Effect of ramelteon, a selective MT(1)/MT (2)-receptor agonist, on respiration during sleep in mild to moderate COPD

Ramelteon, a selective MT(1)/MT(2) melatonin receptor agonist, was evaluated in subjects with mild to moderate chronic obstructive pulmonary disease (COPD) to determine whether it would have a negative effect on measures of safety and respiration. This randomized, double-blind, crossover study in 26 subjects with mild to moderate COPD compared the effects of a single bedtime dose of ramelteon 16 mg and placebo on sleep, oxygenation, and sleep-related abnormal breathing events. Compared with placebo, ramelteon had no statistically significant effect on mean arterial oxygen percent saturation (SaO(2)) for the entire night (92.9 vs 92.9%; 95% confidence interval [CI], -0.6 to 0.6; P = 0.972), for each of the 8 h of the night, for each sleep stage (awake, rapid eye movement, nonrapid eye movement) or for the percentage of the night that SaO(2) was less than 85 and 90%. The mean apnea-hypopnea index was similar between ramelteon and placebo groups (9.0 vs 8.3; 95% CI, -1.5 to 3.0; P = 0.515). Polysomnography documented a significant increase in total sleep time (380.6 vs 353.6, P = 0.015), sleep efficiency (79.3 vs 73.7, P = 0.017), and number of awakenings (11.1 vs 9.5, P = 0.036) with ramelteon vs placebo. Other polysomnography and subject-reported sleep measures were comparable between groups. Only one adverse event was reported; it was not considered treatment related. No clinically meaningful changes in laboratory test results, vital signs, electrocardiogram, and physical examination were observed. In this study, ramelteon 16 mg (two times the recommended therapeutic dose) showed no clinically meaningful or statistically significant effects on oxygenation or abnormal breathing events, was well tolerated, and improved sleep duration and efficiency in subjects with mild to moderate COPD.