A Study to Evaluate the Pharmacokinetic Drug-drug Interactions Between VX-548, Midazolam, and Digoxin

NCT05541471 | Completed Phase 1 FDA Drug

• 1 other identifier: VX21-548-010
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the pharmacokinetics of midazolam and digoxin in the absence and presence of VX-548.

Conditions

Pain

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (7)

• 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

• 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

Study Arms (1)

Arm 1

EXPERIMENTAL

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.

Drug: VX-548; Drug: Midazolam; Drug: Digoxin

Interventions

VX-548 DRUG

Tablets for oral administration.

Also known as: Suzetrigine

Arm 1

Midazolam DRUG

Syrup for oral administration.

Arm 1

Digoxin DRUG

Tablets for oral administration.

Arm 1

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vertex Pharmaceuticals Incorporated: lead

Study Sites (1)

Baltimore - Early Phase Clinical Unit

Baltimore, Maryland, 21225, United States

Location

MeSH Terms

Conditions

Pain

Interventions

Midazolam; Digoxin

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2022
• First Posted: September 15, 2022
• Study Start: September 22, 2022
• Primary Completion: April 16, 2023
• Study Completion: April 28, 2023
• Last Updated: March 20, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)