Study to Evaluate the Abuse Potential of ACT-541468 in Healthy Recreational Drug Users

Study Overview
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Brief Summary
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This placebo- and active controlled study will investigate the abuse potential of ACT-541468 in healthy recreational drug users

Official Title
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Randomized, Double-blind, Double-dummy, Placebo- and Active-controlled, 6-way Cross-over Study to Evaluate the Abuse Potential of Single, Oral Doses of ACT-541468 in Healthy Recreational Drug Users

Conditions
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Healthy Recreational Drug Users

Intervention / Treatment
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* Drug: ACT-541468
* Drug: Suvorexant
* Drug: Zolpidem
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent prior to any study-mandated procedure Male or female healthy subjects, 18-55 years of age (inclusive) at Screening Body mass index of 18.0-33.0 kg/m2 (inclusive) at Screening and a minimum weight of 50.0 kg at Screening Current sedative users who have used sedatives (e.g., benzodiazepines, zolpidem, eszopiclone, gamma-hydroxybutyrate, barbiturates) for recreational (non-therapeutic) purposes (i.e., for psychoactive effects) at least ten times in their life and at least once in the 12 weeks before Screening Women of childbearing potential must consistently and correctly use a reliable method of contraception with a failure rate of < 1% per year, be sexually inactive, or have a vasectomized partner Women of non-childbearing potential Male subjects are required to use a medically acceptable method of contraception throughout the entire study period and for at least 90 days after last study drug administration Exclusion Criteria: History of major medical or surgical disorders which, in the opinion of the investigator, are likely to interfere with the absorption, distribution, metabolism, or excretion of the study treatment(s) Positive HIV or hepatitis B/C test at Screening Female subjects who are currently pregnant or lactating or who are planning to become pregnant within 1 month of the last study treatment administration Modified Swiss Narcolepsy Scale total score < 0 at Screening or history of narcolepsy or cataplexy Substance or alcohol dependence within 2 years prior to Screening or prior participation in a substance or alcohol dependence rehabilitation program Subjects who have a positive urine drug screen at admittance to the qualification or core phase Any sleep-disorder including self-reported insomnia disorder, breathing-related sleep disorders, restless legs syndrome (RLS), nightmare disorder, non-rapid eye movement (REM), sleep arousal disorders, REM sleep behavior disorder, circadian rhythm sleep-wake disorders, or narcolepsy Any of the following SLEEP-50 Questionnaire scores at Screening: ≥ 15 on Apnea subscale; ≥ 7 on Narcolepsy subscale; ≥ 7 on RLS or Periodic limb movement disorder subscale; ≥ 8 on Circadian Rhythm subscale; ≥ 7 on Sleepwalking subscale; ≥ 3 on Item 32 and ≥ 9 on Items 33 to 35 (i.e., on nightmare subscale); ≥ 15 on Impact subscale. Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Single-center, randomized, double-blind, double-dummy, placebo- and active-controlled, 6-way cross-over study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 50 mg ACT-541468<br>ACT-541468 will be administered as tablets for oral use. | Drug: ACT-541468<br>* ACT-541468 will be administered as 50 mg tablets for oral use.<br>|
| Experimental: 100 mg ACT-541468<br>ACT-541468 will be administered as tablets for oral use. | Drug: ACT-541468<br>* ACT-541468 will be administered as 50 mg tablets for oral use.<br>|
| Experimental: 150 mg ACT-541468<br>ACT-541468 will be administered as tablets for oral use. | Drug: ACT-541468<br>* ACT-541468 will be administered as 50 mg tablets for oral use.<br>|
| Active Comparator: 150 mg suvorexant<br>Suvorexant will be administered as tablets for oral use. | Drug: Suvorexant<br>* Suvorexant will be administered as 15 mg over-encapsulated tablets for oral use.<br>|
| Active Comparator: 30 mg zolpidem<br>Zolpidem will be administered as tablets for oral use. | Drug: Zolpidem<br>* Zolpidem will be administered as 10 mg over-encapsulated tablets for oral use.<br>|
| Placebo Comparator: Placebo<br>Placebo will be administered as tablets for oral use. | Drug: Placebo<br>* Matching-placebo will be used.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum effect (Emax) of the Drug Liking VAS ('at this moment') over 24 h post-dose during each treatment period | VAS = visual analogue scale | Duration: for up to 24 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drug Liking VAS (bipolar) | VAS = visual analogue scale | Duration: for up to 24 hours post-dose | 
| Overall Drug Liking VAS (bipolar) | VAS = visual analogue scale | Duration: for up to 12 hours post-dose | 
| Take Drug Again VAS (bipolar) |  | Duration: for up to 12 hours post-dose | 
| Good Effects VAS (unipolar) |  | Duration: for up to 24 hours post-dose | 
| Drug Similarity VAS | VAS = visual analogue scale | Duration: for up to 1 hour post-dose | 
| Bad Effects VAS (unipolar) | VAS = visual analogue scale | Duration: for up to 24 hours post-dose | 
| Alertness/Drowsiness VAS (bipolar) | VAS = visual analogue scale | Duration: for up to 24 hours post-dose | 
| Any Effects VAS (unipolar) | VAS = visual analogue scale | Duration: for up to 24 hours post-dose | 
| Feeling High VAS (unipolar) | VAS = visual analogue scale | Duration: for up to 24 hours post-dose | 
| Bowdle VAS Internal and External Perceptions |  | Duration: for up to 24 hours post-dose | 
| Observer's Assessment of Alertness/Sedation composite and sum scores |  | Duration: for up to 24 hours post-dose | 
| Reaction time task score |  | Duration: for up to 8 hours post-dose | 
| Rapid visual information processing score |  | Duration: for up to 8 hours post-dose | 
| Paired Associates Learning score |  | Duration: for up to 8 hours post-dose |