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The effects of ramelteon on respiration during sleep in subjects with moderate to severe chronic obstructive pulmonary disease

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Abstract

Background

Individuals with moderate to severe chronic obstructive pulmonary disease (COPD) have poor sleep quality. This study evaluated the effects of ramelteon, an MT1/MT2 melatonin receptor agonist indicated for insomnia treatment on respiration in this population.

Materials and methods

This double-blind, crossover study enrolled 25 subjects (≥40 years) with moderate to severe COPD (FEV1/FVC <70% and FEV1 between 50 and 80% of predicted value [moderate], or FEV1/FVC <70% and FEV1 <50% of predicted value [severe]). Subjects received ramelteon 8 mg or placebo for one night 30 min before polysomnographic monitoring, including measurement of oxygen saturation (SaO2) and respiratory effort and flow. Subjects crossed to alternate treatment after a 5- to 10-day washout. The primary endpoint was mean SaO2 for the entire night.

Results

No significant difference in SaO2 for the entire night was observed with ramelteon vs placebo (92.2% vs 92.5%, P = 0.576). Mean SaO2 was similar between ramelteon and placebo for each hour of the night, each sleep stage, the number of minutes that SaO2 was <80% and <90%, and mean apnea–hypopnea index. There was a significant difference in total sleep time (389.0 vs 348.4 min, P = 0.019) and sleep efficiency (81.0 vs 72.6%, P = 0.019), and latency to persistent sleep was shorter (23.1 vs 56.9 min, P = 0.051), with ramelteon vs placebo. All adverse events were mild to moderate; none led to study discontinuation.

Conclusion

Ramelteon did not produce respiratory depressant effects as measured by oxygenation or abnormal breathing events in subjects with moderate to severe COPD. Ramelteon was well tolerated in this population.

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Acknowledgments

Manuscript assistance was provided by Takeda Pharmaceuticals North America. These data were presented at the American Association for Respiratory Care Meeting in Orlando, FL on December 3, 2007. The abstract was published in Respiratory Care (2007; 52(11): p. 1605).

Funding

This study was funded by Takeda Pharmaceutical Company Limited. Disclosure of financial support: Meir Kryger: consultant, Takeda Pharmaceuticals North America; Thomas Roth: grants and consultant, Takeda Pharmaceuticals North America; Sherry Wang-Weigand and Jeffrey Zhang: employees, 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. Sleep Disorders and Research Center, Henry Ford Hospital, Detroit, MI, USA

    Thomas Roth

  3. Takeda Global Research & Development Center, Deerfield, IL, USA

    Sherry Wang-Weigand & Jeffrey Zhang

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

Correspondence to Meir Kryger.

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Kryger, M., Roth, T., Wang-Weigand, S. et al. The effects of ramelteon on respiration during sleep in subjects with moderate to severe chronic obstructive pulmonary disease. Sleep Breath 13, 79–84 (2009). https://doi.org/10.1007/s11325-008-0196-4

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  • DOI: https://doi.org/10.1007/s11325-008-0196-4

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