Ivacaftor. Subjects received Ivacaftor during third intervention period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ivacaftor
    Investigational medicinal product code
    VX-770
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during Cycle 2 Period 1.

    Arm title
    		 Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI) - Intervention 3
    Arm description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received Ivacaftor. Subjects received Placebo matched Ivacaftor during third intervention period.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo-matched-to-ivacaftor
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during Cycle 2 Period 1.

    Number of subjects in period 4
    		Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) - Intervention 3 Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) - Intervention 3 Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) - Intervention 3 Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI) - Intervention 3
    Started
    5
    6
    7
    5
    Completed
    5
    6
    7
    5
    Period 5
    Period 5 title
    Cycle 2 Period 2 (2 Weeks)
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) - Intervention 4
    Arm description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received Ivacaftor. Subjects received Placebo matched to Ivacaftor during fourth intervention period.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo-matched-to-ivacaftor
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during Cycle 2 Period 2.

    Arm title
    		 Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) - Intervention 4
    Arm description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Ivacaftor during fourth intervention period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ivacaftor
    Investigational medicinal product code
    VX-770
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during Cycle 2 Period 2.

    Arm title
    		 Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) - Intervention 4
    Arm description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received Ivacaftor. Subjects received Placebo matched to Ivacaftor during fourth intervention period.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo-matched-to-ivacaftor
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during Cycle 2 Period 2.

    Arm title
    		 Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI) - Intervention 4
    Arm description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Ivacaftor during fourth intervention period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ivacaftor
    Investigational medicinal product code
    VX-770
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during Cycle 2 Period 2.

    Number of subjects in period 5
    		Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) - Intervention 4 Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) - Intervention 4 Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) - Intervention 4 Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI) - Intervention 4
    Started
    5
    6
    7
    5
    Completed
    5
    5
    7
    4
    Not completed
    0
    1
    0
    1
         Non-compliance with Study Drug
    -
    1
    -
    1
    Period 6
    Period 6 title
    Washout Period 2 (4 Weeks)
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) - Washout Period
    Arm description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor.
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    		 Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) - Washout Period
    Arm description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor.
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    		 Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) - Washout Period
    Arm description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor.
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    		 Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI) - Washout Period
    Arm description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor.
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 6
    		Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) - Washout Period Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) - Washout Period Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) - Washout Period Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI) - Washout Period
    Started
    5
    5
    7
    4
    Completed
    5
    5
    7
    4
    Period 7
    Period 7 title
    Open-label Period (8 Weeks)
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP)
    Arm description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ivacaftor
    Investigational medicinal product code
    VX-770
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ivacaftor 150 mg tablet orally every 12 hours for 8 weeks in open-label period.

    Arm title
    		 Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI)
    Arm description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ivacaftor
    Investigational medicinal product code
    VX-770
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ivacaftor 150 mg tablet orally every 12 hours for 8 weeks in open-label period.

    Arm title
    		 Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP)
    Arm description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ivacaftor
    Investigational medicinal product code
    VX-770
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ivacaftor 150 mg tablet orally every 12 hours for 8 weeks in open-label period.

    Arm title
    		 Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI)
    Arm description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ivacaftor
    Investigational medicinal product code
    VX-770
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ivacaftor 150 mg tablet orally every 12 hours for 8 weeks in open-label period.

    Number of subjects in period 7
    		Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI)
    Started
    5
    5
    7
    4
    Completed
    5
    5
    7
    4

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) - Intervention 1
    Reporting group description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Ivacaftor during first intervention period.

    Reporting group title
    Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) - Intervention 1
    Reporting group description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Ivacaftor during first intervention period.

    Reporting group title
    Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) - Intervention 1
    Reporting group description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Placebo matched to Ivacaftor during first intervention period.

    Reporting group title
    Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI) - Intervention 1
    Reporting group description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Placebo matched to Ivacaftor during first intervention period.

    Reporting group values
    		 Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) - Intervention 1 Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) - Intervention 1 Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) - Intervention 1 Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI) - Intervention 1 Total
    Number of subjects
    		 5 6 7 6 24
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 44.8 ( 8.04 ) 29.7 ( 11.66 ) 41.4 ( 13.96 ) 33.8 ( 17.26 ) -
    Gender categorical
    Units: Subjects
        Female
    		 3 4 3 2 12
        Male
    		 2 2 4 4 12
    Genotype
    All subjects were tested for CFTR genotype. Subjects with a documented medical history of either a residual function or a messenger ribonucleic acid (mRNA) splice site (Class V) CFTR mutation were reported.
    Units: Subjects
        mRNA Splice Site (Class V) Mutations
    		 3 3 2 2 10
        Residual Function Mutations
    		 2 3 5 4 14

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) - Intervention 1
    Reporting group description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Ivacaftor during first intervention period.

    Reporting group title
    Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) - Intervention 1
    Reporting group description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Ivacaftor during first intervention period.

    Reporting group title
    Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) - Intervention 1
    Reporting group description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Placebo matched to Ivacaftor during first intervention period.

    Reporting group title
    Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI) - Intervention 1
    Reporting group description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Placebo matched to Ivacaftor during first intervention period.
    Reporting group title
    Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) - Intervention 2
    Reporting group description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Placebo matched to Ivacaftor during second intervention period.

    Reporting group title
    Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) - Intervention 2
    Reporting group description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Placebo matched to Ivacaftor during second intervention period.

    Reporting group title
    Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) - Intervention 2
    Reporting group description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Ivacaftor during second intervention period.

    Reporting group title
    Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI) - Intervention 2
    Reporting group description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Ivacaftor during second intervention period.
    Reporting group title
    Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) - Washout Period
    Reporting group description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor.

    Reporting group title
    Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) - Washout Period
    Reporting group description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor.

    Reporting group title
    Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) - Washout Period
    Reporting group description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor.

    Reporting group title
    Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI) - Washout Period
    Reporting group description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor.
    Reporting group title
    Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) - Intervention 3
    Reporting group description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Ivacaftor during third intervention period.

    Reporting group title
    Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) - Intervention 3
    Reporting group description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Placebo matched to Ivacaftor during third intervention period.

    Reporting group title
    Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) - Intervention 3
    Reporting group description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received Ivacaftor. Subjects received Ivacaftor during third intervention period.

    Reporting group title
    Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI) - Intervention 3
    Reporting group description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received Ivacaftor. Subjects received Placebo matched Ivacaftor during third intervention period.
    Reporting group title
    Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) - Intervention 4
    Reporting group description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received Ivacaftor. Subjects received Placebo matched to Ivacaftor during fourth intervention period.

    Reporting group title
    Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) - Intervention 4
    Reporting group description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Ivacaftor during fourth intervention period.

    Reporting group title
    Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) - Intervention 4
    Reporting group description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received Ivacaftor. Subjects received Placebo matched to Ivacaftor during fourth intervention period.

    Reporting group title
    Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI) - Intervention 4
    Reporting group description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Ivacaftor during fourth intervention period.
    Reporting group title
    Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) - Washout Period
    Reporting group description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor.

    Reporting group title
    Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) - Washout Period
    Reporting group description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor.

    Reporting group title
    Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) - Washout Period
    Reporting group description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor.

    Reporting group title
    Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI) - Washout Period
    Reporting group description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor.
    Reporting group title
    Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP)
    Reporting group description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor.

    Reporting group title
    Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI)
    Reporting group description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor.

    Reporting group title
    Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP)
    Reporting group description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor.

    Reporting group title
    Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI)
    Reporting group description
    		 During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor.

    Subject analysis set title
    Cycle 1: Placebo
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 1.

    Subject analysis set title
    Cycle 1: Ivacaftor
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 1.

    Subject analysis set title
    Cycle 2: Placebo
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 2.

    Subject analysis set title
    Cycle 2: Ivacaftor
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 2.

    Subject analysis set title
    Open-Label Period: Ivacaftor
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Ivacaftor 150 mg tablet orally every 12 hours for 8 weeks during the open-label period after washout period 2.

    Subject analysis set title
    Crossover Double-blind Period: Placebo
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Placebo matched to ivacaftor tablet orally every 12 hours for 2 weeks either during the double blind period 1 or 2 of cycle 1 and cycle 2.

    Subject analysis set title
    Crossover Double-blind Period: Ivacaftor
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks either during the double blind period 1 or 2 of cycle 1 and cycle 2.

    Primary: Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) After 2 Weeks of Treatment

    		 Close Top of page
    End point title
    		 Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) After 2 Weeks of Treatment
    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 percent predicted FEV1 (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 12 to 17 years and for female subjects aged 12 to 15 years. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment, for overall subjects and as per genotype (residual function mutation and mRNA splice site mutation). Full Analysis Set (FAS) included all randomized subjects who received at least 1 dose of study drug (ivacaftor or placebo). Here, number of subjects analyzed signifies subject evaluable for this endpoint and "n" signifies subject who were evaluable for the specified category in each arm, respectively.
    End point type
    Primary
    End point timeframe
    Cycle 1 baseline, Cycle 1 Day 15 (for Cycle 1 reporting arms); Cycle 2 baseline, Cycle 2 Day 15 (for Cycle 2 reporting arms)
    End point values
    		 Cycle 1: Placebo Cycle 1: Ivacaftor Cycle 2: Placebo Cycle 2: Ivacaftor
    Number of subjects analysed
    24
    24
    23
    23
    Units: Percent predicted of FEV1
    arithmetic mean (standard deviation)
        Overall (n=24, 24, 23, 23)
    0.5828 ( 3.67326 )
    2.0898 ( 4.63833 )
    0.8495 ( 4.20641 )
    3.6868 ( 6.13466 )
        mRNA Splice Site(ClassV)Mutations (n=10, 10, 9, 9)
    -0.571 ( 3.39739 )
    0.8196 ( 5.09161 )
    1.7132 ( 3.80933 )
    2.064 ( 3.55493 )
        Residual Function Mutations (n=14, 14, 14, 14)
    1.4069 ( 3.75842 )
    2.9971 ( 4.24124 )
    0.2942 ( 4.49056 )
    4.73 ( 7.27436 )
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    This statistical analysis is for “Overall” category. The posterior distribution of overall treatment difference was obtained using the Bayesian hierarchical model and 95% credible interval of the treatment effect (posterior mean) was calculated.
    Comparison groups
    Cycle 1: Placebo v Cycle 1: Ivacaftor v Cycle 2: Placebo v Cycle 2: Ivacaftor
    Number of subjects included in analysis
    94
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Posterior Mean
    Point estimate
    2.251
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.383
         upper limit
    		 4.144
    Variability estimate
    Standard deviation
    Dispersion value
    0.961

    Secondary: Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Lung Clearance Index (LCI) After 2 Weeks of Treatment

    		 Close Top of page
    End point title
    		 Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Lung Clearance Index (LCI) After 2 Weeks of Treatment
    End point description
    LCI is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test. The LCI was calculated as the number of lung volume turnovers (cumulative expired volume divided by the functional residual capacity [FRC]) required to reduce end-tidal concentration of an inert gas to 1/40th of the starting value. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment, for overall subjects and as per genotype (residual function mutation and mRNA splice site mutation). FAS population. Here, ''number of subjects analyzed'' signifies subjects evaluable for this endpoint and "n" signifies subjects who were evaluable for the specified category in each arm, respectively.
    End point type
    Secondary
    End point timeframe
    Cycle 1 baseline, Cycle 1 Day 15 (for Cycle 1 reporting arms); Cycle 2 baseline, Cycle 2 Day 15 (for Cycle 2 reporting arms)
    End point values
    		 Cycle 1: Placebo Cycle 1: Ivacaftor Cycle 2: Placebo Cycle 2: Ivacaftor
    Number of subjects analysed
    23
    24
    23
    22
    Units: Ratio
    arithmetic mean (standard deviation)
        Overall (n=23, 24, 23, 22)
    0.4596 ( 1.97774 )
    0.2822 ( 3.54741 )
    0.4111 ( 2.3992 )
    0.077 ( 1.98188 )
        mRNA Splice Site(ClassV)Mutations (n=10, 10, 9, 9)
    0.4321 ( 1.9714 )
    -0.5306 ( 1.91374 )
    1.0568 ( 2.12093 )
    -0.3136 ( 1.89562 )
        Residual Function Mutations (n=13, 14, 14, 13)
    0.4808 ( 2.06279 )
    0.8628 ( 4.34252 )
    -0.0039 ( 2.54929 )
    0.3475 ( 2.0699 )
    No statistical analyses for this end point

    Secondary: Open-label Period: Absolute Change From Open-label Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) at Day 57

    		 Close Top of page
    End point title
    		 Open-label Period: Absolute Change From Open-label Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) at Day 57
    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 percent predicted FEV1 (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 12 to 17 years and for female subjects aged 12 to 15 years. Data was to be reported for overall subjects and as per genotype (residual function mutation and mRNA splice site mutation). FAS population. Here, '''number of subjects analyzed'' signifies subjects evaluable for this endpoint and "n" signifies subjects who were evaluable for the specified category.
    End point type
    Secondary
    End point timeframe
    Open-label Baseline, Open-label Day 57
    End point values
    		 Open-Label Period: Ivacaftor
    Number of subjects analysed
    21
    Units: Percent predicted of FEV1
    arithmetic mean (standard deviation)
        Overall (n=21)
    4.6815 ( 4.17934 )
        mRNA Splice Site(ClassV)Mutations (n=9)
    4.3072 ( 2.93624 )
        Residual Function Mutations (n=12)
    4.9622 ( 5.02864 )
    No statistical analyses for this end point

    Secondary: Open-label Period: Absolute Change From Open-label Baseline In Lung Clearance Index (LCI) at Day 57

    		 Close Top of page
    End point title
    		 Open-label Period: Absolute Change From Open-label Baseline In Lung Clearance Index (LCI) at Day 57
    End point description
    LCI is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test. The LCI was calculated as the number of lung volume turnovers (cumulative expired volume divided by the functional residual capacity [FRC]) required to reduce end-tidal concentration of an inert gas to 1/40th of the starting value. Data was to be reported for overall subjects and as per genotype (residual function mutation and mRNA splice site mutation). FAS population. Here, ''number of subjects analyzed'' signifies subjects evaluable for this endpoint and "n" signifies subjects who were evaluable for the specified category.
    End point type
    Secondary
    End point timeframe
    Open-label Baseline, Open-label Day 57
    End point values
    		 Open-Label Period: Ivacaftor
    Number of subjects analysed
    21
    Units: Ratio
    arithmetic mean (standard deviation)
        Overall (n=21)
    -1.5687 ( 2.27137 )
        mRNA Splice Site(ClassV)Mutations (n=9)
    -1.3459 ( 2.88447 )
        Residual Function Mutations (n=12)
    -1.7358 ( 1.80502 )
    No statistical analyses for this end point

    Secondary: Open-label Period: Absolute Change From Study Baseline In Sweat Chloride at Day 57

    		 Close Top of page
    End point title
    		 Open-label Period: Absolute Change From Study Baseline In Sweat Chloride at Day 57
    End point description
    Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of greater than or equal to (>=) 15 microliter was required for determination of sweat chloride. Data was to be reported for overall subjects and as per genotype (residual function mutation and mRNA splice site mutation). FAS population. Here, ''number of subjects analyzed'' signifies subjects evaluable for this endpoint and "n" signifies subjects who were evaluable for the specified category.
    End point type
    Secondary
    End point timeframe
    Study Baseline, Open-label Day 57
    End point values
    		 Open-Label Period: Ivacaftor
    Number of subjects analysed
    19
    Units: Millimole per liter (mmol/L)
    arithmetic mean (standard deviation)
        Overall (n=19)
    -15.74 ( 14.781 )
        mRNA Splice Site(ClassV)Mutations (n=8)
    -14.13 ( 8.254 )
        Residual Function Mutations (n=11)
    -16.91 ( 18.493 )
    No statistical analyses for this end point

    Secondary: Open-label Period: Absolute Change From Open-label Baseline In Weight at Day 57

    		 Close Top of page
    End point title
    		 Open-label Period: Absolute Change From Open-label Baseline In Weight at Day 57
    End point description
    Data was to be reported for overall subjects and as per genotype (residual function mutation and mRNA splice site mutation). FAS population. Here, ''number of subjects analyzed'' signifies subjects evaluable for this endpoint and "n" signifies subjects who were evaluable for the specified category.
    End point type
    Secondary
    End point timeframe
    Open-label Baseline, Open-label Day 57
    End point values
    		 Open-Label Period: Ivacaftor
    Number of subjects analysed
    21
    Units: Kilograms (kg)
    arithmetic mean (standard deviation)
        Overall (n=21)
    1.77 ( 1.906 )
        mRNA Splice Site(ClassV)Mutations (n=9)
    2.32 ( 2.111 )
        Residual Function Mutations (n=12)
    1.35 ( 1.71 )
    No statistical analyses for this end point

    Secondary: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

    		 Close Top of page
    End point title
    		 Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
    End point description
    AEs that started(or increased severity)from first dose of study drug to completion of Follow-up were TEAEs, with exception that if AE started during Washout Period & beyond 14 days from last dose date of preceding cycle, AE was “Washout Period” AE & not TEAE. TEAE was attributed to treatment in which it started/ to treatment in second cycling period of previous Crossover Period if it started during Washout Period. SAE:medical event/condition, which falls into any of these categories, regardless of relationship to study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event. Data was to be reported by drug treatment for double-blind crossover period(Cycle 1 up to Washout Period 2)& open-label period. Safety set:all subjects who received at least 1 dose of study drug. Number of subjects analyzed=subject evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug through completion of follow-up visit (up to 26 weeks)
    End point values
    		 Open-Label Period: Ivacaftor Crossover Double-blind Period: Placebo Crossover Double-blind Period: Ivacaftor
    Number of subjects analysed
    21
    24
    24
    Units: Subjects
        AEs
    20
    17
    18
        SAEs
    0
    0
    1
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From first dose of study drug through completion of follow-up visit (up to 26 weeks)
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    15.0
    Reporting groups
    Reporting group title
    Crossover Double-blind Period: Placebo
    Reporting group description
    		 Placebo matched to ivacaftor tablet orally every 12 hours for 2 weeks either during the double blind period 1 or 2 of cycle 1 and cycle 2.

    Reporting group title
    Crossover Double-blind Period: Ivacaftor
    Reporting group description
    		 Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks either during the double blind period 1 or 2 of cycle 1 and cycle 2.

    Reporting group title
    Open-label Period: Ivacaftor
    Reporting group description
    		 Ivacaftor 150 mg tablet orally every 12 hours for 8 weeks during the open-label period after washout period 2.

    Serious adverse events
    		 Crossover Double-blind Period: Placebo Crossover Double-blind Period: Ivacaftor Open-label Period: Ivacaftor
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Infections and infestations
    Infective pulmonary exacerbation of cystic fibrosis
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    0 / 21 (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
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Crossover Double-blind Period: Placebo Crossover Double-blind Period: Ivacaftor Open-label Period: Ivacaftor
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    17 / 24 (70.83%)
    18 / 24 (75.00%)
    20 / 21 (95.24%)
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    3 / 24 (12.50%)
    0 / 24 (0.00%)
    4 / 21 (19.05%)
         occurrences all number
    3
    0
    5
    Pyrexia
         subjects affected / exposed
    1 / 24 (4.17%)
    3 / 24 (12.50%)
    0 / 21 (0.00%)
         occurrences all number
    1
    3
    0
    Chest discomfort
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Chest pain
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    1
    Chills
         subjects affected / exposed
    1 / 24 (4.17%)
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    1
    0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    1
    Reproductive system and breast disorders
    Postmenopausal haemorrhage
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    6 / 24 (25.00%)
    1 / 24 (4.17%)
    7 / 21 (33.33%)
         occurrences all number
    7
    1
    7
    Haemoptysis
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    2 / 21 (9.52%)
         occurrences all number
    0
    1
    2
    Oropharyngeal pain
         subjects affected / exposed
    1 / 24 (4.17%)
    1 / 24 (4.17%)
    2 / 21 (9.52%)
         occurrences all number
    1
    1
    2
    Paranasal sinus hypersecretion
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    2 / 21 (9.52%)
         occurrences all number
    0
    1
    2
    Sputum increased
         subjects affected / exposed
    7 / 24 (29.17%)
    1 / 24 (4.17%)
    2 / 21 (9.52%)
         occurrences all number
    7
    1
    2
    Respiration abnormal
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    2 / 21 (9.52%)
         occurrences all number
    0
    0
    2
    Sinus congestion
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    1
    Sneezing
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    2 / 21 (9.52%)
         occurrences all number
    1
    0
    2
    Throat irritation
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    2 / 21 (9.52%)
         occurrences all number
    0
    0
    2
    Wheezing
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    2 / 21 (9.52%)
         occurrences all number
    0
    1
    2
    Dyspnoea
         subjects affected / exposed
    4 / 24 (16.67%)
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    4
    0
    1
    Nasal congestion
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    1
    Pleuritic pain
         subjects affected / exposed
    1 / 24 (4.17%)
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    1
    0
    Respiratory tract congestion
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    1
    Rhinorrhoea
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    1
    0
    1
    Upper-airway cough syndrome
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Dysphonia
         subjects affected / exposed
    2 / 24 (8.33%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    2
    0
    0
    Dyspnoea exertional
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    Respiratory tract irritation
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Investigations
    Liver function test abnormal
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    1
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Excoriation
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    1
    Wrist fracture
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    Cardiac disorders
    Cardiac flutter
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Nervous system disorders
    Sinus headache
         subjects affected / exposed
    0 / 24 (0.00%)
    2 / 24 (8.33%)
    2 / 21 (9.52%)
         occurrences all number
    0
    2
    2
    Headache
         subjects affected / exposed
    0 / 24 (0.00%)
    2 / 24 (8.33%)
    1 / 21 (4.76%)
         occurrences all number
    0
    2
    1
    Dizziness
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    1
    Eye disorders
    Lacrimation increased
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Ocular hyperaemia
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    1
    Nausea
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    1
    Vomiting
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    1
    Constipation
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    Skin and subcutaneous tissue disorders
    Heat rash
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    1
    Pruritus
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Urticaria
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    2 / 21 (9.52%)
         occurrences all number
    0
    0
    2
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    1
    Joint swelling
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    1
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Musculoskeletal discomfort
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Osteopenia
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    1
    Pain in extremity
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    1
    Musculoskeletal pain
         subjects affected / exposed
    2 / 24 (8.33%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    2
    0
    0
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 24 (0.00%)
    5 / 24 (20.83%)
    4 / 21 (19.05%)
         occurrences all number
    0
    5
    4
    Infective pulmonary exacerbation of cystic fibrosis
         subjects affected / exposed
    3 / 24 (12.50%)
    1 / 24 (4.17%)
    2 / 21 (9.52%)
         occurrences all number
    4
    1
    2
    Acute sinusitis
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    1
    Incision site infection
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Laryngitis
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Oral viral infection
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Respiratory tract infection viral
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Sinusitis
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Influenza
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    Oral candidiasis
         subjects affected / exposed
    3 / 24 (12.50%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    3
    0
    0
    Pharyngitis streptococcal
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    Rhinitis
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    Viral infection
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Dehydration
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    16 Oct 2012
    - Secondary efficacy endpoint Cystic Fibrosis Questionnaire Revised (CFQ-R) was removed; - Assessment for alanine aminotransferase and aspartate aminotransferase was added; - Pulse oximetry assessment changed to twice daily; - Prior ivacaftor use was added as an exclusion criterion; - The analysis of the primary variable was updated.
    02 Apr 2013
    - Subjects who completed this study were offered to enroll in Study VX12-770-112 (2012-000389-39); The number of subjects to be enrolled was increased
    29 Jul 2013
    - Responder criteria for participation in Study VX12-770-112 were incorporated and relative change in percent predicted FEV1 was amended to absolute change to facilitate comparison of data among ivacaftor clinical studies.

    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
    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.

    European Medicines Agency © 1995-Fri May 30 06:04:08 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA