Study of VX-661 Alone and in Combination With Ivacaftor i... | NCT01531673 | Trialant
NCT01531673
Sponsor
Vertex Pharmaceuticals Incorporated
Status
Completed
Last Update Posted
Apr 13, 2018Actual
Enrollment
194Actual
Phase
Phase 2
Conditions
Cystic Fibrosis
Interventions
VX-661
Ivacaftor
Placebo matched to VX-661
Placebo matched to ivacaftor
Countries
United States
Canada
Germany
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT01531673
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
VX11-661-101
Secondary IDs
ID
Type
Description
Link
2011-003821-93
EudraCT Number
Brief Title
Study of VX-661 Alone and in Combination With Ivacaftor in Subjects Homozygous or Heterozygous to the F508del-Cystic Fibrosis Transmembrane Conductance Regulator(CFTR) Mutation
Official Title
A Phase 2, Multicenter, Double-Blinded, Placebo Controlled Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of VX-661 Monotherapy and VX-661/Ivacaftor Cotherapy in Subjects With Cystic Fibrosis, Homozygous or Heterozygous for the F508del-CFTR Mutation
Acronym
Not provided
Organization
Vertex Pharmaceuticals IncorporatedINDUSTRY
Status Module
Record Verification Date
Mar 2018
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
Feb 2012
Primary Completion Date
Mar 2014Actual
Completion Date
Mar 2014Actual
First Submitted Date
Feb 1, 2012
First Submission Date that Met QC Criteria
Feb 8, 2012
First Posted Date
Feb 13, 2012Estimated
Results Waived
Not provided
Results First Submitted Date
Mar 14, 2018
Results First Submitted that Met QC Criteria
Mar 14, 2018
Results First Posted Date
Apr 13, 2018Actual
Certification/Extension (aka Delayed Results) First Submitted Date
May 5, 2015
Certification/Extension First Submitted that Passed QC Review
May 5, 2015
Certification/Extension First Posted Date
May 22, 2015Estimated
Last Update Submitted Date
Mar 14, 2018
Last Update Posted Date
Apr 13, 2018Actual
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
Not provided
Is FDA Regulated Device
Not provided
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
The purpose of this study is to evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) effects of VX-661 alone and when coadministered with ivacaftor in participants with cystic fibrosis (CF) who are homozygous or heterozygous for the F508del-CFTR mutation.
Detailed Description
This is a Phase 2, randomized, multicenter, double-blinded, placebo-controlled, study of VX-661 monotherapy, and VX-661/ivacaftor co-therapy in participants with CF who are homozygous or heterozygous for the F508del CFTR mutation.
This study is separated into seven groups: Group 1-7, respectively. Approximately 180 participants were randomized in a ratio of 4:1; active drug to matching placebo in each group.
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
194Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Group 1-6d Combined: Placebo
Placebo Comparator
All participants in group 1, 2a, 2b, 3a, 3b, 4, 5a, 5b, 6a and 6d who received placebo matched to VX-661 tablet and/or placebo matched to ivacaftor tablet for up to 28 days.
Drug: Placebo matched to VX-661
Drug: Placebo matched to ivacaftor
Group 1: VX-661 10 mg qd
Experimental
All participants in group 1 who received VX-661 10 milligram (mg) tablet orally once daily (qd) for up to 28 days.
Drug: VX-661
Group 2a: VX-661 30 mg qd
Experimental
All participants in group 2a who received VX-661 30 mg tablet orally qd and placebo matched to Ivacaftor tablet every 12 hours (q12h) for up to 28 days.
Drug: VX-661
Drug: Placebo matched to ivacaftor
Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h
Experimental
All participants in group 2b who received VX-661 10 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
Drug: VX-661
Drug: Ivacaftor
Group 3a: VX-661 100 mg qd
Experimental
All participants in group 3a who received VX-661 100 mg tablet orally qd and placebo matched to Ivacaftor tablet q12h for up to 28 days.
Interventions
Name
Type
Description
Arm Group Labels
Other Names
VX-661
Drug
Group 1: VX-661 10 mg qd
Group 2a: VX-661 30 mg qd
Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h
Group 3a: VX-661 100 mg qd
Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Safety as Determined by Adverse Events (AEs)
An AE is defined as any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the Informed Consent Form is signed. AE includes serious as well as non-serious AEs. Serious Adverse Event (SAE) is any AE that results in any of the following: death; life-threatening condition; inpatient hospitalization or prolongation of hospitalization; persistent or significant disability or incapacity; congenital anomaly or birth defect; or other important medical event. Treatment-emergent adverse events are defined as adverse events that were reported or worsened on or after start of study drug through the Follow-up Visit (28 days after last dose of study drug) or premature discontinuation.
Start of study drug through the Follow-up Visit (Up to Day 56)
Change in Sweat Chloride From Baseline Through Study Day 28 for Group 1-5b
Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug.
Baseline through Day 28
Change in Sweat Chloride From Baseline Through Study Day 28 for Group 6
Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug. As per planned analysis, participants who received placebo in Group 4 and 6 were combined and compared with Group 6.
Baseline through Day 28
Change in Sweat Chloride From Baseline Through Study Day 28 for Group 7
Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug.
Baseline through Day 28
Secondary Outcomes
Measure
Description
Time Frame
Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b
Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug.
Baseline, Day 7, Day 14, Day 21, Day 28
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Male or female with confirmed diagnosis of CF
Must have the F508del-CFTR gene mutation in both alleles (Groups 1, 2, 3, 4, 5, 6). Group 7 participants must have the F508del-CFTR mutation on 1 allele, and gating mutation G551D on the second allele and have been on their physician prescribed 150 mg KalydecoTM q12h (commercially available ivacaftor) for at least 28 days at the Screening Visit.
Forced expiratory volume in 1 second(FEV1) 40% to 90% (inclusive) of predicted normal for age, gender, and height (Knudson standards) at screening
Weight >40 kg and BMI >18.5
Participants of child-bearing potential and who are sexually active must meet the contraception requirements.
Exclusion Criteria:
History of any illness 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 participant.
An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before Study Day 1.
History of solid organ or hematological transplantation
Participation in a clinical study involving administration of either an investigational or a marketed drug within 30 days or 5 terminal half-lives (whichever is longer) before screening
History of alcohol, medication, or illicit drug abuse within 1 year prior to screening
Pregnant, breast-feeding, or not willing to follow contraception requirements
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
12 Years
Maximum Age
Not provided
Standard Ages
ChildAdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Scott Donaldson, MD
University of North Carolina
Principal Investigator
Locations
Facility
Status
City
State
ZIP
Country
Contacts
Vertex Investigational Site
Birmingham
Alabama
United States
Vertex Investigational Site
References Module
No data available
No data is available for this block.
IPD Sharing Statement Module
No data available
No data is available for this block.
Results Section
Participant Flow Module
Pre-assignment Details
A total of 194 participants were randomized of which 190 participants were treated.
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Group 1-6d Combined: Placebo
All participants in group 1, 2a, 2b, 3a, 3b, 4, 5a, 5b, 6a and 6d who received placebo matched to VX-661 tablet and/or placebo matched to ivacaftor tablet for up to 28 days.
All participants in group 3b who received VX-661 30 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
Drug: VX-661
Drug: Ivacaftor
Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h
Experimental
All participants in group 4 who received VX-661 100 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
Drug: VX-661
Drug: Ivacaftor
Group 5a: VX-661 150 mg qd
Experimental
All participants in group 5a who received VX-661 150 mg tablet orally qd for up to 28 days.
Drug: VX-661
Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h
Experimental
All participants in group 5b who received VX-661 150 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
Drug: VX-661
Drug: Ivacaftor
Group 6a: VX-661 100 mg qd/Ivacaftor 50 mg q12h
Experimental
All participants in group 6a who received VX-661 100 mg tablet qd and Ivacaftor 50 mg tablet q12h orally for up to 28 days.
Drug: VX-661
Drug: Ivacaftor
Group 6d: VX-661 50 mg q12h/Ivacaftor 150 mg q12h
Experimental
All participants in group 6d who received VX-661 50 mg tablet and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
Drug: VX-661
Drug: Ivacaftor
Group 7: Placebo
Placebo Comparator
All participants in group 7 who received placebo matched to VX-661 tablet orally qd in combination with physician-prescribed Kalydeco (Ivacaftor) for up to 28 days.
Drug: Ivacaftor
Drug: Placebo matched to VX-661
Group 7: VX-661 100 mg qd
Experimental
All participants in group 7 who received VX-661 100 mg tablet orally qd in combination with physician-prescribed Kalydeco (Ivacaftor) for up to 28 days.
Drug: VX-661
Drug: Ivacaftor
Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h
Group 5a: VX-661 150 mg qd
Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h
Group 6a: VX-661 100 mg qd/Ivacaftor 50 mg q12h
Group 6d: VX-661 50 mg q12h/Ivacaftor 150 mg q12h
Group 7: VX-661 100 mg qd
Ivacaftor
Drug
Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h
Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h
Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h
Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h
Group 6a: VX-661 100 mg qd/Ivacaftor 50 mg q12h
Group 6d: VX-661 50 mg q12h/Ivacaftor 150 mg q12h
Group 7: Placebo
Group 7: VX-661 100 mg qd
Placebo matched to VX-661
Drug
Group 1-6d Combined: Placebo
Group 7: Placebo
Placebo matched to ivacaftor
Drug
Group 1-6d Combined: Placebo
Group 2a: VX-661 30 mg qd
Group 3a: VX-661 100 mg qd
Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 6
Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug. As per planned analysis, participants who received placebo in Group 4 and 6 were combined and compared with Group 6.
Baseline, Day 7, Day 14, Day 21, Day 28
Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 7
Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug.
Baseline, Day 7, Day 14, Day 21, Day 28
Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Baseline, Day 7, Day 14, Day 21, Day 28
Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. As per planned analysis, participants who received placebo in Group 4 and 6 were combined and compared with Group 6.
Baseline, Day 7, Day 14, Day 21, Day 28
Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Baseline, Day 7, Day 14, Day 21, Day 28
Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Baseline, Day 7, Day 14, Day 21, Day 28
Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. As per planned analysis, participants who received placebo in Group 4 and 6 were combined and compared with Group 6.
Baseline, Day 7, Day 14, Day 21, Day 28
Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Baseline, Day 7, Day 14, Day 21, Day 28
Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b
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 (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Baseline, Day 14, Day 28
Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6
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 (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. As per planned analysis, participants who received placebo in Group 4 and 6 were combined and compared with Group 6.
Baseline, Day 14, Day 28
Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7
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 (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Baseline, Day 14, Day 28
Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24h) of VX-661 After Administration of VX-661 Monotherapy
Participants who received VX-661 monotherapy (Group 1, 2a, 3a and 5a) were analyzed for this outcome measure. PK analysis (AUC0-24h) was not planned for placebo reporting arms.
Day 28
AUC0-24h of VX-661 and AUC0-12h of Ivacaftor After Administration of VX-661 in Combination With Ivacaftor
Participants who received VX-661 in combination with Ivacaftor (Group 2b, 3b, 4, 5b, 6a, 6d and 7) were analyzed for this outcome measure. PK analysis was not planned for placebo reporting arms.
Day 28
Oakland
California
United States
Vertex Investigational Site
Boise
Idaho
United States
Vertex Investigational Site
Chicago
Illinois
United States
Vertex Investigational Site
Boston
Massachusetts
United States
Vertex Investigational Site
Grand Rapids
Michigan
United States
Vertex Investigational Site
Kansas City
Missouri
United States
Vertex Investigational Site
Long Branch
New Jersey
United States
Vertex Investigational Site
New Hyde Park
New York
United States
Vertex Investigational Site
Chapel Hill
North Carolina
United States
Vertex Investigational Site
Cincinnati
Ohio
United States
Vertex Investigational Site
Columbus
Ohio
United States
Vertex Investigational Site
Oklahoma City
Oklahoma
United States
Vertex Investigational Site
Hershey
Pennsylvania
United States
Vertex Investigational Site
Pittsburgh
Pennsylvania
United States
Vertex Investigational Site
Charleston
South Carolina
United States
Vertex Investigational Site
Salt Lake City
Utah
United States
Vertex Investigational Site
Burlington
Vermont
United States
Vertex Investigational Site
Seattle
Washington
United States
Vertex Investigational Site
Calgary
Alberta
Canada
Vertex Investigational Site
Vancouver
British Columbia
Canada
Vertex Investigational Site
Halifax
Nova Scotia
Canada
Vertex Investigational Site
Toronto
Ontario
Canada
Vertex Investigational Site
Erlangen
Bavaria
Germany
Vertex Investigational Site
Frankfurt am Main
Hesse
Germany
Vertex Investigational Site
Hanover
Lower Saxony
Germany
Vertex Investigational Site
Cologne
North Rhine-Westphalia
Germany
Vertex Investigational Site
Berlin
Germany
Vertex Investigational Site
Bochum
Germany
Vertex Investigational Site
Jena
Germany
Vertex Investigational Site
Munich
Germany
Vertex Investigational Site
Cambridge
Cambridgeshire
United Kingdom
Vertex Investigational Site
London
Greater London
United Kingdom
Vertex Investigational Site
Manchester
Greater Manchester
United Kingdom
Vertex Investigational Site
Southhampton
Hampshire
United Kingdom
Vertex Investigational Site
Cardiff
Vale of Glamorgen
United Kingdom
All participants in group 1 who received VX-661 10 milligram (mg) tablet orally once daily (qd) for up to 28 days.
FG002
Group 2a: VX-661 30 mg qd
All participants in group 2a who received VX-661 30 mg tablet orally qd and placebo matched to Ivacaftor tablet every 12 hours (q12h) for up to 28 days.
FG003
Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h
All participants in group 2b who received VX-661 10 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
FG004
Group 3a: VX-661 100 mg qd
All participants in group 3a who received VX-661 100 mg tablet orally qd and placebo matched to Ivacaftor tablet q12h for up to 28 days.
FG005
Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h
All participants in group 3b who received VX-661 30 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
FG006
Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h
All participants in group 4 who received VX-661 100 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
FG007
Group 5a: VX-661 150 mg qd
All participants in group 5a who received VX-661 150 mg tablet orally qd for up to 28 days.
FG008
Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h
All participants in group 5b who received VX-661 150 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
FG009
Group 6a: VX-661 100 mg qd/Ivacaftor 50 mg q12h
All participants in group 6a who received VX-661 100 mg tablet qd and Ivacaftor 50 mg tablet q12h orally for up to 28 days.
FG010
Group 6d: VX-661 50 mg q12h/Ivacaftor 150 mg q12h
All participants in group 6d who received VX-661 50 mg tablet and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
FG011
Group 7: Placebo
All participants in group 7 who received placebo matched to VX-661 tablet orally qd in combination with physician-prescribed Kalydeco for up to 28 days.
FG012
Group 7: VX-661 100 mg qd
All participants in group 7 who received VX-661 100 mg tablet orally qd in combination with physician-prescribed Kalydeco for up to 28 days.
FG00033 subjects
FG0018 subjects
FG0028 subjects
FG00318 subjects
FG0048 subjects
FG00519 subjects
FG00617 subjects
FG0079 subjects
FG00817 subjects
FG00919 subjects
FG01016 subjects
FG0114 subjects
FG01214 subjects
COMPLETED
FG00033 subjects
FG0017 subjects
FG0028 subjects
FG00317 subjects
FG0047 subjects
FG00518 subjects
FG00617 subjects
FG0079 subjects
FG00817 subjects
FG00918 subjects
FG01016 subjects
FG0114 subjects
FG01214 subjects
NOT COMPLETED
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0031 subjects
FG0041 subjects
FG0051 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0091 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
Type
Comment
Reasons
Non-Compliance
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0051 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
Adverse Event
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
Lost to Follow-up
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Other
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG004
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Group 1-6d Combined: Placebo
All participants in group 1, 2a, 2b, 3a, 3b, 4, 5a, 5b, 6a and 6d who received placebo matched to VX-661 tablet and/or placebo matched to ivacaftor tablet for up to 28 days.
BG001
Group 1: VX-661 10 mg qd
All participants in group 1 who received VX-661 10 mg tablet orally qd for up to 28 days.
BG002
Group 2a: VX-661 30 mg qd
All participants in group 2a who received VX-661 30 mg tablet orally qd and placebo matched to Ivacaftor tablet q12h for up to 28 days.
BG003
Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h
All participants in group 2b who received VX-661 10 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
BG004
Group 3a: VX-661 100 mg qd
All participants in group 3a who received VX-661 100 mg tablet orally qd and placebo matched to Ivacaftor tablet q12h for up to 28 days.
BG005
Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h
All participants in group 3b who received VX-661 30 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
BG006
Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h
All participants in group 4 who received VX-661 100 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
BG007
Group 5a: VX-661 150 mg qd
All participants in group 5a who received VX-661 150 mg tablet orally qd for up to 28 days.
BG008
Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h
All participants in group 5b who received VX-661 150 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
BG009
Group 6a: VX-661 100 mg qd/Ivacaftor 50 mg q12h
All participants in group 6a who received VX-661 100 mg tablet qd and Ivacaftor 50 mg tablet q12h orally for up to 28 days.
BG010
Group 6d: VX-661 50 mg q12h/Ivacaftor 150 mg q12h
All participants in group 6d who received VX-661 50 mg tablet and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
BG011
Group 7: Placebo
All participants in group 7 who received placebo matched to VX-661 tablet orally qd in combination with physician-prescribed Kalydeco for up to 28 days.
BG012
Group 7: VX-661 100 mg qd
All participants in group 7 who received VX-661 100 mg tablet orally qd in combination with physician-prescribed Kalydeco for up to 28 days.
BG013
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00033
BG0018
BG0028
BG00318
BG0048
BG00519
BG00617
BG0079
BG00817
BG00919
BG01016
BG0114
BG01214
BG013190
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00030.7± 8.42
BG00135.3± 8.26
BG00230.8± 6.63
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00013
BG0014
BG002
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 as Determined by Adverse Events (AEs)
An AE is defined as any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the Informed Consent Form is signed. AE includes serious as well as non-serious AEs. Serious Adverse Event (SAE) is any AE that results in any of the following: death; life-threatening condition; inpatient hospitalization or prolongation of hospitalization; persistent or significant disability or incapacity; congenital anomaly or birth defect; or other important medical event. Treatment-emergent adverse events are defined as adverse events that were reported or worsened on or after start of study drug through the Follow-up Visit (28 days after last dose of study drug) or premature discontinuation.
Analysis was done using safety set which included all participants who received at least 1 dose of study drug.
Posted
Number
participants
Start of study drug through the Follow-up Visit (Up to Day 56)
ID
Title
Description
OG000
Group 1-6d Combined: Placebo
All participants in group 1, 2a, 2b, 3a, 3b, 4, 5a, 5b, 6a and 6d who received placebo matched to VX-661 tablet and/or placebo matched to ivacaftor tablet for up to 28 days.
OG001
Group 1: VX-661 10 mg qd
All participants in group 1 who received VX-661 10 mg tablet orally qd for up to 28 days.
OG002
Group 2a: VX-661 30 mg qd
All participants in group 2a who received VX-661 30 mg tablet orally qd and placebo matched to Ivacaftor tablet q12h for up to 28 days.
OG003
Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h
All participants in group 2b who received VX-661 10 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
OG004
Group 3a: VX-661 100 mg qd
All participants in group 3a who received VX-661 100 mg tablet orally qd and placebo matched to Ivacaftor tablet q12h for up to 28 days.
OG005
Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h
All participants in group 3b who received VX-661 30 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
OG006
Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h
All participants in group 4 who received VX-661 100 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
OG007
Group 5a: VX-661 150 mg qd
Units
Counts
Participants
OG00033
OG0018
OG0028
OG003
Title
Denominators
Categories
Participants with AEs
Title
Measurements
OG00030
OG0018
OG0027
OG003
Primary
Change in Sweat Chloride From Baseline Through Study Day 28 for Group 1-5b
Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug.
The analysis was done using Full Analysis Set (FAS) which included all randomized participants who received at least 1 dose of study drug. Here, 'Number of participants analyzed' = those participants who were evaluable for this endpoint.
Posted
Least Squares Mean
95% Confidence Interval
millimole per liter (mmol/L)
Baseline through Day 28
ID
Title
Description
OG000
Group 1: VX-661 10 mg qd
All participants in group 1 who received VX-661 10 mg tablet orally qd for up to 28 days.
OG001
Group 2a: VX-661 30 mg qd
All participants in group 2a who received VX-661 30 mg tablet orally qd and placebo matched to Ivacaftor tablet q12h for up to 28 days.
OG002
Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h
All participants in group 2b who received VX-661 10 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
Primary
Change in Sweat Chloride From Baseline Through Study Day 28 for Group 6
Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug. As per planned analysis, participants who received placebo in Group 4 and 6 were combined and compared with Group 6.
The analysis was done using Full Analysis Set (FAS) which included all randomized participants who received at least 1 dose of study drug. Here, 'Number of participants analyzed' = those participants who were evaluable for this endpoint.
Posted
Least Squares Mean
95% Confidence Interval
mmol/L
Baseline through Day 28
ID
Title
Description
OG000
Group 6a: VX-661 100 mg qd/Ivacaftor 50 mg q12h
All participants in group 6a who received VX-661 100 mg tablet qd and Ivacaftor 50 mg tablet q12h orally for up to 28 days.
OG001
Group 6d: VX-661 50 mg q12h/Ivacaftor 150 mg q12h
All participants in group 6d who received VX-661 50 mg tablet q12h and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
OG002
Group 4 and 6 Combined: Placebo
All participants in group 4, 6a and 6d who received placebo matched to VX-661 tablet and/or placebo matched to ivacaftor tablet for up to 28 days.
Primary
Change in Sweat Chloride From Baseline Through Study Day 28 for Group 7
Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug.
The analysis was done using FAS which included all randomized participants who received at least 1 dose of study drug. Here, 'Number of participants analyzed' = those participants who were evaluable for this endpoint.
Posted
Least Squares Mean
95% Confidence Interval
mmol/L
Baseline through Day 28
ID
Title
Description
OG000
Group 7: Placebo
All participants in group 7 who received placebo matched to VX-661 tablet orally qd in combination with physician-prescribed Kalydeco for up to 28 days.
OG001
Group 7: VX-661 100 mg qd
All participants in group 7 who received VX-661 100 mg tablet orally qd in combination with physician-prescribed Kalydeco for up to 28 days.
Units
Counts
Participants
Secondary
Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b
Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug.
The analysis was done using FAS which included all randomized participants who received at least 1 dose of study drug. Here, 'Number of participants analyzed' = those participants who were evaluable for this endpoint and 'Number Analyzed' = those participants who were evaluable at the specified time points for each arm, respectively.
Posted
Least Squares Mean
95% Confidence Interval
mmol/L
Baseline, Day 7, Day 14, Day 21, Day 28
ID
Title
Description
OG000
Group 1: VX-661 10 mg qd
All participants in group 1 who received VX-661 10 mg tablet orally qd for up to 28 days.
OG001
Group 2a: VX-661 30 mg qd
All participants in group 2a who received VX-661 30 mg tablet orally qd and placebo matched to Ivacaftor tablet q12h for up to 28 days.
OG002
Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h
All participants in group 2b who received VX-661 10 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
Secondary
Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 6
Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug. As per planned analysis, participants who received placebo in Group 4 and 6 were combined and compared with Group 6.
The analysis was done using FAS which included all randomized participants who received at least 1 dose of study drug. Here, 'Number of participants analyzed' = those participants who were evaluable for this endpoint and 'Number Analyzed' = those participants who were evaluable at the specified time points for each group, respectively.
Posted
Least Squares Mean
95% Confidence Interval
mmol/L
Baseline, Day 7, Day 14, Day 21, Day 28
ID
Title
Description
OG000
Group 6a: VX-661 100 mg qd/Ivacaftor 50 mg q12h
All participants in group 6a who received VX-661 100 mg tablet qd and Ivacaftor 50 mg tablet q12h orally for up to 28 days.
OG001
Group 6d: VX-661 50 mg q12h/Ivacaftor 150 mg q12h
All participants in group 6d who received VX-661 50 mg tablet and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
OG002
Group 4 and 6 Combined: Placebo
Secondary
Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 7
Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug.
The analysis was done using FAS which included all randomized participants who received at least 1 dose of study drug. Here, 'Number Analyzed' = those participants who were evaluable at the specified time points for each group, respectively.
Posted
Least Squares Mean
95% Confidence Interval
mmol/L
Baseline, Day 7, Day 14, Day 21, Day 28
ID
Title
Description
OG000
Group 7: Placebo
All participants in group 7 who received placebo matched to VX-661 tablet orally qd in combination with physician-prescribed Kalydeco for up to 28 days.
OG001
Group 7: VX-661 100 mg qd
All participants in group 7 who received VX-661 100 mg tablet orally qd in combination with physician-prescribed Kalydeco for up to 28 days.
Units
Counts
Participants
Secondary
Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
The analysis was done using FAS which included all randomized participants who received at least 1 dose of study drug. Here, 'Number Analyzed' = those participants who were evaluable at the specified time points for each group, respectively.
Posted
Least Squares Mean
95% Confidence Interval
percent predicted of FEV1
Baseline, Day 7, Day 14, Day 21, Day 28
ID
Title
Description
OG000
Group 1: VX-661 10 mg qd
All participants in group 1 who received VX-661 10 mg tablet orally qd for up to 28 days.
OG001
Group 2a: VX-661 30 mg qd
All participants in group 2a who received VX-661 30 mg tablet orally qd and placebo matched to Ivacaftor tablet q12h for up to 28 days.
OG002
Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h
All participants in group 2b who received VX-661 10 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
Secondary
Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. As per planned analysis, participants who received placebo in Group 4 and 6 were combined and compared with Group 6.
The analysis was done using FAS which included all randomized participants who received at least 1 dose of study drug. Here, 'Number Analyzed' = those participants who were evaluable at the specified time points for each group, respectively.
Posted
Least Squares Mean
95% Confidence Interval
percent predicted of FEV1
Baseline, Day 7, Day 14, Day 21, Day 28
ID
Title
Description
OG000
Group 6a: VX-661 100 mg qd/Ivacaftor 50 mg q12h
All participants in group 6a who received VX-661 100 mg tablet qd and Ivacaftor 50 mg tablet q12h orally for up to 28 days.
OG001
Group 6d: VX-661 50 mg q12h/Ivacaftor 150 mg q12h
All participants in group 6d who received VX-661 50 mg tablet and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
OG002
Group 4 and 6 Combined: Placebo
All participants in group 4, 6a and 6d who received placebo matched to VX-661 tablet and/or placebo matched to ivacaftor tablet for up to 28 days.
Secondary
Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
The analysis was done using FAS which included all randomized participants who received at least 1 dose of study drug.
Posted
Least Squares Mean
95% Confidence Interval
percent predicted of FEV1
Baseline, Day 7, Day 14, Day 21, Day 28
ID
Title
Description
OG000
Group 7: Placebo
All participants in group 7 who received placebo matched to VX-661 tablet orally qd in combination with physician-prescribed Kalydeco for up to 28 days.
OG001
Group 7: VX-661 100 mg qd
All participants in group 7 who received VX-661 100 mg tablet orally qd in combination with physician-prescribed Kalydeco for up to 28 days.
Units
Counts
Participants
OG000
Secondary
Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
The analysis was done using FAS which included all randomized participants who received at least 1 dose of study drug. Here 'Number Analyzed' = those participants who were evaluable at the specified time points for each group, respectively.
Posted
Least Squares Mean
95% Confidence Interval
Liters
Baseline, Day 7, Day 14, Day 21, Day 28
ID
Title
Description
OG000
Group 1: VX-661 10 mg qd
All participants in group 1 who received VX-661 10 mg tablet orally qd for up to 28 days.
OG001
Group 2a: VX-661 30 mg qd
All participants in group 2a who received VX-661 30 mg tablet orally qd and placebo matched to Ivacaftor tablet q12h for up to 28 days.
OG002
Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h
All participants in group 2b who received VX-661 10 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
OG003
Secondary
Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. As per planned analysis, participants who received placebo in Group 4 and 6 were combined and compared with Group 6.
The analysis was done using FAS which included all randomized participants who received at least 1 dose of study drug. Here, 'Number Analyzed' = those participants who were evaluable at the specified time points for each group, respectively.
Posted
Least Squares Mean
95% Confidence Interval
Liters
Baseline, Day 7, Day 14, Day 21, Day 28
ID
Title
Description
OG000
Group 6a: VX-661 100 mg qd/Ivacaftor 50 mg q12h
All participants in group 6a who received VX-661 100 mg tablet qd and Ivacaftor 50 mg tablet q12h orally for up to 28 days.
OG001
Group 6d: VX-661 50 mg q12h/Ivacaftor 150 mg q12h
All participants in group 6d who received VX-661 50 mg tablet and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
OG002
Group 4 and 6 Combined: Placebo
All participants in group 4, 6a and 6d who received placebo matched to VX-661 tablet and/or placebo matched to ivacaftor tablet for up to 28 days.
Secondary
Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
The analysis was done using FAS which included all randomized participants who received at least 1 dose of study drug.
Posted
Least Squares Mean
95% Confidence Interval
Liters
Baseline, Day 7, Day 14, Day 21, Day 28
ID
Title
Description
OG000
Group 7: Placebo
All participants in group 7 who received placebo matched to VX-661 tablet orally qd in combination with physician-prescribed Kalydeco for up to 28 days.
OG001
Group 7: VX-661 100 mg qd
All participants in group 7 who received VX-661 100 mg tablet orally qd in combination with physician-prescribed Kalydeco for up to 28 days.
Units
Counts
Participants
OG000
Secondary
Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b
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 (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
The analysis was done using FAS which included all randomized participants who received at least 1 dose of study drug. Here, 'Number Analyzed' = those participants who were evaluable at the specified time points for each group, respectively.
Posted
Least Squares Mean
95% Confidence Interval
units on a scale
Baseline, Day 14, Day 28
ID
Title
Description
OG000
Group 1: VX-661 10 mg qd
All participants in group 1 who received VX-661 10 mg tablet orally qd for up to 28 days.
OG001
Group 2a: VX-661 30 mg qd
All participants in group 2a who received VX-661 30 mg tablet orally qd and placebo matched to Ivacaftor tablet q12h for up to 28 days.
OG002
Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h
Secondary
Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6
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 (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. As per planned analysis, participants who received placebo in Group 4 and 6 were combined and compared with Group 6.
The analysis was done using FAS which included all randomized participants who received at least 1 dose of study drug. Here, 'Number Analyzed' = those participants who were evaluable at the specified time points for each group, respectively.
Posted
Least Squares Mean
95% Confidence Interval
units on a scale
Baseline, Day 14, Day 28
ID
Title
Description
OG000
Group 6a: VX-661 100 mg qd/Ivacaftor 50 mg q12h
All participants in group 6a who received VX-661 100 mg tablet qd and Ivacaftor 50 mg tablet q12h orally for up to 28 days.
OG001
Group 6d: VX-661 50 mg q12h/Ivacaftor 150 mg q12h
All participants in group 6d who received VX-661 50 mg tablet and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
OG002
Secondary
Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7
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 (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
The analysis was done using FAS which included all randomized participants who received at least 1 dose of study drug. Here, 'Number Analyzed' = those participants who were evaluable at the specified time points for each group, respectively.
Posted
Least Squares Mean
95% Confidence Interval
units on a scale
Baseline, Day 14, Day 28
ID
Title
Description
OG000
Group 7: Placebo
All participants in group 7 who received placebo matched to VX-661 tablet orally qd in combination with physician-prescribed Kalydeco for up to 28 days.
OG001
Group 7: VX-661 100 mg qd
All participants in group 7 who received VX-661 100 mg tablet orally qd in combination with physician-prescribed Kalydeco for up to 28 days.
Secondary
Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24h) of VX-661 After Administration of VX-661 Monotherapy
Participants who received VX-661 monotherapy (Group 1, 2a, 3a and 5a) were analyzed for this outcome measure. PK analysis (AUC0-24h) was not planned for placebo reporting arms.
The analysis was done using Pharmacokinetics (PK) Set.
Posted
Mean
Standard Deviation
nanogram*hour per milliliter (ng*hr/mL)
Day 28
ID
Title
Description
OG000
Group 1: VX-661 10 mg qd
All participants in group 1 who received VX-661 10 mg tablet orally qd for up to 28 days.
OG001
Group 2a: VX-661 30 mg qd
All participants in group 2a who received VX-661 30 mg tablet orally qd and placebo matched to Ivacaftor tablet q12h for up to 28 days.
OG002
Group 3a: VX-661 100 mg qd
All participants in group 3a who received VX-661 100 mg tablet orally qd and placebo matched to Ivacaftor tablet q12h for up to 28 days.
OG003
Group 5a: VX-661 150 mg qd
Secondary
AUC0-24h of VX-661 and AUC0-12h of Ivacaftor After Administration of VX-661 in Combination With Ivacaftor
Participants who received VX-661 in combination with Ivacaftor (Group 2b, 3b, 4, 5b, 6a, 6d and 7) were analyzed for this outcome measure. PK analysis was not planned for placebo reporting arms.
The analysis was done using PK Set.
Posted
Mean
Standard Deviation
ng*h/mL
Day 28
ID
Title
Description
OG000
Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h
All participants in group 2b who received VX-661 10 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
OG001
Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h
All participants in group 3b who received VX-661 30 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
OG002
Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h
All participants in group 4 who received VX-661 100 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
OG003
Group 5b: VX-661 150 mg qd/ Ivacaftor 150 mg q12h
Time Frame
Start of study drug through the Follow-up Visit (Up to Day 56)
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
Group 1-6d Combined: Placebo
All participants in group 1, 2a, 2b, 3a, 3b, 4, 5a, 5b, 6a and 6d who received placebo matched to VX-661 tablet and/or placebo matched to ivacaftor tablet for up to 28 days.
5
33
30
33
EG001
Group 1: VX-661 10 mg qd
All participants in group 1 who received VX-661 10 milligram (mg) tablet orally qd for up to 28 days.
1
8
8
8
EG002
Group 2a: VX-661 30 mg qd
All participants in group 2a who received VX-661 30 mg tablet orally qd and placebo matched to Ivacaftor tablet q12h for up to 28 days.
1
8
7
8
EG003
Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h
All participants in group 2b who received VX-661 10 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
1
18
15
18
EG004
Group 3a: VX-661 100 mg qd
All participants in group 3a who received VX-661 100 mg tablet orally qd and placebo matched to Ivacaftor tablet q12h for up to 28 days.
0
8
7
8
EG005
Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h
All participants in group 3b who received VX-661 30 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
2
19
18
19
EG006
Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h
All participants in group 4 who received VX-661 100 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
2
17
9
17
EG007
Group 5a: VX-661 150 mg qd
All participants in group 5a who received VX-661 150 mg tablet orally qd for up to 28 days.
0
9
8
9
EG008
Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h
All participants in group 5b who received VX-661 150 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
0
17
17
17
EG009
Group 6a: VX-661 100 mg qd/Ivacaftor 50 mg q12h
All participants in group 6a who received VX-661 100 mg tablet qd and Ivacaftor 50 mg tablet q12h orally for up to 28 days.
1
19
16
19
EG010
Group 6d: VX-661 50 mg q12h/Ivacaftor 150 mg q12h
All participants in group 6d who received VX-661 50 mg tablet and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
2
16
16
16
EG011
Group 7: Placebo
All participants in group 7 who received placebo matched to VX-661 tablet orally qd in combination with physician-prescribed Kalydeco for up to 28 days.
0
4
2
4
EG012
Group 7: VX-661 100 mg qd
All participants in group 7 who received VX-661 100 mg tablet orally qd in combination with physician-prescribed Kalydeco for up to 28 days.
1
14
12
14
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Haemoptysis
Respiratory, thoracic and mediastinal disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG0030 affected18 at risk
EG004
Pyrexia
General disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0011 affected8 at risk
EG0020 affected8 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0011 affected8 at risk
EG0020 affected8 at risk
EG003
Arthritis
Musculoskeletal and connective tissue disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Infective pulmonary exacerbation of cystic fibrosis
Infections and infestations
MedDRA (14.1)
Systematic Assessment
EG0005 affected33 at risk
EG0011 affected8 at risk
EG0021 affected8 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0011 affected8 at risk
EG0020 affected8 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Hot flush
Vascular disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG0030 affected18 at risk
EG0040 affected8 at risk
EG0050 affected19 at risk
EG0060 affected17 at risk
EG0070 affected9 at risk
EG0080 affected17 at risk
EG0090 affected19 at risk
EG0100 affected16 at risk
EG0110 affected4 at risk
EG0121 affected14 at risk
Seasonal allergy
Immune system disorders
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Drug hypersensitivity
Immune system disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Hypersensitivity
Immune system disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Fatigue
General disorders
MedDRA (14.1)
Systematic Assessment
EG0003 affected33 at risk
EG0014 affected8 at risk
EG0021 affected8 at risk
EG003
Pyrexia
General disorders
MedDRA (14.1)
Systematic Assessment
EG0002 affected33 at risk
EG0012 affected8 at risk
EG0020 affected8 at risk
EG003
Application site rash
General disorders
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0011 affected8 at risk
EG0020 affected8 at risk
EG003
Pain
General disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0011 affected8 at risk
EG0020 affected8 at risk
EG003
Thirst
General disorders
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Application site erythema
General disorders
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Catheter site haematoma
General disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Chest pain
General disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Disease progression
General disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0011 affected8 at risk
EG0020 affected8 at risk
EG003
Feeling abnormal
General disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Feeling hot
General disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Infusion site pain
General disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0011 affected8 at risk
EG0020 affected8 at risk
EG003
Infusion site swelling
General disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Malaise
General disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Medical device complication
General disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Non-cardiac chest pain
General disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Vessel puncture site haematoma
General disorders
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Vessel puncture site reaction
General disorders
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Abnormal dreams
Psychiatric disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0011 affected8 at risk
EG0020 affected8 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0011 affected8 at risk
EG0020 affected8 at risk
EG003
Depression
Psychiatric disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0021 affected8 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Thinking abnormal
Psychiatric disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Breast tenderness
Reproductive system and breast disorders
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Dysmenorrhoea
Reproductive system and breast disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Menstrual disorder
Reproductive system and breast disorders
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Metrorrhagia
Reproductive system and breast disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Vaginal haemorrhage
Reproductive system and breast disorders
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Muscle strain
Injury, poisoning and procedural complications
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0021 affected8 at risk
EG003
Concussion
Injury, poisoning and procedural complications
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Contusion
Injury, poisoning and procedural complications
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Excoriation
Injury, poisoning and procedural complications
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Laceration
Injury, poisoning and procedural complications
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0021 affected8 at risk
EG003
Ligament sprain
Injury, poisoning and procedural complications
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Limb injury
Injury, poisoning and procedural complications
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Post concussion syndrome
Injury, poisoning and procedural complications
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Procedural pain
Injury, poisoning and procedural complications
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Scratch
Injury, poisoning and procedural complications
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Skeletal injury
Injury, poisoning and procedural complications
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Sunburn
Injury, poisoning and procedural complications
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Pulmonary function test decreased
Investigations
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0011 affected8 at risk
EG0020 affected8 at risk
EG003
Weight decreased
Investigations
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0011 affected8 at risk
EG0020 affected8 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Blood glucose decreased
Investigations
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Hepatic enzyme increased
Investigations
MedDRA (14.1)
Systematic Assessment
EG0002 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Liver function test abnormal
Investigations
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0011 affected8 at risk
EG0020 affected8 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Blood bilirubin increased
Investigations
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Blood bilirubin unconjugated increased
Investigations
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Blood creatinine increased
Investigations
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Blood phosphorus increased
Investigations
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Blood potassium increased
Investigations
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Gastrointestinal examination abnormal
Investigations
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Neutrophil count decreased
Investigations
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Platelet count decreased
Investigations
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Transaminases increased
Investigations
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0011 affected8 at risk
EG0020 affected8 at risk
EG003
Urinary casts present
Investigations
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0021 affected8 at risk
EG003
Urine colour abnormal
Investigations
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Vitamin D decreased
Investigations
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
White blood cell count decreased
Investigations
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
White blood cells urine positive
Investigations
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0021 affected8 at risk
EG003
Cystic fibrosis related diabetes
Congenital, familial and genetic disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Anaemia
Blood and lymphatic system disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA (14.1)
Systematic Assessment
EG0006 affected33 at risk
EG0013 affected8 at risk
EG0023 affected8 at risk
EG003
Sputum increased
Respiratory, thoracic and mediastinal disorders
MedDRA (14.1)
Systematic Assessment
EG0002 affected33 at risk
EG0012 affected8 at risk
EG0022 affected8 at risk
EG003
Haemoptysis
Respiratory, thoracic and mediastinal disorders
MedDRA (14.1)
Systematic Assessment
EG0002 affected33 at risk
EG0012 affected8 at risk
EG0020 affected8 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA (14.1)
Systematic Assessment
EG0003 affected33 at risk
EG0010 affected8 at risk
EG0021 affected8 at risk
EG003
Nasal congestion
Respiratory, thoracic and mediastinal disorders
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0012 affected8 at risk
EG0020 affected8 at risk
EG003
Rales
Respiratory, thoracic and mediastinal disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0012 affected8 at risk
EG0020 affected8 at risk
EG003
Respiration abnormal
Respiratory, thoracic and mediastinal disorders
MedDRA (14.1)
Systematic Assessment
EG0002 affected33 at risk
EG0011 affected8 at risk
EG0020 affected8 at risk
EG003
Respiratory tract congestion
Respiratory, thoracic and mediastinal disorders
MedDRA (14.1)
Systematic Assessment
EG0002 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Sinus congestion
Respiratory, thoracic and mediastinal disorders
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0021 affected8 at risk
EG003
Rhinorrhoea
Respiratory, thoracic and mediastinal disorders
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0011 affected8 at risk
EG0020 affected8 at risk
EG003
Dysphonia
Respiratory, thoracic and mediastinal disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0011 affected8 at risk
EG0020 affected8 at risk
EG003
Dyspnoea exertional
Respiratory, thoracic and mediastinal disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Increased viscosity of bronchial secretion
Respiratory, thoracic and mediastinal disorders
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Productive cough
Respiratory, thoracic and mediastinal disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0011 affected8 at risk
EG0020 affected8 at risk
EG003
Sputum discoloured
Respiratory, thoracic and mediastinal disorders
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Wheezing
Respiratory, thoracic and mediastinal disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0011 affected8 at risk
EG0020 affected8 at risk
EG003
Asthma
Respiratory, thoracic and mediastinal disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Bronchial obstruction
Respiratory, thoracic and mediastinal disorders
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Bronchial secretion retention
Respiratory, thoracic and mediastinal disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Bronchiectasis
Respiratory, thoracic and mediastinal disorders
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Increased bronchial secretion
Respiratory, thoracic and mediastinal disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Nasal obstruction
Respiratory, thoracic and mediastinal disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Nasal oedema
Respiratory, thoracic and mediastinal disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0021 affected8 at risk
EG003
Painful respiration
Respiratory, thoracic and mediastinal disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Paranasal sinus hypersecretion
Respiratory, thoracic and mediastinal disorders
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Respiratory tract irritation
Respiratory, thoracic and mediastinal disorders
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Upper respiratory tract congestion
Respiratory, thoracic and mediastinal disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Headache
Nervous system disorders
MedDRA (14.1)
Systematic Assessment
EG0008 affected33 at risk
EG0011 affected8 at risk
EG0021 affected8 at risk
EG003
Sinus headache
Nervous system disorders
MedDRA (14.1)
Systematic Assessment
EG0002 affected33 at risk
EG0011 affected8 at risk
EG0020 affected8 at risk
EG003
Dizziness
Nervous system disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0023 affected8 at risk
EG003
Lethargy
Nervous system disorders
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Migraine
Nervous system disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0021 affected8 at risk
EG003
Neuralgia
Nervous system disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Dysgeusia
Nervous system disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Partial seizures
Nervous system disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Presyncope
Nervous system disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Somnolence
Nervous system disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Syncope
Nervous system disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Conjunctival haemorrhage
Eye disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Conjunctival irritation
Eye disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Dry eye
Eye disorders
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Vision blurred
Eye disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0011 affected8 at risk
EG0020 affected8 at risk
EG003
Ear pain
Ear and labyrinth disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Ear discomfort
Ear and labyrinth disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Vertigo
Ear and labyrinth disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0011 affected8 at risk
EG0022 affected8 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA (14.1)
Systematic Assessment
EG0002 affected33 at risk
EG0011 affected8 at risk
EG0021 affected8 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0021 affected8 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA (14.1)
Systematic Assessment
EG0002 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0021 affected8 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0021 affected8 at risk
EG003
Flatulence
Gastrointestinal disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0022 affected8 at risk
EG003
Abdominal distension
Gastrointestinal disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Dry mouth
Gastrointestinal disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0021 affected8 at risk
EG003
Abdominal discomfort
Gastrointestinal disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Abdominal pain lower
Gastrointestinal disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Change of bowel habit
Gastrointestinal disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Dental caries
Gastrointestinal disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Enteritis
Gastrointestinal disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Faecaloma
Gastrointestinal disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Faeces discoloured
Gastrointestinal disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Frequent bowel movements
Gastrointestinal disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Paraesthesia oral
Gastrointestinal disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Retching
Gastrointestinal disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Toothache
Gastrointestinal disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Leukocyturia
Renal and urinary disorders
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Pollakiuria
Renal and urinary disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Urine odour abnormal
Renal and urinary disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Night sweats
Skin and subcutaneous tissue disorders
MedDRA (14.1)
Systematic Assessment
EG0002 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Cold sweat
Skin and subcutaneous tissue disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0021 affected8 at risk
EG003
Dry skin
Skin and subcutaneous tissue disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Eczema
Skin and subcutaneous tissue disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Nail disorder
Skin and subcutaneous tissue disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Photosensitivity reaction
Skin and subcutaneous tissue disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Rash erythematous
Skin and subcutaneous tissue disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Rash follicular
Skin and subcutaneous tissue disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Rash macular
Skin and subcutaneous tissue disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Rash papular
Skin and subcutaneous tissue disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Red man syndrome
Skin and subcutaneous tissue disorders
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA (14.1)
Systematic Assessment
EG0003 affected33 at risk
EG0011 affected8 at risk
EG0020 affected8 at risk
EG003
Musculoskeletal chest pain
Musculoskeletal and connective tissue disorders
MedDRA (14.1)
Systematic Assessment
EG0002 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0011 affected8 at risk
EG0020 affected8 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Arthritis
Musculoskeletal and connective tissue disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Joint swelling
Musculoskeletal and connective tissue disorders
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Musculoskeletal pain
Musculoskeletal and connective tissue disorders
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0011 affected8 at risk
EG0020 affected8 at risk
EG003
Hypoglycaemia
Metabolism and nutrition disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Hypocalcaemia
Metabolism and nutrition disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Increased appetite
Metabolism and nutrition disorders
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Vitamin E deficiency
Metabolism and nutrition disorders
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Vitamin K deficiency
Metabolism and nutrition disorders
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Infective pulmonary exacerbation of cystic fibrosis
Infections and infestations
MedDRA (14.1)
Systematic Assessment
EG0008 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA (14.1)
Systematic Assessment
EG0003 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0021 affected8 at risk
EG003
Sinusitis
Infections and infestations
MedDRA (14.1)
Systematic Assessment
EG0003 affected33 at risk
EG0012 affected8 at risk
EG0020 affected8 at risk
EG003
Viral upper respiratory tract infection
Infections and infestations
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Oral candidiasis
Infections and infestations
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0021 affected8 at risk
EG003
Acute sinusitis
Infections and infestations
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0011 affected8 at risk
EG0020 affected8 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0011 affected8 at risk
EG0020 affected8 at risk
EG003
Oral herpes
Infections and infestations
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Bronchitis
Infections and infestations
MedDRA (14.1)
Systematic Assessment
EG0002 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Gastroenteritis viral
Infections and infestations
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Otitis media
Infections and infestations
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Rhinitis
Infections and infestations
MedDRA (14.1)
Systematic Assessment
EG0002 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Bronchopulmonary aspergillosis allergic
Infections and infestations
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Cellulitis
Infections and infestations
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Lower respiratory tract infection viral
Infections and infestations
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Paronychia
Infections and infestations
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Pneumonia
Infections and infestations
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Respiratory syncytial virus infection
Infections and infestations
MedDRA (14.1)
Systematic Assessment
EG0001 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Respiratory tract infection
Infections and infestations
MedDRA (14.1)
Systematic Assessment
EG0000 affected33 at risk
EG0010 affected8 at risk
EG0020 affected8 at risk
EG003
Pharmacokinetic (PK) final data are not yet available. Once the data are available for PK endpoints, the posting will be updated to include the same.
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
Restriction Description: PI is free to publish results of the study after (1)first multi-center publication, (2)if sponsor elects not to publish the results, or(3)18 months after close of the study, whichever occurs first. Proposed publications are to be submitted to the sponsor for review and comment for a period of at least 45 days (which may be extended under certain circumstances related to protection of intellectual property); the sponsor cannot require changes to the proposed publications.
Point of Contact
Title
Organization
Phone
Extension
Email
Medical Monitor
Vertex Pharmaceuticals Incorporated
617-341-6777
medicalinfo@vrtx.com
ID
Term
D003550
Cystic Fibrosis
Ancestor Terms
ID
Term
D010182
Pancreatic Diseases
D004066
Digestive System Diseases
D008171
Lung Diseases
D012140
Respiratory Tract Diseases
D030342
Genetic Diseases, Inborn
D009358
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D007232
Infant, Newborn, Diseases
Browse Leaves
Not provided
Browse Branches
Not provided
ID
Term
C000625213
tezacaftor
C545203
ivacaftor
Ancestor Terms
Not provided
Browse Leaves
Not provided
Browse Branches
Not provided
0 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
1 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
0 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0091 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
28.3
± 7.05
BG00429.1± 7.12
BG00529.2± 6.39
BG00631± 9.3
BG00728.2± 8.6
BG00828.2± 6.46
BG00927.9± 5.58
BG01032.8± 11.92
BG01134.5± 7.59
BG01226.6± 7.01
BG01329.8± 7.97
4
BG0036
BG0043
BG0056
BG00611
BG0073
BG00810
BG0097
BG0107
BG0113
BG0126
BG01383
Male
BG00020
BG0014
BG0024
BG00312
BG0045
BG00513
BG0066
BG0076
BG0087
BG00912
BG0109
BG0111
BG0128
BG013107
All participants in group 5a who received VX-661 150 mg tablet orally qd for up to 28 days.
OG008
Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h
All participants in group 5b who received VX-661 150 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
OG009
Group 6a: VX-661 100 mg qd/Ivacaftor 50 mg q12h
All participants in group 6a who received VX-661 100 mg tablet qd and Ivacaftor 50 mg tablet q12h orally for up to 28 days.
OG010
Group 6d: VX-661 50 mg q12h/Ivacaftor 150 mg q12h
All participants in group 6d who received VX-661 50 mg tablet and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
OG011
Group 7: Placebo
All participants in group 7 who received placebo matched to VX-661 tablet orally qd in combination with physician-prescribed Kalydeco for up to 28 days.
OG012
Group 7: VX-661 100 mg qd
All participants in group 7 who received VX-661 100 mg tablet orally qd in combination with physician-prescribed Kalydeco for up to 28 days.
18
OG0048
OG00519
OG00617
OG0079
OG00817
OG00919
OG01016
OG0114
OG01214
15
OG0047
OG00518
OG00610
OG0078
OG00817
OG00916
OG01016
OG0112
OG01212
Participants with SAEs
Title
Measurements
OG0005
OG0011
OG0021
OG0031
OG0040
OG0052
OG0062
OG0070
OG0080
OG0091
OG0102
OG0110
OG0121
OG003
Group 3a: VX-661 100 mg qd
All participants in group 3a who received VX-661 100 mg tablet orally qd and placebo matched to Ivacaftor tablet q12h for up to 28 days.
OG004
Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h
All participants in group 3b who received VX-661 30 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
OG005
Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h
All participants in group 4 who received VX-661 100 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
OG006
Group 5a: VX-661 150 mg qd
All participants in group 5a who received VX-661 150 mg tablet orally qd for up to 28 days.
OG007
Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h
All participants in group 5b who received VX-661 150 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
OG008
Group 1-5b Combined Placebo
All participants in group 1, 2a, 2b, 3a, 3b, 4, 5a and 5b who received placebo matched to VX-661 tablet and/or placebo matched to ivacaftor tablet for up to 28 days.
Units
Counts
Participants
OG0008
OG0016
OG00218
OG0038
OG00418
OG00517
OG0069
OG00717
OG00824
Title
Denominators
Categories
Title
Measurements
OG0003.92(-0.5 to 8.34)
OG001-4.76(-9.75 to 0.22)
OG002-5.06(-8.02 to -2.09)
OG003-20.43(-24.75 to -16.12)
OG004-6(-8.98 to 3.02)
OG005-6.04(-9.12 to -2.96)
OG006-10.46(-14.53 to -6.39)
OG007-2.63(-5.67 to 0.41)
OG008-0.86(-3.36 to 1.65)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG008
Mixed-effect repeated measure (MMRM)
0.0647
Least Squares (LS) Mean Difference
4.77
2-Sided
95
-0.3
9.84
Superiority
OG001
OG008
MMRM
0.1686
LS Mean Difference
-3.91
2-Sided
95
-9.5
1.68
Superiority
OG002
OG008
MMRM
0.0348
LS Mean Difference
-4.2
2-Sided
95
-8.1
-0.31
Superiority
OG003
OG008
MMRM
<0.0001
LS Mean Difference
-19.58
2-Sided
95
-24.57
-14.59
Superiority
OG004
OG008
MMRM
0.0101
LS Mean Difference
-5.14
2-Sided
95
-9.03
-1.25
Superiority
OG005
OG008
MMRM
0.011
LS Mean Difference
-5.19
2-Sided
95
-9.16
-1.21
Superiority
OG006
OG008
MMRM
0.0001
LS Mean Difference
-9.6
2-Sided
95
-14.38
-4.82
Superiority
OG007
OG008
MMRM
0.3745
LS Mean Difference
-1.77
2-Sided
95
-5.71
2.17
Superiority
Units
Counts
Participants
OG00018
OG00116
OG00214
Title
Denominators
Categories
Title
Measurements
OG000-6.07(-10.84 to -1.31)
OG001-7.89(-12.3 to -3.48)
OG002-1.19(-5.5 to 3.12)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG001
OG002
MMRM
0.0357
LS Mean Difference
-6.7
2-Sided
95
-12.94
-0.46
Superiority
OG0004
OG00113
Title
Denominators
Categories
Title
Measurements
OG00010.18(-2.48 to 22.84)
OG001-7.02(-14.15 to 0.11)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
MMRM
0.0238
LS Mean Difference
-17.2
2-Sided
95
-31.75
-2.65
Superiority
OG003
Group 3a: VX-661 100 mg qd
All participants in group 3a who received VX-661 100 mg tablet orally qd and placebo matched to Ivacaftor tablet q12h for up to 28 days.
OG004
Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h
All participants in group 3b who received VX-661 30 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
OG005
Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h
All participants in group 4 who received VX-661 100 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
OG006
Group 5a: VX-661 150 mg qd
All participants in group 5a who received VX-661 150 mg tablet orally qd for up to 28 days.
OG007
Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h
All participants in group 5b who received VX-661 150 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
OG008
Group 1-5b Combined Placebo
All participants in group 1, 2a, 2b, 3a, 3b, 4, 5a and 5b who received placebo matched to VX-661 tablet and/or placebo matched to ivacaftor tablet for up to 28 days.
Units
Counts
Participants
OG0008
OG0018
OG00218
OG0038
OG00418
OG00517
OG0069
OG00717
OG00824
Title
Denominators
Categories
Day 7
ParticipantsOG0008
ParticipantsOG0016
ParticipantsOG00216
ParticipantsOG0038
ParticipantsOG00416
ParticipantsOG00516
ParticipantsOG0069
ParticipantsOG00717
ParticipantsOG00823
Title
Measurements
OG0001.73(-3.82 to 7.29)
OG001-3.13(-9.5 to 3.25)
OG002-5.37(-9.24 to -1.49)
OG003
Day 14
ParticipantsOG0008
ParticipantsOG0016
ParticipantsOG00217
ParticipantsOG0038
Day 21
ParticipantsOG0007
ParticipantsOG0016
ParticipantsOG00217
ParticipantsOG0038
Day 28
ParticipantsOG0007
ParticipantsOG0016
ParticipantsOG00217
ParticipantsOG0038
All participants in group 4, 6a and 6d who received placebo matched to VX-661 tablet and/or placebo matched to ivacaftor tablet for up to 28 days.
Units
Counts
Participants
OG00019
OG00116
OG00214
Title
Denominators
Categories
Day 7
ParticipantsOG00015
ParticipantsOG00113
ParticipantsOG00213
Title
Measurements
OG000-6.61(-12.06 to -1.16)
OG001-11.04(-16.37 to -5.7)
OG002-0.36(-5.54 to 4.83)
Day 14
ParticipantsOG00017
ParticipantsOG00114
ParticipantsOG00214
Title
Measurements
OG000
Day 21
ParticipantsOG00013
ParticipantsOG00114
ParticipantsOG00213
Title
Measurements
OG000
Day 28
ParticipantsOG00016
ParticipantsOG00115
ParticipantsOG00213
Title
Measurements
OG000
OG0004
OG00114
Title
Denominators
Categories
Day 7
ParticipantsOG0004
ParticipantsOG00112
Title
Measurements
OG0004.87(-8.32 to 18.06)
OG001-7.28(-14.76 to 0.2)
Day 14
ParticipantsOG0004
ParticipantsOG00111
Title
Measurements
OG00010.75(-2.44 to 23.94)
OG001
Day 21
ParticipantsOG0004
ParticipantsOG00110
Title
Measurements
OG0009.37(-3.82 to 22.56)
OG001
Day 28
ParticipantsOG0003
ParticipantsOG00111
Title
Measurements
OG00015.73(1.85 to 29.61)
OG001
OG003
Group 3a: VX-661 100 mg qd
All participants in group 3a who received VX-661 100 mg tablet orally qd and placebo matched to Ivacaftor tablet q12h for up to 28 days.
OG004
Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h
All participants in group 3b who received VX-661 30 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
OG005
Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h
All participants in group 4 who received VX-661 100 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
OG006
Group 5a: VX-661 150 mg qd
All participants in group 5a who received VX-661 150 mg tablet orally qd for up to 28 days.
OG007
Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h
All participants in group 5b who received VX-661 150 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
OG008
Group 1-5b Combined Placebo
All participants in group 1, 2a, 2b, 3a, 3b, 4, 5a and 5b who received placebo matched to VX-661 tablet and/or placebo matched to ivacaftor tablet for up to 28 days.
Units
Counts
Participants
OG0008
OG0018
OG00218
OG0038
OG00419
OG00517
OG0069
OG00717
OG00824
Title
Denominators
Categories
Post-Baseline Through Day 28
ParticipantsOG0008
ParticipantsOG0018
ParticipantsOG00218
ParticipantsOG0038
ParticipantsOG00419
ParticipantsOG00517
ParticipantsOG0069
ParticipantsOG00717
ParticipantsOG00824
Title
Measurements
OG0003.49(0.21 to 6.77)
OG0011.63(-1.62 to 4.87)
OG0021.3(-0.87 to 3.47)
OG003
Day 7
ParticipantsOG0008
ParticipantsOG0018
ParticipantsOG00218
ParticipantsOG0038
Day 14
ParticipantsOG0008
ParticipantsOG0018
ParticipantsOG00218
ParticipantsOG0038
Day 21
ParticipantsOG0007
ParticipantsOG0018
ParticipantsOG00218
ParticipantsOG0038
Day 28
ParticipantsOG0007
ParticipantsOG0018
ParticipantsOG00217
ParticipantsOG0038
Units
Counts
Participants
OG00019
OG00116
OG00214
Title
Denominators
Categories
Post-Baseline Through Day 28
ParticipantsOG00018
ParticipantsOG00116
ParticipantsOG00214
Title
Measurements
OG0000.94(-1.42 to 3.3)
OG0012.31(-0.19 to 4.8)
OG0021.47(-1.2 to 4.13)
Day 7
ParticipantsOG00018
ParticipantsOG00116
ParticipantsOG00214
Title
Measurements
OG000
Day 14
ParticipantsOG00017
ParticipantsOG00116
ParticipantsOG00214
Title
Measurements
OG000
Day 21
ParticipantsOG00017
ParticipantsOG00116
ParticipantsOG00213
Title
Measurements
OG000
Day 28
ParticipantsOG00016
ParticipantsOG00116
ParticipantsOG00213
Title
Measurements
OG000
4
OG00114
Title
Denominators
Categories
Post-Baseline Through Day 28
Title
Measurements
OG0001.4(-5.04 to 7.83)
OG0014.6(1.17 to 8.03)
Day 7
Title
Measurements
OG0003(-3.55 to 9.55)
OG0014.14(0.65 to 7.63)
Day 14
Title
Measurements
OG0000.98(-5.56 to 7.53)
OG0015.22(1.73 to 8.71)
Day 21
Title
Measurements
OG0002.72(-3.83 to 9.27)
OG0013.88(0.39 to 7.38)
Day 28
Title
Measurements
OG000-1.12(-7.66 to 5.43)
OG0015.16(1.67 to 8.65)
Group 3a: VX-661 100 mg qd
All participants in group 3a who received VX-661 100 mg tablet orally qd and placebo matched to Ivacaftor tablet q12h for up to 28 days.
OG004
Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h
All participants in group 3b who received VX-661 30 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
OG005
Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h
All participants in group 4 who received VX-661 100 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
OG006
Group 5a: VX-661 150 mg qd
All participants in group 5a who received VX-661 150 mg tablet orally qd for up to 28 days.
OG007
Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h
All participants in group 5b who received VX-661 150 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
OG008
Group 1-5b Combined Placebo
All participants in group 1, 2a, 2b, 3a, 3b, 4, 5a and 5b who received placebo matched to VX-661 tablet and/or placebo matched to ivacaftor tablet for up to 28 days.
Units
Counts
Participants
OG0008
OG0018
OG00218
OG0038
OG00419
OG00517
OG0069
OG00717
OG00824
Title
Denominators
Categories
PB Through Day 28
ParticipantsOG0008
ParticipantsOG0018
ParticipantsOG00218
ParticipantsOG0038
ParticipantsOG00419
ParticipantsOG00517
ParticipantsOG0069
ParticipantsOG00717
ParticipantsOG00824
Title
Measurements
OG0000.14(0.02 to 0.26)
OG0010.07(-0.05 to 0.19)
OG0020.05(-0.03 to 0.13)
OG003
Day 7
ParticipantsOG0008
ParticipantsOG0018
ParticipantsOG00218
ParticipantsOG0038
Day 14
ParticipantsOG0008
ParticipantsOG0018
ParticipantsOG00218
ParticipantsOG0038
Day 21
ParticipantsOG0007
ParticipantsOG0018
ParticipantsOG00218
ParticipantsOG0038
Day 28
ParticipantsOG0007
ParticipantsOG0018
ParticipantsOG00217
ParticipantsOG0038
Units
Counts
Participants
OG00019
OG00116
OG00214
Title
Denominators
Categories
Post-Baseline Through Day 28
ParticipantsOG00018
ParticipantsOG00116
ParticipantsOG00214
Title
Measurements
OG0000.02(-0.07 to 0.11)
OG0010.09(-0.01 to 0.18)
OG0020.07(-0.04 to 0.17)
Day 7
ParticipantsOG00018
ParticipantsOG00116
ParticipantsOG00214
Title
Measurements
OG000
Day 14
ParticipantsOG00017
ParticipantsOG00116
ParticipantsOG00214
Title
Measurements
OG000
Day 21
ParticipantsOG00017
ParticipantsOG00116
ParticipantsOG00213
Title
Measurements
OG000
Day 28
ParticipantsOG00016
ParticipantsOG00116
ParticipantsOG00213
Title
Measurements
OG000
4
OG00114
Title
Denominators
Categories
Post-Baseline Through Day 28
Title
Measurements
OG0000.09(-0.16 to 0.34)
OG0010.16(0.03 to 0.29)
Day 7
Title
Measurements
OG0000.14(-0.11 to 0.39)
OG0010.15(0.01 to 0.28)
Day 14
Title
Measurements
OG0000.08(-0.17 to 0.33)
OG0010.18(0.05 to 0.32)
Day 21
Title
Measurements
OG0000.14(-0.11 to 0.4)
OG0010.13(-0.01 to 0.26)
Day 28
Title
Measurements
OG000-0.01(-0.26 to 0.25)
OG0010.19(0.05 to 0.32)
All participants in group 2b who received VX-661 10 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
OG003
Group 3a: VX-661 100 mg qd
All participants in group 3a who received VX-661 100 mg tablet orally qd and placebo matched to Ivacaftor tablet q12h for up to 28 days.
OG004
Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h
All participants in group 3b who received VX-661 30 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
OG005
Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h
All participants in group 4 who received VX-661 100 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
OG006
Group 5a: VX-661 150 mg qd
All participants in group 5a who received VX-661 150 mg tablet orally qd for up to 28 days.
OG007
Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h
All participants in group 5b who received VX-661 150 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
OG008
Group 1-5b Combined Placebo
All participants in group 1, 2a, 2b, 3a, 3b, 4, 5a and 5b who received placebo matched to VX-661 tablet and/or placebo matched to ivacaftor tablet for up to 28 days.
Units
Counts
Participants
OG0008
OG0018
OG00218
OG0038
OG00419
OG00517
OG0069
OG00717
OG00824
Title
Denominators
Categories
PB Through Day 28
ParticipantsOG0008
ParticipantsOG0018
ParticipantsOG00218
ParticipantsOG0038
ParticipantsOG00418
ParticipantsOG00515
ParticipantsOG0069
ParticipantsOG00716
ParticipantsOG00824
Title
Measurements
OG0004.02(-4.38 to 12.43)
OG0015.54(-2.72 to 13.79)
OG0023.8(-1.74 to 9.35)
OG003
Day 14
ParticipantsOG0008
ParticipantsOG0018
ParticipantsOG00218
ParticipantsOG0038
Day 28
ParticipantsOG0007
ParticipantsOG0018
ParticipantsOG00217
ParticipantsOG0038
Group 4 and 6 Combined: Placebo
All participants in group 4, 6a and 6d who received placebo matched to VX-661 tablet and/or placebo matched to ivacaftor tablet for up to 28 days.
Units
Counts
Participants
OG00019
OG00116
OG00214
Title
Denominators
Categories
Post-Baseline Through Day 28
ParticipantsOG00017
ParticipantsOG00116
ParticipantsOG00214
Title
Measurements
OG0000.87(-4.44 to 6.19)
OG0011.91(-3.5 to 7.33)
OG0021.65(-4.18 to 7.49)
Day 14
ParticipantsOG00017
ParticipantsOG00116
ParticipantsOG00214
Title
Measurements
OG000
Day 28
ParticipantsOG00017
ParticipantsOG00116
ParticipantsOG00213
Title
Measurements
OG000
Units
Counts
Participants
OG0004
OG00114
Title
Denominators
Categories
Post-Baseline Through Day 28
ParticipantsOG0004
ParticipantsOG00114
Title
Measurements
OG000-3.02(-13.52 to 7.47)
OG0013.79(-1.78 to 9.36)
Day 14
ParticipantsOG0004
ParticipantsOG00113
Title
Measurements
OG0001.83(-10.64 to 14.3)
OG001
Day 28
ParticipantsOG0004
ParticipantsOG00114
Title
Measurements
OG000-7.87(-20.34 to 4.6)
OG001
All participants in group 5a who received VX-661 150 mg tablet orally qd for up to 28 days.
Units
Counts
Participants
OG0007
OG0018
OG0028
OG0039
Title
Denominators
Categories
Title
Measurements
OG0006260± 2650
OG00123000± 6550
OG00288100± 51100
OG00398900± 20200
All participants in group 5b who received VX-661 150 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
OG004
Group 6a: VX-661 100 mg qd/ Ivacaftor 50 mg q12h
All participants in group 6a who received VX-661 100 mg tablet qd and Ivacaftor 50 mg tablet q12h orally for up to 28 days.
OG005
Group 6d: VX-661 50 mg q12h/ Ivacaftor 150 mg q12h
All participants in group 6d who received VX-661 50 mg tablet and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
OG006
Group 7: VX-661 100 mg qd
All participants in group 7 who received VX-661 100 mg tablet orally qd in combination with physician prescribed Kalydeco for up to 28 days.