Clinical trial NCT00671632: Behavioral and Subjective Efficacy of Ramelteon in Subjects With a History of Polydrug Abuse
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Drug Abuse
Keywords: Addiction
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2008-05-05
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Peak liking score from the Drug Effect Questionnaire as recorded during the 24 hours following administration.
timeFrame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit
Secondary outcomes:
measure: Next Day Questionnaire.
timeFrame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit
measure: Addiction Research Center Inventory.
timeFrame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit
measure: Drug Effect Questionnaire.
timeFrame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit
measure: Subjective Effects Questionnaire.
timeFrame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit
measure: Pharmacologic Class Questionnaire.
timeFrame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit
measure: Drug Versus Money Multiple Choice Procedure.
timeFrame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit
measure: Observer Rated Questionnaire.
timeFrame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit
measure: Word Recall/Recognition Task.
timeFrame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit
measure: Enter and Recall Task.
timeFrame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit
measure: Balance task.
timeFrame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit
measure: Digit Symbol Substitution Task.
timeFrame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit
measure: Circular lights task.
timeFrame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit
measure: Neuropsychometric Testing
timeFrame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit
measure: Adverse Events
timeFrame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit
measure: Laboratory Test Results
timeFrame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit
measure: Vital Signs
timeFrame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit
measure: Electrocardiograms
timeFrame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit
measure: Physical Examination Findings.
timeFrame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit
Other outcomes:
Locations:
city: Baltimore
country: United States
state: Maryland
Study officials:
affiliation: Takeda
name: VP Clinical Science
role: STUDY_DIRECTOR
References:
citation: Johnson MW, Suess PE, Griffiths RR. Ramelteon: a novel hypnotic lacking abuse liability and sedative adverse effects. Arch Gen Psychiatry. 2006 Oct;63(10):1149-57. doi: 10.1001/archpsyc.63.10.1149.