A randomized Phase 2 study to evaluate the orexin-2 receptor antagonist seltorexant in individuals with insomnia without psychiatric comorbidity.

Abstract

BACKGROUND:

Seltorexant is a potent and selective antagonist of the orexin-2 receptor that is being developed for the treatment of insomnia and major depressive disorder.

AIMS:

The primary objective was to investigate the effect of seltorexant on sleep efficiency after single and multiple dose administration in subjects with insomnia disorder without psychiatric comorbidity. Secondary objectives included evaluation of total sleep time, latency to persistent sleep, and wake after sleep onset. Subjects received 40 mg of seltorexant for five days during Period 1 and placebo during Period 2 or vice versa in this randomized, two-way crossover study. Objective sleep parameters were evaluated by polysomnography over 8 h on Day 1/2 (single dose) and on Day 5/6 (multiple doses). Subjective sleep parameters were assessed by questionnaires.

RESULTS:

Twenty-seven subjects completed the study. The mean changes in sleep efficiency (% (SD)) of seltorexant from placebo at Day 1/2 were 5.8 (9.2), and 7.9 (9.8) at Day 5/6 ( p < 0.001 at both time points); in total sleep time (min (SD)) 27.7 (44.3) and 37.9 (47.1), respectively; in latency to persistent sleep (min (SD)) -18.8 (21.3) and -29.9 (27.7), respectively; and in wake after sleep onset (min (SD)) -11.1 (36.4) and -11.3 (46.5). The most common adverse events were headache and somnolence.

CONCLUSIONS:

Sleep efficiency was increased with seltorexant treatment compared with placebo. Treatment with seltorexant resulted in a prolonged total sleep time, shorter latency to persistent sleep and wake after sleep onset. There were no unexpected safety findings.

• Authors: Peter De Boer, Wayne C Drevets, Hany Rofael, Peter van der Ark, Justine M Kent, Iva Kezic, Silvia Parapatics, Georg Dorffner, Joop van Gerven, Heike Beneš, Christian Keicher, Holger Jahn, David J Seiden, Remy Luthringer
• Journal: Journal of psychopharmacology (Oxford, England) (J Psychopharmacol) Vol. 32 Issue 6 Pg. 668-677 (06 2018) ISSN: 1461-7285 [Electronic] United States
• PMID: 29848147 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Orexin Receptor Antagonists
• Orexin Receptors
• Pyrimidines
• Pyrroles
• Triazoles
• seltorexant

Topics

• Adult
• Cross-Over Studies
• Double-Blind Method
• Female
• Headache (chemically induced)
• Humans
• Male
• Middle Aged
• Orexin Receptor Antagonists (administration & dosage, adverse effects, therapeutic use)
• Orexin Receptors (drug effects, metabolism)
• Polysomnography
• Pyrimidines (administration & dosage, adverse effects, therapeutic use)
• Pyrroles (administration & dosage, adverse effects, therapeutic use)
• Sleep (drug effects)
• Sleep Initiation and Maintenance Disorders (drug therapy)
• Sleepiness
• Surveys and Questionnaires
• Time Factors
• Treatment Outcome
• Triazoles (administration & dosage, adverse effects, therapeutic use)
• Young Adult