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

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

Detailed Description
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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.).

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

Conditions
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Pain

Intervention / Treatment
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* Drug: VX-548
* Drug: Midazolam
* Drug: Digoxin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>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<br>* Tablets for oral administration.<br>Drug: Midazolam<br>* Syrup for oral administration.<br>Drug: Digoxin<br>* Tablets for oral administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 |