From rxpgnews.com
Ramelteon demonstrates no abuse potential
By Takeda Pharmaceuticals North America, Inc.
May 24, 2005 - 12:42:00 PM
Results of a clinical study indicated that ramelteon, an investigational compound currently under review by the FDA for insomnia treatment, had no more potential for abuse than placebo in individuals with a history of polydrug abuse. These results, presented at the 2005 American Psychiatric Association Annual Meeting, showed that patients exhibited no abuse potential or behavioral impairment at up to 20 times the proposed therapeutic dose of ramelteon compared to placebo.
"In the treatment of insomnia, drug abuse potential is a significant concern to patients as well as to prescribing physicians," said Roland Griffiths, PhD, Professor in the departments of Psychiatry and Neuroscience, Johns Hopkins Bayview Medical Center, Baltimore, MD. "The chronic nature of some types of insomnia may necessitate treatment for an extended period, underscoring the need for sleep medications with little or no abuse potential."
It is estimated that 60 million Americans suffer from insomnia at least a few nights per week. Most currently prescribed sleep agents and some investigational drugs work by targeting gamma-aminobutyric acid (GABA) receptors, which are located throughout the brain. In pre-clinical studies, ramelteon has shown no affinity for GABA or opiate receptors.
This study was a placebo-controlled, crossover clinical study of fourteen adults with a history of polydrug or multiple-drug abuse. These subjects were entered into a 7-day double-blind treatment period, comparing behavioral effects and abuse potential of ramelteon and triazolam, a benzodiazepine sedative-hypnotic.
During the treatment period, study medication was administered to patients in a randomly-assigned sequence and included:
* ramelteon (16 mg, 80 mg, 160 mg);
* triazolam (0.25 mg, 0.50 mg, 0.75 mg); and,
* placebo.
Measures of "drug-liking," were assessed each day using questionnaires completed at intervals between 0.5 hours pre-dose, up to 24 hours after dose administration. Memory, reaction time and standing balance tasks were also performed at each of these time intervals. Analysis of peak drug-liking scores showed a dose-response effect in patients receiving triazolam, with significantly greater peak liking reported at the higher doses (0.50 mg, 0.75 mg) as compared with placebo. Ramelteon showed no statistically significant dose-related effect compared to placebo.
Results also showed that triazolam treatment (0.50 mg, 0.75 mg) produced a dose related impairment of task performance as compared to that of placebo. Ramelteon did not produce any significant changes in task performance comparative to that of placebo at any dose.
"Obtaining abuse potential results similar to that of placebo is an important step in establishing a safety profile for ramelteon," said Steve Sainati, MD, PhD, vice president of Clinical Research, Takeda Global Research & Development, Lincolnshire, Ill. "Comparing ramelteon's effects versus a benzodiazepine sedative-hypnotic provides information that is valuable scientifically, as well as clinically relevant."
Ramelteon offers a completely new mechanism of action, specifically targeting two receptors in the brain, MT1 and MT2. The MT1 and MT2 receptors are located in the brain's suprachiasmatic nuclei (SCN). The SCN is known as the body's "master clock" because it regulates the 24-hour sleep-wake cycle.
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