Clinical trial NCT01987739: Study to Evaluate the Relative Abuse Potential of Almorexant in Recreational Drug Users
Official title: A Single Center, Randomized, Double-blind, Double-dummy, Placebo- and Active-controlled, Six-way Crossover Single-dose Study to Evaluate the Relative Abuse Potential of Almorexant in Recreational Central Nervous System (CNS) Depressant Drug Users
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Abuse Potential Study
Keywords: Almorexant
Zolpidem
Lead sponsor: Midnight Pharma, LLC
Sponsor class: INDUSTRY
First posted: 2013-11-19
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: This was a six-way crossover study with six single-dose treatment sessions. The profile of acute effects on abuse potential measures of different almorexant doses was compared to that of placebo and two doses of zolpidem

Detailed description: This was a prospective, randomized, double-blind, double-dummy, balanced, placebo and active-controlled, six-way crossover Phase 1 study with six single-dose treatment sessions. The profile of acute effects on pharmacodynamic abuse potential measures of different almorexant doses was compared with that of placebo and two doses of zolpidem.

Eligibility criteria: Inclusion Criteria:

* Healthy male or female subjects 18 to 55 years of age, inclusive.
* Recreational drug use with a history of CNS depressant use, defined as at least 10 lifetime occasions of non-medical use of drugs with depressant/sedative properties (e.g., benzodiazepines, barbiturates, gammahydroxybutyric acid (GHB), zopiclone, zolpidem, cannabis, etc.), and at least one instance of non-medical use in the past year.
* Body mass index (BMI) within the range of 18 to 32 kg/m\^2, inclusive, and a minimum weight of 50 kg.
* Female subjects of childbearing potential must have been practicing strict sexual abstinence or using a medically acceptable and reliable form of birth control with a failure rate of \< 1% per year from at least 1 month prior to Screening (at least 3 months for oral contraceptives) and for at least 1 month after the last study drug administration. Accepted methods of contraception included implants, injectables, combined oral hormonal contraceptives, some intrauterine devices, sexual abstinence, tubal ligation, or vasectomized partner.
* Female subjects of non-childbearing potential must have been amenorrheic for at least 1 year following natural menopause or had a hysterectomy and/or bilateral oophorectomy (as determined by subject medical history).
* Female subjects must have had a negative pregnancy test at Screening and at each admission.
* Must have passed Qualification Visit eligibility criteria.
* Must have been able to speak, read, and understand English sufficiently to understand the nature of the study, to provide written informed consent, and to allow completion of all study assessments.
* Willing and able to abide by all study requirements and restrictions.
* Give voluntary written informed consent to participate in the study.

Exclusion Criteria:

* Received an investigational drug in a clinical trial within 30 days prior to the Screening Visit.
* Drug or alcohol dependence (except nicotine or caffeine) in the past 2 years as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), including subjects who had ever been in a drug rehabilitation program (other than treatment for smoking cessation).
* Unwillingness or inability to abstain from recreational drug use as required for the study.
* Positive urine drug screen at admission to Qualification or any Treatment Visit greater than the established threshold value, except for cannabinoids (THC; due to slow release from adipose tissue). If THC was positive, inclusion was at the discretion of the investigator or designee. Subjects with a positive urine drug screen were rescheduled up to 2-times at the investigator's/designee's discretion.
* Positive breath alcohol test at Screening or at any admission.
* Clinically significant abnormalities on physical examination, medical history, 12-lead electrocardiogram (ECG), vital signs, or laboratory tests, including a history or presence of psychiatric, cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or oncologic disease or any other condition, which in the opinion of the investigator would have jeopardized the safety of the subject or the validity of the study results.
* Previous history of fainting, collapses, syncope, orthostatic hypotension, or vasovagal reactions.
* Use of non-prescription medication, prescription medication, or natural health products (except vitamin or mineral supplements, acceptable forms of birth control, and hormone replacement) within 7 days prior to first drug administration in the Qualification Visit and throughout the study. Up to 1 g per day of acetaminophen was allowed at the discretion of the investigator. Concomitant medication known to inhibit or induce the cytochrome P3A4 isoenzyme was not allowed. Treatment with drugs metabolized by the cytochrome P2D6 isoenzyme was not allowed.
* History of allergy or hypersensitivity to study drugs, related drugs (e.g., benzodiazepines or gamma-aminobutyric acid related drugs) or excipients (including lactose).

Primary outcomes:
measure: Maximum effect (Emax) over 24 h post-dose for "At the moment" Drug Liking Visual Analogue Scale (VAS) score during each Treatment Visit
timeFrame: 24 hours
Secondary outcomes:
measure: Minimum Effect (Emin) and Time-weighted mean effect (TWMean) over 24 h post-dose for "At the moment" Drug Liking VAS score during each Treatment Visit
timeFrame: 24 hours
measure: Overall Drug Liking VAS score (Emax, Emin, and arithmetic mean effect of 8 h and 24 h post-dose assessments during each Treatment Visit)
timeFrame: 24 hours
measure: Good/Bad Drug Effects VAS score (Emax, Emin, and TWMean over 24 h post-dose during each Treatment Visit)
timeFrame: 24 hours
measure: Take Drug Again VAS score (Emax and arithmetic mean of 8 h and 24 h post-dose assessments during each Treatment Visit)
timeFrame: 24 hours
measure: Subjective Drug Value (SDV) (Emax and arithmetic mean of 8 h and 24 h post-dose assessment during each Treatment Visit)
timeFrame: 24 hours
measure: Feeling High VAS score (Emax and TWMean over 24 h post-dose during each Treatment Visit)
timeFrame: 24 hours
measure: Good Drug Effects VAS score (Emax and TWMean over 24 h post-dose during each Treatment Visit)
timeFrame: 24 hours
measure: Addiction Research Center Inventory (ARCI) Morphine Benzedrine Group (MBG) scale (Emax and TWMean over 24 h postdose during each Treatment Visit)
timeFrame: 24 hours
measure: Bad Drug Effects VAS score (Emax and TWMean over 24 h post-dose during each Treatment Visit)
timeFrame: 24 hours
measure: ARCI Lysergic acid diethylamide (LSD) scale (Emax and TWMean over 24 h post-dose during each Treatment Visit
timeFrame: 24 hours
measure: ARCI Pentobarbital Chlorpromazine Alcohol Group (PCAG) scale (Emax and TWMean over 24 h post-dose during each Treatment Visit)
timeFrame: 24 hours
measure: Alertness/Drowsiness VAS score (Emin [drowsiness] and TWMean over 24 h post-dose during each Treatment Visit)
timeFrame: 24 hours
measure: Bowdle VAS scores (Emax and TWMean over 24 h post-dose during each Treatment Visit)
timeFrame: 24 hours
measure: Any Drug Effects VAS score (Emax and TWMean over 24 h post-dose during each Treatment Visit)
timeFrame: 24 hours
measure: Drug Familiarity VAS score (Hour 12 during each Treatment Visit)
timeFrame: 12 hours
measure: Drug Similarity VAS score (Hour 12 during each Treatment Visit)
timeFrame: 12 hours
Other outcomes:
Locations:
Study officials:
affiliation: Kendle Early Stage - Toronto
name: Edward M Sellers, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: