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.
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
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.
- 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
- 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,
- 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.
- 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
- 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.