Healthy
Conditions
Brief summary
A study to investigate the drug-drug interactions between ACT-541468 and ethanol in healthy subjects
Interventions
DRUGACT-541468
One tablet of 50 mg ACT-541468 will be administered orally.
OTHERACT-541468 placebo
Matching ACT-541468 placebo will be administered orally as 1 tablet.
OTHEREthanol 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.
OTHEREthanol placebo
Matching placebo for the ethanol infusion (i.e., 5% glucose solution) will be administered i.v. for 5 h.
Sponsors
Idorsia Pharmaceuticals Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Double-dummy, four-way crossover study design
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| 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
| 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 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 |
| 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 |
| 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 |
| 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 |
Countries
Netherlands
Outcome results
None listed