Daridorexant, a new dual orexin receptor antagonist, in elderly subjects with insomnia disorder

To assess the dose-response of daridorexant, a new dual orexin receptor antagonist, on wake after sleep onset (WASO). Elderly (≥65 years) participants (n = 58) with insomnia were randomly allocated (Latin square design) to receive 5 treatments (5, 10, 25, and 50 mg daridorexant and placebo) during 5...

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Vydáno v:Neurology Ročník 94; číslo 21; s. e2222
Hlavní autoři: Zammit, Gary, Dauvilliers, Yves, Pain, Scott, Sebök Kinter, Dalma, Mansour, Yosef, Kunz, Dieter
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 26.05.2020
ISSN:1526-632X, 1526-632X
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Shrnutí:To assess the dose-response of daridorexant, a new dual orexin receptor antagonist, on wake after sleep onset (WASO). Elderly (≥65 years) participants (n = 58) with insomnia were randomly allocated (Latin square design) to receive 5 treatments (5, 10, 25, and 50 mg daridorexant and placebo) during 5 treatment periods, each consisting of 2 treatment nights followed by a 5- to 12-day washout period. Main efficacy endpoints were the absolute change from baseline in WASO (primary) and latency to persistent sleep (LPS; secondary) to days 1 and 2 (mean of 2 treatment nights assessed by polysomnography) in each period. Safety and tolerability were also assessed. Of 58 participants included, 67% were female, and the median age was 69 years (range 65-85 years). WASO and LPS were dose-dependently reduced from baseline to days 1 and 2 after daridorexant administration (multiple comparison procedure modeling, < 0.0001 and = 0.004, respectively); reductions were statistically significant for doses ≥10 mg compared with placebo (WASO: -32.0, -45.1, -61.4 minutes; LPS: -44.9, -43.8, -45.4 minutes for 10, 25, and 50 mg, respectively, ≤ 0.025). Treatment-emergent adverse events were similar for daridorexant and placebo; the most frequent were fatigue, nasopharyngitis, gait disturbance, and headache (≤7% in any group). Daridorexant was well tolerated. Dose-dependent improvements in WASO and LPS were statistically significant (dose range 10-50 mg) in elderly people with insomnia disorder. NCT02841709. This study provides Class I evidence that, for elderly people with insomnia, daridorexant reduced WASO.
Bibliografie:ObjectType-Article-1
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ISSN:1526-632X
1526-632X
DOI:10.1212/WNL.0000000000009475