Cystic Fibrosis
Conditions
Brief summary
The purpose of the study is to evaluate safety, tolerability, and pharmacokinetics of VX-828 and VX-828 in triple combination (TC) with Tezacaftor (TEZ)/ VX-118 or TEZ/ deutivacaftor (D-IVA) in healthy participants and VX-828 in combination with D-IVA with or without TEZ in participants with cystic fibrosis (CF).
Detailed description
This clinical trial information was submitted voluntarily under the applicable law and, therefore, certain submission deadlines may not apply. (That is, clinical trial information for this applicable clinical trial was submitted under section 402(j)(4)(A) of the Public Health Service Act and 42 CFR 11.60 and is not subject to the deadlines established by sections 402(j)(2) and (3) of the Public Health Service Act or 42 CFR 11.24 and 11.44.).
Interventions
DRUGVX-828
Suspension for Oral Administration
DRUGPlacebo
Suspension for Oral Administration
DRUGItraconazole
Solution for Oral Administration
DRUGMidazolam
Syrup for Oral Administration
DRUGTezacaftor
Tablets for Oral Administration
DRUGVX-118
Tablets for Oral Administration
DRUGDeutivacaftor
Tablets 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: Parts A-D: * Participants between the ages of 18 and 55 years * Body mass index (BMI) of 18.0 to 32.0 kilogram per meter square (kg/m\^2) * A total body weight of more than (\>) 50 kg * Nonsmoker or ex-smoker for at least 3 months before screening with current nonsmoking status confirmed by urine or blood cotinine at screening * Cohort C2 only: Willing to provide a single DNA sample Part E: * Participants 18 years or older * Confirmed diagnosis of CF as determined by the investigator * A total body weight of more than or equal to (\>=) 35 kg * Participants must be heterozygous for F508del with a second CFTR allele carrying a minimal function mutation that is not responsive to ELX/TEZ/IVA therapy * Participants must have a forced expiratory volume in 1 second (FEV1) of greater than or equal to (≥) 40% of predicted normal for age, sex, and height Key
Exclusion criteria
Parts A-D: * History of febrile illness or other acute illness within 14 days before the first dose of study drug * Any condition possibly affecting drug absorption Part E: * An acute illness not related to CF (e.g., gastroenteritis) within 14 days before the first dose of study drug * History of solid organ or hematological transplantation * History of clinically significant cirrhosis with or without portal hypertension * Lung infection with organisms associated with a more rapid decline in pulmonary status Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | From Signing of Informed Consent Form (ICF) up to Safety Follow Up (Up to Day 67) |
| Part B: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | From Signing of Informed Consent Form (ICF) up to Safety Follow Up (Up to Day 80) |
| Part D: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | From Signing of Informed Consent Form (ICF) up to Safety Follow Up (Up to Day 80) |
| Part E: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | From Signing of Informed Consent Form (ICF) up to End of Study (Up to Day 111) |
| Part C: Maximum Observed Concentration (Cmax) of VX-828 in Plasma in the Absence and Presence of Itraconazole | From Day 1 up to Day 71 |
| Part C: Area Under the Concentration Versus Time Curve (AUC) of VX-828 in Plasma in the Absence and Presence of Itraconazole | From Day 1 up to Day 71 |
| Part C: Maximum Observed Concentration (Cmax) of Midazolam in Plasma in the Absence and Presence of VX-828/TEZ/D-IVA | From Day 1 up to Day 30 |
| Part C: Area Under the Concentration Versus Time Curve (AUC) of Midazolam in Plasma in the Absence and Presence of VX-828/TEZ/D-IVA | From Day 1 up to Day 30 |
Secondary
| Measure | Time frame |
|---|---|
| Part A: Maximum Observed Concentration (Cmax) of VX-828 in Plasma | From Day 1 up to Day 67 |
| Part A: Area Under the Concentration Versus Time Curve (AUC) of VX-828 in Plasma | From Day 1 up to Day 67 |
| Part B: Maximum Observed Concentration (Cmax) of VX-828 at Day 28 in Plasma | From Day 1 up to Day 80 |
| Part B: Area Under the Concentration Versus Time Curve (AUC) of VX-828 at Day 28 in Plasma | From Day 1 up to Day 80 |
| Part C: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | From Signing of Informed Consent Form (ICF) up to Safety Follow Up (Up to Day 82) |
| Part D: Maximum Observed Concentration (Cmax) of VX-828, TEZ and D-IVA and their Metabolites at Day 28 in Plasma | Day 28 |
| Part D: Area Under the Concentration Versus Time Curve (AUC) of VX-828, TEZ and D-IVA and their Metabolites at Day 28 in Plasma | Day 28 |
| Part E: Maximum Observed Concentration (Cmax) of VX-828, TEZ, and D-IVA and their Metabolites in Plasma | Day 1 and Day 28 |
| Part E: Area Under the Concentration Versus Time Curve (AUC) of VX-828, TEZ, and D-IVA and their Metabolites in Plasma | Day 28 |
| Part E: Pre-dose Plasma Concentration (Ctrough) of VX-828, TEZ, D-IVA and its Metabolites | Pre-dose at Day 4, Day 8, Day 15, Day 22, Day 35, Day 49, Day 63, Day 80 |
| Part E: Absolute Change in Sweat Chloride | From Baseline and At Day 28 |
Countries
United States
Outcome results
None listed