A Study to Evaluate the Pharmacokinetic Drug-drug Interactions Between VX-548, Midazolam, and Digoxin
- Registration Number
- NCT05541471
- Lead Sponsor
- Vertex Pharmaceuticals Incorporated
- 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.).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 37
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/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Arm 1 VX-548 Participants will receive a single dose of midazolam and digoxin on Day 1 in dosing period 1 followed by VX-548 every 12 hours (q12h) on Days 6 through 23 in dosing period 2. On Day 19, single doses of midazolam and digoxin will be administered with the morning dose of VX-548. Arm 1 Midazolam Participants will receive a single dose of midazolam and digoxin on Day 1 in dosing period 1 followed by VX-548 every 12 hours (q12h) on Days 6 through 23 in dosing period 2. On Day 19, single doses of midazolam and digoxin will be administered with the morning dose of VX-548. Arm 1 Digoxin Participants will receive a single dose of midazolam and digoxin on Day 1 in dosing period 1 followed by VX-548 every 12 hours (q12h) on Days 6 through 23 in dosing period 2. On Day 19, single doses of midazolam and digoxin will be administered with the morning dose of VX-548.
- Primary Outcome Measures
Name Time Method 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 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 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 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 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
- Secondary Outcome Measures
Name Time Method 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 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 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 Columbia-Suicide Severity Rating Scale (C-SSRS) Score Pre-dose up to Day 39 Safety and Tolerability as Assessed by Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) Day 1 up to Day 39
Trial Locations
- Locations (1)
Baltimore - Early Phase Clinical Unit
🇺🇸Baltimore, Maryland, United States