Clinical trial NCT03657355: Study to Evaluate the Abuse Potential of ACT-541468 in Healthy Recreational Drug Users
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Recreational Drug Users
Lead sponsor: Idorsia Pharmaceuticals Ltd.
Sponsor class: INDUSTRY
First posted: 2018-09-05
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Single-center, randomized, double-blind, double-dummy, placebo- and active-controlled, 6-way cross-over study
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Maximum effect (Emax) of the Drug Liking VAS ('at this moment') over 24 h post-dose during each treatment period
timeFrame: Duration: for up to 24 hours post-dose
Secondary outcomes:
measure: Drug Liking VAS (bipolar)
timeFrame: Duration: for up to 24 hours post-dose
measure: Overall Drug Liking VAS (bipolar)
timeFrame: Duration: for up to 12 hours post-dose
measure: Take Drug Again VAS (bipolar)
timeFrame: Duration: for up to 12 hours post-dose
measure: Good Effects VAS (unipolar)
timeFrame: Duration: for up to 24 hours post-dose
measure: Drug Similarity VAS
timeFrame: Duration: for up to 1 hour post-dose
measure: Bad Effects VAS (unipolar)
timeFrame: Duration: for up to 24 hours post-dose
measure: Alertness/Drowsiness VAS (bipolar)
timeFrame: Duration: for up to 24 hours post-dose
measure: Any Effects VAS (unipolar)
timeFrame: Duration: for up to 24 hours post-dose
measure: Feeling High VAS (unipolar)
timeFrame: Duration: for up to 24 hours post-dose
measure: Bowdle VAS Internal and External Perceptions
timeFrame: Duration: for up to 24 hours post-dose
measure: Observer's Assessment of Alertness/Sedation composite and sum scores
timeFrame: Duration: for up to 24 hours post-dose
measure: Reaction time task score
timeFrame: Duration: for up to 8 hours post-dose
measure: Rapid visual information processing score
timeFrame: Duration: for up to 8 hours post-dose
measure: Paired Associates Learning score
timeFrame: Duration: for up to 8 hours post-dose
Other outcomes:
measure: AUC(0-t) of ACT-541468
timeFrame: Duration: for up to 24 hours post-dose
measure: AUC(0-∞) of ACT-541468
timeFrame: Duration: for up to 24 hours post-dose
measure: Cmax of ACT-541468
timeFrame: Duration: for up to 24 hours post-dose
measure: tmax of ACT-541468
timeFrame: Duration: for up to 24 hours post-dose
measure: t½ of ACT-541468
timeFrame: Duration: for up to 24 hours post-dose
measure: Treatment-emergent adverse events (AEs)
timeFrame: All AEs from (first) admittance on Day -1 up to EOS, i.e. for up to 9 weeks
measure: Treatment-emergent serious AEs (SAEs)
timeFrame: SAE reporting: from signature of informed consent up to EOS, i.e. for up to 13 weeks
Locations:
city: Overland Park
country: United States
facility: Altasciences Clinical Kansas, Inc. (former Vince and Associates Clinical Research, Inc.)
state: Kansas
city: Montreal
country: Canada
facility: Altasciences Company Inc.
Study officials:
affiliation: Idorsia Pharmaceuticals Ltd.
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.