Cystic Fibrosis
Conditions
Brief summary
This is a first-in-human and proof-of-concept study of VX-445. The study includes 6 parts. Parts A, B, and C were conducted in healthy subjects. Parts D, E, and F were conducted in subjects with Cystic Fibrosis (CF) who are homozygous for the F508del mutation of the CF transmembrane conductance regulator (CFTR) gene (F/F genotype), or who are heterozygous for the F508del mutation and a minimal function (MF) CFTR mutation not likely to respond to TEZ, IVA, or TEZ/IVA (F/MF genotypes).
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
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: Parts A, B, and C: * Female subjects must be of non-childbearing potential. * Between the ages of 18 and 55 years, inclusive. * Body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive, and a total body weight \>50 kg Parts D, E, and F: * Body weight ≥35 kg. * Subjects must have an eligible CFTR genotype: * Parts D and F: Heterozygous for F508del and an MF mutation (F/MF) * Part E: Homozygous for F508del (F/F) * FEV1 value ≥40% and ≤90% of predicted mean for age, sex, and height. Key
Exclusion criteria
Parts A, B, and C: * Any condition possibly affecting drug absorption. * History of febrile illness within 14 days before the first study drug dose. * Glucose-6-phosphate dehydrogenase (G6PD) deficiency. Parts D, E, and F: * History of clinically significant cirrhosis with or without portal hypertension. * Glucose-6-phosphate dehydrogenase (G6PD) deficiency. * Lung infection with organisms associated with a more rapid decline in pulmonary status. * History of solid organ or hematological transplantation. Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Parts A, B and C: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | From first dose of study drug in treatment period up to safety follow-up (up to 28 days) | — |
| Parts D, E and F: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | From first dose of study drug in TC treatment period up to 28 days after last dose of study drug (up to 5 weeks) | — |
| Part D: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | From Baseline through Day 29 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. |
| Part E: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | From Baseline through Day 29 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. |
| Part F: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | From Baseline through Day 29 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | Pre-dose to 96 hours post-dose on Day 1, Day 7 and Day 14 | — |
| Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | Pre-dose to 96 hours post-dose on Day 1, Day 7 and Day 14 | — |
| Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA) | Pre-dose to 96 hours post-dose on Day 1, Day 7 and Day 14 | — |
| Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of IVA and Its Metabolites (M1-IVA and M6-IVA) | Pre-dose to 96 hours post-dose on Day 1, Day 7 and Day 14 | — |
| Part C: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | Pre-dose on Day 7 and Day 14 | — |
| Part C: Observed Pre-dose Concentration (Ctrough) of IVA and Its Metabolites (M1-IVA and M6-IVA) | Pre-dose on Day 7 and Day 14 | — |
| Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA) | Pre-dose on Day 15 and Day 29 | — |
| Part E: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and IVA and Its Metabolite (M1-IVA) | Pre-dose on Day 15 and Day 29 | — |
| Part F: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and VX-561 | Pre-dose on Day 15 and Day 29 | — |
| Part A: Maximum Observed Concentration (Cmax) of VX-445 | Cohort A1-A5: Pre-dose to 96 hours post-dose; Cohort A7: Pre-dose to 120 hours post-dose | — |
| Part E: Absolute Change in Sweat Chloride Concentration | From Baseline through Day 29 | Sweat samples were collected using an approved collection device. |
| Part F: Absolute Change in Sweat Chloride Concentration | From Baseline through Day 29 | Sweat samples were collected using an approved collection device. |
| Part D: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | From Baseline through Day 29 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. |
| Part E: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | From Baseline through Day 29 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. |
| Part F: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | From Baseline through Day 29 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. |
| Part D: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score | From Baseline through Day 29 | The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. |
| Part E: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score | From Baseline through Day 29 | The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. |
| Part F: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score | From Baseline through Day 29 | The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. |
| Part D: Absolute Change in Sweat Chloride Concentration | From Baseline through Day 29 | Sweat samples were collected using an approved collection device. |
| Part A: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445 | Cohort A1-5: Pre-dose to 96 hours post-dose; Cohort A7: Pre-dose to 120 hours post-dose | — |
| Part B: Maximum Observed Concentration (Cmax) of VX-445 | Pre-dose to 96 hours post-dose on Day 1 and Day 10 | — |
| Part B: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445 | Pre-dose to 96 hours post-dose on Day 1 and Day 10 | — |
| Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445 | Pre-dose on Day 10 | — |
Countries
Australia, Belgium, Netherlands, United States
Participant flow
Pre-assignment details
This study included 6 parts: Parts A, B, and C were conducted in healthy adult participants; Part D, E, and F were conducted in adult cystic fibrosis (CF) participants.
Participants by arm
| Arm | Count |
|---|---|
| Part A: Pooled Placebo (Except Cohort A7) Participants without CF who received single dose of placebo matched to VX-445 in Cohort A1 to A5. | 9 |
| Part A: VX-445 (Except Cohort A7) Participants without CF who received single ascending dose of VX-445 tablet starting from 20 mg to 360 mg in Cohort A1 to A5. | 30 |
| Part A: VX-445 (Cohort A7) Participants without CF who received single dose of VX-445 100 mg tablet on Day 1 in fasted state and on Day 7 in fed state, followed by VX-445 20 mg IV injection on Day 13 in fed state in Cohort A7. | 8 |
| Part B: Pooled Placebo (Cohort B1 to B4) Participants without CF who received multiple doses of placebo matched to VX-445 qd for 10 days in Cohort B1 to B4. | 7 |
| Part B: VX-445 (Cohort B1 to B4) Participants without CF who received VX-445 tablet once daily for 10 days in Cohort B1 (60 mg), B2 (120 mg), B3 (240 mg) and B4 (340 mg). | 25 |
| Part C: Pooled Placebo (Cohort C1 to C3) Participants without CF who received placebo matched to VX-445/TEZ/IVA TC qd in the morning and placebo matched to IVA in the evening for 14 days. | 6 |
| Part C: VX-445/TEZ/IVA TC (Cohort C1 to C3) Participants without CF who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C1; VX-445 280 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C2 and VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C3 for 14 days. | 17 |
| Part D: Placebo Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/IVA TC qd in the morning and placebo matched to IVA in the evening for 4 weeks in the TC treatment period. | 12 |
| Part D: VX-445/TEZ/IVA TC - Low Dose Participants with CF, F/MF genotype who received VX-445 50 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period. | 10 |
| Part D: VX-445/TEZ/IVA TC - Medium Dose Participants with CF, F/MF genotype who received VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period. | 22 |
| Part D: VX-445/TEZ/IVA TC - High Dose Participants with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period. | 21 |
| Part E: TEZ/IVA Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received TEZ 100 mg qd/IVA 150 mg q12h and placebo matched to VX-445 for 4 weeks in the TC treatment period. | 7 |
| Part E: VX-445/TEZ/IVA TC Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period. | 21 |
| Part F: Placebo Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/VX-561 for 4 weeks in the TC treatment period. | 8 |
| Part F: VX-445/TEZ/VX-561 TC Participants with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/VX-561 150 mg qd for 4 weeks in the TC treatment period. | 21 |
| Total | 224 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Randomized, Never Dosed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Part A: VX-445 (Except Cohort A7) | Part A: VX-445 (Cohort A7) | Part B: Pooled Placebo (Cohort B1 to B4) | Part B: VX-445 (Cohort B1 to B4) | Part A: Pooled Placebo (Except Cohort A7) | Part C: Pooled Placebo (Cohort C1 to C3) | Part C: VX-445/TEZ/IVA TC (Cohort C1 to C3) | Part D: Placebo | Part D: VX-445/TEZ/IVA TC - Low Dose | Part D: VX-445/TEZ/IVA TC - Medium Dose | Part D: VX-445/TEZ/IVA TC - High Dose | Part E: TEZ/IVA | Part E: VX-445/TEZ/IVA TC | Part F: Placebo | Part F: VX-445/TEZ/VX-561 TC |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 224 Participants | 30 Participants | 8 Participants | 7 Participants | 25 Participants | 9 Participants | 6 Participants | 17 Participants | 12 Participants | 10 Participants | 22 Participants | 21 Participants | 7 Participants | 21 Participants | 8 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 2 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 5 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 210 Participants | 28 Participants | 6 Participants | 7 Participants | 24 Participants | 9 Participants | 5 Participants | 12 Participants | 12 Participants | 10 Participants | 22 Participants | 20 Participants | 7 Participants | 20 Participants | 8 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 42 Participants | 16 Participants | 4 Participants | 3 Participants | 9 Participants | 4 Participants | 4 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 178 Participants | 14 Participants | 4 Participants | 2 Participants | 16 Participants | 5 Participants | 2 Participants | 16 Participants | 12 Participants | 8 Participants | 22 Participants | 21 Participants | 7 Participants | 21 Participants | 8 Participants | 20 Participants |
| Sex: Female, Male Female | 58 Participants | 2 Participants | 0 Participants | 0 Participants | 3 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants | 6 Participants | 7 Participants | 11 Participants | 1 Participants | 9 Participants | 5 Participants | 10 Participants |
| Sex: Female, Male Male | 166 Participants | 28 Participants | 8 Participants | 7 Participants | 22 Participants | 7 Participants | 6 Participants | 17 Participants | 10 Participants | 4 Participants | 15 Participants | 10 Participants | 6 Participants | 12 Participants | 3 Participants | 11 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 | EG013 affected / at risk | EG014 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 30 | 0 / 8 | 0 / 7 | 0 / 25 | 0 / 6 | 0 / 17 | 0 / 12 | 0 / 10 | 0 / 22 | 0 / 21 | 0 / 7 | 0 / 21 | 0 / 8 | 0 / 21 |
| other Total, other adverse events | 0 / 9 | 3 / 30 | 1 / 8 | 2 / 7 | 2 / 25 | 2 / 6 | 5 / 17 | 12 / 12 | 10 / 10 | 19 / 22 | 17 / 21 | 5 / 7 | 18 / 21 | 7 / 8 | 17 / 21 |
| serious Total, serious adverse events | 0 / 9 | 0 / 30 | 0 / 8 | 0 / 7 | 0 / 25 | 0 / 6 | 0 / 17 | 2 / 12 | 1 / 10 | 2 / 22 | 0 / 21 | 1 / 7 | 0 / 21 | 1 / 8 | 0 / 21 |
Outcome results
Primary
Part D: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time frame: From Baseline through Day 29
Population: The full analysis set (FAS) included all randomized participants who carry the intended CFTR allele mutation and have received at least 1 dose of study drug in the TC treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo (Except Cohort A7) | Part D: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | 0.0 percentage points | Standard Error 2 |
| Part A: VX-445 (Except Cohort A7) | Part D: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | 11.1 percentage points | Standard Error 2.1 |
| Part A: VX-445 (Cohort A7) | Part D: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | 7.9 percentage points | Standard Error 1.4 |
| Part B: Pooled Placebo (Cohort B1 to B4) | Part D: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | 13.8 percentage points | Standard Error 1.4 |
p-value: 0.9943Mixed-effects model for repeated measure
p-value: <0.0001Mixed-effects model for repeated measure
p-value: <0.0001Mixed-effects model for repeated measure
p-value: <0.0001Mixed-effects model for repeated measure
Primary
Part E: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time frame: From Baseline through Day 29
Population: FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo (Except Cohort A7) | Part E: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | 0.4 percentage points | Standard Error 2.8 |
| Part A: VX-445 (Except Cohort A7) | Part E: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | 11.0 percentage points | Standard Error 1.5 |
p-value: 0.8869Mixed-effects model for repeated measure
p-value: <0.0001Mixed-effects model for repeated measure
Primary
Part F: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time frame: From Baseline through Day 29
Population: FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo (Except Cohort A7) | Part F: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | 1.2 percentage points | Standard Error 2.6 |
| Part A: VX-445 (Except Cohort A7) | Part F: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | 11.7 percentage points | Standard Error 1.6 |
p-value: 0.6407Mixed-effects model for repeated measure
p-value: <0.0001mixed-effects model for repeated measure
Primary
Parts A, B and C: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: From first dose of study drug in treatment period up to safety follow-up (up to 28 days)
Population: Safety Set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Pooled Placebo (Except Cohort A7) | Parts A, B and C: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 0 Participants |
| Part A: Pooled Placebo (Except Cohort A7) | Parts A, B and C: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 Participants |
| Part A: VX-445 (Except Cohort A7) | Parts A, B and C: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 3 Participants |
| Part A: VX-445 (Except Cohort A7) | Parts A, B and C: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 Participants |
| Part A: VX-445 (Cohort A7) | Parts A, B and C: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 1 Participants |
| Part A: VX-445 (Cohort A7) | Parts A, B and C: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 Participants |
| Part B: Pooled Placebo (Cohort B1 to B4) | Parts A, B and C: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 2 Participants |
| Part B: Pooled Placebo (Cohort B1 to B4) | Parts A, B and C: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 Participants |
| Part B: VX-445 (Cohort B1 to B4) | Parts A, B and C: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 2 Participants |
| Part B: VX-445 (Cohort B1 to B4) | Parts A, B and C: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 Participants |
| Part C: Pooled Placebo (Cohort C1 to C3) | Parts A, B and C: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 2 Participants |
| Part C: Pooled Placebo (Cohort C1 to C3) | Parts A, B and C: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 Participants |
| Part C: VX-445/TEZ/IVA TC (Cohort C1 to C3) | Parts A, B and C: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 5 Participants |
| Part C: VX-445/TEZ/IVA TC (Cohort C1 to C3) | Parts A, B and C: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 Participants |
Primary
Parts D, E and F: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: From first dose of study drug in TC treatment period up to 28 days after last dose of study drug (up to 5 weeks)
Population: The Safety Set will include all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Pooled Placebo (Except Cohort A7) | Parts D, E and F: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 12 Participants |
| Part A: Pooled Placebo (Except Cohort A7) | Parts D, E and F: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 2 Participants |
| Part A: VX-445 (Except Cohort A7) | Parts D, E and F: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 49 Participants |
| Part A: VX-445 (Except Cohort A7) | Parts D, E and F: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 3 Participants |
| Part A: VX-445 (Cohort A7) | Parts D, E and F: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 5 Participants |
| Part A: VX-445 (Cohort A7) | Parts D, E and F: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 1 Participants |
| Part B: Pooled Placebo (Cohort B1 to B4) | Parts D, E and F: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 19 Participants |
| Part B: Pooled Placebo (Cohort B1 to B4) | Parts D, E and F: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 Participants |
| Part B: VX-445 (Cohort B1 to B4) | Parts D, E and F: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 7 Participants |
| Part B: VX-445 (Cohort B1 to B4) | Parts D, E and F: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 1 Participants |
| Part C: Pooled Placebo (Cohort C1 to C3) | Parts D, E and F: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 19 Participants |
| Part C: Pooled Placebo (Cohort C1 to C3) | Parts D, E and F: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 Participants |
Secondary
Part A: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445
Time frame: Cohort A1-5: Pre-dose to 96 hours post-dose; Cohort A7: Pre-dose to 120 hours post-dose
Population: The Pharmacokinetic Set.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo (Except Cohort A7) | Part A: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445 | 11.4 microgram*hour per milliliter | Geometric Coefficient of Variation 34.2 |
| Part A: VX-445 (Except Cohort A7) | Part A: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445 | 30.8 microgram*hour per milliliter | Geometric Coefficient of Variation 21.2 |
| Part A: VX-445 (Cohort A7) | Part A: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445 | 87.1 microgram*hour per milliliter | Geometric Coefficient of Variation 39.9 |
| Part B: Pooled Placebo (Cohort B1 to B4) | Part A: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445 | 125 microgram*hour per milliliter | Geometric Coefficient of Variation 34.2 |
| Part B: VX-445 (Cohort B1 to B4) | Part A: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445 | 286 microgram*hour per milliliter | Geometric Coefficient of Variation 9.3 |
| Part C: Pooled Placebo (Cohort C1 to C3) | Part A: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445 | 21.8 microgram*hour per milliliter | Geometric Coefficient of Variation 31.5 |
| Part C: VX-445/TEZ/IVA TC (Cohort C1 to C3) | Part A: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445 | 55.1 microgram*hour per milliliter | Geometric Coefficient of Variation 14.9 |
| Part A: VX-445 (Cohort A7-IV) | Part A: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445 | 13.6 microgram*hour per milliliter | Geometric Coefficient of Variation 19.7 |
Secondary
Part A: Maximum Observed Concentration (Cmax) of VX-445
Time frame: Cohort A1-A5: Pre-dose to 96 hours post-dose; Cohort A7: Pre-dose to 120 hours post-dose
Population: The Pharmacokinetic Set included all participants who received at least 1 dose of study drug and for whom the primary PK data are considered sufficient and interpretable.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo (Except Cohort A7) | Part A: Maximum Observed Concentration (Cmax) of VX-445 | 0.398 microgram per milliliter | Geometric Coefficient of Variation 23 |
| Part A: VX-445 (Except Cohort A7) | Part A: Maximum Observed Concentration (Cmax) of VX-445 | 0.989 microgram per milliliter | Geometric Coefficient of Variation 35.1 |
| Part A: VX-445 (Cohort A7) | Part A: Maximum Observed Concentration (Cmax) of VX-445 | 2.52 microgram per milliliter | Geometric Coefficient of Variation 13 |
| Part B: Pooled Placebo (Cohort B1 to B4) | Part A: Maximum Observed Concentration (Cmax) of VX-445 | 4.56 microgram per milliliter | Geometric Coefficient of Variation 28.2 |
| Part B: VX-445 (Cohort B1 to B4) | Part A: Maximum Observed Concentration (Cmax) of VX-445 | 7.07 microgram per milliliter | Geometric Coefficient of Variation 19.1 |
| Part C: Pooled Placebo (Cohort C1 to C3) | Part A: Maximum Observed Concentration (Cmax) of VX-445 | 0.486 microgram per milliliter | Geometric Coefficient of Variation 27.4 |
| Part C: VX-445/TEZ/IVA TC (Cohort C1 to C3) | Part A: Maximum Observed Concentration (Cmax) of VX-445 | 1.76 microgram per milliliter | Geometric Coefficient of Variation 14.6 |
| Part A: VX-445 (Cohort A7-IV) | Part A: Maximum Observed Concentration (Cmax) of VX-445 | 0.740 microgram per milliliter | Geometric Coefficient of Variation 27.1 |
Secondary
Part B: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445
Time frame: Pre-dose to 96 hours post-dose on Day 1 and Day 10
Population: The Pharmacokinetic Set. Here Number analyzed signifies those participants who were evaluated for this outcome measure at specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Pooled Placebo (Except Cohort A7) | Part B: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445 | Day 1 | 17.9 microgram*hour per milliliter | Geometric Coefficient of Variation 20 |
| Part A: Pooled Placebo (Except Cohort A7) | Part B: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445 | Day 10 | 61.4 microgram*hour per milliliter | Geometric Coefficient of Variation 21.8 |
| Part A: VX-445 (Except Cohort A7) | Part B: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445 | Day 10 | 183 microgram*hour per milliliter | Geometric Coefficient of Variation 32.7 |
| Part A: VX-445 (Except Cohort A7) | Part B: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445 | Day 1 | 42.2 microgram*hour per milliliter | Geometric Coefficient of Variation 19.5 |
| Part A: VX-445 (Cohort A7) | Part B: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445 | Day 1 | 57.9 microgram*hour per milliliter | Geometric Coefficient of Variation 42.8 |
| Part A: VX-445 (Cohort A7) | Part B: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445 | Day 10 | 452 microgram*hour per milliliter | Geometric Coefficient of Variation 41.5 |
| Part B: Pooled Placebo (Cohort B1 to B4) | Part B: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445 | Day 1 | 119 microgram*hour per milliliter | Geometric Coefficient of Variation 27.5 |
| Part B: Pooled Placebo (Cohort B1 to B4) | Part B: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445 | Day 10 | 692 microgram*hour per milliliter | Geometric Coefficient of Variation 47.6 |
Secondary
Part B: Maximum Observed Concentration (Cmax) of VX-445
Time frame: Pre-dose to 96 hours post-dose on Day 1 and Day 10
Population: The Pharmacokinetic Set.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Pooled Placebo (Except Cohort A7) | Part B: Maximum Observed Concentration (Cmax) of VX-445 | Day 1 | 1.18 microgram per milliliter | Geometric Coefficient of Variation 19.9 |
| Part A: Pooled Placebo (Except Cohort A7) | Part B: Maximum Observed Concentration (Cmax) of VX-445 | Day 10 | 2.13 microgram per milliliter | Geometric Coefficient of Variation 15 |
| Part A: VX-445 (Except Cohort A7) | Part B: Maximum Observed Concentration (Cmax) of VX-445 | Day 10 | 5.83 microgram per milliliter | Geometric Coefficient of Variation 28.1 |
| Part A: VX-445 (Except Cohort A7) | Part B: Maximum Observed Concentration (Cmax) of VX-445 | Day 1 | 2.82 microgram per milliliter | Geometric Coefficient of Variation 25.5 |
| Part A: VX-445 (Cohort A7) | Part B: Maximum Observed Concentration (Cmax) of VX-445 | Day 1 | 3.47 microgram per milliliter | Geometric Coefficient of Variation 52.9 |
| Part A: VX-445 (Cohort A7) | Part B: Maximum Observed Concentration (Cmax) of VX-445 | Day 10 | 11.4 microgram per milliliter | Geometric Coefficient of Variation 27.2 |
| Part B: Pooled Placebo (Cohort B1 to B4) | Part B: Maximum Observed Concentration (Cmax) of VX-445 | Day 1 | 9.56 microgram per milliliter | Geometric Coefficient of Variation 65.6 |
| Part B: Pooled Placebo (Cohort B1 to B4) | Part B: Maximum Observed Concentration (Cmax) of VX-445 | Day 10 | 18.2 microgram per milliliter | Geometric Coefficient of Variation 29.5 |
Secondary
Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445
Time frame: Pre-dose on Day 10
Population: The Pharmacokinetic Set.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo (Except Cohort A7) | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445 | 1.05 microgram per milliliter | Geometric Coefficient of Variation 24.5 |
| Part A: VX-445 (Except Cohort A7) | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445 | 2.81 microgram per milliliter | Geometric Coefficient of Variation 33.2 |
| Part A: VX-445 (Cohort A7) | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445 | 7.10 microgram per milliliter | Geometric Coefficient of Variation 30.1 |
| Part B: Pooled Placebo (Cohort B1 to B4) | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445 | 11.5 microgram per milliliter | Geometric Coefficient of Variation 32 |
Secondary
Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of IVA and Its Metabolites (M1-IVA and M6-IVA)
Time frame: Pre-dose to 96 hours post-dose on Day 1, Day 7 and Day 14
Population: The Pharmacokinetic Set. Here Number analyzed signified those subjects who were evaluated at specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 7 | 47500 nanogram*hour per milliliter | Geometric Coefficient of Variation 43.6 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 1 | 16900 nanogram*hour per milliliter | Geometric Coefficient of Variation 38.9 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 7 | 21600 nanogram*hour per milliliter | Geometric Coefficient of Variation 65.6 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 1 | 6350 nanogram*hour per milliliter | Geometric Coefficient of Variation 40.9 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 14 | 27900 nanogram*hour per milliliter | Geometric Coefficient of Variation 48.7 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 7 | 39700 nanogram*hour per milliliter | Geometric Coefficient of Variation 38.8 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 14 | 75300 nanogram*hour per milliliter | Geometric Coefficient of Variation 42.7 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 14 | 66300 nanogram*hour per milliliter | Geometric Coefficient of Variation 44.9 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 1 | 11100 nanogram*hour per milliliter | Geometric Coefficient of Variation 49.9 |
| Part A: VX-445 (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 14 | 123000 nanogram*hour per milliliter | Geometric Coefficient of Variation 23.1 |
| Part A: VX-445 (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 7 | 46300 nanogram*hour per milliliter | Geometric Coefficient of Variation 30.6 |
| Part A: VX-445 (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 14 | 97000 nanogram*hour per milliliter | Geometric Coefficient of Variation 31.3 |
| Part A: VX-445 (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 1 | 6210 nanogram*hour per milliliter | Geometric Coefficient of Variation 45.5 |
| Part A: VX-445 (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 7 | 18800 nanogram*hour per milliliter | Geometric Coefficient of Variation 50.7 |
| Part A: VX-445 (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 14 | 35000 nanogram*hour per milliliter | Geometric Coefficient of Variation 44.8 |
| Part A: VX-445 (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 1 | 14800 nanogram*hour per milliliter | Geometric Coefficient of Variation 32.3 |
| Part A: VX-445 (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 1 | 14100 nanogram*hour per milliliter | Geometric Coefficient of Variation 20.3 |
| Part A: VX-445 (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 7 | 51400 nanogram*hour per milliliter | Geometric Coefficient of Variation 13 |
| Part A: VX-445 (Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 14 | 86100 nanogram*hour per milliliter | Geometric Coefficient of Variation 30.2 |
| Part A: VX-445 (Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 14 | 67100 nanogram*hour per milliliter | Geometric Coefficient of Variation 42.3 |
| Part A: VX-445 (Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 1 | 13300 nanogram*hour per milliliter | Geometric Coefficient of Variation 21.1 |
| Part A: VX-445 (Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 1 | 9050 nanogram*hour per milliliter | Geometric Coefficient of Variation 26.1 |
| Part A: VX-445 (Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 7 | 36400 nanogram*hour per milliliter | Geometric Coefficient of Variation 25.9 |
| Part A: VX-445 (Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 7 | 16900 nanogram*hour per milliliter | Geometric Coefficient of Variation 28.4 |
| Part A: VX-445 (Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 14 | 32600 nanogram*hour per milliliter | Geometric Coefficient of Variation 40.6 |
| Part A: VX-445 (Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 1 | 5480 nanogram*hour per milliliter | Geometric Coefficient of Variation 28.5 |
| Part A: VX-445 (Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 7 | 29100 nanogram*hour per milliliter | Geometric Coefficient of Variation 36 |
Secondary
Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ)
Time frame: Pre-dose to 96 hours post-dose on Day 1, Day 7 and Day 14
Population: The Pharmacokinetic Set. Here Number analyzed signified those subjects who were evaluated at specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | VX-445: Day 14 | 345 microgram*hour per milliliter | Geometric Coefficient of Variation 30.7 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M2-TEZ: Day 1 | 6.65 microgram*hour per milliliter | Geometric Coefficient of Variation 48.6 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M2-TEZ: Day 7 | 108 microgram*hour per milliliter | Geometric Coefficient of Variation 31.2 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | VX-445: Day 7 | 156 microgram*hour per milliliter | Geometric Coefficient of Variation 37.1 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M2-TEZ: Day 14 | 617 microgram*hour per milliliter | Geometric Coefficient of Variation 23.2 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | TEZ: Day 14 | 252 microgram*hour per milliliter | Geometric Coefficient of Variation 35.1 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | VX-445: Day 1 | 48.6 microgram*hour per milliliter | Geometric Coefficient of Variation 22.7 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M1-TEZ: Day 7 | 90.9 microgram*hour per milliliter | Geometric Coefficient of Variation 29.9 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | TEZ: Day 7 | 103 microgram*hour per milliliter | Geometric Coefficient of Variation 35.8 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | TEZ: Day 1 | 41.4 microgram*hour per milliliter | Geometric Coefficient of Variation 27.5 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M1-TEZ: Day 14 | 380 microgram*hour per milliliter | Geometric Coefficient of Variation 22.1 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M1-TEZ: Day 1 | 17.7 microgram*hour per milliliter | Geometric Coefficient of Variation 37.2 |
| Part A: VX-445 (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | VX-445: Day 14 | 506 microgram*hour per milliliter | Geometric Coefficient of Variation 31.5 |
| Part A: VX-445 (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M2-TEZ: Day 7 | 143 microgram*hour per milliliter | Geometric Coefficient of Variation 34.1 |
| Part A: VX-445 (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M1-TEZ: Day 1 | 20.1 microgram*hour per milliliter | Geometric Coefficient of Variation 35.2 |
| Part A: VX-445 (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M1-TEZ: Day 7 | 110 microgram*hour per milliliter | Geometric Coefficient of Variation 17.8 |
| Part A: VX-445 (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M1-TEZ: Day 14 | 477 microgram*hour per milliliter | Geometric Coefficient of Variation 16 |
| Part A: VX-445 (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M2-TEZ: Day 1 | 8.19 microgram*hour per milliliter | Geometric Coefficient of Variation 52.5 |
| Part A: VX-445 (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M2-TEZ: Day 14 | 831 microgram*hour per milliliter | Geometric Coefficient of Variation 29.5 |
| Part A: VX-445 (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | VX-445: Day 1 | 72.5 microgram*hour per milliliter | Geometric Coefficient of Variation 20.7 |
| Part A: VX-445 (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | VX-445: Day 7 | 177 microgram*hour per milliliter | Geometric Coefficient of Variation 30 |
| Part A: VX-445 (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | TEZ: Day 1 | 43.8 microgram*hour per milliliter | Geometric Coefficient of Variation 9.91 |
| Part A: VX-445 (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | TEZ: Day 7 | 105 microgram*hour per milliliter | Geometric Coefficient of Variation 16.5 |
| Part A: VX-445 (Except Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | TEZ: Day 14 | 288 microgram*hour per milliliter | Geometric Coefficient of Variation 13.6 |
| Part A: VX-445 (Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | VX-445: Day 7 | 65.4 microgram*hour per milliliter | Geometric Coefficient of Variation 20.7 |
| Part A: VX-445 (Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M1-TEZ: Day 14 | 512 microgram*hour per milliliter | Geometric Coefficient of Variation 17.9 |
| Part A: VX-445 (Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | VX-445: Day 14 | 183 microgram*hour per milliliter | Geometric Coefficient of Variation 18.8 |
| Part A: VX-445 (Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M1-TEZ: Day 7 | 125 microgram*hour per milliliter | Geometric Coefficient of Variation 14.1 |
| Part A: VX-445 (Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M2-TEZ: Day 7 | 123 microgram*hour per milliliter | Geometric Coefficient of Variation 28.7 |
| Part A: VX-445 (Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | TEZ: Day 1 | 42.7 microgram*hour per milliliter | Geometric Coefficient of Variation 20.9 |
| Part A: VX-445 (Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | TEZ: Day 14 | 275 microgram*hour per milliliter | Geometric Coefficient of Variation 19.5 |
| Part A: VX-445 (Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M2-TEZ: Day 14 | 652 microgram*hour per milliliter | Geometric Coefficient of Variation 31.2 |
| Part A: VX-445 (Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | TEZ: Day 7 | 96.9 microgram*hour per milliliter | Geometric Coefficient of Variation 18.9 |
| Part A: VX-445 (Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | VX-445: Day 1 | 26.4 microgram*hour per milliliter | Geometric Coefficient of Variation 13.8 |
| Part A: VX-445 (Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M2-TEZ: Day 1 | 9.00 microgram*hour per milliliter | Geometric Coefficient of Variation 16.6 |
| Part A: VX-445 (Cohort A7) | Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M1-TEZ: Day 1 | 25.5 microgram*hour per milliliter | Geometric Coefficient of Variation 19.1 |
Secondary
Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA)
Time frame: Pre-dose to 96 hours post-dose on Day 1, Day 7 and Day 14
Population: The Pharmacokinetic Set. Here Number analyzed signified those subjects who were evaluated at specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 14 | 1360 nanogram per milliliter | Geometric Coefficient of Variation 21.9 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 7 | 1960 nanogram per milliliter | Geometric Coefficient of Variation 38.1 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 7 | 2460 nanogram per milliliter | Geometric Coefficient of Variation 26.8 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 1 | 1250 nanogram per milliliter | Geometric Coefficient of Variation 29.9 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 14 | 2060 nanogram per milliliter | Geometric Coefficient of Variation 30.1 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 1 | 901 nanogram per milliliter | Geometric Coefficient of Variation 38.2 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 7 | 1290 nanogram per milliliter | Geometric Coefficient of Variation 41.1 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 1 | 425 nanogram per milliliter | Geometric Coefficient of Variation 29.8 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 14 | 2680 nanogram per milliliter | Geometric Coefficient of Variation 19.4 |
| Part A: VX-445 (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 1 | 1190 nanogram per milliliter | Geometric Coefficient of Variation 28.1 |
| Part A: VX-445 (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 14 | 3350 nanogram per milliliter | Geometric Coefficient of Variation 17.4 |
| Part A: VX-445 (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 1 | 461 nanogram per milliliter | Geometric Coefficient of Variation 49.3 |
| Part A: VX-445 (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 7 | 1190 nanogram per milliliter | Geometric Coefficient of Variation 42.4 |
| Part A: VX-445 (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 14 | 1920 nanogram per milliliter | Geometric Coefficient of Variation 33.7 |
| Part A: VX-445 (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 7 | 2590 nanogram per milliliter | Geometric Coefficient of Variation 28.1 |
| Part A: VX-445 (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 14 | 3900 nanogram per milliliter | Geometric Coefficient of Variation 21.4 |
| Part A: VX-445 (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 1 | 1180 nanogram per milliliter | Geometric Coefficient of Variation 16.6 |
| Part A: VX-445 (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 7 | 2590 nanogram per milliliter | Geometric Coefficient of Variation 7.3 |
| Part A: VX-445 (Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 7 | 1070 nanogram per milliliter | Geometric Coefficient of Variation 20 |
| Part A: VX-445 (Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 14 | 1980 nanogram per milliliter | Geometric Coefficient of Variation 34.7 |
| Part A: VX-445 (Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 14 | 2990 nanogram per milliliter | Geometric Coefficient of Variation 28.3 |
| Part A: VX-445 (Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 1 | 437 nanogram per milliliter | Geometric Coefficient of Variation 9.63 |
| Part A: VX-445 (Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 7 | 1400 nanogram per milliliter | Geometric Coefficient of Variation 29.8 |
| Part A: VX-445 (Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 1 | 1070 nanogram per milliliter | Geometric Coefficient of Variation 28.6 |
| Part A: VX-445 (Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 14 | 1410 nanogram per milliliter | Geometric Coefficient of Variation 25.5 |
| Part A: VX-445 (Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 1 | 631 nanogram per milliliter | Geometric Coefficient of Variation 31.1 |
| Part A: VX-445 (Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 7 | 2070 nanogram per milliliter | Geometric Coefficient of Variation 23.1 |
Secondary
Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ)
Time frame: Pre-dose to 96 hours post-dose on Day 1, Day 7 and Day 14
Population: The Pharmacokinetic Set. Here Number analyzed signified those subjects who were evaluated at specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M2-TEZ: Day 7 | 4.72 microgram per milliliter | Geometric Coefficient of Variation 30.3 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M1-TEZ: Day 1 | 0.929 microgram per milliliter | Geometric Coefficient of Variation 35 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | TEZ: Day 7 | 7.09 microgram per milliliter | Geometric Coefficient of Variation 19.4 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | VX-445: Day 14 | 8.71 microgram per milliliter | Geometric Coefficient of Variation 9.65 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | TEZ: Day 14 | 8.11 microgram per milliliter | Geometric Coefficient of Variation 21.2 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M2-TEZ: Day 14 | 7.69 microgram per milliliter | Geometric Coefficient of Variation 23.7 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M2-TEZ: Day 1 | 0.553 microgram per milliliter | Geometric Coefficient of Variation 47 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M1-TEZ: Day 14 | 5.77 microgram per milliliter | Geometric Coefficient of Variation 24.6 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M1-TEZ: Day 7 | 4.34 microgram per milliliter | Geometric Coefficient of Variation 28.7 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | VX-445: Day 1 | 3.04 microgram per milliliter | Geometric Coefficient of Variation 23.2 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | VX-445: Day 7 | 8.29 microgram per milliliter | Geometric Coefficient of Variation 31.9 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | TEZ: Day 1 | 3.81 microgram per milliliter | Geometric Coefficient of Variation 16.4 |
| Part A: VX-445 (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | VX-445: Day 1 | 4.86 microgram per milliliter | Geometric Coefficient of Variation 25.4 |
| Part A: VX-445 (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | VX-445: Day 14 | 14.0 microgram per milliliter | Geometric Coefficient of Variation 19.2 |
| Part A: VX-445 (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | VX-445: Day 7 | 10.3 microgram per milliliter | Geometric Coefficient of Variation 18.4 |
| Part A: VX-445 (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | TEZ: Day 1 | 5.67 microgram per milliliter | Geometric Coefficient of Variation 17.2 |
| Part A: VX-445 (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | TEZ: Day 7 | 8.29 microgram per milliliter | Geometric Coefficient of Variation 13.6 |
| Part A: VX-445 (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | TEZ: Day 14 | 9.07 microgram per milliliter | Geometric Coefficient of Variation 7.6 |
| Part A: VX-445 (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M1-TEZ: Day 1 | 0.988 microgram per milliliter | Geometric Coefficient of Variation 31.7 |
| Part A: VX-445 (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M1-TEZ: Day 7 | 5.19 microgram per milliliter | Geometric Coefficient of Variation 16.8 |
| Part A: VX-445 (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M1-TEZ: Day 14 | 6.79 microgram per milliliter | Geometric Coefficient of Variation 14.9 |
| Part A: VX-445 (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M2-TEZ: Day 1 | 0.667 microgram per milliliter | Geometric Coefficient of Variation 39.6 |
| Part A: VX-445 (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M2-TEZ: Day 7 | 6.41 microgram per milliliter | Geometric Coefficient of Variation 33.2 |
| Part A: VX-445 (Except Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M2-TEZ: Day 14 | 10.1 microgram per milliliter | Geometric Coefficient of Variation 24.2 |
| Part A: VX-445 (Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M1-TEZ: Day 1 | 1.30 microgram per milliliter | Geometric Coefficient of Variation 17.3 |
| Part A: VX-445 (Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M2-TEZ: Day 7 | 5.46 microgram per milliliter | Geometric Coefficient of Variation 29.4 |
| Part A: VX-445 (Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M1-TEZ: Day 14 | 7.54 microgram per milliliter | Geometric Coefficient of Variation 11.8 |
| Part A: VX-445 (Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | VX-445: Day 14 | 4.73 microgram per milliliter | Geometric Coefficient of Variation 15.9 |
| Part A: VX-445 (Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | VX-445: Day 1 | 1.72 microgram per milliliter | Geometric Coefficient of Variation 16.5 |
| Part A: VX-445 (Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | TEZ: Day 7 | 7.01 microgram per milliliter | Geometric Coefficient of Variation 14.7 |
| Part A: VX-445 (Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M2-TEZ: Day 1 | 0.716 microgram per milliliter | Geometric Coefficient of Variation 17 |
| Part A: VX-445 (Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | TEZ: Day 14 | 8.60 microgram per milliliter | Geometric Coefficient of Variation 12.8 |
| Part A: VX-445 (Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | TEZ: Day 1 | 5.38 microgram per milliliter | Geometric Coefficient of Variation 19.2 |
| Part A: VX-445 (Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | VX-445: Day 7 | 3.58 microgram per milliliter | Geometric Coefficient of Variation 14.8 |
| Part A: VX-445 (Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M1-TEZ: Day 7 | 5.86 microgram per milliliter | Geometric Coefficient of Variation 11.3 |
| Part A: VX-445 (Cohort A7) | Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M2-TEZ: Day 14 | 7.93 microgram per milliliter | Geometric Coefficient of Variation 28.3 |
Secondary
Part C: Observed Pre-dose Concentration (Ctrough) of IVA and Its Metabolites (M1-IVA and M6-IVA)
Time frame: Pre-dose on Day 7 and Day 14
Population: The Pharmacokinetic Set.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 7 | 753 nanogram per milliliter | Geometric Coefficient of Variation 75 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 14 | 610 nanogram per milliliter | Geometric Coefficient of Variation 55.6 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 7 | 1790 nanogram per milliliter | Geometric Coefficient of Variation 43.7 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 14 | 1600 nanogram per milliliter | Geometric Coefficient of Variation 46.2 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 7 | 1530 nanogram per milliliter | Geometric Coefficient of Variation 31.5 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 14 | 1360 nanogram per milliliter | Geometric Coefficient of Variation 49.1 |
| Part A: VX-445 (Except Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 14 | 2600 nanogram per milliliter | Geometric Coefficient of Variation 18 |
| Part A: VX-445 (Except Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 7 | 759 nanogram per milliliter | Geometric Coefficient of Variation 45.7 |
| Part A: VX-445 (Except Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 14 | 2210 nanogram per milliliter | Geometric Coefficient of Variation 19.8 |
| Part A: VX-445 (Except Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 7 | 2260 nanogram per milliliter | Geometric Coefficient of Variation 11.9 |
| Part A: VX-445 (Except Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 14 | 990 nanogram per milliliter | Geometric Coefficient of Variation 43.4 |
| Part A: VX-445 (Except Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 7 | 1960 nanogram per milliliter | Geometric Coefficient of Variation 21.4 |
| Part A: VX-445 (Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 14 | 881 nanogram per milliliter | Geometric Coefficient of Variation 35.3 |
| Part A: VX-445 (Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 7 | 1400 nanogram per milliliter | Geometric Coefficient of Variation 21.3 |
| Part A: VX-445 (Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 14 | 1640 nanogram per milliliter | Geometric Coefficient of Variation 27 |
| Part A: VX-445 (Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 14 | 1930 nanogram per milliliter | Geometric Coefficient of Variation 16.9 |
| Part A: VX-445 (Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 7 | 604 nanogram per milliliter | Geometric Coefficient of Variation 32.8 |
| Part A: VX-445 (Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 7 | 1270 nanogram per milliliter | Geometric Coefficient of Variation 32.1 |
Secondary
Part C: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ)
Time frame: Pre-dose on Day 7 and Day 14
Population: The Pharmacokinetic Set.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M1-TEZ: Day 7 | 3.36 microgram per milliliter | Geometric Coefficient of Variation 27.1 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | TEZ: Day 14 | 3.10 microgram per milliliter | Geometric Coefficient of Variation 33.4 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | VX-445: Day 14 | 4.45 microgram per milliliter | Geometric Coefficient of Variation 38.9 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M2-TEZ: Day 7 | 4.06 microgram per milliliter | Geometric Coefficient of Variation 32.8 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | TEZ: Day 7 | 2.73 microgram per milliliter | Geometric Coefficient of Variation 48.7 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M1-TEZ: Day 14 | 4.38 microgram per milliliter | Geometric Coefficient of Variation 20.5 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M2-TEZ: Day 14 | 6.46 microgram per milliliter | Geometric Coefficient of Variation 22.5 |
| Part A: Pooled Placebo (Except Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | VX-445: Day 7 | 4.63 microgram per milliliter | Geometric Coefficient of Variation 46.8 |
| Part A: VX-445 (Except Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M2-TEZ: Day 7 | 5.63 microgram per milliliter | Geometric Coefficient of Variation 37.5 |
| Part A: VX-445 (Except Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | VX-445: Day 7 | 5.91 microgram per milliliter | Geometric Coefficient of Variation 35.5 |
| Part A: VX-445 (Except Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | TEZ: Day 7 | 2.77 microgram per milliliter | Geometric Coefficient of Variation 19.2 |
| Part A: VX-445 (Except Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M2-TEZ: Day 14 | 8.85 microgram per milliliter | Geometric Coefficient of Variation 29.9 |
| Part A: VX-445 (Except Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | VX-445: Day 14 | 7.60 microgram per milliliter | Geometric Coefficient of Variation 29.8 |
| Part A: VX-445 (Except Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | TEZ: Day 14 | 3.70 microgram per milliliter | Geometric Coefficient of Variation 16 |
| Part A: VX-445 (Except Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M1-TEZ: Day 7 | 3.98 microgram per milliliter | Geometric Coefficient of Variation 16.8 |
| Part A: VX-445 (Except Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M1-TEZ: Day 14 | 5.42 microgram per milliliter | Geometric Coefficient of Variation 16.1 |
| Part A: VX-445 (Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M2-TEZ: Day 14 | 7.38 microgram per milliliter | Geometric Coefficient of Variation 29.6 |
| Part A: VX-445 (Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | TEZ: Day 14 | 3.62 microgram per milliliter | Geometric Coefficient of Variation 24.6 |
| Part A: VX-445 (Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M1-TEZ: Day 7 | 4.71 microgram per milliliter | Geometric Coefficient of Variation 14 |
| Part A: VX-445 (Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M2-TEZ: Day 7 | 4.92 microgram per milliliter | Geometric Coefficient of Variation 27.7 |
| Part A: VX-445 (Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | TEZ: Day 7 | 2.52 microgram per milliliter | Geometric Coefficient of Variation 23 |
| Part A: VX-445 (Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | VX-445: Day 14 | 2.92 microgram per milliliter | Geometric Coefficient of Variation 13.2 |
| Part A: VX-445 (Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | VX-445: Day 7 | 2.09 microgram per milliliter | Geometric Coefficient of Variation 14.9 |
| Part A: VX-445 (Cohort A7) | Part C: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) | M1-TEZ: Day 14 | 5.52 microgram per milliliter | Geometric Coefficient of Variation 12.9 |
Secondary
Part D: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Time frame: From Baseline through Day 29
Population: FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo (Except Cohort A7) | Part D: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score | 4.2 units on a scale | Standard Error 4.9 |
| Part A: VX-445 (Except Cohort A7) | Part D: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score | 20.8 units on a scale | Standard Error 5.4 |
| Part A: VX-445 (Cohort A7) | Part D: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score | 15.4 units on a scale | Standard Error 3.7 |
| Part B: Pooled Placebo (Cohort B1 to B4) | Part D: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score | 25.7 units on a scale | Standard Error 3.7 |
p-value: 0.394Mixed-effects model for repeated measure
p-value: 0.0003Mixed-effects model for repeated measure
p-value: <0.0001Mixed-effects model for repeated measure
p-value: <0.0001Mixed-effects model for repeated measure
Secondary
Part D: Absolute Change in Sweat Chloride Concentration
Sweat samples were collected using an approved collection device.
Time frame: From Baseline through Day 29
Population: FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo (Except Cohort A7) | Part D: Absolute Change in Sweat Chloride Concentration | -2.2 millimole per liter (mmol/L) | Standard Error 3.9 |
| Part A: VX-445 (Except Cohort A7) | Part D: Absolute Change in Sweat Chloride Concentration | -38.2 millimole per liter (mmol/L) | Standard Error 4.2 |
| Part A: VX-445 (Cohort A7) | Part D: Absolute Change in Sweat Chloride Concentration | -33.2 millimole per liter (mmol/L) | Standard Error 2.8 |
| Part B: Pooled Placebo (Cohort B1 to B4) | Part D: Absolute Change in Sweat Chloride Concentration | -39.1 millimole per liter (mmol/L) | Standard Error 2.9 |
p-value: 0.5802Mixed-effects model for repeated measure
p-value: <0.0001Mixed-effects model for repeated measure
p-value: <0.0001Mixed-effects model for repeated measure
p-value: <0.0001Mixed-effects model for repeated measure
Secondary
Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA)
Time frame: Pre-dose on Day 15 and Day 29
Population: FAS. Here number analyzed signifies those participants who were evaluated at specified time points for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Pooled Placebo (Except Cohort A7) | Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA) | VX-445: Day 15 | 1.04 microgram per milliliter | Standard Deviation 0.612 |
| Part A: Pooled Placebo (Except Cohort A7) | Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA) | VX-445: Day 29 | 1.27 microgram per milliliter | Standard Deviation 0.53 |
| Part A: Pooled Placebo (Except Cohort A7) | Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA) | TEZ: Day 15 | 1.85 microgram per milliliter | Standard Deviation 1.26 |
| Part A: Pooled Placebo (Except Cohort A7) | Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA) | TEZ: Day 29 | 2.16 microgram per milliliter | Standard Deviation 1.27 |
| Part A: Pooled Placebo (Except Cohort A7) | Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA) | M1-TEZ: Day 15 | 4.46 microgram per milliliter | Standard Deviation 1.96 |
| Part A: Pooled Placebo (Except Cohort A7) | Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA) | M1-TEZ: Day 29 | 4.77 microgram per milliliter | Standard Deviation 2.04 |
| Part A: Pooled Placebo (Except Cohort A7) | Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA) | IVA: Day 15 | 0.720 microgram per milliliter | Standard Deviation 0.484 |
| Part A: Pooled Placebo (Except Cohort A7) | Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA) | IVA: Day 29 | 0.753 microgram per milliliter | Standard Deviation 0.424 |
| Part A: Pooled Placebo (Except Cohort A7) | Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA) | M1-IVA: Day 15 | 1.29 microgram per milliliter | Standard Deviation 0.748 |
| Part A: Pooled Placebo (Except Cohort A7) | Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA) | M1-IVA: Day 29 | 1.57 microgram per milliliter | Standard Deviation 0.83 |
| Part A: VX-445 (Except Cohort A7) | Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA) | M1-IVA: Day 15 | 1.21 microgram per milliliter | Standard Deviation 0.666 |
| Part A: VX-445 (Except Cohort A7) | Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA) | VX-445: Day 15 | 2.15 microgram per milliliter | Standard Deviation 0.977 |
| Part A: VX-445 (Except Cohort A7) | Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA) | M1-TEZ: Day 29 | 4.30 microgram per milliliter | Standard Deviation 1.55 |
| Part A: VX-445 (Except Cohort A7) | Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA) | M1-TEZ: Day 15 | 4.11 microgram per milliliter | Standard Deviation 1.47 |
| Part A: VX-445 (Except Cohort A7) | Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA) | VX-445: Day 29 | 2.18 microgram per milliliter | Standard Deviation 1.26 |
| Part A: VX-445 (Except Cohort A7) | Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA) | M1-IVA: Day 29 | 1.20 microgram per milliliter | Standard Deviation 0.717 |
| Part A: VX-445 (Except Cohort A7) | Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA) | IVA: Day 29 | 0.704 microgram per milliliter | Standard Deviation 0.414 |
| Part A: VX-445 (Except Cohort A7) | Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA) | TEZ: Day 15 | 1.68 microgram per milliliter | Standard Deviation 0.7 |
| Part A: VX-445 (Except Cohort A7) | Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA) | IVA: Day 15 | 0.665 microgram per milliliter | Standard Deviation 0.414 |
| Part A: VX-445 (Except Cohort A7) | Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA) | TEZ: Day 29 | 1.77 microgram per milliliter | Standard Deviation 0.833 |
| Part A: VX-445 (Cohort A7) | Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA) | IVA: Day 29 | 0.658 microgram per milliliter | Standard Deviation 0.386 |
| Part A: VX-445 (Cohort A7) | Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA) | TEZ: Day 29 | 2.22 microgram per milliliter | Standard Deviation 1.62 |
| Part A: VX-445 (Cohort A7) | Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA) | M1-TEZ: Day 15 | 4.43 microgram per milliliter | Standard Deviation 1.79 |
| Part A: VX-445 (Cohort A7) | Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA) | M1-TEZ: Day 29 | 4.74 microgram per milliliter | Standard Deviation 1.89 |
| Part A: VX-445 (Cohort A7) | Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA) | M1-IVA: Day 15 | 1.45 microgram per milliliter | Standard Deviation 1.22 |
| Part A: VX-445 (Cohort A7) | Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA) | IVA: Day 15 | 0.701 microgram per milliliter | Standard Deviation 0.593 |
| Part A: VX-445 (Cohort A7) | Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA) | VX-445: Day 15 | 5.77 microgram per milliliter | Standard Deviation 4.14 |
| Part A: VX-445 (Cohort A7) | Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA) | M1-IVA: Day 29 | 1.29 microgram per milliliter | Standard Deviation 0.797 |
| Part A: VX-445 (Cohort A7) | Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA) | VX-445: Day 29 | 5.57 microgram per milliliter | Standard Deviation 2.8 |
| Part A: VX-445 (Cohort A7) | Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA) | TEZ: Day 15 | 1.76 microgram per milliliter | Standard Deviation 0.96 |
Secondary
Part D: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time frame: From Baseline through Day 29
Population: FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo (Except Cohort A7) | Part D: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | 0.3 percent change | Standard Error 4 |
| Part A: VX-445 (Except Cohort A7) | Part D: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | 19.3 percent change | Standard Error 4.2 |
| Part A: VX-445 (Cohort A7) | Part D: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | 13.8 percent change | Standard Error 2.8 |
| Part B: Pooled Placebo (Cohort B1 to B4) | Part D: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | 26.2 percent change | Standard Error 2.9 |
p-value: 0.9453Mixed-effects model for repeated measure
p-value: <0.0001Mixed-effects model for repeated measure
p-value: <0.0001Mixed-effects model for repeated measure
p-value: <0.0001Mixed-effects model for repeated measure
Secondary
Part E: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Time frame: From Baseline through Day 29
Population: FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo (Except Cohort A7) | Part E: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score | 5.2 units on a scale | Standard Error 7.1 |
| Part A: VX-445 (Except Cohort A7) | Part E: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score | 20.7 units on a scale | Standard Error 4 |
p-value: 0.4757mixed-effects model for repeated measure
p-value: <0.0001mixed-effects model for repeated measure
Secondary
Part E: Absolute Change in Sweat Chloride Concentration
Sweat samples were collected using an approved collection device.
Time frame: From Baseline through Day 29
Population: FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo (Except Cohort A7) | Part E: Absolute Change in Sweat Chloride Concentration | 0.8 mmol/L | Standard Error 4.9 |
| Part A: VX-445 (Except Cohort A7) | Part E: Absolute Change in Sweat Chloride Concentration | -39.6 mmol/L | Standard Error 2.8 |
p-value: 0.8712mixed-effects model for repeated measure
p-value: <0.0001mixed-effects model for repeated measure
Secondary
Part E: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and IVA and Its Metabolite (M1-IVA)
Time frame: Pre-dose on Day 15 and Day 29
Population: FAS. Here Number analyzed signifies those participants who were evaluated at specified time points for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Pooled Placebo (Except Cohort A7) | Part E: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and IVA and Its Metabolite (M1-IVA) | M1-IVA: Day 29 | 0.943 microgram per milliliter | Standard Deviation 0.431 |
| Part A: Pooled Placebo (Except Cohort A7) | Part E: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and IVA and Its Metabolite (M1-IVA) | TEZ: Day 15 | 1.85 microgram per milliliter | Standard Deviation 0.863 |
| Part A: Pooled Placebo (Except Cohort A7) | Part E: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and IVA and Its Metabolite (M1-IVA) | TEZ: Day 29 | 1.84 microgram per milliliter | Standard Deviation 1.28 |
| Part A: Pooled Placebo (Except Cohort A7) | Part E: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and IVA and Its Metabolite (M1-IVA) | M1-TEZ: Day 15 | 3.96 microgram per milliliter | Standard Deviation 1.76 |
| Part A: Pooled Placebo (Except Cohort A7) | Part E: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and IVA and Its Metabolite (M1-IVA) | M1-TEZ: Day 29 | 3.73 microgram per milliliter | Standard Deviation 1.51 |
| Part A: Pooled Placebo (Except Cohort A7) | Part E: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and IVA and Its Metabolite (M1-IVA) | IVA: Day 15 | 0.766 microgram per milliliter | Standard Deviation 0.366 |
| Part A: Pooled Placebo (Except Cohort A7) | Part E: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and IVA and Its Metabolite (M1-IVA) | IVA: Day 29 | 0.595 microgram per milliliter | Standard Deviation 0.303 |
| Part A: Pooled Placebo (Except Cohort A7) | Part E: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and IVA and Its Metabolite (M1-IVA) | M1-IVA: Day 15 | 1.22 microgram per milliliter | Standard Deviation 0.47 |
| Part A: VX-445 (Except Cohort A7) | Part E: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and IVA and Its Metabolite (M1-IVA) | M1-TEZ: Day 15 | 4.57 microgram per milliliter | Standard Deviation 1.73 |
| Part A: VX-445 (Except Cohort A7) | Part E: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and IVA and Its Metabolite (M1-IVA) | IVA: Day 29 | 0.798 microgram per milliliter | Standard Deviation 0.901 |
| Part A: VX-445 (Except Cohort A7) | Part E: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and IVA and Its Metabolite (M1-IVA) | M1-TEZ: Day 29 | 4.71 microgram per milliliter | Standard Deviation 1.86 |
| Part A: VX-445 (Except Cohort A7) | Part E: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and IVA and Its Metabolite (M1-IVA) | VX-445: Day 15 | 5.07 microgram per milliliter | Standard Deviation 2.47 |
| Part A: VX-445 (Except Cohort A7) | Part E: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and IVA and Its Metabolite (M1-IVA) | VX-445: Day 29 | 5.35 microgram per milliliter | Standard Deviation 3.73 |
| Part A: VX-445 (Except Cohort A7) | Part E: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and IVA and Its Metabolite (M1-IVA) | M1-IVA: Day 29 | 1.43 microgram per milliliter | Standard Deviation 1.54 |
| Part A: VX-445 (Except Cohort A7) | Part E: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and IVA and Its Metabolite (M1-IVA) | TEZ: Day 15 | 1.86 microgram per milliliter | Standard Deviation 1.09 |
| Part A: VX-445 (Except Cohort A7) | Part E: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and IVA and Its Metabolite (M1-IVA) | IVA: Day 15 | 0.659 microgram per milliliter | Standard Deviation 0.529 |
| Part A: VX-445 (Except Cohort A7) | Part E: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and IVA and Its Metabolite (M1-IVA) | TEZ: Day 29 | 1.99 microgram per milliliter | Standard Deviation 1.55 |
| Part A: VX-445 (Except Cohort A7) | Part E: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and IVA and Its Metabolite (M1-IVA) | M1-IVA: Day 15 | 1.09 microgram per milliliter | Standard Deviation 0.973 |
Secondary
Part E: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time frame: From Baseline through Day 29
Population: FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo (Except Cohort A7) | Part E: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | 1.4 percent change | Standard Error 5 |
| Part A: VX-445 (Except Cohort A7) | Part E: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | 19.2 percent change | Standard Error 2.7 |
p-value: 0.7849mixed-effects model for repeated measure
p-value: <0.0001mixed-effects model for repeated measure
Secondary
Part F: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Time frame: From Baseline through Day 29
Population: FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo (Except Cohort A7) | Part F: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score | 20.2 units on a scale | Standard Error 6.9 |
| Part A: VX-445 (Except Cohort A7) | Part F: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score | 20.2 units on a scale | Standard Error 4.3 |
p-value: 0.007mixed-effects model for repeated measure
p-value: <0.0001mixed-effects model for repeated measure
Secondary
Part F: Absolute Change in Sweat Chloride Concentration
Sweat samples were collected using an approved collection device.
Time frame: From Baseline through Day 29
Population: FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo (Except Cohort A7) | Part F: Absolute Change in Sweat Chloride Concentration | 1.0 mmol/L | Standard Error 4.6 |
| Part A: VX-445 (Except Cohort A7) | Part F: Absolute Change in Sweat Chloride Concentration | -33.6 mmol/L | Standard Error 2.8 |
p-value: 0.8359mixed-effects model for repeated measure
p-value: <0.0001mixed-effects model for repeated measure
Secondary
Part F: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and VX-561
Time frame: Pre-dose on Day 15 and Day 29
Population: FAS. Here, Number analyzed signifies those participants who were evaluated at specified time points for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Pooled Placebo (Except Cohort A7) | Part F: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and VX-561 | VX-445: Day 15 | 4.40 microgram per milliliter | Standard Deviation 1.54 |
| Part A: Pooled Placebo (Except Cohort A7) | Part F: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and VX-561 | VX-445: Day 29 | 5.25 microgram per milliliter | Standard Deviation 2.88 |
| Part A: Pooled Placebo (Except Cohort A7) | Part F: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and VX-561 | TEZ: Day 15 | 1.80 microgram per milliliter | Standard Deviation 0.658 |
| Part A: Pooled Placebo (Except Cohort A7) | Part F: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and VX-561 | TEZ: Day 29 | 2.22 microgram per milliliter | Standard Deviation 1.65 |
| Part A: Pooled Placebo (Except Cohort A7) | Part F: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and VX-561 | M1-TEZ: Day 15 | 4.99 microgram per milliliter | Standard Deviation 1.71 |
| Part A: Pooled Placebo (Except Cohort A7) | Part F: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and VX-561 | M1-TEZ: Day 29 | 5.09 microgram per milliliter | Standard Deviation 1.37 |
| Part A: Pooled Placebo (Except Cohort A7) | Part F: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and VX-561 | VX-561: Day 15 | 0.441 microgram per milliliter | Standard Deviation 0.174 |
| Part A: Pooled Placebo (Except Cohort A7) | Part F: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and VX-561 | VX-561: Day 29 | 0.597 microgram per milliliter | Standard Deviation 0.473 |
Secondary
Part F: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time frame: From Baseline through Day 29
Population: FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo (Except Cohort A7) | Part F: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | 1.6 percent change | Standard Error 4.6 |
| Part A: VX-445 (Except Cohort A7) | Part F: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | 19.9 percent change | Standard Error 2.8 |
p-value: 0.7356mixed-effects model for repeated measure
p-value: <0.0001mixed-effects model for repeated measure