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Effect of Ramelteon, a selective MT1/MT2-receptor agonist, on respiration during sleep in mild to moderate COPD

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Abstract

Ramelteon, a selective MT1/MT2 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 (SaO2) 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 SaO2 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.

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Acknowledgements

The authors would like to thank the following investigators for their assistance with data collection: Alejandro Chediak, Bruce Corser, Faisal Fakih, Paul Haberman, G. Vernon Pegram, Jr., and David Winslow. This study was funded by Takeda Pharmaceutical Company Limited.

Author Financial Disclosure

Meir Kryger: Consultant, Takeda Pharmaceuticals North America; Thomas Roth: Grants and Consultant, Takeda Pharmaceuticals North America; Sherry Wang-Weigand: Employee, Takeda Global Research and Development Center; Jeffrey Zhang: Employee, Takeda Global Research and Development Center

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Authors and Affiliations

  1. Sleep Research and Education, Gaylord Hospital, 400 Gaylord Farm Road, Wallingford, CT, 06492, USA

    Meir Kryger

  2. Takeda Global Research and Development Center, Deerfield, IL, USA

    Sherry Wang-Weigand & Jeffrey Zhang

  3. Sleep Disorders and Research Center, Henry Ford Hospital, Detroit, MI, USA

    Thomas Roth

Authors
  1. Meir Kryger
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  2. Sherry Wang-Weigand
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  3. Jeffrey Zhang
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  4. Thomas Roth
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Correspondence to Meir Kryger.

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Kryger, M., Wang-Weigand, S., Zhang, J. et al. Effect of Ramelteon, a selective MT1/MT2-receptor agonist, on respiration during sleep in mild to moderate COPD. Sleep Breath 12, 243–250 (2008). https://doi.org/10.1007/s11325-007-0156-4

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  • DOI: https://doi.org/10.1007/s11325-007-0156-4

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