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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: ACT-541468; Other: Ethanol 10%; Other: Ethanol placebo; Other: ACT-541468 placebo

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Leiden, Netherlands, 2333
    • Centre for Human Drug Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A (ethanol + ACT-541468); 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; One tablet of 50 mg ACT-541468 will be administered orally.; Other: Ethanol 10%; 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.
Experimental: Treatment B (ethanol placebo + ACT-541468); 5 h i.v. placebo clamp in combination with a single oral dose of ACT-541468 (50 mg)	Drug: ACT-541468; One tablet of 50 mg ACT-541468 will be administered orally.; Other: Ethanol placebo; Matching placebo for the ethanol infusion (i.e., 5% glucose solution) will be administered i.v. for 5 h.
Experimental: Treatment C (ethanol + ACT-541468 placebo); 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: Ethanol 10%; 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.; Other: ACT-541468 placebo; Matching ACT-541468 placebo will be administered orally as 1 tablet.
Experimental: Treatment D (ethanol placebo + ACT-541468 placebo); 5 h i.v. placebo clamp in combination with a single oral dose of matching ACT-541468 placebo	Other: Ethanol placebo; Matching placebo for the ethanol infusion (i.e., 5% glucose solution) will be administered i.v. for 5 h.; Other: ACT-541468 placebo; Matching ACT-541468 placebo will be administered orally as 1 tablet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Other Outcome Measures

Outcome Measure	Time Frame
Change from baseline for smooth pursuit (%) to assess eye movement coordination and attention	Several timepoints on Day 1; for up to 24 hours post-dose
Change from baseline for adaptive tracking (%) to assess visuo-motor control and vigilance	Several timepoints on Day 1; for up to 24 hours post-dose
Change from baseline for body sway (antero-posterior in mm / 2 min) to assess postural stability	Several timepoints on Day 1; for up to 24 hours post-dose
Change from baseline for visual analog scales (VAS) Bond & Lader to assess subjective alertness, mood, and calmness	Several timepoints on Day 1; for up to 24 hours post-dose
Change from baseline for VAS for alcohol intoxication to assess subjective effects of ethanol	Several timepoints on Day 1; for up to 24 hours post-dose
ACT-541468 PK endpoints for treatments A and B: Area under the plasma concentration-time curve (AUC) from time zero to 24 h (AUC0-24)	Several timepoints from Day 1 to Day 2 (EOT/EOS); for up to 24 hours post-dose
ACT-541468 PK endpoints for treatments A and B: AUC from zero to infinity (AUC0-∞)	Several timepoints from Day 1 to Day 2 (EOT/EOS); for up to 24 hours post-dose
ACT-541468 PK endpoints for treatments A and B: Maximum plasma concentration (Cmax)	Several timepoints from Day 1 to Day 2 (EOT/EOS); for up to 24 hours post-dose
ACT-541468 PK endpoints for treatments A and B: Time to reach Cmax (tmax)	Several timepoints from Day 1 to Day 2 (EOT/EOS); for up to 24 hours post-dose
ACT-541468 PK endpoints for treatments A and B: Terminal elimination half-life (t½)	Several timepoints from Day 1 to Day 2 (EOT/EOS); for up to 24 hours post-dose
Ethanol PK endpoints for treatments A and C: Breath ethanol concentrations (BrEC)	Several timepoints on Day 1; for up to 24 hours post-dose
Ethanol PK endpoints for treatments A and C: Total ethanol dose (in grams) required to maintain the 0.6 g/L ethanol clamp	Several timepoints on Day 1; for up to 5 hours
Safety endpoints: Treatment-emergent AEs from study treatment administration up to EOT in each treatment period	AEs from Day 1 to Day 2 (EOT/EOS); for up to 2 days post-dose
Safety endpoints: Treatment-emergent SAEs from study treatment administration up to EOT in each treatment period	SAEs from Screening to Safety follow up; for up to 14 weeks

Collaborators and Investigators

• Sponsor: Idorsia Pharmaceuticals Ltd.
• Investigators: Study Director: Pascale Gasser, Idorsia Pharmaceuticals Ltd.

Publications and helpful links

General Publications

• Berger B, Brooks S, Zuiker R, Richard M, Muehlan C, Dingemanse J. Pharmacological Interactions between the Dual Orexin Receptor Antagonist Daridorexant and Ethanol in a Double-Blind, Randomized, Placebo-Controlled, Double-Dummy, Four-Way Crossover Phase I Study in Healthy Subjects. CNS Drugs. 2020 Dec;34(12):1253-1266. doi: 10.1007/s40263-020-00768-8. Epub 2020 Nov 18.

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2018
• Primary Completion (Actual): October 9, 2018
• Study Completion (Actual): October 9, 2018

Study Registration Dates

• First Submitted: July 25, 2018
• First Submitted That Met QC Criteria: July 25, 2018
• First Posted (Actual): August 1, 2018

Study Record Updates

• Last Update Posted (Actual): October 15, 2018
• Last Update Submitted That Met QC Criteria: October 12, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Anti-Infective Agents, Local; Anti-Infective Agents; Central Nervous System Depressants; Ethanol
• Other Study ID Numbers: ID-078-111

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No