Study to Evaluate the Relative Abuse Potential of Almorexant in Recreational Drug Users

Midnight Pharma

Status and phase: Completed; Phase 1

Conditions: Abuse Potential Study

Treatments: Drug: 40 mg zolpidem; Drug: 400 mg almorexant; Drug: 1000 mg almorexant; Drug: placebo; Drug: 20 mg zolpidem; Drug: 200 mg almorexant

Study type: Interventional

Funder types: Industry

Identifiers

NCT01987739

AC-057-116

Details and patient eligibility

About

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

Full 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.

Enrollment: 42 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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).

Trial design

42 participants in 6 patient groups

Arm 1

Experimental group

Description:

Subjects were randomized to receive single, oral doses of study medication in the sequence ABFCED, where, Treatment A was: 200 mg almorexant; Treatment B was 400 mg almorexant; Treatment C was 1000 mg almorexant; Treatment D was 20 mg zolpidem; Treatment E was 40 mg zolpidem; and Treatment F was placebo. The duration of each Treatment Visit was 1 day/2 nights. Study drug was administered on Day 1 of each Treatment Visit. Each treatment was separated by a washout period of at least 10 days.

Treatment:

Drug: 1000 mg almorexant

Drug: 400 mg almorexant

Drug: placebo

Drug: 200 mg almorexant

Drug: 40 mg zolpidem

Drug: 20 mg zolpidem

Arm 2

Experimental group

Description:

Subjects were randomized to receive single, oral doses of study medication in the sequence BCADFE, where, Treatment A was: 200 mg almorexant; Treatment B was 400 mg almorexant; Treatment C was 1000 mg almorexant; Treatment D was 20 mg zolpidem; Treatment E was 40 mg zolpidem; and Treatment F was placebo. The duration of each Treatment Visit was 1 day/2 nights. Study drug was administered on Day 1 of each Treatment Visit. Each treatment was separated by a washout period of at least 10 days.

Treatment:

Drug: 1000 mg almorexant

Drug: 400 mg almorexant

Drug: placebo

Drug: 200 mg almorexant

Drug: 40 mg zolpidem

Drug: 20 mg zolpidem

Arm 3

Experimental group

Description:

Subjects were randomized to receive single, oral doses of study medication in the sequence CDBEAF, where, Treatment A was: 200 mg almorexant; Treatment B was 400 mg almorexant; Treatment C was 1000 mg almorexant; Treatment D was 20 mg zolpidem; Treatment E was 40 mg zolpidem; and Treatment F was placebo. The duration of each Treatment Visit was 1 day/2 nights. Study drug was administered on Day 1 of each Treatment Visit. Each treatment was separated by a washout period of at least 10 days.

Treatment:

Drug: 1000 mg almorexant

Drug: 400 mg almorexant

Drug: placebo

Drug: 200 mg almorexant

Drug: 40 mg zolpidem

Drug: 20 mg zolpidem

Arm 4

Experimental group

Description:

Subjects were randomized to receive single, oral doses of study medication in the sequence DECFBA, where, Treatment A was: 200 mg almorexant; Treatment B was 400 mg almorexant; Treatment C was 1000 mg almorexant; Treatment D was 20 mg zolpidem; Treatment E was 40 mg zolpidem; and Treatment F was placebo. The duration of each Treatment Visit was 1 day/2 nights. Study drug was administered on Day 1 of each Treatment Visit. Each treatment was separated by a washout period of at least 10 days.

Treatment:

Drug: 1000 mg almorexant

Drug: 400 mg almorexant

Drug: placebo

Drug: 200 mg almorexant

Drug: 40 mg zolpidem

Drug: 20 mg zolpidem

Arm 5

Experimental group

Description:

Subjects were randomized to receive single, oral doses of study medication in the sequence EFDACB, where, Treatment A was: 200 mg almorexant; Treatment B was 400 mg almorexant; Treatment C was 1000 mg almorexant; Treatment D was 20 mg zolpidem; Treatment E was 40 mg zolpidem; and Treatment F was placebo. The duration of each Treatment Visit was 1 day/2 nights. Study drug was administered on Day 1 of each Treatment Visit. Each treatment was separated by a washout period of at least 10 days.

Treatment:

Drug: 1000 mg almorexant

Drug: 400 mg almorexant

Drug: placebo

Drug: 200 mg almorexant

Drug: 40 mg zolpidem

Drug: 20 mg zolpidem

Arm 6

Experimental group

Description:

Subjects were randomized to receive single, oral doses of study medication in the sequence FAEBDC, where, Treatment A was: 200 mg almorexant; Treatment B was 400 mg almorexant; Treatment C was 1000 mg almorexant; Treatment D was 20 mg zolpidem; Treatment E was 40 mg zolpidem; and Treatment F was placebo. The duration of each Treatment Visit was 1 day/2 nights. Study drug was administered on Day 1 of each Treatment Visit. Each treatment was separated by a washout period of at least 10 days.

Treatment:

Drug: 1000 mg almorexant

Drug: 400 mg almorexant

Drug: placebo

Drug: 200 mg almorexant

Drug: 40 mg zolpidem

Drug: 20 mg zolpidem