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A Study Evaluating the Safety of VX-152 Combination Therapy in Adults With Cystic Fibrosis

Sponsor
Vertex Pharmaceuticals Incorporated (Industry)
Overall Status
Completed
CT.gov ID
NCT02951195
Collaborator
(none)
80
Enrollment
16
Locations
8
Arms
14
Actual Duration (Months)
5
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 active-controlled, parallel group, multicenter study designed to evaluate the safety and tolerability of VX-152 in Triple Combination (TC) with tezacaftor (TEZ; VX-661) and ivacaftor (IVA; VX-770) in subjects with cystic fibrosis (CF) who are heterozygous for the F508del mutation and a minimal function (MF) CFTR mutation not likely to respond to TEZ and/or IVA therapy (F508del/MF), or who are homozygous for the F508del mutation of the CF transmembrane conductance regulator (CFTR) gene (F508del/F508del).

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
80 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase 2, Randomized, Double Blind, Controlled Study to Evaluate the Safety of VX-152 Combination Therapy in Adults With Cystic Fibrosis
Actual Study Start Date :
Nov 1, 2016
Actual Primary Completion Date :
Jan 1, 2018
Actual Study Completion Date :
Jan 1, 2018

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Part 1: Placebo

Drug: Placebo
Placebo matched to VX-152/TEZ/IVA triple combination (TC).
Experimental: Part 1 Cohort 1A: TC

Drug: VX-152
Tablet for oral administration.

Drug: 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 Cohort 1B: TC

    Drug: VX-152
    Tablet for oral administration.

    Drug: 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 Cohort 1C: TC

    Drug: VX-152
    Tablet for oral administration.

    Drug: 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 Cohort 2A: TEZ/IVA

    Drug: 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

    • Drug: Placebo
    Placebo matched to VX-152.
    Experimental: Part 2 Cohort 2A: TC

    Drug: VX-152
    Tablet for oral administration.

    Drug: 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 Cohort 2B: TEZ/IVA

    Drug: 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

    • Drug: Placebo
    Placebo matched to VX-152.
    Experimental: Part 2 Cohort 2B: TC

    Drug: VX-152
    Tablet for oral administration.

    Drug: 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

    		•

    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 Visit (Up to Day 43 for Part 1 and Day 71 for Part 2)]

    2. Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 15 for Part 1 and Part 2 Cohort 2A [From Baseline at Day 15]

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

    3. Absolute Change in ppFEV1 Through Day 29 for Part 2 Cohort 2B [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 at Day 15 for Part 1 and Part 2 Cohort 2A [From Baseline at Day 15]

      Sweat samples were collected using an approved collection device.

    2. Absolute Change in Sweat Chloride Concentrations Through Day 29 for Part 2 Cohort 2B [From Baseline Through Day 29]

      Sweat samples were collected using an approved collection device.

    3. Relative Change in ppFEV1 at Day 15 for Part 1 and Part 2 Cohort 2A [From Baseline at Day 15]

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

    4. Relative Change in ppFEV1 Through Day 29 for Part 2 Cohort 2B [From Baseline Through Day 29]

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

    5. Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Day 15 for Part 1 and Part 2 Cohort 2A [From Baseline at Day 15]

      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.

    6. Absolute Change From Baseline in CFQ-R Respiratory Domain Score at Day 29 for Part 2 Cohort 2B [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.

    7. Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA [Pre-dose at Day 8, 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
    Inclusion Criteria:

    • Willing and able to comply with scheduled visits, treatment pan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures.

    • Body weight ≥35 kg.

    • Sweat chloride value ≥ 60 mmol/L from test results obtained during screening.

    • Subjects must have an eligible CFTR genotype:

    • Cohorts 1A, 1B, 1C: Heterozygous for F508del and a minimal function mutation known or predicted not to respond to TEZ and/or IVA.

    • Cohorts 2A, 2B: Homozygous for F508del.

    • Subjects must have an FEV1 ≥40% and ≤90% of predicted normal for age, sex, and height at the Screening Visit.

    • Stable CF disease as judged by the investigator.

    • Willing to remain on a stable CF medication regimen through the planned end of treatment or if applicable the Safety Follow-up Visit.

    Exclusion Criteria:

    • History of any comorbidity that in the opinion of the investigator might confound the results of the study or pose an additional risk in administering study drug to the subject.

    • History of cirrhosis with portal hypertension.

    • Risk factors for Torsade de Pointes.

    • History of hemolysis.

    • Glucose-6-phosphate dehydrogenase (G6PD) deficiency assessed at Screening.

    • Clinically significant abnormal laboratory values at screening.

    • An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 28 days before the first dose of study drug.

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

    • An acute illness not related to CF within 14 days before the first dose of study drug.

    • A standard digital ECG demonstrating QTc >450 msec at screening.

    • History of solid organ or hematological transplantation.

    • History or evidence of cataract or lens opacity determined to be clinically significant by the ophthalmologist or optometrist, based on the ophthalmologic examination during the Screening Period.

    • History of alcohol or drug abuse in the past year, including but not limited to, cannabis, cocaine, and opiates, as deemed by the investigator.

    • Ongoing or prior participation in an investigational drug study with certain exceptions.

    • Use of commercially available CFTR modulator within 14 days before screening (applies only to Cohorts 1A, 1B, and 1C).

    • Pregnant or nursing females: Females of childbearing potential must have a negative pregnancy test at screening and Day 1.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Birmingham Alabama United States
    2 La Jolla California United States
    3 Los Angeles California United States
    4 Orlando Florida United States
    5 Chicago Illinois United States
    6 Peoria Illinois United States
    7 Saint Louis Missouri United States
    8 Chapel Hill North Carolina United States
    9 Akron Ohio United States
    10 Cleveland Ohio United States
    11 Portland Oregon United States
    12 Philadelphia Pennsylvania United States
    13 Charleston South Carolina United States
    14 Fort Worth Texas United States
    15 Houston Texas United States
    16 Madison Wisconsin United States

    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:
    NCT02951195
    Other Study ID Numbers:
    • VX16-152-102
    First Posted:
    Nov 1, 2016
    Last Update Posted:
    Jan 28, 2021
    Last Verified:
    Jan 1, 2021
    Additional relevant MeSH terms:
    Cystic Fibrosis
    Fibrosis
    Ivacaftor

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail A total of 80 participants were enrolled in the study (34 participants in Part 1 and 46 participants in Part 2). Out of 46 participants enrolled in Part 2, 4 participants discontinued during the run-in period and were not randomized in the treatment period. Therefore, results are presented for 76 participants in this study.
    Arm/Group Title Part 1: Placebo Part 1 Cohort 1A: TC Part 1 Cohort 1B: TC Part 1 Cohort 1C: TC Part 2 Cohort 2A: TEZ/IVA Part 2 Cohort 2A: TC Part 2 Cohort 2B: TEZ/IVA Part 2 Cohort 2B: TC
    Arm/Group Description Participants received placebo matched to VX-152/TEZ/IVA triple combination (TC) for 2 weeks. Participants received VX-152 100 milligram (mg) every 12 hours (q12h)/TEZ 100 mg once daily (qd)/IVA 150 mg q12h TC for 2 weeks. Participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks. Participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
    Period Title: Overall Study
    STARTED 8 6 10 10 4 10 7 21
    COMPLETED 8 6 10 10 4 10 7 21
    NOT COMPLETED 0 0 0 0 0 0 0 0

    Baseline Characteristics

    Arm/Group Title Part 1: Placebo Part 1 Cohort 1A: TC Part 1 Cohort 1B: TC Part 1 Cohort 1C: TC Part 2 Cohort 2A: TEZ/IVA Part 2 Cohort 2A: TC Part 2 Cohort 2B: TEZ/IVA Part 2 Cohort 2B: TC Total
    Arm/Group Description Participants received placebo matched to VX-152/TEZ/IVA TC for 2 weeks. Participants received VX-152 100 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks. Participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks. Participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. Total of all reporting groups
    Overall Participants 8 6 10 10 4 10 7 21 76
    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
    8
    100%
    6
    100%
    10
    100%
    10
    100%
    4
    100%
    10
    100%
    7
    100%
    21
    100%
    76
    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
    50%
    2
    33.3%
    4
    40%
    3
    30%
    2
    50%
    6
    60%
    4
    57.1%
    14
    66.7%
    39
    51.3%
    Male
    4
    50%
    4
    66.7%
    6
    60%
    7
    70%
    2
    50%
    4
    40%
    3
    42.9%
    7
    33.3%
    37
    48.7%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    2
    25%
    0
    0%
    0
    0%
    1
    10%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3
    3.9%
    Not Hispanic or Latino
    6
    75%
    6
    100%
    10
    100%
    9
    90%
    4
    100%
    10
    100%
    7
    100%
    21
    100%
    73
    96.1%
    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%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    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%
    0
    0%
    0
    0%
    White
    7
    87.5%
    5
    83.3%
    10
    100%
    10
    100%
    4
    100%
    10
    100%
    7
    100%
    21
    100%
    74
    97.4%
    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
    1
    12.5%
    1
    16.7%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    2.6%
    Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) (Count of Participants)
    <40 percent
    1
    12.5%
    0
    0%
    2
    20%
    1
    10%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    4
    5.3%
    ≥40 to <70 percent
    5
    62.5%
    6
    100%
    7
    70%
    4
    40%
    3
    75%
    10
    100%
    5
    71.4%
    18
    85.7%
    58
    76.3%
    ≥70 to ≤90 percent
    2
    25%
    0
    0%
    1
    10%
    5
    50%
    1
    25%
    0
    0%
    2
    28.6%
    3
    14.3%
    14
    18.4%
    >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 Visit (Up to Day 43 for Part 1 and Day 71 for Part 2)

    Outcome Measure Data

    Analysis Population Description
    Safety Set included all participants who received at least 1 dose of study drug in the treatment period.
    Arm/Group Title Part 1: Placebo Part 1 Cohort 1A: TC Part 1 Cohort 1B: TC Part 1 Cohort 1C: TC Part 2 Cohort 2A: TEZ/IVA Part 2 Cohort 2A: TC Part 2 Cohort 2B: TEZ/IVA Part 2 Cohort 2B: TC
    Arm/Group Description Participants received placebo matched to VX-152/TEZ/IVA TC for 2 weeks. Participants received VX-152 100 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks. Participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks. Participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
    Measure Participants 8 6 10 10 4 10 7 21
    Participants with TEAEs
    8
    100%
    3
    50%
    7
    70%
    10
    100%
    3
    75%
    6
    60%
    5
    71.4%
    19
    90.5%
    Participants with SAEs
    2
    25%
    0
    0%
    0
    0%
    1
    10%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2. Primary Outcome
    Title Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 15 for Part 1 and Part 2 Cohort 2A
    Description FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
    Time Frame From Baseline at Day 15

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS) included all randomized participants with the intended cystic fibrosis transmembrane conductance regulator protein (CFTR) allele mutation who received at least 1 dose of study drug in the treatment period. As pre-specified in analysis plan, only Part 1 and Part 2 Cohort 2A arms were assessed for this outcome measure.
    Arm/Group Title Part 1: Placebo Part 1 Cohort 1A: TC Part 1 Cohort 1B: TC Part 1 Cohort 1C: TC Part 2 Cohort 2A: TEZ/IVA Part 2 Cohort 2A: TC
    Arm/Group Description Participants received placebo matched to VX-152/TEZ/IVA TC for 2 weeks. Participants received VX-152 100 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks. Participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks. Participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
    Measure Participants 8 6 10 10 4 10
    Least Squares Mean (95% Confidence Interval) [percentage points]
    -0.8
    5.7
    9.7
    8.0
    -1.0
    7.3
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1 Cohort 1A: TC
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0207
    Comments
    Method Mixed-effects Model for Repeated Measure
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 6.4
    Confidence Interval (2-Sided) 95%
    0.3 to 12.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1 Cohort 1B: TC
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0002
    Comments
    Method Mixed-effects Model for Repeated Measure
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 10.5
    Confidence Interval (2-Sided) 95%
    5.0 to 15.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1 Cohort 1C: TC
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0019
    Comments
    Method Mixed-effects Model for Repeated Measure
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 8.8
    Confidence Interval (2-Sided) 95%
    3.0 to 14.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Part 2 Cohort 2A: TEZ/IVA, Part 2 Cohort 2A: TC
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0540
    Comments
    Method Mixed-effects Model for Repeated Measure
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 8.3
    Confidence Interval (2-Sided) 95%
    -2.1 to 18.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Primary Outcome
    Title Absolute Change in ppFEV1 Through Day 29 for Part 2 Cohort 2B
    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. As pre-specified in analysis plan, only Part 2 Cohort 2B arms were assessed for this outcome measure.
    Arm/Group Title Part 2 Cohort 2B: TEZ/IVA Part 2 Cohort 2B: TC
    Arm/Group Description Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
    Measure Participants 7 21
    Least Squares Mean (95% Confidence Interval) [percentage points]
    -2.2
    6.5
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1 Cohort 1A: TC
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0007
    Comments
    Method Mixed-effects Model for Repeated Measure
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 8.7
    Confidence Interval (2-Sided) 95%
    3.7 to 13.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Absolute Change in Sweat Chloride Concentrations at Day 15 for Part 1 and Part 2 Cohort 2A
    Description Sweat samples were collected using an approved collection device.
    Time Frame From Baseline at Day 15

    Outcome Measure Data

    Analysis Population Description
    FAS. As pre-specified in analysis plan, only Part 1 and Part 2 Cohort 2A arms were assessed for this outcome measure.
    Arm/Group Title Part 1: Placebo Part 1 Cohort 1A: TC Part 1 Cohort 1B: TC Part 1 Cohort 1C: TC Part 2 Cohort 2A: TEZ/IVA Part 2 Cohort 2A: TC
    Arm/Group Description Participants received placebo matched to VX-152/TEZ/IVA TC for 2 weeks. Participants received VX-152 100 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks. Participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks. Participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
    Measure Participants 8 6 10 10 4 10
    Least Squares Mean (95% Confidence Interval) [millimole per liter (mmol/L)]
    -0.1
    -19.5
    -13.6
    -27.5
    3.5
    -21.3
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1 Cohort 1A: TC
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0018
    Comments
    Method Mixed-effects Model for Repeated Measure
    Comments
    Method of Estimation Estimation Parameter Least Squares (LS) Mean Difference
    Estimated Value -19.5
    Confidence Interval (2-Sided) 95%
    -32.2 to -6.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1 Cohort 1B: TC
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0106
    Comments
    Method Mixed-effects Model for Repeated Measure
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -13.6
    Confidence Interval (2-Sided) 95%
    -25.0 to -2.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1 Cohort 1C: TC
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Mixed-effects Model for Repeated Measure
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -27.5
    Confidence Interval (2-Sided) 95%
    -38.6 to -16.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Part 2 Cohort 2A: TEZ/IVA, Part 2 Cohort 2A: TC
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0017
    Comments
    Method Mixed-effects Model for Repeated Measure
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -24.8
    Confidence Interval (2-Sided) 95%
    -40.0 to -9.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title Absolute Change in Sweat Chloride Concentrations Through Day 29 for Part 2 Cohort 2B
    Description Sweat samples were collected using an approved collection device.
    Time Frame From Baseline Through Day 29

    Outcome Measure Data

    Analysis Population Description
    FAS. As pre-specified in analysis plan, only Part 2 Cohort 2B arms were assessed for this outcome measure.
    Arm/Group Title Part 2 Cohort 2B: TEZ/IVA Part 2 Cohort 2B: TC
    Arm/Group Description Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
    Measure Participants 7 21
    Least Squares Mean (95% Confidence Interval) [mmol/L]
    1.6
    -22.3
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1 Cohort 1A: TC
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Mixed-effects Model for Repeated Measure
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -23.9
    Confidence Interval (2-Sided) 95%
    -33.7 to -14.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Relative Change in ppFEV1 at Day 15 for Part 1 and Part 2 Cohort 2A
    Description FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
    Time Frame From Baseline at Day 15

    Outcome Measure Data

    Analysis Population Description
    FAS. As pre-specified in analysis plan, only Part 1 and Part 2 Cohort 2A arms were assessed for this outcome measure.
    Arm/Group Title Part 1: Placebo Part 1 Cohort 1A: TC Part 1 Cohort 1B: TC Part 1 Cohort 1C: TC Part 2 Cohort 2A: TEZ/IVA Part 2 Cohort 2A: TC
    Arm/Group Description Participants received placebo matched to VX-152/TEZ/IVA for 2 weeks. Participants received VX-152 100 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks. Participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks. Participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
    Measure Participants 8 6 10 10 4 10
    Least Squares Mean (95% Confidence Interval) [percent change]
    -2.3
    10.3
    19.0
    14.8
    -1.4
    13.2
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1 Cohort 1A: TC
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0166
    Comments
    Method Mixed-effects Model for Repeated Measure
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 12.5
    Confidence Interval (2-Sided) 95%
    1.1 to 24.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1 Cohort 1B: TC
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Mixed-effects Model for Repeated Measure
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 21.3
    Confidence Interval (2-Sided) 95%
    11.2 to 31.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1 Cohort 1C: TC
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0013
    Comments
    Method Mixed-effects Model for Repeated Measure
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 17.1
    Confidence Interval (2-Sided) 95%
    6.3 to 27.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Part 2 Cohort 2A: TEZ/IVA, Part 2 Cohort 2A: TC
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0563
    Comments
    Method Mixed-effects Model for Repeated Measure
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 14.5
    Confidence Interval (2-Sided) 95%
    -3.8 to 32.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title Relative Change in ppFEV1 Through Day 29 for Part 2 Cohort 2B
    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. As pre-specified in analysis plan, only Part 2 Cohort 2B arms were assessed for this outcome measure.
    Arm/Group Title Part 2 Cohort 2B: TEZ/IVA Part 2 Cohort 2B: TC
    Arm/Group Description Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
    Measure Participants 7 21
    Least Squares Mean (95% Confidence Interval) [percent change]
    -2.0
    11.5
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1 Cohort 1A: TC
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0012
    Comments
    Method Mixed-effects Model for Repeated Measure
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 13.6
    Confidence Interval (2-Sided) 95%
    5.3 to 21.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. Secondary Outcome
    Title Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Day 15 for Part 1 and Part 2 Cohort 2A
    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 15

    Outcome Measure Data

    Analysis Population Description
    FAS. As pre-specified in analysis plan, only Part 1 and Part 2 Cohort 2A arms were assessed for this outcome measure.
    Arm/Group Title Part 1: Placebo Part 1 Cohort 1A: TC Part 1 Cohort 1B: TC Part 1 Cohort 1C: TC Part 2 Cohort 2A: TEZ/IVA Part 2 Cohort 2A: TC
    Arm/Group Description Participants received placebo matched to VX-152/TEZ/IVA for 2 weeks. Participants received VX-152 100 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks. Participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks. Participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
    Measure Participants 8 6 10 10 4 10
    Least Squares Mean (95% Confidence Interval) [units on a scale]
    -7.6
    6.6
    21.8
    18.6
    5.8
    10.6
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1 Cohort 1A: TC
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0476
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 14.1
    Confidence Interval (2-Sided) 95%
    -2.6 to 30.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1 Cohort 1B: TC
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 29.4
    Confidence Interval (2-Sided) 95%
    14.8 to 44.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1 Cohort 1C: TC
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0006
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 26.2
    Confidence Interval (2-Sided) 95%
    11.3 to 41.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Part 2 Cohort 2A: TEZ/IVA, Part 2 Cohort 2A: TC
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2714
    Comments
    Method Mixed-effects Model for Repeated Measure
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 4.8
    Confidence Interval (2-Sided) 95%
    -11.6 to 21.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    9. Secondary Outcome
    Title Absolute Change From Baseline in CFQ-R Respiratory Domain Score at Day 29 for Part 2 Cohort 2B
    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. As pre-specified in analysis plan, only Part 2 Cohort 2B arms were assessed for this outcome measure.
    Arm/Group Title Part 2 Cohort 2B: TEZ/IVA Part 2 Cohort 2B: TC
    Arm/Group Description Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
    Measure Participants 7 21
    Least Squares Mean (95% Confidence Interval) [units on a scale]
    4.8
    16.1
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1 Cohort 1A: TC
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0138
    Comments
    Method Mixed-effects Model for Repeated Measure
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 11.3
    Confidence Interval (2-Sided) 95%
    1.3 to 21.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    10. Secondary Outcome
    Title Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA
    Description
    Time Frame Pre-dose at Day 8, Day 15 and Day 29

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Set (PK) included all participants who received at least 1 dose of study drug in treatment period. Here "Number Analyzed" signifies those participants who were evaluable at specified time points. Day 29 assessments were planned for Part 2: Cohort 2B groups only. VX-152 Ctrough category was not applicable to Part 2: TEZ/IVA groups.
    Arm/Group Title Part 1 Cohort 1A: TC Part 1 Cohort 1B: TC Part 1 Cohort 1C: TC Part 2 Cohort 2A: TEZ/IVA Part 2 Cohort 2A: TC Part 2 Cohort 2B: TEZ/IVA Part 2 Cohort 2B: TC
    Arm/Group Description Participants received VX-152 100 mg q12h/TEZ 100 qd/IVA 150 mg q12h TC for 2 weeks. Participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks. Participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
    Measure Participants 6 10 10 4 10 7 21
    Day 8: VX-152
    167
    (65.4)
    240
    (370)
    538
    (576)
    355
    (287)
    463
    (730)
    Day 15: VX-152
    173
    (72.1)
    278
    (212)
    804
    (812)
    554
    (429)
    560
    (657)
    Day 29: VX-152
    698
    (1040)
    Day 8: TEZ
    2610
    (1400)
    1500
    (1140)
    1680
    (996)
    1900
    (1730)
    1830
    (693)
    2010
    (669)
    1460
    (1470)
    Day 15: TEZ
    2450
    (2000)
    1220
    (545)
    1180
    (495)
    1120
    (135)
    1620
    (1030)
    1970
    (1040)
    1050
    (543)
    Day 29: TEZ
    2470
    (1060)
    1190
    (422)
    Day 8: M1-TEZ
    4520
    (1090)
    3060
    (1480)
    3490
    (1640)
    3760
    (1100)
    4900
    (1050)
    4980
    (1450)
    4150
    (1280)
    Day 15: M1-TEZ
    4680
    (1020)
    2890
    (898)
    3310
    (1220)
    3430
    (824)
    4270
    (1280)
    4420
    (1810)
    3650
    (1320)
    Day 29: M1-TEZ
    4280
    (1650)
    3680
    (742)
    Day 8: IVA
    779
    (442)
    522
    (401)
    545
    (234)
    702
    (425)
    610
    (262)
    953
    (360)
    434
    (251)
    Day 15: IVA
    841
    (588)
    535
    (310)
    467
    (236)
    441
    (300)
    645
    (373)
    863
    (488)
    389
    (222)
    Day 29: IVA
    1010
    (446)
    468
    (279)
    Day 8: M1-IVA
    1590
    (1050)
    1040
    (947)
    1330
    (747)
    1660
    (1200)
    1470
    (671)
    1810
    (665)
    1170
    (551)
    Day 15: M1-IVA
    1230
    (326)
    1200
    (848)
    1140
    (550)
    1030
    (762)
    1510
    (891)
    1620
    (760)
    1100
    (598)
    Day 29: M1-IVA
    1890
    (659)
    1240
    (705)

    Adverse Events

    Time Frame Day 1 Through Safety Follow-up Visit (Up to Day 43 for Part 1 and Day 71 for Part 2)
    Adverse Event Reporting Description
    Arm/Group Title Part 1: Placebo Part 1 Cohort 1A: TC Part 1 Cohort 1B: TC Part 1 Cohort 1C: TC Part 2 Cohort 2A: TEZ/IVA Part 2 Cohort 2A: TC Part 2 Cohort 2B: TEZ/IVA Part 2 Cohort 2B: TC
    Arm/Group Description Participants received placebo matched to VX-152/TEZ/IVA TC for 2 weeks. Participants received VX-152 100 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks. Participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks. Participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
    All Cause Mortality
    Part 1: Placebo Part 1 Cohort 1A: TC Part 1 Cohort 1B: TC Part 1 Cohort 1C: TC Part 2 Cohort 2A: TEZ/IVA Part 2 Cohort 2A: TC Part 2 Cohort 2B: TEZ/IVA Part 2 Cohort 2B: 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 0/8 (0%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Serious Adverse Events
    Part 1: Placebo Part 1 Cohort 1A: TC Part 1 Cohort 1B: TC Part 1 Cohort 1C: TC Part 2 Cohort 2A: TEZ/IVA Part 2 Cohort 2A: TC Part 2 Cohort 2B: TEZ/IVA Part 2 Cohort 2B: 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 2/8 (25%) 0/6 (0%) 0/10 (0%) 1/10 (10%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Infections and infestations
    Infective pulmonary exacerbation of cystic fibrosis 1/8 (12.5%) 0/6 (0%) 0/10 (0%) 1/10 (10%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Viral infection 1/8 (12.5%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Other (Not Including Serious) Adverse Events
    Part 1: Placebo Part 1 Cohort 1A: TC Part 1 Cohort 1B: TC Part 1 Cohort 1C: TC Part 2 Cohort 2A: TEZ/IVA Part 2 Cohort 2A: TC Part 2 Cohort 2B: TEZ/IVA Part 2 Cohort 2B: 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 8/8 (100%) 3/6 (50%) 7/10 (70%) 9/10 (90%) 3/4 (75%) 6/10 (60%) 5/7 (71.4%) 18/21 (85.7%)
    Blood and lymphatic system disorders
    Anaemia 0/8 (0%) 0/6 (0%) 0/10 (0%) 1/10 (10%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Lymphadenopathy 1/8 (12.5%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Ear and labyrinth disorders
    Ear discomfort 1/8 (12.5%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Eye disorders
    Eye swelling 0/8 (0%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 0/4 (0%) 1/10 (10%) 0/7 (0%) 0/21 (0%)
    Gastrointestinal disorders
    Abdominal discomfort 0/8 (0%) 0/6 (0%) 0/10 (0%) 1/10 (10%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Abdominal distension 0/8 (0%) 1/6 (16.7%) 0/10 (0%) 0/10 (0%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 1/21 (4.8%)
    Abdominal pain 0/8 (0%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 2/21 (9.5%)
    Colitis 1/8 (12.5%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Constipation 0/8 (0%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 2/21 (9.5%)
    Diarrhoea 0/8 (0%) 2/6 (33.3%) 2/10 (20%) 1/10 (10%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 3/21 (14.3%)
    Dyspepsia 0/8 (0%) 0/6 (0%) 0/10 (0%) 1/10 (10%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Faeces soft 0/8 (0%) 0/6 (0%) 1/10 (10%) 0/10 (0%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Flatulence 0/8 (0%) 0/6 (0%) 0/10 (0%) 1/10 (10%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 2/21 (9.5%)
    Nausea 1/8 (12.5%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 1/4 (25%) 0/10 (0%) 0/7 (0%) 2/21 (9.5%)
    Post-tussive vomiting 0/8 (0%) 0/6 (0%) 1/10 (10%) 0/10 (0%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Vomiting 1/8 (12.5%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 0/4 (0%) 0/10 (0%) 1/7 (14.3%) 0/21 (0%)
    General disorders
    Chest discomfort 0/8 (0%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 0/4 (0%) 0/10 (0%) 1/7 (14.3%) 0/21 (0%)
    Fatigue 0/8 (0%) 1/6 (16.7%) 2/10 (20%) 1/10 (10%) 0/4 (0%) 1/10 (10%) 0/7 (0%) 2/21 (9.5%)
    Pyrexia 0/8 (0%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 2/21 (9.5%)
    Thirst 0/8 (0%) 0/6 (0%) 0/10 (0%) 1/10 (10%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Vessel puncture site haemorrhage 1/8 (12.5%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Immune system disorders
    Seasonal allergy 0/8 (0%) 0/6 (0%) 1/10 (10%) 0/10 (0%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Infections and infestations
    Chronic sinusitis 0/8 (0%) 0/6 (0%) 0/10 (0%) 1/10 (10%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Gastroenteritis 0/8 (0%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 1/4 (25%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Infective pulmonary exacerbation of cystic fibrosis 3/8 (37.5%) 0/6 (0%) 1/10 (10%) 0/10 (0%) 0/4 (0%) 1/10 (10%) 3/7 (42.9%) 5/21 (23.8%)
    Nasopharyngitis 0/8 (0%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 0/4 (0%) 1/10 (10%) 1/7 (14.3%) 0/21 (0%)
    Pneumonia 0/8 (0%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 0/4 (0%) 1/10 (10%) 0/7 (0%) 0/21 (0%)
    Upper respiratory tract infection 1/8 (12.5%) 0/6 (0%) 1/10 (10%) 0/10 (0%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 1/21 (4.8%)
    Viral upper respiratory tract infection 1/8 (12.5%) 0/6 (0%) 0/10 (0%) 1/10 (10%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 1/21 (4.8%)
    Injury, poisoning and procedural complications
    Incision site pain 0/8 (0%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 0/4 (0%) 1/10 (10%) 0/7 (0%) 0/21 (0%)
    Muscle strain 0/8 (0%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 1/4 (25%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Procedural dizziness 0/8 (0%) 0/6 (0%) 0/10 (0%) 1/10 (10%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Procedural haemorrhage 0/8 (0%) 0/6 (0%) 1/10 (10%) 0/10 (0%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Investigations
    Alanine aminotransferase increased 0/8 (0%) 0/6 (0%) 0/10 (0%) 1/10 (10%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 1/21 (4.8%)
    Aspartate aminotransferase increased 1/8 (12.5%) 0/6 (0%) 0/10 (0%) 1/10 (10%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 1/21 (4.8%)
    Blood alkaline phosphatase increased 1/8 (12.5%) 0/6 (0%) 0/10 (0%) 1/10 (10%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Blood bilirubin increased 0/8 (0%) 0/6 (0%) 1/10 (10%) 0/10 (0%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 1/21 (4.8%)
    Gamma-glutamyltransferase increased 1/8 (12.5%) 0/6 (0%) 0/10 (0%) 1/10 (10%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Platelet count increased 0/8 (0%) 0/6 (0%) 0/10 (0%) 1/10 (10%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Weight decreased 0/8 (0%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 1/4 (25%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Metabolism and nutrition disorders
    Hypoglycaemia 0/8 (0%) 1/6 (16.7%) 0/10 (0%) 0/10 (0%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/8 (0%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 1/4 (25%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Musculoskeletal chest pain 0/8 (0%) 1/6 (16.7%) 0/10 (0%) 0/10 (0%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Tendon pain 0/8 (0%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 1/4 (25%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Nervous system disorders
    Dizziness 1/8 (12.5%) 1/6 (16.7%) 0/10 (0%) 0/10 (0%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Dysgeusia 0/8 (0%) 0/6 (0%) 0/10 (0%) 1/10 (10%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Headache 0/8 (0%) 1/6 (16.7%) 1/10 (10%) 3/10 (30%) 1/4 (25%) 0/10 (0%) 0/7 (0%) 4/21 (19%)
    Migraine 1/8 (12.5%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 1/21 (4.8%)
    Sinus headache 0/8 (0%) 0/6 (0%) 1/10 (10%) 1/10 (10%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Psychiatric disorders
    Anxiety 1/8 (12.5%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Insomnia 0/8 (0%) 0/6 (0%) 1/10 (10%) 0/10 (0%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 1/21 (4.8%)
    Renal and urinary disorders
    Chromaturia 0/8 (0%) 0/6 (0%) 0/10 (0%) 1/10 (10%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 4/21 (19%)
    Reproductive system and breast disorders
    Breast discomfort 0/8 (0%) 0/6 (0%) 0/10 (0%) 1/10 (10%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Breast tenderness 0/8 (0%) 0/6 (0%) 0/10 (0%) 1/10 (10%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 1/21 (4.8%)
    Respiratory, thoracic and mediastinal disorders
    Bronchospasm 0/8 (0%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 0/4 (0%) 1/10 (10%) 0/7 (0%) 0/21 (0%)
    Cough 1/8 (12.5%) 0/6 (0%) 3/10 (30%) 1/10 (10%) 1/4 (25%) 1/10 (10%) 0/7 (0%) 6/21 (28.6%)
    Dysphonia 1/8 (12.5%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Dyspnoea 1/8 (12.5%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 1/4 (25%) 0/10 (0%) 1/7 (14.3%) 2/21 (9.5%)
    Dyspnoea exertional 0/8 (0%) 0/6 (0%) 1/10 (10%) 0/10 (0%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Haemoptysis 0/8 (0%) 1/6 (16.7%) 0/10 (0%) 1/10 (10%) 1/4 (25%) 1/10 (10%) 0/7 (0%) 2/21 (9.5%)
    Increased viscosity of bronchial secretion 0/8 (0%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 2/21 (9.5%)
    Lower respiratory tract congestion 0/8 (0%) 1/6 (16.7%) 1/10 (10%) 1/10 (10%) 1/4 (25%) 0/10 (0%) 1/7 (14.3%) 0/21 (0%)
    Nasal congestion 1/8 (12.5%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 1/21 (4.8%)
    Oropharyngeal pain 1/8 (12.5%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 2/21 (9.5%)
    Pleuritic pain 0/8 (0%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 2/21 (9.5%)
    Productive cough 0/8 (0%) 2/6 (33.3%) 2/10 (20%) 2/10 (20%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 3/21 (14.3%)
    Pulmonary pain 0/8 (0%) 0/6 (0%) 0/10 (0%) 1/10 (10%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Respiration abnormal 0/8 (0%) 0/6 (0%) 1/10 (10%) 2/10 (20%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 2/21 (9.5%)
    Respiratory tract congestion 0/8 (0%) 0/6 (0%) 0/10 (0%) 1/10 (10%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Rhinorrhoea 0/8 (0%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 1/4 (25%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Sinus congestion 2/8 (25%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 1/21 (4.8%)
    Sputum discoloured 0/8 (0%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 0/4 (0%) 1/10 (10%) 0/7 (0%) 1/21 (4.8%)
    Sputum increased 1/8 (12.5%) 1/6 (16.7%) 2/10 (20%) 1/10 (10%) 0/4 (0%) 1/10 (10%) 1/7 (14.3%) 6/21 (28.6%)
    Upper respiratory tract congestion 0/8 (0%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 1/4 (25%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Wheezing 0/8 (0%) 0/6 (0%) 1/10 (10%) 1/10 (10%) 1/4 (25%) 0/10 (0%) 1/7 (14.3%) 0/21 (0%)
    Skin and subcutaneous tissue disorders
    Acne 0/8 (0%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 2/21 (9.5%)
    Erythema 0/8 (0%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 1/4 (25%) 0/10 (0%) 0/7 (0%) 0/21 (0%)
    Night sweats 0/8 (0%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 0/4 (0%) 1/10 (10%) 0/7 (0%) 0/21 (0%)
    Rash 0/8 (0%) 0/6 (0%) 0/10 (0%) 0/10 (0%) 0/4 (0%) 0/10 (0%) 0/7 (0%) 2/21 (9.5%)

    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:
    NCT02951195
    Other Study ID Numbers:
    • VX16-152-102
    First Posted:
    Nov 1, 2016
    Last Update Posted:
    Jan 28, 2021
    Last Verified:
    Jan 1, 2021