Behavioral and Subjective Efficacy of Ramelteon in Subjects With a History of Polydrug Abuse

Study Overview
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Brief Summary
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The purpose of this study is to determine the relative abuse potential of ramelteon, once daily (QD), compared to triazolam in subjects with a history of drug abuse.

Detailed Description
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Insomnia is characterized by a complaint of either difficulties initiating and maintaining sleep, or of nonrestorative and non-refreshing sleep. Transient insomnia affects approximately one-third to one-half of the US population, based on the results of 2 surveys of representative samples of the adult US population conducted by the Gallup Organization in which respondents were asked if they had ever had difficulty sleeping. Based on reports of regular or frequent sleep difficulty, results from the same studies suggest that approximately one-tenth of the US population experiences chronic insomnia. The ideal treatment for insomnia would reduce the latency to onset of sleep and increase total sleep time, without a negative impact on sleep architecture and without safety concerns or next-day effects. Ramelteon is a melatonin-1 receptor agonist under global development by Takeda Chemical Industries, Ltd., for the treatment of transient and chronic insomnia and for the treatment of Circadian Rhythm Sleep Disorders. Participation in this study is anticipated to be about 1 month.

Official Title
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A Randomized, Single Center, Double-Blind, Multiple-Dose, Placebo-Controlled, Crossover, Double-Dummy Study of The Acute Behavioral and Subjective Effects of Ramelteon in Subjects With a History of Polydrug Abuse.

Conditions
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Drug Abuse

Intervention / Treatment
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* Drug: Ramelteon, triazolam, and placebo (56 possible combinations total)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study. Must be in good health as determined by a physician (ie, via medical history and physical examination). Clinical laboratory evaluations (including clinical chemistry, hematology, and complete urinalysis) within the reference range for the testing laboratory unless the results are deemed not clinically significant by the investigator or sponsor. Must have a history of substance abuse or dependence, on a commonly abuse recreational psychoactive drug (e.g., benzodiazepines, cocaine, opiates, cannabinoids). Must have a negative urine sample for substances of abuse and a negative breathalyzer test before the first dose of study medication is administered. Must be free of any signs/symptoms of withdrawal from substances after admittance to the research unit and prior to the first dose of study medication. Must report liking for study medication given on Day -2 and liking must be of greater magnitude that than the liking for study medication given on Day -1. Exclusion Criteria Known hypersensitivity to ramelteon or related compounds including melatonin. Known hypersensitivity to benzodiazepines or related compounds. Current diagnosis of any type of physical drug dependence other than nicotine or caffeine. Positive HBsAg are excluded. Positive human immunodeficiency virus antibody at screening. Diastolic blood pressure greater than 90 mm Hg or a systolic pressure of greater than 140 mm Hg at screening. Previous history of cancer, other than basal cell carcinoma, that has not been in remission for at least 5 years prior to the first dose of study drug. Body weight is less than 99 or greater than 264 pounds. Subjects that are morbidly obese as defined by greater than 2 times ideal body weight Significant urine concentration of any drug that could interfere with the study. Clinically significant abnormal finding on physical examination or electrocardiogram. Subjects with a clinically significant illness in the past 30 days. Current Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Revised diagnosis of a serious psychiatric condition (e.g. Schizophrenia, Major Depression). Currently is participating in another investigational study or has participated in an investigational study within the past 30 days. Any other serious disease or condition at screening or at randomization that might affect life expectancy or make it difficult to successfully manage and follow the subject according to the protocol. Is required to take or continues taking any disallowed medication, prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ramelteon, triazolam, and placebo (56 poss. combinations)<br>Ramelteon, triazolam, and placebo (56 possible combinations total) | Drug: Ramelteon, triazolam, and placebo (56 possible combinations total)<br>* Randomized sequence over eight consecutive days to include the following: Ramelteon 16 mg, tablets, orally, one day only; Ramelteon 80 mg, tablets, orally, one day only; Ramelteon 160 mg, tablets, orally, one day only; Triazolam 0.25 mg, capsules, orally, one day only; Triazolam 0.50 mg, capsules, orally, one day only; Triazolam 0.75 mg, capsules, orally, one day only; Ramelteon placebo-matching tablets, orally, one day only, OR Triazolam placebo-matching capsules, orally, one day only; Additional dose of study medication or placebo, tablets or capsules, orally, one day only.<br>* Other names: TAK-375;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak liking score from the Drug Effect Questionnaire as recorded during the 24 hours following administration. |  | Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Next Day Questionnaire. |  | Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit | 
| Addiction Research Center Inventory. |  | Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit | 
| Drug Effect Questionnaire. |  | Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit | 
| Subjective Effects Questionnaire. |  | Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit | 
| Pharmacologic Class Questionnaire. |  | Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit | 
| Drug Versus Money Multiple Choice Procedure. |  | Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit | 
| Observer Rated Questionnaire. |  | Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit | 
| Word Recall/Recognition Task. |  | Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit | 
| Enter and Recall Task. |  | Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit | 
| Balance task. |  | Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit | 
| Digit Symbol Substitution Task. |  | Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit | 
| Circular lights task. |  | Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit | 
| Neuropsychometric Testing |  | Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit | 
| Adverse Events |  | Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit | 
| Laboratory Test Results |  | Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit | 
| Vital Signs |  | Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit | 
| Electrocardiograms |  | Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit | 
| Physical Examination Findings. |  | Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Addiction