Cystic Fibrosis
Conditions
Brief summary
This is a Phase 2, randomized, double blind, placebo and active-controlled, parallel group, multicenter study designed to evaluate the safety and tolerability of VX-152 in Triple Combination (TC) with tezacaftor (TEZ; VX-661) and ivacaftor (IVA; VX-770) in subjects with cystic fibrosis (CF) who are heterozygous for the F508del mutation and a minimal function (MF) CFTR mutation not likely to respond to TEZ and/or IVA therapy (F508del/MF), or who are homozygous for the F508del mutation of the CF transmembrane conductance regulator (CFTR) gene (F508del/F508del).
Interventions
DRUGTEZ/IVA
Fixed-dose combination tablet for oral administration.
DRUGIVA
Tablet for oral administration.
DRUGPlacebo
Placebo matched to VX-152.
DRUGVX-152
Tablet for oral administration.
Sponsors
Vertex Pharmaceuticals Incorporated
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Willing and able to comply with scheduled visits, treatment pan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures. * Body weight ≥35 kg. * Sweat chloride value ≥ 60 mmol/L from test results obtained during screening. * Subjects must have an eligible CFTR genotype: * Cohorts 1A, 1B, 1C: Heterozygous for F508del and a minimal function mutation known or predicted not to respond to TEZ and/or IVA. * Cohorts 2A, 2B: Homozygous for F508del. * Subjects must have an FEV1 ≥40% and ≤90% of predicted normal for age, sex, and height at the Screening Visit. * Stable CF disease as judged by the investigator. * Willing to remain on a stable CF medication regimen through the planned end of treatment or if applicable the Safety Follow-up Visit.
Exclusion criteria
* History of any comorbidity that in the opinion of the investigator might confound the results of the study or pose an additional risk in administering study drug to the subject. * History of cirrhosis with portal hypertension. * Risk factors for Torsade de Pointes. * History of hemolysis. * Glucose-6-phosphate dehydrogenase (G6PD) deficiency assessed at Screening. * Clinically significant abnormal laboratory values at screening. * An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 28 days before the first dose of study drug. * Lung infection with organisms associated with a more rapid decline in pulmonary status. * An acute illness not related to CF within 14 days before the first dose of study drug. * A standard digital ECG demonstrating QTc \>450 msec at screening. * History of solid organ or hematological transplantation. * History or evidence of cataract or lens opacity determined to be clinically significant by the ophthalmologist or optometrist, based on the ophthalmologic examination during the Screening Period. * History of alcohol or drug abuse in the past year, including but not limited to, cannabis, cocaine, and opiates, as deemed by the investigator. * Ongoing or prior participation in an investigational drug study with certain exceptions. * Use of commercially available CFTR modulator within 14 days before screening (applies only to Cohorts 1A, 1B, and 1C). * Pregnant or nursing females: Females of childbearing potential must have a negative pregnancy test at screening and Day 1.
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 Visit (Up to Day 43 for Part 1 and Day 71 for Part 2) | — |
| Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 15 for Part 1 and Part 2 Cohort 2A | From Baseline at Day 15 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. |
| Absolute Change in ppFEV1 Through Day 29 for Part 2 Cohort 2B | 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 |
|---|---|---|
| Relative Change in ppFEV1 Through Day 29 for Part 2 Cohort 2B | 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 at Day 15 for Part 1 and Part 2 Cohort 2A | From Baseline at Day 15 | 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. |
| Absolute Change in Sweat Chloride Concentrations at Day 15 for Part 1 and Part 2 Cohort 2A | From Baseline at Day 15 | Sweat samples were collected using an approved collection device. |
| Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Pre-dose at Day 8, Day 15 and Day 29 | — |
| Absolute Change From Baseline in CFQ-R Respiratory Domain Score at Day 29 for Part 2 Cohort 2B | 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. |
| Absolute Change in Sweat Chloride Concentrations Through Day 29 for Part 2 Cohort 2B | From Baseline Through Day 29 | Sweat samples were collected using an approved collection device. |
| Relative Change in ppFEV1 at Day 15 for Part 1 and Part 2 Cohort 2A | From Baseline at Day 15 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. |
Countries
United States
Participant flow
Pre-assignment details
A total of 80 participants were enrolled in the study (34 participants in Part 1 and 46 participants in Part 2). Out of 46 participants enrolled in Part 2, 4 participants discontinued during the run-in period and were not randomized in the treatment period. Therefore, results are presented for 76 participants in this study.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Placebo Participants received placebo matched to VX-152/TEZ/IVA TC for 2 weeks. | 8 |
| Part 1 Cohort 1A: TC Participants received VX-152 100 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks. | 6 |
| Part 1 Cohort 1B: TC Participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks. | 10 |
| Part 1 Cohort 1C: TC Participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks. | 10 |
| Part 2 Cohort 2A: TEZ/IVA Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. | 4 |
| Part 2 Cohort 2A: TC Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. | 10 |
| Part 2 Cohort 2B: TEZ/IVA Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. | 7 |
| Part 2 Cohort 2B: TC Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. | 21 |
| Total | 76 |
Baseline characteristics
| Characteristic | Part 1: Placebo | Part 1 Cohort 1A: TC | Part 1 Cohort 1B: TC | Part 1 Cohort 1C: TC | Part 2 Cohort 2A: TEZ/IVA | Part 2 Cohort 2A: TC | Part 2 Cohort 2B: TEZ/IVA | Part 2 Cohort 2B: TC | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized >=18 and <65 years | 8 Participants | 6 Participants | 10 Participants | 10 Participants | 4 Participants | 10 Participants | 7 Participants | 21 Participants | 76 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 | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 6 Participants | 10 Participants | 9 Participants | 4 Participants | 10 Participants | 7 Participants | 21 Participants | 73 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 | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants |
| Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) ≥40 to <70 percent | 5 Participants | 6 Participants | 7 Participants | 4 Participants | 3 Participants | 10 Participants | 5 Participants | 18 Participants | 58 Participants |
| Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) ≥70 to ≤90 percent | 2 Participants | 0 Participants | 1 Participants | 5 Participants | 1 Participants | 0 Participants | 2 Participants | 3 Participants | 14 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| 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 | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 7 Participants | 5 Participants | 10 Participants | 10 Participants | 4 Participants | 10 Participants | 7 Participants | 21 Participants | 74 Participants |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 4 Participants | 3 Participants | 2 Participants | 6 Participants | 4 Participants | 14 Participants | 39 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 6 Participants | 7 Participants | 2 Participants | 4 Participants | 3 Participants | 7 Participants | 37 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 / 8 | 0 / 6 | 0 / 10 | 0 / 10 | 0 / 4 | 0 / 10 | 0 / 7 | 0 / 21 |
| other Total, other adverse events | 8 / 8 | 3 / 6 | 7 / 10 | 9 / 10 | 3 / 4 | 6 / 10 | 5 / 7 | 18 / 21 |
| serious Total, serious adverse events | 2 / 8 | 0 / 6 | 0 / 10 | 1 / 10 | 0 / 4 | 0 / 10 | 0 / 7 | 0 / 21 |
Outcome results
Primary
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 15 for Part 1 and Part 2 Cohort 2A
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time frame: From Baseline at Day 15
Population: Full Analysis Set (FAS) included all randomized participants with the intended cystic fibrosis transmembrane conductance regulator protein (CFTR) allele mutation who received at least 1 dose of study drug in the treatment period. As pre-specified in analysis plan, only Part 1 and Part 2 Cohort 2A arms were assessed for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Placebo | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 15 for Part 1 and Part 2 Cohort 2A | -0.8 percentage points |
| Part 1 Cohort 1A: TC | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 15 for Part 1 and Part 2 Cohort 2A | 5.7 percentage points |
| Part 1 Cohort 1B: TC | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 15 for Part 1 and Part 2 Cohort 2A | 9.7 percentage points |
| Part 1 Cohort 1C: TC | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 15 for Part 1 and Part 2 Cohort 2A | 8.0 percentage points |
| Part 2 Cohort 2A: TEZ/IVA | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 15 for Part 1 and Part 2 Cohort 2A | -1.0 percentage points |
| Part 2 Cohort 2A: TC | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 15 for Part 1 and Part 2 Cohort 2A | 7.3 percentage points |
p-value: 0.020795% CI: [0.3, 12.6]Mixed-effects Model for Repeated Measure
p-value: 0.000295% CI: [5, 15.9]Mixed-effects Model for Repeated Measure
p-value: 0.001995% CI: [3, 14.5]Mixed-effects Model for Repeated Measure
p-value: 0.05495% CI: [-2.1, 18.7]Mixed-effects Model for Repeated Measure
Primary
Absolute Change in ppFEV1 Through Day 29 for Part 2 Cohort 2B
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. As pre-specified in analysis plan, only Part 2 Cohort 2B arms were assessed for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Placebo | Absolute Change in ppFEV1 Through Day 29 for Part 2 Cohort 2B | -2.2 percentage points |
| Part 1 Cohort 1A: TC | Absolute Change in ppFEV1 Through Day 29 for Part 2 Cohort 2B | 6.5 percentage points |
p-value: 0.000795% CI: [3.7, 13.8]Mixed-effects Model for Repeated Measure
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 Visit (Up to Day 43 for Part 1 and Day 71 for Part 2)
Population: Safety Set included all participants who received at least 1 dose of study drug in the 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 | 8 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 | 2 participants |
| Part 1 Cohort 1A: TC | 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 1 Cohort 1A: TC | 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 1 Cohort 1B: TC | 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 1 Cohort 1B: TC | 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 1 Cohort 1C: TC | 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 Cohort 1C: 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 2 Cohort 2A: 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 | 3 participants |
| Part 2 Cohort 2A: 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 |
| Part 2 Cohort 2A: TC | 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 2 Cohort 2A: TC | 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 2 Cohort 2B: 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 |
| Part 2 Cohort 2B: 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 | 5 participants |
| Part 2 Cohort 2B: TC | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 19 participants |
| Part 2 Cohort 2B: TC | 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
Absolute Change From Baseline in CFQ-R Respiratory Domain Score at Day 29 for Part 2 Cohort 2B
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. As pre-specified in analysis plan, only Part 2 Cohort 2B arms were assessed for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Placebo | Absolute Change From Baseline in CFQ-R Respiratory Domain Score at Day 29 for Part 2 Cohort 2B | 4.8 units on a scale |
| Part 1 Cohort 1A: TC | Absolute Change From Baseline in CFQ-R Respiratory Domain Score at Day 29 for Part 2 Cohort 2B | 16.1 units on a scale |
p-value: 0.013895% CI: [1.3, 21.2]Mixed-effects Model for Repeated Measure
Secondary
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Day 15 for Part 1 and Part 2 Cohort 2A
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 15
Population: FAS. As pre-specified in analysis plan, only Part 1 and Part 2 Cohort 2A arms were assessed for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Placebo | Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Day 15 for Part 1 and Part 2 Cohort 2A | -7.6 units on a scale |
| Part 1 Cohort 1A: TC | Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Day 15 for Part 1 and Part 2 Cohort 2A | 6.6 units on a scale |
| Part 1 Cohort 1B: TC | Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Day 15 for Part 1 and Part 2 Cohort 2A | 21.8 units on a scale |
| Part 1 Cohort 1C: TC | Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Day 15 for Part 1 and Part 2 Cohort 2A | 18.6 units on a scale |
| Part 2 Cohort 2A: TEZ/IVA | Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Day 15 for Part 1 and Part 2 Cohort 2A | 5.8 units on a scale |
| Part 2 Cohort 2A: TC | Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Day 15 for Part 1 and Part 2 Cohort 2A | 10.6 units on a scale |
p-value: 0.047695% CI: [-2.6, 30.9]ANCOVA
p-value: 0.000195% CI: [14.8, 44]ANCOVA
p-value: 0.000695% CI: [11.3, 41.1]ANCOVA
p-value: 0.271495% CI: [-11.6, 21.2]Mixed-effects Model for Repeated Measure
Secondary
Absolute Change in Sweat Chloride Concentrations at Day 15 for Part 1 and Part 2 Cohort 2A
Sweat samples were collected using an approved collection device.
Time frame: From Baseline at Day 15
Population: FAS. As pre-specified in analysis plan, only Part 1 and Part 2 Cohort 2A arms were assessed for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Placebo | Absolute Change in Sweat Chloride Concentrations at Day 15 for Part 1 and Part 2 Cohort 2A | -0.1 millimole per liter (mmol/L) |
| Part 1 Cohort 1A: TC | Absolute Change in Sweat Chloride Concentrations at Day 15 for Part 1 and Part 2 Cohort 2A | -19.5 millimole per liter (mmol/L) |
| Part 1 Cohort 1B: TC | Absolute Change in Sweat Chloride Concentrations at Day 15 for Part 1 and Part 2 Cohort 2A | -13.6 millimole per liter (mmol/L) |
| Part 1 Cohort 1C: TC | Absolute Change in Sweat Chloride Concentrations at Day 15 for Part 1 and Part 2 Cohort 2A | -27.5 millimole per liter (mmol/L) |
| Part 2 Cohort 2A: TEZ/IVA | Absolute Change in Sweat Chloride Concentrations at Day 15 for Part 1 and Part 2 Cohort 2A | 3.5 millimole per liter (mmol/L) |
| Part 2 Cohort 2A: TC | Absolute Change in Sweat Chloride Concentrations at Day 15 for Part 1 and Part 2 Cohort 2A | -21.3 millimole per liter (mmol/L) |
p-value: 0.001895% CI: [-32.2, -6.8]Mixed-effects Model for Repeated Measure
p-value: 0.010695% CI: [-25, -2.1]Mixed-effects Model for Repeated Measure
p-value: <0.000195% CI: [-38.6, -16.3]Mixed-effects Model for Repeated Measure
p-value: 0.001795% CI: [-40, -9.7]Mixed-effects Model for Repeated Measure
Secondary
Absolute Change in Sweat Chloride Concentrations Through Day 29 for Part 2 Cohort 2B
Sweat samples were collected using an approved collection device.
Time frame: From Baseline Through Day 29
Population: FAS. As pre-specified in analysis plan, only Part 2 Cohort 2B arms were assessed for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Placebo | Absolute Change in Sweat Chloride Concentrations Through Day 29 for Part 2 Cohort 2B | 1.6 mmol/L |
| Part 1 Cohort 1A: TC | Absolute Change in Sweat Chloride Concentrations Through Day 29 for Part 2 Cohort 2B | -22.3 mmol/L |
p-value: <0.000195% CI: [-33.7, -14.1]Mixed-effects Model for Repeated Measure
Secondary
Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA
Time frame: Pre-dose at Day 8, Day 15 and Day 29
Population: Pharmacokinetic Set (PK) included all participants who received at least 1 dose of study drug in treatment period. Here Number Analyzed signifies those participants who were evaluable at specified time points. Day 29 assessments were planned for Part 2: Cohort 2B groups only. VX-152 Ctrough category was not applicable to Part 2: TEZ/IVA groups.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Placebo | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 15: TEZ | 2450 nanogram per milliliter (ng/mL) | Standard Deviation 2000 |
| Part 1: Placebo | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 8: M1-TEZ | 4520 nanogram per milliliter (ng/mL) | Standard Deviation 1090 |
| Part 1: Placebo | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 15: M1-IVA | 1230 nanogram per milliliter (ng/mL) | Standard Deviation 326 |
| Part 1: Placebo | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 8: IVA | 779 nanogram per milliliter (ng/mL) | Standard Deviation 442 |
| Part 1: Placebo | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 8: M1-IVA | 1590 nanogram per milliliter (ng/mL) | Standard Deviation 1050 |
| Part 1: Placebo | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 15: VX-152 | 173 nanogram per milliliter (ng/mL) | Standard Deviation 72.1 |
| Part 1: Placebo | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 15: IVA | 841 nanogram per milliliter (ng/mL) | Standard Deviation 588 |
| Part 1: Placebo | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 8: TEZ | 2610 nanogram per milliliter (ng/mL) | Standard Deviation 1400 |
| Part 1: Placebo | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 15: M1-TEZ | 4680 nanogram per milliliter (ng/mL) | Standard Deviation 1020 |
| Part 1: Placebo | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 8: VX-152 | 167 nanogram per milliliter (ng/mL) | Standard Deviation 65.4 |
| Part 1 Cohort 1A: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 15: M1-TEZ | 2890 nanogram per milliliter (ng/mL) | Standard Deviation 898 |
| Part 1 Cohort 1A: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 15: VX-152 | 278 nanogram per milliliter (ng/mL) | Standard Deviation 212 |
| Part 1 Cohort 1A: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 8: M1-TEZ | 3060 nanogram per milliliter (ng/mL) | Standard Deviation 1480 |
| Part 1 Cohort 1A: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 15: M1-IVA | 1200 nanogram per milliliter (ng/mL) | Standard Deviation 848 |
| Part 1 Cohort 1A: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 8: VX-152 | 240 nanogram per milliliter (ng/mL) | Standard Deviation 370 |
| Part 1 Cohort 1A: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 15: TEZ | 1220 nanogram per milliliter (ng/mL) | Standard Deviation 545 |
| Part 1 Cohort 1A: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 8: IVA | 522 nanogram per milliliter (ng/mL) | Standard Deviation 401 |
| Part 1 Cohort 1A: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 8: TEZ | 1500 nanogram per milliliter (ng/mL) | Standard Deviation 1140 |
| Part 1 Cohort 1A: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 15: IVA | 535 nanogram per milliliter (ng/mL) | Standard Deviation 310 |
| Part 1 Cohort 1A: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 8: M1-IVA | 1040 nanogram per milliliter (ng/mL) | Standard Deviation 947 |
| Part 1 Cohort 1B: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 8: M1-IVA | 1330 nanogram per milliliter (ng/mL) | Standard Deviation 747 |
| Part 1 Cohort 1B: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 15: IVA | 467 nanogram per milliliter (ng/mL) | Standard Deviation 236 |
| Part 1 Cohort 1B: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 15: VX-152 | 804 nanogram per milliliter (ng/mL) | Standard Deviation 812 |
| Part 1 Cohort 1B: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 15: M1-IVA | 1140 nanogram per milliliter (ng/mL) | Standard Deviation 550 |
| Part 1 Cohort 1B: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 8: TEZ | 1680 nanogram per milliliter (ng/mL) | Standard Deviation 996 |
| Part 1 Cohort 1B: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 15: TEZ | 1180 nanogram per milliliter (ng/mL) | Standard Deviation 495 |
| Part 1 Cohort 1B: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 8: VX-152 | 538 nanogram per milliliter (ng/mL) | Standard Deviation 576 |
| Part 1 Cohort 1B: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 8: M1-TEZ | 3490 nanogram per milliliter (ng/mL) | Standard Deviation 1640 |
| Part 1 Cohort 1B: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 15: M1-TEZ | 3310 nanogram per milliliter (ng/mL) | Standard Deviation 1220 |
| Part 1 Cohort 1B: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 8: IVA | 545 nanogram per milliliter (ng/mL) | Standard Deviation 234 |
| Part 1 Cohort 1C: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 15: IVA | 441 nanogram per milliliter (ng/mL) | Standard Deviation 300 |
| Part 1 Cohort 1C: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 8: M1-TEZ | 3760 nanogram per milliliter (ng/mL) | Standard Deviation 1100 |
| Part 1 Cohort 1C: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 8: M1-IVA | 1660 nanogram per milliliter (ng/mL) | Standard Deviation 1200 |
| Part 1 Cohort 1C: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 8: TEZ | 1900 nanogram per milliliter (ng/mL) | Standard Deviation 1730 |
| Part 1 Cohort 1C: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 8: IVA | 702 nanogram per milliliter (ng/mL) | Standard Deviation 425 |
| Part 1 Cohort 1C: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 15: M1-TEZ | 3430 nanogram per milliliter (ng/mL) | Standard Deviation 824 |
| Part 1 Cohort 1C: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 15: M1-IVA | 1030 nanogram per milliliter (ng/mL) | Standard Deviation 762 |
| Part 1 Cohort 1C: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 15: TEZ | 1120 nanogram per milliliter (ng/mL) | Standard Deviation 135 |
| Part 2 Cohort 2A: TEZ/IVA | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 8: M1-IVA | 1470 nanogram per milliliter (ng/mL) | Standard Deviation 671 |
| Part 2 Cohort 2A: TEZ/IVA | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 15: M1-TEZ | 4270 nanogram per milliliter (ng/mL) | Standard Deviation 1280 |
| Part 2 Cohort 2A: TEZ/IVA | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 15: M1-IVA | 1510 nanogram per milliliter (ng/mL) | Standard Deviation 891 |
| Part 2 Cohort 2A: TEZ/IVA | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 8: IVA | 610 nanogram per milliliter (ng/mL) | Standard Deviation 262 |
| Part 2 Cohort 2A: TEZ/IVA | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 8: M1-TEZ | 4900 nanogram per milliliter (ng/mL) | Standard Deviation 1050 |
| Part 2 Cohort 2A: TEZ/IVA | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 8: VX-152 | 355 nanogram per milliliter (ng/mL) | Standard Deviation 287 |
| Part 2 Cohort 2A: TEZ/IVA | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 15: TEZ | 1620 nanogram per milliliter (ng/mL) | Standard Deviation 1030 |
| Part 2 Cohort 2A: TEZ/IVA | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 8: TEZ | 1830 nanogram per milliliter (ng/mL) | Standard Deviation 693 |
| Part 2 Cohort 2A: TEZ/IVA | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 15: VX-152 | 554 nanogram per milliliter (ng/mL) | Standard Deviation 429 |
| Part 2 Cohort 2A: TEZ/IVA | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 15: IVA | 645 nanogram per milliliter (ng/mL) | Standard Deviation 373 |
| Part 2 Cohort 2A: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 29: M1-IVA | 1890 nanogram per milliliter (ng/mL) | Standard Deviation 659 |
| Part 2 Cohort 2A: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 8: TEZ | 2010 nanogram per milliliter (ng/mL) | Standard Deviation 669 |
| Part 2 Cohort 2A: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 15: TEZ | 1970 nanogram per milliliter (ng/mL) | Standard Deviation 1040 |
| Part 2 Cohort 2A: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 29: TEZ | 2470 nanogram per milliliter (ng/mL) | Standard Deviation 1060 |
| Part 2 Cohort 2A: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 8: M1-TEZ | 4980 nanogram per milliliter (ng/mL) | Standard Deviation 1450 |
| Part 2 Cohort 2A: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 15: M1-TEZ | 4420 nanogram per milliliter (ng/mL) | Standard Deviation 1810 |
| Part 2 Cohort 2A: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 29: M1-TEZ | 4280 nanogram per milliliter (ng/mL) | Standard Deviation 1650 |
| Part 2 Cohort 2A: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 8: IVA | 953 nanogram per milliliter (ng/mL) | Standard Deviation 360 |
| Part 2 Cohort 2A: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 15: IVA | 863 nanogram per milliliter (ng/mL) | Standard Deviation 488 |
| Part 2 Cohort 2A: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 29: IVA | 1010 nanogram per milliliter (ng/mL) | Standard Deviation 446 |
| Part 2 Cohort 2A: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 8: M1-IVA | 1810 nanogram per milliliter (ng/mL) | Standard Deviation 665 |
| Part 2 Cohort 2A: TC | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 15: M1-IVA | 1620 nanogram per milliliter (ng/mL) | Standard Deviation 760 |
| Part 2 Cohort 2B: TEZ/IVA | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 8: IVA | 434 nanogram per milliliter (ng/mL) | Standard Deviation 251 |
| Part 2 Cohort 2B: TEZ/IVA | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 29: M1-TEZ | 3680 nanogram per milliliter (ng/mL) | Standard Deviation 742 |
| Part 2 Cohort 2B: TEZ/IVA | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 15: M1-TEZ | 3650 nanogram per milliliter (ng/mL) | Standard Deviation 1320 |
| Part 2 Cohort 2B: TEZ/IVA | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 8: M1-TEZ | 4150 nanogram per milliliter (ng/mL) | Standard Deviation 1280 |
| Part 2 Cohort 2B: TEZ/IVA | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 29: TEZ | 1190 nanogram per milliliter (ng/mL) | Standard Deviation 422 |
| Part 2 Cohort 2B: TEZ/IVA | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 15: M1-IVA | 1100 nanogram per milliliter (ng/mL) | Standard Deviation 598 |
| Part 2 Cohort 2B: TEZ/IVA | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 8: M1-IVA | 1170 nanogram per milliliter (ng/mL) | Standard Deviation 551 |
| Part 2 Cohort 2B: TEZ/IVA | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 15: TEZ | 1050 nanogram per milliliter (ng/mL) | Standard Deviation 543 |
| Part 2 Cohort 2B: TEZ/IVA | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 8: TEZ | 1460 nanogram per milliliter (ng/mL) | Standard Deviation 1470 |
| Part 2 Cohort 2B: TEZ/IVA | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 29: VX-152 | 698 nanogram per milliliter (ng/mL) | Standard Deviation 1040 |
| Part 2 Cohort 2B: TEZ/IVA | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 15: VX-152 | 560 nanogram per milliliter (ng/mL) | Standard Deviation 657 |
| Part 2 Cohort 2B: TEZ/IVA | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 8: VX-152 | 463 nanogram per milliliter (ng/mL) | Standard Deviation 730 |
| Part 2 Cohort 2B: TEZ/IVA | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 15: IVA | 389 nanogram per milliliter (ng/mL) | Standard Deviation 222 |
| Part 2 Cohort 2B: TEZ/IVA | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 29: M1-IVA | 1240 nanogram per milliliter (ng/mL) | Standard Deviation 705 |
| Part 2 Cohort 2B: TEZ/IVA | Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA | Day 29: IVA | 468 nanogram per milliliter (ng/mL) | Standard Deviation 279 |
Secondary
Relative Change in ppFEV1 at Day 15 for Part 1 and Part 2 Cohort 2A
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time frame: From Baseline at Day 15
Population: FAS. As pre-specified in analysis plan, only Part 1 and Part 2 Cohort 2A arms were assessed for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Placebo | Relative Change in ppFEV1 at Day 15 for Part 1 and Part 2 Cohort 2A | -2.3 percent change |
| Part 1 Cohort 1A: TC | Relative Change in ppFEV1 at Day 15 for Part 1 and Part 2 Cohort 2A | 10.3 percent change |
| Part 1 Cohort 1B: TC | Relative Change in ppFEV1 at Day 15 for Part 1 and Part 2 Cohort 2A | 19.0 percent change |
| Part 1 Cohort 1C: TC | Relative Change in ppFEV1 at Day 15 for Part 1 and Part 2 Cohort 2A | 14.8 percent change |
| Part 2 Cohort 2A: TEZ/IVA | Relative Change in ppFEV1 at Day 15 for Part 1 and Part 2 Cohort 2A | -1.4 percent change |
| Part 2 Cohort 2A: TC | Relative Change in ppFEV1 at Day 15 for Part 1 and Part 2 Cohort 2A | 13.2 percent change |
p-value: 0.016695% CI: [1.1, 24]Mixed-effects Model for Repeated Measure
p-value: <0.000195% CI: [11.2, 31.4]Mixed-effects Model for Repeated Measure
p-value: 0.001395% CI: [6.3, 27.8]Mixed-effects Model for Repeated Measure
p-value: 0.056395% CI: [-3.8, 32.9]Mixed-effects Model for Repeated Measure
Secondary
Relative Change in ppFEV1 Through Day 29 for Part 2 Cohort 2B
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. As pre-specified in analysis plan, only Part 2 Cohort 2B arms were assessed for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Placebo | Relative Change in ppFEV1 Through Day 29 for Part 2 Cohort 2B | -2.0 percent change |
| Part 1 Cohort 1A: TC | Relative Change in ppFEV1 Through Day 29 for Part 2 Cohort 2B | 11.5 percent change |
p-value: 0.001295% CI: [5.3, 21.9]Mixed-effects Model for Repeated Measure