Cystic Fibrosis
Conditions
Keywords
∆F508, F508del, Cystic Fibrosis Transmembrane Conductance Regulator, CFTR, Pancreatic diseases, Lung diseases, Genetic disease, inborn, Infant, newborn, diseases
Brief summary
The primary objective of the study was to evaluate the safety and tolerability of VX-809 in participants with cystic fibrosis (CF) who are homozygous for the F508del mutation on the CF transmembrane conductance regulator (CFTR) gene.
Detailed description
This was a Phase 2, randomized, double-blind, placebo-controlled, multiple-dose study of orally-administered VX-809 in participants with CF who are homozygous for the specific CFTR mutation known as ∆F508 or F508del. Enrollment was planned for 90 participants at approximately 20 centers. Participants were planned to be randomized in a 4:1 ratio to receive 1 of 4 doses of VX-809 or placebo once a day for 28 days in a parallel design. Participants were outpatients during the study, except for overnight stays on Day 1 and 28.
Interventions
DRUGVX-809
Capsules
DRUGPlacebo
Placebo matched to VX-809 capsules.
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
* Confirmed diagnosis of CF with ∆F508-CFTR mutation in both alleles * Forced expiratory volume in 1 second (FEV1) greater than or equal to (\>=) 40 percent (%) of predicted normal for age, gender, and height * Weight \>=40 kilograms (kg) and body mass index greater than or equal to 18.5 kilogram per square meter (kg/m\^2) * Screening laboratory values, tests, and physical examination within acceptable ranges * Negative pregnancy test (for women of child-bearing potential) * Able and willing to follow contraceptive requirements * Willing to remain on a stable medication regimen for the duration of study participation
Exclusion criteria
* History of any illness, or any ongoing acute illness, that could impact the safety of the study participant or may confound results of study * Pulmonary exacerbation or changes in therapy for pulmonary disease within 14 days before receiving the first dose of study drug * Impaired hepatic or renal function * History of organ or hematological transplant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability Based on Adverse Events (AEs) | Up to 14 days after last dose (last dose = Day 28) | 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. Serious adverse event (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, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Number of participants with AEs and SAEs are reported. An AE that started at or after initial dosing of study drug, or increased in severity after initial dosing of study drug visit is considered treatment-emergent. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Percent Predicted FEV1 at Day 28 | Baseline, Day 28 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Predicted FEV1 (for age, gender, and height) was calculated using the Knudson method. |
| Change From Baseline in Forced Vital Capacity (FVC) at Day 28 | Baseline, Day 28 | FVC is the volume of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. |
| Change From Baseline in Forced Expiratory Flow Over the Middle Half of the FVC (FEF25-75) at Day 28 | Baseline, Day 28 | FEF25-75 is total volume of air exhaled from the lungs over the middle half of the FVC test, expressed as liters per second (L/sec). |
| Change From Baseline in Sweat Chloride at Day 28 | Baseline, Day 28 | Sweat samples were collected using an approved Macroduct (Wescor) collection device. A volume of greater than or equal to (\>=) 15 microliter was required for determination of sweat chloride. |
| Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Day 28 | Baseline, Day 28 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. |
| Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Baseline, Day 28 | The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. CFQ-R domains include: Body, Digestion, Eat, Emotion, Health Perceptions, Physical, Respiratory, Role, Social, Treatment Burden, Vitality, and Weight. Individual domain score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. |
| Maximum Plasma Concentration (Cmax) of VX-809 | Day 1 (pre dose, 0.75, 1.5, 3, 4, 6, 9, 12, and 24 hours post-dose), Day 28 (pre dose, 0.75, 1.5, 3, 4, 6, 9, 12, 24, and 30-60 hours post dose) | Only participants who received VX-809 were analyzed for this outcome measure. |
| Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of VX-809 | Day 1 (pre dose, 0.75, 1.5, 3, 4, 6, 9, 12, and 24 hours post-dose), Day 28 (pre dose, 0.75, 1.5, 3, 4, 6, 9, 12, and 24 hours post dose) | Only participants who received VX-809 were analyzed for this outcome measure. |
| Change From Baseline in Nasal Potential Difference (NPD) of Zero Chloride Plus Isoproterenol Response at Day 28 | Baseline, Day 28 | Nasal potential difference (NPD) provides a direct and sensitive evaluation of sodium and chloride transport in secretory epithelial cells via assessment of transepithelial bioelectric properties. NPD under conditions of zero chloride concentration perfusion solution in the presence of isoproterenol is reported. NPDs were performed according to Cystic Fibrosis Foundation Therapeutics Development Network (CFFT TDN) Standard Operating Procedure (SOP) 528.00 Standardization of Measurement of Nasal Membrane Transepithelial Potential Difference (NPD) - electronic data capture (EDC) and Perfusion or Perfusion-Free Probe. |
Countries
Belgium, Canada, Germany, Netherlands, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo matched to VX-809 capsule orally once daily for 28 days. | 17 |
| VX-809, 25 mg VX-809, 25 mg capsule orally once daily for 28 days. | 18 |
| VX-809, 50 mg VX-809, 50 mg capsule orally once daily for 28 days. | 18 |
| VX-809, 100 mg VX-809, 100 mg capsule orally once daily for 28 days. | 17 |
| VX-809, 200 mg VX-809, 200 mg capsule orally once daily for 28 days. | 19 |
| Total | 89 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Randomized but not Treated | 2 | 0 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo | VX-809, 25 mg | VX-809, 50 mg | VX-809, 100 mg | VX-809, 200 mg | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 31.5 years STANDARD_DEVIATION 9.35 | 27.7 years STANDARD_DEVIATION 8.98 | 27.1 years STANDARD_DEVIATION 8.2 | 30.1 years STANDARD_DEVIATION 11.55 | 26.7 years STANDARD_DEVIATION 6.82 | 28.6 years STANDARD_DEVIATION 9.1 |
| Sex: Female, Male Female | 6 Participants | 9 Participants | 9 Participants | 5 Participants | 7 Participants | 36 Participants |
| Sex: Female, Male Male | 11 Participants | 9 Participants | 9 Participants | 12 Participants | 12 Participants | 53 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 | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 17 / 17 | 16 / 18 | 15 / 18 | 16 / 17 | 18 / 19 |
| serious Total, serious adverse events | 1 / 17 | 5 / 18 | 1 / 18 | 0 / 17 | 3 / 19 |
Outcome results
Primary
Safety and Tolerability Based on Adverse Events (AEs)
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. Serious adverse event (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, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Number of participants with AEs and SAEs are reported. An AE that started at or after initial dosing of study drug, or increased in severity after initial dosing of study drug visit is considered treatment-emergent.
Time frame: Up to 14 days after last dose (last dose = Day 28)
Population: Safety set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Safety and Tolerability Based on Adverse Events (AEs) | Participants With Any AE | 17 participants |
| Placebo | Safety and Tolerability Based on Adverse Events (AEs) | Participants With SAE | 1 participants |
| VX-809, 25 mg | Safety and Tolerability Based on Adverse Events (AEs) | Participants With Any AE | 16 participants |
| VX-809, 25 mg | Safety and Tolerability Based on Adverse Events (AEs) | Participants With SAE | 5 participants |
| VX-809, 50 mg | Safety and Tolerability Based on Adverse Events (AEs) | Participants With Any AE | 15 participants |
| VX-809, 50 mg | Safety and Tolerability Based on Adverse Events (AEs) | Participants With SAE | 1 participants |
| VX-809, 100 mg | Safety and Tolerability Based on Adverse Events (AEs) | Participants With SAE | 0 participants |
| VX-809, 100 mg | Safety and Tolerability Based on Adverse Events (AEs) | Participants With Any AE | 16 participants |
| VX-809, 200 mg | Safety and Tolerability Based on Adverse Events (AEs) | Participants With Any AE | 18 participants |
| VX-809, 200 mg | Safety and Tolerability Based on Adverse Events (AEs) | Participants With SAE | 3 participants |
Secondary
Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of VX-809
Only participants who received VX-809 were analyzed for this outcome measure.
Time frame: Day 1 (pre dose, 0.75, 1.5, 3, 4, 6, 9, 12, and 24 hours post-dose), Day 28 (pre dose, 0.75, 1.5, 3, 4, 6, 9, 12, and 24 hours post dose)
Population: FAS. Here, n = participants evaluable for specified category for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of VX-809 | Day 1 (n= 18, 18, 17, 19) | 7190 hour*nanogram per milliliter (hr*ng/mL) | Standard Deviation 2190 |
| Placebo | Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of VX-809 | Day 28 (n= 17, 17, 16, 18) | 12900 hour*nanogram per milliliter (hr*ng/mL) | Standard Deviation 4920 |
| VX-809, 25 mg | Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of VX-809 | Day 28 (n= 17, 17, 16, 18) | 28800 hour*nanogram per milliliter (hr*ng/mL) | Standard Deviation 13100 |
| VX-809, 25 mg | Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of VX-809 | Day 1 (n= 18, 18, 17, 19) | 16600 hour*nanogram per milliliter (hr*ng/mL) | Standard Deviation 6290 |
| VX-809, 50 mg | Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of VX-809 | Day 1 (n= 18, 18, 17, 19) | 29000 hour*nanogram per milliliter (hr*ng/mL) | Standard Deviation 11400 |
| VX-809, 50 mg | Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of VX-809 | Day 28 (n= 17, 17, 16, 18) | 54100 hour*nanogram per milliliter (hr*ng/mL) | Standard Deviation 31600 |
| VX-809, 100 mg | Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of VX-809 | Day 1 (n= 18, 18, 17, 19) | 59500 hour*nanogram per milliliter (hr*ng/mL) | Standard Deviation 26400 |
| VX-809, 100 mg | Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of VX-809 | Day 28 (n= 17, 17, 16, 18) | 119000 hour*nanogram per milliliter (hr*ng/mL) | Standard Deviation 73700 |
Secondary
Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. CFQ-R domains include: Body, Digestion, Eat, Emotion, Health Perceptions, Physical, Respiratory, Role, Social, Treatment Burden, Vitality, and Weight. Individual domain score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Time frame: Baseline, Day 28
Population: FAS. Number of participants analyzed signifies participants evaluable for this outcome.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Vitality | -2.178 units on a scale |
| Placebo | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Respiratory | 4.534 units on a scale |
| Placebo | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Social | -0.554 units on a scale |
| Placebo | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Weight | 0.304 units on a scale |
| Placebo | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Emotion | 4.859 units on a scale |
| Placebo | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Physical | 1.225 units on a scale |
| Placebo | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Eat | 2.110 units on a scale |
| Placebo | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Body | -1.341 units on a scale |
| Placebo | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Digestion | 4.620 units on a scale |
| Placebo | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Health Perceptions | 5.034 units on a scale |
| Placebo | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Role | 2.210 units on a scale |
| Placebo | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Treatment Burden | 2.463 units on a scale |
| VX-809, 25 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Body | -0.206 units on a scale |
| VX-809, 25 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Vitality | -4.645 units on a scale |
| VX-809, 25 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Physical | -5.968 units on a scale |
| VX-809, 25 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Weight | 5.410 units on a scale |
| VX-809, 25 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Respiratory | -5.223 units on a scale |
| VX-809, 25 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Digestion | 2.284 units on a scale |
| VX-809, 25 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Eat | -3.662 units on a scale |
| VX-809, 25 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Treatment Burden | 4.185 units on a scale |
| VX-809, 25 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Emotion | -3.222 units on a scale |
| VX-809, 25 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Social | -0.001 units on a scale |
| VX-809, 25 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Role | -5.941 units on a scale |
| VX-809, 25 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Health Perceptions | -2.839 units on a scale |
| VX-809, 50 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Treatment Burden | -5.962 units on a scale |
| VX-809, 50 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Role | -4.599 units on a scale |
| VX-809, 50 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Digestion | -0.719 units on a scale |
| VX-809, 50 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Social | -1.013 units on a scale |
| VX-809, 50 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Eat | -7.269 units on a scale |
| VX-809, 50 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Body | -1.626 units on a scale |
| VX-809, 50 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Emotion | -1.358 units on a scale |
| VX-809, 50 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Vitality | -7.227 units on a scale |
| VX-809, 50 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Health Perceptions | -6.967 units on a scale |
| VX-809, 50 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Weight | 2.175 units on a scale |
| VX-809, 50 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Physical | -7.384 units on a scale |
| VX-809, 50 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Respiratory | -6.324 units on a scale |
| VX-809, 100 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Eat | 3.242 units on a scale |
| VX-809, 100 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Body | 2.611 units on a scale |
| VX-809, 100 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Digestion | 0.251 units on a scale |
| VX-809, 100 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Weight | 8.827 units on a scale |
| VX-809, 100 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Emotion | 3.489 units on a scale |
| VX-809, 100 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Health Perceptions | -0.435 units on a scale |
| VX-809, 100 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Physical | -3.464 units on a scale |
| VX-809, 100 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Respiratory | -1.290 units on a scale |
| VX-809, 100 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Role | 1.097 units on a scale |
| VX-809, 100 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Social | 0.469 units on a scale |
| VX-809, 100 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Treatment Burden | 1.421 units on a scale |
| VX-809, 100 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Vitality | -1.516 units on a scale |
| VX-809, 200 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Respiratory | 2.215 units on a scale |
| VX-809, 200 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Body | 0.058 units on a scale |
| VX-809, 200 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Treatment Burden | -0.676 units on a scale |
| VX-809, 200 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Physical | -0.976 units on a scale |
| VX-809, 200 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Health Perceptions | -1.896 units on a scale |
| VX-809, 200 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Emotion | -2.624 units on a scale |
| VX-809, 200 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Weight | -4.186 units on a scale |
| VX-809, 200 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Vitality | 0.730 units on a scale |
| VX-809, 200 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Eat | -2.576 units on a scale |
| VX-809, 200 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Digestion | 2.578 units on a scale |
| VX-809, 200 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Social | -2.640 units on a scale |
| VX-809, 200 mg | Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 | Role | -6.533 units on a scale |
Secondary
Change From Baseline in Forced Expiratory Flow Over the Middle Half of the FVC (FEF25-75) at Day 28
FEF25-75 is total volume of air exhaled from the lungs over the middle half of the FVC test, expressed as liters per second (L/sec).
Time frame: Baseline, Day 28
Population: FAS. Number of participants analyzed signifies participants evaluable for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Forced Expiratory Flow Over the Middle Half of the FVC (FEF25-75) at Day 28 | -0.030 liters per second (L/sec) | Standard Deviation 0.173 |
| VX-809, 25 mg | Change From Baseline in Forced Expiratory Flow Over the Middle Half of the FVC (FEF25-75) at Day 28 | -0.011 liters per second (L/sec) | Standard Deviation 0.3231 |
| VX-809, 50 mg | Change From Baseline in Forced Expiratory Flow Over the Middle Half of the FVC (FEF25-75) at Day 28 | -0.029 liters per second (L/sec) | Standard Deviation 0.4373 |
| VX-809, 100 mg | Change From Baseline in Forced Expiratory Flow Over the Middle Half of the FVC (FEF25-75) at Day 28 | 0.045 liters per second (L/sec) | Standard Deviation 0.2702 |
| VX-809, 200 mg | Change From Baseline in Forced Expiratory Flow Over the Middle Half of the FVC (FEF25-75) at Day 28 | -0.052 liters per second (L/sec) | Standard Deviation 0.3558 |
Secondary
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Day 28
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time frame: Baseline, Day 28
Population: Full Analysis Set (FAS) included all randomized participants who received at least 1 dose of study drug. Number of participants analyzed signifies participants evaluable for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Day 28 | 0.029 liters |
| VX-809, 25 mg | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Day 28 | -0.049 liters |
| VX-809, 50 mg | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Day 28 | -0.031 liters |
| VX-809, 100 mg | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Day 28 | 0.015 liters |
| VX-809, 200 mg | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Day 28 | -0.009 liters |
Secondary
Change From Baseline in Forced Vital Capacity (FVC) at Day 28
FVC is the volume of air that can be forcibly exhaled from the lungs after taking the deepest breath possible.
Time frame: Baseline, Day 28
Population: FAS. Number of participants analyzed signifies participants evaluable for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) at Day 28 | 0.085 liters | Standard Deviation 0.2857 |
| VX-809, 25 mg | Change From Baseline in Forced Vital Capacity (FVC) at Day 28 | -0.055 liters | Standard Deviation 0.2331 |
| VX-809, 50 mg | Change From Baseline in Forced Vital Capacity (FVC) at Day 28 | -0.020 liters | Standard Deviation 0.3494 |
| VX-809, 100 mg | Change From Baseline in Forced Vital Capacity (FVC) at Day 28 | -0.004 liters | Standard Deviation 0.1916 |
| VX-809, 200 mg | Change From Baseline in Forced Vital Capacity (FVC) at Day 28 | -0.023 liters | Standard Deviation 0.3668 |
Secondary
Change From Baseline in Nasal Potential Difference (NPD) of Zero Chloride Plus Isoproterenol Response at Day 28
Nasal potential difference (NPD) provides a direct and sensitive evaluation of sodium and chloride transport in secretory epithelial cells via assessment of transepithelial bioelectric properties. NPD under conditions of zero chloride concentration perfusion solution in the presence of isoproterenol is reported. NPDs were performed according to Cystic Fibrosis Foundation Therapeutics Development Network (CFFT TDN) Standard Operating Procedure (SOP) 528.00 Standardization of Measurement of Nasal Membrane Transepithelial Potential Difference (NPD) - electronic data capture (EDC) and Perfusion or Perfusion-Free Probe.
Time frame: Baseline, Day 28
Population: FAS. Number of participants analyzed signifies participants evaluable for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline in Nasal Potential Difference (NPD) of Zero Chloride Plus Isoproterenol Response at Day 28 | -1.017 millivolts (mV) |
| VX-809, 25 mg | Change From Baseline in Nasal Potential Difference (NPD) of Zero Chloride Plus Isoproterenol Response at Day 28 | 0.832 millivolts (mV) |
| VX-809, 50 mg | Change From Baseline in Nasal Potential Difference (NPD) of Zero Chloride Plus Isoproterenol Response at Day 28 | 0.142 millivolts (mV) |
| VX-809, 100 mg | Change From Baseline in Nasal Potential Difference (NPD) of Zero Chloride Plus Isoproterenol Response at Day 28 | 1.382 millivolts (mV) |
| VX-809, 200 mg | Change From Baseline in Nasal Potential Difference (NPD) of Zero Chloride Plus Isoproterenol Response at Day 28 | 1.583 millivolts (mV) |
Secondary
Change From Baseline in Percent Predicted FEV1 at Day 28
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Predicted FEV1 (for age, gender, and height) was calculated using the Knudson method.
Time frame: Baseline, Day 28
Population: FAS. Number of participants analyzed signifies participants evaluable for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline in Percent Predicted FEV1 at Day 28 | 0.285 Percent predicted of FEV1 |
| VX-809, 25 mg | Change From Baseline in Percent Predicted FEV1 at Day 28 | -1.637 Percent predicted of FEV1 |
| VX-809, 50 mg | Change From Baseline in Percent Predicted FEV1 at Day 28 | -0.375 Percent predicted of FEV1 |
| VX-809, 100 mg | Change From Baseline in Percent Predicted FEV1 at Day 28 | 0.168 Percent predicted of FEV1 |
| VX-809, 200 mg | Change From Baseline in Percent Predicted FEV1 at Day 28 | -0.165 Percent predicted of FEV1 |
Secondary
Change From Baseline in Sweat Chloride at Day 28
Sweat samples were collected using an approved Macroduct (Wescor) collection device. A volume of greater than or equal to (\>=) 15 microliter was required for determination of sweat chloride.
Time frame: Baseline, Day 28
Population: FAS. Number of participants analyzed signifies participants evaluable for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline in Sweat Chloride at Day 28 | 0.84 millimole per liter (mmol/L) |
| VX-809, 25 mg | Change From Baseline in Sweat Chloride at Day 28 | 0.93 millimole per liter (mmol/L) |
| VX-809, 50 mg | Change From Baseline in Sweat Chloride at Day 28 | -3.77 millimole per liter (mmol/L) |
| VX-809, 100 mg | Change From Baseline in Sweat Chloride at Day 28 | -5.29 millimole per liter (mmol/L) |
| VX-809, 200 mg | Change From Baseline in Sweat Chloride at Day 28 | -7.38 millimole per liter (mmol/L) |
Secondary
Maximum Plasma Concentration (Cmax) of VX-809
Only participants who received VX-809 were analyzed for this outcome measure.
Time frame: Day 1 (pre dose, 0.75, 1.5, 3, 4, 6, 9, 12, and 24 hours post-dose), Day 28 (pre dose, 0.75, 1.5, 3, 4, 6, 9, 12, 24, and 30-60 hours post dose)
Population: FAS. Here, n = participants evaluable for specified category for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Maximum Plasma Concentration (Cmax) of VX-809 | Day 1 (n= 18, 18, 17, 19) | 760 nanogram per milliliter (ng/mL) | Standard Deviation 280 |
| Placebo | Maximum Plasma Concentration (Cmax) of VX-809 | Day 28 (n= 17, 17, 16, 18) | 1100 nanogram per milliliter (ng/mL) | Standard Deviation 443 |
| VX-809, 25 mg | Maximum Plasma Concentration (Cmax) of VX-809 | Day 28 (n= 17, 17, 16, 18) | 2660 nanogram per milliliter (ng/mL) | Standard Deviation 1010 |
| VX-809, 25 mg | Maximum Plasma Concentration (Cmax) of VX-809 | Day 1 (n= 18, 18, 17, 19) | 1850 nanogram per milliliter (ng/mL) | Standard Deviation 697 |
| VX-809, 50 mg | Maximum Plasma Concentration (Cmax) of VX-809 | Day 1 (n= 18, 18, 17, 19) | 2930 nanogram per milliliter (ng/mL) | Standard Deviation 916 |
| VX-809, 50 mg | Maximum Plasma Concentration (Cmax) of VX-809 | Day 28 (n= 17, 17, 16, 18) | 4620 nanogram per milliliter (ng/mL) | Standard Deviation 1840 |
| VX-809, 100 mg | Maximum Plasma Concentration (Cmax) of VX-809 | Day 1 (n= 18, 18, 17, 19) | 6410 nanogram per milliliter (ng/mL) | Standard Deviation 2550 |
| VX-809, 100 mg | Maximum Plasma Concentration (Cmax) of VX-809 | Day 28 (n= 17, 17, 16, 18) | 10300 nanogram per milliliter (ng/mL) | Standard Deviation 4490 |