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   43861   clinical trials with a EudraCT protocol, of which   7284   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 Phase 1/2 Study of VX-445 in Subjects With Cystic Fibrosis

    Summary
    EudraCT number
    		 2017-000797-11
    Trial protocol
    		 NL   BE  
    Global end of trial date
    27 Mar 2018

    Results information
    Results version number
    		 v2(current)
    This version publication date
    28 Apr 2022
    First version publication date
    12 Apr 2019
    Other versions
    		 v1
    Version creation reason
    • New data added to full data set
    Addition of secondary endpoints

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    VX16-445-001
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03227471
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Vertex Pharmaceuticals Incorporated
    Sponsor organisation address
    50 Northern Avenue, Boston, Massachusetts, United States,
    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?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    13 Apr 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    27 Mar 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    27 Mar 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the safety, tolerability, and efficacy of VX-445 in triple combination (TC) with Tezacaftor/Ivacaftor (TEZ/IVA) or with TEZ/VX-561.
    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
    19 Jun 2017
    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
    United States: 88
    Country: Number of subjects enrolled
    Australia: 15
    Country: Number of subjects enrolled
    Belgium: 6
    Country: Number of subjects enrolled
    Netherlands: 16
    Worldwide total number of subjects
    125
    EEA total number of subjects
    22
    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)
    0
    Adults (18-64 years)
    125
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 This study included 6 parts: Part D, E, and F were conducted in adult subjects with cystic fibrosis (CF).

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Part D: Placebo
    Arm description
    		 Subjects with CF, F/MF genotype who received placebo matched to VX-445/TEZ/IVA TC once daily in the morning and placebo matched to IVA in the evening for 4 weeks in the TC treatment period.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo (matched to VX-445)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received placebo matched to VX-445 once daily.

    Investigational medicinal product name
    Placebo (matched to TEZ/IVA)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received placebo matched to TEZ/IVA once daily in the morning.

    Investigational medicinal product name
    Placebo (matched to IVA)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received placebo matched to IVA once daily in the evening.

    Arm title
    		 Part D: VX-445/TEZ/IVA TC - Low Dose
    Arm description
    		 Subjects with CF, F/MF genotype who received VX-445 50 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    VX-445
    Investigational medicinal product code
    VX-445
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received VX-445 low dose once daily.

    Investigational medicinal product name
    TEZ/IVA
    Investigational medicinal product code
    VX-661/VX-770
    Other name
    Tezacaftor/Ivacaftor fixed dose combination
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received TEZ/IVA once daily in the morning.

    Investigational medicinal product name
    IVA
    Investigational medicinal product code
    VX-770
    Other name
    Ivacaftor
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received IVA once daily in the evening.

    Arm title
    		 Part D: VX-445/TEZ/IVA TC - Medium Dose
    Arm description
    		 Subjects with CF, F/MF genotype who received VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    VX-445
    Investigational medicinal product code
    VX-445
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received VX-445 medium dose once daily.

    Investigational medicinal product name
    TEZ/IVA
    Investigational medicinal product code
    VX-661/VX-770
    Other name
    Tezacaftor/Ivacaftor fixed dose combination
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received TEZ/IVA once daily in the morning.

    Investigational medicinal product name
    IVA
    Investigational medicinal product code
    VX-770
    Other name
    Ivacaftor
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received IVA once daily in the evening.

    Arm title
    		 Part D: VX-445/TEZ/IVA TC - High Dose
    Arm description
    		 Subjects with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    VX-445
    Investigational medicinal product code
    VX-445
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received VX-445 high dose once daily.

    Investigational medicinal product name
    TEZ/IVA
    Investigational medicinal product code
    VX-661/VX-770
    Other name
    Tezacaftor/Ivacaftor fixed dose combination
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received TEZ/IVA once daily in the morning.

    Investigational medicinal product name
    IVA
    Investigational medicinal product code
    VX-770
    Other name
    Ivacaftor
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received IVA once daily in the evening.

    Arm title
    		 Part E: TEZ/IVA
    Arm description
    		 Following run-in period of 4 weeks with TEZ/IVA, subjects with CF, F/F genotype who received TEZ 100 mg qd/IVA 150 mg q12h and placebo matched to VX-445 for 4 weeks in the TC treatment period.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Placebo (matched to VX-445)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received placebo matched to VX-445 once daily.

    Investigational medicinal product name
    TEZ/IVA
    Investigational medicinal product code
    VX-661/VX-770
    Other name
    Tezacaftor/Ivacaftor fixed dose combination
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received TEZ/IVA once daily in the morning.

    Investigational medicinal product name
    IVA
    Investigational medicinal product code
    VX-770
    Other name
    Ivacaftor
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received IVA once daily in the evening.

    Arm title
    		 Part E: VX-445/TEZ/IVA TC
    Arm description
    		 Following run-in period of 4 weeks with TEZ/IVA, subjects with CF, F/F genotype who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    VX-445
    Investigational medicinal product code
    VX-445
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received VX-445 once daily.

    Investigational medicinal product name
    TEZ/IVA
    Investigational medicinal product code
    VX-661/VX-770
    Other name
    Tezacaftor/Ivacaftor fixed dose combination
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received TEZ/IVA once daily in the morning.

    Investigational medicinal product name
    IVA
    Investigational medicinal product code
    VX-770
    Other name
    Ivacaftor
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received IVA once daily in the evening.

    Arm title
    		 Part F: Placebo
    Arm description
    		 Subjects with CF, F/MF genotype who received placebo matched to VX-445/TEZ/VX-561 for 4 weeks in the TC treatment period.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo (matched to VX-445)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received placebo matched to VX-445 once daily.

    Investigational medicinal product name
    Placebo (matched to TEZ)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received placebo matched to TEZ once daily.

    Investigational medicinal product name
    Placebo (matched to VX-561)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received placebo matched to VX-561 once daily.

    Arm title
    		 Part F: VX-445/TEZ/VX-561 TC
    Arm description
    		 Subjects with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/VX-561 150 mg qd for 4 weeks in the TC treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    VX-445
    Investigational medicinal product code
    VX-445
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received VX-445 once daily.

    Investigational medicinal product name
    TEZ
    Investigational medicinal product code
    VX-661
    Other name
    Tezacaftor
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received TEZ once daily.

    Investigational medicinal product name
    VX-561
    Investigational medicinal product code
    VX-561
    Other name
    CTP-656
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received VX-561 once daily.

    Number of subjects in period 1 [1]
    		Part D: Placebo Part D: VX-445/TEZ/IVA TC - Low Dose Part D: VX-445/TEZ/IVA TC - Medium Dose Part D: VX-445/TEZ/IVA TC - High Dose Part E: TEZ/IVA Part E: VX-445/TEZ/IVA TC Part F: Placebo Part F: VX-445/TEZ/VX-561 TC
    Started
    12
    10
    22
    21
    7
    21
    8
    21
    Completed
    12
    10
    22
    21
    7
    20
    8
    21
    Not completed
    0
    0
    0
    0
    0
    1
    0
    0
         Withdrawal of consent (not due to AE)
    -
    -
    -
    -
    -
    1
    -
    -
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: 125 subjects were enrolled in the Parts DEF. 2 subjects were dosed in the run-in period in Part E, but never got dosed in TC period. 1 subject in Part F was randomized but never dosed in TC period. Therefore, 122 over the total of 125 enrolled subjects entered the TC period.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Part D: Placebo
    Reporting group description
    		 Subjects with CF, F/MF genotype who received placebo matched to VX-445/TEZ/IVA TC once daily in the morning and placebo matched to IVA in the evening for 4 weeks in the TC treatment period.

    Reporting group title
    Part D: VX-445/TEZ/IVA TC - Low Dose
    Reporting group description
    		 Subjects with CF, F/MF genotype who received VX-445 50 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.

    Reporting group title
    Part D: VX-445/TEZ/IVA TC - Medium Dose
    Reporting group description
    		 Subjects with CF, F/MF genotype who received VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.

    Reporting group title
    Part D: VX-445/TEZ/IVA TC - High Dose
    Reporting group description
    		 Subjects with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.

    Reporting group title
    Part E: TEZ/IVA
    Reporting group description
    		 Following run-in period of 4 weeks with TEZ/IVA, subjects with CF, F/F genotype who received TEZ 100 mg qd/IVA 150 mg q12h and placebo matched to VX-445 for 4 weeks in the TC treatment period.

    Reporting group title
    Part E: VX-445/TEZ/IVA TC
    Reporting group description
    		 Following run-in period of 4 weeks with TEZ/IVA, subjects with CF, F/F genotype who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.

    Reporting group title
    Part F: Placebo
    Reporting group description
    		 Subjects with CF, F/MF genotype who received placebo matched to VX-445/TEZ/VX-561 for 4 weeks in the TC treatment period.

    Reporting group title
    Part F: VX-445/TEZ/VX-561 TC
    Reporting group description
    		 Subjects with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/VX-561 150 mg qd for 4 weeks in the TC treatment period.

    Reporting group values
    		 Part D: Placebo Part D: VX-445/TEZ/IVA TC - Low Dose Part D: VX-445/TEZ/IVA TC - Medium Dose Part D: VX-445/TEZ/IVA TC - High Dose Part E: TEZ/IVA Part E: VX-445/TEZ/IVA TC Part F: Placebo Part F: VX-445/TEZ/VX-561 TC Total
    Number of subjects
    		 12 10 22 21 7 21 8 21 122
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 29.7 ( 7.5 ) 27.1 ( 7.4 ) 31.8 ( 8.3 ) 33.3 ( 10.3 ) 27.9 ( 8.0 ) 29.9 ( 7.6 ) 27.8 ( 5.2 ) 30.6 ( 9.5 ) -
    Gender categorical
    Units: Subjects
        Female
    		 2 6 7 11 1 9 5 10 51
        Male
    		 10 4 15 10 6 12 3 11 71
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 0 0 0 1 0 1 0 0 2
        Not Hispanic or Latino
    		 12 10 22 20 7 20 8 20 119
        Unknown or Not Reported
    		 0 0 0 0 0 0 0 1 1
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0 0 0 0 0 0
        Asian
    		 0 0 0 0 0 0 0 0 0
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 0 0 0 0 0
        Black or African American
    		 0 1 0 0 0 0 0 0 1
        White
    		 12 8 22 21 7 21 8 20 119
        More than one race
    		 0 0 0 0 0 0 0 0 0
        Unknown or Not Reported
    		 0 1 0 0 0 0 0 1 2

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Part D: Placebo
    Reporting group description
    		 Subjects with CF, F/MF genotype who received placebo matched to VX-445/TEZ/IVA TC once daily in the morning and placebo matched to IVA in the evening for 4 weeks in the TC treatment period.

    Reporting group title
    Part D: VX-445/TEZ/IVA TC - Low Dose
    Reporting group description
    		 Subjects with CF, F/MF genotype who received VX-445 50 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.

    Reporting group title
    Part D: VX-445/TEZ/IVA TC - Medium Dose
    Reporting group description
    		 Subjects with CF, F/MF genotype who received VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.

    Reporting group title
    Part D: VX-445/TEZ/IVA TC - High Dose
    Reporting group description
    		 Subjects with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.

    Reporting group title
    Part E: TEZ/IVA
    Reporting group description
    		 Following run-in period of 4 weeks with TEZ/IVA, subjects with CF, F/F genotype who received TEZ 100 mg qd/IVA 150 mg q12h and placebo matched to VX-445 for 4 weeks in the TC treatment period.

    Reporting group title
    Part E: VX-445/TEZ/IVA TC
    Reporting group description
    		 Following run-in period of 4 weeks with TEZ/IVA, subjects with CF, F/F genotype who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.

    Reporting group title
    Part F: Placebo
    Reporting group description
    		 Subjects with CF, F/MF genotype who received placebo matched to VX-445/TEZ/VX-561 for 4 weeks in the TC treatment period.

    Reporting group title
    Part F: VX-445/TEZ/VX-561 TC
    Reporting group description
    		 Subjects with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/VX-561 150 mg qd for 4 weeks in the TC treatment period.

    Primary: Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)

    		 Close Top of page
    End point title
    		 Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) [1]
    End point description
    The Safety Set will include all subjects who received at least 1 dose of study drug.
    End point type
    Primary
    End point timeframe
    From first dose of study drug in TC treatment period up to 28 days after last dose of study drug (up to 5 weeks)
    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: Only descriptive statistics were planned. No statistical comparisons were planned for primary safety endpoint.
    End point values
    		 Part D: Placebo Part D: VX-445/TEZ/IVA TC - Low Dose Part D: VX-445/TEZ/IVA TC - Medium Dose Part D: VX-445/TEZ/IVA TC - High Dose Part E: TEZ/IVA Part E: VX-445/TEZ/IVA TC Part F: Placebo Part F: VX-445/TEZ/VX-561 TC
    Number of subjects analysed
    12
    10
    22
    21
    7
    21
    8
    21
    Units: Subjects
        Subjects with AEs
    12
    10
    21
    18
    5
    19
    7
    19
        Subjects with SAEs
    2
    1
    2
    0
    1
    0
    1
    0
    No statistical analyses for this end point

    Primary: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)

    		 Close Top of page
    End point title
    		 Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) [2]
    End point description
    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. The Full analysis set (FAS) included all randomized subjects who carry the intended CFTR allele mutation and have received at least 1 dose of study drug in the TC treatment period.
    End point type
    Primary
    End point timeframe
    From Baseline through Day 29
    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: The study was designed to perform within treatment group comparisons. Because only between treatment comparisons can be reported in the EudraCT database, no statistical analyses are reported.
    End point values
    		 Part D: Placebo Part D: VX-445/TEZ/IVA TC - Low Dose Part D: VX-445/TEZ/IVA TC - Medium Dose Part D: VX-445/TEZ/IVA TC - High Dose Part E: TEZ/IVA Part E: VX-445/TEZ/IVA TC Part F: Placebo Part F: VX-445/TEZ/VX-561 TC
    Number of subjects analysed
    12
    10
    22
    21
    7
    21
    8
    21
    Units: Percentage points
        least squares mean (standard error)
    0.0 ( 2.0 )
    11.1 ( 2.1 )
    7.9 ( 1.4 )
    13.8 ( 1.4 )
    0.4 ( 2.8 )
    11.0 ( 1.5 )
    1.2 ( 2.6 )
    11.7 ( 1.6 )
    No statistical analyses for this end point

    Secondary: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, VX-561, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA)

    		 Close Top of page
    End point title
    		 Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, VX-561, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA) [3]
    End point description
    FAS. Here "n" signifies those subjects who were evaluable at specified time points for each reporting group respectively and "99999" represents "not applicable" categories for Ctrough assessment.
    End point type
    Secondary
    End point timeframe
    Pre-dose on Day 15 and Day 29
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only TC and TEZ/IVA groups were applicable for this endpoint. The Parts D and F placebo groups were not applicable and hence not included in this endpoint.
    End point values
    		 Part D: VX-445/TEZ/IVA TC - Low Dose Part D: VX-445/TEZ/IVA TC - Medium Dose Part D: VX-445/TEZ/IVA TC - High Dose Part E: TEZ/IVA Part E: VX-445/TEZ/IVA TC Part F: VX-445/TEZ/VX-561 TC
    Number of subjects analysed
    10
    21
    21
    7
    21
    20
    Units: Microgram per milliliter
    arithmetic mean (standard deviation)
        VX-445: Day 15 (n=10,21,20,0,21,19)
    1.04 ( 0.612 )
    2.15 ( 0.977 )
    5.77 ( 4.14 )
    99999 ( 99999 )
    5.07 ( 2.47 )
    4.40 ( 1.54 )
        VX-445: Day 29 (n=10,21,21,0,20,20)
    1.27 ( 0.530 )
    2.18 ( 1.26 )
    5.57 ( 2.80 )
    99999 ( 99999 )
    5.35 ( 3.73 )
    5.25 ( 2.88 )
        TEZ: Day 15 (n=10,21,20,7,21,19)
    1.85 ( 1.26 )
    1.68 ( 0.700 )
    1.76 ( 0.960 )
    1.85 ( 0.863 )
    1.86 ( 1.09 )
    1.80 ( 0.658 )
        TEZ: Day 29 (n=10,21,21,7,20,20)
    2.16 ( 1.27 )
    1.77 ( 0.833 )
    2.22 ( 1.62 )
    1.84 ( 1.28 )
    1.99 ( 1.55 )
    2.22 ( 1.65 )
        M1-TEZ: Day 15 (n=10,21,20,7,21,19)
    4.46 ( 1.96 )
    4.11 ( 1.47 )
    4.43 ( 1.79 )
    3.96 ( 1.76 )
    4.57 ( 1.73 )
    4.99 ( 1.71 )
        M1-TEZ: Day 29 (n=10,21,21,7,20,20)
    4.77 ( 2.04 )
    4.30 ( 1.55 )
    4.74 ( 1.89 )
    3.73 ( 1.51 )
    4.71 ( 1.86 )
    5.09 ( 1.37 )
        IVA: Day 15 (n=10,21,20,7,21,0)
    0.720 ( 0.484 )
    0.665 ( 0.414 )
    0.701 ( 0.593 )
    0.766 ( 0.366 )
    0.659 ( 0.529 )
    99999 ( 99999 )
        IVA: Day 29 (n=10,21,21,7,20,0)
    0.753 ( 0.424 )
    0.704 ( 0.414 )
    0.658 ( 0.386 )
    0.595 ( 0.303 )
    0.798 ( 0.901 )
    99999 ( 99999 )
        M1-IVA: Day 15 (n=10,21,20,7,21,0)
    1.29 ( 0.748 )
    1.21 ( 0.666 )
    1.45 ( 1.22 )
    1.22 ( 0.470 )
    1.09 ( 0.973 )
    99999 ( 99999 )
        M1-IVA: Day 29 (n=10,20,21,7,20,0)
    1.57 ( 0.830 )
    1.20 ( 0.717 )
    1.29 ( 0.797 )
    0.943 ( 0.431 )
    1.43 ( 1.54 )
    99999 ( 99999 )
        VX-561: Day 15 (n=0,0,0,0,0,19)
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    0.441 ( 0.174 )
        VX-561: Day 29 (n=0,0,0,0,0,20)
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    0.597 ( 0.473 )
    No statistical analyses for this end point

    Secondary: Absolute Change in Sweat Chloride Concentration

    		 Close Top of page
    End point title
    		 Absolute Change in Sweat Chloride Concentration
    End point description
    Sweat samples were collected using an approved collection device. FAS.
    End point type
    Secondary
    End point timeframe
    From Baseline through Day 29
    End point values
    		 Part D: Placebo Part D: VX-445/TEZ/IVA TC - Low Dose Part D: VX-445/TEZ/IVA TC - Medium Dose Part D: VX-445/TEZ/IVA TC - High Dose Part E: TEZ/IVA Part E: VX-445/TEZ/IVA TC Part F: Placebo Part F: VX-445/TEZ/VX-561 TC
    Number of subjects analysed
    12
    10
    22
    21
    7
    21
    8
    21
    Units: Millimole per liter (mmol/L)
        least squares mean (standard error)
    -2.2 ( 3.9 )
    -38.2 ( 4.2 )
    -33.2 ( 2.8 )
    -39.1 ( 2.9 )
    0.8 ( 4.9 )
    -39.6 ( 2.8 )
    1.0 ( 4.6 )
    -33.6 ( 2.8 )
    No statistical analyses for this end point

    Secondary: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)

    		 Close Top of page
    End point title
    		 Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
    End point description
    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. FAS.
    End point type
    Secondary
    End point timeframe
    From Baseline through Day 29
    End point values
    		 Part D: Placebo Part D: VX-445/TEZ/IVA TC - Low Dose Part D: VX-445/TEZ/IVA TC - Medium Dose Part D: VX-445/TEZ/IVA TC - High Dose Part E: TEZ/IVA Part E: VX-445/TEZ/IVA TC Part F: Placebo Part F: VX-445/TEZ/VX-561 TC
    Number of subjects analysed
    12
    10
    22
    21
    7
    21
    8
    21
    Units: Percent change
        least squares mean (standard error)
    0.3 ( 4.0 )
    19.3 ( 4.2 )
    13.8 ( 2.8 )
    26.2 ( 2.9 )
    1.4 ( 5.0 )
    19.2 ( 2.7 )
    1.6 ( 4.6 )
    19.9 ( 2.8 )
    No statistical analyses for this end point

    Secondary: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score

    		 Close Top of page
    End point title
    		 Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
    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, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. FAS.
    End point type
    Secondary
    End point timeframe
    From Baseline through Day 29
    End point values
    		 Part D: Placebo Part D: VX-445/TEZ/IVA TC - Low Dose Part D: VX-445/TEZ/IVA TC - Medium Dose Part D: VX-445/TEZ/IVA TC - High Dose Part E: TEZ/IVA Part E: VX-445/TEZ/IVA TC Part F: Placebo Part F: VX-445/TEZ/VX-561 TC
    Number of subjects analysed
    12
    10
    22
    21
    7
    21
    8
    21
    Units: Units on a scale
        least squares mean (standard error)
    4.2 ( 4.9 )
    20.8 ( 5.4 )
    15.4 ( 3.7 )
    25.7 ( 3.7 )
    5.2 ( 7.1 )
    20.7 ( 4.0 )
    20.2 ( 6.9 )
    20.2 ( 4.3 )
    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 in TC treatment period up to 28 days after last dose of study drug (up to 5 weeks)
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.1
    Reporting groups
    Reporting group title
    Part D: Placebo
    Reporting group description
    		 Subjects with CF, F/MF genotype who received placebo matched to VX-445/TEZ/IVA TC once daily in the morning and placebo matched to IVA in the evening for 4 weeks in the TC treatment period.

    Reporting group title
    Part D: VX-445/TEZ/IVA TC - Low Dose
    Reporting group description
    		 Subjects with CF, F/MF genotype who received VX-445 50 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.

    Reporting group title
    Part D: VX-445/TEZ/IVA TC - Medium Dose
    Reporting group description
    		 Subjects with CF, F/MF genotype who received VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.

    Reporting group title
    Part D: VX-445/TEZ/IVA TC - High Dose
    Reporting group description
    		 Subjects with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.

    Reporting group title
    Part E: TEZ/IVA
    Reporting group description
    		 Following run-in period of 4 weeks with TEZ/IVA, subjects with CF, F/F genotype who received TEZ 100 mg qd/IVA 150 mg q12h and placebo matched to VX-445 for 4 weeks in the TC treatment period.

    Reporting group title
    Part E: VX-445/TEZ/IVA TC
    Reporting group description
    		 Following run-in period of 4 weeks with TEZ/IVA, subjects with CF, F/F genotype who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.

    Reporting group title
    Part F: Placebo
    Reporting group description
    		 Subjects with CF, F/MF genotype who received placebo matched to VX-445/TEZ/VX-561 for 4 weeks in the TC treatment period.

    Reporting group title
    Part F: VX-445/TEZ/VX-561 TC
    Reporting group description
    		 Subjects with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/VX-561 150 mg qd for 4 weeks in the TC treatment period.

    Serious adverse events
    		 Part D: Placebo Part D: VX-445/TEZ/IVA TC - Low Dose Part D: VX-445/TEZ/IVA TC - Medium Dose Part D: VX-445/TEZ/IVA TC - High Dose Part E: TEZ/IVA Part E: VX-445/TEZ/IVA TC Part F: Placebo Part F: VX-445/TEZ/VX-561 TC
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 12 (16.67%)
    1 / 10 (10.00%)
    2 / 22 (9.09%)
    0 / 21 (0.00%)
    1 / 7 (14.29%)
    0 / 21 (0.00%)
    1 / 8 (12.50%)
    0 / 21 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Investigations
    Influenza A virus test positive
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 22 (4.55%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    0 / 21 (0.00%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Jugular vein thrombosis
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    0 / 21 (0.00%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Distal intestinal obstruction syndrome
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    0 / 21 (0.00%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Haemoptysis
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    0 / 21 (0.00%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Infective pulmonary exacerbation of cystic fibrosis
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 10 (10.00%)
    2 / 22 (9.09%)
    0 / 21 (0.00%)
    1 / 7 (14.29%)
    0 / 21 (0.00%)
    1 / 8 (12.50%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Part D: Placebo Part D: VX-445/TEZ/IVA TC - Low Dose Part D: VX-445/TEZ/IVA TC - Medium Dose Part D: VX-445/TEZ/IVA TC - High Dose Part E: TEZ/IVA Part E: VX-445/TEZ/IVA TC Part F: Placebo Part F: VX-445/TEZ/VX-561 TC
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    12 / 12 (100.00%)
    10 / 10 (100.00%)
    19 / 22 (86.36%)
    17 / 21 (80.95%)
    5 / 7 (71.43%)
    18 / 21 (85.71%)
    7 / 8 (87.50%)
    17 / 21 (80.95%)
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    4 / 12 (33.33%)
    1 / 10 (10.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    4 / 21 (19.05%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    4
    1
    0
    0
    0
    4
    0
    0
    Pyrexia
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    5 / 22 (22.73%)
    1 / 21 (4.76%)
    1 / 7 (14.29%)
    3 / 21 (14.29%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    5
    1
    1
    3
    0
    0
    Malaise
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    1 / 22 (4.55%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    1 / 21 (4.76%)
    0 / 8 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    1
    0
    1
    0
    0
    1
    0
    1
    Pain
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 22 (0.00%)
    1 / 21 (4.76%)
    1 / 7 (14.29%)
    1 / 21 (4.76%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    1
    1
    1
    0
    0
    Chest pain
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    1 / 21 (4.76%)
    0 / 8 (0.00%)
    2 / 21 (9.52%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    2
    Chills
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    3 / 21 (14.29%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    3
    0
    0
    Chest discomfort
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    0 / 21 (0.00%)
    1 / 8 (12.50%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 12 (8.33%)
    4 / 10 (40.00%)
    5 / 22 (22.73%)
    7 / 21 (33.33%)
    1 / 7 (14.29%)
    7 / 21 (33.33%)
    2 / 8 (25.00%)
    5 / 21 (23.81%)
         occurrences all number
    1
    4
    6
    9
    1
    8
    2
    5
    Sputum increased
         subjects affected / exposed
    3 / 12 (25.00%)
    3 / 10 (30.00%)
    4 / 22 (18.18%)
    5 / 21 (23.81%)
    0 / 7 (0.00%)
    8 / 21 (38.10%)
    1 / 8 (12.50%)
    3 / 21 (14.29%)
         occurrences all number
    3
    4
    4
    7
    0
    10
    1
    4
    Haemoptysis
         subjects affected / exposed
    2 / 12 (16.67%)
    0 / 10 (0.00%)
    5 / 22 (22.73%)
    2 / 21 (9.52%)
    0 / 7 (0.00%)
    3 / 21 (14.29%)
    1 / 8 (12.50%)
    1 / 21 (4.76%)
         occurrences all number
    3
    0
    9
    4
    0
    4
    3
    1
    Oropharyngeal pain
         subjects affected / exposed
    2 / 12 (16.67%)
    2 / 10 (20.00%)
    2 / 22 (9.09%)
    2 / 21 (9.52%)
    1 / 7 (14.29%)
    1 / 21 (4.76%)
    2 / 8 (25.00%)
    5 / 21 (23.81%)
         occurrences all number
    2
    2
    2
    2
    1
    1
    2
    5
    Nasal congestion
         subjects affected / exposed
    2 / 12 (16.67%)
    2 / 10 (20.00%)
    2 / 22 (9.09%)
    2 / 21 (9.52%)
    0 / 7 (0.00%)
    0 / 21 (0.00%)
    1 / 8 (12.50%)
    3 / 21 (14.29%)
         occurrences all number
    3
    2
    2
    2
    0
    0
    1
    3
    Dyspnoea
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    1 / 22 (4.55%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    1 / 21 (4.76%)
    1 / 8 (12.50%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    2
    0
    0
    1
    2
    0
    Sinus congestion
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 22 (4.55%)
    1 / 21 (4.76%)
    1 / 7 (14.29%)
    1 / 21 (4.76%)
    0 / 8 (0.00%)
    2 / 21 (9.52%)
         occurrences all number
    0
    0
    1
    1
    1
    1
    0
    2
    Paranasal sinus hypersecretion
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    1 / 22 (4.55%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    1 / 21 (4.76%)
    0 / 8 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    2
    0
    0
    1
    0
    1
    Productive cough
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    0 / 21 (0.00%)
    1 / 8 (12.50%)
    2 / 21 (9.52%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    3
    Respiration abnormal
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 22 (4.55%)
    1 / 21 (4.76%)
    0 / 7 (0.00%)
    2 / 21 (9.52%)
    1 / 8 (12.50%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    2
    1
    0
    Sputum discoloured
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 22 (4.55%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    2 / 21 (9.52%)
    1 / 8 (12.50%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    1
    0
    0
    2
    1
    1
    Paranasal sinus discomfort
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    1 / 21 (4.76%)
    0 / 8 (0.00%)
    2 / 21 (9.52%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    0
    2
    Rhinorrhoea
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    3 / 22 (13.64%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    1 / 21 (4.76%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    1
    0
    0
    Epistaxis
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 22 (4.55%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    1 / 21 (4.76%)
    1 / 8 (12.50%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    1
    0
    Wheezing
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 22 (0.00%)
    1 / 21 (4.76%)
    0 / 7 (0.00%)
    1 / 21 (4.76%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    1
    0
    0
    Lower respiratory tract congestion
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
    1 / 7 (14.29%)
    0 / 21 (0.00%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    0
    0
    Pleuritic pain
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 22 (0.00%)
    1 / 21 (4.76%)
    0 / 7 (0.00%)
    0 / 21 (0.00%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    0
    0
    Upper-airway cough syndrome
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    2 / 22 (9.09%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    0 / 21 (0.00%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    0
    Bronchiectasis
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    0 / 21 (0.00%)
    1 / 8 (12.50%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Pulmonary mass
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    0 / 21 (0.00%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
    1 / 7 (14.29%)
    0 / 21 (0.00%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Investigations
    Blood bilirubin increased
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 22 (4.55%)
    2 / 21 (9.52%)
    1 / 7 (14.29%)
    0 / 21 (0.00%)
    0 / 8 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    1
    2
    2
    0
    0
    1
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 22 (0.00%)
    1 / 21 (4.76%)
    0 / 7 (0.00%)
    4 / 21 (19.05%)
    0 / 8 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    0
    1
    0
    4
    0
    1
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 22 (0.00%)
    1 / 21 (4.76%)
    0 / 7 (0.00%)
    3 / 21 (14.29%)
    0 / 8 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    0
    1
    0
    3
    0
    1
    Forced expiratory volume decreased
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 22 (0.00%)
    1 / 21 (4.76%)
    0 / 7 (0.00%)
    0 / 21 (0.00%)
    0 / 8 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    0
    1
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    2 / 21 (9.52%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    0
    Blood triglycerides increased
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    0 / 21 (0.00%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Pulmonary function test decreased
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
    1 / 7 (14.29%)
    0 / 21 (0.00%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Injury, poisoning and procedural complications
    Radiation injury
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    0 / 21 (0.00%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    2 / 12 (16.67%)
    2 / 10 (20.00%)
    2 / 22 (9.09%)
    2 / 21 (9.52%)
    1 / 7 (14.29%)
    0 / 21 (0.00%)
    1 / 8 (12.50%)
    1 / 21 (4.76%)
         occurrences all number
    2
    2
    2
    3
    1
    0
    2
    1
    Dizziness
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 22 (4.55%)
    1 / 21 (4.76%)
    0 / 7 (0.00%)
    0 / 21 (0.00%)
    1 / 8 (12.50%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    1
    0
    Dysgeusia
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    0 / 21 (0.00%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Ear and labyrinth disorders
    Tinnitus
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    0 / 21 (0.00%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Eye disorders
    Visual impairment
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    0 / 21 (0.00%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 10 (10.00%)
    3 / 22 (13.64%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    0 / 21 (0.00%)
    1 / 8 (12.50%)
    1 / 21 (4.76%)
         occurrences all number
    1
    1
    3
    0
    0
    0
    1
    1
    Nausea
         subjects affected / exposed
    2 / 12 (16.67%)
    2 / 10 (20.00%)
    3 / 22 (13.64%)
    1 / 21 (4.76%)
    1 / 7 (14.29%)
    1 / 21 (4.76%)
    3 / 8 (37.50%)
    2 / 21 (9.52%)
         occurrences all number
    3
    2
    3
    1
    1
    2
    6
    3
    Abdominal pain
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    1 / 22 (4.55%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    2 / 21 (9.52%)
    1 / 8 (12.50%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    3
    1
    0
    Vomiting
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 22 (4.55%)
    1 / 21 (4.76%)
    1 / 7 (14.29%)
    0 / 21 (0.00%)
    2 / 8 (25.00%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    1
    1
    1
    0
    2
    0
    Abdominal pain upper
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    1 / 22 (4.55%)
    1 / 21 (4.76%)
    1 / 7 (14.29%)
    0 / 21 (0.00%)
    0 / 8 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    1
    1
    1
    0
    0
    1
    Abdominal discomfort
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    0 / 21 (0.00%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    0 / 21 (0.00%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Dyspepsia
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    1 / 21 (4.76%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    0
    0
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    0 / 21 (0.00%)
    1 / 8 (12.50%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Acne
         subjects affected / exposed
    0 / 12 (0.00%)
    2 / 10 (20.00%)
    0 / 22 (0.00%)
    1 / 21 (4.76%)
    0 / 7 (0.00%)
    0 / 21 (0.00%)
    0 / 8 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    2
    0
    1
    0
    0
    0
    1
    Pruritus generalised
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    0 / 21 (0.00%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    0
    Eczema
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    0 / 21 (0.00%)
    1 / 8 (12.50%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Renal and urinary disorders
    Pollakiuria
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    0 / 21 (0.00%)
    1 / 8 (12.50%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    0 / 21 (0.00%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 22 (4.55%)
    0 / 21 (0.00%)
    1 / 7 (14.29%)
    0 / 21 (0.00%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    2
    0
    1
    0
    0
    0
    Neck pain
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 22 (0.00%)
    1 / 21 (4.76%)
    1 / 7 (14.29%)
    1 / 21 (4.76%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    1
    0
    0
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    0 / 21 (0.00%)
    1 / 8 (12.50%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    0
    Infections and infestations
    Infective pulmonary exacerbation of cystic fibrosis
         subjects affected / exposed
    4 / 12 (33.33%)
    2 / 10 (20.00%)
    4 / 22 (18.18%)
    2 / 21 (9.52%)
    0 / 7 (0.00%)
    5 / 21 (23.81%)
    3 / 8 (37.50%)
    3 / 21 (14.29%)
         occurrences all number
    4
    2
    4
    2
    0
    6
    4
    3
    Nasopharyngitis
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 22 (0.00%)
    4 / 21 (19.05%)
    1 / 7 (14.29%)
    1 / 21 (4.76%)
    1 / 8 (12.50%)
    0 / 21 (0.00%)
         occurrences all number
    0
    2
    0
    4
    1
    1
    1
    0
    Sinusitis
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 22 (4.55%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    0 / 21 (0.00%)
    1 / 8 (12.50%)
    1 / 21 (4.76%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    1
    1
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 22 (0.00%)
    1 / 21 (4.76%)
    0 / 7 (0.00%)
    0 / 21 (0.00%)
    0 / 8 (0.00%)
    2 / 21 (9.52%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    2
    Oral candidiasis
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    1 / 21 (4.76%)
    1 / 8 (12.50%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    0
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    1 / 21 (4.76%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    0
    0
    Catheter site infection
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    0 / 21 (0.00%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
    1 / 7 (14.29%)
    0 / 21 (0.00%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Otitis media
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
    0 / 7 (0.00%)
    0 / 21 (0.00%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Tonsillitis
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
    1 / 7 (14.29%)
    0 / 21 (0.00%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Viral infection
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 22 (0.00%)
    0 / 21 (0.00%)
    1 / 7 (14.29%)
    0 / 21 (0.00%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 22 (0.00%)
    1 / 21 (4.76%)
    0 / 7 (0.00%)
    1 / 21 (4.76%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    1
    0
    0
    Hypoglycaemia
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 22 (0.00%)
    1 / 21 (4.76%)
    0 / 7 (0.00%)
    0 / 21 (0.00%)
    0 / 8 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    2
    0
    0
    0
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    30 Mar 2017
    - Revised study design to include Parts D and E
    28 Jun 2017
    - Updated eligibility criteria, revised data analysis plans, defined dose levels for parts D and E
    08 Aug 2017
    - Revised study design to include Part F

    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 Apr 26 04:17:35 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA