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.
Name: VX-661
Name: Ivacaftor
Name: Placebo matched to VX-661
Name: Placebo matched to ivacaftor
Description: 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.
Measure: Safety as Determined by Adverse Events (AEs) Time: Start of study drug through the Follow-up Visit (Up to Day 56)Description: 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.
Measure: Change in Sweat Chloride From Baseline Through Study Day 28 for Group 1-5b Time: Baseline through Day 28Description: 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.
Measure: Change in Sweat Chloride From Baseline Through Study Day 28 for Group 6 Time: Baseline through Day 28Description: 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.
Measure: Change in Sweat Chloride From Baseline Through Study Day 28 for Group 7 Time: Baseline through Day 28Description: 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.
Measure: Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b Time: Baseline, Day 7, Day 14, Day 21, Day 28Description: 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.
Measure: Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 6 Time: Baseline, Day 7, Day 14, Day 21, Day 28Description: 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.
Measure: Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 7 Time: Baseline, Day 7, Day 14, Day 21, Day 28Description: FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Measure: 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 Time: Baseline, Day 7, Day 14, Day 21, Day 28Description: 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.
Measure: 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 Time: Baseline, Day 7, Day 14, Day 21, Day 28Description: FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Measure: 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 Time: Baseline, Day 7, Day 14, Day 21, Day 28Description: FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Measure: Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b Time: Baseline, Day 7, Day 14, Day 21, Day 28Description: 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.
Measure: Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6 Time: Baseline, Day 7, Day 14, Day 21, Day 28Description: FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Measure: Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7 Time: Baseline, Day 7, Day 14, Day 21, Day 28Description: 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.
Measure: 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 Time: Baseline, Day 14, Day 28Description: 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.
Measure: 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 Time: Baseline, Day 14, Day 28Description: 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.
Measure: 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 Time: Baseline, Day 14, Day 28Description: 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.
Measure: Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24h) of VX-661 After Administration of VX-661 Monotherapy Time: Day 28Description: 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.
Measure: AUC0-24h of VX-661 and AUC0-12h of Ivacaftor After Administration of VX-661 in Combination With Ivacaftor Time: Day 28Allocation: Randomized
Parallel Assignment
There is one SNP
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. --- G551D ---