A Clinical Study to Assess Next-day Driving Performance Following Administration of ACT-541468 in Middle-aged and Elderly Subjects

Study Overview
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Brief Summary
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A clinical study to assess next-day driving performance following evening administrations of ACT-541468 in middle-aged and elderly subjects

Official Title
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A Single-center, Randomized, Double-blind, Double-dummy, Placebo- and Active-controlled, 4-way Cross-over Study to Assess Next-day Driving Performance Following Single and Multiple Evening Administrations of ACT-541468 in Middle-aged and Elderly Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: ACT-541468
* Drug: Zopiclone 7.5 mg
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria General criteria: Signed informed consent prior to any study-mandated procedure. Male and female subjects aged between 50 and 80 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 highly effective method of contraception, be sexually inactive, or have a vasectomized partner. Women of non-childbearing potential (i.e., postmenopausal, XY genotype, Turner syndrome, uterine agenesis). Study-specific criteria Subject has a valid driving license for more than 5 years, has driven at least 3000 km/year on average in the past 2 years. Normal visual acuity (corrected or uncorrected). Exclusion Criteria: General criteria: Pregnant or lactating women. Any known factor or disease that might interfere with treatment compliance, study conduct, or interpretation of the results. History or presence of rhythm disorders Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol. Study-specific criteria: Current or previous diagnosis of insomnia-related disorder according to the Diagnostic and Statistical Manual of Mental Disorders version 5 (DSM-5) criteria. History of alcoholism, drug abuse, or regular use of sedative drugs or hypnotics within 3 years prior to Screening. 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). One unit is equivalent to a half-pint (approx. 250 mL) of beer or 1 measure (25 mL) of spirits or 1 glass (125 mL) of wine. Modified Swiss Narcolepsy Scale total score < 0 at Screening or history of narcolepsy or cataplexy. Activities that disturb the circadian rhythm (e.g., working night shift, travelling across 3 time zones) within 2 weeks before (each) study treatment.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 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: 4-way cross-over study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A (50 mg ACT-541468)<br>1 tablet of ACT-541468 50 mg + 1 tablet of ACT-541468 matching placebo + zopiclone matching placebo administered in the evening on Days 1-4 of Treatment Period A. | Drug: ACT-541468<br>* Film-coated tablet for oral use at a dose strength of 50 mg.<br>Other: Placebo<br>* Matching to maintain blinding.<br>|
| Experimental: Treatment B (100 mg ACT-541468)<br>2 tablets of ACT-541468 50 mg + zopiclone matching placebo administered in the evening on Days 1-4 of Treatment Period B. | Drug: ACT-541468<br>* Film-coated tablet for oral use at a dose strength of 50 mg.<br>Other: Placebo<br>* Matching to maintain blinding.<br>|
| Experimental: Treatment C (7.5 mg zopiclone)<br>2 tablets of ACT-541468 matching placebo + 1 capsule of zopiclone 7.5 mg administered in the evening on Days 1 and 4 of Treatment Period C. In the evenings of Days 2 and 3, subjects will receive placebo (i.e., 2 tablets of ACT-541468 matching placebo + zopiclone matching placebo). | Drug: Zopiclone 7.5 mg<br>* Over-encapsulated to maintain blinding.<br>Other: Placebo<br>* Matching to maintain blinding.<br>|
| Experimental: Treatment D (placebo)<br>2 tablets of ACT-541468 matching placebo + zopiclone matching placebo administered in the evening on Days 1-4 of Treatment Period D. | Other: Placebo<br>* Matching to maintain blinding.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamic endpoint: Driving performance as measured by the SDLB (difference from placebo, cm) using the Green Dino driving simulator - Day 2 | SDLP = standard deviation of the lateral position | On Day 2 at 9 hours post dose. Duration of the test: 1 hour | 
| Pharmacodynamic endpoint: Driving performance as measured by the SDLB (difference from placebo, cm) using the Green Dino driving simulator - Day 5 | SDLP = standard deviation of the lateral position | On Day 5 at 9 hours post dose. Duration of the test: 1 hour |