Orexin receptor antagonism, a new sleep-enabling paradigm: a proof-of-concept clinical trial
Publisher DOI
PubMed ID
22549286
Abstract
The orexin system is a key regulator of sleep and wakefulness. In a multicenter, double-blind, randomized, placebo-controlled, two-way crossover study, 161 primary insomnia patients received either the dual orexin receptor antagonist almorexant, at 400, 200, 100, or 50 mg in consecutive stages, or placebo on treatment nights at 1-week intervals. The primary end point was sleep efficiency (SE) measured by polysomnography; secondary end points were objective latency to persistent sleep (LPS), wake after sleep onset (WASO), safety, and tolerability. Dose-dependent almorexant effects were observed on SE , LPS , and WASO . SE improved significantly after almorexant 400 mg vs. placebo (mean treatment effect 14.4%; P < 0.001). LPS (–18 min (P = 0.02)) and WASO (–54 min (P < 0.001)) decreased significantly at 400 mg vs. placebo. Adverse-event incidence was dose-related. Almorexant consistently and dose-dependently improved sleep variables. The orexin system may offer a new treatment approach for primary insomnia.
Date Issued
2012
Publication Type
Article
Language(s)
en
Author(s)
Hoever, P | |
Dorffner, G | |
Beneš, H | |
Penzel, T | |
Danker-Hopfe, H | |
Barbanoj, M J | |
Pillar, G | |
Saletu, B | |
Polo, O | |
Kunz, D | |
Zeitlhofer, J | |
Berg, S | |
Partinen, M | |
Högl, B | |
Ebrahim, I O | |
Holsboer-Trachsler, E | |
Bengtsson, H | |
Peker, Y | |
Hemmeter, U-M | |
Chiossi, E | |
Hajak, G | |
Dingemanse, J |
Additional Credits
Journal
Clinical pharmacology & therapeutics
Publisher
Nature Publishing Group
ISSN
0009-9236
Access(Rights)
metadata.only