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

Pain Clinical Trial

Official title:

A Phase 1, Open-label Study to Evaluate Pharmacokinetic Drug-drug Interactions Between VX-548 and Midazolam and Digoxin in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05541471
• Other study ID #: VX21-548-010
• Status: Completed
• Phase: Phase 1
• Start date: September 22, 2022
• Est. completion date: April 28, 2023

Study information

• Verified date: March 2024
• Source: Vertex Pharmaceuticals Incorporated
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: April 28, 2023
• Est. primary completion date: April 16, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Pain

Intervention

Drug:
• VX-548
Tablets for oral administration.
• Midazolam
Syrup for oral administration.
• Digoxin
Tablets for oral administration.

Locations

Country	Name	City	State
United States	Baltimore - Early Phase Clinical Unit	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Vertex Pharmaceuticals Incorporated

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Safety and Tolerability as Assessed by Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)		Day 1 up to Day 39
Secondary	Columbia-Suicide Severity Rating Scale (C-SSRS) Score		Pre-dose up to Day 39