Safety, Tolerability, and Pharmacokinetics of Suvorexant: A Randomized Rising-Dose Trial in Healthy Men

@article{Yee2018SafetyTA,
  title={Safety, Tolerability, and Pharmacokinetics of Suvorexant: A Randomized Rising-Dose Trial in Healthy Men},
  author={Ka Lai Yee and Jacqueline B McCrea and Deborah L. Panebianco and Wen Liu and Nicole Lewis and Tamara D. Cabalu and Steven Ramael and Rebecca Ellen Wrishko},
  journal={Clinical Drug Investigation},
  year={2018},
  volume={38},
  pages={631-638}
}
Background and ObjectivesSuvorexant (MK-4305) is an orexin receptor antagonist approved for the treatment of insomnia in the USA and other regions. This randomized, double-blind, placebo-controlled, sequential-panel, Phase 1 trial assessed the safety, tolerability, and pharmacokinetic data following single and multiple dosing of suvorexant in healthy men (aged 18–45 years).MethodsWithin allocated panels, subjects (n = 8) were randomized to receive nightly doses of suvorexant (10, 20, 40, 80… 

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Correction to: Effect of CYP3A Inhibition and Induction on the Pharmacokinetics of Suvorexant: Two Phase I, Open-Label, Fixed-Sequence Trials in Healthy Subjects

TLDR
The original version of this article unfortunately contained a mistake and has been edited for brevity.

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References

SHOWING 1-10 OF 22 REFERENCES

Suvorexant in Elderly Patients with Insomnia: Pooled Analyses of Data from Phase III Randomized Controlled Clinical Trials.

  • W. HerringK. Connor D. Michelson
  • Medicine, Psychology
    The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry
  • 2017

Suvorexant in Patients with Insomnia: Pooled Analyses of Three-Month Data from Phase-3 Randomized Controlled Clinical Trials.

  • W. HerringK. Connor D. Michelson
  • Medicine, Psychology
    Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine
  • 2016
TLDR
Suvorexant 20/15 mg improved sleep onset and maintenance over 3 months of nightly treatment and was generally safe and well tolerated, and there was no systematic evidence of rebound or withdrawal signs or symptoms when suvoreXant was discontinued after 3 months.

Suvorexant in Patients With Insomnia: Results From Two 3-Month Randomized Controlled Clinical Trials

In vitro and in vivo characterisation of the metabolism and disposition of suvorexant in humans

TLDR
Suvorexant is a first-in-class dual orexin receptor antagonist approved in the USA and Japan for the treatment of insomnia and its absorption, disposition and potential for CYP-mediated drug interactions in humans is described.

Orexin receptor antagonism for treatment of insomnia

TLDR
The data suggest that orexin receptor antagonism offers a novel approach to treating insomnia, and Class I evidence that suvorexant improves sleep efficiency over 4 weeks in nonelderly adult patients with primary insomnia.

Promotion of Sleep by Suvorexant—A Novel Dual Orexin Receptor Antagonist

TLDR
Dosed orally Suvorexant significantly and dose-dependently reduced locomotor activity and promoted sleep in rats, dogs, and rhesus monkeys, highlighting a unique opportunity to develop dual orexin antagonists as a novel therapy for insomnia.

Discovery and development of orexin receptor antagonists as therapeutics for insomnia

TLDR
Based on the publication of recent non‐clinical and clinical data, orexin receptor antagonists potentially represent a targeted, effective and well‐tolerated new class of medications for insomnia.

Issues in the use of benzodiazepine therapy.

In selecting a hypnotic for the symptomatic management of insomnia, clinicians should look for those that most favorably balance sleep induction and sleep maintenance with potential adverse side