A Study Evaluating the Safety and Efficacy of VX-659 Comb... | NCT03224351 | Trialant
NCT03224351
Sponsor
Vertex Pharmaceuticals Incorporated
Status
Completed
Last Update Posted
Apr 22, 2021Actual
Enrollment
124Actual
Phase
Phase 2
Conditions
Cystic Fibrosis
Interventions
VX-659
TEZ/IVA
IVA
Placebo (matched to VX-659/TEZ/IVA)
TEZ
VX-561
Placebo (matched to VX-659/TEZ/VX-561)
Countries
United States
Ireland
Israel
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT03224351
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
VX16-659-101
Secondary IDs
ID
Type
Description
Link
2016-003585-11
EudraCT Number
Brief Title
A Study Evaluating the Safety and Efficacy of VX-659 Combination Therapy in Subjects With Cystic Fibrosis
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
Acronym
Not provided
Organization
Vertex Pharmaceuticals IncorporatedINDUSTRY
Status Module
Record Verification Date
Feb 2021
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Aug 8, 2017Actual
Primary Completion Date
Feb 28, 2018Actual
Completion Date
Feb 28, 2018Actual
First Submitted Date
Jul 18, 2017
First Submission Date that Met QC Criteria
Jul 18, 2017
First Posted Date
Jul 21, 2017Actual
Results Waived
Not provided
Results First Submitted Date
Feb 25, 2021
Results First Submitted that Met QC Criteria
Mar 29, 2021
Results First Posted Date
Apr 22, 2021Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Feb 28, 2019
Certification/Extension First Submitted that Passed QC Review
Mar 29, 2021
Certification/Extension First Posted Date
Apr 22, 2021Actual
Last Update Submitted Date
Mar 29, 2021
Last Update Posted Date
Apr 22, 2021Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Vertex Pharmaceuticals IncorporatedINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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).
Detailed Description
Not provided
Conditions Module
Conditions
Cystic Fibrosis
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
124Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Part 1: Placebo
Placebo Comparator
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)
Part 1: VX-659/TEZ/IVA TC - Low Dose
Experimental
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
Drug: TEZ/IVA
Drug: IVA
Part 1: VX-659/TEZ/IVA TC - Medium Dose
Experimental
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
Drug: TEZ/IVA
Drug: IVA
Part 1: VX-659/TEZ/IVA TC - High Dose
Experimental
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
Drug: TEZ/IVA
Drug: IVA
Part 2: TEZ/IVA
Active Comparator
Interventions
Name
Type
Description
Arm Group Labels
Other Names
VX-659
Drug
Tablet for oral administration.
Part 1: VX-659/TEZ/IVA TC - High Dose
Part 1: VX-659/TEZ/IVA TC - Low Dose
Part 1: VX-659/TEZ/IVA TC - Medium Dose
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
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)
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
From Baseline Through Day 29
Secondary Outcomes
Measure
Description
Time Frame
Absolute Change in Sweat Chloride Concentrations
Sweat samples were collected using an approved collection device.
From Baseline Through Day 29
Relative Change in ppFEV1
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
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.
Heneghan M, Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2023 Nov 20;11(11):CD010966. doi: 10.1002/14651858.CD010966.pub4.
This study included 3 parts and was conducted in adult participants with cystic fibrosis (CF).
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.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Part 1: Placebo
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.
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
Drug: IVA
Part 2: VX-659/TEZ/IVA TC
Experimental
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
Drug: TEZ/IVA
Drug: IVA
Part 3: Placebo
Placebo Comparator
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)
Part 3: VX-659/TEZ/VX-561 TC
Experimental
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
Drug: TEZ
Drug: VX-561
Part 2: VX-659/TEZ/IVA TC
Part 3: VX-659/TEZ/VX-561 TC
TEZ/IVA
Drug
TEZ/IVA fixed-dose combination tablet for oral administration.
Part 1: VX-659/TEZ/IVA TC - High Dose
Part 1: VX-659/TEZ/IVA TC - Low Dose
Part 1: VX-659/TEZ/IVA TC - Medium Dose
Part 2: TEZ/IVA
Part 2: VX-659/TEZ/IVA TC
VX-661/VX-770
Tezacaftor/Ivacaftor
IVA
Drug
Tablet for oral administration.
Part 1: VX-659/TEZ/IVA TC - High Dose
Part 1: VX-659/TEZ/IVA TC - Low Dose
Part 1: VX-659/TEZ/IVA TC - Medium Dose
Part 2: TEZ/IVA
Part 2: VX-659/TEZ/IVA TC
VX-770
Ivacaftor
Placebo (matched to VX-659/TEZ/IVA)
Drug
Placebo matched to VX-659 and TEZ/IVA.
Part 1: Placebo
TEZ
Drug
Tablet for oral administration.
Part 3: VX-659/TEZ/VX-561 TC
VX-661
Tezacaftor
VX-561
Drug
Tablet for oral administration.
Part 3: VX-659/TEZ/VX-561 TC
CTP-656
Placebo (matched to VX-659/TEZ/VX-561)
Drug
Placebo matched to VX-659, TEZ and VX-561.
Part 3: Placebo
From Baseline Through Day 29
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
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.
From Baseline at Day 29
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
Miami
Florida
33136
United States
Advocate Children's Hospital - Park Ridge / North Suburban Pulmonary and Critical Care Consultants
Morton Grove
Illinois
60053
United States
Indiana University Health
Indianapolis
Indiana
46202
United States
The University of Iowa Hospitals and Clinics
Iowa City
Iowa
52242
United States
The Johns Hopkins Hospital/ Johns Hopkins Hospital, David Rubenstein Child Health Building
Baltimore
Maryland
21287
United States
Boston Children's Hospital
Boston
Massachusetts
02155
United States
University of Massachusetts Memorial Medical Center
Worcester
Massachusetts
01655
United States
University of Michigan Health System
Ann Arbor
Michigan
48109
United States
Helen DeVos Children's Hospital CF Center
Grand Rapids
Michigan
49503
United States
Children's Mercy Hospital
Kansas City
Missouri
64108
United States
Rutgers-Robert Wood Johnson Medical School/ Rutgers-Robert Wood Johnson Medical School, Clinical Research Center
New Brunswick
New Jersey
08902
United States
Albany Medical College
Albany
New York
12208
United States
Northwell Health, Long Island Jewish Medical Center
New Hyde Park
New York
11040
United States
Columbia University Medical Center
New York
New York
10032
United States
SUNY Upstate Medical University
Syracuse
New York
13210
United States
Respiratory Diseases of Children & Adolescents
Oklahoma City
Oklahoma
73112
United States
Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center
Pittsburgh
Pennsylvania
15224
United States
Sanford Research / USD
Sioux Falls
South Dakota
57104
United States
University of Tennessee Medical Center-Adult Cystic Fibrosis Clinic
Knoxville
Tennessee
37920
United States
Children's Foundation Research Center / Le Bonheur Children's Hospital
Memphis
Tennessee
38103
United States
Vanderbilt University Medical Center
Nashville
Tennessee
37232
United States
University of Utah / Primary Children's Medical Center
Ruth Children's Hospital Rambam Health Care Campus
Haifa
Israel
Hadassah Medical Organization
Jerusalem
Israel
The Chaim Sheba medical center
Ramat Gan
Israel
Schneider Children's Medical Center
Tikvah
Israel
Birmingham Heartlands Hospital
Birmingham
B95SS
United Kingdom
Papworth Hospital NHS Foundation Trust, Papworth Everard
Cambridge
United Kingdom
University Hospital Llandough in Cardiff
Cardiff
United Kingdom
Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital
Devon
United Kingdom
The Newcastle upon Tyne Hospitals NHS Foundation Trust, The Royal Victoria Infirmary
Fulham
United Kingdom
Greater Glasgow and Clyde NHS Board, Glasgow Clinical Research Facility
Glasgow
United Kingdom
Southampton University Hospitals NHS Foundation Trust
Hampshire
United Kingdom
Regional Respiratory Centre Belfast City Hospital
London
United Kingdom
Royal Brompton & Harefied NHS Foundation Trust
London
United Kingdom
University Hospital of South Manchester NHS Trust, North West Lung Centre
Manchester
United Kingdom
Liverpool Heart and Chest Hospital
Merseyside
United Kingdom
Nottingham University Hospitals NHS Trust
Nottingham
United Kingdom
Ruth Children's Hospital Rambam Health Care Campus
Nottingham
United Kingdom
Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3.
Davies JC, Moskowitz SM, Brown C, Horsley A, Mall MA, McKone EF, Plant BJ, Prais D, Ramsey BW, Taylor-Cousar JL, Tullis E, Uluer A, McKee CM, Robertson S, Shilling RA, Simard C, Van Goor F, Waltz D, Xuan F, Young T, Rowe SM; VX16-659-101 Study Group. VX-659-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles. N Engl J Med. 2018 Oct 25;379(17):1599-1611. doi: 10.1056/NEJMoa1807119. Epub 2018 Oct 18.
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.
FG002
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.
FG003
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.
FG004
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.
FG005
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.
FG006
Part 3: Placebo
Participants received placebo matched to VX-659/TEZ/VX-561 in TC treatment period for 4 weeks.
FG007
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.
FG00010 subjects
FG00111 subjects
FG00220 subjects
FG00322 subjects
FG00411 subjects
FG00518 subjects
FG0066 subjects
FG00719 subjects
COMPLETED
FG00010 subjects
FG00111 subjects
FG00220 subjects
FG00322 subjects
FG00411 subjects
FG00518 subjects
FG0066 subjects
FG00719 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Part 1: Placebo
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.
BG001
Part 1: VX-659/TEZ/IVA TC - Low Dose
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.
BG002
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.
BG003
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.
BG004
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.
BG005
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.
BG006
Part 3: Placebo
Participants received placebo matched to VX-659/TEZ/VX-561 in TC treatment period for 4 weeks.
BG007
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.
BG008
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00010
BG00111
BG00220
BG00322
BG00411
BG00518
BG0066
BG00719
BG008117
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Customized
Count of Participants
Participants
Title
Denominators
Categories
<18 years
Title
Measurements
BG0000
BG0010
BG0020
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0004
BG0017
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0000
BG0010
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
<40 percent
BG0002
BG0010
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Safety Set included all participants who received at least 1 dose of study drug in TC treatment period.
Posted
Number
participants
Day 1 Through Safety Follow-up (up to Day 61 for Part 1, Day 85 for Part 2 and Day 57 for Part 3)
ID
Title
Description
OG000
Part 1: Placebo
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.
OG001
Part 1: VX-659/TEZ/IVA TC - Low Dose
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.
OG002
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.
OG003
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.
OG004
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.
OG005
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.
OG006
Part 3: Placebo
Participants received placebo matched to VX-659/TEZ/VX-561 in TC treatment period for 4 weeks.
OG007
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.
Units
Counts
Participants
OG00010
OG00111
OG00220
OG003
Title
Denominators
Categories
Participants with TEAEs
Title
Measurements
OG0009
OG00110
OG00215
OG003
Primary
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
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.
Posted
Least Squares Mean
95% Confidence Interval
percentage points
From Baseline Through Day 29
ID
Title
Description
OG000
Part 1: Placebo
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.
OG001
Part 1: VX-659/TEZ/IVA TC - Low Dose
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.
OG002
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.
Secondary
Absolute Change in Sweat Chloride Concentrations
Sweat samples were collected using an approved collection device.
FAS.
Posted
Least Squares Mean
95% Confidence Interval
millimole per liter (mmol/L)
From Baseline Through Day 29
ID
Title
Description
OG000
Part 1: Placebo
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.
OG001
Part 1: VX-659/TEZ/IVA TC - Low Dose
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.
OG002
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.
OG003
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.
Secondary
Relative Change in ppFEV1
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
FAS.
Posted
Least Squares Mean
95% Confidence Interval
percent change
From Baseline Through Day 29
ID
Title
Description
OG000
Part 1: Placebo
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.
OG001
Part 1: VX-659/TEZ/IVA TC - Low Dose
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.
OG002
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.
OG003
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.
Secondary
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
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.
FAS.
Posted
Least Squares Mean
95% Confidence Interval
units on a scale
From Baseline at Day 29
ID
Title
Description
OG000
Part 1: Placebo
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.
OG001
Part 1: VX-659/TEZ/IVA TC - Low Dose
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.
OG002
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.
Secondary
Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561
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.
Posted
Mean
Standard Deviation
nanogram per milliliter (ng/mL)
Pre-dose at Day 15 and Day 29
ID
Title
Description
OG000
Part 1: VX-659/TEZ/IVA TC - Low Dose
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.
OG001
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.
OG002
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.
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)
Description
Not provided
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Part 1: Placebo
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.
0
10
3
10
8
10
EG001
Part 1: VX-659/TEZ/IVA TC - Low Dose
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.
0
11
1
11
10
11
EG002
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.
0
20
4
20
15
20
EG003
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.
0
22
1
22
17
22
EG004
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.
0
11
2
11
8
11
EG005
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.
0
18
1
18
15
18
EG006
Part 3: Placebo
Participants received placebo matched to VX-659/TEZ/VX-561 in TC treatment period for 4 weeks.
0
6
3
6
5
6
EG007
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.
0
19
2
19
18
19
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Pulmonary function test decreased
Investigations
MedDRA 20.1
Systematic Assessment
EG0001 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG0030 affected22 at risk
EG0040 affected11 at risk
EG0050 affected18 at risk
EG0060 affected6 at risk
EG0070 affected19 at risk
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Pleuritic pain
Respiratory, thoracic and mediastinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Pyrexia
General disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Infective pulmonary exacerbation of cystic fibrosis
Infections and infestations
MedDRA 20.1
Systematic Assessment
EG0002 affected10 at risk
EG0011 affected11 at risk
EG0022 affected20 at risk
EG003
Influenza
Infections and infestations
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0021 affected20 at risk
EG003
Respiratory tract infection viral
Infections and infestations
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0021 affected20 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Hot flush
Vascular disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0021 affected20 at risk
EG0030 affected22 at risk
EG0040 affected11 at risk
EG0050 affected18 at risk
EG0060 affected6 at risk
EG0070 affected19 at risk
Fibroadenoma of breast
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Drug hypersensitivity
Immune system disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Pyrexia
General disorders
MedDRA 20.1
Systematic Assessment
EG0001 affected10 at risk
EG0011 affected11 at risk
EG0021 affected20 at risk
EG003
Fatigue
General disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0012 affected11 at risk
EG0022 affected20 at risk
EG003
Pain
General disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Application site rash
General disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Asthenia
General disorders
MedDRA 20.1
Systematic Assessment
EG0001 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Exercise tolerance decreased
General disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Influenza like illness
General disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0021 affected20 at risk
EG003
Irritability
Psychiatric disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0021 affected20 at risk
EG003
Testicular pain
Reproductive system and breast disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Vaginal discharge
Reproductive system and breast disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0011 affected11 at risk
EG0020 affected20 at risk
EG003
Vaginal haemorrhage
Reproductive system and breast disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Laceration
Injury, poisoning and procedural complications
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Wound
Injury, poisoning and procedural complications
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Blood creatine phosphokinase increased
Investigations
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0011 affected11 at risk
EG0021 affected20 at risk
EG003
Neutrophil count increased
Investigations
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA 20.1
Systematic Assessment
EG0001 affected10 at risk
EG0011 affected11 at risk
EG0020 affected20 at risk
EG003
Bacterial test positive
Investigations
MedDRA 20.1
Systematic Assessment
EG0001 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Blood glucose increased
Investigations
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
International normalised ratio increased
Investigations
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Lymphocyte count decreased
Investigations
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Prothrombin time prolonged
Investigations
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Weight increased
Investigations
MedDRA 20.1
Systematic Assessment
EG0001 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Activated partial thromboplastin time prolonged
Investigations
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0011 affected11 at risk
EG0020 affected20 at risk
EG003
Blood glucose decreased
Investigations
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Blood triglycerides increased
Investigations
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Pulmonary function test decreased
Investigations
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Blood alkaline phosphatase increased
Investigations
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Blood chloride decreased
Investigations
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Blood creatinine decreased
Investigations
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Blood glucose fluctuation
Investigations
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Blood lactate dehydrogenase increased
Investigations
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Blood potassium increased
Investigations
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Blood sodium decreased
Investigations
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Body temperature increased
Investigations
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0011 affected11 at risk
EG0020 affected20 at risk
EG003
Coronavirus test positive
Investigations
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Crystal urine present
Investigations
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Forced expiratory volume decreased
Investigations
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Glucose urine present
Investigations
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Haemoglobin decreased
Investigations
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0011 affected11 at risk
EG0020 affected20 at risk
EG003
Monocyte count increased
Investigations
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Red blood cells urine positive
Investigations
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Urinary sediment present
Investigations
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Weight decreased
Investigations
MedDRA 20.1
Systematic Assessment
EG0001 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
White blood cell count increased
Investigations
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA 20.1
Systematic Assessment
EG0001 affected10 at risk
EG0013 affected11 at risk
EG0026 affected20 at risk
EG003
Sputum increased
Respiratory, thoracic and mediastinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0012 affected11 at risk
EG0021 affected20 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0023 affected20 at risk
EG003
Haemoptysis
Respiratory, thoracic and mediastinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0012 affected11 at risk
EG0021 affected20 at risk
EG003
Respiration abnormal
Respiratory, thoracic and mediastinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0011 affected11 at risk
EG0021 affected20 at risk
EG003
Nasal congestion
Respiratory, thoracic and mediastinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0021 affected20 at risk
EG003
Sinus congestion
Respiratory, thoracic and mediastinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA 20.1
Systematic Assessment
EG0001 affected10 at risk
EG0011 affected11 at risk
EG0021 affected20 at risk
EG003
Lower respiratory tract congestion
Respiratory, thoracic and mediastinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Productive cough
Respiratory, thoracic and mediastinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0012 affected11 at risk
EG0021 affected20 at risk
EG003
Wheezing
Respiratory, thoracic and mediastinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0023 affected20 at risk
EG003
Paranasal sinus discomfort
Respiratory, thoracic and mediastinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0011 affected11 at risk
EG0020 affected20 at risk
EG003
Rales
Respiratory, thoracic and mediastinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Rhinorrhoea
Respiratory, thoracic and mediastinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Sinus pain
Respiratory, thoracic and mediastinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Sputum discoloured
Respiratory, thoracic and mediastinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0021 affected20 at risk
EG003
Bronchospasm
Respiratory, thoracic and mediastinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDRA 20.1
Systematic Assessment
EG0001 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Nasal discharge discolouration
Respiratory, thoracic and mediastinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0021 affected20 at risk
EG003
Throat irritation
Respiratory, thoracic and mediastinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Throat tightness
Respiratory, thoracic and mediastinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Lymphopenia
Blood and lymphatic system disorders
MedDRA 20.1
Systematic Assessment
EG0001 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Headache
Nervous system disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0011 affected11 at risk
EG0024 affected20 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Lethargy
Nervous system disorders
MedDRA 20.1
Systematic Assessment
EG0001 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Migraine
Nervous system disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Sinus headache
Nervous system disorders
MedDRA 20.1
Systematic Assessment
EG0001 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Syncope
Nervous system disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Vertigo
Ear and labyrinth disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0021 affected20 at risk
EG003
Ear congestion
Ear and labyrinth disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Motion sickness
Ear and labyrinth disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0021 affected20 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0011 affected11 at risk
EG0020 affected20 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0011 affected11 at risk
EG0021 affected20 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Flatulence
Gastrointestinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Faeces discoloured
Gastrointestinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0021 affected20 at risk
EG003
Food poisoning
Gastrointestinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Gastrooesophageal reflux disease
Gastrointestinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0021 affected20 at risk
EG003
Pancreatic failure
Gastrointestinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Parotid gland enlargement
Gastrointestinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Salivary hypersecretion
Gastrointestinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0021 affected20 at risk
EG003
Toothache
Gastrointestinal disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0021 affected20 at risk
EG003
Micturition urgency
Renal and urinary disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0021 affected20 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Acne
Skin and subcutaneous tissue disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Dermatitis
Skin and subcutaneous tissue disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Rash erythematous
Skin and subcutaneous tissue disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0021 affected20 at risk
EG003
Skin disorder
Skin and subcutaneous tissue disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0021 affected20 at risk
EG003
Flank pain
Musculoskeletal and connective tissue disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Intervertebral disc protrusion
Musculoskeletal and connective tissue disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Musculoskeletal pain
Musculoskeletal and connective tissue disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Vitamin D deficiency
Metabolism and nutrition disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0011 affected11 at risk
EG0020 affected20 at risk
EG003
Abnormal loss of weight
Metabolism and nutrition disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Hypophosphataemia
Metabolism and nutrition disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Increased appetite
Metabolism and nutrition disorders
MedDRA 20.1
Systematic Assessment
EG0000 affected10 at risk
EG0010 affected11 at risk
EG0020 affected20 at risk
EG003
Infective pulmonary exacerbation of cystic fibrosis
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D007232
Infant, Newborn, Diseases
Browse Leaves
Not provided
Browse Branches
Not provided
ID
Term
C000629057
VX-659
C000654124
tezacaftor, ivacaftor drug combination
C545203
ivacaftor
C000625213
tezacaftor
Ancestor Terms
Not provided
Browse Leaves
Not provided
Browse Branches
Not provided
0
BG0040
BG0050
BG0060
BG0070
BG0080
>=18 and <65 years
Title
Measurements
BG00010
BG00111
BG00220
BG00322
BG00411
BG00518
BG0066
BG00719
BG008117
>=65 years
Title
Measurements
BG0000
BG0010
BG0020
BG0030
BG0040
BG0050
BG0060
BG0070
BG0080
7
BG00312
BG0044
BG0056
BG0063
BG00711
BG00854
Male
BG0006
BG0014
BG00213
BG00310
BG0047
BG00512
BG0063
BG0078
BG00863
2
BG0030
BG0041
BG0051
BG0061
BG0071
BG0086
Not Hispanic or Latino
BG00010
BG00111
BG00218
BG00322
BG00410
BG00517
BG0065
BG00718
BG008111
Unknown or Not Reported
BG0000
BG0010
BG0020
BG0030
BG0040
BG0050
BG0060
BG0070
BG0080
0
BG0030
BG0040
BG0050
BG0060
BG0070
BG0080
Asian
BG0000
BG0010
BG0020
BG0030
BG0040
BG0051
BG0060
BG0070
BG0081
Native Hawaiian or Other Pacific Islander
BG0000
BG0010
BG0020
BG0030
BG0040
BG0050
BG0060
BG0070
BG0080
Black or African American
BG0000
BG0010
BG0020
BG0030
BG0040
BG0050
BG0060
BG0072
BG0082
White
BG00010
BG00111
BG00220
BG00322
BG00411
BG00516
BG0066
BG00717
BG008113
More than one race
BG0000
BG0010
BG0020
BG0030
BG0040
BG0050
BG0060
BG0070
BG0080
Unknown or Not Reported
BG0000
BG0010
BG0020
BG0030
BG0040
BG0051
BG0060
BG0070
BG0081
BG002
1
BG0032
BG0040
BG0051
BG0060
BG0072
BG0088
≥40 to <70 percent
BG0006
BG0019
BG00213
BG00313
BG0048
BG00512
BG0065
BG00713
BG00879
≥70 to ≤90 percent
BG0002
BG0012
BG0026
BG0037
BG0043
BG0055
BG0061
BG0074
BG00830
>90 percent
BG0000
BG0010
BG0020
BG0030
BG0040
BG0050
BG0060
BG0070
BG0080
22
OG00411
OG00518
OG0066
OG00719
17
OG0049
OG00515
OG0066
OG00718
Participants with SAEs
Title
Measurements
OG0003
OG0011
OG0024
OG0031
OG0042
OG0051
OG0063
OG0072
OG003
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.
OG004
Part 2: TEZ/IVA
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.
OG005
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.
OG006
Part 3: Placebo
Participants received placebo matched to VX-659/TEZ/VX-561 in TC treatment period for 4 weeks.
OG007
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.
Units
Counts
Participants
OG00010
OG00111
OG00220
OG00322
OG00411
OG00518
OG0066
OG00719
Title
Denominators
Categories
Title
Measurements
OG0000.4(-5.3 to 6.1)
OG00110.2(4.8 to 15.5)
OG00212.0(8.0 to 16.0)
OG00313.3(9.5 to 17.1)
OG0040.0(-3.9 to 3.9)
OG0059.7(6.6 to 12.7)
OG006-5.0(-12.2 to 2.1)
OG00712.2(8.3 to 16.2)
OG004
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.
OG005
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.
OG006
Part 3: Placebo
Participants received placebo matched to VX-659/TEZ/VX-561 in TC treatment period for 4 weeks.
OG007
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.
Units
Counts
Participants
OG00010
OG00111
OG00220
OG00322
OG00411
OG00518
OG0066
OG00719
Title
Denominators
Categories
Title
Measurements
OG0002.9(-6.3 to 12.2)
OG001-45.7(-54.4 to -37.0)
OG002-43.8(-50.7 to -37.0)
OG003-51.4(-57.8 to -44.9)
OG0043.0(-2.8 to 8.9)
OG005-42.2(-46.8 to -37.7)
OG006-1.3(-12.4 to 9.8)
OG007-38.1(-44.4 to -31.8)
OG004
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.
OG005
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.
OG006
Part 3: Placebo
Participants received placebo matched to VX-659/TEZ/VX-561 in TC treatment period for 4 weeks.
OG007
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.
Units
Counts
Participants
OG00010
OG00111
OG00220
OG00322
OG00411
OG00518
OG0066
OG00719
Title
Denominators
Categories
Title
Measurements
OG0000.0(-10.5 to 10.4)
OG00118.8(8.9 to 28.7)
OG00221.1(13.8 to 28.5)
OG00324.6(17.6 to 31.6)
OG0040.1(-7.1 to 7.3)
OG00517.3(11.7 to 23.0)
OG006-11.3(-23.7 to 1.1)
OG00721.5(14.6 to 28.4)
OG003
Part 1: VX-659/TEZ/IVA TC - High Dose
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.
OG004
Part 2: TEZ/IVA
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.
OG005
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.
OG006
Part 3: Placebo
Participants received placebo matched to VX-659/TEZ/VX-561 in TC treatment period for 4 weeks.
OG007
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.
Units
Counts
Participants
OG00010
OG00111
OG00220
OG00322
OG00411
OG00518
OG0066
OG00719
Title
Denominators
Categories
Title
Measurements
OG0004.7(-7.5 to 16.8)
OG00124.6(13.0 to 36.2)
OG00219.8(11.0 to 28.6)
OG00321.8(13.6 to 30.0)
OG0042.9(-5.2 to 11.1)
OG00519.5(13.1 to 25.9)
OG006-4.1(-17.8 to 9.6)
OG00714.7(7.1 to 22.4)
OG003
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.
OG004
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.
OG005
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.