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    Clinical Trial Results:
    A Phase 1/2 Study of VX-121 in Healthy Subjects and in Subjects with Cystic Fibrosis

    Summary
    EudraCT number
    2018-000126-55
    Trial protocol
    NL  
    Global end of trial date
    03 May 2019

    Results information
    Results version number
    v2(current)
    This version publication date
    03 Jul 2022
    First version publication date
    17 May 2020
    Other versions
    v1
    Version creation reason
    • New data added to full data set
    Updating secondary outcomes

    Trial information

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    Trial identification
    Sponsor protocol code
    VX17-121-001
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT03768089
    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
    28 May 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    03 May 2019
    Global end of trial reached?
    Yes
    Global end of trial date
    03 May 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the safety and tolerability of single or multiple ascending doses of VX-121 alone or in combination with Tezacaftor/Ivacaftor (TEZ/IVA).
    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
    20 Mar 2018
    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
    Netherlands: 109
    Country: Number of subjects enrolled
    United Kingdom: 6
    Worldwide total number of subjects
    115
    EEA total number of subjects
    115
    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)
    115
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    This study included 4 parts: Parts A, B, and C were conducted in healthy adult subjects; Part D was conducted in adult cystic fibrosis (CF) subjects.

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

    Arms
    Are arms mutually exclusive
    No

    Arm title
    Part A: Pooled Placebo (Except Cohorts A3 and A9)
    Arm description
    Subjects received single dose of placebo matched to VX-121 in Cohorts A1 to A5 (Except Cohorts A3 and A9).
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo (matched to VX-121)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received single dose of placebo matched to VX-121.

    Arm title
    Part A: VX-121 (Except Cohorts A3 and A9)
    Arm description
    Subjects received single dose of VX-121 in Cohorts A1 (10 milligrams [mg]), A2 (20 mg), A4 (40 mg), A5 (60 mg).
    Arm type
    Experimental

    Investigational medicinal product name
    VX-121
    Investigational medicinal product code
    VX-121
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received single ascending dose of VX-121 in Cohorts A1 to A5 (except Cohorts A3 and A9).

    Arm title
    Part A: VX-121 (Cohort A3)
    Arm description
    Subjects received single dose of VX-121 5 mg or matched placebo without milk, followed by open label VX-121 5 mg with milk in Cohort A3.
    Arm type
    Experimental

    Investigational medicinal product name
    VX-121
    Investigational medicinal product code
    VX-121
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received single dose VX-121 without milk, followed by VX-121 with milk in Cohort A3.

    Investigational medicinal product name
    Placebo (matched to VX-121)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received placebo matched to VX-121 without milk, followed by VX-121 with milk in Cohort A3.

    Arm title
    Part A: VX-121 (Cohort A9)
    Arm description
    Subjects received single dose of VX-121 10 mg suspension on Day 1, VX-121 10 mg tablet without milk on Day 9, followed by VX-121 10 mg tablet with milk on Day 17 in Cohort A9.
    Arm type
    Experimental

    Investigational medicinal product name
    VX-121
    Investigational medicinal product code
    VX-121
    Other name
    Pharmaceutical forms
    Tablet, Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received single dose of VX-121 suspension on Day 1, VX-121 tablet on Day 9, and then VX-121 tablet with milk on Day 17 in Cohort A9.

    Arm title
    Part B: Pooled Placebo (Cohorts B1 to B4)
    Arm description
    Subjects received placebo matched to VX-121 in Cohorts B1 to B4 for 10 days.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo (matched to VX-121)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received multiple doses of placebo matched to VX-121 once daily.

    Arm title
    Part B: VX-121 (Cohorts B1 to B4)
    Arm description
    Subjects received VX-121 once daily (qd) in Cohorts B1 (10 mg), B2 (20 mg), B3 (40 mg) and B4 (60 mg) for 10 days.
    Arm type
    Experimental

    Investigational medicinal product name
    VX-121
    Investigational medicinal product code
    VX-121
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received multiple ascending doses of VX-121 once daily.

    Arm title
    Part C: Pooled Placebo (Cohorts C1 to C3)
    Arm description
    Subjects received placebo matched to VX-121/TEZ/IVA in Cohorts C1 to C3 for 14 days.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo (matched to VX-121)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received placebo matched to VX-121 suspension 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 C: VX-121/TEZ/IVA (Cohorts C1 to C3)
    Arm description
    Subjects received VX-121 10 mg qd/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in Cohort C1; VX-121 20 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C2; VX-121 5 mg/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C3 for 14 days.
    Arm type
    Experimental

    Investigational medicinal product name
    VX-121
    Investigational medicinal product code
    VX-121
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received VX-121 suspension 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: Placebo
    Arm description
    Subjects received placebo matched to VX-121/TEZ/IVA for 4 weeks.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo (matched to VX-121)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects with CF received placebo matched to VX-121 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 with CF 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 with CF received placebo matched to IVA once daily in the evening.

    Arm title
    Part D: VX-121/TEZ/IVA
    Arm description
    Subjects received VX-121 5 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    VX-121
    Investigational medicinal product code
    VX-121
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects with CF received VX-121 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 with CF 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 with CF received IVA once daily in the evening.

    Number of subjects in period 1
    Part A: Pooled Placebo (Except Cohorts A3 and A9) Part A: VX-121 (Except Cohorts A3 and A9) Part A: VX-121 (Cohort A3) Part A: VX-121 (Cohort A9) Part B: Pooled Placebo (Cohorts B1 to B4) Part B: VX-121 (Cohorts B1 to B4) Part C: Pooled Placebo (Cohorts C1 to C3) Part C: VX-121/TEZ/IVA (Cohorts C1 to C3) Part D: Placebo Part D: VX-121/TEZ/IVA
    Started
    8
    23
    6
    8
    9
    24
    6
    19
    3
    9
    Completed
    8
    22
    6
    8
    9
    24
    6
    19
    3
    9
    Not completed
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
         Lost to follow-up
    -
    1
    -
    -
    -
    -
    -
    -
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups [1]
    Reporting group title
    Part A: Pooled Placebo (Except Cohorts A3 and A9)
    Reporting group description
    Subjects received single dose of placebo matched to VX-121 in Cohorts A1 to A5 (Except Cohorts A3 and A9).

    Reporting group title
    Part A: VX-121 (Except Cohorts A3 and A9)
    Reporting group description
    Subjects received single dose of VX-121 in Cohorts A1 (10 milligrams [mg]), A2 (20 mg), A4 (40 mg), A5 (60 mg).

    Reporting group title
    Part A: VX-121 (Cohort A3)
    Reporting group description
    Subjects received single dose of VX-121 5 mg or matched placebo without milk, followed by open label VX-121 5 mg with milk in Cohort A3.

    Reporting group title
    Part A: VX-121 (Cohort A9)
    Reporting group description
    Subjects received single dose of VX-121 10 mg suspension on Day 1, VX-121 10 mg tablet without milk on Day 9, followed by VX-121 10 mg tablet with milk on Day 17 in Cohort A9.

    Reporting group title
    Part B: Pooled Placebo (Cohorts B1 to B4)
    Reporting group description
    Subjects received placebo matched to VX-121 in Cohorts B1 to B4 for 10 days.

    Reporting group title
    Part B: VX-121 (Cohorts B1 to B4)
    Reporting group description
    Subjects received VX-121 once daily (qd) in Cohorts B1 (10 mg), B2 (20 mg), B3 (40 mg) and B4 (60 mg) for 10 days.

    Reporting group title
    Part C: Pooled Placebo (Cohorts C1 to C3)
    Reporting group description
    Subjects received placebo matched to VX-121/TEZ/IVA in Cohorts C1 to C3 for 14 days.

    Reporting group title
    Part C: VX-121/TEZ/IVA (Cohorts C1 to C3)
    Reporting group description
    Subjects received VX-121 10 mg qd/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in Cohort C1; VX-121 20 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C2; VX-121 5 mg/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C3 for 14 days.

    Reporting group title
    Part D: Placebo
    Reporting group description
    Subjects received placebo matched to VX-121/TEZ/IVA for 4 weeks.

    Reporting group title
    Part D: VX-121/TEZ/IVA
    Reporting group description
    Subjects received VX-121 5 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks.

    Notes
    [1] - The number of subjects reported to be in the baseline period is not equal to the worldwide number of subjects enrolled in the trial. It is expected that these numbers will be the same.
    Justification: There were 115 unique enrolled subjects in the study. One subject was randomized, but not dosed. Therefore, baseline accounts for 114 unique dosed subjects (one subject participated in 2 parts and thus was counted twice in Baseline section).
    Reporting group values
    Part A: Pooled Placebo (Except Cohorts A3 and A9) Part A: VX-121 (Except Cohorts A3 and A9) Part A: VX-121 (Cohort A3) Part A: VX-121 (Cohort A9) Part B: Pooled Placebo (Cohorts B1 to B4) Part B: VX-121 (Cohorts B1 to B4) Part C: Pooled Placebo (Cohorts C1 to C3) Part C: VX-121/TEZ/IVA (Cohorts C1 to C3) Part D: Placebo Part D: VX-121/TEZ/IVA Total
    Number of subjects
    8 23 6 8 9 24 6 19 3 9
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    29.8 ± 10.6 30.3 ± 11.5 25.8 ± 4.16 33.9 ± 11.5 31.7 ± 14.0 29.6 ± 10.5 30.3 ± 12.1 36.6 ± 13.2 22.8 ± 4.9 34.8 ± 12.8 -
    Gender categorical
    Units: Subjects
        Female
    0 2 0 0 1 0 0 1 0 1 5
        Male
    8 21 6 8 8 24 6 18 3 8 109
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    0 2 1 1 0 0 0 1 0 0 5
        Not Hispanic or Latino
    8 21 5 7 9 24 6 18 3 9 109
        Unknown or Not Reported
    0 0 0 0 0 0 0 0 0 0 0
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    0 1 0 1 0 0 0 0 0 0 2
        Asian
    1 2 0 1 0 1 1 1 0 0 7
        Native Hawaiian or Other Pacific Islander
    0 0 0 0 0 0 0 0 0 0 0
        Black or African American
    1 0 2 1 2 0 0 1 0 0 7
        White
    5 20 4 4 6 22 4 15 3 8 90
        More than one race
    1 0 0 1 1 1 1 1 0 1 7
        Unknown or Not Reported
    0 0 0 0 0 0 0 1 0 0 1

    End points

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    End points reporting groups
    Reporting group title
    Part A: Pooled Placebo (Except Cohorts A3 and A9)
    Reporting group description
    Subjects received single dose of placebo matched to VX-121 in Cohorts A1 to A5 (Except Cohorts A3 and A9).

    Reporting group title
    Part A: VX-121 (Except Cohorts A3 and A9)
    Reporting group description
    Subjects received single dose of VX-121 in Cohorts A1 (10 milligrams [mg]), A2 (20 mg), A4 (40 mg), A5 (60 mg).

    Reporting group title
    Part A: VX-121 (Cohort A3)
    Reporting group description
    Subjects received single dose of VX-121 5 mg or matched placebo without milk, followed by open label VX-121 5 mg with milk in Cohort A3.

    Reporting group title
    Part A: VX-121 (Cohort A9)
    Reporting group description
    Subjects received single dose of VX-121 10 mg suspension on Day 1, VX-121 10 mg tablet without milk on Day 9, followed by VX-121 10 mg tablet with milk on Day 17 in Cohort A9.

    Reporting group title
    Part B: Pooled Placebo (Cohorts B1 to B4)
    Reporting group description
    Subjects received placebo matched to VX-121 in Cohorts B1 to B4 for 10 days.

    Reporting group title
    Part B: VX-121 (Cohorts B1 to B4)
    Reporting group description
    Subjects received VX-121 once daily (qd) in Cohorts B1 (10 mg), B2 (20 mg), B3 (40 mg) and B4 (60 mg) for 10 days.

    Reporting group title
    Part C: Pooled Placebo (Cohorts C1 to C3)
    Reporting group description
    Subjects received placebo matched to VX-121/TEZ/IVA in Cohorts C1 to C3 for 14 days.

    Reporting group title
    Part C: VX-121/TEZ/IVA (Cohorts C1 to C3)
    Reporting group description
    Subjects received VX-121 10 mg qd/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in Cohort C1; VX-121 20 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C2; VX-121 5 mg/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C3 for 14 days.

    Reporting group title
    Part D: Placebo
    Reporting group description
    Subjects received placebo matched to VX-121/TEZ/IVA for 4 weeks.

    Reporting group title
    Part D: VX-121/TEZ/IVA
    Reporting group description
    Subjects received VX-121 5 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks.

    Subject analysis set title
    Part A: VX-121 (Cohort A1)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects received single dose of VX-121 10 mg in Cohort A1.

    Subject analysis set title
    Part A: VX-121 (Cohort A2)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects received single dose of VX-121 20 mg in Cohort A2.

    Subject analysis set title
    Part A: VX-121 (Cohort A3: Without Milk)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects received single dose of VX-121 5 mg without milk in Cohort A3.

    Subject analysis set title
    Part A: VX-121 (Cohort A3: With Milk)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects received single dose of VX-121 5 mg with milk in Cohort A3.

    Subject analysis set title
    Part A: VX-121 (Cohort A4)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects received single dose of VX-121 40 mg in Cohort A4.

    Subject analysis set title
    Part A: VX-121 (Cohort A5)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects received single dose of VX-121 60 mg in Cohort A5.

    Subject analysis set title
    Part A: VX-121 (Cohort A9: Suspension)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects received single dose of VX-121 10 mg suspension on Day 1 in Cohort A9.

    Subject analysis set title
    Part A: VX-121 (Cohort A9: Tablet Without Milk)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects received single dose of VX-121 10 mg tablet without milk on Day 9 in Cohort A9.

    Subject analysis set title
    Part A: VX-121 (Cohort A9: Tablet With Milk)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects received single dose of VX-121 10 mg tablet with milk on Day 17 in Cohort A9.

    Subject analysis set title
    Part B: VX-121 (Cohort B1)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects received VX-121 10 mg qd for 10 days.

    Subject analysis set title
    Part B: VX-121 (Cohort B2)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects received VX-121 20 mg qd for 10 days

    Subject analysis set title
    Part B: VX-121 (Cohort B3)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects received VX-121 40 mg qd for 10 days.

    Subject analysis set title
    Part B: VX-121 (Cohort B4)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects received VX-121 60 mg qd for 10 days.

    Subject analysis set title
    Part C: VX-121 (Cohort C1)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects received VX-121 10 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 14 days.

    Subject analysis set title
    Part C: VX-121 (Cohort C2)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects received VX-121 20 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 14 days.

    Subject analysis set title
    Part C: VX-121 (Cohort C3)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects received VX-121 5 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 14 days.

    Primary: Safety and Tolerability as Assessed by Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

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    End point title
    Safety and Tolerability as Assessed by Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [1]
    End point description
    Safety Set included all subjects who received at least 1 dose of study drug.
    End point type
    Primary
    End point timeframe
    Day 1 Through Safety Follow-up (up to Day 12 for Part A [except Cohorts A3 and A9], up to Day 20 for Cohort A3, up to Day 28 for Cohort A9, up to Day 21 for Part B, up to Day 25 for Part C and up to Week 9 for Part D)
    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 A: Pooled Placebo (Except Cohorts A3 and A9) Part A: VX-121 (Except Cohorts A3 and A9) Part A: VX-121 (Cohort A3) Part A: VX-121 (Cohort A9) Part B: Pooled Placebo (Cohorts B1 to B4) Part B: VX-121 (Cohorts B1 to B4) Part C: Pooled Placebo (Cohorts C1 to C3) Part C: VX-121/TEZ/IVA (Cohorts C1 to C3) Part D: Placebo Part D: VX-121/TEZ/IVA
    Number of subjects analysed
    8
    23
    6
    8
    9
    24
    6
    19
    3
    9
    Units: Subjects
        Subjects with AEs
    1
    9
    4
    7
    7
    17
    4
    12
    2
    7
        Subjects with SAEs
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    No statistical analyses for this end point

    Secondary: Part A: Maximum Observed Concentration (Cmax) of VX-121

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    End point title
    Part A: Maximum Observed Concentration (Cmax) of VX-121
    End point description
    End point type
    Secondary
    End point timeframe
    Cohorts A1-5 (Except A3): Pre-dose up to 240 hours post-dose; Cohorts A3 and A9: Pre-dose up to 168 hours post-dose
    End point values
    Part A: VX-121 (Cohort A1) Part A: VX-121 (Cohort A2) Part A: VX-121 (Cohort A3: Without Milk) Part A: VX-121 (Cohort A3: With Milk) Part A: VX-121 (Cohort A4) Part A: VX-121 (Cohort A5) Part A: VX-121 (Cohort A9: Suspension) Part A: VX-121 (Cohort A9: Tablet Without Milk) Part A: VX-121 (Cohort A9: Tablet With Milk)
    Number of subjects analysed
    5
    6
    5
    5
    6
    6
    8
    8
    8
    Units: microgram per milliliter (mcg/mL)
        arithmetic mean (standard deviation)
    0.134 ± 0.0295
    0.247 ± 0.0515
    0.0705 ± 0.0152
    0.061 ± 0.0143
    0.893 ± 0.216
    1.04 ± 0.263
    0.181 ± 0.0458
    0.178 ± 0.0447
    0.156 ± 0.0352
    No statistical analyses for this end point

    Secondary: Part A: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121

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    End point title
    Part A: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121
    End point description
    PK set.
    End point type
    Secondary
    End point timeframe
    Cohorts A1-5 (Except A3): Pre-dose up to 240 hours post-dose; Cohorts A3 and A9: Pre-dose up to 168 hours post-dose
    End point values
    Part A: VX-121 (Cohort A1) Part A: VX-121 (Cohort A2) Part A: VX-121 (Cohort A3: Without Milk) Part A: VX-121 (Cohort A3: With Milk) Part A: VX-121 (Cohort A4) Part A: VX-121 (Cohort A5) Part A: VX-121 (Cohort A9: Suspension) Part A: VX-121 (Cohort A9: Tablet Without Milk) Part A: VX-121 (Cohort A9: Tablet With Milk)
    Number of subjects analysed
    5
    6
    5
    5
    6
    6
    8
    8
    8
    Units: microgram*hour per milliliter (mcg*h/mL)
        arithmetic mean (standard deviation)
    7.72 ± 1.93
    20.7 ± 7.03
    6.32 ± 2.54
    5.36 ± 2.09
    72.2 ± 28.9
    66.6 ± 9.18
    15.7 ± 3.88
    14.6 ± 3.85
    13.1 ± 2.56
    No statistical analyses for this end point

    Secondary: Part B: Maximum Observed Concentration (Cmax) of VX-121

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    End point title
    Part B: Maximum Observed Concentration (Cmax) of VX-121
    End point description
    PK set. Here, the "n" signifies those subjects who were evaluable for this endpoint at specified time points for each arm respectively.
    End point type
    Secondary
    End point timeframe
    Day 1, Day 5, and Day 10
    End point values
    Part B: VX-121 (Cohort B1) Part B: VX-121 (Cohort B2) Part B: VX-121 (Cohort B3) Part B: VX-121 (Cohort B4)
    Number of subjects analysed
    6
    6
    6
    6
    Units: mcg/mL
    arithmetic mean (standard deviation)
        Day 1 (n=6, 6, 6 ,6)
    0.153 ± 0.0260
    0.418 ± 0.0667
    0.803 ± 0.0529
    1.43 ± 0.217
        Day 5 (n=6, 6, 6, 6)
    0.497 ± 0.0889
    1.41 ± 0.316
    2.67 ± 0.564
    4.36 ± 0.789
        Day 10 (n=6, 6, 5, 5)
    0.574 ± 0.122
    1.94 ± 0.410
    3.07 ± 0.667
    5.07 ± 0.803
    No statistical analyses for this end point

    Secondary: Part B: Area Under the Concentration Versus Time Curve During the Dosing Interval (AUCtau) of VX-121

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    End point title
    Part B: Area Under the Concentration Versus Time Curve During the Dosing Interval (AUCtau) of VX-121
    End point description
    PK set. Here, the "n" signifies those subjects who were evaluable for this endpoint at specified time points for each arm respectively.
    End point type
    Secondary
    End point timeframe
    Day 1, Day 5, and Day 10
    End point values
    Part B: VX-121 (Cohort B1) Part B: VX-121 (Cohort B2) Part B: VX-121 (Cohort B3) Part B: VX-121 (Cohort B4)
    Number of subjects analysed
    6
    6
    6
    6
    Units: mcg*h/mL
    arithmetic mean (standard deviation)
        Day 1 (n=6, 6, 6, 6)
    2.62 ± 0.435
    7.11 ± 1.27
    14.4 ± 1.08
    27.5 ± 4.30
        Day 5 (n=6, 6, 6, 6)
    10.3 ± 1.84
    30.1 ± 6.76
    53.8 ± 10.7
    86.6 ± 16.6
        Day 10 (n=6, 6, 5, 5)
    11.5 ± 2.52
    38.2 ± 9.26
    58.7 ± 12.6
    97.5 ± 17.2
    No statistical analyses for this end point

    Secondary: Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-121

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    End point title
    Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-121
    End point description
    PK set. Here, the "n" signifies those subjects who were evaluable for this endpoint at specified time points for each arm respectively.
    End point type
    Secondary
    End point timeframe
    Pre-dose at Day 5 and Day 10
    End point values
    Part B: VX-121 (Cohort B1) Part B: VX-121 (Cohort B2) Part B: VX-121 (Cohort B3) Part B: VX-121 (Cohort B4)
    Number of subjects analysed
    6
    6
    6
    6
    Units: mcg/mL
    arithmetic mean (standard deviation)
        Day 5 (n=6, 6, 6, 6)
    0.391 ± 0.0694
    1.16 ± 0.266
    2.07 ± 0.537
    2.94 ± 0.759
        Day 10 (n=6, 6, 5, 5)
    0.484 ± 0.109
    1.64 ± 0.414
    2.40 ± 0.637
    3.81 ± 0.792
    No statistical analyses for this end point

    Secondary: Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA)

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    End point title
    Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA)
    End point description
    End point type
    Secondary
    End point timeframe
    Day 1, Day 7, and Day 14
    End point values
    Part C: VX-121 (Cohort C1) Part C: VX-121 (Cohort C2) Part C: VX-121 (Cohort C3)
    Number of subjects analysed
    6
    7
    6
    Units: mcg/mL
    arithmetic mean (standard deviation)
        VX-121: Day 1 (n=6, 7, 6)
    0.212 ± 0.0501
    0.408 ± 0.122
    0.0728 ± 0.0102
        VX-121: Day 7 (n=5, 6, 6)
    1.18 ± 0.735
    1.77 ± 0.416
    0.364 ± 0.122
        VX-121: Day 14 (n=5, 6, 4)
    1.39 ± 0.651
    2.14 ± 0.476
    0.385 ± 0.108
        TEZ: Day 1 (n=6, 7, 6)
    5.97 ± 1.33
    6.75 ± 0.936
    5.11 ± 1.35
        TEZ: Day 7 (n=5, 6, 6)
    9.48 ± 3.09
    8.72 ± 0.561
    7.50 ± 1.24
        TEZ: Day 14 (n=5, 6, 4)
    9.49 ± 3.76
    9.08 ± 0.547
    7.27 ± 1.40
        M1-TEZ: Day 1 (n=6, 7, 6)
    1.09 ± 0.327
    1.24 ± 0.399
    1.12 ± 0.259
        M1-TEZ: Day 7 (n=5, 6, 6)
    5.07 ± 1.10
    6.48 ± 1.48
    5.20 ± 0.606
        M1-TEZ: Day 14 (n=5, 6, 4)
    6.44 ± 1.36
    8.12 ± 1.41
    6.70 ± 1.19
        M2-TEZ: Day 1 (n=6, 7, 6)
    0.521 ± 0.191
    0.622 ± 0.390
    0.662 ± 0.320
        M2-TEZ: Day 7 (n=5, 6, 6)
    4.79 ± 2.03
    6.16 ± 2.17
    5.56 ± 3.67
        M2-TEZ: Day 14 (n=5, 6, 4)
    6.45 ± 2.88
    8.78 ± 3.54
    9.07 ± 6.13
        IVA: Day 1 (n=6, 7, 6)
    1.02 ± 0.158
    1.00 ± 0.235
    0.770 ± 0.169
        IVA: Day 7 (n=5, 6, 6)
    2.15 ± 1.27
    1.40 ± 0.288
    1.37 ± 0.309
        IVA: Day 14 (n=5, 6, 4)
    2.14 ± 1.20
    1.35 ± 0.231
    1.20 ± 0.402
        M1-IVA: Day 1 (n=6, 7, 6)
    1.91 ± 0.573
    2.34 ± 0.602
    1.51 ± 0.349
        M1-IVA: Day 7 (n=5, 6, 6)
    3.91 ± 1.80
    3.42 ± 0.534
    2.65 ± 0.434
        M1-IVA: Day 14 (n=5, 6, 4)
    4.11 ± 1.86
    2.97 ± 0.640
    3.14 ± 1.32
    No statistical analyses for this end point

    Secondary: Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA)

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    End point title
    Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA)
    End point description
    PK set. Here, the "n" signifies those subjects who were evaluable for this endpoint at specified time points for each arm respectively.
    End point type
    Secondary
    End point timeframe
    Day 1, Day 7, and Day 14
    End point values
    Part C: VX-121 (Cohort C1) Part C: VX-121 (Cohort C2) Part C: VX-121 (Cohort C3)
    Number of subjects analysed
    6
    7
    6
    Units: mcg*h/mL
    arithmetic mean (standard deviation)
        VX-121: Day 1 (n=6, 7, 6)
    3.51 ± 0.813
    7.96 ± 0.789
    1.18 ± 0.130
        VX-121: Day 7 (n=5, 6, 6)
    21.7 ± 10.6
    35.4 ± 8.27
    6.52 ± 1.20
        VX-121: Day 14 (n=5, 6, 4)
    26.6 ± 14.5
    41.1 ± 8.29
    7.34 ± 1.63
        TEZ: Day 1 (n=6, 7, 6)
    56.1 ± 16.6
    50.9 ± 7.11
    44.6 ± 11.5
        TEZ: Day 7 (n=5, 6, 6)
    133 ± 60.8
    103 ± 13.9
    88.8 ± 21.0
        TEZ: Day 14 (n=5, 6, 4)
    20.7 ± 7.03
    112 ± 10.4
    87.6 ± 28.6
        M1-TEZ: Day 1 (n=6, 7, 6)
    107 ± 24.8
    24.9 ± 6.61
    20.7 ± 4.99
        M1-TEZ: Day 7 (n=5, 6, 6)
    139 ± 29.7
    130 ± 22.3
    109 ± 14.1
        M1-TEZ: Day 14 (n=5, 6, 4)
    6.68 ± 2.49
    167 ± 24.7
    142 ± 27.0
        M2-TEZ: Day 1 (n=6, 7, 6)
    103 ± 41.1
    9.61 ± 5.51
    7.57 ± 3.18
        M2-TEZ: Day 7 (n=5, 6, 6)
    143 ± 64.1
    130 ± 46.7
    117 ± 72.6
        M2-TEZ: Day 14 (n=5, 6, 4)
    6.16 ± 1.36
    194 ± 82.7
    200 ± 144
        IVA: Day 1 (n=6, 7, 6)
    18.8 ± 12.3
    5.85 ± 1.64
    4.30 ± 0.504
        IVA: Day 7 (n=5, 6, 6)
    18.4 ± 10.7
    11.6 ± 3.26
    11.0 ± 3.73
        IVA: Day 14 (n=5, 6, 4)
    11.5 ± 3.01
    11.2 ± 3.26
    9.02 ± 2.62
        M1-IVA: Day 1 (n=6, 7, 6)
    32.6 ± 17.3
    14.1 ± 1.68
    9.37 ± 1.97
        M1-IVA: Day 7 (n=5, 6, 6)
    32.2 ± 17.3
    27.3 ± 4.79
    22.3 ± 3.70
        M1-IVA: Day 14 (n=5, 6, 4)
    32.2 ± 17.3
    25.3 ± 4.35
    24.2 ± 3.70
        M6-IVA: Day 1 (n=6, 7, 6)
    4.08 ± 1.63
    9.42 ± 4.83
    4.99 ± 2.99
        M6-IVA: Day 7 (n=5, 6, 6)
    15.2 ± 9.34
    26.5 ± 12.7
    19.2 ± 12.8
        M6-IVA: Day 14 (n=5, 6, 4)
    17.6 ± 10.2
    22.6 ± 8.19
    26.4 ± 24.3
    No statistical analyses for this end point

    Secondary: Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA)

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    End point title
    Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA)
    End point description
    PK set. Here, the "number of subjects analysed" signifies those subjects who were evaluable for this endpoint and "n" signifies those subjects who were evaluable for this endpoint at specified timepoints for each arm respectively.
    End point type
    Secondary
    End point timeframe
    Pre-dose at Day 7 and Day 14
    End point values
    Part C: VX-121 (Cohort C1) Part C: VX-121 (Cohort C2) Part C: VX-121 (Cohort C3)
    Number of subjects analysed
    5
    6
    6
    Units: mcg/mL
    arithmetic mean (standard deviation)
        VX-121: Day 7 (n=5, 6, 6)
    0.916 ± 0.369
    1.37 ± 0.321
    0.258 ± 0.0426
        VX-121: Day 14 (n=5, 6, 4)
    1.24 ± 0.665
    1.72 ± 0.452
    0.357 ± 0.0966
        TEZ: Day 7 (n=5, 6, 6)
    3.95 ± 1.84
    2.57 ± 0.776
    2.31 ± 0.735
        TEZ: Day 14 (n=5, 6, 4)
    4.55 ± 2.50
    3.27 ± 0.646
    2.27 ± 0.851
        M1-TEZ: Day 7 (n=5, 6, 6)
    4.09 ± 1.22
    4.53 ± 0.512
    3.96 ± 0.685
        M1-TEZ: Day 14 (n=5, 6, 4)
    5.45 ± 1.46
    6.40 ± 1.17
    5.03 ± 1.18
        M2-TEZ: Day 7 (n=5, 6, 6)
    4.30 ± 1.66
    5.08 ± 2.06
    4.75 ± 2.97
        M2-TEZ: Day 14 (n=5, 6, 4)
    6.20 ± 2.60
    5.51 ± 1.72
    8.63 ± 6.24
        IVA: Day 7 (n=5, 6, 6)
    1.33 ± 0.834
    0.768 ± 0.230
    0.780 ± 0.317
        IVA: Day 14 (n=5, 6, 4)
    1.34 ± 0.889
    0.750 ± 0.252
    0.601 ± 0.164
        M1-IVA: Day 7 (n=5, 6, 6)
    2.46 ± 1.53
    2.00 ± 0.589
    1.67 ± 0.334
        M1-IVA: Day 14 (n=5, 6, 4)
    2.45 ± 1.37
    1.87 ± 0.509
    1.73 ± 0.977
        M6-IVA: Day 7 (n=5, 6, 6)
    1.28 ± 0.763
    2.09 ± 1.11
    1.67 ± 1.31
        M6-IVA: Day 14 (n=5, 6, 4)
    1.60 ± 0.926
    1.85 ± 0.738
    2.27 ± 2.26
    No statistical analyses for this end point

    Secondary: Part D: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA)

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    End point title
    Part D: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) [2]
    End point description
    PK set.
    End point type
    Secondary
    End point timeframe
    Day 1 and Day 15
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The only Part D arm was applicable for this endpoint.
    End point values
    Part D: VX-121/TEZ/IVA
    Number of subjects analysed
    9
    Units: mcg/mL
    arithmetic mean (standard deviation)
        VX-121: Day 1
    0.553 ± 0.0207
        VX-121: Day 15
    0.389 ± 0.116
        TEZ: Day 1
    5.38 ± 1.39
        TEZ: Day 15
    6.80 ± 2.13
        M1-TEZ: Day 1
    1.26 ± 0.162
        M1-TEZ: Day 15
    5.56 ± 1.19
        M2-TEZ: Day 1
    0.243 ± 0.0629
        M2-TEZ: Day 15
    3.99 ± 1.41
        IVA: Day 1
    0.745 ± 0.279
        IVA: Day 15
    1.47 ± 0.472
        M1-IVA: Day 1
    1.34 ± 0.478
        M1-IVA: Day 15
    2.69 ± 0.829
        M6-IVA: Day 1
    0.531 ± 0.229
        M6-IVA: Day 15
    1.17 ± 0.589
    No statistical analyses for this end point

    Secondary: Part D: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA)

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    End point title
    Part D: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) [3]
    End point description
    PK set.
    End point type
    Secondary
    End point timeframe
    Day 1 and Day 15
    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: The only Part D arm was applicable for this endpoint.
    End point values
    Part D: VX-121/TEZ/IVA
    Number of subjects analysed
    9
    Units: mcg*h/mL
    arithmetic mean (standard deviation)
        VX-121: Day 1
    0.160 ± 0.0766
        VX-121: Day 15
    2.50 ± 1.07
        TEZ: Day 1
    21.9 ± 5.48
        TEZ: Day 15
    37.4 ± 16.0
        M1-TEZ: Day 1
    4.66 ± 1.42
        M1-TEZ: Day 15
    37.8 ± 14.3
        M2-TEZ: Day 1
    0.630 ± 0.213
        M2-TEZ: Day 15
    28.6 ± 13.7
        IVA: Day 1
    2.74 ± 1.24
        IVA: Day 15
    9.27 ± 4.06
        M1-IVA: Day 1
    4.51 ± 1.97
        M1-IVA: Day 15
    16.4 ± 6.70
        M6-IVA: Day 1
    1.25 ± 0.529
        M6-IVA: Day 15
    7.58 ± 4.49
    No statistical analyses for this end point

    Secondary: Part D: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA)

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    End point title
    Part D: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) [4]
    End point description
    PK set.
    End point type
    Secondary
    End point timeframe
    Pre-dose at Day 8, Day 15, and Day 29
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The only Part D arm was applicable for this endpoint.
    End point values
    Part D: VX-121/TEZ/IVA
    Number of subjects analysed
    9
    Units: mcg/mL
    arithmetic mean (standard deviation)
        VX-121: Day 8
    0.258 ± 0.0834
        VX-121: Day 15
    0.348 ± 0.109
        VX-121: Day 29
    0.323 ± 0.110
        TEZ: Day 8
    1.78 ± 0.525
        TEZ: Day 15
    2.01 ± 0.543
        TEZ: Day 29
    2.02 ± 0.927
        M1-TEZ: Day 8
    4.15 ± 0.648
        M1-TEZ: Day 15
    4.52 ± 1.06
        M1-TEZ: Day 29
    5.11 ± 1.50
        M2-TEZ: Day 8
    3.29 ± 1.41
        M2-TEZ: Day 15
    3.76 ± 1.29
        M2-TEZ: Day 29
    4.57 ± 2.28
        IVA: Day 8
    0.873 ± 0.367
        IVA: Day 15
    0.998 ± 0.367
        IVA: Day 29
    0.916 ± 0.586
        M1-IVA: Day 8
    1.38 ± 0.427
        M1-IVA: Day 15
    1.76 ± 0.619
        M1-IVA: Day 29
    1.62 ± 0.620
        M6-IVA: Day 8
    0.823 ± 0.573
        M6-IVA: Day 15
    0.819 ± 0.412
        M6-IVA: Day 29
    0.990 ± 0.632
    No statistical analyses for this end point

    Secondary: Part D: Absolute Change in Sweat Chloride (SwCl) Concentrations

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    End point title
    Part D: Absolute Change in Sweat Chloride (SwCl) Concentrations [5]
    End point description
    Sweat samples were collected using an approved collection device. Full analysis set (FAS) included all randomized subjects who carry the intended CF transmembrane conductance regulator protein (CFTR) allele mutation and have received at least 1 dose of study drug in the treatment period.
    End point type
    Secondary
    End point timeframe
    From Baseline Through Day 29
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The only Part D arm was applicable for this endpoint.
    End point values
    Part D: Placebo Part D: VX-121/TEZ/IVA
    Number of subjects analysed
    3
    9
    Units: millimole per liter (mmol/L)
        least squares mean (confidence interval 95%)
    2.6 (-19.7 to 24.9)
    -47.7 (-58.2 to -37.2)
    No statistical analyses for this end point

    Secondary: Part D: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)

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    End point title
    Part D: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) [6]
    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
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The only Part D arm was applicable for this endpoint.
    End point values
    Part D: Placebo Part D: VX-121/TEZ/IVA
    Number of subjects analysed
    3
    9
    Units: percentage points
        least squares mean (confidence interval 95%)
    -2.0 (-12.9 to 8.9)
    8.3 (2.8 to 13.8)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Day 1 Through Safety Follow-up (up to Day 12 for Part A [except Cohorts A3 and A9], up to Day 20 for Cohort A3, up to Day 28 for Cohort A9, up to Day 21 for Part B, up to Day 25 for Part C and up to Week 9 for Part D)
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    22.0
    Reporting groups
    Reporting group title
    Part A: VX-121 (Except Cohorts A3 and A9)
    Reporting group description
    Subjects received single dose of VX-121 in Cohorts A1 (10 milligrams [mg]), A2 (20 mg), A4 (40 mg), A5 (60 mg).

    Reporting group title
    Part A: Pooled Placebo (Except Cohorts A3 and A9)
    Reporting group description
    Subjects received single dose of placebo matched to VX-121 in Cohorts A1 to A5 (Except Cohorts A3 and A9).

    Reporting group title
    Part A: VX-121 (Cohort A9)
    Reporting group description
    Subjects received single dose of VX-121 10 mg suspension on Day 1, VX-121 10 mg tablet without milk on Day 9, followed by VX-121 10 mg tablet with milk on Day 17 in Cohort A9.

    Reporting group title
    Part A: VX-121 (Cohort A3)
    Reporting group description
    Subjects received single dose of VX-121 5 mg or matched placebo without milk, followed by open label VX-121 5 mg with milk in Cohort A3.

    Reporting group title
    Part B: Pooled Placebo (Cohorts B1 to B4)
    Reporting group description
    Subjects received placebo matched to VX-121 in Cohorts B1 to B4 for 10 days.

    Reporting group title
    Part B: VX-121 (Cohorts B1 to B4)
    Reporting group description
    Subjects received VX-121 qd in Cohorts B1 (10 mg), B2 (20 mg), B3 (40 mg) and B4 (60 mg) for 10 days.

    Reporting group title
    Part C: Pooled Placebo (Cohorts C1 to C3)
    Reporting group description
    Subjects received placebo matched to VX-121/TEZ/IVA in Cohorts C1 to C3 for 14 days.

    Reporting group title
    Part C: VX-121/TEZ/IVA (Cohorts C1 to C3)
    Reporting group description
    Subjects received VX-121 10 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C1; VX-121 20 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C2; VX-121 5 mg/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C3 for 14 days.

    Reporting group title
    Part D: Placebo
    Reporting group description
    Subjects received placebo matched to VX-121/TEZ/IVA for 4 weeks.

    Reporting group title
    Part D: VX-121/TEZ/IVA
    Reporting group description
    Subjects received VX-121 5 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks.

    Serious adverse events
    Part A: VX-121 (Except Cohorts A3 and A9) Part A: Pooled Placebo (Except Cohorts A3 and A9) Part A: VX-121 (Cohort A9) Part A: VX-121 (Cohort A3) Part B: Pooled Placebo (Cohorts B1 to B4) Part B: VX-121 (Cohorts B1 to B4) Part C: Pooled Placebo (Cohorts C1 to C3) Part C: VX-121/TEZ/IVA (Cohorts C1 to C3) Part D: Placebo Part D: VX-121/TEZ/IVA
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    0 / 19 (0.00%)
    1 / 3 (33.33%)
    0 / 9 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Infections and infestations
    Infective pulmonary exacerbation of cystic fibrosis
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    0 / 19 (0.00%)
    1 / 3 (33.33%)
    0 / 9 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Part A: VX-121 (Except Cohorts A3 and A9) Part A: Pooled Placebo (Except Cohorts A3 and A9) Part A: VX-121 (Cohort A9) Part A: VX-121 (Cohort A3) Part B: Pooled Placebo (Cohorts B1 to B4) Part B: VX-121 (Cohorts B1 to B4) Part C: Pooled Placebo (Cohorts C1 to C3) Part C: VX-121/TEZ/IVA (Cohorts C1 to C3) Part D: Placebo Part D: VX-121/TEZ/IVA
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    9 / 23 (39.13%)
    1 / 8 (12.50%)
    7 / 8 (87.50%)
    4 / 6 (66.67%)
    7 / 9 (77.78%)
    16 / 24 (66.67%)
    4 / 6 (66.67%)
    12 / 19 (63.16%)
    2 / 3 (66.67%)
    7 / 9 (77.78%)
    Vascular disorders
    Phlebitis
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    1 / 19 (5.26%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 24 (4.17%)
    0 / 6 (0.00%)
    0 / 19 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    0
    0
    0
    0
    Catheter site bruise
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    1 / 6 (16.67%)
    3 / 19 (15.79%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    3
    0
    0
    Catheter site erythema
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    0 / 19 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Catheter site irritation
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
    2 / 24 (8.33%)
    0 / 6 (0.00%)
    0 / 19 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    2
    0
    0
    0
    0
    Catheter site pain
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    1 / 9 (11.11%)
    2 / 24 (8.33%)
    0 / 6 (0.00%)
    1 / 19 (5.26%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    1
    2
    2
    0
    4
    0
    0
    Catheter site pruritus
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    0 / 19 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Chest discomfort
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    0 / 19 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    0
    0
    0
    Fatigue
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 8 (0.00%)
    2 / 8 (25.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    1 / 19 (5.26%)
    1 / 3 (33.33%)
    1 / 9 (11.11%)
         occurrences all number
    1
    0
    5
    0
    0
    0
    0
    1
    1
    1
    Feeling cold
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    0 / 19 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Feeling hot
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    1 / 19 (5.26%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Puncture site pain
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    0 / 19 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Vessel puncture site bruise
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
    3 / 24 (12.50%)
    0 / 6 (0.00%)
    0 / 19 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    4
    0
    0
    0
    0
    Vessel puncture site pain
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    0 / 19 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    0 / 19 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Insomnia
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    1 / 24 (4.17%)
    0 / 6 (0.00%)
    3 / 19 (15.79%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    1
    0
    3
    0
    0
    Tension
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    0 / 19 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Arthropod bite
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    2 / 24 (8.33%)
    0 / 6 (0.00%)
    1 / 19 (5.26%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    2
    0
    1
    0
    0
    Contusion
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    2 / 24 (8.33%)
    0 / 6 (0.00%)
    1 / 19 (5.26%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    2
    0
    1
    0
    0
    Procedural complication
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    0 / 19 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    0 / 19 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Faecal volume decreased
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    1 / 19 (5.26%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Influenza A virus test positive
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    0 / 19 (0.00%)
    0 / 3 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Blood and lymphatic system disorders
    Lymphadenopathy
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    1 / 19 (5.26%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 24 (4.17%)
    0 / 6 (0.00%)
    1 / 19 (5.26%)
    1 / 3 (33.33%)
    2 / 9 (22.22%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    1
    1
    3
    Dyspnoea
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    1 / 19 (5.26%)
    0 / 3 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    2
    0
    1
    Epistaxis
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    2 / 19 (10.53%)
    1 / 3 (33.33%)
    2 / 9 (22.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    2
    1
    2
    Nasal congestion
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    1 / 19 (5.26%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    1
    0
    0
    Oropharyngeal pain
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    2 / 19 (10.53%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    2
    0
    0
    Painful respiration
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    0 / 19 (0.00%)
    0 / 3 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Productive cough
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    2 / 19 (10.53%)
    0 / 3 (0.00%)
    2 / 9 (22.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    2
    0
    2
    Rhinorrhoea
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    1 / 19 (5.26%)
    0 / 3 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    1
    Sputum increased
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    0 / 19 (0.00%)
    0 / 3 (0.00%)
    3 / 9 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    4
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 24 (4.17%)
    2 / 6 (33.33%)
    4 / 19 (21.05%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    3
    4
    0
    0
    Dizziness postural
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    2 / 19 (10.53%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    2
    0
    0
    Headache
         subjects affected / exposed
    2 / 23 (8.70%)
    1 / 8 (12.50%)
    4 / 8 (50.00%)
    1 / 6 (16.67%)
    2 / 9 (22.22%)
    3 / 24 (12.50%)
    1 / 6 (16.67%)
    6 / 19 (31.58%)
    0 / 3 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    2
    1
    4
    1
    2
    3
    2
    7
    0
    1
    Nerve compression
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    1 / 6 (16.67%)
    0 / 19 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Somnolence
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    1 / 9 (11.11%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    1 / 19 (5.26%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    1
    0
    0
    Eye disorders
    Eye irritation
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    1 / 19 (5.26%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    0
    0
    Ocular hyperaemia
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    1 / 19 (5.26%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    0
    1
    0
    0
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    1 / 19 (5.26%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    1 / 19 (5.26%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    2
    0
    0
    Abdominal pain
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    0 / 19 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Abdominal pain upper
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    0 / 19 (0.00%)
    0 / 3 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Constipation
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    1 / 19 (5.26%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Defaecation urgency
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    1 / 19 (5.26%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Diarrhoea
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    2 / 19 (10.53%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    4
    0
    0
    Dyspepsia
         subjects affected / exposed
    2 / 23 (8.70%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    1 / 6 (16.67%)
    2 / 19 (10.53%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    1
    2
    0
    0
    Flatulence
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    1 / 24 (4.17%)
    0 / 6 (0.00%)
    2 / 19 (10.53%)
    0 / 3 (0.00%)
    2 / 9 (22.22%)
         occurrences all number
    1
    0
    0
    0
    1
    1
    0
    2
    0
    2
    Nausea
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    1 / 24 (4.17%)
    0 / 6 (0.00%)
    2 / 19 (10.53%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    3
    0
    0
    Oral pain
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    1 / 19 (5.26%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Salivary hypersecretion
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    1 / 19 (5.26%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Toothache
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    2 / 24 (8.33%)
    0 / 6 (0.00%)
    0 / 19 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    Vomiting
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    0 / 19 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Renal and urinary disorders
    Pollakiuria
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 24 (4.17%)
    0 / 6 (0.00%)
    2 / 19 (10.53%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    2
    0
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    3 / 24 (12.50%)
    0 / 6 (0.00%)
    0 / 19 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    3
    0
    0
    0
    0
    Dermal cyst
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    0 / 19 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Erythema
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 24 (4.17%)
    0 / 6 (0.00%)
    2 / 19 (10.53%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    2
    0
    0
    Hyperhidrosis
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    2 / 19 (10.53%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    0
    0
    Papule
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    1 / 19 (5.26%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Pruritus
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 24 (4.17%)
    0 / 6 (0.00%)
    1 / 19 (5.26%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    2
    0
    0
    Pruritus generalised
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 24 (4.17%)
    0 / 6 (0.00%)
    1 / 19 (5.26%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    1
    0
    0
    Rash
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 24 (4.17%)
    1 / 6 (16.67%)
    1 / 19 (5.26%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    1
    1
    0
    0
    Rash macular
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    2 / 24 (8.33%)
    0 / 6 (0.00%)
    0 / 19 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    3
    0
    0
    0
    0
    Rash maculo-papular
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    2 / 24 (8.33%)
    0 / 6 (0.00%)
    1 / 19 (5.26%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    1
    0
    0
    Seborrhoeic dermatitis
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    1 / 19 (5.26%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Skin hypertrophy
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    1 / 6 (16.67%)
    0 / 19 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Skin hypopigmentation
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    0 / 19 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    Skin irritation
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 24 (4.17%)
    0 / 6 (0.00%)
    0 / 19 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    0
    0
    0
    0
    Swelling face
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    1 / 19 (5.26%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    4 / 9 (44.44%)
    2 / 24 (8.33%)
    1 / 6 (16.67%)
    0 / 19 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    4
    2
    1
    0
    0
    0
    Flank pain
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    0 / 19 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Muscle twitching
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    0 / 19 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    1 / 6 (16.67%)
    0 / 19 (0.00%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Myalgia
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    1 / 19 (5.26%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    1
    0
    0
    Infections and infestations
    Infective pulmonary exacerbation of cystic fibrosis
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    0 / 19 (0.00%)
    1 / 3 (33.33%)
    2 / 9 (22.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    2
    Nasopharyngitis
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    1 / 6 (16.67%)
    3 / 19 (15.79%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    1
    3
    0
    0
    Periodontitis
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 24 (0.00%)
    0 / 6 (0.00%)
    1 / 19 (5.26%)
    0 / 3 (0.00%)
    0 / 9 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    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
    09 May 2018
    Refined study design and revised exclusion criteria
    27 Jul 2018
    Updated dosing guidance and prohibited medications

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

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