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

Healthy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03609775
• Other study ID #: ID-078-111
• Status: Completed
• Phase: Phase 1
• Start date: August 28, 2018
• Est. completion date: October 9, 2018

Study information

• Verified date: October 2018
• Source: Idorsia Pharmaceuticals Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: October 9, 2018
• Est. primary completion date: October 9, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• ACT-541468
One tablet of 50 mg ACT-541468 will be administered orally.

Other:
• ACT-541468 placebo
Matching ACT-541468 placebo will be administered orally as 1 tablet.
• 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.
• Ethanol placebo
Matching placebo for the ethanol infusion (i.e., 5% glucose solution) will be administered i.v. for 5 h.

Locations

Country	Name	City	State
Netherlands	Centre For Human Drug Research	Leiden

Sponsors (1)

Lead Sponsor	Collaborator
Idorsia Pharmaceuticals Ltd.

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	ACT-541468 PK endpoints for treatments A and B: AUC from zero to infinity (AUC0-8)		Several timepoints from Day 1 to Day 2 (EOT/EOS); for up to 24 hours post-dose
Other	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
Other	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
Other	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
Other	Ethanol PK endpoints for treatments A and C: Breath ethanol concentrations (BrEC)		Several timepoints on Day 1; for up to 24 hours post-dose
Other	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
Other	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
Other	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
Primary	Change from baseline for saccadic peak velocity (degrees/sec) to assess sedation		Several timepoints on Day 1; for up to 24 hours post-dose