Clinical trial NCT05541471: A Study to Evaluate the Pharmacokinetic Drug-drug Interactions Between VX-548, Midazolam, and Digoxin
Official title: A Phase 1, Open-label Study to Evaluate Pharmacokinetic Drug-drug Interactions Between VX-548 and Midazolam and Digoxin in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pain
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2022-09-15
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

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.).

Eligibility 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/Exclusion criteria may apply.

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of Midazolam in the Absence and Presence of VX-548
timeFrame: Days 1 and 19: Pre-dose up to 24 hours post midazolam dose
measure: Maximum Observed Plasma Concentration (Cmax) of Digoxin in the Absence and Presence of VX-548
timeFrame: Days 1 and 19: Pre-dose up to 120 hours post digoxin dose
measure: 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
timeFrame: Days 1 and 19: Pre-dose up to 24 hours post midazolam dose
measure: 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
timeFrame: Days 1 and 19: Pre-dose up to 120 hours post digoxin dose
measure: 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
timeFrame: Days 1 and 19: Pre-dose up to 24 hours post midazolam dose
measure: 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
timeFrame: Days 1 and 19: Pre-dose up to 120 hours post digoxin dose
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of 1-hydroxy-Midazolam in the Absence and Presence of VX-548
timeFrame: Days 1 and 19: Pre-dose up to 24 hours post midazolam dose
measure: 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
timeFrame: Days 1 and 19: Pre-dose up to 24 hours post midazolam dose
measure: 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
timeFrame: Days 1 and 19: Pre-dose up to 24 hours post midazolam dose
measure: Renal Clearance (CLr) of Digoxin as Determined by Urine Analysis in the Absence and Presence of VX-548
timeFrame: Days 1 and 19: Pre-dose up to 120 hours post digoxin dose
measure: Fraction of Systematically Available Digoxin Dose Excreted Unchanged (fe) in Urine in the Absence and Presence of VX-548
timeFrame: Days 1 and 19: Pre-dose up to 120 hours post digoxin dose
measure: Safety and Tolerability as Assessed by Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Day 1 up to Day 39
measure: Columbia-Suicide Severity Rating Scale (C-SSRS) Score
timeFrame: Pre-dose up to Day 39
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Baltimore - Early Phase Clinical Unit
state: Maryland
Study officials:
References: