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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Recreational Drug Users
• Intervention / Treatment: Drug: ACT-541468; Drug: Suvorexant; Drug: Zolpidem; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Montreal, Canada, H3P 3P1
    • Altasciences Company Inc.
• United States
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • Altasciences Clinical Kansas, Inc. (former Vince and Associates Clinical Research, Inc.)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 50 mg ACT-541468; ACT-541468 will be administered as tablets for oral use.	Drug: ACT-541468; ACT-541468 will be administered as 50 mg tablets for oral use.
EXPERIMENTAL: 100 mg ACT-541468; ACT-541468 will be administered as tablets for oral use.	Drug: ACT-541468; ACT-541468 will be administered as 50 mg tablets for oral use.
EXPERIMENTAL: 150 mg ACT-541468; ACT-541468 will be administered as tablets for oral use.	Drug: ACT-541468; ACT-541468 will be administered as 50 mg tablets for oral use.
ACTIVE_COMPARATOR: 150 mg suvorexant; Suvorexant will be administered as tablets for oral use.	Drug: Suvorexant; Suvorexant will be administered as 15 mg over-encapsulated tablets for oral use.
ACTIVE_COMPARATOR: 30 mg zolpidem; Zolpidem will be administered as tablets for oral use.	Drug: Zolpidem; Zolpidem will be administered as 10 mg over-encapsulated tablets for oral use.
PLACEBO_COMPARATOR: Placebo; Placebo will be administered as tablets for oral use.	Drug: Placebo; Matching-placebo will be used.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Time Frame
AUC(0-t) of ACT-541468	Duration: for up to 24 hours post-dose
AUC(0-∞) of ACT-541468	Duration: for up to 24 hours post-dose
Cmax of ACT-541468	Duration: for up to 24 hours post-dose
tmax of ACT-541468	Duration: for up to 24 hours post-dose
t½ of ACT-541468	Duration: for up to 24 hours post-dose
Treatment-emergent adverse events (AEs)	All AEs from (first) admittance on Day -1 up to EOS, i.e. for up to 9 weeks
Treatment-emergent serious AEs (SAEs)	SAE reporting: from signature of informed consent up to EOS, i.e. for up to 13 weeks

Collaborators and Investigators

• Sponsor: Idorsia Pharmaceuticals Ltd.

Publications and helpful links

General Publications

• Ufer M, Kelsh D, Schoedel KA, Dingemanse J. Abuse potential assessment of the new dual orexin receptor antagonist daridorexant in recreational sedative drug users as compared to suvorexant and zolpidem. Sleep. 2022 Mar 14;45(3):zsab224. doi: 10.1093/sleep/zsab224.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 7, 2018
• Primary Completion (ACTUAL): August 8, 2019
• Study Completion (ACTUAL): August 8, 2019

Study Registration Dates

• First Submitted: August 31, 2018
• First Submitted That Met QC Criteria: August 31, 2018
• First Posted (ACTUAL): September 5, 2018

Study Record Updates

• Last Update Posted (ACTUAL): September 19, 2019
• Last Update Submitted That Met QC Criteria: September 18, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Hypnotics and Sedatives; GABA Agents; Sleep Aids, Pharmaceutical; Orexin Receptor Antagonists; GABA-A Receptor Agonists; GABA Agonists; Suvorexant; Zolpidem
• Other Study ID Numbers: ID-078-107

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No