A Study of VX-445 in Healthy Subjects and Subjects With C... | NCT03227471 | Trialant
NCT03227471
Sponsor
Vertex Pharmaceuticals Incorporated
Status
Completed
Last Update Posted
Jan 18, 2022Actual
Enrollment
225Actual
Phase
Phase 1Phase 2
Conditions
Cystic Fibrosis
Interventions
IVA
TEZ/IVA
VX-445
Matched Placebo
TEZ
VX-561
VX-445
Countries
United States
Australia
Belgium
Netherlands
Protocol Section
Identification Module
NCT ID
NCT03227471
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
VX16-445-001
Secondary IDs
ID
Type
Description
Link
2017-000797-11
EudraCT Number
Brief Title
A Study of VX-445 in Healthy Subjects and Subjects With Cystic Fibrosis
Official Title
A Phase 1/2 Study of VX-445 in Healthy Subjects and Subjects With Cystic Fibrosis
Acronym
Not provided
Organization
Vertex Pharmaceuticals IncorporatedINDUSTRY
Status Module
Record Verification Date
Dec 2021
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Jan 23, 2017Actual
Primary Completion Date
Mar 27, 2018Actual
Completion Date
Mar 27, 2018Actual
First Submitted Date
Jul 18, 2017
First Submission Date that Met QC Criteria
Jul 21, 2017
First Posted Date
Jul 24, 2017Actual
Results Waived
Not provided
Results First Submitted Date
Nov 9, 2021
Results First Submitted that Met QC Criteria
Dec 16, 2021
Results First Posted Date
Jan 18, 2022Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Mar 26, 2019
Certification/Extension First Submitted that Passed QC Review
Dec 16, 2021
Certification/Extension First Posted Date
Jan 18, 2022Actual
Last Update Submitted Date
Dec 16, 2021
Last Update Posted Date
Jan 18, 2022Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Vertex Pharmaceuticals IncorporatedINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
This is a first-in-human and proof-of-concept study of VX-445. The study includes 6 parts. Parts A, B, and C were conducted in healthy subjects. Parts D, E, and F were conducted in subjects with Cystic Fibrosis (CF) who are homozygous for the F508del mutation of the CF transmembrane conductance regulator (CFTR) gene (F/F genotype), or who are heterozygous for the F508del mutation and a minimal function (MF) CFTR mutation not likely to respond to TEZ, IVA, or TEZ/IVA (F/MF genotypes).
Detailed Description
Not provided
Conditions Module
Conditions
Cystic Fibrosis
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 1Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
225Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Part A: Pooled Placebo (Except Cohort A7)
Placebo Comparator
Participants without CF who received single dose of placebo matched to VX-445 in Cohort A1 to A5.
Drug: Matched Placebo
Part A: VX-445 (Except Cohort A7)
Experimental
Participants without CF who received single ascending dose of VX-445 tablet starting from 20 milligrams (mg) to 360 mg in Cohort A1 to A5.
Drug: VX-445
Part A: VX-445 (Cohort A7)
Experimental
Participants without CF who received single dose of VX-445 100 mg tablet on Day 1 in fasted state and on Day 7 in fed state, followed by VX-445 20 mg intravenous (IV) injection on Day 13 in fed state in Cohort A7.
Drug: VX-445
Part B: Pooled Placebo (Cohort B1 to B4)
Placebo Comparator
Participants without CF who received multiple doses of placebo matched to VX-445 once daily (qd) for 10 days in Cohort B1 to B4.
Drug: Matched Placebo
Part B: VX-445 (Cohort B1 to B4)
Experimental
Participants without CF who received VX-445 tablet qd for 10 days in Cohort B1 (60 mg), B2 (120 mg), B3 (240 mg) and B4 (340 mg).
Interventions
Name
Type
Description
Arm Group Labels
Other Names
IVA
Drug
IVA tablet for oral administration
Part C: VX-445/TEZ/IVA TC (Cohort C1 to C3)
Part D: VX-445/TEZ/IVA TC - High Dose
Part D: VX-445/TEZ/IVA TC - Low Dose
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Parts A, B and C: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
From first dose of study drug in treatment period up to safety follow-up (up to 28 days)
Parts D, E and F: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
From first dose of study drug in TC treatment period up to 28 days after last dose of study drug (up to 5 weeks)
Part D: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
From Baseline through Day 29
Part E: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
From Baseline through Day 29
Part F: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
From Baseline through Day 29
Secondary Outcomes
Measure
Description
Time Frame
Part A: Maximum Observed Concentration (Cmax) of VX-445
Cohort A1-A5: Pre-dose to 96 hours post-dose; Cohort A7: Pre-dose to 120 hours post-dose
Part A: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Key Inclusion Criteria:
Parts A, B, and C:
Female subjects must be of non-childbearing potential.
Between the ages of 18 and 55 years, inclusive.
Body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive, and a total body weight >50 kg
Parts D, E, and F:
Body weight ≥35 kg.
Subjects must have an eligible CFTR genotype:
Parts D and F: Heterozygous for F508del and an MF mutation (F/MF)
Part E: Homozygous for F508del (F/F)
FEV1 value ≥40% and ≤90% of predicted mean for age, sex, and height.
Key Exclusion Criteria:
Parts A, B, and C:
Any condition possibly affecting drug absorption.
History of febrile illness within 14 days before the first study drug dose.
Heneghan M, Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2023 Nov 20;11(11):CD010966. doi: 10.1002/14651858.CD010966.pub4.
This study included 6 parts: Parts A, B, and C were conducted in healthy adult participants; Part D, E, and F were conducted in adult cystic fibrosis (CF) participants.
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Part A: Pooled Placebo (Except Cohort A7)
Participants without CF who received single dose of placebo matched to VX-445 in Cohort A1 to A5.
Participants without CF who received placebo matched to VX-445/TEZ/IVA triple combination (TC) qd in the morning and placebo matched to IVA in the evening for 14 days.
Drug: Matched Placebo
Part C: VX-445/TEZ/IVA TC (Cohort C1 to C3)
Experimental
Participants without CF who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C1; VX-445 280 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C2 and VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C3 for 14 days.
Drug: IVA
Drug: TEZ/IVA
Drug: VX-445
Part D: Placebo
Placebo Comparator
Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/IVA TC qd in the morning and placebo matched to IVA qd in the evening for 4 weeks in the TC treatment period.
Drug: Matched Placebo
Part D: VX-445/TEZ/IVA TC - Low Dose
Experimental
Participants with CF, F/MF genotype who received VX-445 50 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
Drug: IVA
Drug: TEZ/IVA
Drug: VX-445
Part D: VX-445/TEZ/IVA TC - Medium Dose
Experimental
Participants with CF, F/MF genotype who received VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
Drug: IVA
Drug: TEZ/IVA
Drug: VX-445
Part D: VX-445/TEZ/IVA TC - High Dose
Experimental
Participants with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
Drug: IVA
Drug: TEZ/IVA
Drug: VX-445
Part E: TEZ/IVA
Active Comparator
Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received TEZ 100 mg qd/IVA 150 mg q12h and placebo matched to VX-445 for 4 weeks in the TC treatment period.
Drug: TEZ/IVA
Part E: VX-445/TEZ/IVA TC
Experimental
Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received VX-445 200 mg qd/TEZ 100 mg qd /IVA 150 mg q12h for 4 weeks in the TC treatment period.
Drug: IVA
Drug: TEZ/IVA
Drug: VX-445
Part F: Placebo
Placebo Comparator
Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/VX-561 for 4 weeks in the TC treatment period.
Drug: Matched Placebo
Part F: VX-445/TEZ/VX-561 TC
Experimental
Participants with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/VX-561 150 mg qd for 4 weeks in the TC treatment period.
Drug: VX-445
Drug: TEZ
Drug: VX-561
Part D: VX-445/TEZ/IVA TC - Medium Dose
Part E: VX-445/TEZ/IVA TC
VX-770
ivacaftor
TEZ/IVA
Drug
TEZ/IVA fixed-dose combination for oral administration.
Part C: VX-445/TEZ/IVA TC (Cohort C1 to C3)
Part D: VX-445/TEZ/IVA TC - High Dose
Part D: VX-445/TEZ/IVA TC - Low Dose
Part D: VX-445/TEZ/IVA TC - Medium Dose
Part E: TEZ/IVA
Part E: VX-445/TEZ/IVA TC
VX-661/VX-770
tezacaftor/ivacaftor
VX-445
Drug
VX-445 tablet for oral administration.
Part A: VX-445 (Cohort A7)
Part A: VX-445 (Except Cohort A7)
Part B: VX-445 (Cohort B1 to B4)
Part C: VX-445/TEZ/IVA TC (Cohort C1 to C3)
Part D: VX-445/TEZ/IVA TC - High Dose
Part D: VX-445/TEZ/IVA TC - Low Dose
Part D: VX-445/TEZ/IVA TC - Medium Dose
Part E: VX-445/TEZ/IVA TC
Part F: VX-445/TEZ/VX-561 TC
ELX
elexacaftor
Matched Placebo
Drug
Matched placebo.
Part A: Pooled Placebo (Except Cohort A7)
Part B: Pooled Placebo (Cohort B1 to B4)
Part C: Pooled Placebo (Cohort C1 to C3)
Part D: Placebo
Part F: Placebo
TEZ
Drug
Tablet for oral administration.
Part F: VX-445/TEZ/VX-561 TC
VX-661
tezacaftor
VX-561
Drug
Tablet for oral administration.
Part F: VX-445/TEZ/VX-561 TC
CTP-656
VX-445
Drug
VX-445 IV injection
Part A: VX-445 (Cohort A7)
ELX
elexacaftor
Cohort A1-5: Pre-dose to 96 hours post-dose; Cohort A7: Pre-dose to 120 hours post-dose
Part B: Maximum Observed Concentration (Cmax) of VX-445
Pre-dose to 96 hours post-dose on Day 1 and Day 10
Part B: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445
Pre-dose to 96 hours post-dose on Day 1 and Day 10
Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445
Pre-dose on Day 10
Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ)
Pre-dose to 96 hours post-dose on Day 1, Day 7 and Day 14
Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ)
Pre-dose to 96 hours post-dose on Day 1, Day 7 and Day 14
Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA)
Pre-dose to 96 hours post-dose on Day 1, Day 7 and Day 14
Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of IVA and Its Metabolites (M1-IVA and M6-IVA)
Pre-dose to 96 hours post-dose on Day 1, Day 7 and Day 14
Part C: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ)
Pre-dose on Day 7 and Day 14
Part C: Observed Pre-dose Concentration (Ctrough) of IVA and Its Metabolites (M1-IVA and M6-IVA)
Pre-dose on Day 7 and Day 14
Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA)
Pre-dose on Day 15 and Day 29
Part E: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and IVA and Its Metabolite (M1-IVA)
Pre-dose on Day 15 and Day 29
Part F: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and VX-561
Pre-dose on Day 15 and Day 29
Part D: Absolute Change in Sweat Chloride Concentration
Sweat samples were collected using an approved collection device.
From Baseline through Day 29
Part E: Absolute Change in Sweat Chloride Concentration
Sweat samples were collected using an approved collection device.
From Baseline through Day 29
Part F: Absolute Change in Sweat Chloride Concentration
Sweat samples were collected using an approved collection device.
From Baseline through Day 29
Part D: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
From Baseline through Day 29
Part E: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
From Baseline through Day 29
Part F: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
From Baseline through Day 29
Part D: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
From Baseline through Day 29
Part E: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
From Baseline through Day 29
Part F: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
From Baseline through Day 29
Little Rock
Arkansas
72205
United States
Valley Children's Healthcare
Madera
California
93636
United States
(Kaiser Permanente) Oakland Medical Center
Oakland
California
96411
United States
National Jewish Health
Denver
Colorado
80206
United States
Central Florida Pulmonary Group
Orlando
Florida
32803
United States
Tampa General Hospital Cardiac and Lung Transplant Clinic
Tampa
Florida
33606
United States
Children's Specialty Services at North Druid Hills
Atlanta
Georgia
30324
United States
Northwestern Memorial Hospital
Chicago
Illinois
60611
United States
Covance Clinical Research Unit Inc., Evansville Clinic [Parts A, B, C only]
Evansville
Indiana
47710
United States
University of Kansas Medical Center
Kansas City
Kansas
66160
United States
Tulane Medical Center
New Orleans
Louisiana
70112
United States
Harper University Hospital
Detroit
Michigan
48201
United States
Children's Respiratory and Critical Care Specialists, P.A., Children's Hospitals and Clinics of Minn
Minneapolis
Minnesota
55404
United States
Morristown Medical Center
Morristown
New Jersey
07960
United States
University of New Mexico School of Medicine
Albuquerque
New Mexico
87131
United States
UC Health Office of Clinical Research
Cincinnati
Ohio
45267
United States
University Hospitals Cleveland Medical Center/Rainbow Babies and Children's Hospital
Cleveland
Ohio
44106
United States
Nationwide Children's Hospital
Columbus
Ohio
43205
United States
Austin Children's Chest Associates
Austin
Texas
78723
United States
The University of Vermont
Burlington
Vermont
05401
United States
University of Virginia Health System
Charlottesville
Virginia
22908
United States
West Virginia University Hospitals
Morgantown
Virginia
26506
United States
Children's Hospital of the King's Daughters
Norfolk
Virginia
23507
United States
Virginia Commonwealth University
Richmond
Virginia
23298
United States
Medical College of Wisconsin
Milwaukee
Wisconsin
53226
United States
Monash Medical Center
Clayton
Victoria
Australia
The Alfred Hospital
Melbourne
Victoria
Australia
The Royal Children's Hospital Melbourne
Parkville
Victoria
Australia
Mater Adult Hospital
Brisbane
Australia
Royal Prince Alfred Hospital
Sydney
Australia
Westmead Hospital
Sydney
Australia
Antwerp University Hospital
Edegem
Belgium
Universitair Ziekenhuis Gent
Ghent
Belgium
Academic Medical Centre
Amsterdam
Netherlands
Radboud UMC
Nijmegen
Netherlands
Erasmus Medical Center
Rotterdam
Netherlands
HagaZiekenhuis van den Haag
The Hague
Netherlands
Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3.
Keating D, Marigowda G, Burr L, Daines C, Mall MA, McKone EF, Ramsey BW, Rowe SM, Sass LA, Tullis E, McKee CM, Moskowitz SM, Robertson S, Savage J, Simard C, Van Goor F, Waltz D, Xuan F, Young T, Taylor-Cousar JL; VX16-445-001 Study Group. VX-445-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles. N Engl J Med. 2018 Oct 25;379(17):1612-1620. doi: 10.1056/NEJMoa1807120. Epub 2018 Oct 18.
Participants without CF who received single ascending dose of VX-445 tablet starting from 20 milligrams (mg) to 360 mg in Cohort A1 to A5.
FG002
Part A: VX-445 (Cohort A7)
Participants without CF who received single dose of VX-445 100 mg tablet on Day 1 in fasted state and on Day 7 in fed state, followed by VX-445 20 mg intravenous (IV) injection on Day 13 in fed state in Cohort A7.
FG003
Part B: Pooled Placebo (Cohort B1 to B4)
Participants without CF who received multiple doses of placebo matched to VX-445 once daily (qd) for 10 days in Cohort B1 to B4.
FG004
Part B: VX-445 (Cohort B1 to B4)
Participants without CF who received VX-445 tablet once daily for 10 days in Cohort B1 (60 mg), B2 (120 mg), B3 (240 mg) and B4 (340 mg).
FG005
Part C: Pooled Placebo (Cohort C1 to C3)
Participants without CF who received placebo matched to VX-445/TEZ/IVA triple combination (TC) once daily in the morning and placebo matched to IVA in the evening for 14 days.
FG006
Part C: VX-445/TEZ/IVA TC (Cohort C1 to C3)
Participants without CF who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C1; VX-445 280 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C2 and VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C3 for 14 days.
FG007
Part D: Placebo
Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/IVA TC once daily in the morning and placebo matched to IVA in the evening for 4 weeks in the TC treatment period.
FG008
Part D: VX-445/TEZ/IVA TC - Low Dose
Participants with CF, F/MF genotype who received VX-445 50 mg qd /TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
FG009
Part D: VX-445/TEZ/IVA TC - Medium Dose
Participants with CF, F/MF genotype who received VX-445 100 mg qd /TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
FG010
Part D: VX-445/TEZ/IVA TC - High Dose
Participants with CF, F/MF genotype who received VX-445 200 mg qd /TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
FG011
Part E: TEZ/IVA
Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received TEZ 100 mg qd/IVA 150 mg q12h and placebo matched to VX-445 for 4 weeks in the TC treatment period.
FG012
Part E: VX-445/TEZ/IVA TC
Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received VX-445 200 mg qd/TEZ 100 mg qd /IVA 150 mg q12h for 4 weeks in the TC treatment period.
FG013
Part F: Placebo
Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/VX-561 for 4 weeks in the TC treatment period.
FG014
Part F: VX-445/TEZ/VX-561 TC
Participants with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/VX-561 150 mg qd for 4 weeks in the TC treatment period.
FG0009 subjects
FG00130 subjects
FG0028 subjects
FG0037 subjects
FG00425 subjects
FG0056 subjects
FG00617 subjects
FG00712 subjects
FG00810 subjects
FG00922 subjects
FG01021 subjects
FG0117 subjects
FG01221 subjects
FG0138 subjects
FG01422 subjects
Safety Set
Received at least 1 dose of study drug.
FG0009 subjects
FG00130 subjects
FG0028 subjects
FG0037 subjects
FG00425 subjects
FG0056 subjects
FG00617 subjects
FG00712 subjects
FG00810 subjects
FG00922 subjects
FG01021 subjects
FG0117 subjects
FG01221 subjects
FG0138 subjects
FG01421 subjects
COMPLETED
FG0009 subjects
FG00130 subjects
FG0028 subjects
FG0037 subjects
FG00424 subjects
FG0056 subjects
FG00617 subjects
FG00712 subjects
FG00810 subjects
FG00922 subjects
FG01021 subjects
FG0117 subjects
FG01220 subjects
FG0138 subjects
FG01421 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0041 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0121 subjects
FG0130 subjects
FG0141 subjects
Type
Comment
Reasons
Withdrawal by Subject
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0041 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0121 subjects
FG0130 subjects
FG0140 subjects
Randomized, Never Dosed
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Part A: Pooled Placebo (Except Cohort A7)
Participants without CF who received single dose of placebo matched to VX-445 in Cohort A1 to A5.
BG001
Part A: VX-445 (Except Cohort A7)
Participants without CF who received single ascending dose of VX-445 tablet starting from 20 mg to 360 mg in Cohort A1 to A5.
BG002
Part A: VX-445 (Cohort A7)
Participants without CF who received single dose of VX-445 100 mg tablet on Day 1 in fasted state and on Day 7 in fed state, followed by VX-445 20 mg IV injection on Day 13 in fed state in Cohort A7.
BG003
Part B: Pooled Placebo (Cohort B1 to B4)
Participants without CF who received multiple doses of placebo matched to VX-445 qd for 10 days in Cohort B1 to B4.
BG004
Part B: VX-445 (Cohort B1 to B4)
Participants without CF who received VX-445 tablet once daily for 10 days in Cohort B1 (60 mg), B2 (120 mg), B3 (240 mg) and B4 (340 mg).
BG005
Part C: Pooled Placebo (Cohort C1 to C3)
Participants without CF who received placebo matched to VX-445/TEZ/IVA TC qd in the morning and placebo matched to IVA in the evening for 14 days.
BG006
Part C: VX-445/TEZ/IVA TC (Cohort C1 to C3)
Participants without CF who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C1; VX-445 280 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C2 and VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C3 for 14 days.
BG007
Part D: Placebo
Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/IVA TC qd in the morning and placebo matched to IVA in the evening for 4 weeks in the TC treatment period.
BG008
Part D: VX-445/TEZ/IVA TC - Low Dose
Participants with CF, F/MF genotype who received VX-445 50 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
BG009
Part D: VX-445/TEZ/IVA TC - Medium Dose
Participants with CF, F/MF genotype who received VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
BG010
Part D: VX-445/TEZ/IVA TC - High Dose
Participants with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
BG011
Part E: TEZ/IVA
Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received TEZ 100 mg qd/IVA 150 mg q12h and placebo matched to VX-445 for 4 weeks in the TC treatment period.
BG012
Part E: VX-445/TEZ/IVA TC
Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
BG013
Part F: Placebo
Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/VX-561 for 4 weeks in the TC treatment period.
BG014
Part F: VX-445/TEZ/VX-561 TC
Participants with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/VX-561 150 mg qd for 4 weeks in the TC treatment period.
BG015
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0009
BG00130
BG0028
BG0037
BG00425
BG0056
BG00617
BG00712
BG00810
BG00922
BG01021
BG0117
BG01221
BG0138
BG01421
BG015224
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Categorical
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
<=18 years
BG0000
BG0010
BG0020
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0002
BG0012
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0000
BG0012
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
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
Parts A, B and C: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Safety Set included all participants who received at least 1 dose of study drug.
Posted
Count of Participants
Participants
From first dose of study drug in treatment period up to safety follow-up (up to 28 days)
ID
Title
Description
OG000
Part A: Pooled Placebo (Except Cohort A7)
Participants without CF who received single dose of placebo matched to VX-445 in Cohort A1 to A5.
OG001
Part A: VX-445 (Except Cohort A7)
Participants without CF who received single ascending dose of VX-445 tablet starting from 20 milligrams (mg) to 360 mg in Cohort A1 to A5.
OG002
Part A: VX-445 (Cohort A7)
Participants without CF who received single dose of VX-445 100 mg tablet on Day 1 in fasted state and on Day 7 in fed state, followed by VX-445 20 mg intravenous (IV) injection on Day 13 in fed state in Cohort A7.
OG003
Part B: Pooled Placebo (Cohort B1 to B4)
Participants without CF who received multiple doses of placebo matched to VX-445 qd for 10 days in Cohort B1 to B4.
OG004
Part B: VX-445 (Cohort B1 to B4)
Participants without CF who received VX-445 tablet once daily for 10 days in Cohort B1 (60 mg), B2 (120 mg), B3 (240 mg) and B4 (340 mg).
OG005
Part C: Pooled Placebo (Cohort C1 to C3)
Participants without CF who received placebo matched to VX-445/TEZ/IVA triple combination (TC) once daily in the morning and placebo matched to IVA in the evening for 14 days.
OG006
Part C: VX-445/TEZ/IVA TC (Cohort C1 to C3)
Participants without CF who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C1; VX-445 280 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C2 and VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C3 for 14 days.
Units
Counts
Participants
OG0009
OG00130
OG0028
OG003
Title
Denominators
Categories
Participants with AEs
Title
Measurements
OG0000
OG0013
OG0021
OG003
Primary
Parts D, E and F: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
The Safety Set will include all participants who received at least 1 dose of study drug.
Posted
Count of Participants
Participants
From first dose of study drug in TC treatment period up to 28 days after last dose of study drug (up to 5 weeks)
ID
Title
Description
OG000
Part D: Placebo
Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/IVA TC once daily in the morning and placebo matched to IVA in the evening for 4 weeks in the TC treatment period.
OG001
Part D: VX-445/TEZ/IVA TC
Participants with CF, F/MF genotype who received VX-445/TEZ/IVA TC for 4 weeks in the TC treatment period.
OG002
Part E: TEZ/IVA
Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received TEZ 100 mg qd/IVA 150 mg q12h and placebo matched to VX-445 for 4 weeks in the TC treatment period.
OG003
Part E: VX-445/TEZ/IVA TC
Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
Primary
Part D: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
The full analysis set (FAS) included all randomized participants who carry the intended CFTR allele mutation and have received at least 1 dose of study drug in the TC treatment period.
Posted
Least Squares Mean
Standard Error
percentage points
From Baseline through Day 29
ID
Title
Description
OG000
Part D: Placebo
Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/IVA TC once daily in the morning and placebo matched to IVA in the evening for 4 weeks in the TC treatment period.
OG001
Part D: VX-445/TEZ/IVA TC - Low Dose
Participants with CF, F/MF genotype who received VX-445 50 mg qd /TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
OG002
Part D: VX-445/TEZ/IVA TC - Medium Dose
Participants with CF, F/MF genotype who received VX-445 100 mg qd /TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
OG003
Primary
Part E: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
FAS.
Posted
Least Squares Mean
Standard Error
percentage points
From Baseline through Day 29
ID
Title
Description
OG000
Part E: TEZ/IVA
Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received TEZ 100 mg qd/IVA 150 mg q12h and placebo matched to VX-445 for 4 weeks in the TC treatment period.
OG001
Part E: VX-445/TEZ/IVA TC
Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received VX-445 200 mg qd/TEZ 100 mg qd /IVA 150 mg q12h for 4 weeks in the TC treatment period.
Units
Counts
Participants
OG000
Primary
Part F: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
FAS.
Posted
Least Squares Mean
Standard Error
percentage points
From Baseline through Day 29
ID
Title
Description
OG000
Part F: Placebo
Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/VX-561 for 4 weeks in the TC treatment period.
OG001
Part F: VX-445/TEZ/VX-561 TC
Participants with CF, F/MF genotype who received VX-445 200 mg/TEZ 100 mg/VX-561 150 mg qd for 4 weeks in the TC treatment period.
Units
Counts
Participants
OG000
Secondary
Part A: Maximum Observed Concentration (Cmax) of VX-445
The Pharmacokinetic Set included all participants who received at least 1 dose of study drug and for whom the primary PK data are considered sufficient and interpretable.
Posted
Geometric Mean
Geometric Coefficient of Variation
microgram per milliliter
Cohort A1-A5: Pre-dose to 96 hours post-dose; Cohort A7: Pre-dose to 120 hours post-dose
ID
Title
Description
OG000
Part A: VX-445 (Cohort A1)
Participants received single dose of VX-445 20 mg tablet in Cohort A1.
OG001
Part A: VX-445 (Cohort A2)
Participants received single dose of VX-445 60 mg tablet in Cohort A2.
OG002
Part A: VX-445 (Cohort A3)
Participants received single dose of VX-445 120 mg tablet in Cohort A3.
OG003
Part A: VX-445 (Cohort A4)
Participants received single dose of VX-445 240 mg tablet in Cohort A4.
OG004
Secondary
Part A: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445
The Pharmacokinetic Set.
Posted
Geometric Mean
Geometric Coefficient of Variation
microgram*hour per milliliter
Cohort A1-5: Pre-dose to 96 hours post-dose; Cohort A7: Pre-dose to 120 hours post-dose
ID
Title
Description
OG000
Part A: VX-445 (Cohort A1)
Participants received single dose of VX-445 20 mg tablet in Cohort A1.
OG001
Part A: VX-445 (Cohort A2)
Participants received single dose of VX-445 60 mg tablet in Cohort A2.
OG002
Part A: VX-445 (Cohort A3)
Participants received single dose of VX-445 120 mg tablet in Cohort A3.
OG003
Part A: VX-445 (Cohort A4)
Participants received single dose of VX-445 240 mg tablet in Cohort A4.
OG004
Part A: VX-445 (Cohort A5)
Secondary
Part B: Maximum Observed Concentration (Cmax) of VX-445
The Pharmacokinetic Set.
Posted
Geometric Mean
Geometric Coefficient of Variation
microgram per milliliter
Pre-dose to 96 hours post-dose on Day 1 and Day 10
ID
Title
Description
OG000
Part B: VX-445 (Cohort B1)
Participants received VX-445 60 mg tablet once daily for 10 days in Cohort B1.
OG001
Part B: VX-445 (Cohort B2)
Participants received VX-445 120 mg tablet once daily for 10 days in Cohort B2.
OG002
Part B: VX-445 (Cohort B3)
Participants received VX-445 240 mg tablet once daily for 10 days in Cohort B3.
OG003
Part B: VX-445 (Cohort B4)
Participants received VX-445 340 mg tablet once daily for 10 days in Cohort B4.
Units
Counts
Secondary
Part B: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445
The Pharmacokinetic Set. Here "Number analyzed" signifies those participants who were evaluated for this outcome measure at specified time points.
Posted
Geometric Mean
Geometric Coefficient of Variation
microgram*hour per milliliter
Pre-dose to 96 hours post-dose on Day 1 and Day 10
ID
Title
Description
OG000
Part B: VX-445 (Cohort B1)
Participants received VX-445 60 mg tablet once daily for 10 days in Cohort B1.
OG001
Part B: VX-445 (Cohort B2)
Participants received VX-445 120 mg tablet once daily for 10 days in Cohort B2.
OG002
Part B: VX-445 (Cohort B3)
Participants received VX-445 240 mg tablet once daily for 10 days in Cohort B3.
OG003
Part B: VX-445 (Cohort B4)
Participants received VX-445 340 mg tablet once daily for 10 days in Cohort B4.
Secondary
Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445
The Pharmacokinetic Set.
Posted
Geometric Mean
Geometric Coefficient of Variation
microgram per milliliter
Pre-dose on Day 10
ID
Title
Description
OG000
Part B: VX-445 (Cohort B1)
Participants received VX-445 60 mg tablet once daily for 10 days in Cohort B1.
OG001
Part B: VX-445 (Cohort B2)
Participants received VX-445 120 mg tablet once daily for 10 days in Cohort B2.
OG002
Part B: VX-445 (Cohort B3)
Participants received VX-445 240 mg tablet once daily for 10 days in Cohort B3.
OG003
Part B: VX-445 (Cohort B4)
Participants received VX-445 340 mg tablet once daily for 10 days in Cohort B4.
Units
Counts
Secondary
Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ)
The Pharmacokinetic Set. Here "Number analyzed" signified those subjects who were evaluated at specified time points.
Posted
Geometric Mean
Geometric Coefficient of Variation
microgram per milliliter
Pre-dose to 96 hours post-dose on Day 1, Day 7 and Day 14
ID
Title
Description
OG000
Part C: VX-445/TEZ/IVA TC (Cohort C1)
Participants received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C1 for 14 days.
OG001
Part C: VX-445/TEZ/IVA TC (Cohort C2)
Participants received VX-445 280 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C2 for 14 days.
OG002
Part C: VX-445/TEZ/IVA TC (Cohort C3)
Participants received VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C3 for 14 days.
Units
Counts
Participants
Secondary
Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ)
The Pharmacokinetic Set. Here "Number analyzed" signified those subjects who were evaluated at specified time points.
Posted
Geometric Mean
Geometric Coefficient of Variation
microgram*hour per milliliter
Pre-dose to 96 hours post-dose on Day 1, Day 7 and Day 14
ID
Title
Description
OG000
Part C: VX-445/TEZ/IVA TC (Cohort C1)
Participants received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C1 for 14 days.
OG001
Part C: VX-445/TEZ/IVA TC (Cohort C2)
Participants received VX-445 280 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C2 for 14 days.
OG002
Part C: VX-445/TEZ/IVA TC (Cohort C3)
Participants received VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C3 for 14 days.
Units
Counts
Participants
Secondary
Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA)
The Pharmacokinetic Set. Here "Number analyzed" signified those subjects who were evaluated at specified time points.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanogram per milliliter
Pre-dose to 96 hours post-dose on Day 1, Day 7 and Day 14
ID
Title
Description
OG000
Part C: VX-445/TEZ/IVA TC (Cohort C1)
Participants received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C1 for 14 days.
OG001
Part C: VX-445/TEZ/IVA TC (Cohort C2)
Participants received VX-445 280 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C2 for 14 days.
OG002
Part C: VX-445/TEZ/IVA TC (Cohort C3)
Participants received VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C3 for 14 days.
Units
Counts
Participants
Secondary
Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of IVA and Its Metabolites (M1-IVA and M6-IVA)
The Pharmacokinetic Set. Here "Number analyzed" signified those subjects who were evaluated at specified time points.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanogram*hour per milliliter
Pre-dose to 96 hours post-dose on Day 1, Day 7 and Day 14
ID
Title
Description
OG000
Part C: VX-445/TEZ/IVA TC (Cohort C1)
Participants received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C1 for 14 days.
OG001
Part C: VX-445/TEZ/IVA TC (Cohort C2)
Participants received VX-445 280 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C2 for 14 days.
OG002
Part C: VX-445/TEZ/IVA TC (Cohort C3)
Participants received VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C3 for 14 days.
Units
Counts
Participants
Secondary
Part C: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ)
The Pharmacokinetic Set.
Posted
Geometric Mean
Geometric Coefficient of Variation
microgram per milliliter
Pre-dose on Day 7 and Day 14
ID
Title
Description
OG000
Part C: VX-445/TEZ/IVA TC (Cohort C1)
Participants received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C1 for 14 days.
OG001
Part C: VX-445/TEZ/IVA TC (Cohort C2)
Participants received VX-445 280 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C2 for 14 days.
OG002
Part C: VX-445/TEZ/IVA TC (Cohort C3)
Participants received VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C3 for 14 days.
Units
Counts
Participants
OG000
Secondary
Part C: Observed Pre-dose Concentration (Ctrough) of IVA and Its Metabolites (M1-IVA and M6-IVA)
The Pharmacokinetic Set.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanogram per milliliter
Pre-dose on Day 7 and Day 14
ID
Title
Description
OG000
Part C: VX-445/TEZ/IVA TC (Cohort C1)
Participants received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C1 for 14 days.
OG001
Part C: VX-445/TEZ/IVA TC (Cohort C2)
Participants received VX-445 280 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C2 for 14 days.
OG002
Part C: VX-445/TEZ/IVA TC (Cohort C3)
Participants received VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C3 for 14 days.
Units
Counts
Participants
OG000
Secondary
Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA)
FAS. Here "number analyzed" signifies those participants who were evaluated at specified time points for this outcome measure.
Posted
Mean
Standard Deviation
microgram per milliliter
Pre-dose on Day 15 and Day 29
ID
Title
Description
OG000
Part D: VX-445/TEZ/IVA TC - Low Dose
Participants with CF, F/MF genotype who received VX-445 50 mg qd /TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
OG001
Part D: VX-445/TEZ/IVA TC - Medium Dose
Participants with CF, F/MF genotype who received VX-445 100 mg qd /TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
OG002
Part D: VX-445/TEZ/IVA TC - High Dose
Participants with CF, F/MF genotype who received VX-445 200 mg qd /TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
Units
Counts
Secondary
Part E: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and IVA and Its Metabolite (M1-IVA)
FAS. Here "Number analyzed" signifies those participants who were evaluated at specified time points for this outcome measure.
Posted
Mean
Standard Deviation
microgram per milliliter
Pre-dose on Day 15 and Day 29
ID
Title
Description
OG000
Part E: TEZ/IVA
Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received TEZ 100 mg qd/IVA 150 mg q12h and placebo matched to VX-445 for 4 weeks in the TC treatment period.
OG001
Part E: VX-445/TEZ/IVA TC
Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received VX-445 200 mg qd/TEZ 100 mg qd /IVA 150 mg q12h for 4 weeks in the TC treatment period.
Units
Counts
Participants
OG000
Secondary
Part F: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and VX-561
FAS. Here, "Number analyzed" signifies those participants who were evaluated at specified time points for this outcome measure.
Posted
Mean
Standard Deviation
microgram per milliliter
Pre-dose on Day 15 and Day 29
ID
Title
Description
OG000
Part F: VX-445/TEZ/VX-561 TC
Participants with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/VX-561 150 mg qd for 4 weeks in the TC treatment period.
Units
Counts
Participants
OG00020
Secondary
Part D: Absolute Change in Sweat Chloride Concentration
Sweat samples were collected using an approved collection device.
FAS.
Posted
Least Squares Mean
Standard Error
millimole per liter (mmol/L)
From Baseline through Day 29
ID
Title
Description
OG000
Part D: Placebo
Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/IVA TC once daily in the morning and placebo matched to IVA in the evening for 4 weeks in the TC treatment period.
OG001
Part D: VX-445/TEZ/IVA TC - Low Dose
Participants with CF, F/MF genotype who received VX-445 50 mg qd /TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
OG002
Part D: VX-445/TEZ/IVA TC - Medium Dose
Participants with CF, F/MF genotype who received VX-445 100 mg qd /TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
OG003
Part D: VX-445/TEZ/IVA TC - High Dose
Participants with CF, F/MF genotype who received VX-445 200 mg qd /TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
Secondary
Part E: Absolute Change in Sweat Chloride Concentration
Sweat samples were collected using an approved collection device.
FAS.
Posted
Least Squares Mean
Standard Error
mmol/L
From Baseline through Day 29
ID
Title
Description
OG000
Part E: TEZ/IVA
Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received TEZ 100 mg qd/IVA 150 mg q12h and placebo matched to VX-445 for 4 weeks in the TC treatment period.
OG001
Part E: VX-445/TEZ/IVA TC
Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received VX-445 200 mg qd/TEZ 100 mg qd /IVA 150 mg q12h for 4 weeks in the TC treatment period.
Units
Counts
Participants
OG000
Secondary
Part F: Absolute Change in Sweat Chloride Concentration
Sweat samples were collected using an approved collection device.
FAS.
Posted
Least Squares Mean
Standard Error
mmol/L
From Baseline through Day 29
ID
Title
Description
OG000
Part F: Placebo
Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/VX-561 for 4 weeks in the TC treatment period.
OG001
Part F: VX-445/TEZ/VX-561 TC
Participants with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/VX-561 150 mg qd for 4 weeks in the TC treatment period.
Units
Counts
Participants
OG000
Secondary
Part D: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
FAS.
Posted
Least Squares Mean
Standard Error
percent change
From Baseline through Day 29
ID
Title
Description
OG000
Part D: Placebo
Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/IVA TC once daily in the morning and placebo matched to IVA in the evening for 4 weeks in the TC treatment period.
OG001
Part D: VX-445/TEZ/IVA TC - Low Dose
Participants with CF, F/MF genotype who received VX-445 50 mg qd /TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
OG002
Part D: VX-445/TEZ/IVA TC - Medium Dose
Participants with CF, F/MF genotype who received VX-445 100 mg qd /TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
OG003
Part D: VX-445/TEZ/IVA TC - High Dose
Participants with CF, F/MF genotype who received VX-445 200 mg qd /TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
Secondary
Part E: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
FAS.
Posted
Least Squares Mean
Standard Error
percent change
From Baseline through Day 29
ID
Title
Description
OG000
Part E: TEZ/IVA
Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received TEZ 100 mg qd/IVA 150 mg q12h and placebo matched to VX-445 for 4 weeks in the TC treatment period.
OG001
Part E: VX-445/TEZ/IVA TC
Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received VX-445 200 mg qd/TEZ 100 mg qd /IVA 150 mg q12h for 4 weeks in the TC treatment period.
Units
Counts
Participants
OG000
Secondary
Part F: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
FAS.
Posted
Least Squares Mean
Standard Error
percent change
From Baseline through Day 29
ID
Title
Description
OG000
Part F: Placebo
Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/VX-561 for 4 weeks in the TC treatment period.
OG001
Part F: VX-445/TEZ/VX-561 TC
Participants with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/VX-561 150 mg qd for 4 weeks in the TC treatment period.
Units
Counts
Participants
OG000
Secondary
Part D: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
FAS.
Posted
Least Squares Mean
Standard Error
units on a scale
From Baseline through Day 29
ID
Title
Description
OG000
Part D: Placebo
Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/IVA TC once daily in the morning and placebo matched to IVA in the evening for 4 weeks in the TC treatment period.
OG001
Part D: VX-445/TEZ/IVA TC - Low Dose
Participants with CF, F/MF genotype who received VX-445 50 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
OG002
Part D: VX-445/TEZ/IVA TC - Medium Dose
Participants with CF, F/MF genotype who received VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
OG003
Secondary
Part E: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
FAS.
Posted
Least Squares Mean
Standard Error
units on a scale
From Baseline through Day 29
ID
Title
Description
OG000
Part E: TEZ/IVA
Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received TEZ 100 mg qd/IVA 150 mg q12h and placebo matched to VX-445 for 4 weeks in the TC treatment period.
OG001
Part E: VX-445/TEZ/IVA TC
Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
Units
Counts
Participants
Secondary
Part F: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
FAS.
Posted
Least Squares Mean
Standard Error
units on a scale
From Baseline through Day 29
ID
Title
Description
OG000
Part F: Placebo
Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/VX-561 for 4 weeks in the TC treatment period.
OG001
Part F: VX-445/TEZ/VX-561 TC
Participants with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/VX-561 150 mg qd for 4 weeks in the TC treatment period.
Units
Counts
Participants
OG000
Time Frame
Parts A, B and C: From first dose of study drug in treatment period up to safety follow-up (up to 28 days); Parts D, E and F: From first dose of study drug in TC treatment period up to 28 days after last dose of study drug (up to 5 weeks)
Description
MedDRA version 19.1 for Parts A, B and C and MedDRA version 20.1 for Parts D, E and F.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Part A: Pooled Placebo (Except Cohort A7)
Participants without CF who received single dose of placebo matched to VX-445 in Cohort A1 to A5.
0
9
0
9
0
9
EG001
Part A: VX-445 (Except Cohort A7)
Participants without CF who received single ascending dose of VX-445 tablet starting from 20 mg to 360 mg in Cohort A1 to A5.
0
30
0
30
3
30
EG002
Part A: VX-445 (Cohort A7)
Participants without CF who received single dose of VX-445 100 mg tablet on Day 1 in fasted state and on Day 7 in fed state, followed by VX-445 20 mg IV injection on Day 13 in fed state in Cohort A7.
0
8
0
8
1
8
EG003
Part B: Pooled Placebo (Cohort B1 to B4)
Participants without CF who received multiple doses of placebo matched to VX-445 qd for 10 days in Cohort B1 to B4.
0
7
0
7
2
7
EG004
Part B: VX-445 (Cohort B1 to B4)
Participants without CF who received VX-445 tablet once daily for 10 days in Cohort B1 (60 mg), B2 (120 mg), B3 (240 mg) and B4 (340 mg).
0
25
0
25
2
25
EG005
Part C: Pooled Placebo (Cohort C1 to C3)
Participants without CF who received placebo matched to VX-445/TEZ/IVA TC once daily in the morning and placebo matched to IVA in the evening for 14 days.
0
6
0
6
2
6
EG006
Part C: VX-445/TEZ/IVA TC (Cohort C1 to C3)
Participants without CF who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C1; VX-445 280 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C2 and VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C3 for 14 days.
0
17
0
17
5
17
EG007
Part D: Placebo
Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/IVA TC once daily in the morning and placebo matched to IVA in the evening for 4 weeks in the TC treatment period.
0
12
2
12
12
12
EG008
Part D: VX-445/TEZ/IVA TC - Low Dose
Participants with CF, F/MF genotype who received VX-445 50 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
0
10
1
10
10
10
EG009
Part D: VX-445/TEZ/IVA TC - Medium Dose
Participants with CF, F/MF genotype who received VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
0
22
2
22
19
22
EG010
Part D: VX-445/TEZ/IVA TC - High Dose
Participants with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
0
21
0
21
17
21
EG011
Part E: TEZ/IVA
Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received TEZ 100 mg qd/IVA 150 mg q12h and placebo matched to VX-445 for 4 weeks in the TC treatment period.
0
7
1
7
5
7
EG012
Part E: VX-445/TEZ/IVA TC
Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
0
21
0
21
18
21
EG013
Part F: Placebo
Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/VX-561 for 4 weeks in the TC treatment period.
0
8
1
8
7
8
EG014
Part F: VX-445/TEZ/VX-561 TC
Participants with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/VX-561 150 mg qd for 4 weeks in the TC treatment period.
0
21
0
21
17
21
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Infective pulmonary exacerbation of cystic fibrosis
Infections and infestations
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG0030 affected7 at risk
EG004
Distal intestinal obstruction syndrome
Gastrointestinal disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Influenza A virus test positive
Investigations
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Haemoptysis
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Jugular vein thrombosis
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Diarrhoea
Gastrointestinal disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0011 affected30 at risk
EG0020 affected8 at risk
EG0030 affected7 at risk
EG0040 affected25 at risk
EG0051 affected6 at risk
EG0061 affected17 at risk
EG0071 affected12 at risk
EG0081 affected10 at risk
EG0093 affected22 at risk
EG0100 affected21 at risk
EG0110 affected7 at risk
EG0120 affected21 at risk
EG0131 affected8 at risk
EG0141 affected21 at risk
Nausea
Gastrointestinal disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0011 affected30 at risk
EG0020 affected8 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Dysphagia
Gastrointestinal disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Salivary hypersecretion
Gastrointestinal disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Abdominal discomfort
Gastrointestinal disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Gastrooesophageal reflux disease
Gastrointestinal disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0011 affected30 at risk
EG0020 affected8 at risk
EG003
Musculoskeletal pain
Musculoskeletal and connective tissue disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Musculoskeletal chest pain
Musculoskeletal and connective tissue disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Catheter site pain
General disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0021 affected8 at risk
EG003
Infusion site pain
General disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Fatigue
General disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Headache
Nervous system disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Dysgeusia
Nervous system disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Dermatitis
Skin and subcutaneous tissue disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Acne
Skin and subcutaneous tissue disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Pruritus generalised
Skin and subcutaneous tissue disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Eczema
Skin and subcutaneous tissue disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Conjunctivitis
Infections and infestations
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Abnormal dreams
Psychiatric disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Sputum increased
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Haemoptysis
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Nasal congestion
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Sinus congestion
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Paranasal sinus hypersecretion
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Productive cough
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Respiration abnormal
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Sputum discoloured
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Rhinorrhoea
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Wheezing
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Lower respiratory tract congestion
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Pleuritic pain
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Bronchiectasis
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Pulmonary mass
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Sinusitis
Infections and infestations
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Oral candidiasis
Infections and infestations
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Viral upper respiratory tract infection
Infections and infestations
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Gastroenteritis viral
Infections and infestations
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Otitis media
Infections and infestations
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Tonsillitis
Infections and infestations
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Viral infection
Infections and infestations
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Pyrexia
General disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Malaise
General disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Pain
General disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Chest pain
General disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Chills
General disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Chest discomfort
General disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Blood bilirubin increased
Investigations
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Blood creatine phosphokinase increased
Investigations
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Forced expiratory volume decreased
Investigations
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Blood triglycerides increased
Investigations
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Pulmonary function test decreased
Investigations
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Tinnitus
Ear and labyrinth disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Visual impairment
Eye disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Radiation injury
Injury, poisoning and procedural complications
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Pollakiuria
Renal and urinary disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Paranasal sinus discomfort
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA 19.1, 20.1
Systematic Assessment
EG0000 affected9 at risk
EG0010 affected30 at risk
EG0020 affected8 at risk
EG003
Infective pulmonary exacerbation of cystic fibrosis