NCT00755495

Safety and Efficacy of Ramelteon and Doxepin in Subjects With Chronic Insomnia

A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Multicenter Proof-of-Concept Study to Evaluate the Safety and Efficacy of Ramelteon Taken in Combination With Doxepin for the Treatment of Subjects With Chronic Insomnia

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 472 (actual)
• Sponsor: Takeda · Industry
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine the efficacy of ramelteon, once daily (QD), combined with doxepin in treating subjects with insomnia.

Detailed description

Approximately 60 to 70 million adults in the United States alone are affected by insomnia. Daytime symptoms of insomnia include tiredness, lack of energy, difficulty concentrating, and irritability. Recent epidemiologic research focusing on quality of life has identified significant insomnia-related morbidities that relate to work productivity, health care utilization, and risk of depression. Insomnia is also associated with diminished work output, absenteeism, and greater rates of accidents. Gamma-aminobutyric acid is the major inhibitory transmitter in the central nervous system and most currently prescribed sleep agents are benzodiazepine receptor agonists, which induce sleep by binding to the benzodiazepine receptor site of the gamma-aminobutyric acid -A receptor complex. In addition to sleep, benzodiazepine receptor agonists can cause a wide range of ancillary effects not directly related to sleep, including sedative, anxiolytic, muscle-relaxant, and amnesic effects, and have risks of tolerance, dependence, and abuse potential. Doxepin is one of a class of psychotherapeutic agents known as dibenzoxepin tricyclic compounds. Doxepin is indicated for the treatment of depression, anxiety, and psychotic depressive disorders. The most common adverse event associated with the use of doxepin is drowsiness. A limited number of controlled studies have been performed to examine the effects of low doxepin on insomnia. TAK-375 (Ramelteon) is a melatonin receptor agonist with affinity for the human melatonin receptor subtype 1 (MT1), melatonin receptor subtype 2 (MT2) and selectivity over the melatonin receptor subtype 3 (MT3) receptor. This trial will determine if the co-administration of ramelteon and doxepin will decrease both latency to persistent sleep and wake time after sleep onset. Study participation is anticipated to be about 2 months.

Conditions

• Sleep Initiation and Maintenance Disorders

Interventions

Type	Name	Description
DRUG	Ramelteon and doxepin	Ramelteon 8 mg, tablets, orally, once daily and doxepin 3 mg, liquid, orally, once daily for up to five weeks.
DRUG	Ramelteon	Ramelteon 8 mg, tablets, orally, once daily and doxepin placebo-matching liquid, orally, once daily for up to five weeks.
DRUG	Doxepin	Ramelteon placebo-matching tablets, orally, once daily and doxepin 3 mg, liquid, orally, once daily for up to five weeks.
DRUG	Placebo	Ramelteon placebo-matching tablets, orally, once daily and doxepin placebo-matching liquid, orally, once daily for up to five weeks.

Timeline

• Start date: 2006-07-01
• Primary completion: 2007-03-01
• Completion: 2007-03-01
• First posted: 2008-09-19
• Last updated: 2012-02-28