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

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

For blinding purposes, suvorexant and zolpidem will be over-encapsulated, whereas a matching-placebo will be used for ACT-541468.