Cystic Fibrosis
Conditions
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.
Interventions
Sponsors
Vertex Pharmaceuticals Incorporated
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety as Determined by Adverse Events (AEs) | Start of study drug through the Follow-up Visit (Up to Day 56) | 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. |
| Change in Sweat Chloride From Baseline Through Study Day 28 for Group 1-5b | Baseline through Day 28 | 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. |
| Change in Sweat Chloride From Baseline Through Study Day 28 for Group 6 | Baseline through Day 28 | 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. |
| Change in Sweat Chloride From Baseline Through Study Day 28 for Group 7 | Baseline through Day 28 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline, Day 7, Day 14, Day 21, Day 28 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. |
| 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 | Baseline, Day 7, Day 14, Day 21, Day 28 | 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. |
| 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 | Baseline, Day 7, Day 14, Day 21, Day 28 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. |
| Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Baseline, Day 7, Day 14, Day 21, Day 28 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. |
| Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6 | Baseline, Day 7, Day 14, Day 21, Day 28 | 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. |
| Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7 | Baseline, Day 7, Day 14, Day 21, Day 28 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. |
| 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 | Baseline, Day 14, Day 28 | 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. |
| 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 | Baseline, Day 14, Day 28 | 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. |
| Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24h) of VX-661 After Administration of VX-661 Monotherapy | Day 28 | 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. |
| AUC0-24h of VX-661 and AUC0-12h of Ivacaftor After Administration of VX-661 in Combination With Ivacaftor | Day 28 | 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. |
| 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 | Baseline, Day 14, Day 28 | 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. |
| Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Baseline, Day 7, Day 14, Day 21, Day 28 | 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. |
| Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 6 | Baseline, Day 7, Day 14, Day 21, Day 28 | 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. |
| Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 7 | Baseline, Day 7, Day 14, Day 21, Day 28 | 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. |
Countries
Canada, Germany, United Kingdom, United States
Participant flow
Pre-assignment details
A total of 194 participants were randomized of which 190 participants were treated.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 33 |
| 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. | 8 |
| 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. | 8 |
| 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. | 18 |
| 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. | 8 |
| 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. | 19 |
| 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. | 17 |
| 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. | 9 |
| 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. | 17 |
| 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. | 19 |
| 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. | 16 |
| 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. | 4 |
| 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. | 14 |
| Total | 190 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Non-Compliance | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Other | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Group 1-6d Combined: Placebo | 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 | 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: Placebo | Group 7: VX-661 100 mg qd | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 30.7 years STANDARD_DEVIATION 8.42 | 35.3 years STANDARD_DEVIATION 8.26 | 30.8 years STANDARD_DEVIATION 6.63 | 28.3 years STANDARD_DEVIATION 7.05 | 29.1 years STANDARD_DEVIATION 7.12 | 29.2 years STANDARD_DEVIATION 6.39 | 31 years STANDARD_DEVIATION 9.3 | 28.2 years STANDARD_DEVIATION 8.6 | 28.2 years STANDARD_DEVIATION 6.46 | 27.9 years STANDARD_DEVIATION 5.58 | 32.8 years STANDARD_DEVIATION 11.92 | 34.5 years STANDARD_DEVIATION 7.59 | 26.6 years STANDARD_DEVIATION 7.01 | 29.8 years STANDARD_DEVIATION 7.97 |
| Sex: Female, Male Female | 13 Participants | 4 Participants | 4 Participants | 6 Participants | 3 Participants | 6 Participants | 11 Participants | 3 Participants | 10 Participants | 7 Participants | 7 Participants | 3 Participants | 6 Participants | 83 Participants |
| Sex: Female, Male Male | 20 Participants | 4 Participants | 4 Participants | 12 Participants | 5 Participants | 13 Participants | 6 Participants | 6 Participants | 7 Participants | 12 Participants | 9 Participants | 1 Participants | 8 Participants | 107 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 30 / 33 | 8 / 8 | 7 / 8 | 15 / 18 | 7 / 8 | 18 / 19 | 9 / 17 | 8 / 9 | 17 / 17 | 16 / 19 | 16 / 16 | 2 / 4 | 12 / 14 |
| serious Total, serious adverse events | 5 / 33 | 1 / 8 | 1 / 8 | 1 / 18 | 0 / 8 | 2 / 19 | 2 / 17 | 0 / 9 | 0 / 17 | 1 / 19 | 2 / 16 | 0 / 4 | 1 / 14 |
Outcome results
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.
Time frame: Baseline through Day 28
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Group 1-6d Combined: Placebo | Change in Sweat Chloride From Baseline Through Study Day 28 for Group 1-5b | 3.92 millimole per liter (mmol/L) |
| Group 1: VX-661 10 mg qd | Change in Sweat Chloride From Baseline Through Study Day 28 for Group 1-5b | -4.76 millimole per liter (mmol/L) |
| Group 2a: VX-661 30 mg qd | Change in Sweat Chloride From Baseline Through Study Day 28 for Group 1-5b | -5.06 millimole per liter (mmol/L) |
| Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h | Change in Sweat Chloride From Baseline Through Study Day 28 for Group 1-5b | -20.43 millimole per liter (mmol/L) |
| Group 3a: VX-661 100 mg qd | Change in Sweat Chloride From Baseline Through Study Day 28 for Group 1-5b | -6 millimole per liter (mmol/L) |
| Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h | Change in Sweat Chloride From Baseline Through Study Day 28 for Group 1-5b | -6.04 millimole per liter (mmol/L) |
| Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h | Change in Sweat Chloride From Baseline Through Study Day 28 for Group 1-5b | -10.46 millimole per liter (mmol/L) |
| Group 5a: VX-661 150 mg qd | Change in Sweat Chloride From Baseline Through Study Day 28 for Group 1-5b | -2.63 millimole per liter (mmol/L) |
| Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h | Change in Sweat Chloride From Baseline Through Study Day 28 for Group 1-5b | -0.86 millimole per liter (mmol/L) |
p-value: 0.064795% CI: [-0.3, 9.84]Mixed-effect repeated measure (MMRM)
p-value: 0.168695% CI: [-9.5, 1.68]MMRM
p-value: 0.034895% CI: [-8.1, -0.31]MMRM
p-value: <0.000195% CI: [-24.57, -14.59]MMRM
p-value: 0.010195% CI: [-9.03, -1.25]MMRM
p-value: 0.01195% CI: [-9.16, -1.21]MMRM
p-value: 0.000195% CI: [-14.38, -4.82]MMRM
p-value: 0.374595% CI: [-5.71, 2.17]MMRM
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.
Time frame: Baseline through Day 28
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Group 1-6d Combined: Placebo | Change in Sweat Chloride From Baseline Through Study Day 28 for Group 6 | -6.07 mmol/L |
| Group 1: VX-661 10 mg qd | Change in Sweat Chloride From Baseline Through Study Day 28 for Group 6 | -7.89 mmol/L |
| Group 2a: VX-661 30 mg qd | Change in Sweat Chloride From Baseline Through Study Day 28 for Group 6 | -1.19 mmol/L |
p-value: 0.035795% CI: [-12.94, -0.46]MMRM
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.
Time frame: Baseline through Day 28
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Group 1-6d Combined: Placebo | Change in Sweat Chloride From Baseline Through Study Day 28 for Group 7 | 10.18 mmol/L |
| Group 1: VX-661 10 mg qd | Change in Sweat Chloride From Baseline Through Study Day 28 for Group 7 | -7.02 mmol/L |
p-value: 0.023895% CI: [-31.75, -2.65]MMRM
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.
Time frame: Start of study drug through the Follow-up Visit (Up to Day 56)
Population: Analysis was done using safety set which included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1-6d Combined: Placebo | Safety as Determined by Adverse Events (AEs) | Participants with AEs | 30 participants |
| Group 1-6d Combined: Placebo | Safety as Determined by Adverse Events (AEs) | Participants with SAEs | 5 participants |
| Group 1: VX-661 10 mg qd | Safety as Determined by Adverse Events (AEs) | Participants with AEs | 8 participants |
| Group 1: VX-661 10 mg qd | Safety as Determined by Adverse Events (AEs) | Participants with SAEs | 1 participants |
| Group 2a: VX-661 30 mg qd | Safety as Determined by Adverse Events (AEs) | Participants with AEs | 7 participants |
| Group 2a: VX-661 30 mg qd | Safety as Determined by Adverse Events (AEs) | Participants with SAEs | 1 participants |
| Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h | Safety as Determined by Adverse Events (AEs) | Participants with AEs | 15 participants |
| Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h | Safety as Determined by Adverse Events (AEs) | Participants with SAEs | 1 participants |
| Group 3a: VX-661 100 mg qd | Safety as Determined by Adverse Events (AEs) | Participants with SAEs | 0 participants |
| Group 3a: VX-661 100 mg qd | Safety as Determined by Adverse Events (AEs) | Participants with AEs | 7 participants |
| Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h | Safety as Determined by Adverse Events (AEs) | Participants with SAEs | 2 participants |
| Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h | Safety as Determined by Adverse Events (AEs) | Participants with AEs | 18 participants |
| Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h | Safety as Determined by Adverse Events (AEs) | Participants with AEs | 10 participants |
| Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h | Safety as Determined by Adverse Events (AEs) | Participants with SAEs | 2 participants |
| Group 5a: VX-661 150 mg qd | Safety as Determined by Adverse Events (AEs) | Participants with AEs | 8 participants |
| Group 5a: VX-661 150 mg qd | Safety as Determined by Adverse Events (AEs) | Participants with SAEs | 0 participants |
| Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h | Safety as Determined by Adverse Events (AEs) | Participants with AEs | 17 participants |
| Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h | Safety as Determined by Adverse Events (AEs) | Participants with SAEs | 0 participants |
| Group 6a: VX-661 100 mg qd/Ivacaftor 50 mg q12h | Safety as Determined by Adverse Events (AEs) | Participants with SAEs | 1 participants |
| Group 6a: VX-661 100 mg qd/Ivacaftor 50 mg q12h | Safety as Determined by Adverse Events (AEs) | Participants with AEs | 16 participants |
| Group 6d: VX-661 50 mg q12h/Ivacaftor 150 mg q12h | Safety as Determined by Adverse Events (AEs) | Participants with SAEs | 2 participants |
| Group 6d: VX-661 50 mg q12h/Ivacaftor 150 mg q12h | Safety as Determined by Adverse Events (AEs) | Participants with AEs | 16 participants |
| Group 7: Placebo | Safety as Determined by Adverse Events (AEs) | Participants with AEs | 2 participants |
| Group 7: Placebo | Safety as Determined by Adverse Events (AEs) | Participants with SAEs | 0 participants |
| Group 7: VX-661 100 mg qd | Safety as Determined by Adverse Events (AEs) | Participants with SAEs | 1 participants |
| Group 7: VX-661 100 mg qd | Safety as Determined by Adverse Events (AEs) | Participants with AEs | 12 participants |
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.
Time frame: Day 28
Population: The analysis was done using Pharmacokinetics (PK) Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1-6d Combined: Placebo | Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24h) of VX-661 After Administration of VX-661 Monotherapy | 6260 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 2650 |
| Group 1: VX-661 10 mg qd | Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24h) of VX-661 After Administration of VX-661 Monotherapy | 23000 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 6550 |
| Group 2a: VX-661 30 mg qd | Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24h) of VX-661 After Administration of VX-661 Monotherapy | 88100 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 51100 |
| Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h | Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24h) of VX-661 After Administration of VX-661 Monotherapy | 98900 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 20200 |
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.
Time frame: Day 28
Population: The analysis was done using PK Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1-6d Combined: Placebo | AUC0-24h of VX-661 and AUC0-12h of Ivacaftor After Administration of VX-661 in Combination With Ivacaftor | AUC0-24h of VX-661 | 8950 ng*h/mL | Standard Deviation 2370 |
| Group 1-6d Combined: Placebo | AUC0-24h of VX-661 and AUC0-12h of Ivacaftor After Administration of VX-661 in Combination With Ivacaftor | AUC0-12h of Ivacaftor | 10100 ng*h/mL | Standard Deviation 4380 |
| Group 1: VX-661 10 mg qd | AUC0-24h of VX-661 and AUC0-12h of Ivacaftor After Administration of VX-661 in Combination With Ivacaftor | AUC0-24h of VX-661 | 26300 ng*h/mL | Standard Deviation 5870 |
| Group 1: VX-661 10 mg qd | AUC0-24h of VX-661 and AUC0-12h of Ivacaftor After Administration of VX-661 in Combination With Ivacaftor | AUC0-12h of Ivacaftor | 11700 ng*h/mL | Standard Deviation 4870 |
| Group 2a: VX-661 30 mg qd | AUC0-24h of VX-661 and AUC0-12h of Ivacaftor After Administration of VX-661 in Combination With Ivacaftor | AUC0-24h of VX-661 | 82700 ng*h/mL | Standard Deviation 23300 |
| Group 2a: VX-661 30 mg qd | AUC0-24h of VX-661 and AUC0-12h of Ivacaftor After Administration of VX-661 in Combination With Ivacaftor | AUC0-12h of Ivacaftor | 10900 ng*h/mL | Standard Deviation 3890 |
| Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h | AUC0-24h of VX-661 and AUC0-12h of Ivacaftor After Administration of VX-661 in Combination With Ivacaftor | AUC0-24h of VX-661 | 138000 ng*h/mL | Standard Deviation 49700 |
| Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h | AUC0-24h of VX-661 and AUC0-12h of Ivacaftor After Administration of VX-661 in Combination With Ivacaftor | AUC0-12h of Ivacaftor | 16000 ng*h/mL | Standard Deviation 10400 |
| Group 3a: VX-661 100 mg qd | AUC0-24h of VX-661 and AUC0-12h of Ivacaftor After Administration of VX-661 in Combination With Ivacaftor | AUC0-24h of VX-661 | 77600 ng*h/mL | Standard Deviation 17800 |
| Group 3a: VX-661 100 mg qd | AUC0-24h of VX-661 and AUC0-12h of Ivacaftor After Administration of VX-661 in Combination With Ivacaftor | AUC0-12h of Ivacaftor | 3690 ng*h/mL | Standard Deviation 1460 |
| Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h | AUC0-24h of VX-661 and AUC0-12h of Ivacaftor After Administration of VX-661 in Combination With Ivacaftor | AUC0-24h of VX-661 | 73300 ng*h/mL | Standard Deviation 22900 |
| Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h | AUC0-24h of VX-661 and AUC0-12h of Ivacaftor After Administration of VX-661 in Combination With Ivacaftor | AUC0-12h of Ivacaftor | 11700 ng*h/mL | Standard Deviation 5450 |
| Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h | AUC0-24h of VX-661 and AUC0-12h of Ivacaftor After Administration of VX-661 in Combination With Ivacaftor | AUC0-24h of VX-661 | 90600 ng*h/mL | Standard Deviation 30800 |
| Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h | AUC0-24h of VX-661 and AUC0-12h of Ivacaftor After Administration of VX-661 in Combination With Ivacaftor | AUC0-12h of Ivacaftor | 12400 ng*h/mL | Standard Deviation 6170 |
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.
Time frame: Baseline, Day 14, Day 28
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Group 1-6d Combined: Placebo | 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 | PB Through Day 28 | 4.02 units on a scale |
| Group 1-6d Combined: Placebo | 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 | Day 28 | 1.38 units on a scale |
| Group 1-6d Combined: Placebo | 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 | Day 14 | 6.67 units on a scale |
| Group 1: VX-661 10 mg qd | 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 | Day 28 | 6.23 units on a scale |
| Group 1: VX-661 10 mg qd | 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 | Day 14 | 4.84 units on a scale |
| Group 1: VX-661 10 mg qd | 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 | PB Through Day 28 | 5.54 units on a scale |
| Group 2a: VX-661 30 mg qd | 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 | Day 14 | 4.29 units on a scale |
| Group 2a: VX-661 30 mg qd | 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 | PB Through Day 28 | 3.8 units on a scale |
| Group 2a: VX-661 30 mg qd | 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 | Day 28 | 3.31 units on a scale |
| Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h | 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 | Day 28 | 0.95 units on a scale |
| Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h | 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 | PB Through Day 28 | 0.61 units on a scale |
| Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h | 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 | Day 14 | 0.27 units on a scale |
| Group 3a: VX-661 100 mg qd | 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 | Day 14 | 2.81 units on a scale |
| Group 3a: VX-661 100 mg qd | 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 | PB Through Day 28 | 3.52 units on a scale |
| Group 3a: VX-661 100 mg qd | 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 | Day 28 | 4.22 units on a scale |
| Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h | 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 | Day 14 | 4.41 units on a scale |
| Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h | 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 | PB Through Day 28 | 5.15 units on a scale |
| Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h | 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 | Day 28 | 5.9 units on a scale |
| Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h | 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 | Day 28 | 1.03 units on a scale |
| Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h | 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 | PB Through Day 28 | 2.58 units on a scale |
| Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h | 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 | Day 14 | 4.13 units on a scale |
| Group 5a: VX-661 150 mg qd | 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 | Day 14 | 7.13 units on a scale |
| Group 5a: VX-661 150 mg qd | 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 | Day 28 | 8.1 units on a scale |
| Group 5a: VX-661 150 mg qd | 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 | PB Through Day 28 | 7.62 units on a scale |
| Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h | 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 | Day 14 | 0.53 units on a scale |
| Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h | 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 | Day 28 | 2.85 units on a scale |
| Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h | 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 | PB Through Day 28 | 1.69 units on a scale |
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.
Time frame: Baseline, Day 14, Day 28
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Group 1-6d Combined: Placebo | 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 | Day 14 | 2.02 units on a scale |
| Group 1-6d Combined: Placebo | 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 | Post-Baseline Through Day 28 | 0.87 units on a scale |
| Group 1-6d Combined: Placebo | 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 | Day 28 | -0.27 units on a scale |
| Group 1: VX-661 10 mg qd | 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 | Day 14 | 0.87 units on a scale |
| Group 1: VX-661 10 mg qd | 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 | Post-Baseline Through Day 28 | 1.91 units on a scale |
| Group 1: VX-661 10 mg qd | 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 | Day 28 | 2.96 units on a scale |
| Group 2a: VX-661 30 mg qd | 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 | Post-Baseline Through Day 28 | 1.65 units on a scale |
| Group 2a: VX-661 30 mg qd | 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 | Day 28 | 0.53 units on a scale |
| Group 2a: VX-661 30 mg qd | 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 | Day 14 | 2.78 units on a scale |
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.
Time frame: Baseline, Day 14, Day 28
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Group 1-6d Combined: Placebo | 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 | Post-Baseline Through Day 28 | -3.02 units on a scale |
| Group 1-6d Combined: Placebo | 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 | Day 14 | 1.83 units on a scale |
| Group 1-6d Combined: Placebo | 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 | Day 28 | -7.87 units on a scale |
| Group 1: VX-661 10 mg qd | 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 | Post-Baseline Through Day 28 | 3.79 units on a scale |
| Group 1: VX-661 10 mg qd | 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 | Day 14 | 5.24 units on a scale |
| Group 1: VX-661 10 mg qd | 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 | Day 28 | 2.33 units on a scale |
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.
Time frame: Baseline, Day 7, Day 14, Day 21, Day 28
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Group 1-6d Combined: Placebo | Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6 | Day 21 | -0.01 Liters |
| Group 1-6d Combined: Placebo | Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6 | Day 14 | 0.03 Liters |
| Group 1-6d Combined: Placebo | Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6 | Post-Baseline Through Day 28 | 0.02 Liters |
| Group 1-6d Combined: Placebo | Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6 | Day 7 | 0.04 Liters |
| Group 1-6d Combined: Placebo | Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6 | Day 28 | 0.02 Liters |
| Group 1: VX-661 10 mg qd | Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6 | Day 14 | 0.1 Liters |
| Group 1: VX-661 10 mg qd | Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6 | Post-Baseline Through Day 28 | 0.09 Liters |
| Group 1: VX-661 10 mg qd | Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6 | Day 7 | 0.06 Liters |
| Group 1: VX-661 10 mg qd | Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6 | Day 21 | 0.13 Liters |
| Group 1: VX-661 10 mg qd | Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6 | Day 28 | 0.06 Liters |
| Group 2a: VX-661 30 mg qd | Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6 | Day 28 | 0.08 Liters |
| Group 2a: VX-661 30 mg qd | Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6 | Day 21 | 0.08 Liters |
| Group 2a: VX-661 30 mg qd | Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6 | Post-Baseline Through Day 28 | 0.07 Liters |
| Group 2a: VX-661 30 mg qd | Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6 | Day 14 | 0.06 Liters |
| Group 2a: VX-661 30 mg qd | Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6 | Day 7 | 0.05 Liters |
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.
Time frame: Baseline, Day 7, Day 14, Day 21, Day 28
Population: The analysis was done using FAS which included all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Group 1-6d Combined: Placebo | Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7 | Day 7 | 0.14 Liters |
| Group 1-6d Combined: Placebo | Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7 | Day 21 | 0.14 Liters |
| Group 1-6d Combined: Placebo | Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7 | Day 14 | 0.08 Liters |
| Group 1-6d Combined: Placebo | Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7 | Day 28 | -0.01 Liters |
| Group 1-6d Combined: Placebo | Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7 | Post-Baseline Through Day 28 | 0.09 Liters |
| Group 1: VX-661 10 mg qd | Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7 | Day 28 | 0.19 Liters |
| Group 1: VX-661 10 mg qd | Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7 | Post-Baseline Through Day 28 | 0.16 Liters |
| Group 1: VX-661 10 mg qd | Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7 | Day 7 | 0.15 Liters |
| Group 1: VX-661 10 mg qd | Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7 | Day 14 | 0.18 Liters |
| Group 1: VX-661 10 mg qd | Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7 | Day 21 | 0.13 Liters |
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.
Time frame: Baseline, Day 7, Day 14, Day 21, Day 28
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Group 1-6d Combined: Placebo | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Day 14 | 0.2 Liters |
| Group 1-6d Combined: Placebo | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Day 7 | 0.11 Liters |
| Group 1-6d Combined: Placebo | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Day 28 | 0.13 Liters |
| Group 1-6d Combined: Placebo | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Day 21 | 0.12 Liters |
| Group 1-6d Combined: Placebo | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | PB Through Day 28 | 0.14 Liters |
| Group 1: VX-661 10 mg qd | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Day 14 | 0.14 Liters |
| Group 1: VX-661 10 mg qd | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Day 7 | 0.02 Liters |
| Group 1: VX-661 10 mg qd | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | PB Through Day 28 | 0.07 Liters |
| Group 1: VX-661 10 mg qd | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Day 21 | 0.08 Liters |
| Group 1: VX-661 10 mg qd | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Day 28 | 0.03 Liters |
| Group 2a: VX-661 30 mg qd | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Day 7 | 0.02 Liters |
| Group 2a: VX-661 30 mg qd | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Day 14 | 0.03 Liters |
| Group 2a: VX-661 30 mg qd | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Day 28 | 0.08 Liters |
| Group 2a: VX-661 30 mg qd | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Day 21 | 0.07 Liters |
| Group 2a: VX-661 30 mg qd | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | PB Through Day 28 | 0.05 Liters |
| Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Day 14 | 0.04 Liters |
| Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Day 28 | 0.04 Liters |
| Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | PB Through Day 28 | 0.04 Liters |
| Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Day 7 | 0.09 Liters |
| Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Day 21 | 0 Liters |
| Group 3a: VX-661 100 mg qd | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Day 14 | 0.05 Liters |
| Group 3a: VX-661 100 mg qd | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Day 21 | 0.14 Liters |
| Group 3a: VX-661 100 mg qd | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Day 7 | 0.1 Liters |
| Group 3a: VX-661 100 mg qd | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | PB Through Day 28 | 0.1 Liters |
| Group 3a: VX-661 100 mg qd | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Day 28 | 0.1 Liters |
| Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Day 7 | 0.11 Liters |
| Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Day 14 | 0.17 Liters |
| Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Day 21 | 0.13 Liters |
| Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Day 28 | 0.16 Liters |
| Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | PB Through Day 28 | 0.14 Liters |
| Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Day 21 | 0.18 Liters |
| Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Day 7 | 0.02 Liters |
| Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Day 14 | 0.11 Liters |
| Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | PB Through Day 28 | 0.1 Liters |
| Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Day 28 | 0.09 Liters |
| Group 5a: VX-661 150 mg qd | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | PB Through Day 28 | 0.12 Liters |
| Group 5a: VX-661 150 mg qd | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Day 7 | 0.08 Liters |
| Group 5a: VX-661 150 mg qd | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Day 14 | 0.12 Liters |
| Group 5a: VX-661 150 mg qd | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Day 28 | 0.15 Liters |
| Group 5a: VX-661 150 mg qd | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Day 21 | 0.14 Liters |
| Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | PB Through Day 28 | 0.01 Liters |
| Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Day 21 | 0.02 Liters |
| Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Day 14 | 0.02 Liters |
| Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Day 7 | -0.01 Liters |
| Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h | Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b | Day 28 | 0.01 Liters |
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.
Time frame: Baseline, Day 7, Day 14, Day 21, Day 28
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Group 1-6d Combined: Placebo | 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 | Day 7 | 2.72 percent predicted of FEV1 |
| Group 1-6d Combined: Placebo | 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 | Day 28 | 3.26 percent predicted of FEV1 |
| Group 1-6d Combined: Placebo | 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 | Post-Baseline Through Day 28 | 3.49 percent predicted of FEV1 |
| Group 1-6d Combined: Placebo | 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 | Day 21 | 2.71 percent predicted of FEV1 |
| Group 1-6d Combined: Placebo | 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 | Day 14 | 5.25 percent predicted of FEV1 |
| Group 1: VX-661 10 mg qd | 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 | Day 14 | 3.72 percent predicted of FEV1 |
| Group 1: VX-661 10 mg qd | 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 | Post-Baseline Through Day 28 | 1.63 percent predicted of FEV1 |
| Group 1: VX-661 10 mg qd | 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 | Day 28 | 0.19 percent predicted of FEV1 |
| Group 1: VX-661 10 mg qd | 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 | Day 7 | 0.8 percent predicted of FEV1 |
| Group 1: VX-661 10 mg qd | 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 | Day 21 | 1.8 percent predicted of FEV1 |
| Group 2a: VX-661 30 mg qd | 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 | Day 21 | 1.84 percent predicted of FEV1 |
| Group 2a: VX-661 30 mg qd | 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 | Day 14 | 0.91 percent predicted of FEV1 |
| Group 2a: VX-661 30 mg qd | 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 | Post-Baseline Through Day 28 | 1.3 percent predicted of FEV1 |
| Group 2a: VX-661 30 mg qd | 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 | Day 28 | 1.99 percent predicted of FEV1 |
| Group 2a: VX-661 30 mg qd | 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 | Day 7 | 0.47 percent predicted of FEV1 |
| Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h | 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 | Day 28 | 1.55 percent predicted of FEV1 |
| Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h | 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 | Day 7 | 3 percent predicted of FEV1 |
| Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h | 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 | Day 21 | 0.25 percent predicted of FEV1 |
| Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h | 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 | Post-Baseline Through Day 28 | 1.6 percent predicted of FEV1 |
| Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h | 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 | Day 14 | 1.61 percent predicted of FEV1 |
| Group 3a: VX-661 100 mg qd | 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 | Day 14 | 1.79 percent predicted of FEV1 |
| Group 3a: VX-661 100 mg qd | 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 | Post-Baseline Through Day 28 | 2.9 percent predicted of FEV1 |
| Group 3a: VX-661 100 mg qd | 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 | Day 7 | 2.9 percent predicted of FEV1 |
| Group 3a: VX-661 100 mg qd | 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 | Day 21 | 3.88 percent predicted of FEV1 |
| Group 3a: VX-661 100 mg qd | 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 | Day 28 | 3.02 percent predicted of FEV1 |
| Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h | 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 | Day 7 | 2.66 percent predicted of FEV1 |
| Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h | 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 | Day 14 | 4.52 percent predicted of FEV1 |
| Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h | 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 | Day 21 | 3.37 percent predicted of FEV1 |
| Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h | 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 | Day 28 | 4.44 percent predicted of FEV1 |
| Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h | 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 | Post-Baseline Through Day 28 | 3.75 percent predicted of FEV1 |
| Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h | 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 | Day 14 | 2.79 percent predicted of FEV1 |
| Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h | 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 | Day 7 | 0.5 percent predicted of FEV1 |
| Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h | 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 | Post-Baseline Through Day 28 | 2.54 percent predicted of FEV1 |
| Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h | 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 | Day 21 | 4.52 percent predicted of FEV1 |
| Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h | 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 | Day 28 | 2.34 percent predicted of FEV1 |
| Group 5a: VX-661 150 mg qd | 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 | Day 14 | 3.72 percent predicted of FEV1 |
| Group 5a: VX-661 150 mg qd | 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 | Day 7 | 2.51 percent predicted of FEV1 |
| Group 5a: VX-661 150 mg qd | 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 | Day 28 | 4.13 percent predicted of FEV1 |
| Group 5a: VX-661 150 mg qd | 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 | Day 21 | 4.08 percent predicted of FEV1 |
| Group 5a: VX-661 150 mg qd | 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 | Post-Baseline Through Day 28 | 3.61 percent predicted of FEV1 |
| Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h | 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 | Day 28 | -0.36 percent predicted of FEV1 |
| Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h | 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 | Post-Baseline Through Day 28 | -0.14 percent predicted of FEV1 |
| Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h | 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 | Day 21 | 0.18 percent predicted of FEV1 |
| Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h | 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 | Day 7 | -0.41 percent predicted of FEV1 |
| Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h | 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 | Day 14 | 0.03 percent predicted of FEV1 |
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.
Time frame: Baseline, Day 7, Day 14, Day 21, Day 28
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Group 1-6d Combined: Placebo | 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 | Day 21 | 0.36 percent predicted of FEV1 |
| Group 1-6d Combined: Placebo | 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 | Day 14 | 1.2 percent predicted of FEV1 |
| Group 1-6d Combined: Placebo | 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 | Post-Baseline Through Day 28 | 0.94 percent predicted of FEV1 |
| Group 1-6d Combined: Placebo | 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 | Day 7 | 1.37 percent predicted of FEV1 |
| Group 1-6d Combined: Placebo | 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 | Day 28 | 0.81 percent predicted of FEV1 |
| Group 1: VX-661 10 mg qd | 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 | Day 14 | 2.52 percent predicted of FEV1 |
| Group 1: VX-661 10 mg qd | 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 | Post-Baseline Through Day 28 | 2.31 percent predicted of FEV1 |
| Group 1: VX-661 10 mg qd | 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 | Day 7 | 1.95 percent predicted of FEV1 |
| Group 1: VX-661 10 mg qd | 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 | Day 21 | 3.21 percent predicted of FEV1 |
| Group 1: VX-661 10 mg qd | 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 | Day 28 | 1.56 percent predicted of FEV1 |
| Group 2a: VX-661 30 mg qd | 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 | Day 28 | 1.67 percent predicted of FEV1 |
| Group 2a: VX-661 30 mg qd | 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 | Day 21 | 1.73 percent predicted of FEV1 |
| Group 2a: VX-661 30 mg qd | 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 | Post-Baseline Through Day 28 | 1.47 percent predicted of FEV1 |
| Group 2a: VX-661 30 mg qd | 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 | Day 14 | 1.37 percent predicted of FEV1 |
| Group 2a: VX-661 30 mg qd | 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 | Day 7 | 1.09 percent predicted of FEV1 |
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.
Time frame: Baseline, Day 7, Day 14, Day 21, Day 28
Population: The analysis was done using FAS which included all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Group 1-6d Combined: Placebo | 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 | Day 7 | 3 percent predicted of FEV1 |
| Group 1-6d Combined: Placebo | 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 | Day 21 | 2.72 percent predicted of FEV1 |
| Group 1-6d Combined: Placebo | 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 | Day 14 | 0.98 percent predicted of FEV1 |
| Group 1-6d Combined: Placebo | 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 | Day 28 | -1.12 percent predicted of FEV1 |
| Group 1-6d Combined: Placebo | 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 | Post-Baseline Through Day 28 | 1.4 percent predicted of FEV1 |
| Group 1: VX-661 10 mg qd | 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 | Day 28 | 5.16 percent predicted of FEV1 |
| Group 1: VX-661 10 mg qd | 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 | Post-Baseline Through Day 28 | 4.6 percent predicted of FEV1 |
| Group 1: VX-661 10 mg qd | 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 | Day 7 | 4.14 percent predicted of FEV1 |
| Group 1: VX-661 10 mg qd | 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 | Day 14 | 5.22 percent predicted of FEV1 |
| Group 1: VX-661 10 mg qd | 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 | Day 21 | 3.88 percent predicted of FEV1 |
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.
Time frame: Baseline, Day 7, Day 14, Day 21, Day 28
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Group 1-6d Combined: Placebo | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Day 21 | 4.84 mmol/L |
| Group 1-6d Combined: Placebo | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Day 14 | 0.91 mmol/L |
| Group 1-6d Combined: Placebo | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Day 7 | 1.73 mmol/L |
| Group 1-6d Combined: Placebo | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Day 28 | 8.19 mmol/L |
| Group 1: VX-661 10 mg qd | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Day 7 | -3.13 mmol/L |
| Group 1: VX-661 10 mg qd | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Day 21 | -4.61 mmol/L |
| Group 1: VX-661 10 mg qd | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Day 28 | -3.44 mmol/L |
| Group 1: VX-661 10 mg qd | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Day 14 | -7.88 mmol/L |
| Group 2a: VX-661 30 mg qd | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Day 21 | -3.7 mmol/L |
| Group 2a: VX-661 30 mg qd | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Day 14 | -6.55 mmol/L |
| Group 2a: VX-661 30 mg qd | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Day 28 | -4.62 mmol/L |
| Group 2a: VX-661 30 mg qd | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Day 7 | -5.37 mmol/L |
| Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Day 21 | -18.78 mmol/L |
| Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Day 28 | -15.23 mmol/L |
| Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Day 14 | -28.23 mmol/L |
| Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Day 7 | -19.48 mmol/L |
| Group 3a: VX-661 100 mg qd | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Day 21 | -5.83 mmol/L |
| Group 3a: VX-661 100 mg qd | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Day 7 | -5.02 mmol/L |
| Group 3a: VX-661 100 mg qd | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Day 28 | -6.37 mmol/L |
| Group 3a: VX-661 100 mg qd | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Day 14 | -6.77 mmol/L |
| Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Day 14 | -7.37 mmol/L |
| Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Day 21 | -4.26 mmol/L |
| Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Day 7 | -6.85 mmol/L |
| Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Day 28 | -5.68 mmol/L |
| Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Day 21 | -12.17 mmol/L |
| Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Day 14 | -10.28 mmol/L |
| Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Day 28 | -5.5 mmol/L |
| Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Day 7 | -13.89 mmol/L |
| Group 5a: VX-661 150 mg qd | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Day 14 | -2.4 mmol/L |
| Group 5a: VX-661 150 mg qd | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Day 21 | -3.9 mmol/L |
| Group 5a: VX-661 150 mg qd | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Day 7 | -0.59 mmol/L |
| Group 5a: VX-661 150 mg qd | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Day 28 | -3.62 mmol/L |
| Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Day 28 | -1.27 mmol/L |
| Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Day 21 | -1.05 mmol/L |
| Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Day 7 | 0.22 mmol/L |
| Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b | Day 14 | -1.32 mmol/L |
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.
Time frame: Baseline, Day 7, Day 14, Day 21, Day 28
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Group 1-6d Combined: Placebo | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 6 | Day 28 | -3.44 mmol/L |
| Group 1-6d Combined: Placebo | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 6 | Day 14 | -7.9 mmol/L |
| Group 1-6d Combined: Placebo | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 6 | Day 7 | -6.61 mmol/L |
| Group 1-6d Combined: Placebo | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 6 | Day 21 | -6.34 mmol/L |
| Group 1: VX-661 10 mg qd | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 6 | Day 28 | -6.43 mmol/L |
| Group 1: VX-661 10 mg qd | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 6 | Day 21 | -6.98 mmol/L |
| Group 1: VX-661 10 mg qd | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 6 | Day 14 | -7.11 mmol/L |
| Group 1: VX-661 10 mg qd | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 6 | Day 7 | -11.04 mmol/L |
| Group 2a: VX-661 30 mg qd | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 6 | Day 21 | -2.47 mmol/L |
| Group 2a: VX-661 30 mg qd | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 6 | Day 14 | -2.1 mmol/L |
| Group 2a: VX-661 30 mg qd | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 6 | Day 7 | -0.36 mmol/L |
| Group 2a: VX-661 30 mg qd | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 6 | Day 28 | 0.19 mmol/L |
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.
Time frame: Baseline, Day 7, Day 14, Day 21, Day 28
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Group 1-6d Combined: Placebo | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 7 | Day 7 | 4.87 mmol/L |
| Group 1-6d Combined: Placebo | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 7 | Day 14 | 10.75 mmol/L |
| Group 1-6d Combined: Placebo | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 7 | Day 21 | 9.37 mmol/L |
| Group 1-6d Combined: Placebo | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 7 | Day 28 | 15.73 mmol/L |
| Group 1: VX-661 10 mg qd | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 7 | Day 28 | -7.72 mmol/L |
| Group 1: VX-661 10 mg qd | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 7 | Day 7 | -7.28 mmol/L |
| Group 1: VX-661 10 mg qd | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 7 | Day 21 | -4.14 mmol/L |
| Group 1: VX-661 10 mg qd | Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 7 | Day 14 | -8.95 mmol/L |