Safety and Efficacy of Ramelteon in Healthy Subjects

NCT ID: NCT00671190

Last Updated: 2012-02-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

75 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-03-31

Study Completion Date

2005-05-31

Brief Summary

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The purpose of this study is to determine the phase-advance in circadian rhythms in healthy adults subjects taking ramelteon, once daily (QD).

Detailed Description

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Circadian rhythms are the innate daily fluctuation of physiologic or behavior functions, included sleep-wake states, generally tied to the 24-hour daily dark-light cycle. Circadian Rhythm Sleep Disorders share a common chronophysiologic basis in which the major feature is a misalignment between the patient's sleep pattern and the sleep pattern that is desired or regarded as the societal norm.

Circadian Rhythm Sleep Disorders affect a sizable portion of the United States population, representing a significant underserved need. It has been estimated that 7% of all adolescents suffer from Delayed Sleep Phase Syndrome. Approximately 1% of all middle-aged people have Advanced Sleep Phase Syndrome. There are 21 million people who are shift workers and between 5% to 20% of these workers develop severe symptoms of Shift Work Sleep Disorder soon after starting shift work. Time Zone Change (Jet Lag) Syndrome can affect millions of travelers each year. Most symptoms are a result of sleep deprivation.

Current treatment of these disorders include behavioral therapy, light therapy and use of hypnotics and stimulants. Melatonin has also been used with mixed results.

The effects of melatonin on circadian phase depend on the time at which it is administered, and are generally opposite those of light. Specifically, melatonin given in the evening results in an advance of the circadian system to an earlier hour ("phase advance"). While melatonin appears to be useful in the treatment of sleep disruption in the blind, the phase shifting ability of native melatonin is much less than that of light, limiting its utility in the treatment of circadian dysfunction in sighted individuals.

Ramelteon is under global development as a sleep-promoting agent. Ramelteon demonstrates affinity and selectivity for human melatonin-1 or melatonin-2 receptors. Ramelteon also demonstrates full agonist activity relative to melatonin in cells expressing human melatonin-1 or melatonin-2 receptors.

The purpose of this study is to determine whether ramelteon given over multiple days can produce a phase advance in circadian rhythms as measured in salivary melatonin levels in dim-light conditions. Participation in this study is anticipated to be about 4 weeks.

Conditions

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Sleep Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Ramelteon 1 mg QD

Group Type EXPERIMENTAL

Ramelteon

Intervention Type DRUG

Ramelteon 1 mg, tablets, orally once daily for up to 5 days

Ramelteon 2 mg QD

Group Type EXPERIMENTAL

Ramelteon

Intervention Type DRUG

Ramelteon 2 mg, tablets, orally once daily for up to 5 days

Ramelteon 4 mg QD

Group Type EXPERIMENTAL

Ramelteon

Intervention Type DRUG

Ramelteon 4 mg, tablets, orally once daily for up to 5 days

Ramelteon 8 mg QD

Group Type EXPERIMENTAL

Ramelteon

Intervention Type DRUG

Ramelteon 8 mg, tablets, orally once daily for up to 5 days

Placebo QD

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Ramelteon placebo-matching tablets, orally once daily for up to 5 days

Interventions

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Ramelteon

Ramelteon 1 mg, tablets, orally once daily for up to 5 days

Intervention Type DRUG

Ramelteon

Ramelteon 2 mg, tablets, orally once daily for up to 5 days

Intervention Type DRUG

Ramelteon

Ramelteon 4 mg, tablets, orally once daily for up to 5 days

Intervention Type DRUG

Ramelteon

Ramelteon 8 mg, tablets, orally once daily for up to 5 days

Intervention Type DRUG

Placebo

Ramelteon placebo-matching tablets, orally once daily for up to 5 days

Intervention Type DRUG

Other Intervention Names

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Rozerem™ TAK-375 Rozerem™ TAK-375 Rozerem™ TAK-375 Rozerem™ TAK-375

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
* Habitual bedtime is between 10:00 p.m. and 1:00 a.m.
* Body mass index between 18 and 30, inclusive.
* Medial subjective sleep latency of less than 30 minutes and a median subjective total sleep time of greater than 6.5 but less than 9 hours.

Exclusion Criteria

* Known hypersensitivity to ramelteon or related compounds, including melatonin, and melatonin related compounds.
* Previously participated in a study involving ramelteon.
* Participated in any other investigational study and/or taken any investigational drug within 30 days or five half-lives prior to the first dose of single-blind study medication, whichever is longer.
* Sleep schedule changes required by employment (eg, shift worker) within three months prior to the administration of single-blind study medication.
* Flown across greater than three time zones within 21 days prior to or during screening.
* Participated in a weight loss program or has substantially altered their exercise routine within 30 days prior to the administration of single-blind study medication.
* Ever had a history of seizures, sleep apnea, restless leg syndrome, periodic limb movement syndrome, chronic obstructive pulmonary disease, schizophrenia, bipolar disorder, mental retardation, or cognitive disorder.
* History of primary sleep disorders as determined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Revised within the past 6 months.
* History of psychiatric disorder (including anxiety or depression) within the past 12 months.
* History of alcohol abuse within the past 12 months, as defined in Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Revised, or regularly consumes more than 14 alcoholic drinks per week, or consumes any alcoholic drinks 2 hours prior to bedtime.
* History of drug abuse within the past 12 months.
* Current neurological, hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, hematologic, or metabolic disease.
* Apnea hypopnea index (per hour of sleep) greater than 10.
* Periodic leg movement syndrome with arousal index (per hour of sleep) greater than 10 as seen on the polysomnography screening night.
* Positive urine drug screen.
* Smokes greater than 3 cigarettes per day or uses tobacco products during nightly awakenings.
* Reports high caffeine consumption (greater than 500 mg daily).
* Any clinically important abnormal finding as determined by a medical history, physical examination, electrocardiogram, or clinical laboratory tests, as determined by the investigator.
* Positive hepatitis panel including anti-hepatitis.
* Unwilling to remain in the sleep laboratory in dim-light conditions for 5 days and nights or fully cooperate with site personnel.
* Any additional condition(s) that in the Investigator's opinion would:

* affect sleep/wake function
* prohibit the subject from completing the study
* not be in the best interest of the subject.
* Is required to take or continues taking any disallowed medication, prescription medication, herbal treatment or over-the counter medication, including:

* Anxiolytics
* Central nervous system active drugs (including herbal)
* Antipsychotics
* Narcotic analgesics
* Antidepressants
* Beta blockers
* Anticonvulsants
* St. John's Wort
* Sedating H1 antihistamines
* Kava-kava
* Systemic steroids
* Ginkgo-biloba
* Respiratory stimulants
* Over the counter and prescription stimulants
* Decongestants
* Over-the-counter and prescription diet aids
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Takeda

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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VP Clinical Science

Role: STUDY_DIRECTOR

Takeda

Locations

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Hot Springs, Arkansas, United States

Site Status

Los Angeles, California, United States

Site Status

San Diego, California, United States

Site Status

Miami, Florida, United States

Site Status

Atlanta, Georgia, United States

Site Status

Macon, Georgia, United States

Site Status

Danville, Indiana, United States

Site Status

Overland Park, Kansas, United States

Site Status

Metairie, Louisiana, United States

Site Status

Chevy Chase, Maryland, United States

Site Status

Las Vegas, Nevada, United States

Site Status

Dublin, Ohio, United States

Site Status

Columbia, South Carolina, United States

Site Status

Countries

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United States

References

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Richardson GS, Zee PC, Wang-Weigand S, Rodriguez L, Peng X. Circadian phase-shifting effects of repeated ramelteon administration in healthy adults. J Clin Sleep Med. 2008 Oct 15;4(5):456-61.

Reference Type RESULT
PMID: 18853704 (View on PubMed)

Related Links

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Other Identifiers

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U1111-1114-8304

Identifier Type: REGISTRY

Identifier Source: secondary_id

01-02-TL-375-018

Identifier Type: -

Identifier Source: org_study_id

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