Behavioral and Subjective Efficacy of Ramelteon in Subjects With a History of Polydrug Abuse - Full Text View

Purpose

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.

Condition	Intervention	Phase
Drug Abuse	Drug: Ramelteon, triazolam, and placebo (56 possible combinations total)	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
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.

Resource links provided by NLM:

Drug Information available for: Triazolam Ramelteon

U.S. FDA Resources

Further study details as provided by Takeda Global Research & Development Center, Inc.:

Primary Outcome Measures:

Peak liking score from the Drug Effect Questionnaire as recorded during the 24 hours following administration. [ Time Frame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Next Day Questionnaire. [ Time Frame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit ] [ Designated as safety issue: No ]
Addiction Research Center Inventory. [ Time Frame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit ] [ Designated as safety issue: No ]
Drug Effect Questionnaire. [ Time Frame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit ] [ Designated as safety issue: No ]
Subjective Effects Questionnaire. [ Time Frame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit ] [ Designated as safety issue: No ]
Pharmacologic Class Questionnaire. [ Time Frame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit ] [ Designated as safety issue: No ]
Drug Versus Money Multiple Choice Procedure. [ Time Frame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit ] [ Designated as safety issue: No ]
Observer Rated Questionnaire. [ Time Frame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit ] [ Designated as safety issue: No ]
Word Recall/Recognition Task. [ Time Frame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit ] [ Designated as safety issue: No ]
Enter and Recall Task. [ Time Frame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit ] [ Designated as safety issue: No ]
Balance task. [ Time Frame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit ] [ Designated as safety issue: No ]
Digit Symbol Substitution Task. [ Time Frame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit ] [ Designated as safety issue: No ]
Circular lights task. [ Time Frame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit ] [ Designated as safety issue: No ]
Neuropsychometric Testing [ Time Frame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit ] [ Designated as safety issue: No ]
Adverse Events [ Time Frame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit ] [ Designated as safety issue: Yes ]
Laboratory Test Results [ Time Frame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit ] [ Designated as safety issue: Yes ]
Vital Signs [ Time Frame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit ] [ Designated as safety issue: Yes ]
Electrocardiograms [ Time Frame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit ] [ Designated as safety issue: Yes ]
Physical Examination Findings. [ Time Frame: Days 1, 2, 3, 4, 5, 6, 7, and 8 or Final Visit ] [ Designated as safety issue: Yes ]

Enrollment:	14
Study Start Date:	June 2003
Study Completion Date:	December 2003
Primary Completion Date:	December 2003 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Ramelteon, triazolam, and placebo (56 poss. combinations) Ramelteon, triazolam, and placebo (56 possible combinations total)	Drug: Ramelteon, triazolam, and placebo (56 possible combinations total) 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. Other Names: Rozerem™ TAK-375

Arms

Assigned Interventions

Experimental: Ramelteon, triazolam, and placebo (56 poss. combinations)

Ramelteon, triazolam, and placebo (56 possible combinations total)

Drug: Ramelteon, triazolam, and placebo (56 possible combinations total)

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.

Other Names:

Rozerem™
TAK-375

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

Ages Eligible for Study:	18 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00671632

Locations

United States, Maryland

Baltimore, Maryland, United States

Sponsors and Collaborators

Takeda Global Research & Development Center, Inc.

Investigators

Study Director:

VP Clinical Science

Takeda Global Research & Development Center, Inc.

More Information

Additional Information:

Rozerem Package Insert This link exits the ClinicalTrials.gov site

FDA Safety Alerts and Recalls This link exits the ClinicalTrials.gov site

Publications:

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.

Responsible Party:	Takeda Global Research & Development Center, Inc.
ClinicalTrials.gov Identifier:	NCT00671632 History of Changes
Other Study ID Numbers:	01-02-TL-375-015, U1111-1114-3109
Study First Received:	May 1, 2008
Last Updated:	February 27, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Takeda Global Research & Development Center, Inc.:

Addiction

Additional relevant MeSH terms:

Substance-Related Disorders
Mental Disorders
Triazolam
Adjuvants, Anesthesia
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Anxiety Agents

Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 16, 2013