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Clinical profile of suvorexant for the treatment of insomnia over 3 months in women and men: subgroup analysis of pooled phase-3 data

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Abstract

Rationale

Sex-related differences in the clinical profiles of some insomnia medications have been previously reported.

Objective

To evaluate the clinical profile of suvorexant, a novel orexin receptor antagonist approved for treating insomnia at doses up to 20 mg, by sex subgroups.

Methods

Efficacy analyses by sex were based on pooled data from two similar phase 3, randomized, double-blind, placebo-controlled, 3-month trials in elderly (≥65 years) and non-elderly (18–64 years) insomnia patients. Two age-adjusted (non-elderly/elderly) dose regimes of 40/30 and 20/15 mg were evaluated, with fewer patients assigned to 20/15 mg. Efficacy was assessed by patient-reported outcomes (N = 1264 women, 707 men) and by polysomnography endpoints in ~75% of patients. Safety analyses by sex (N = 1744 women, 1065 men) included pooled data from the two 3-month trials plus 3-month data from a safety trial of 40/30 mg.

Results

The sex subgroup efficacy analyses mirrored the improvements seen for suvorexant 40/30 and 20/15 mg over placebo on patient-reported outcomes and polysomnography sleep maintenance and onset endpoints in the primary analyses; 95% CIs excluded zero in favor of suvorexant for most endpoints in both sexes, and similar efficacy was observed between sexes (95% CIs overlapped). Suvorexant was well-tolerated in women and men, although women in all treatment groups (including placebo) reported more adverse events than men. The most frequent adverse event was somnolence (women: 11.1% for 40/30 mg, 8.5% for 20/15 mg, 2.3% for placebo; men: 10.1% for 40/30 mg, 3.4% for 20/15 mg, 4.2% for placebo).

Conclusion

Suvorexant was generally effective and well-tolerated in both women and men with insomnia.

ClinicalTrials.gov trial registration numbers: NCT01097616, NCT01097629, NCT01021813.

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Acknowledgements

These studies were funded by Merck & Co., Inc., Kenilworth, NJ, USA. Mingqui Wu, formerly from Merck & Co., Inc., contributed to the statistical analysis. Sheila Erespe from Merck & Co., Inc. assisted with the submission.

Contributors

WJH was involved in study concept and design, interpretation of data, and drafting of manuscript. KMC, DBS, YZ, RMB, ADK, JKW, TR, and DM were involved in study concept and design and interpretation of data. JH was involved in study concept and design and acquisition of data. ES was involved in study concept and design, analysis and interpretation of data, and drafting of manuscript. DM-W was involved in interpretation of data. CL was involved in interpretation of data and drafting of manuscript. All authors reviewed and/or revised the manuscript for intellectual content and approved the final version of the manuscript.

Author information

Authors and Affiliations

  1. Merck & Co., Inc., Kenilworth, NJ, USA

    W. Joseph Herring, Kathryn M. Connor, Ellen Snyder, Duane B. Snavely, Ying Zhang, Jill Hutzelmann, Deborah Matzura-Wolfe, Christopher Lines & David Michelson

  2. Merck & Co., Inc., UG 4C-13, PO Box 1000, North Wales, PA, 19454-1099, USA

    W. Joseph Herring

  3. Department of Psychiatry and Human Behavior, University of California-Irvine, Irvine, CA, USA

    Ruth M. Benca

  4. Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA

    Andrew D. Krystal

  5. Sleep Medicine and Research Center, St., Luke’s Hospital, St. Louis, MO, USA

    James K. Walsh

  6. Henry Ford Hospital Sleep Center, Detroit, MI, USA

    Thomas Roth

Authors
  1. W. Joseph Herring
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  2. Kathryn M. Connor
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  3. Ellen Snyder
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  4. Duane B. Snavely
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  5. Ying Zhang
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  6. Jill Hutzelmann
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  7. Deborah Matzura-Wolfe
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  8. Ruth M. Benca
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  9. Andrew D. Krystal
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  10. James K. Walsh
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  11. Christopher Lines
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  12. Thomas Roth
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  13. David Michelson
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Corresponding author

Correspondence to W. Joseph Herring.

Ethics declarations

The trials were conducted in accordance with principles of Good Clinical Practice and were approved by the appropriate institutional review boards and regulatory agencies for each site. Informed consent was obtained from all patients. The trials were registered at ClinicalTrials.gov (NCT01097616, NCT01097629, NCT01021813).

Conflict of interests

WJH, KMC, ES, DBS, YZ, JH, DM-W, CL, and DM are current or former employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ USA and own or owned stock/stock options in the Company.

RMB has served as a consultant to and receives research support from Merck & Co., Inc., and has served as a consultant to Janssen and Jazz over the past 2 years.

ADK has received grants/research support from NIH, Teva, Sunovion, Astellas, Abbott, Neosync, Brainsway, Janssen, ANS St. Jude, Novartis. He has served as a consultant to Abbott, Astellas, AstraZeneca, Attentiv, BMS, Teva, Eisai, Eli Lilly, GlaxoSmithKline, Jazz, Janssen, Merck, Neurocrine, Novartis, Otsuka, Lundbeck, Roche, Sanofi-Aventis, Somnus, Sunovion, Somaxon, Takeda, Transcept, Vantia.

JKW has received research support from the following in the past 2 years: Apnex, Merck & Co., Inc., Novo Nordisk, Respironics, Vanda, and has provided consulting services to Merck & Co., Inc., Somnus, Transcept, Vanda, Ventus, and Vivus.

TR has received grants/research support from Aventis, Cephalon, GlaxoSmithKline, Neurocrine, Pfizer, Sanofi, Schering-Plough, Sepracor, Somaxon, Syrex, Takeda, TransOral, Wyeth and Xenoport; has acted as a consultant for Abbott, Acadia, Acoglix, Actelion, Alchemers, Alza, Ancil, Arena, AstraZeneca, Aventis, AVER, BMS, BTG, Cephalon, Cypress, Dove, Elan, Eli Lilly, Evotec, Forest, GlaxoSmithKline, Hypnion, Impax, Intec, Intra-Cellular, Jazz, Johnson–Johnson, King, Lundbeck, McNeil, MediciNova, Merck & Co., Inc., Neurim, Neurocrine, Neurogen, Novartis, Orexo, Organon, Prestwick, Procter–Gamble, Pfizer, Purdue, Resteva, Roche, Sanofi, Schering-Plough, Sepracor, Servier, Shire, Somaxon, Syrex, Takeda, TransOral, Vanda, Vivometrics, Wyeth, Yamanuchi, and Xenoport; and has participated in speaking engagements supported by Cephalon, Sanofi, and Takeda.

Funding

The studies were funded by Merck & Co., Inc., Kenilworth, NJ, USA. A Scientific Advisory Committee comprised Merck and non-Merck investigators contributed to the development of the protocols, statistical analysis plans, analysis and interpretation of data, served as authors of the manuscript and was responsible for the decision to submit the manuscript for publication. The funding organization was involved in the design and conduct of the studies, the collection, management, analysis, interpretation of data, and preparation, review, and approval of the manuscript.

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Herring, W., Connor, K.M., Snyder, E. et al. Clinical profile of suvorexant for the treatment of insomnia over 3 months in women and men: subgroup analysis of pooled phase-3 data. Psychopharmacology 234, 1703–1711 (2017). https://doi.org/10.1007/s00213-017-4573-1

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  • DOI: https://doi.org/10.1007/s00213-017-4573-1

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