Cystic Fibrosis
Conditions
Brief summary
The purpose of this study is to evaluate safety and tolerability of VX-121 in healthy subjects and in subjects with cystic fibrosis (CF).
Interventions
DRUGPlacebo (matched to VX-121 suspension)
Placebo matched to VX-121 suspension for oral administration.
DRUGVX-121 (Suspension)
Suspension for oral administration.
DRUGTEZ/IVA
Fixed-dose combination tablet for oral administration.
DRUGIVA
Tablet for oral administration.
DRUGPlacebo (matched to TEZ/IVA)
Placebo matched to TEZ/IVA for oral administration.
Placebo matched to IVA for oral administration.
DRUGVX-121 (Tablet)
Tablet for oral administration.
DRUGPlacebo (matched to VX-121 tablet)
Placebo matched to VX-121 tablet for oral administration.
Sponsors
Vertex Pharmaceuticals Incorporated
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
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: * Part A, B, and C: Healthy Volunteers * 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 * Part D: Subjects with CF * Heterozygous for F508del and an MF mutation (F/MF) * FEV1 value ≥40% and ≤90% of predicted mean for age, sex, and height * Body weight ≥35 kg Key
Exclusion criteria
* Part A, B and C: Healthy Volunteers * Any condition possibly affecting drug absorption * History of febrile illness or other acute illness within 5 days before the first study drug dose * Part D: Subjects with CF * History of clinically significant cirrhosis with or without portal hypertension * History of solid organ or hematological transplantation * Lung infection with organisms associated with a more rapid decline in pulmonary status Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From Day 1 Through Safety Follow-up (up to Day 15 for Part A [except Cohorts A3 and A9], up to Day 26 for Cohort A3, up to Day 34 for Cohort A9, up to Day 20 for Part B, up to Day 24 for Part C and up to Week 9 for Part D) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121 | Cohorts A1-5 (Except A3): Pre-dose up to 240 hours post-dose; Cohorts A3 and A9: Pre-dose up to 168 hours post-dose | — |
| Part B: Maximum Observed Concentration (Cmax) of VX-121 | Day 1, Day 5, and Day 10 | — |
| Part B: Area Under the Concentration Versus Time Curve During the Dosing Interval (AUCtau) of VX-121 | Day 1, Day 5, and Day 10 | — |
| Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-121 | Pre-dose at Day 5 and Day 10 | — |
| Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | Day 1, Day 7, and Day 14 | — |
| Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | Day 1, Day 7, and Day 14 | — |
| Part A: Maximum Observed Concentration (Cmax) of VX-121 | Cohorts A1-5 (Except A3): Pre-dose up to 240 hours post-dose; Cohorts A3 and A9: Pre-dose up to 168 hours post-dose | — |
| Part D: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | Day 1 and Day 15 | — |
| Part D: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | Day 1 and Day 15 | — |
| Part D: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | Pre-dose at Day 8, Day 15, and Day 29 | — |
| Part D: Absolute Change in Sweat Chloride (SwCl) Concentrations | From Baseline Through Day 29 | Sweat samples were collected using an approved collection device. |
| 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 C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | Pre-dose at Day 7 and Day 14 | — |
Countries
Netherlands, United Kingdom
Participant flow
Recruitment details
A total of 115 unique participants enrolled in this study.
Pre-assignment details
This study included 4 parts: Parts A, B, and C were conducted in healthy adult participants; Part D was conducted in adult cystic fibrosis (CF) participants.
Participants by arm
| Arm | Count |
|---|---|
| Part A: Pooled Placebo (Cohorts A1-5; Except A3) Participants received single dose of placebo matched to VX-121. | 8 |
| Part A: VX-121 (Cohort A1) Participants received single dose of VX-121 10 mg. | 5 |
| Part A: VX-121 (Cohort A2) Participants received single dose of VX-121 20 mg. | 6 |
| Part A: VX-121 (Cohort A3) Participants received single dose of VX-121 5 mg or matched placebo without milk, followed by open label VX-121 5 mg with milk. | 6 |
| Part A: VX-121 (Cohort A4) Participants received single dose of VX-121 40 mg. | 6 |
| Part A: VX-121 (Cohort A5) Participants received single dose of VX-121 60 mg. | 6 |
| Part A: Cohort A9 Participants received single dose of VX-121 10 mg suspension on Day 1, VX-121 10 mg tablet on Day 9, followed by VX-121 10 mg tablet with milk on Day 17. | 8 |
| Part B: Pooled Placebo (Cohorts B1-4) Participants received placebo matched to VX-121 for 10 days. | 9 |
| Part B: VX-121 (Cohort B1) Participants received VX-121 10 mg qd for 10 days. | 6 |
| Part B: VX-121 (Cohort B2) Participants received VX-121 20 mg qd for 10 days. | 6 |
| Part B: VX-121 (Cohort B3) Participants received VX-121 40 mg qd for 10 days. | 5 |
| Part B: VX-121 (Cohort B4) Participants received VX-121 60 mg qd for 10 days. | 6 |
| Part C: Pooled Placebo (Cohorts C1-3) Participants received placebo matched to VX-121/TEZ/IVA in for 14 days. | 6 |
| Part C: VX-121 (Cohort C1) Participants received VX-121 10 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 14 days. | 6 |
| Part C: VX-121 (Cohort C2) Participants received VX-121 20 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 14 days. | 7 |
| Part C: VX-121 (Cohort C3) Participants received VX-121 5 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 14 days. | 6 |
| Part D: Placebo Participants received placebo matched to VX-121/TEZ/IVA for 4 weeks. | 3 |
| Part D: VX-121/TEZ/IVA Participants received VX-121 5 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks. | 9 |
| Total | 114 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part A | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part C | Randomized, Never Dosed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Part A: VX-121 (Cohort A1) | Part A: VX-121 (Cohort A2) | Part A: VX-121 (Cohort A3) | Part A: Pooled Placebo (Cohorts A1-5; Except A3) | Part A: VX-121 (Cohort A4) | Part A: VX-121 (Cohort A5) | Part A: Cohort A9 | Part B: Pooled Placebo (Cohorts B1-4) | Part B: VX-121 (Cohort B1) | Part B: VX-121 (Cohort B2) | Part B: VX-121 (Cohort B3) | Part B: VX-121 (Cohort B4) | Part C: Pooled Placebo (Cohorts C1-3) | Part C: VX-121 (Cohort C1) | Part C: VX-121 (Cohort C2) | Part C: VX-121 (Cohort C3) | Part D: Placebo | Part D: VX-121/TEZ/IVA |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | 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 | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 114 Participants | 5 Participants | 6 Participants | 6 Participants | 8 Participants | 6 Participants | 6 Participants | 8 Participants | 9 Participants | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 6 Participants | 6 Participants | 7 Participants | 6 Participants | 3 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 109 Participants | 5 Participants | 5 Participants | 5 Participants | 8 Participants | 6 Participants | 5 Participants | 7 Participants | 9 Participants | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 6 Participants | 5 Participants | 7 Participants | 6 Participants | 3 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 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 | 6 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 7 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (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 | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 90 Participants | 5 Participants | 6 Participants | 4 Participants | 5 Participants | 4 Participants | 5 Participants | 4 Participants | 6 Participants | 5 Participants | 6 Participants | 5 Participants | 5 Participants | 4 Participants | 5 Participants | 5 Participants | 5 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Female | 5 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 109 Participants | 5 Participants | 6 Participants | 6 Participants | 8 Participants | 5 Participants | 5 Participants | 8 Participants | 8 Participants | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 3 Participants | 8 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 | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 | 0 / 9 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 6 | 0 / 3 | 0 / 9 |
| other Total, other adverse events | 1 / 8 | 4 / 5 | 2 / 6 | 4 / 6 | 1 / 6 | 2 / 6 | 7 / 8 | 7 / 9 | 3 / 6 | 5 / 6 | 4 / 6 | 5 / 6 | 4 / 6 | 3 / 6 | 6 / 7 | 3 / 6 | 2 / 3 | 7 / 9 |
| serious Total, serious adverse events | 0 / 8 | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 | 0 / 9 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 6 | 1 / 3 | 0 / 9 |
Outcome results
Primary
Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: From Day 1 Through Safety Follow-up (up to Day 15 for Part A [except Cohorts A3 and A9], up to Day 26 for Cohort A3, up to Day 34 for Cohort A9, up to Day 20 for Part B, up to Day 24 for Part C and up to Week 9 for Part D)
Population: Safety Set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part B: VX-121 (Cohort B1) | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With TEAEs | 1 participants |
| Part B: VX-121 (Cohort B1) | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 0 participants |
| Part B: VX-121 (Cohort B2) | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With TEAEs | 4 participants |
| Part B: VX-121 (Cohort B2) | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 0 participants |
| Part B: VX-121 (Cohort B3) | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With TEAEs | 2 participants |
| Part B: VX-121 (Cohort B3) | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 0 participants |
| Part A: VX-121 (Cohort A3: With Milk) | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With TEAEs | 4 participants |
| Part A: VX-121 (Cohort A3: With Milk) | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 0 participants |
| Part A: VX-121 (Cohort A4) | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 0 participants |
| Part A: VX-121 (Cohort A4) | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With TEAEs | 1 participants |
| Part A: VX-121 (Cohort A5) | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 0 participants |
| Part A: VX-121 (Cohort A5) | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With TEAEs | 2 participants |
| Part A: VX-121 (Cohort A9: Suspension) | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With TEAEs | 7 participants |
| Part A: VX-121 (Cohort A9: Suspension) | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 0 participants |
| Part A: VX-121 (Cohort A9: Tablet Without Milk) | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With TEAEs | 7 participants |
| Part A: VX-121 (Cohort A9: Tablet Without Milk) | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 0 participants |
| Part A: VX-121 (Cohort A9: Tablet With Milk) | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 0 participants |
| Part A: VX-121 (Cohort A9: Tablet With Milk) | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With TEAEs | 3 participants |
| Part B: VX-121 (Cohort B2) | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 0 participants |
| Part B: VX-121 (Cohort B2) | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With TEAEs | 5 participants |
| Part B: VX-121 (Cohort B3) | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 0 participants |
| Part B: VX-121 (Cohort B3) | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With TEAEs | 4 participants |
| Part B: VX-121 (Cohort B4) | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 0 participants |
| Part B: VX-121 (Cohort B4) | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With TEAEs | 5 participants |
| Part C: Pooled Placebo (Cohorts C1-3) | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With TEAEs | 4 participants |
| Part C: Pooled Placebo (Cohorts C1-3) | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 0 participants |
| Part C: VX-121 (Cohort C1) | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With TEAEs | 3 participants |
| Part C: VX-121 (Cohort C1) | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 0 participants |
| Part C: VX-121 (Cohort C2) | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With TEAEs | 6 participants |
| Part C: VX-121 (Cohort C2) | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 0 participants |
| Part C: VX-121 (Cohort C3) | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With TEAEs | 3 participants |
| Part C: VX-121 (Cohort C3) | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 0 participants |
| Part D: Placebo | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With TEAEs | 2 participants |
| Part D: Placebo | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 1 participants |
| Part D: VX-121/TEZ/IVA | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With TEAEs | 7 participants |
| Part D: VX-121/TEZ/IVA | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 0 participants |
Secondary
Part A: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121
Time frame: Cohorts A1-5 (Except A3): Pre-dose up to 240 hours post-dose; Cohorts A3 and A9: Pre-dose up to 168 hours post-dose
Population: PK set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part B: VX-121 (Cohort B1) | Part A: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121 | 7.72 microgram*hour per milliliter (mcg*h/mL) | Standard Deviation 1.93 |
| Part B: VX-121 (Cohort B2) | Part A: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121 | 20.7 microgram*hour per milliliter (mcg*h/mL) | Standard Deviation 7.03 |
| Part B: VX-121 (Cohort B3) | Part A: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121 | 6.32 microgram*hour per milliliter (mcg*h/mL) | Standard Deviation 2.54 |
| Part A: VX-121 (Cohort A3: With Milk) | Part A: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121 | 5.36 microgram*hour per milliliter (mcg*h/mL) | Standard Deviation 2.09 |
| Part A: VX-121 (Cohort A4) | Part A: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121 | 72.2 microgram*hour per milliliter (mcg*h/mL) | Standard Deviation 28.9 |
| Part A: VX-121 (Cohort A5) | Part A: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121 | 66.6 microgram*hour per milliliter (mcg*h/mL) | Standard Deviation 9.18 |
| Part A: VX-121 (Cohort A9: Suspension) | Part A: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121 | 15.7 microgram*hour per milliliter (mcg*h/mL) | Standard Deviation 3.88 |
| Part A: VX-121 (Cohort A9: Tablet Without Milk) | Part A: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121 | 14.6 microgram*hour per milliliter (mcg*h/mL) | Standard Deviation 3.85 |
| Part A: VX-121 (Cohort A9: Tablet With Milk) | Part A: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121 | 13.1 microgram*hour per milliliter (mcg*h/mL) | Standard Deviation 2.56 |
Secondary
Part A: Maximum Observed Concentration (Cmax) of VX-121
Time frame: Cohorts A1-5 (Except A3): Pre-dose up to 240 hours post-dose; Cohorts A3 and A9: Pre-dose up to 168 hours post-dose
Population: The pharmacokinetic (PK) 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 (MEAN) | Dispersion |
|---|---|---|---|
| Part B: VX-121 (Cohort B1) | Part A: Maximum Observed Concentration (Cmax) of VX-121 | 0.134 microgram per milliliter (mcg/mL) | Standard Deviation 0.0295 |
| Part B: VX-121 (Cohort B2) | Part A: Maximum Observed Concentration (Cmax) of VX-121 | 0.247 microgram per milliliter (mcg/mL) | Standard Deviation 0.0515 |
| Part B: VX-121 (Cohort B3) | Part A: Maximum Observed Concentration (Cmax) of VX-121 | 0.0705 microgram per milliliter (mcg/mL) | Standard Deviation 0.0152 |
| Part A: VX-121 (Cohort A3: With Milk) | Part A: Maximum Observed Concentration (Cmax) of VX-121 | 0.061 microgram per milliliter (mcg/mL) | Standard Deviation 0.0143 |
| Part A: VX-121 (Cohort A4) | Part A: Maximum Observed Concentration (Cmax) of VX-121 | 0.893 microgram per milliliter (mcg/mL) | Standard Deviation 0.216 |
| Part A: VX-121 (Cohort A5) | Part A: Maximum Observed Concentration (Cmax) of VX-121 | 1.04 microgram per milliliter (mcg/mL) | Standard Deviation 0.263 |
| Part A: VX-121 (Cohort A9: Suspension) | Part A: Maximum Observed Concentration (Cmax) of VX-121 | 0.181 microgram per milliliter (mcg/mL) | Standard Deviation 0.0458 |
| Part A: VX-121 (Cohort A9: Tablet Without Milk) | Part A: Maximum Observed Concentration (Cmax) of VX-121 | 0.178 microgram per milliliter (mcg/mL) | Standard Deviation 0.0447 |
| Part A: VX-121 (Cohort A9: Tablet With Milk) | Part A: Maximum Observed Concentration (Cmax) of VX-121 | 0.156 microgram per milliliter (mcg/mL) | Standard Deviation 0.0352 |
Secondary
Part B: Area Under the Concentration Versus Time Curve During the Dosing Interval (AUCtau) of VX-121
Time frame: Day 1, Day 5, and Day 10
Population: PK set. Here, the number analyzed signifies those participants who were evaluable for this outcome measure at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part B: VX-121 (Cohort B1) | Part B: Area Under the Concentration Versus Time Curve During the Dosing Interval (AUCtau) of VX-121 | Day 1 | 2.62 mcg*h/mL | Standard Deviation 0.435 |
| Part B: VX-121 (Cohort B1) | Part B: Area Under the Concentration Versus Time Curve During the Dosing Interval (AUCtau) of VX-121 | Day 10 | 11.5 mcg*h/mL | Standard Deviation 2.52 |
| Part B: VX-121 (Cohort B1) | Part B: Area Under the Concentration Versus Time Curve During the Dosing Interval (AUCtau) of VX-121 | Day 5 | 10.3 mcg*h/mL | Standard Deviation 1.84 |
| Part B: VX-121 (Cohort B2) | Part B: Area Under the Concentration Versus Time Curve During the Dosing Interval (AUCtau) of VX-121 | Day 1 | 7.11 mcg*h/mL | Standard Deviation 1.27 |
| Part B: VX-121 (Cohort B2) | Part B: Area Under the Concentration Versus Time Curve During the Dosing Interval (AUCtau) of VX-121 | Day 10 | 38.2 mcg*h/mL | Standard Deviation 9.26 |
| Part B: VX-121 (Cohort B2) | Part B: Area Under the Concentration Versus Time Curve During the Dosing Interval (AUCtau) of VX-121 | Day 5 | 30.1 mcg*h/mL | Standard Deviation 6.76 |
| Part B: VX-121 (Cohort B3) | Part B: Area Under the Concentration Versus Time Curve During the Dosing Interval (AUCtau) of VX-121 | Day 5 | 53.8 mcg*h/mL | Standard Deviation 10.7 |
| Part B: VX-121 (Cohort B3) | Part B: Area Under the Concentration Versus Time Curve During the Dosing Interval (AUCtau) of VX-121 | Day 1 | 14.4 mcg*h/mL | Standard Deviation 1.08 |
| Part B: VX-121 (Cohort B3) | Part B: Area Under the Concentration Versus Time Curve During the Dosing Interval (AUCtau) of VX-121 | Day 10 | 58.7 mcg*h/mL | Standard Deviation 12.6 |
| Part A: VX-121 (Cohort A3: With Milk) | Part B: Area Under the Concentration Versus Time Curve During the Dosing Interval (AUCtau) of VX-121 | Day 1 | 27.5 mcg*h/mL | Standard Deviation 4.3 |
| Part A: VX-121 (Cohort A3: With Milk) | Part B: Area Under the Concentration Versus Time Curve During the Dosing Interval (AUCtau) of VX-121 | Day 10 | 97.5 mcg*h/mL | Standard Deviation 17.2 |
| Part A: VX-121 (Cohort A3: With Milk) | Part B: Area Under the Concentration Versus Time Curve During the Dosing Interval (AUCtau) of VX-121 | Day 5 | 86.6 mcg*h/mL | Standard Deviation 16.6 |
Secondary
Part B: Maximum Observed Concentration (Cmax) of VX-121
Time frame: Day 1, Day 5, and Day 10
Population: PK set. Here, the number analyzed signifies those participants who were evaluable for this outcome measure at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part B: VX-121 (Cohort B1) | Part B: Maximum Observed Concentration (Cmax) of VX-121 | Day 1 | 0.153 mcg/mL | Standard Deviation 0.026 |
| Part B: VX-121 (Cohort B1) | Part B: Maximum Observed Concentration (Cmax) of VX-121 | Day 10 | 0.574 mcg/mL | Standard Deviation 0.122 |
| Part B: VX-121 (Cohort B1) | Part B: Maximum Observed Concentration (Cmax) of VX-121 | Day 5 | 0.497 mcg/mL | Standard Deviation 0.0889 |
| Part B: VX-121 (Cohort B2) | Part B: Maximum Observed Concentration (Cmax) of VX-121 | Day 1 | 0.418 mcg/mL | Standard Deviation 0.0667 |
| Part B: VX-121 (Cohort B2) | Part B: Maximum Observed Concentration (Cmax) of VX-121 | Day 10 | 1.94 mcg/mL | Standard Deviation 0.41 |
| Part B: VX-121 (Cohort B2) | Part B: Maximum Observed Concentration (Cmax) of VX-121 | Day 5 | 1.41 mcg/mL | Standard Deviation 0.316 |
| Part B: VX-121 (Cohort B3) | Part B: Maximum Observed Concentration (Cmax) of VX-121 | Day 5 | 2.67 mcg/mL | Standard Deviation 0.564 |
| Part B: VX-121 (Cohort B3) | Part B: Maximum Observed Concentration (Cmax) of VX-121 | Day 1 | 0.803 mcg/mL | Standard Deviation 0.0529 |
| Part B: VX-121 (Cohort B3) | Part B: Maximum Observed Concentration (Cmax) of VX-121 | Day 10 | 3.07 mcg/mL | Standard Deviation 0.667 |
| Part A: VX-121 (Cohort A3: With Milk) | Part B: Maximum Observed Concentration (Cmax) of VX-121 | Day 1 | 1.43 mcg/mL | Standard Deviation 0.217 |
| Part A: VX-121 (Cohort A3: With Milk) | Part B: Maximum Observed Concentration (Cmax) of VX-121 | Day 10 | 5.07 mcg/mL | Standard Deviation 0.803 |
| Part A: VX-121 (Cohort A3: With Milk) | Part B: Maximum Observed Concentration (Cmax) of VX-121 | Day 5 | 4.36 mcg/mL | Standard Deviation 0.789 |
Secondary
Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-121
Time frame: Pre-dose at Day 5 and Day 10
Population: PK set. Here, the number analyzed signifies those participants who were evaluable for this outcome measure at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part B: VX-121 (Cohort B1) | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-121 | Day 5 | 0.391 mcg/mL | Standard Deviation 0.0694 |
| Part B: VX-121 (Cohort B1) | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-121 | Day 10 | 0.484 mcg/mL | Standard Deviation 0.109 |
| Part B: VX-121 (Cohort B2) | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-121 | Day 10 | 1.64 mcg/mL | Standard Deviation 0.414 |
| Part B: VX-121 (Cohort B2) | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-121 | Day 5 | 1.16 mcg/mL | Standard Deviation 0.266 |
| Part B: VX-121 (Cohort B3) | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-121 | Day 5 | 2.07 mcg/mL | Standard Deviation 0.537 |
| Part B: VX-121 (Cohort B3) | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-121 | Day 10 | 2.40 mcg/mL | Standard Deviation 0.637 |
| Part A: VX-121 (Cohort A3: With Milk) | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-121 | Day 5 | 2.94 mcg/mL | Standard Deviation 0.759 |
| Part A: VX-121 (Cohort A3: With Milk) | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-121 | Day 10 | 3.81 mcg/mL | Standard Deviation 0.792 |
Secondary
Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA)
Time frame: Day 1, Day 7, and Day 14
Population: PK set. Here, the number analyzed signifies those participants who were evaluable for this outcome measure at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part B: VX-121 (Cohort B1) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-TEZ: Day 7 | 107 mcg*h/mL | Standard Deviation 24.8 |
| Part B: VX-121 (Cohort B1) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | VX-121: Day 1 | 3.51 mcg*h/mL | Standard Deviation 0.813 |
| Part B: VX-121 (Cohort B1) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 14 | 18.4 mcg*h/mL | Standard Deviation 10.7 |
| Part B: VX-121 (Cohort B1) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-TEZ: Day 14 | 139 mcg*h/mL | Standard Deviation 29.7 |
| Part B: VX-121 (Cohort B1) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | TEZ: Day 1 | 56.1 mcg*h/mL | Standard Deviation 16.6 |
| Part B: VX-121 (Cohort B1) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 7 | 18.8 mcg*h/mL | Standard Deviation 12.3 |
| Part B: VX-121 (Cohort B1) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M2-TEZ: Day 1 | 6.68 mcg*h/mL | Standard Deviation 2.49 |
| Part B: VX-121 (Cohort B1) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 14 | 17.6 mcg*h/mL | Standard Deviation 10.2 |
| Part B: VX-121 (Cohort B1) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 1 | 6.16 mcg*h/mL | Standard Deviation 1.36 |
| Part B: VX-121 (Cohort B1) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M2-TEZ: Day 7 | 103 mcg*h/mL | Standard Deviation 41.1 |
| Part B: VX-121 (Cohort B1) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 1 | 4.08 mcg*h/mL | Standard Deviation 1.63 |
| Part B: VX-121 (Cohort B1) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M2-TEZ: Day 14 | 143 mcg*h/mL | Standard Deviation 64.1 |
| Part B: VX-121 (Cohort B1) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | TEZ: Day 7 | 133 mcg*h/mL | Standard Deviation 51.6 |
| Part B: VX-121 (Cohort B1) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 7 | 15.2 mcg*h/mL | Standard Deviation 9.34 |
| Part B: VX-121 (Cohort B1) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 14 | 32.2 mcg*h/mL | Standard Deviation 17.3 |
| Part B: VX-121 (Cohort B1) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | TEZ: Day 14 | 138 mcg*h/mL | Standard Deviation 60.8 |
| Part B: VX-121 (Cohort B1) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | VX-121: Day 14 | 26.6 mcg*h/mL | Standard Deviation 14.5 |
| Part B: VX-121 (Cohort B1) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 7 | 32.6 mcg*h/mL | Standard Deviation 17.3 |
| Part B: VX-121 (Cohort B1) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-TEZ: Day 1 | 20.7 mcg*h/mL | Standard Deviation 7.03 |
| Part B: VX-121 (Cohort B1) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | VX-121: Day 7 | 21.7 mcg*h/mL | Standard Deviation 10.6 |
| Part B: VX-121 (Cohort B1) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 1 | 11.5 mcg*h/mL | Standard Deviation 3.01 |
| Part B: VX-121 (Cohort B2) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 1 | 9.42 mcg*h/mL | Standard Deviation 4.83 |
| Part B: VX-121 (Cohort B2) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | VX-121: Day 1 | 7.96 mcg*h/mL | Standard Deviation 0.789 |
| Part B: VX-121 (Cohort B2) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | VX-121: Day 7 | 35.4 mcg*h/mL | Standard Deviation 8.27 |
| Part B: VX-121 (Cohort B2) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | VX-121: Day 14 | 41.1 mcg*h/mL | Standard Deviation 8.29 |
| Part B: VX-121 (Cohort B2) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | TEZ: Day 1 | 50.9 mcg*h/mL | Standard Deviation 7.11 |
| Part B: VX-121 (Cohort B2) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | TEZ: Day 7 | 103 mcg*h/mL | Standard Deviation 13.9 |
| Part B: VX-121 (Cohort B2) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | TEZ: Day 14 | 112 mcg*h/mL | Standard Deviation 10.4 |
| Part B: VX-121 (Cohort B2) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-TEZ: Day 1 | 24.9 mcg*h/mL | Standard Deviation 6.61 |
| Part B: VX-121 (Cohort B2) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-TEZ: Day 7 | 130 mcg*h/mL | Standard Deviation 22.3 |
| Part B: VX-121 (Cohort B2) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-TEZ: Day 14 | 167 mcg*h/mL | Standard Deviation 24.7 |
| Part B: VX-121 (Cohort B2) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M2-TEZ: Day 1 | 9.61 mcg*h/mL | Standard Deviation 5.51 |
| Part B: VX-121 (Cohort B2) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M2-TEZ: Day 7 | 130 mcg*h/mL | Standard Deviation 46.7 |
| Part B: VX-121 (Cohort B2) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M2-TEZ: Day 14 | 194 mcg*h/mL | Standard Deviation 82.7 |
| Part B: VX-121 (Cohort B2) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 1 | 5.85 mcg*h/mL | Standard Deviation 1.64 |
| Part B: VX-121 (Cohort B2) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 7 | 11.6 mcg*h/mL | Standard Deviation 3.26 |
| Part B: VX-121 (Cohort B2) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 14 | 11.2 mcg*h/mL | Standard Deviation 2.75 |
| Part B: VX-121 (Cohort B2) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 1 | 14.1 mcg*h/mL | Standard Deviation 1.68 |
| Part B: VX-121 (Cohort B2) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 7 | 27.3 mcg*h/mL | Standard Deviation 4.79 |
| Part B: VX-121 (Cohort B2) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 14 | 25.3 mcg*h/mL | Standard Deviation 4.35 |
| Part B: VX-121 (Cohort B2) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 7 | 26.5 mcg*h/mL | Standard Deviation 12.7 |
| Part B: VX-121 (Cohort B2) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 14 | 22.6 mcg*h/mL | Standard Deviation 8.19 |
| Part B: VX-121 (Cohort B3) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-TEZ: Day 7 | 109 mcg*h/mL | Standard Deviation 14.1 |
| Part B: VX-121 (Cohort B3) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | VX-121: Day 7 | 6.52 mcg*h/mL | Standard Deviation 1.2 |
| Part B: VX-121 (Cohort B3) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 14 | 9.02 mcg*h/mL | Standard Deviation 2.62 |
| Part B: VX-121 (Cohort B3) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-TEZ: Day 1 | 20.7 mcg*h/mL | Standard Deviation 4.99 |
| Part B: VX-121 (Cohort B3) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 14 | 26.4 mcg*h/mL | Standard Deviation 24.3 |
| Part B: VX-121 (Cohort B3) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 1 | 9.37 mcg*h/mL | Standard Deviation 1.97 |
| Part B: VX-121 (Cohort B3) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | TEZ: Day 14 | 87.6 mcg*h/mL | Standard Deviation 28.6 |
| Part B: VX-121 (Cohort B3) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 7 | 19.2 mcg*h/mL | Standard Deviation 12.8 |
| Part B: VX-121 (Cohort B3) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 7 | 22.3 mcg*h/mL | Standard Deviation 3.7 |
| Part B: VX-121 (Cohort B3) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | TEZ: Day 7 | 88.8 mcg*h/mL | Standard Deviation 21 |
| Part B: VX-121 (Cohort B3) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | VX-121: Day 1 | 1.18 mcg*h/mL | Standard Deviation 0.13 |
| Part B: VX-121 (Cohort B3) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 14 | 24.2 mcg*h/mL | Standard Deviation 12.3 |
| Part B: VX-121 (Cohort B3) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M2-TEZ: Day 7 | 117 mcg*h/mL | Standard Deviation 72.6 |
| Part B: VX-121 (Cohort B3) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | TEZ: Day 1 | 44.6 mcg*h/mL | Standard Deviation 11.5 |
| Part B: VX-121 (Cohort B3) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M2-TEZ: Day 14 | 200 mcg*h/mL | Standard Deviation 144 |
| Part B: VX-121 (Cohort B3) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M2-TEZ: Day 1 | 7.57 mcg*h/mL | Standard Deviation 3.18 |
| Part B: VX-121 (Cohort B3) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | VX-121: Day 14 | 7.34 mcg*h/mL | Standard Deviation 1.63 |
| Part B: VX-121 (Cohort B3) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 1 | 4.30 mcg*h/mL | Standard Deviation 0.504 |
| Part B: VX-121 (Cohort B3) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-TEZ: Day 14 | 142 mcg*h/mL | Standard Deviation 27 |
| Part B: VX-121 (Cohort B3) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 1 | 4.99 mcg*h/mL | Standard Deviation 2.99 |
| Part B: VX-121 (Cohort B3) | Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 7 | 11.0 mcg*h/mL | Standard Deviation 3.73 |
Secondary
Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA)
Time frame: Day 1, Day 7, and Day 14
Population: PK set. Here, the number analyzed signifies those participants who were evaluable for this outcome measure at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part B: VX-121 (Cohort B1) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-TEZ: Day 7 | 5.07 mcg/mL | Standard Deviation 1.1 |
| Part B: VX-121 (Cohort B1) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | VX-121: Day 1 | 0.212 mcg/mL | Standard Deviation 0.0501 |
| Part B: VX-121 (Cohort B1) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 14 | 2.14 mcg/mL | Standard Deviation 1.2 |
| Part B: VX-121 (Cohort B1) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-TEZ: Day 14 | 6.44 mcg/mL | Standard Deviation 1.36 |
| Part B: VX-121 (Cohort B1) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | TEZ: Day 1 | 5.97 mcg/mL | Standard Deviation 1.33 |
| Part B: VX-121 (Cohort B1) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 7 | 2.15 mcg/mL | Standard Deviation 1.27 |
| Part B: VX-121 (Cohort B1) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | M2-TEZ: Day 1 | 0.521 mcg/mL | Standard Deviation 0.191 |
| Part B: VX-121 (Cohort B1) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 14 | 1.77 mcg/mL | Standard Deviation 0.941 |
| Part B: VX-121 (Cohort B1) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 1 | 1.02 mcg/mL | Standard Deviation 0.158 |
| Part B: VX-121 (Cohort B1) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | M2-TEZ: Day 7 | 4.79 mcg/mL | Standard Deviation 2.03 |
| Part B: VX-121 (Cohort B1) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 1 | 0.779 mcg/mL | Standard Deviation 0.343 |
| Part B: VX-121 (Cohort B1) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | M2-TEZ: Day 14 | 6.45 mcg/mL | Standard Deviation 2.88 |
| Part B: VX-121 (Cohort B1) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | TEZ: Day 7 | 9.48 mcg/mL | Standard Deviation 3.09 |
| Part B: VX-121 (Cohort B1) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 7 | 1.52 mcg/mL | Standard Deviation 0.889 |
| Part B: VX-121 (Cohort B1) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 14 | 4.11 mcg/mL | Standard Deviation 1.86 |
| Part B: VX-121 (Cohort B1) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | TEZ: Day 14 | 9.49 mcg/mL | Standard Deviation 3.76 |
| Part B: VX-121 (Cohort B1) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | VX-121: Day 14 | 1.39 mcg/mL | Standard Deviation 0.651 |
| Part B: VX-121 (Cohort B1) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 7 | 3.91 mcg/mL | Standard Deviation 1.8 |
| Part B: VX-121 (Cohort B1) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-TEZ: Day 1 | 1.09 mcg/mL | Standard Deviation 0.327 |
| Part B: VX-121 (Cohort B1) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | VX-121: Day 7 | 1.18 mcg/mL | Standard Deviation 0.735 |
| Part B: VX-121 (Cohort B1) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 1 | 1.91 mcg/mL | Standard Deviation 0.573 |
| Part B: VX-121 (Cohort B2) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 1 | 1.29 mcg/mL | Standard Deviation 0.796 |
| Part B: VX-121 (Cohort B2) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | VX-121: Day 1 | 0.408 mcg/mL | Standard Deviation 0.122 |
| Part B: VX-121 (Cohort B2) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | VX-121: Day 7 | 1.77 mcg/mL | Standard Deviation 0.416 |
| Part B: VX-121 (Cohort B2) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | VX-121: Day 14 | 2.14 mcg/mL | Standard Deviation 0.476 |
| Part B: VX-121 (Cohort B2) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | TEZ: Day 1 | 6.75 mcg/mL | Standard Deviation 0.936 |
| Part B: VX-121 (Cohort B2) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | TEZ: Day 7 | 8.72 mcg/mL | Standard Deviation 0.561 |
| Part B: VX-121 (Cohort B2) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | TEZ: Day 14 | 9.08 mcg/mL | Standard Deviation 0.547 |
| Part B: VX-121 (Cohort B2) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-TEZ: Day 1 | 1.24 mcg/mL | Standard Deviation 0.399 |
| Part B: VX-121 (Cohort B2) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-TEZ: Day 7 | 6.48 mcg/mL | Standard Deviation 1.48 |
| Part B: VX-121 (Cohort B2) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-TEZ: Day 14 | 8.12 mcg/mL | Standard Deviation 1.41 |
| Part B: VX-121 (Cohort B2) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | M2-TEZ: Day 1 | 0.622 mcg/mL | Standard Deviation 0.39 |
| Part B: VX-121 (Cohort B2) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | M2-TEZ: Day 7 | 6.16 mcg/mL | Standard Deviation 2.17 |
| Part B: VX-121 (Cohort B2) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | M2-TEZ: Day 14 | 8.78 mcg/mL | Standard Deviation 3.54 |
| Part B: VX-121 (Cohort B2) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 1 | 1.00 mcg/mL | Standard Deviation 0.235 |
| Part B: VX-121 (Cohort B2) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 7 | 1.40 mcg/mL | Standard Deviation 0.288 |
| Part B: VX-121 (Cohort B2) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 14 | 1.35 mcg/mL | Standard Deviation 0.231 |
| Part B: VX-121 (Cohort B2) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 1 | 2.34 mcg/mL | Standard Deviation 0.602 |
| Part B: VX-121 (Cohort B2) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 7 | 3.42 mcg/mL | Standard Deviation 0.534 |
| Part B: VX-121 (Cohort B2) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 14 | 2.97 mcg/mL | Standard Deviation 0.64 |
| Part B: VX-121 (Cohort B2) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 7 | 2.62 mcg/mL | Standard Deviation 1.2 |
| Part B: VX-121 (Cohort B2) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 14 | 2.26 mcg/mL | Standard Deviation 0.744 |
| Part B: VX-121 (Cohort B3) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-TEZ: Day 7 | 5.20 mcg/mL | Standard Deviation 0.606 |
| Part B: VX-121 (Cohort B3) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | VX-121: Day 7 | 0.364 mcg/mL | Standard Deviation 0.122 |
| Part B: VX-121 (Cohort B3) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 14 | 1.20 mcg/mL | Standard Deviation 0.402 |
| Part B: VX-121 (Cohort B3) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-TEZ: Day 1 | 1.12 mcg/mL | Standard Deviation 0.259 |
| Part B: VX-121 (Cohort B3) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 14 | 2.55 mcg/mL | Standard Deviation 2.2 |
| Part B: VX-121 (Cohort B3) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 1 | 1.51 mcg/mL | Standard Deviation 0.349 |
| Part B: VX-121 (Cohort B3) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | TEZ: Day 14 | 7.27 mcg/mL | Standard Deviation 1.4 |
| Part B: VX-121 (Cohort B3) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 7 | 1.88 mcg/mL | Standard Deviation 1.21 |
| Part B: VX-121 (Cohort B3) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 7 | 2.65 mcg/mL | Standard Deviation 0.434 |
| Part B: VX-121 (Cohort B3) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | TEZ: Day 7 | 7.50 mcg/mL | Standard Deviation 1.24 |
| Part B: VX-121 (Cohort B3) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | VX-121: Day 1 | 0.0728 mcg/mL | Standard Deviation 0.0102 |
| Part B: VX-121 (Cohort B3) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 14 | 3.14 mcg/mL | Standard Deviation 1.32 |
| Part B: VX-121 (Cohort B3) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | M2-TEZ: Day 7 | 5.56 mcg/mL | Standard Deviation 3.67 |
| Part B: VX-121 (Cohort B3) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | TEZ: Day 1 | 5.11 mcg/mL | Standard Deviation 1.35 |
| Part B: VX-121 (Cohort B3) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | M2-TEZ: Day 14 | 9.07 mcg/mL | Standard Deviation 6.13 |
| Part B: VX-121 (Cohort B3) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | M2-TEZ: Day 1 | 0.662 mcg/mL | Standard Deviation 0.32 |
| Part B: VX-121 (Cohort B3) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | VX-121: Day 14 | 0.385 mcg/mL | Standard Deviation 0.108 |
| Part B: VX-121 (Cohort B3) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 1 | 0.770 mcg/mL | Standard Deviation 0.169 |
| Part B: VX-121 (Cohort B3) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-TEZ: Day 14 | 6.70 mcg/mL | Standard Deviation 1.19 |
| Part B: VX-121 (Cohort B3) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 1 | 1.24 mcg/mL | Standard Deviation 0.727 |
| Part B: VX-121 (Cohort B3) | Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 7 | 1.37 mcg/mL | Standard Deviation 0.309 |
Secondary
Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA)
Time frame: Pre-dose at Day 7 and Day 14
Population: PK set. Here, the overall number of participants analyzed signifies those participants who were evaluable for this outcome measure and number analyzed signifies those participants who were evaluable for this outcome measure at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part B: VX-121 (Cohort B1) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 7 | 2.46 mcg/mL | Standard Deviation 1.53 |
| Part B: VX-121 (Cohort B1) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-TEZ: Day 14 | 5.45 mcg/mL | Standard Deviation 1.46 |
| Part B: VX-121 (Cohort B1) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | TEZ: Day 7 | 3.95 mcg/mL | Standard Deviation 1.84 |
| Part B: VX-121 (Cohort B1) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 14 | 1.34 mcg/mL | Standard Deviation 0.889 |
| Part B: VX-121 (Cohort B1) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M2-TEZ: Day 7 | 4.30 mcg/mL | Standard Deviation 1.66 |
| Part B: VX-121 (Cohort B1) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | VX-121: Day 14 | 1.24 mcg/mL | Standard Deviation 0.665 |
| Part B: VX-121 (Cohort B1) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 7 | 1.33 mcg/mL | Standard Deviation 0.834 |
| Part B: VX-121 (Cohort B1) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M2-TEZ: Day 14 | 6.20 mcg/mL | Standard Deviation 2.6 |
| Part B: VX-121 (Cohort B1) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 14 | 2.45 mcg/mL | Standard Deviation 1.37 |
| Part B: VX-121 (Cohort B1) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | TEZ: Day 14 | 4.55 mcg/mL | Standard Deviation 2.5 |
| Part B: VX-121 (Cohort B1) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 14 | 1.60 mcg/mL | Standard Deviation 0.926 |
| Part B: VX-121 (Cohort B1) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | VX-121: Day 7 | 0.916 mcg/mL | Standard Deviation 0.369 |
| Part B: VX-121 (Cohort B1) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-TEZ: Day 7 | 4.09 mcg/mL | Standard Deviation 1.22 |
| Part B: VX-121 (Cohort B1) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 7 | 1.28 mcg/mL | Standard Deviation 0.763 |
| Part B: VX-121 (Cohort B2) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 7 | 2.00 mcg/mL | Standard Deviation 0.589 |
| Part B: VX-121 (Cohort B2) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | VX-121: Day 7 | 1.37 mcg/mL | Standard Deviation 0.321 |
| Part B: VX-121 (Cohort B2) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | VX-121: Day 14 | 1.72 mcg/mL | Standard Deviation 0.452 |
| Part B: VX-121 (Cohort B2) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | TEZ: Day 7 | 2.57 mcg/mL | Standard Deviation 0.776 |
| Part B: VX-121 (Cohort B2) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | TEZ: Day 14 | 3.27 mcg/mL | Standard Deviation 0.646 |
| Part B: VX-121 (Cohort B2) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-TEZ: Day 7 | 4.53 mcg/mL | Standard Deviation 0.512 |
| Part B: VX-121 (Cohort B2) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-TEZ: Day 14 | 6.40 mcg/mL | Standard Deviation 1.17 |
| Part B: VX-121 (Cohort B2) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M2-TEZ: Day 7 | 5.08 mcg/mL | Standard Deviation 2.06 |
| Part B: VX-121 (Cohort B2) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M2-TEZ: Day 14 | 5.51 mcg/mL | Standard Deviation 1.72 |
| Part B: VX-121 (Cohort B2) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 7 | 0.768 mcg/mL | Standard Deviation 0.23 |
| Part B: VX-121 (Cohort B2) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 14 | 0.750 mcg/mL | Standard Deviation 0.252 |
| Part B: VX-121 (Cohort B2) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 14 | 1.87 mcg/mL | Standard Deviation 0.509 |
| Part B: VX-121 (Cohort B2) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 7 | 2.09 mcg/mL | Standard Deviation 1.11 |
| Part B: VX-121 (Cohort B2) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 14 | 1.85 mcg/mL | Standard Deviation 0.738 |
| Part B: VX-121 (Cohort B3) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 7 | 1.67 mcg/mL | Standard Deviation 1.31 |
| Part B: VX-121 (Cohort B3) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 14 | 0.601 mcg/mL | Standard Deviation 0.164 |
| Part B: VX-121 (Cohort B3) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-TEZ: Day 7 | 3.96 mcg/mL | Standard Deviation 0.685 |
| Part B: VX-121 (Cohort B3) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | TEZ: Day 14 | 2.27 mcg/mL | Standard Deviation 0.851 |
| Part B: VX-121 (Cohort B3) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 7 | 1.67 mcg/mL | Standard Deviation 0.334 |
| Part B: VX-121 (Cohort B3) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | TEZ: Day 7 | 2.31 mcg/mL | Standard Deviation 0.735 |
| Part B: VX-121 (Cohort B3) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | VX-121: Day 7 | 0.258 mcg/mL | Standard Deviation 0.0426 |
| Part B: VX-121 (Cohort B3) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 14 | 1.73 mcg/mL | Standard Deviation 0.977 |
| Part B: VX-121 (Cohort B3) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | VX-121: Day 14 | 0.357 mcg/mL | Standard Deviation 0.0966 |
| Part B: VX-121 (Cohort B3) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M2-TEZ: Day 14 | 8.63 mcg/mL | Standard Deviation 6.24 |
| Part B: VX-121 (Cohort B3) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M2-TEZ: Day 7 | 4.75 mcg/mL | Standard Deviation 2.97 |
| Part B: VX-121 (Cohort B3) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 14 | 2.27 mcg/mL | Standard Deviation 2.26 |
| Part B: VX-121 (Cohort B3) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 7 | 0.780 mcg/mL | Standard Deviation 0.317 |
| Part B: VX-121 (Cohort B3) | Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-TEZ: Day 14 | 5.03 mcg/mL | Standard Deviation 1.18 |
Secondary
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: FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part B: VX-121 (Cohort B1) | Part D: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | -2.0 percentage points |
| Part B: VX-121 (Cohort B2) | Part D: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | 8.3 percentage points |
Secondary
Part D: Absolute Change in Sweat Chloride (SwCl) Concentrations
Sweat samples were collected using an approved collection device.
Time frame: From Baseline Through Day 29
Population: Full analysis set (FAS) included all randomized participants who carry the intended CF transmembrane conductance regulator protein (CFTR) allele mutation and have received at least 1 dose of study drug in the treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part B: VX-121 (Cohort B1) | Part D: Absolute Change in Sweat Chloride (SwCl) Concentrations | 2.6 millimole per liter (mmol/L) |
| Part B: VX-121 (Cohort B2) | Part D: Absolute Change in Sweat Chloride (SwCl) Concentrations | -47.7 millimole per liter (mmol/L) |
Secondary
Part D: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA)
Time frame: Day 1 and Day 15
Population: PK set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part B: VX-121 (Cohort B1) | Part D: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | VX-121: Day 1 | 0.160 mcg*h/mL | Standard Deviation 0.0766 |
| Part B: VX-121 (Cohort B1) | Part D: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | VX-121: Day 15 | 2.50 mcg*h/mL | Standard Deviation 1.07 |
| Part B: VX-121 (Cohort B1) | Part D: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | TEZ: Day 1 | 21.9 mcg*h/mL | Standard Deviation 5.48 |
| Part B: VX-121 (Cohort B1) | Part D: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | TEZ: Day 15 | 37.4 mcg*h/mL | Standard Deviation 16 |
| Part B: VX-121 (Cohort B1) | Part D: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-TEZ: Day 1 | 4.66 mcg*h/mL | Standard Deviation 1.42 |
| Part B: VX-121 (Cohort B1) | Part D: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-TEZ: Day 15 | 37.8 mcg*h/mL | Standard Deviation 14.3 |
| Part B: VX-121 (Cohort B1) | Part D: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M2-TEZ: Day 1 | 0.630 mcg*h/mL | Standard Deviation 0.213 |
| Part B: VX-121 (Cohort B1) | Part D: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M2-TEZ: Day 15 | 28.6 mcg*h/mL | Standard Deviation 13.7 |
| Part B: VX-121 (Cohort B1) | Part D: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 1 | 2.74 mcg*h/mL | Standard Deviation 1.24 |
| Part B: VX-121 (Cohort B1) | Part D: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 15 | 9.27 mcg*h/mL | Standard Deviation 4.06 |
| Part B: VX-121 (Cohort B1) | Part D: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 1 | 4.51 mcg*h/mL | Standard Deviation 1.97 |
| Part B: VX-121 (Cohort B1) | Part D: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 15 | 16.4 mcg*h/mL | Standard Deviation 6.7 |
| Part B: VX-121 (Cohort B1) | Part D: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 1 | 1.25 mcg*h/mL | Standard Deviation 0.529 |
| Part B: VX-121 (Cohort B1) | Part D: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 15 | 7.58 mcg*h/mL | Standard Deviation 4.49 |
Secondary
Part D: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA)
Time frame: Day 1 and Day 15
Population: PK set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part B: VX-121 (Cohort B1) | Part D: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | VX-121: Day 1 | 0.0553 mcg/mL | Standard Deviation 0.0207 |
| Part B: VX-121 (Cohort B1) | Part D: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | VX-121: Day 15 | 0.389 mcg/mL | Standard Deviation 0.116 |
| Part B: VX-121 (Cohort B1) | Part D: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | TEZ: Day 1 | 5.38 mcg/mL | Standard Deviation 1.39 |
| Part B: VX-121 (Cohort B1) | Part D: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | TEZ: Day 15 | 6.80 mcg/mL | Standard Deviation 2.13 |
| Part B: VX-121 (Cohort B1) | Part D: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-TEZ: Day 1 | 1.26 mcg/mL | Standard Deviation 0.162 |
| Part B: VX-121 (Cohort B1) | Part D: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-TEZ: Day 15 | 5.56 mcg/mL | Standard Deviation 1.19 |
| Part B: VX-121 (Cohort B1) | Part D: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M2-TEZ: Day 1 | 0.243 mcg/mL | Standard Deviation 0.0629 |
| Part B: VX-121 (Cohort B1) | Part D: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M2-TEZ: Day 15 | 3.99 mcg/mL | Standard Deviation 1.41 |
| Part B: VX-121 (Cohort B1) | Part D: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 1 | 0.745 mcg/mL | Standard Deviation 0.279 |
| Part B: VX-121 (Cohort B1) | Part D: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 15 | 1.47 mcg/mL | Standard Deviation 0.472 |
| Part B: VX-121 (Cohort B1) | Part D: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 1 | 1.34 mcg/mL | Standard Deviation 0.478 |
| Part B: VX-121 (Cohort B1) | Part D: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 15 | 2.69 mcg/mL | Standard Deviation 0.829 |
| Part B: VX-121 (Cohort B1) | Part D: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 1 | 0.531 mcg/mL | Standard Deviation 0.229 |
| Part B: VX-121 (Cohort B1) | Part D: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 15 | 1.17 mcg/mL | Standard Deviation 0.589 |
Secondary
Part D: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA)
Time frame: Pre-dose at Day 8, Day 15, and Day 29
Population: PK set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part B: VX-121 (Cohort B1) | Part D: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 15 | 0.819 mcg/mL | Standard Deviation 0.412 |
| Part B: VX-121 (Cohort B1) | Part D: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | VX-121: Day 8 | 0.258 mcg/mL | Standard Deviation 0.0834 |
| Part B: VX-121 (Cohort B1) | Part D: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | VX-121: Day 15 | 0.348 mcg/mL | Standard Deviation 0.109 |
| Part B: VX-121 (Cohort B1) | Part D: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | VX-121: Day 29 | 0.323 mcg/mL | Standard Deviation 0.11 |
| Part B: VX-121 (Cohort B1) | Part D: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | TEZ: Day 8 | 1.78 mcg/mL | Standard Deviation 0.525 |
| Part B: VX-121 (Cohort B1) | Part D: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | TEZ: Day 15 | 2.01 mcg/mL | Standard Deviation 0.543 |
| Part B: VX-121 (Cohort B1) | Part D: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | TEZ: Day 29 | 2.02 mcg/mL | Standard Deviation 0.927 |
| Part B: VX-121 (Cohort B1) | Part D: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-TEZ: Day 8 | 4.15 mcg/mL | Standard Deviation 0.648 |
| Part B: VX-121 (Cohort B1) | Part D: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-TEZ: Day 15 | 4.52 mcg/mL | Standard Deviation 1.06 |
| Part B: VX-121 (Cohort B1) | Part D: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-TEZ: Day 29 | 5.11 mcg/mL | Standard Deviation 1.5 |
| Part B: VX-121 (Cohort B1) | Part D: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M2-TEZ: Day 8 | 3.29 mcg/mL | Standard Deviation 1.41 |
| Part B: VX-121 (Cohort B1) | Part D: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M2-TEZ: Day 15 | 3.76 mcg/mL | Standard Deviation 1.29 |
| Part B: VX-121 (Cohort B1) | Part D: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M2-TEZ: Day 29 | 4.57 mcg/mL | Standard Deviation 2.28 |
| Part B: VX-121 (Cohort B1) | Part D: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 8 | 0.873 mcg/mL | Standard Deviation 0.367 |
| Part B: VX-121 (Cohort B1) | Part D: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 15 | 0.998 mcg/mL | Standard Deviation 0.367 |
| Part B: VX-121 (Cohort B1) | Part D: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | IVA: Day 29 | 0.916 mcg/mL | Standard Deviation 0.586 |
| Part B: VX-121 (Cohort B1) | Part D: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 8 | 1.38 mcg/mL | Standard Deviation 0.427 |
| Part B: VX-121 (Cohort B1) | Part D: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 15 | 1.76 mcg/mL | Standard Deviation 0.619 |
| Part B: VX-121 (Cohort B1) | Part D: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M1-IVA: Day 29 | 1.62 mcg/mL | Standard Deviation 0.62 |
| Part B: VX-121 (Cohort B1) | Part D: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 8 | 0.823 mcg/mL | Standard Deviation 0.573 |
| Part B: VX-121 (Cohort B1) | Part D: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA) | M6-IVA: Day 29 | 0.990 mcg/mL | Standard Deviation 0.632 |