Cystic Fibrosis
Conditions
Brief summary
This is a Phase 2, randomized, double-blind, placebo- and tezacaftor/ivacaftor (TEZ/IVA)-controlled, parallel-group, 3-part, multicenter study designed to evaluate the safety and efficacy of VX-659 in triple combination (TC) with TEZ and IVA in subjects with cystic fibrosis (CF) who are homozygous for the F508del mutation of the CF transmembrane conductance regulator (CFTR) gene (F/F genotype), or who are heterozygous for the F508del mutation and a minimal function (MF) CFTR mutation not likely to respond to TEZ, IVA, or TEZ/IVA (F/MF genotypes).
Interventions
DRUGVX-659
Tablet for oral administration.
DRUGTEZ/IVA
TEZ/IVA fixed-dose combination tablet for oral administration.
DRUGIVA
Tablet for oral administration.
DRUGPlacebo (matched to VX-659/TEZ/IVA)
Placebo matched to VX-659 and TEZ/IVA.
DRUGTEZ
Tablet for oral administration.
DRUGVX-561
Tablet for oral administration.
DRUGPlacebo (matched to VX-659/TEZ/VX-561)
Placebo matched to VX-659, TEZ and VX-561.
Sponsors
Vertex Pharmaceuticals Incorporated
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Body weight ≥35 kg. * Subjects must have an eligibleCFTR genotype. * Part 1 and Part 3: Heterozygous for F508del and an MF mutation (F/MF) * Part 2: Homozygous for F508del (F/F) * FEV1 value ≥40% and ≤90% of predicted mean for age, sex, and height Key
Exclusion criteria
* History of clinically significant cirrhosis with or without portal hypertension. * Glucose-6-phosphate dehydrogenase (G6PD) deficiency * Lung infection with organisms associated with a more rapid decline in pulmonary status. * History of solid organ or hematological transplantation. Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Day 1 Through Safety Follow-up (up to Day 61 for Part 1, Day 85 for Part 2 and Day 57 for Part 3) | — |
| Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | From Baseline Through Day 29 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change in Sweat Chloride Concentrations | From Baseline Through Day 29 | Sweat samples were collected using an approved collection device. |
| Relative Change in ppFEV1 | From Baseline Through Day 29 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. |
| Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score | From Baseline at Day 29 | The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. |
| Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | Pre-dose at Day 15 and Day 29 | — |
Countries
Ireland, Israel, United Kingdom, United States
Participant flow
Recruitment details
Total of 124 participants were enrolled in this study (63 in Part 1, 36 in Part 2 and 25 in Part C). Out of 36 participants enrolled in Part 2, 7 participants discontinued treatment in run-in period and were not randomized in triple combination (TC) treatment period. Therefore, below results are presented for 117 participants.
Pre-assignment details
This study included 3 parts and was conducted in adult participants with cystic fibrosis (CF).
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Placebo Participants received placebo matched to VX-659/TEZ/IVA in TC treatment period for 4 weeks and placebo matched to TEZ/IVA in washout period for 4 days. | 10 |
| Part 1: VX-659/TEZ/IVA TC - Low Dose Participants received VX-659 80 mg qd/TEZ 100 mg qd/IVA 150 mg every 12 q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. | 11 |
| Part 1: VX-659/TEZ/IVA TC - Medium Dose Participants received VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. | 20 |
| Part 1: VX-659/TEZ/IVA TC - High Dose Participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. | 22 |
| Part 2: TEZ/IVA Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks. | 11 |
| Part 2: VX-659/TEZ/IVA TC Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks. | 18 |
| Part 3: Placebo Participants received placebo matched to VX-659/TEZ/VX-561 in TC treatment period for 4 weeks. | 6 |
| Part 3: VX-659/TEZ/VX-561 TC Participants received VX-659 400 mg qd/TEZ 100 mg qd/VX-561 200 mg qd in TC treatment period for 4 weeks. | 19 |
| Total | 117 |
Baseline characteristics
| Characteristic | Part 1: Placebo | Part 1: VX-659/TEZ/IVA TC - Low Dose | Part 1: VX-659/TEZ/IVA TC - Medium Dose | Part 1: VX-659/TEZ/IVA TC - High Dose | Part 2: TEZ/IVA | Part 2: VX-659/TEZ/IVA TC | Part 3: Placebo | Part 3: VX-659/TEZ/VX-561 TC | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized >=18 and <65 years | 10 Participants | 11 Participants | 20 Participants | 22 Participants | 11 Participants | 18 Participants | 6 Participants | 19 Participants | 117 Participants |
| Age, Customized <18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 11 Participants | 18 Participants | 22 Participants | 10 Participants | 17 Participants | 5 Participants | 18 Participants | 111 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 |
| Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) <40 percent | 2 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 8 Participants |
| Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) ≥40 to <70 percent | 6 Participants | 9 Participants | 13 Participants | 13 Participants | 8 Participants | 12 Participants | 5 Participants | 13 Participants | 79 Participants |
| Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) ≥70 to ≤90 percent | 2 Participants | 2 Participants | 6 Participants | 7 Participants | 3 Participants | 5 Participants | 1 Participants | 4 Participants | 30 Participants |
| Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) >90 percent | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 10 Participants | 11 Participants | 20 Participants | 22 Participants | 11 Participants | 16 Participants | 6 Participants | 17 Participants | 113 Participants |
| Sex: Female, Male Female | 4 Participants | 7 Participants | 7 Participants | 12 Participants | 4 Participants | 6 Participants | 3 Participants | 11 Participants | 54 Participants |
| Sex: Female, Male Male | 6 Participants | 4 Participants | 13 Participants | 10 Participants | 7 Participants | 12 Participants | 3 Participants | 8 Participants | 63 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 |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 11 | 0 / 20 | 0 / 22 | 0 / 11 | 0 / 18 | 0 / 6 | 0 / 19 |
| other Total, other adverse events | 8 / 10 | 10 / 11 | 15 / 20 | 17 / 22 | 8 / 11 | 15 / 18 | 5 / 6 | 18 / 19 |
| serious Total, serious adverse events | 3 / 10 | 1 / 11 | 4 / 20 | 1 / 22 | 2 / 11 | 1 / 18 | 3 / 6 | 2 / 19 |
Outcome results
Primary
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: Full Analysis Set (FAS) included all randomized participants with an eligible cystic fibrosis transmembrane conductance regulator protein (CFTR) genotype and received at least 1 dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Placebo | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | 0.4 percentage points |
| Part 1: VX-659/TEZ/IVA TC - Low Dose | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | 10.2 percentage points |
| Part 1: VX-659/TEZ/IVA TC - Medium Dose | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | 12.0 percentage points |
| Part 1: VX-659/TEZ/IVA TC - High Dose | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | 13.3 percentage points |
| Part 2: TEZ/IVA | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | 0.0 percentage points |
| Part 2: VX-659/TEZ/IVA TC | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | 9.7 percentage points |
| Part 3: Placebo | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | -5.0 percentage points |
| Part 3: VX-659/TEZ/VX-561 TC | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | 12.2 percentage points |
Primary
Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: Day 1 Through Safety Follow-up (up to Day 61 for Part 1, Day 85 for Part 2 and Day 57 for Part 3)
Population: Safety Set included all participants who received at least 1 dose of study drug in TC treatment period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: Placebo | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 9 participants |
| Part 1: Placebo | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 3 participants |
| Part 1: VX-659/TEZ/IVA TC - Low Dose | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 10 participants |
| Part 1: VX-659/TEZ/IVA TC - Low Dose | 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 1: VX-659/TEZ/IVA TC - Medium Dose | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 15 participants |
| Part 1: VX-659/TEZ/IVA TC - Medium Dose | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 4 participants |
| Part 1: VX-659/TEZ/IVA TC - High Dose | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 17 participants |
| Part 1: VX-659/TEZ/IVA TC - High Dose | 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 2: 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 | 9 participants |
| Part 2: 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 | 2 participants |
| Part 2: VX-659/TEZ/IVA TC | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 15 participants |
| Part 2: VX-659/TEZ/IVA TC | 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 3: Placebo | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 3 participants |
| Part 3: Placebo | 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 3: VX-659/TEZ/VX-561 TC | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 18 participants |
| Part 3: VX-659/TEZ/VX-561 TC | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 2 participants |
Secondary
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Time frame: From Baseline at Day 29
Population: FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Placebo | Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score | 4.7 units on a scale |
| Part 1: VX-659/TEZ/IVA TC - Low Dose | Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score | 24.6 units on a scale |
| Part 1: VX-659/TEZ/IVA TC - Medium Dose | Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score | 19.8 units on a scale |
| Part 1: VX-659/TEZ/IVA TC - High Dose | Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score | 21.8 units on a scale |
| Part 2: TEZ/IVA | Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score | 2.9 units on a scale |
| Part 2: VX-659/TEZ/IVA TC | Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score | 19.5 units on a scale |
| Part 3: Placebo | Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score | -4.1 units on a scale |
| Part 3: VX-659/TEZ/VX-561 TC | Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score | 14.7 units on a scale |
Secondary
Absolute Change in Sweat Chloride Concentrations
Sweat samples were collected using an approved collection device.
Time frame: From Baseline Through Day 29
Population: FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Placebo | Absolute Change in Sweat Chloride Concentrations | 2.9 millimole per liter (mmol/L) |
| Part 1: VX-659/TEZ/IVA TC - Low Dose | Absolute Change in Sweat Chloride Concentrations | -45.7 millimole per liter (mmol/L) |
| Part 1: VX-659/TEZ/IVA TC - Medium Dose | Absolute Change in Sweat Chloride Concentrations | -43.8 millimole per liter (mmol/L) |
| Part 1: VX-659/TEZ/IVA TC - High Dose | Absolute Change in Sweat Chloride Concentrations | -51.4 millimole per liter (mmol/L) |
| Part 2: TEZ/IVA | Absolute Change in Sweat Chloride Concentrations | 3.0 millimole per liter (mmol/L) |
| Part 2: VX-659/TEZ/IVA TC | Absolute Change in Sweat Chloride Concentrations | -42.2 millimole per liter (mmol/L) |
| Part 3: Placebo | Absolute Change in Sweat Chloride Concentrations | -1.3 millimole per liter (mmol/L) |
| Part 3: VX-659/TEZ/VX-561 TC | Absolute Change in Sweat Chloride Concentrations | -38.1 millimole per liter (mmol/L) |
Secondary
Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561
Time frame: Pre-dose at Day 15 and Day 29
Population: Pharmacokinetic Set (PK) included all participants who have received at least 1 dose of study drug in TC treatment period. Here Number Analyzed signifies those participants who were evaluable at specified time points. VX-659 category was not applicable for Part 2: TEZ/IVA group. VX-561 category was applicable for Part 3: TC group only. IVA and M1-IVA categories were not applicable for Part 3: TC group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Placebo | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | TEZ: Day 29 | 1910 nanogram per milliliter (ng/mL) | Standard Deviation 1230 |
| Part 1: Placebo | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | VX-659: Day 15 | 393 nanogram per milliliter (ng/mL) | Standard Deviation 604 |
| Part 1: Placebo | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | M1-IVA: Day 15 | 1200 nanogram per milliliter (ng/mL) | Standard Deviation 711 |
| Part 1: Placebo | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | IVA: Day 29 | 719 nanogram per milliliter (ng/mL) | Standard Deviation 604 |
| Part 1: Placebo | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | TEZ: Day 15 | 1910 nanogram per milliliter (ng/mL) | Standard Deviation 1360 |
| Part 1: Placebo | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | M1-TEZ: Day 29 | 4300 nanogram per milliliter (ng/mL) | Standard Deviation 774 |
| Part 1: Placebo | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | VX-659: Day 29 | 566 nanogram per milliliter (ng/mL) | Standard Deviation 861 |
| Part 1: Placebo | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | IVA: Day 15 | 824 nanogram per milliliter (ng/mL) | Standard Deviation 781 |
| Part 1: Placebo | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | M1-IVA Day 29 | 1130 nanogram per milliliter (ng/mL) | Standard Deviation 682 |
| Part 1: Placebo | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | M1-TEZ: Day 15 | 4390 nanogram per milliliter (ng/mL) | Standard Deviation 949 |
| Part 1: VX-659/TEZ/IVA TC - Low Dose | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | M1-TEZ: Day 15 | 3710 nanogram per milliliter (ng/mL) | Standard Deviation 1230 |
| Part 1: VX-659/TEZ/IVA TC - Low Dose | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | TEZ: Day 15 | 1250 nanogram per milliliter (ng/mL) | Standard Deviation 907 |
| Part 1: VX-659/TEZ/IVA TC - Low Dose | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | M1-IVA Day 29 | 1140 nanogram per milliliter (ng/mL) | Standard Deviation 950 |
| Part 1: VX-659/TEZ/IVA TC - Low Dose | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | TEZ: Day 29 | 1050 nanogram per milliliter (ng/mL) | Standard Deviation 553 |
| Part 1: VX-659/TEZ/IVA TC - Low Dose | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | IVA: Day 15 | 522 nanogram per milliliter (ng/mL) | Standard Deviation 567 |
| Part 1: VX-659/TEZ/IVA TC - Low Dose | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | M1-IVA: Day 15 | 1050 nanogram per milliliter (ng/mL) | Standard Deviation 852 |
| Part 1: VX-659/TEZ/IVA TC - Low Dose | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | VX-659: Day 15 | 622 nanogram per milliliter (ng/mL) | Standard Deviation 429 |
| Part 1: VX-659/TEZ/IVA TC - Low Dose | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | IVA: Day 29 | 443 nanogram per milliliter (ng/mL) | Standard Deviation 398 |
| Part 1: VX-659/TEZ/IVA TC - Low Dose | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | M1-TEZ: Day 29 | 3650 nanogram per milliliter (ng/mL) | Standard Deviation 1280 |
| Part 1: VX-659/TEZ/IVA TC - Low Dose | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | VX-659: Day 29 | 699 nanogram per milliliter (ng/mL) | Standard Deviation 489 |
| Part 1: VX-659/TEZ/IVA TC - Medium Dose | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | M1-TEZ: Day 29 | 3870 nanogram per milliliter (ng/mL) | Standard Deviation 1020 |
| Part 1: VX-659/TEZ/IVA TC - Medium Dose | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | M1-IVA: Day 15 | 1170 nanogram per milliliter (ng/mL) | Standard Deviation 674 |
| Part 1: VX-659/TEZ/IVA TC - Medium Dose | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | M1-IVA Day 29 | 1030 nanogram per milliliter (ng/mL) | Standard Deviation 460 |
| Part 1: VX-659/TEZ/IVA TC - Medium Dose | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | VX-659: Day 15 | 1100 nanogram per milliliter (ng/mL) | Standard Deviation 731 |
| Part 1: VX-659/TEZ/IVA TC - Medium Dose | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | VX-659: Day 29 | 1080 nanogram per milliliter (ng/mL) | Standard Deviation 582 |
| Part 1: VX-659/TEZ/IVA TC - Medium Dose | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | TEZ: Day 15 | 1110 nanogram per milliliter (ng/mL) | Standard Deviation 455 |
| Part 1: VX-659/TEZ/IVA TC - Medium Dose | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | TEZ: Day 29 | 1010 nanogram per milliliter (ng/mL) | Standard Deviation 479 |
| Part 1: VX-659/TEZ/IVA TC - Medium Dose | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | M1-TEZ: Day 15 | 4280 nanogram per milliliter (ng/mL) | Standard Deviation 1190 |
| Part 1: VX-659/TEZ/IVA TC - Medium Dose | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | IVA: Day 15 | 423 nanogram per milliliter (ng/mL) | Standard Deviation 261 |
| Part 1: VX-659/TEZ/IVA TC - Medium Dose | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | IVA: Day 29 | 371 nanogram per milliliter (ng/mL) | Standard Deviation 220 |
| Part 1: VX-659/TEZ/IVA TC - High Dose | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | TEZ: Day 29 | 1150 nanogram per milliliter (ng/mL) | Standard Deviation 480 |
| Part 1: VX-659/TEZ/IVA TC - High Dose | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | IVA: Day 29 | 490 nanogram per milliliter (ng/mL) | Standard Deviation 179 |
| Part 1: VX-659/TEZ/IVA TC - High Dose | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | M1-TEZ: Day 15 | 4160 nanogram per milliliter (ng/mL) | Standard Deviation 1260 |
| Part 1: VX-659/TEZ/IVA TC - High Dose | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | M1-TEZ: Day 29 | 3790 nanogram per milliliter (ng/mL) | Standard Deviation 1080 |
| Part 1: VX-659/TEZ/IVA TC - High Dose | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | IVA: Day 15 | 458 nanogram per milliliter (ng/mL) | Standard Deviation 239 |
| Part 1: VX-659/TEZ/IVA TC - High Dose | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | M1-IVA Day 29 | 1240 nanogram per milliliter (ng/mL) | Standard Deviation 321 |
| Part 1: VX-659/TEZ/IVA TC - High Dose | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | TEZ: Day 15 | 1050 nanogram per milliliter (ng/mL) | Standard Deviation 473 |
| Part 1: VX-659/TEZ/IVA TC - High Dose | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | M1-IVA: Day 15 | 1310 nanogram per milliliter (ng/mL) | Standard Deviation 684 |
| Part 2: TEZ/IVA | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | M1-TEZ: Day 15 | 4010 nanogram per milliliter (ng/mL) | Standard Deviation 1210 |
| Part 2: TEZ/IVA | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | M1-IVA: Day 15 | 844 nanogram per milliliter (ng/mL) | Standard Deviation 622 |
| Part 2: TEZ/IVA | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | M1-TEZ: Day 29 | 3810 nanogram per milliliter (ng/mL) | Standard Deviation 1120 |
| Part 2: TEZ/IVA | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | M1-IVA Day 29 | 866 nanogram per milliliter (ng/mL) | Standard Deviation 691 |
| Part 2: TEZ/IVA | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | IVA: Day 29 | 296 nanogram per milliliter (ng/mL) | Standard Deviation 175 |
| Part 2: TEZ/IVA | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | TEZ: Day 29 | 955 nanogram per milliliter (ng/mL) | Standard Deviation 422 |
| Part 2: TEZ/IVA | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | VX-659: Day 29 | 1070 nanogram per milliliter (ng/mL) | Standard Deviation 914 |
| Part 2: TEZ/IVA | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | IVA: Day 15 | 313 nanogram per milliliter (ng/mL) | Standard Deviation 158 |
| Part 2: TEZ/IVA | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | TEZ: Day 15 | 1350 nanogram per milliliter (ng/mL) | Standard Deviation 1440 |
| Part 2: TEZ/IVA | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | VX-659: Day 15 | 835 nanogram per milliliter (ng/mL) | Standard Deviation 474 |
| Part 2: VX-659/TEZ/IVA TC | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | VX-659: Day 15 | 1140 nanogram per milliliter (ng/mL) | Standard Deviation 646 |
| Part 2: VX-659/TEZ/IVA TC | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | VX-659: Day 29 | 923 nanogram per milliliter (ng/mL) | Standard Deviation 582 |
| Part 2: VX-659/TEZ/IVA TC | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | VX-561: Day 29 | 288 nanogram per milliliter (ng/mL) | Standard Deviation 165 |
| Part 2: VX-659/TEZ/IVA TC | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | TEZ: Day 15 | 1000 nanogram per milliliter (ng/mL) | Standard Deviation 305 |
| Part 2: VX-659/TEZ/IVA TC | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | M1-TEZ: Day 15 | 4060 nanogram per milliliter (ng/mL) | Standard Deviation 660 |
| Part 2: VX-659/TEZ/IVA TC | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | M1-TEZ: Day 29 | 3660 nanogram per milliliter (ng/mL) | Standard Deviation 1190 |
| Part 2: VX-659/TEZ/IVA TC | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | VX-561: Day 15 | 380 nanogram per milliliter (ng/mL) | Standard Deviation 240 |
| Part 2: VX-659/TEZ/IVA TC | Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 | TEZ: Day 29 | 776 nanogram per milliliter (ng/mL) | Standard Deviation 321 |
Secondary
Relative Change in 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 1: Placebo | Relative Change in ppFEV1 | 0.0 percent change |
| Part 1: VX-659/TEZ/IVA TC - Low Dose | Relative Change in ppFEV1 | 18.8 percent change |
| Part 1: VX-659/TEZ/IVA TC - Medium Dose | Relative Change in ppFEV1 | 21.1 percent change |
| Part 1: VX-659/TEZ/IVA TC - High Dose | Relative Change in ppFEV1 | 24.6 percent change |
| Part 2: TEZ/IVA | Relative Change in ppFEV1 | 0.1 percent change |
| Part 2: VX-659/TEZ/IVA TC | Relative Change in ppFEV1 | 17.3 percent change |
| Part 3: Placebo | Relative Change in ppFEV1 | -11.3 percent change |
| Part 3: VX-659/TEZ/VX-561 TC | Relative Change in ppFEV1 | 21.5 percent change |