Cystic Fibrosis
Conditions
Keywords
CF
Brief summary
The objective of this study was to evaluate the safety and efficacy of VX-661in combination with ivacaftor in participants with cystic fibrosis (CF) who are homozygous for F508del cystic fibrosis transmembrane conductance regulator (CFTR) mutation
Interventions
DRUGVX-661
Tablet, oral use
DRUGIvacaftor
Film coated tablet, oral use
Tablet, oral use
Film coated tablet, oral use
Sponsors
Vertex Pharmaceuticals Incorporated
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Homozygous for the F508del CFTR mutation * FEV1 ≥40% and ≤90% of predicted normal for age, sex, and height * Stable CF disease as judged by the investigator
Exclusion criteria
* History of any comorbidity 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 * Pregnant and nursing females: Females of childbearing potential must have a negative pregnancy test at screening and Day 1 of the PC Phase and Day -7 or Day 1 of the OLE Phase (whichever was applicable) * Sexually active participants of reproductive potential who are not willing to follow the contraception requirements * The participant or a close relative of the participant is the investigator or sub investigator, research assistant, pharmacist, study coordinator, or other staff directly involved with the conduct of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PC Phase: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline (PC Phase) up to 112 days | AE: 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. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, Inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. AEs with start date or increased severity on or after the first dose of study drug through the end of study participation considered treatment-emergent. Baseline was defined as Day 1 of PC Phase. |
| OLE Phase: Number of Participants With Treatment-Emergent AEs and SAEs | Baseline (OLE Phase) up to 364 days | AE: 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. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, Inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. AEs with start date or increased severity on or after the first dose of study drug through the end of study participation considered treatment-emergent. Baseline was defined as Day 1 of the OLE Phase. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PC Phase: Relative Change From Baseline in Percent Predicted FEV1 Through Week 12 | Baseline (PC Phase), Through Week 12 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Baseline was defined as Day 1 of PC Phase. |
| OLE Phase: Relative Change From Baseline in Percent Predicted FEV1 Through Week 40 | Baseline (OLE Phase), Through Week 40 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Baseline was defined as Day 1 of the OLE Phase. |
| PC Phase: Absolute Change From Baseline in Sweat Chloride Through Week 12 | Baseline (PC Phase), Through Week 12 | Sweat samples were collected using an approved collection device. Baseline was defined as Day 1 of PC Phase. |
| OLE Phase: Absolute Change From Baseline in Sweat Chloride Through Week 40 | Baseline (OLE Phase), Through Week 40 | Sweat samples were collected using an approved collection device. Baseline was defined as Day 1 of the OLE Phase. |
| PC Phase: Absolute Change From Baseline in Body Weight at Week 12 | Baseline (PC Phase), Week 12 | Baseline was defined as Day 1 of PC Phase. |
| OLE Phase: Absolute Change From Baseline in Body Weight at Week 40 | Baseline (OLE Phase), Week 40 | Baseline was defined as Day 1 of the OLE Phase. |
| PC Phase: Absolute Change From Baseline Body Mass Index (BMI) at Week 12 | Baseline (PC Phase), Week 12 | BMI was calculated using following formula: BMI = Weight in kg/height in square meter (m\^2). Baseline was defined as Day 1 of PC Phase. |
| PC Phase: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 12 | Baseline (PC Phase), Through Week 12 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Baseline was defined as Day 1 of PC Phase. |
| PC Phase: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 12 | Baseline (PC Phase), Through Week 12 | The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Baseline was defined as Day 1 of PC Phase. |
| OLE Phase: Absolute Change From Baseline in CFQ-R Respiratory Domain Score Through Week 40 | Baseline (OLE Phase), Through Week 40 | The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Baseline was defined as Day 1 of the OLE Phase. |
| PC Phase: Maximum Plasma Concentration (Cmax) of VX-661 and IVA | Pre-dose, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 85 | — |
| PC Phase: Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24h) of VX-661 | Pre-dose, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 85 | Pharmacokinetic (PK) sampling was performed up to 12 hours post-dose on Day 85. For Arm VX-661 50 mg q12h + IVA 150 mg q12h (VX-661 q12h regimen), area under the concentration versus time curve from time 0 to 12 hours (AUC0-12h) was multiplied by 2 to obtain AUC0-24h. |
| PC Phase: Area Under the Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12h) of IVA | Pre-dose, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 85 | — |
| PC Phase: Time to Reach Cmax (Tmax) of VX-661 and IVA | Pre-dose, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 85 | — |
| OLE Phase: Absolute Change From Baseline BMI at Week 40 | Baseline (OLE Phase), Week 40 | BMI was calculated using following formula: BMI = Weight in kg/height in m\^2. Baseline was defined as Day 1 of the OLE Phase. |
| OLE Phase: Absolute Change From Baseline in Percent Predicted FEV1 Through Week 40 | Baseline (OLE Phase), Through Week 40 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Baseline was defined as Day 1 of the OLE Phase. |
Countries
United States
Participant flow
Pre-assignment details
The study consisted of 2 phases: a randomized, double-blind, placebo-controlled (PC) phase in which participants received either VX-661 in combination with Ivacaftor (IVA), or matched placebo and an open-label extension (OLE) phase in which participants received VX-661 in combination with IVA.
Participants by arm
| Arm | Count |
|---|---|
| PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h Participants received VX-661 50 mg tablet plus IVA 150 mg tablet q12h for 12 weeks. | 6 |
| PC Phase: VX-661 Placebo q12h + IVA Placebo q12h Participants received placebo matched to VX-661 tablet plus placebo matched to IVA tablet q12h for 12 weeks. | 5 |
| PC Phase: VX-661 100 mg qd + IVA 150 mg q12h Participants received two VX-661 50 mg tablets qd plus IVA 150 mg tablet q12h for 12 weeks. | 15 |
| PC Phase: VX -661 Placebo qd + IVA Placebo q12h Participants received two placebo matched to VX-661 tablets qd plus placebo matched to IVA tablet q12h for 12 weeks. | 13 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| OLE Phase (48 Weeks) | Other | 0 | 0 | 0 | 0 | 1 |
| OLE Phase (48 Weeks) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 2 |
| PC Phase (12 Weeks) | Randomized, but not treated | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | PC Phase: VX-661 Placebo q12h + IVA Placebo q12h | PC Phase: VX-661 100 mg qd + IVA 150 mg q12h | PC Phase: VX -661 Placebo qd + IVA Placebo q12h | Total |
|---|---|---|---|---|---|
| Age, Continuous | 33.0 years STANDARD_DEVIATION 10.6 | 24.2 years STANDARD_DEVIATION 2.2 | 27.3 years STANDARD_DEVIATION 5.2 | 30.3 years STANDARD_DEVIATION 10.8 | 28.8 years STANDARD_DEVIATION 8.3 |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 7 Participants | 3 Participants | 14 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 8 Participants | 10 Participants | 25 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 5 | 0 / 15 | 0 / 13 | 0 / 27 |
| other Total, other adverse events | 6 / 6 | 5 / 5 | 15 / 15 | 13 / 13 | 25 / 27 |
| serious Total, serious adverse events | 1 / 6 | 2 / 5 | 4 / 15 | 5 / 13 | 6 / 27 |
Outcome results
Primary
OLE Phase: Number of Participants With Treatment-Emergent AEs and SAEs
AE: 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. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, Inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. AEs with start date or increased severity on or after the first dose of study drug through the end of study participation considered treatment-emergent. Baseline was defined as Day 1 of the OLE Phase.
Time frame: Baseline (OLE Phase) up to 364 days
Population: Safety Set was defined as all participants who received at least 1 dose of study drug in OLE Phase.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | OLE Phase: Number of Participants With Treatment-Emergent AEs and SAEs | Participants with AEs | 25 Participants |
| PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | OLE Phase: Number of Participants With Treatment-Emergent AEs and SAEs | Participants with SAEs | 6 Participants |
Primary
PC Phase: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
AE: 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. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, Inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. AEs with start date or increased severity on or after the first dose of study drug through the end of study participation considered treatment-emergent. Baseline was defined as Day 1 of PC Phase.
Time frame: Baseline (PC Phase) up to 112 days
Population: Safety Set was defined as all participants who received at least 1 dose of study drug in PC Phase.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | PC Phase: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 6 Participants |
| PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | PC Phase: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 1 Participants |
| PC Phase: VX-661 Placebo q12h + IVA Placebo q12h | PC Phase: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 2 Participants |
| PC Phase: VX-661 Placebo q12h + IVA Placebo q12h | PC Phase: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 5 Participants |
| PC Phase: VX-661 100 mg qd + IVA 150 mg q12h | PC Phase: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 15 Participants |
| PC Phase: VX-661 100 mg qd + IVA 150 mg q12h | PC Phase: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 4 Participants |
| PC Phase: VX -661 Placebo qd + IVA Placebo q12h | PC Phase: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 13 Participants |
| PC Phase: VX -661 Placebo qd + IVA Placebo q12h | PC Phase: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 5 Participants |
Secondary
OLE Phase: Absolute Change From Baseline BMI at Week 40
BMI was calculated using following formula: BMI = Weight in kg/height in m\^2. Baseline was defined as Day 1 of the OLE Phase.
Time frame: Baseline (OLE Phase), Week 40
Population: Analysis population was defined as all participants who received at least 1 dose of study drug in the OLE Phase.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | OLE Phase: Absolute Change From Baseline BMI at Week 40 | 0.33 kg/m^2 |
Secondary
OLE Phase: Absolute Change From Baseline in Body Weight at Week 40
Baseline was defined as Day 1 of the OLE Phase.
Time frame: Baseline (OLE Phase), Week 40
Population: Analysis population was defined as all participants who received at least 1 dose of study drug in the OLE Phase.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | OLE Phase: Absolute Change From Baseline in Body Weight at Week 40 | 1.0 kg |
Secondary
OLE Phase: Absolute Change From Baseline in CFQ-R Respiratory Domain Score Through Week 40
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Baseline was defined as Day 1 of the OLE Phase.
Time frame: Baseline (OLE Phase), Through Week 40
Population: Analysis population was defined as all participants who received at least 1 dose of study drug in the OLE Phase.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | OLE Phase: Absolute Change From Baseline in CFQ-R Respiratory Domain Score Through Week 40 | -0.6 units on a scale |
Secondary
OLE Phase: Absolute Change From Baseline in Percent Predicted FEV1 Through Week 40
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Baseline was defined as Day 1 of the OLE Phase.
Time frame: Baseline (OLE Phase), Through Week 40
Population: Analysis population was defined as all participants who received at least 1 dose of study drug in OLE phase.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | OLE Phase: Absolute Change From Baseline in Percent Predicted FEV1 Through Week 40 | 2.7 Percent predicted of FEV1 |
Secondary
OLE Phase: Absolute Change From Baseline in Sweat Chloride Through Week 40
Sweat samples were collected using an approved collection device. Baseline was defined as Day 1 of the OLE Phase.
Time frame: Baseline (OLE Phase), Through Week 40
Population: Analysis population was defined as all participants who received at least 1 dose of study drug in the OLE Phase. Here, Number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | OLE Phase: Absolute Change From Baseline in Sweat Chloride Through Week 40 | -6.6 mmol/L |
Secondary
OLE Phase: Relative Change From Baseline in Percent Predicted FEV1 Through Week 40
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Baseline was defined as Day 1 of the OLE Phase.
Time frame: Baseline (OLE Phase), Through Week 40
Population: Analysis population was defined as all participants who received at least 1 dose of study drug in the OLE Phase.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | OLE Phase: Relative Change From Baseline in Percent Predicted FEV1 Through Week 40 | 6.1 Percent change |
Secondary
PC Phase: Absolute Change From Baseline Body Mass Index (BMI) at Week 12
BMI was calculated using following formula: BMI = Weight in kg/height in square meter (m\^2). Baseline was defined as Day 1 of PC Phase.
Time frame: Baseline (PC Phase), Week 12
Population: FAS was defined as all randomized participants who received at least 1 dose of study drug in PC Phase.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | PC Phase: Absolute Change From Baseline Body Mass Index (BMI) at Week 12 | 0.38 Kilogram per square meter (kg/m^2) |
| PC Phase: VX-661 Placebo q12h + IVA Placebo q12h | PC Phase: Absolute Change From Baseline Body Mass Index (BMI) at Week 12 | 0.54 Kilogram per square meter (kg/m^2) |
| PC Phase: VX-661 100 mg qd + IVA 150 mg q12h | PC Phase: Absolute Change From Baseline Body Mass Index (BMI) at Week 12 | 0.18 Kilogram per square meter (kg/m^2) |
| PC Phase: VX -661 Placebo qd + IVA Placebo q12h | PC Phase: Absolute Change From Baseline Body Mass Index (BMI) at Week 12 | 0.11 Kilogram per square meter (kg/m^2) |
Secondary
PC Phase: Absolute Change From Baseline in Body Weight at Week 12
Baseline was defined as Day 1 of PC Phase.
Time frame: Baseline (PC Phase), Week 12
Population: FAS was defined as all randomized participants who received at least 1 dose of study drug in PC Phase.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | PC Phase: Absolute Change From Baseline in Body Weight at Week 12 | 1.0 kilogram (kg) |
| PC Phase: VX-661 Placebo q12h + IVA Placebo q12h | PC Phase: Absolute Change From Baseline in Body Weight at Week 12 | 1.6 kilogram (kg) |
| PC Phase: VX-661 100 mg qd + IVA 150 mg q12h | PC Phase: Absolute Change From Baseline in Body Weight at Week 12 | 0.5 kilogram (kg) |
| PC Phase: VX -661 Placebo qd + IVA Placebo q12h | PC Phase: Absolute Change From Baseline in Body Weight at Week 12 | 0.3 kilogram (kg) |
Secondary
PC Phase: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 12
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Baseline was defined as Day 1 of PC Phase.
Time frame: Baseline (PC Phase), Through Week 12
Population: FAS was defined as all randomized participants who received at least 1 dose of study drug in PC Phase.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | PC Phase: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 12 | 5.6 units on a scale |
| PC Phase: VX-661 Placebo q12h + IVA Placebo q12h | PC Phase: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 12 | -4.6 units on a scale |
| PC Phase: VX-661 100 mg qd + IVA 150 mg q12h | PC Phase: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 12 | 1.0 units on a scale |
| PC Phase: VX -661 Placebo qd + IVA Placebo q12h | PC Phase: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 12 | 0.4 units on a scale |
Secondary
PC Phase: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 12
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Baseline was defined as Day 1 of PC Phase.
Time frame: Baseline (PC Phase), Through Week 12
Population: FAS was defined as all randomized participants who received at least 1 dose of study drug in PC Phase.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | PC Phase: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 12 | 0.9 Percent predicted of FEV1 |
| PC Phase: VX-661 Placebo q12h + IVA Placebo q12h | PC Phase: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 12 | -0.1 Percent predicted of FEV1 |
| PC Phase: VX-661 100 mg qd + IVA 150 mg q12h | PC Phase: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 12 | 3.0 Percent predicted of FEV1 |
| PC Phase: VX -661 Placebo qd + IVA Placebo q12h | PC Phase: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 12 | 1.9 Percent predicted of FEV1 |
Secondary
PC Phase: Absolute Change From Baseline in Sweat Chloride Through Week 12
Sweat samples were collected using an approved collection device. Baseline was defined as Day 1 of PC Phase.
Time frame: Baseline (PC Phase), Through Week 12
Population: FAS was defined as all randomized participants who received at least 1 dose of study drug in PC Phase. Here, Number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | PC Phase: Absolute Change From Baseline in Sweat Chloride Through Week 12 | -10.6 Millimole per liter (mmol/L) |
| PC Phase: VX-661 Placebo q12h + IVA Placebo q12h | PC Phase: Absolute Change From Baseline in Sweat Chloride Through Week 12 | 2.9 Millimole per liter (mmol/L) |
| PC Phase: VX-661 100 mg qd + IVA 150 mg q12h | PC Phase: Absolute Change From Baseline in Sweat Chloride Through Week 12 | -4.7 Millimole per liter (mmol/L) |
| PC Phase: VX -661 Placebo qd + IVA Placebo q12h | PC Phase: Absolute Change From Baseline in Sweat Chloride Through Week 12 | 0.8 Millimole per liter (mmol/L) |
Secondary
PC Phase: Area Under the Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12h) of IVA
Time frame: Pre-dose, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 85
Population: Analysis population included all participants who received a dose of VX-661 and IVA, whether the participant completed dosing or not and if the dataset(s) supported the noncompartmental analyses. Here, Number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | PC Phase: Area Under the Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12h) of IVA | 14700 hr*ng/mL | Standard Deviation 11600 |
| PC Phase: VX-661 Placebo q12h + IVA Placebo q12h | PC Phase: Area Under the Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12h) of IVA | 10100 hr*ng/mL | Standard Deviation 4890 |
Secondary
PC Phase: Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24h) of VX-661
Pharmacokinetic (PK) sampling was performed up to 12 hours post-dose on Day 85. For Arm VX-661 50 mg q12h + IVA 150 mg q12h (VX-661 q12h regimen), area under the concentration versus time curve from time 0 to 12 hours (AUC0-12h) was multiplied by 2 to obtain AUC0-24h.
Time frame: Pre-dose, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 85
Population: Analysis population included all participants who received a dose of VX-661 and IVA, whether the participant completed dosing or not and if the dataset(s) supported the noncompartmental analyses. Here, Number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | PC Phase: Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24h) of VX-661 | 84900 Hour*nanogram per milliliter (hr*ng/mL) | Standard Deviation 55900 |
| PC Phase: VX-661 Placebo q12h + IVA Placebo q12h | PC Phase: Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24h) of VX-661 | 75500 Hour*nanogram per milliliter (hr*ng/mL) | Standard Deviation 20300 |
Secondary
PC Phase: Maximum Plasma Concentration (Cmax) of VX-661 and IVA
Time frame: Pre-dose, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 85
Population: Analysis population included all participants who received a dose of VX-661 and IVA, whether the participant completed dosing or not and if the dataset(s) supported the noncompartmental analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | PC Phase: Maximum Plasma Concentration (Cmax) of VX-661 and IVA | VX-661 | 4890 Nanogram per milliliter (ng/mL) | Standard Deviation 3150 |
| PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | PC Phase: Maximum Plasma Concentration (Cmax) of VX-661 and IVA | IVA | 1490 Nanogram per milliliter (ng/mL) | Standard Deviation 1150 |
| PC Phase: VX-661 Placebo q12h + IVA Placebo q12h | PC Phase: Maximum Plasma Concentration (Cmax) of VX-661 and IVA | VX-661 | 6460 Nanogram per milliliter (ng/mL) | Standard Deviation 1240 |
| PC Phase: VX-661 Placebo q12h + IVA Placebo q12h | PC Phase: Maximum Plasma Concentration (Cmax) of VX-661 and IVA | IVA | 1210 Nanogram per milliliter (ng/mL) | Standard Deviation 585 |
Secondary
PC Phase: Relative Change From Baseline in Percent Predicted FEV1 Through Week 12
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Baseline was defined as Day 1 of PC Phase.
Time frame: Baseline (PC Phase), Through Week 12
Population: FAS was defined as all randomized participants who received at least 1 dose of study drug in PC Phase.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | PC Phase: Relative Change From Baseline in Percent Predicted FEV1 Through Week 12 | 2.6 Percent change |
| PC Phase: VX-661 Placebo q12h + IVA Placebo q12h | PC Phase: Relative Change From Baseline in Percent Predicted FEV1 Through Week 12 | 1.0 Percent change |
| PC Phase: VX-661 100 mg qd + IVA 150 mg q12h | PC Phase: Relative Change From Baseline in Percent Predicted FEV1 Through Week 12 | 6.0 Percent change |
| PC Phase: VX -661 Placebo qd + IVA Placebo q12h | PC Phase: Relative Change From Baseline in Percent Predicted FEV1 Through Week 12 | 4.2 Percent change |
Secondary
PC Phase: Time to Reach Cmax (Tmax) of VX-661 and IVA
Time frame: Pre-dose, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 85
Population: Analysis population included all participants who received a dose of VX-661 and IVA, whether the participant completed dosing or not and if the dataset(s) supported the noncompartmental analyses.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | PC Phase: Time to Reach Cmax (Tmax) of VX-661 and IVA | VX-661 | 2.48 hour |
| PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | PC Phase: Time to Reach Cmax (Tmax) of VX-661 and IVA | IVA | 3.59 hour |
| PC Phase: VX-661 Placebo q12h + IVA Placebo q12h | PC Phase: Time to Reach Cmax (Tmax) of VX-661 and IVA | VX-661 | 3.23 hour |
| PC Phase: VX-661 Placebo q12h + IVA Placebo q12h | PC Phase: Time to Reach Cmax (Tmax) of VX-661 and IVA | IVA | 4.00 hour |