A Study to Investigate the Drug-drug Interactions Between ACT-541468 and Ethanol in Healthy Subjects

Study Overview
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Brief Summary
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A study to investigate the drug-drug interactions between ACT-541468 and ethanol in healthy subjects

Official Title
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A Double-blind, Randomized, Placebo-controlled, Double-dummy, Four-way Crossover Study to Investigate the Drug-drug Interactions Between ACT-541468 and Ethanol in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: ACT-541468
* Other: ACT-541468 placebo
* Other: Ethanol 10%
* Other: Ethanol placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent prior to any study-mandated procedure. Healthy male and female subjects aged between 18 and 45 years (inclusive) at screening. Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test on Day 1 pre-dose of each treatment period. They must consistently and correctly use a reliable method of contraception, be sexually inactive, or have a vasectomized partner. Women of non-childbearing potential (i.e., postmenopausal). Body mass index of 18.0 to 32.0 kg/m2 (inclusive) at screening. Healthy on the basis of medical history, physical examination, cardiovascular assessments and serology and laboratory tests. Previous experience with alcohol consumption and, therefore, familiar with the effects of alcohol. Exclusion Criteria: Pregnant or lactating women. Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol. Excessive caffeine consumption, defined as ≥ 800 mg per day at screening. Nicotine intake within 3 months prior to screening and inability to refrain from nicotine intake from screening until End-of-Study (EOS). Previous treatment with any prescribed medications (including vaccines) or over-the-counter (OTC) medications (including herbal medicines such as St John's Wort, homeopathic preparations, vitamins, and minerals) within 2 weeks prior to first study treatment administration. History or clinical evidence of alcoholism or drug abuse. History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of more than 21 units or an average daily intake of more than 3 units (males), or defined as an average weekly intake of more than 14 units or an average daily intake of more than 2 units (females). Individuals of Asian descent or other individuals reporting ethanol intolerance. Modified Swiss Narcolepsy Scale total score < 0 at screening or history of narcolepsy or cataplexy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Double-dummy, four-way crossover study design
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A (ethanol + ACT-541468)<br>5 h i.v. ethanol clamp at a level of 0.6 g/L in combination with a single oral dose of ACT-541468 (50 mg) | Drug: ACT-541468<br>* One tablet of 50 mg ACT-541468 will be administered orally.<br>Other: Ethanol 10%<br>* Ethanol 10% w/v solution in 5% glucose will be administered i.v. for 5 h and clamped at an ethanol level of 0.6 g/L.<br>|
| Experimental: Treatment B (ethanol placebo + ACT-541468)<br>5 h i.v. placebo clamp in combination with a single oral dose of ACT-541468 (50 mg) | Drug: ACT-541468<br>* One tablet of 50 mg ACT-541468 will be administered orally.<br>Other: Ethanol placebo<br>* Matching placebo for the ethanol infusion (i.e., 5% glucose solution) will be administered i.v. for 5 h.<br>|
| Experimental: Treatment C (ethanol + ACT-541468 placebo)<br>5 h i.v. ethanol clamp at a level of 0.6 g/L in combination with a single oral dose of matching ACT-541468 placebo | Other: ACT-541468 placebo<br>* Matching ACT-541468 placebo will be administered orally as 1 tablet.<br>Other: Ethanol 10%<br>* Ethanol 10% w/v solution in 5% glucose will be administered i.v. for 5 h and clamped at an ethanol level of 0.6 g/L.<br>|
| Experimental: Treatment D (ethanol placebo + ACT-541468 placebo)<br>5 h i.v. placebo clamp in combination with a single oral dose of matching ACT-541468 placebo | Other: ACT-541468 placebo<br>* Matching ACT-541468 placebo will be administered orally as 1 tablet.<br>Other: Ethanol placebo<br>* Matching placebo for the ethanol infusion (i.e., 5% glucose solution) will be administered i.v. for 5 h.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline for saccadic peak velocity (degrees/sec) to assess sedation |  | Several timepoints on Day 1; for up to 24 hours post-dose |