Efficacy and Safety of Ramelteon Combined With Gabapentin in Treating Patients With Insomnia
|ClinicalTrials.gov Identifier: NCT00755508|
Recruitment Status : Completed
First Posted : September 19, 2008
Last Update Posted : February 28, 2012
|Condition or disease||Intervention/treatment||Phase|
|Sleep Initiation and Maintenance Disorders||Drug: Ramelteon and gabapentin Drug: Ramelteon Drug: Gabapentin Drug: Placebo||Phase 2|
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.
Gabapentin is a novel anti-epileptic drug, which is currently used in subjects with partial seizures. Some studies have shown that gabapentin also has an effect on sleep architecture. In several studies, which included healthy subjects, epileptic subjects, and subjects with restless leg syndrome, the use of gabapentin been shown to prolong slow-wave sleep, increase total sleep time and sleep efficiency, and decrease number of awakenings.
Ramelteon is a melatonin receptor agonist with affinity for the human melatonin receptor subtype 1, melatonin receptor subtype 2 and selectivity over the melatonin receptor subtype 3 receptor. It also demonstrates agonist activity in vitro relative to melatonin in cells expressing human melatonin receptor subtype 1 or melatonin receptor subtype 2 receptors. The binding of melatonin at these receptors is thought to contribute to maintenance of the circadian rhythm underlying the normal sleep-wake cycle.
The purpose of this trial is to determine if the co-administration of Ramelteon and gabapentin may produce increased sleep efficiency through reduction of wake time after persistent sleep onset, in addition to the reduction in sleep latency and increase in sleep duration. Study participation is anticipated to be about one month.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||378 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Multicenter, Proof-of-Concept Study to Evaluate the Safety and Efficacy of ROZEREM™ Taken in Combination With Gabapentin for the Treatment of Subjects With Chronic Insomnia|
|Study Start Date :||November 2005|
|Primary Completion Date :||September 2006|
|Study Completion Date :||September 2006|
|Experimental: Ramelteon 4 mg QD and Gabapentin 400 mg QD||
Drug: Ramelteon and gabapentin
Ramelteon 4 mg, tablets, orally, once daily and gabapentin 400 mg, capsules, orally, once daily for up to one week.
|Experimental: Ramelteon 8 mg QD and Gabapentin 800 mg QD||
Drug: Ramelteon and gabapentin
Ramelteon 8 mg, tablets, orally, once daily and gabapentin 800 mg, capsules, orally, once daily for up to one week.
|Experimental: Ramelteon 8 mg QD and Gabapentin Placebo QD||
Ramelteon 8 mg, tablets, orally, once daily and gabapentin placebo-matching capsules, orally, once daily for up to one week.
|Active Comparator: Gabapentin 800 mg QD||
Ramelteon placebo-matching tablets, orally, once daily and gabapentin 800 mg, capsules, orally, once daily for up to one week.
|Placebo Comparator: Placebo||
Ramelteon placebo-matching tablets, orally, once daily and gabapentin placebo-matching capsules, orally, once daily for up to one week.
Other Name: Rozerem
- Mean objective wake time after persistent sleep onset in sleep lab. [ Time Frame: Nights: 1 and 2. ]
- Subjective wake time after persistent sleep onset determined by the post-sleep questionnaire. [ Time Frame: Nights: 1, 2, 3, 4, 5, 6 and 7. ]
- Number of awakenings after persistent sleep polysomnography. [ Time Frame: Nights: 1 and 2 ]
- Subjective number of awakenings as determined by post-sleep questionnaire. [ Time Frame: Nights: 1, 2, 3, 4, 5, 6 and 7. ]
- Latency to persistent sleep and total sleep time as determined by polysomnography. [ Time Frame: Nights: 1 and 2 ]
- Subjective sleep latency, subjective total sleep time and subjective sleep quality determined by post-sleep questionnaire. [ Time Frame: Nights: 1, 2, 3, 4, 5, 6 and 7. ]
- Daytime functioning determined by pre-sleep questionnaire. [ Time Frame: Nights: 1, 2, 3, 4, 5, 6 and 7. ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00755508
|Study Director:||Sr. VP Clinical Science||Takeda|