Safety and Efficacy of Ramelteon in Healthy Subjects
The purpose of this study is to determine the phase-advance in circadian rhythms in healthy adults subjects taking ramelteon, once daily (QD).
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-Ranging Study to Evaluate the Phase-Shifting Effects of Repeated Daily Dosing of Ramelteon in Healthy Subjects|
- Dim Light Melatonin Secretion Offset Time. [ Time Frame: Days 1, 2, 3, and 4 or Final Visit. ] [ Designated as safety issue: No ]
- Dim-Light Melatonin Onset (DLMOn) time. [ Time Frame: Days 1, 2, 3, and 4 or Final Visit. ] [ Designated as safety issue: No ]
|Study Start Date:||March 2005|
|Study Completion Date:||May 2005|
|Primary Completion Date:||May 2005 (Final data collection date for primary outcome measure)|
|Experimental: Ramelteon 1 mg QD||
Ramelteon 1 mg, tablets, orally once daily for up to 5 days
|Experimental: Ramelteon 2 mg QD||
Ramelteon 2 mg, tablets, orally once daily for up to 5 days
|Experimental: Ramelteon 4 mg QD||
Ramelteon 4 mg, tablets, orally once daily for up to 5 days
|Experimental: Ramelteon 8 mg QD||
Ramelteon 8 mg, tablets, orally once daily for up to 5 days
|Placebo Comparator: Placebo QD||
Ramelteon placebo-matching tablets, orally once daily for up to 5 days
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.
|United States, Arkansas|
|Hot Springs, Arkansas, United States|
|United States, California|
|Los Angeles, California, United States|
|San Diego, California, United States|
|United States, Florida|
|Miami, Florida, United States|
|United States, Georgia|
|Atlanta, Georgia, United States|
|Macon, Georgia, United States|
|United States, Indiana|
|Danville, Indiana, United States|
|United States, Kansas|
|Overland Park, Kansas, United States|
|United States, Louisiana|
|Metairie, Louisiana, United States|
|United States, Maryland|
|Chevy Chase, Maryland, United States|
|United States, Nevada|
|Las Vegas, Nevada, United States|
|United States, Ohio|
|Dublin, Ohio, United States|
|United States, South Carolina|
|Columbia, South Carolina, United States|
|Study Director:||VP Clinical Science||Takeda Global Research & Development Center, Inc.|