Clinical trial NCT03609775: A Study to Investigate the Drug-drug Interactions Between ACT-541468 and Ethanol in Healthy Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Idorsia Pharmaceuticals Ltd.
Sponsor class: INDUSTRY
First posted: 2018-08-01
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Double-dummy, four-way crossover study design
Primary purpose: OTHER

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


Eligibility criteria: 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.

Primary outcomes:
measure: Change from baseline for saccadic peak velocity (degrees/sec) to assess sedation
timeFrame: Several timepoints on Day 1; for up to 24 hours post-dose
Secondary outcomes:
Other outcomes:
measure: Change from baseline for smooth pursuit (%) to assess eye movement coordination and attention
timeFrame: Several timepoints on Day 1; for up to 24 hours post-dose
measure: Change from baseline for adaptive tracking (%) to assess visuo-motor control and vigilance
timeFrame: Several timepoints on Day 1; for up to 24 hours post-dose
measure: Change from baseline for body sway (antero-posterior in mm / 2 min) to assess postural stability
timeFrame: Several timepoints on Day 1; for up to 24 hours post-dose
measure: Change from baseline for visual analog scales (VAS) Bond & Lader to assess subjective alertness, mood, and calmness
timeFrame: Several timepoints on Day 1; for up to 24 hours post-dose
measure: Change from baseline for VAS for alcohol intoxication to assess subjective effects of ethanol
timeFrame: Several timepoints on Day 1; for up to 24 hours post-dose
measure: 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)
timeFrame: Several timepoints from Day 1 to Day 2 (EOT/EOS); for up to 24 hours post-dose
measure: ACT-541468 PK endpoints for treatments A and B: AUC from zero to infinity (AUC0-∞)
timeFrame: Several timepoints from Day 1 to Day 2 (EOT/EOS); for up to 24 hours post-dose
measure: ACT-541468 PK endpoints for treatments A and B: Maximum plasma concentration (Cmax)
timeFrame: Several timepoints from Day 1 to Day 2 (EOT/EOS); for up to 24 hours post-dose
measure: ACT-541468 PK endpoints for treatments A and B: Time to reach Cmax (tmax)
timeFrame: Several timepoints from Day 1 to Day 2 (EOT/EOS); for up to 24 hours post-dose
measure: ACT-541468 PK endpoints for treatments A and B: Terminal elimination half-life (t½)
timeFrame: Several timepoints from Day 1 to Day 2 (EOT/EOS); for up to 24 hours post-dose
measure: Ethanol PK endpoints for treatments A and C: Breath ethanol concentrations (BrEC)
timeFrame: Several timepoints on Day 1; for up to 24 hours post-dose
measure: Ethanol PK endpoints for treatments A and C: Total ethanol dose (in grams) required to maintain the 0.6 g/L ethanol clamp
timeFrame: Several timepoints on Day 1; for up to 5 hours
measure: Safety endpoints: Treatment-emergent AEs from study treatment administration up to EOT in each treatment period
timeFrame: AEs from Day 1 to Day 2 (EOT/EOS); for up to 2 days post-dose
measure: Safety endpoints: Treatment-emergent SAEs from study treatment administration up to EOT in each treatment period
timeFrame: SAEs from Screening to Safety follow up; for up to 14 weeks
Locations:
city: Leiden
country: Netherlands
facility: Centre For Human Drug Research
Study officials:
affiliation: Idorsia Pharmaceuticals Ltd.
name: Pascale Gasser
role: STUDY_DIRECTOR
References:
citation: 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.