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

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

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

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: VX-548; Drug: Midazolam; Drug: Digoxin

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.).

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21225
      • Baltimore - Early Phase Clinical Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; 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; Tablets for oral administration.; Other Names: Suzetrigine; Drug: Midazolam; Syrup for oral administration.; Drug: Digoxin; Tablets for oral administration.

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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
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
Columbia-Suicide Severity Rating Scale (C-SSRS) Score	Pre-dose up to Day 39

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2022
• Primary Completion (Actual): April 16, 2023
• Study Completion (Actual): April 28, 2023

Study Registration Dates

• First Submitted: September 12, 2022
• First Submitted That Met QC Criteria: September 12, 2022
• First Posted (Actual): September 15, 2022

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Enzyme Inhibitors; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Protective Agents; Cardiotonic Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Digoxin; Midazolam
• Other Study ID Numbers: VX21-548-010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/independent-research/clinical-trial-data-sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No