Pain
Conditions
Brief summary
The purpose of this study is to evaluate the pharmacokinetics of midazolam and digoxin in the absence and presence of VX-548.
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-548
Tablets for oral administration.
DRUGMidazolam
Syrup for oral administration.
DRUGDigoxin
Tablets for oral administration.
Sponsors
Vertex Pharmaceuticals Incorporated
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: * Body mass index (BMI) of 18.0 to 32.0 kilogram per meter square (Kg/m\^2) * A total body weight greater than (\>) 50 kilogram (kg) * Females of non-childbearing potential Key
Exclusion criteria
* History of febrile illness or other acute illness that has not fully resolved within 5 days before the first dose of study drug * Any condition possibly affecting drug absorption * History of cardiovascular disease, cardiac dysrhythmias or central nervous system disease * Hypersensitivity to midazolam, other benzodiazepines, or digoxin Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Midazolam in the Absence and Presence of VX-548 | Days 1 and 19: Pre-dose up to 24 hours post midazolam dose |
| Maximum Observed Plasma Concentration (Cmax) of Digoxin in the Absence and Presence of VX-548 | Days 1 and 19: Pre-dose up to 120 hours post digoxin dose |
| Area Under the Concentration Versus Time Curve From the Time of Dosing Extrapolated to Infinity (AUC0-inf) of Midazolam in the Absence and Presence of VX-548 | Days 1 and 19: Pre-dose up to 24 hours post midazolam dose |
| Area Under the Concentration Versus Time Curve From the Time of Dosing Extrapolated to Infinity (AUC0-inf) of Digoxin in the Absence and Presence of VX-548 | Days 1 and 19: Pre-dose up to 120 hours post digoxin dose |
| Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of Midazolam in the Absence and Presence of VX-548 | Days 1 and 19: Pre-dose up to 24 hours post midazolam dose |
| Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of Digoxin in the Absence and Presence of VX-548 | Days 1 and 19: Pre-dose up to 120 hours post digoxin dose |
Secondary
| Measure | Time frame |
|---|---|
| Maximum Observed Plasma Concentration (Cmax) of 1-hydroxy-Midazolam in the Absence and Presence of VX-548 | Days 1 and 19: Pre-dose up to 24 hours post midazolam dose |
| Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Pre-dose up to Day 39 |
| Area Under the Concentration Versus Time Curve From the Time of Dosing Extrapolated to Infinity (AUC0-inf) of 1-hydroxy-Midazolam in the Absence and Presence of VX-548 | Days 1 and 19: Pre-dose up to 24 hours post midazolam dose |
| Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of 1-hydroxy-Midazolam in the Absence and Presence of VX-548 | Days 1 and 19: Pre-dose up to 24 hours post midazolam dose |
| Renal Clearance (CLr) of Digoxin as Determined by Urine Analysis in the Absence and Presence of VX-548 | Days 1 and 19: Pre-dose up to 120 hours post digoxin dose |
| Fraction of Systematically Available Digoxin Dose Excreted Unchanged (fe) in Urine in the Absence and Presence of VX-548 | Days 1 and 19: Pre-dose up to 120 hours post digoxin dose |
| Safety and Tolerability as Assessed by Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) | Day 1 up to Day 39 |
Countries
United States
Outcome results
None listed