Orexin Receptor Antagonism, a New Sleep-enabling Paradigm: a Proof-of-concept Clinical Trial

Overview

Journal Clin Pharmacol Ther

Publisher Wiley

Specialty Pharmacology

Date 2012 May 3

PMID 22549286

Citations 35

Authors

P Hoever

G Dorffner

H Benes

T Penzel

H Danker-Hopfe

M J Barbanoj

G Pillar

B Saletu

O Polo

D Kunz

J Zeitlhofer

S Berg

M Partinen

C L Bassetti

B Hogl

I O Ebrahim

E Holsboer-Trachsler

H Bengtsson

Y Peker

U-M Hemmeter

E Chiossi

G Hajak

J Dingemanse

Affiliations

Soon will be listed here.

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.

Citing Articles

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Seigneur E, De Lecea L Med Drug Discov. 2024; 8.

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The Underlying Mechanisms of Sleep Deprivation Exacerbating Neuropathic Pain.

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Nonclinical pharmacology of daridorexant: a new dual orexin receptor antagonist for the treatment of insomnia.

Roch C, Bergamini G, Steiner M, Clozel M Psychopharmacology (Berl). 2021; 238(10):2693-2708.

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Pharmacokinetics of daridorexant, a dual orexin receptor antagonist, are not affected by renal impairment.

Berger B, Muehlan C, Klein G, Dingemanse J Clin Transl Sci. 2021; 14(6):2132-2138.

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Effect of Liver Cirrhosis on the Pharmacokinetics, Metabolism, and Tolerability of Daridorexant, A Novel Dual Orexin Receptor Antagonist.

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