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A Study Evaluating the Safety and Efficacy of VX-659 Combination Therapy in Subjects With Cystic Fibrosis

Sponsor
Vertex Pharmaceuticals Incorporated (Industry)
Overall Status
Completed
CT.gov ID
NCT03224351
Collaborator
(none)
124
Enrollment
47
Locations
8
Arms
6.7
Actual Duration (Months)
2.6
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase 2, randomized, double-blind, placebo- and tezacaftor/ivacaftor (TEZ/IVA)-controlled, parallel-group, 3-part, multicenter study designed to evaluate the safety and efficacy of VX-659 in triple combination (TC) with TEZ and IVA in subjects with cystic fibrosis (CF) who are homozygous for the F508del mutation of the CF transmembrane conductance regulator (CFTR) gene (F/F genotype), or who are heterozygous for the F508del mutation and a minimal function (MF) CFTR mutation not likely to respond to TEZ, IVA, or TEZ/IVA (F/MF genotypes).

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
124 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 2, Randomized, Double-blind, Controlled Study to Evaluate the Safety and Efficacy of VX-659 Combination Therapy in Subjects Aged 18 Years and Older With Cystic Fibrosis
Actual Study Start Date :
Aug 8, 2017
Actual Primary Completion Date :
Feb 28, 2018
Actual Study Completion Date :
Feb 28, 2018

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Part 1: Placebo

Participants received placebo matched to VX-659/TEZ/IVA in TC treatment period for 4 weeks and placebo matched TEZ/IVA in washout period for 4 days.

Drug: Placebo (matched to VX-659/TEZ/IVA)
Placebo matched to VX-659 and TEZ/IVA.
Experimental: Part 1: VX-659/TEZ/IVA TC - Low Dose

Participants received VX-659 80 milligram (mg) once daily (qd)/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days.

Drug: VX-659
Tablet for oral administration.

Drug: TEZ/IVA
TEZ/IVA fixed-dose combination tablet for oral administration.
Other Names:
  • VX-661/VX-770
  • Tezacaftor/Ivacaftor

    • Drug: IVA
    Tablet for oral administration.
    Other Names:
  • VX-770
  • Ivacaftor

    		•
    Experimental: Part 1: VX-659/TEZ/IVA TC - Medium Dose

    Participants received VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days.

    Drug: VX-659
    Tablet for oral administration.

    Drug: TEZ/IVA
    TEZ/IVA fixed-dose combination tablet for oral administration.
    Other Names:
  • VX-661/VX-770
  • Tezacaftor/Ivacaftor

    • Drug: IVA
    Tablet for oral administration.
    Other Names:
  • VX-770
  • Ivacaftor

    		•
    Experimental: Part 1: VX-659/TEZ/IVA TC - High Dose

    Participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days.

    Drug: VX-659
    Tablet for oral administration.

    Drug: TEZ/IVA
    TEZ/IVA fixed-dose combination tablet for oral administration.
    Other Names:
  • VX-661/VX-770
  • Tezacaftor/Ivacaftor

    • Drug: IVA
    Tablet for oral administration.
    Other Names:
  • VX-770
  • Ivacaftor

    		•
    Active Comparator: Part 2: TEZ/IVA

    Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks.

    Drug: TEZ/IVA
    TEZ/IVA fixed-dose combination tablet for oral administration.
    Other Names:
  • VX-661/VX-770
  • Tezacaftor/Ivacaftor

    • Drug: IVA
    Tablet for oral administration.
    Other Names:
  • VX-770
  • Ivacaftor

    		•
    Experimental: Part 2: VX-659/TEZ/IVA TC

    Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks.

    Drug: VX-659
    Tablet for oral administration.

    Drug: TEZ/IVA
    TEZ/IVA fixed-dose combination tablet for oral administration.
    Other Names:
  • VX-661/VX-770
  • Tezacaftor/Ivacaftor

    • Drug: IVA
    Tablet for oral administration.
    Other Names:
  • VX-770
  • Ivacaftor

    		•
    Placebo Comparator: Part 3: Placebo

    Participants received placebo matched to VX-659/TEZ/VX-561 in TC treatment period for 4 weeks.

    Drug: Placebo (matched to VX-659/TEZ/VX-561)
    Placebo matched to VX-659, TEZ and VX-561.
    Experimental: Part 3: VX-659/TEZ/VX-561 TC

    Participants received VX-659 400 mg qd/TEZ 100 mg qd/VX-561 200 mg qd in TC treatment period for 4 weeks.

    Drug: VX-659
    Tablet for oral administration.

    Drug: TEZ
    Tablet for oral administration.
    Other Names:
  • VX-661
  • Tezacaftor

    • Drug: VX-561
    Tablet for oral administration.
    Other Names:
  • CTP-656

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [Day 1 Through Safety Follow-up (up to Day 61 for Part 1, Day 85 for Part 2 and Day 57 for Part 3)]

    2. Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) [From Baseline Through Day 29]

      FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

    Secondary Outcome Measures

    1. Absolute Change in Sweat Chloride Concentrations [From Baseline Through Day 29]

      Sweat samples were collected using an approved collection device.

    2. Relative Change in ppFEV1 [From Baseline Through Day 29]

      FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

    3. Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score [From Baseline at Day 29]

      The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.

    4. Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 [Pre-dose at Day 15 and Day 29]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:

    • Body weight ≥35 kg.

    • Subjects must have an eligibleCFTR genotype.

    • Part 1 and Part 3: Heterozygous for F508del and an MF mutation (F/MF)

    • Part 2: Homozygous for F508del (F/F)

    • FEV1 value ≥40% and ≤90% of predicted mean for age, sex, and height

    Key Exclusion Criteria:

    • History of clinically significant cirrhosis with or without portal hypertension.

    • Glucose-6-phosphate dehydrogenase (G6PD) deficiency

    • Lung infection with organisms associated with a more rapid decline in pulmonary status.

    • History of solid organ or hematological transplantation.

    Other protocol defined Inclusion/Exclusion criteria may apply.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Yale New Haven Hospital New Haven Connecticut United States 06520
    2 University of Miami/Miller School of Medicine Miami Florida United States 33136
    3 Advocate Children's Hospital - Park Ridge / North Suburban Pulmonary and Critical Care Consultants Morton Grove Illinois United States 60053
    4 Indiana University Health Indianapolis Indiana United States 46202
    5 The University of Iowa Hospitals and Clinics Iowa City Iowa United States 52242
    6 The Johns Hopkins Hospital/ Johns Hopkins Hospital, David Rubenstein Child Health Building Baltimore Maryland United States 21287
    7 Boston Children's Hospital Boston Massachusetts United States 02155
    8 University of Massachusetts Memorial Medical Center Worcester Massachusetts United States 01655
    9 University of Michigan Health System Ann Arbor Michigan United States 48109
    10 Helen DeVos Children's Hospital CF Center Grand Rapids Michigan United States 49503
    11 Children's Mercy Hospital Kansas City Missouri United States 64108
    12 Rutgers-Robert Wood Johnson Medical School/ Rutgers-Robert Wood Johnson Medical School, Clinical Research Center New Brunswick New Jersey United States 08902
    13 Albany Medical College Albany New York United States 12208
    14 Northwell Health, Long Island Jewish Medical Center New Hyde Park New York United States 11040
    15 Columbia University Medical Center New York New York United States 10032
    16 SUNY Upstate Medical University Syracuse New York United States 13210
    17 Respiratory Diseases of Children & Adolescents Oklahoma City Oklahoma United States 73112
    18 Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center Pittsburgh Pennsylvania United States 15224
    19 Sanford Research / USD Sioux Falls South Dakota United States 57104
    20 University of Tennessee Medical Center-Adult Cystic Fibrosis Clinic Knoxville Tennessee United States 37920
    21 Children's Foundation Research Center / Le Bonheur Children's Hospital Memphis Tennessee United States 38103
    22 Vanderbilt University Medical Center Nashville Tennessee United States 37232
    23 University of Utah / Primary Children's Medical Center Salt Lake City Utah United States 84014
    24 Seattle Children's Hospital Seattle Washington United States 98105
    25 Providence Pediatric Pulmonary & Allergy/Immunology Clinic Spokane Washington United States 99204
    26 Cork University Hospital Cork Ireland
    27 St. Vincent's University Hosptial Dublin Ireland
    28 Galway University Hospitals Galway Ireland
    29 University Hospital Limerick Limerick Ireland
    30 Carmel Medical Center Haifa Israel
    31 Ruth Children's Hospital Rambam Health Care Campus Haifa Israel
    32 Hadassah Medical Organization Jerusalem Israel
    33 The Chaim Sheba medical center Ramat Gan Israel
    34 Schneider Children's Medical Center Tikvah Israel
    35 Birmingham Heartlands Hospital Birmingham United Kingdom B95SS
    36 Papworth Hospital NHS Foundation Trust, Papworth Everard Cambridge United Kingdom
    37 University Hospital Llandough in Cardiff Cardiff United Kingdom
    38 Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital Devon United Kingdom
    39 The Newcastle upon Tyne Hospitals NHS Foundation Trust, The Royal Victoria Infirmary Fulham United Kingdom
    40 Greater Glasgow and Clyde NHS Board, Glasgow Clinical Research Facility Glasgow United Kingdom
    41 Southampton University Hospitals NHS Foundation Trust Hampshire United Kingdom
    42 Regional Respiratory Centre Belfast City Hospital London United Kingdom
    43 Royal Brompton & Harefied NHS Foundation Trust London United Kingdom
    44 University Hospital of South Manchester NHS Trust, North West Lung Centre Manchester United Kingdom
    45 Liverpool Heart and Chest Hospital Merseyside United Kingdom
    46 Nottingham University Hospitals NHS Trust Nottingham United Kingdom
    47 Ruth Children's Hospital Rambam Health Care Campus Nottingham United Kingdom

    Sponsors and Collaborators

    • Vertex Pharmaceuticals Incorporated

    Investigators

    None specified.

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Vertex Pharmaceuticals Incorporated
    ClinicalTrials.gov Identifier:
    NCT03224351
    Other Study ID Numbers:
    • VX16-659-101
    • 2016-003585-11
    First Posted:
    Jul 21, 2017
    Last Update Posted:
    Apr 22, 2021
    Last Verified:
    Feb 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Cystic Fibrosis
    Fibrosis
    Ivacaftor
    VX-659

    Study Results

    Participant Flow

    Recruitment Details Total of 124 participants were enrolled in this study (63 in Part 1, 36 in Part 2 and 25 in Part C). Out of 36 participants enrolled in Part 2, 7 participants discontinued treatment in run-in period and were not randomized in triple combination (TC) treatment period. Therefore, below results are presented for 117 participants.
    Pre-assignment Detail This study included 3 parts and was conducted in adult participants with cystic fibrosis (CF).
    Arm/Group Title Part 1: Placebo Part 1: VX-659/TEZ/IVA TC - Low Dose Part 1: VX-659/TEZ/IVA TC - Medium Dose Part 1: VX-659/TEZ/IVA TC - High Dose Part 2: TEZ/IVA Part 2: VX-659/TEZ/IVA TC Part 3: Placebo Part 3: VX-659/TEZ/VX-561 TC
    Arm/Group Description Participants received placebo matched to VX-659/TEZ/IVA in TC treatment period for 4 weeks and placebo matched to TEZ/IVA in washout period for 4 days. Participants received VX-659 80 milligram (mg) once daily (qd)/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. Participants received VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. Participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks. Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks. Participants received placebo matched to VX-659/TEZ/VX-561 in TC treatment period for 4 weeks. Participants received VX-659 400 mg qd/TEZ 100 mg qd/VX-561 200 mg qd in TC treatment period for 4 weeks.
    Period Title: Overall Study
    STARTED 10 11 20 22 11 18 6 19
    COMPLETED 10 11 20 22 11 18 6 19
    NOT COMPLETED 0 0 0 0 0 0 0 0

    Baseline Characteristics

    Arm/Group Title Part 1: Placebo Part 1: VX-659/TEZ/IVA TC - Low Dose Part 1: VX-659/TEZ/IVA TC - Medium Dose Part 1: VX-659/TEZ/IVA TC - High Dose Part 2: TEZ/IVA Part 2: VX-659/TEZ/IVA TC Part 3: Placebo Part 3: VX-659/TEZ/VX-561 TC Total
    Arm/Group Description Participants received placebo matched to VX-659/TEZ/IVA in TC treatment period for 4 weeks and placebo matched to TEZ/IVA in washout period for 4 days. Participants received VX-659 80 mg qd/TEZ 100 mg qd/IVA 150 mg every 12 q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. Participants received VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. Participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks. Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks. Participants received placebo matched to VX-659/TEZ/VX-561 in TC treatment period for 4 weeks. Participants received VX-659 400 mg qd/TEZ 100 mg qd/VX-561 200 mg qd in TC treatment period for 4 weeks. Total of all reporting groups
    Overall Participants 10 11 20 22 11 18 6 19 117
    Age, Customized (Count of Participants)
    <18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    >=18 and <65 years
    10
    100%
    11
    100%
    20
    100%
    22
    100%
    11
    100%
    18
    100%
    6
    100%
    19
    100%
    117
    100%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Sex: Female, Male (Count of Participants)
    Female
    4
    40%
    7
    63.6%
    7
    35%
    12
    54.5%
    4
    36.4%
    6
    33.3%
    3
    50%
    11
    57.9%
    54
    46.2%
    Male
    6
    60%
    4
    36.4%
    13
    65%
    10
    45.5%
    7
    63.6%
    12
    66.7%
    3
    50%
    8
    42.1%
    63
    53.8%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    2
    10%
    0
    0%
    1
    9.1%
    1
    5.6%
    1
    16.7%
    1
    5.3%
    6
    5.1%
    Not Hispanic or Latino
    10
    100%
    11
    100%
    18
    90%
    22
    100%
    10
    90.9%
    17
    94.4%
    5
    83.3%
    18
    94.7%
    111
    94.9%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    5.6%
    0
    0%
    0
    0%
    1
    0.9%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    10.5%
    2
    1.7%
    White
    10
    100%
    11
    100%
    20
    100%
    22
    100%
    11
    100%
    16
    88.9%
    6
    100%
    17
    89.5%
    113
    96.6%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    5.6%
    0
    0%
    0
    0%
    1
    0.9%
    Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) (Count of Participants)
    <40 percent
    2
    20%
    0
    0%
    1
    5%
    2
    9.1%
    0
    0%
    1
    5.6%
    0
    0%
    2
    10.5%
    8
    6.8%
    ≥40 to <70 percent
    6
    60%
    9
    81.8%
    13
    65%
    13
    59.1%
    8
    72.7%
    12
    66.7%
    5
    83.3%
    13
    68.4%
    79
    67.5%
    ≥70 to ≤90 percent
    2
    20%
    2
    18.2%
    6
    30%
    7
    31.8%
    3
    27.3%
    5
    27.8%
    1
    16.7%
    4
    21.1%
    30
    25.6%
    >90 percent
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%

    Outcome Measures

    1. Primary Outcome
    Title Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
    Description
    Time Frame Day 1 Through Safety Follow-up (up to Day 61 for Part 1, Day 85 for Part 2 and Day 57 for Part 3)

    Outcome Measure Data

    Analysis Population Description
    Safety Set included all participants who received at least 1 dose of study drug in TC treatment period.
    Arm/Group Title Part 1: Placebo Part 1: VX-659/TEZ/IVA TC - Low Dose Part 1: VX-659/TEZ/IVA TC - Medium Dose Part 1: VX-659/TEZ/IVA TC - High Dose Part 2: TEZ/IVA Part 2: VX-659/TEZ/IVA TC Part 3: Placebo Part 3: VX-659/TEZ/VX-561 TC
    Arm/Group Description Participants received placebo matched to VX-659/TEZ/IVA in TC treatment period for 4 weeks and placebo matched to TEZ/IVA in washout period for 4 days. Participants received VX-659 80 mg qd/TEZ 100 mg qd/IVA 150 mg every 12 q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. Participants received VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. Participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks. Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks. Participants received placebo matched to VX-659/TEZ/VX-561 in TC treatment period for 4 weeks. Participants received VX-659 400 mg qd/TEZ 100 mg qd/VX-561 200 mg qd in TC treatment period for 4 weeks.
    Measure Participants 10 11 20 22 11 18 6 19
    Participants with TEAEs
    9
    90%
    10
    90.9%
    15
    75%
    17
    77.3%
    9
    81.8%
    15
    83.3%
    6
    100%
    18
    94.7%
    Participants with SAEs
    3
    30%
    1
    9.1%
    4
    20%
    1
    4.5%
    2
    18.2%
    1
    5.6%
    3
    50%
    2
    10.5%
    2. Primary Outcome
    Title Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
    Description FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
    Time Frame From Baseline Through Day 29

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS) included all randomized participants with an eligible cystic fibrosis transmembrane conductance regulator protein (CFTR) genotype and received at least 1 dose of study drug.
    Arm/Group Title Part 1: Placebo Part 1: VX-659/TEZ/IVA TC - Low Dose Part 1: VX-659/TEZ/IVA TC - Medium Dose Part 1: VX-659/TEZ/IVA TC - High Dose Part 2: TEZ/IVA Part 2: VX-659/TEZ/IVA TC Part 3: Placebo Part 3: VX-659/TEZ/VX-561 TC
    Arm/Group Description Participants received placebo matched to VX-659/TEZ/IVA in TC treatment period for 4 weeks and placebo matched to TEZ/IVA in washout period for 4 days. Participants received VX-659 80 mg qd/TEZ 100 mg qd/IVA 150 mg every 12 q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. Participants received VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. Participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks. Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks. Participants received placebo matched to VX-659/TEZ/VX-561 in TC treatment period for 4 weeks. Participants received VX-659 400 mg qd/TEZ 100 mg qd/VX-561 200 mg qd in TC treatment period for 4 weeks.
    Measure Participants 10 11 20 22 11 18 6 19
    Least Squares Mean (95% Confidence Interval) [percentage points]
    0.4
    10.2
    12.0
    13.3
    0.0
    9.7
    -5.0
    12.2
    3. Secondary Outcome
    Title Absolute Change in Sweat Chloride Concentrations
    Description Sweat samples were collected using an approved collection device.
    Time Frame From Baseline Through Day 29

    Outcome Measure Data

    Analysis Population Description
    FAS.
    Arm/Group Title Part 1: Placebo Part 1: VX-659/TEZ/IVA TC - Low Dose Part 1: VX-659/TEZ/IVA TC - Medium Dose Part 1: VX-659/TEZ/IVA TC - High Dose Part 2: TEZ/IVA Part 2: VX-659/TEZ/IVA TC Part 3: Placebo Part 3: VX-659/TEZ/VX-561 TC
    Arm/Group Description Participants received placebo matched to VX-659/TEZ/IVA in TC treatment period for 4 weeks and placebo matched to TEZ/IVA in washout period for 4 days. Participants received VX-659 80 mg qd/TEZ 100 mg qd/IVA 150 mg every 12 q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. Participants received VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. Participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks. Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks. Participants received placebo matched to VX-659/TEZ/VX-561 in TC treatment period for 4 weeks. Participants received VX-659 400 mg qd/TEZ 100 mg qd/VX-561 200 mg qd in TC treatment period for 4 weeks.
    Measure Participants 10 11 20 22 11 18 6 19
    Least Squares Mean (95% Confidence Interval) [millimole per liter (mmol/L)]
    2.9
    -45.7
    -43.8
    -51.4
    3.0
    -42.2
    -1.3
    -38.1
    4. Secondary Outcome
    Title Relative Change in ppFEV1
    Description FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
    Time Frame From Baseline Through Day 29

    Outcome Measure Data

    Analysis Population Description
    FAS.
    Arm/Group Title Part 1: Placebo Part 1: VX-659/TEZ/IVA TC - Low Dose Part 1: VX-659/TEZ/IVA TC - Medium Dose Part 1: VX-659/TEZ/IVA TC - High Dose Part 2: TEZ/IVA Part 2: VX-659/TEZ/IVA TC Part 3: Placebo Part 3: VX-659/TEZ/VX-561 TC
    Arm/Group Description Participants received placebo matched to VX-659/TEZ/IVA in TC treatment period for 4 weeks and placebo matched to TEZ/IVA in washout period for 4 days. Participants received VX-659 80 mg qd/TEZ 100 mg qd/IVA 150 mg every 12 q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. Participants received VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. Participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks. Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks. Participants received placebo matched to VX-659/TEZ/VX-561 in TC treatment period for 4 weeks. Participants received VX-659 400 mg qd/TEZ 100 mg qd/VX-561 200 mg qd in TC treatment period for 4 weeks.
    Measure Participants 10 11 20 22 11 18 6 19
    Least Squares Mean (95% Confidence Interval) [percent change]
    0.0
    18.8
    21.1
    24.6
    0.1
    17.3
    -11.3
    21.5
    5. Secondary Outcome
    Title Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
    Description The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
    Time Frame From Baseline at Day 29

    Outcome Measure Data

    Analysis Population Description
    FAS.
    Arm/Group Title Part 1: Placebo Part 1: VX-659/TEZ/IVA TC - Low Dose Part 1: VX-659/TEZ/IVA TC - Medium Dose Part 1: VX-659/TEZ/IVA TC - High Dose Part 2: TEZ/IVA Part 2: VX-659/TEZ/IVA TC Part 3: Placebo Part 3: VX-659/TEZ/VX-561 TC
    Arm/Group Description Participants received placebo matched to VX-659/TEZ/IVA in TC treatment period for 4 weeks and placebo matched to TEZ/IVA in washout period for 4 days. Participants received VX-659 80 mg qd/TEZ 100 mg qd/IVA 150 mg every 12 q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. Participants received VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. Participants received VX-659 400 mg qd/TEZ 100 mg/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks. Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks. Participants received placebo matched to VX-659/TEZ/VX-561 in TC treatment period for 4 weeks. Participants received VX-659 400 mg qd/TEZ 100 mg qd/VX-561 200 mg qd in TC treatment period for 4 weeks.
    Measure Participants 10 11 20 22 11 18 6 19
    Least Squares Mean (95% Confidence Interval) [units on a scale]
    4.7
    24.6
    19.8
    21.8
    2.9
    19.5
    -4.1
    14.7
    6. Secondary Outcome
    Title Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561
    Description
    Time Frame Pre-dose at Day 15 and Day 29

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Set (PK) included all participants who have received at least 1 dose of study drug in TC treatment period. Here "Number Analyzed" signifies those participants who were evaluable at specified time points. VX-659 category was not applicable for Part 2: TEZ/IVA group. VX-561 category was applicable for Part 3: TC group only. IVA and M1-IVA categories were not applicable for Part 3: TC group.
    Arm/Group Title Part 1: VX-659/TEZ/IVA TC - Low Dose Part 1: VX-659/TEZ/IVA TC - Medium Dose Part 1: VX-659/TEZ/IVA TC - High Dose Part 2: TEZ/IVA Part 2: VX-659/TEZ/IVA TC Part 3: VX-659/TEZ/VX-561 TC
    Arm/Group Description Participants received VX-659 80 mg qd/TEZ 100 mg qd/IVA 150 mg every 12 q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. Participants received VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. Participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks. Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks. Participants received VX-659 400 mg qd/TEZ 100 mg qd/VX-561 200 mg qd in TC treatment period for 4 weeks.
    Measure Participants 11 20 22 11 18 19
    VX-659: Day 15
    393
    (604)
    622
    (429)
    1100
    (731)
    835
    (474)
    1140
    (646)
    VX-659: Day 29
    566
    (861)
    699
    (489)
    1080
    (582)
    1070
    (914)
    923
    (582)
    TEZ: Day 15
    1910
    (1360)
    1250
    (907)
    1110
    (455)
    1050
    (473)
    1350
    (1440)
    1000
    (305)
    TEZ: Day 29
    1910
    (1230)
    1050
    (553)
    1010
    (479)
    1150
    (480)
    955
    (422)
    776
    (321)
    M1-TEZ: Day 15
    4390
    (949)
    3710
    (1230)
    4280
    (1190)
    4160
    (1260)
    4010
    (1210)
    4060
    (660)
    M1-TEZ: Day 29
    4300
    (774)
    3650
    (1280)
    3870
    (1020)
    3790
    (1080)
    3810
    (1120)
    3660
    (1190)
    IVA: Day 15
    824
    (781)
    522
    (567)
    423
    (261)
    458
    (239)
    313
    (158)
    IVA: Day 29
    719
    (604)
    443
    (398)
    371
    (220)
    490
    (179)
    296
    (175)
    M1-IVA: Day 15
    1200
    (711)
    1050
    (852)
    1170
    (674)
    1310
    (684)
    844
    (622)
    M1-IVA Day 29
    1130
    (682)
    1140
    (950)
    1030
    (460)
    1240
    (321)
    866
    (691)
    VX-561: Day 15
    380
    (240)
    VX-561: Day 29
    288
    (165)

    Adverse Events

    Time Frame Day 1 Through Safety Follow-up (up to Day 61 for Part 1, Day 85 for Part 2 and Day 57 for Part 3)
    Adverse Event Reporting Description
    Arm/Group Title Part 1: Placebo Part 1: VX-659/TEZ/IVA TC - Low Dose Part 1: VX-659/TEZ/IVA TC - Medium Dose Part 1: VX-659/TEZ/IVA TC - High Dose Part 2: TEZ/IVA Part 2: VX-659/TEZ/IVA TC Part 3: Placebo Part 3: VX-659/TEZ/VX-561 TC
    Arm/Group Description Participants received placebo matched to VX-659/TEZ/IVA in TC treatment period for 4 weeks and placebo matched to TEZ/IVA in washout period for 4 days. Participants received VX-659 80 mg qd/TEZ 100 mg qd/IVA 150 mg every 12 q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. Participants received VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. Participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks. Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks. Participants received placebo matched to VX-659/TEZ/VX-561 in TC treatment period for 4 weeks. Participants received VX-659 400 mg qd/TEZ 100 mg qd/VX-561 200 mg qd in TC treatment period for 4 weeks.
    All Cause Mortality
    Part 1: Placebo Part 1: VX-659/TEZ/IVA TC - Low Dose Part 1: VX-659/TEZ/IVA TC - Medium Dose Part 1: VX-659/TEZ/IVA TC - High Dose Part 2: TEZ/IVA Part 2: VX-659/TEZ/IVA TC Part 3: Placebo Part 3: VX-659/TEZ/VX-561 TC
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 0/19 (0%)
    Serious Adverse Events
    Part 1: Placebo Part 1: VX-659/TEZ/IVA TC - Low Dose Part 1: VX-659/TEZ/IVA TC - Medium Dose Part 1: VX-659/TEZ/IVA TC - High Dose Part 2: TEZ/IVA Part 2: VX-659/TEZ/IVA TC Part 3: Placebo Part 3: VX-659/TEZ/VX-561 TC
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/10 (30%) 1/11 (9.1%) 4/20 (20%) 1/22 (4.5%) 2/11 (18.2%) 1/18 (5.6%) 3/6 (50%) 2/19 (10.5%)
    General disorders
    Pyrexia 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 1/19 (5.3%)
    Infections and infestations
    Infective pulmonary exacerbation of cystic fibrosis 2/10 (20%) 1/11 (9.1%) 2/20 (10%) 1/22 (4.5%) 2/11 (18.2%) 1/18 (5.6%) 3/6 (50%) 1/19 (5.3%)
    Influenza 0/10 (0%) 0/11 (0%) 1/20 (5%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 0/19 (0%)
    Respiratory tract infection viral 0/10 (0%) 0/11 (0%) 1/20 (5%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 0/19 (0%)
    Pneumonia 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 1/19 (5.3%)
    Investigations
    Pulmonary function test decreased 1/10 (10%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 0/19 (0%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 1/19 (5.3%)
    Pleuritic pain 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 1/19 (5.3%)
    Other (Not Including Serious) Adverse Events
    Part 1: Placebo Part 1: VX-659/TEZ/IVA TC - Low Dose Part 1: VX-659/TEZ/IVA TC - Medium Dose Part 1: VX-659/TEZ/IVA TC - High Dose Part 2: TEZ/IVA Part 2: VX-659/TEZ/IVA TC Part 3: Placebo Part 3: VX-659/TEZ/VX-561 TC
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 8/10 (80%) 10/11 (90.9%) 15/20 (75%) 17/22 (77.3%) 8/11 (72.7%) 15/18 (83.3%) 5/6 (83.3%) 18/19 (94.7%)
    Blood and lymphatic system disorders
    Lymphopenia 1/10 (10%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 0/19 (0%)
    Ear and labyrinth disorders
    Vertigo 0/10 (0%) 0/11 (0%) 1/20 (5%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 1/19 (5.3%)
    Ear congestion 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 1/19 (5.3%)
    Motion sickness 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 1/19 (5.3%)
    Gastrointestinal disorders
    Nausea 0/10 (0%) 0/11 (0%) 0/20 (0%) 3/22 (13.6%) 2/11 (18.2%) 2/18 (11.1%) 0/6 (0%) 2/19 (10.5%)
    Vomiting 0/10 (0%) 0/11 (0%) 0/20 (0%) 1/22 (4.5%) 2/11 (18.2%) 2/18 (11.1%) 0/6 (0%) 1/19 (5.3%)
    Constipation 0/10 (0%) 0/11 (0%) 1/20 (5%) 3/22 (13.6%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 1/19 (5.3%)
    Diarrhoea 0/10 (0%) 1/11 (9.1%) 0/20 (0%) 1/22 (4.5%) 0/11 (0%) 2/18 (11.1%) 0/6 (0%) 1/19 (5.3%)
    Abdominal pain 0/10 (0%) 1/11 (9.1%) 1/20 (5%) 0/22 (0%) 1/11 (9.1%) 1/18 (5.6%) 0/6 (0%) 0/19 (0%)
    Abdominal pain upper 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 2/18 (11.1%) 0/6 (0%) 0/19 (0%)
    Flatulence 0/10 (0%) 0/11 (0%) 0/20 (0%) 1/22 (4.5%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 1/19 (5.3%)
    Faeces discoloured 0/10 (0%) 0/11 (0%) 1/20 (5%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 0/19 (0%)
    Food poisoning 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 1/11 (9.1%) 0/18 (0%) 0/6 (0%) 0/19 (0%)
    Gastrooesophageal reflux disease 0/10 (0%) 0/11 (0%) 1/20 (5%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 0/19 (0%)
    Pancreatic failure 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 1/11 (9.1%) 0/18 (0%) 0/6 (0%) 0/19 (0%)
    Parotid gland enlargement 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 1/18 (5.6%) 0/6 (0%) 0/19 (0%)
    Salivary hypersecretion 0/10 (0%) 0/11 (0%) 1/20 (5%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 0/19 (0%)
    Toothache 0/10 (0%) 0/11 (0%) 1/20 (5%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 0/19 (0%)
    General disorders
    Pyrexia 1/10 (10%) 1/11 (9.1%) 1/20 (5%) 1/22 (4.5%) 1/11 (9.1%) 2/18 (11.1%) 0/6 (0%) 3/19 (15.8%)
    Fatigue 0/10 (0%) 2/11 (18.2%) 2/20 (10%) 0/22 (0%) 1/11 (9.1%) 0/18 (0%) 1/6 (16.7%) 0/19 (0%)
    Pain 0/10 (0%) 0/11 (0%) 0/20 (0%) 1/22 (4.5%) 1/11 (9.1%) 0/18 (0%) 0/6 (0%) 2/19 (10.5%)
    Application site rash 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 1/19 (5.3%)
    Asthenia 1/10 (10%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 0/19 (0%)
    Exercise tolerance decreased 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 1/6 (16.7%) 0/19 (0%)
    Influenza like illness 0/10 (0%) 0/11 (0%) 1/20 (5%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 0/19 (0%)
    Immune system disorders
    Drug hypersensitivity 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 1/19 (5.3%)
    Infections and infestations
    Infective pulmonary exacerbation of cystic fibrosis 1/10 (10%) 2/11 (18.2%) 1/20 (5%) 3/22 (13.6%) 1/11 (9.1%) 4/18 (22.2%) 0/6 (0%) 2/19 (10.5%)
    Nasopharyngitis 1/10 (10%) 2/11 (18.2%) 1/20 (5%) 3/22 (13.6%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 1/19 (5.3%)
    Upper respiratory tract infection 1/10 (10%) 0/11 (0%) 0/20 (0%) 2/22 (9.1%) 0/11 (0%) 2/18 (11.1%) 0/6 (0%) 0/19 (0%)
    Sinusitis 0/10 (0%) 0/11 (0%) 0/20 (0%) 1/22 (4.5%) 0/11 (0%) 1/18 (5.6%) 0/6 (0%) 1/19 (5.3%)
    Influenza 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 2/19 (10.5%)
    Cellulitis 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 1/19 (5.3%)
    Chronic sinusitis 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 1/11 (9.1%) 0/18 (0%) 0/6 (0%) 0/19 (0%)
    Genital infection fungal 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 1/18 (5.6%) 0/6 (0%) 0/19 (0%)
    Lower respiratory tract infection 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 1/19 (5.3%)
    Oral candidiasis 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 1/18 (5.6%) 0/6 (0%) 0/19 (0%)
    Respiratory tract infection viral 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 1/18 (5.6%) 0/6 (0%) 0/19 (0%)
    Viral upper respiratory tract infection 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 1/19 (5.3%)
    Vulvovaginal mycotic infection 1/10 (10%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 0/19 (0%)
    Injury, poisoning and procedural complications
    Laceration 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 1/19 (5.3%)
    Wound 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 1/19 (5.3%)
    Investigations
    Blood creatine phosphokinase increased 0/10 (0%) 1/11 (9.1%) 1/20 (5%) 3/22 (13.6%) 2/11 (18.2%) 1/18 (5.6%) 0/6 (0%) 0/19 (0%)
    Neutrophil count increased 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 1/18 (5.6%) 1/6 (16.7%) 0/19 (0%)
    Aspartate aminotransferase increased 1/10 (10%) 1/11 (9.1%) 0/20 (0%) 0/22 (0%) 1/11 (9.1%) 1/18 (5.6%) 1/6 (16.7%) 0/19 (0%)
    Bacterial test positive 1/10 (10%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 1/18 (5.6%) 0/6 (0%) 1/19 (5.3%)
    Blood glucose increased 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 1/11 (9.1%) 1/18 (5.6%) 0/6 (0%) 0/19 (0%)
    International normalised ratio increased 0/10 (0%) 0/11 (0%) 0/20 (0%) 1/22 (4.5%) 0/11 (0%) 1/18 (5.6%) 0/6 (0%) 1/19 (5.3%)
    Lymphocyte count decreased 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 1/18 (5.6%) 1/6 (16.7%) 0/19 (0%)
    Prothrombin time prolonged 0/10 (0%) 0/11 (0%) 0/20 (0%) 1/22 (4.5%) 0/11 (0%) 1/18 (5.6%) 0/6 (0%) 1/19 (5.3%)
    Weight increased 1/10 (10%) 0/11 (0%) 0/20 (0%) 1/22 (4.5%) 0/11 (0%) 1/18 (5.6%) 0/6 (0%) 0/19 (0%)
    Activated partial thromboplastin time prolonged 0/10 (0%) 0/11 (0%) 0/20 (0%) 1/22 (4.5%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 1/19 (5.3%)
    Alanine aminotransferase increased 0/10 (0%) 1/11 (9.1%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 1/18 (5.6%) 0/6 (0%) 0/19 (0%)
    Blood glucose decreased 0/10 (0%) 0/11 (0%) 0/20 (0%) 1/22 (4.5%) 0/11 (0%) 0/18 (0%) 1/6 (16.7%) 0/19 (0%)
    Blood triglycerides increased 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 1/11 (9.1%) 0/18 (0%) 1/6 (16.7%) 0/19 (0%)
    Pulmonary function test decreased 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 1/18 (5.6%) 0/6 (0%) 1/19 (5.3%)
    Blood alkaline phosphatase increased 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 1/18 (5.6%) 0/6 (0%) 0/19 (0%)
    Blood chloride decreased 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 1/6 (16.7%) 0/19 (0%)
    Blood creatinine decreased 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 1/18 (5.6%) 0/6 (0%) 0/19 (0%)
    Blood glucose fluctuation 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 1/18 (5.6%) 0/6 (0%) 0/19 (0%)
    Blood lactate dehydrogenase increased 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 1/11 (9.1%) 0/18 (0%) 0/6 (0%) 0/19 (0%)
    Blood potassium increased 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 1/11 (9.1%) 0/18 (0%) 0/6 (0%) 0/19 (0%)
    Blood sodium decreased 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 1/6 (16.7%) 0/19 (0%)
    Body temperature increased 0/10 (0%) 1/11 (9.1%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 0/19 (0%)
    Coronavirus test positive 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 1/11 (9.1%) 0/18 (0%) 0/6 (0%) 0/19 (0%)
    Crystal urine present 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 1/19 (5.3%)
    Forced expiratory volume decreased 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 1/11 (9.1%) 0/18 (0%) 0/6 (0%) 0/19 (0%)
    Glucose urine present 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 1/18 (5.6%) 0/6 (0%) 0/19 (0%)
    Haemoglobin decreased 0/10 (0%) 1/11 (9.1%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 0/19 (0%)
    Monocyte count increased 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 1/6 (16.7%) 0/19 (0%)
    Red blood cells urine positive 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 1/19 (5.3%)
    Urinary sediment present 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 1/19 (5.3%)
    Weight decreased 1/10 (10%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 0/19 (0%)
    White blood cell count increased 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 1/6 (16.7%) 0/19 (0%)
    Metabolism and nutrition disorders
    Vitamin D deficiency 0/10 (0%) 1/11 (9.1%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 1/6 (16.7%) 0/19 (0%)
    Abnormal loss of weight 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 1/18 (5.6%) 0/6 (0%) 0/19 (0%)
    Decreased appetite 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 1/18 (5.6%) 0/6 (0%) 0/19 (0%)
    Hypophosphataemia 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 1/19 (5.3%)
    Increased appetite 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 1/19 (5.3%)
    Musculoskeletal and connective tissue disorders
    Back pain 0/10 (0%) 0/11 (0%) 1/20 (5%) 0/22 (0%) 1/11 (9.1%) 1/18 (5.6%) 0/6 (0%) 0/19 (0%)
    Flank pain 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 1/19 (5.3%)
    Intervertebral disc protrusion 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 1/6 (16.7%) 0/19 (0%)
    Musculoskeletal pain 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 1/19 (5.3%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Fibroadenoma of breast 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 1/19 (5.3%)
    Nervous system disorders
    Headache 0/10 (0%) 1/11 (9.1%) 4/20 (20%) 4/22 (18.2%) 0/11 (0%) 3/18 (16.7%) 1/6 (16.7%) 1/19 (5.3%)
    Dizziness 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 1/19 (5.3%)
    Lethargy 1/10 (10%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 0/19 (0%)
    Migraine 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 1/18 (5.6%) 0/6 (0%) 0/19 (0%)
    Sinus headache 1/10 (10%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 0/19 (0%)
    Syncope 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 1/19 (5.3%)
    Psychiatric disorders
    Irritability 0/10 (0%) 0/11 (0%) 1/20 (5%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 0/19 (0%)
    Renal and urinary disorders
    Micturition urgency 0/10 (0%) 0/11 (0%) 1/20 (5%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 0/19 (0%)
    Reproductive system and breast disorders
    Testicular pain 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 1/19 (5.3%)
    Vaginal discharge 0/10 (0%) 1/11 (9.1%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 0/19 (0%)
    Vaginal haemorrhage 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 1/18 (5.6%) 0/6 (0%) 0/19 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough 1/10 (10%) 3/11 (27.3%) 6/20 (30%) 4/22 (18.2%) 2/11 (18.2%) 4/18 (22.2%) 2/6 (33.3%) 4/19 (21.1%)
    Sputum increased 0/10 (0%) 2/11 (18.2%) 1/20 (5%) 3/22 (13.6%) 1/11 (9.1%) 3/18 (16.7%) 0/6 (0%) 1/19 (5.3%)
    Oropharyngeal pain 0/10 (0%) 0/11 (0%) 3/20 (15%) 4/22 (18.2%) 0/11 (0%) 2/18 (11.1%) 0/6 (0%) 2/19 (10.5%)
    Haemoptysis 0/10 (0%) 2/11 (18.2%) 1/20 (5%) 0/22 (0%) 1/11 (9.1%) 1/18 (5.6%) 1/6 (16.7%) 0/19 (0%)
    Respiration abnormal 0/10 (0%) 1/11 (9.1%) 1/20 (5%) 3/22 (13.6%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 0/19 (0%)
    Nasal congestion 0/10 (0%) 0/11 (0%) 1/20 (5%) 0/22 (0%) 0/11 (0%) 4/18 (22.2%) 0/6 (0%) 0/19 (0%)
    Sinus congestion 0/10 (0%) 0/11 (0%) 0/20 (0%) 2/22 (9.1%) 1/11 (9.1%) 0/18 (0%) 0/6 (0%) 2/19 (10.5%)
    Dyspnoea 1/10 (10%) 1/11 (9.1%) 1/20 (5%) 0/22 (0%) 1/11 (9.1%) 0/18 (0%) 0/6 (0%) 0/19 (0%)
    Lower respiratory tract congestion 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 1/11 (9.1%) 2/18 (11.1%) 0/6 (0%) 1/19 (5.3%)
    Productive cough 0/10 (0%) 2/11 (18.2%) 1/20 (5%) 0/22 (0%) 0/11 (0%) 1/18 (5.6%) 0/6 (0%) 0/19 (0%)
    Wheezing 0/10 (0%) 0/11 (0%) 3/20 (15%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 0/19 (0%)
    Paranasal sinus discomfort 0/10 (0%) 1/11 (9.1%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 1/18 (5.6%) 0/6 (0%) 0/19 (0%)
    Rales 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 2/6 (33.3%) 0/19 (0%)
    Rhinorrhoea 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 1/18 (5.6%) 0/6 (0%) 0/19 (0%)
    Sinus pain 0/10 (0%) 0/11 (0%) 0/20 (0%) 2/22 (9.1%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 0/19 (0%)
    Sputum discoloured 0/10 (0%) 0/11 (0%) 1/20 (5%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 0/19 (0%)
    Bronchospasm 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 1/19 (5.3%)
    Epistaxis 1/10 (10%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 0/19 (0%)
    Nasal discharge discolouration 0/10 (0%) 0/11 (0%) 1/20 (5%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 0/19 (0%)
    Throat irritation 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 1/18 (5.6%) 0/6 (0%) 0/19 (0%)
    Throat tightness 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 1/18 (5.6%) 0/6 (0%) 0/19 (0%)
    Skin and subcutaneous tissue disorders
    Rash 0/10 (0%) 0/11 (0%) 0/20 (0%) 1/22 (4.5%) 0/11 (0%) 2/18 (11.1%) 0/6 (0%) 2/19 (10.5%)
    Acne 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 1/18 (5.6%) 0/6 (0%) 1/19 (5.3%)
    Dermatitis 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 1/11 (9.1%) 0/18 (0%) 0/6 (0%) 0/19 (0%)
    Rash erythematous 0/10 (0%) 0/11 (0%) 1/20 (5%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 0/19 (0%)
    Skin disorder 0/10 (0%) 0/11 (0%) 0/20 (0%) 0/22 (0%) 0/11 (0%) 1/18 (5.6%) 0/6 (0%) 0/19 (0%)
    Vascular disorders
    Hot flush 0/10 (0%) 0/11 (0%) 1/20 (5%) 0/22 (0%) 0/11 (0%) 0/18 (0%) 0/6 (0%) 0/19 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Results Point of Contact

    Name/Title Medical Monitor
    Organization Vertex Pharmaceuticals Incorporated
    Phone 617-341-6777
    Email medicalinfo@vrtx.com
    Responsible Party:
    Vertex Pharmaceuticals Incorporated
    ClinicalTrials.gov Identifier:
    NCT03224351
    Other Study ID Numbers:
    • VX16-659-101
    • 2016-003585-11
    First Posted:
    Jul 21, 2017
    Last Update Posted:
    Apr 22, 2021
    Last Verified:
    Feb 1, 2021