Phase 2 Discovery, Inc.

While melatonin agonists are known to regulate circadian sleep rhythms, it is not clear whether melatonin agonists have a direct soporific effect. It has been suggested that melatonin's soporific effect is secondary to its ability to induce hypothermia. beta-Methyl-6-chloromelatonin is a high-affinity melatonin receptor agonist that is not associated with hypothermia. The purpose of the present study was to determine if the melatonin agonist beta-methyl-6-chloromelatonin has a direct soporific effect in subjects with primary insomnia.

A double-blind, placebo-controlled, crossover safety and efficacy study of 20 mg, 50 mg, and 100 mg of beta-methyl-6-chloromelatonin and placebo was conducted in subjects with DSM-IV-TR primary insomnia. Of 84 subjects screened, 40 progressed to randomly receive each of 3 beta-methyl-6-chloromelatonin doses or placebo on each of 2 consecutive nights with 5-day washout periods between treatments. The effect of treatment on both polysomnographic and subjectively measured sleep parameters, next-morning psychomotor performance, and safety measures was determined. The primary outcome measure was latency to persistent sleep measured by polysomnography.

A significant effect of beta-methyl-6-chloromelatonin on the primary efficacy variable, latency to persistent sleep, was observed (p = .0003). The 20-mg dose resulted in a significant 31% improvement in sleep latency compared with placebo, while significant 32% and 41% improvements were observed at the 50-mg and 100-mg doses, respectively (20 mg, p = .0082; 50 mg, p = .0062; 100 mg, p < .0001). Similarly, a significant effect of beta-methyl-6-chloromelatonin on subjective measures of time to fall asleep occurred (p = .0050), with significant improvement observed at both the 50-mg and 100-mg doses (p = .0350 and .0198, respectively) and a trend toward improvement observed at the 20-mg dose (p = .0582). Adverse events were mild to moderate in severity and did not differ in frequency between beta-methyl-6-chloromelatonin and placebo treatments.

beta-Methyl-6-chloromelatonin significantly decreases both objective and subjective measures of sleep latency in subjects with primary insomnia. Thus, these data suggest that mel-atonin agonists may exert a direct soporific effect, as previous research indicates that beta-methyl-6-chloromelatonin is not associated with changes in body temperature, heart rate, or blood pressure.

While melatonin agonists are known to regulate circadian sleep rhythms, it is not clear whether melatonin agonists have a direct soporific effect.It has been suggested that melatonin's soporific effect is secondary to its ability to induce hypothermia.β-Methyl-6-chloromelatonin is a high-affinity melatonin receptor agonist that is not associated with hypothermia.The purpose of the present study was to determine if the melatonin agonist β-methyl-6-chloromelatonin has a direct soporific effect in subjects with primary insomnia.A double blind, placebo-controlled, crossover safety and efficacy study of 20 mg, 50 mg, and 100 mg of β-methyl-6-chloromelatonin and placebo was conducted in subjects with DSM-IV-TR primary insomnia.Of 84 subjects screened, 40 progressed to randomly receive each of 3 β-methyl-6-chloromelatonin doses or placebo on each of 2 consecutive nights with 5-day washout periods between treatments.The effect of treatment on both polysomnog. and subjectively measured sleep parameters, next-morning psychomotor performance, and safety measures was determinedThe primary outcome measure was latency to persistent sleep measured by polysomnog.Results: A significant effect of β-methyl-6-chloromelatonin on the primary efficacy variable, latency to persistent sleep, was observed (p = .0003).The 20-mg dose resulted in a significant 31% improvement in sleep latency compared with placebo, while significant 32% and 41% improvements were observed at the 50-mg and 100-mg doses, resp. (20 mg, p = .0082; 50 mg, p = .0062; 100 mg, p < .0001).Similarly, a significant effect of β-methyl-6-chloromelatonin on subjective measures of time to fall asleep occurred (p = .0050), with significant improvement observed at both the 50-mg and 100-mg doses (p = .0350 and .0198, resp.) and a trend toward improvement observed at the 20-mg dose (p = .0582).Adverse events were mild to moderate in severity and did not differ in frequency between β-methyl-6-chloromelatonin and placebo treatments.β-Methyl-6-chloromelatonin significantly decreases both objective and subjective measures of sleep latency in subjects with primary insomnia.Thus, these data suggest that melatonin agonists may exert a direct soporific effect, as previous research indicates that β-methyl-6-chloromelatonin is not associated with changes in body temperature, heart rate, or blood pressure.