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Dose-response of daridorexant in insomnia disorder: An analysis of Phase 2 and 3 studies.
Luyet, Pierre-Philippe; McCall, William V; Bassetti, Claudio L A; Braunstein, Guy; Laurent, Johann; Olivieri, Antonio; Hedner, Jan.
Afiliación
  • Luyet PP; Idorsia Pharmaceuticals Ltd, Hegenheimermattweg 91, 4123, Allschwil, Switzerland. Electronic address: pierre-philippe.luyet@idorsia.com.
  • McCall WV; Department of Psychiatry and Health Behavior, Medical College of Georgia, Augusta University, 997 St Sebastian Way, Augusta, GA, 30912, USA. Electronic address: wmccall@augusta.edu.
  • Bassetti CLA; Claudio Bassetti: Department of Neurology, Inselspital, University of Bern, Bern, Switzerland. Electronic address: claudio.bassetti@unibe.ch.
  • Braunstein G; Idorsia Pharmaceuticals Ltd, Hegenheimermattweg 91, 4123, Allschwil, Switzerland. Electronic address: guy.braunstein@ext.idorsia.com.
  • Laurent J; Idorsia Pharmaceuticals Ltd, Hegenheimermattweg 91, 4123, Allschwil, Switzerland. Electronic address: johann.laurent@idorsia.com.
  • Olivieri A; Idorsia Pharmaceuticals Ltd, Hegenheimermattweg 91, 4123, Allschwil, Switzerland. Electronic address: antonio.olivieri@idorsia.com.
  • Hedner J; Center for Sleep and Vigilance Disorders, Institute of Medicine University of Gothenburg, Gothenburg, Sweden. Electronic address: jan.hedner@lungall.gu.se.
Sleep Med ; 121: 315-325, 2024 Sep.
Article en En | MEDLINE | ID: mdl-39047305
ABSTRACT

OBJECTIVE:

Daridorexant is approved for the treatment of insomnia at two dose levels (25 and 50 mg). Dose-efficacy and -safety response relationships were evaluated using Phase 2 and 3 data.

METHODS:

Data (N = 2153) from one Phase 2 (daridorexant 5, 10, 25, 50 mg, placebo once daily for 1 month) and two Phase 3 studies (daridorexant 10 and 25 or 25 and 50 mg, placebo once daily for 3 months) were pooled. Dose-response analyses at 1 month of double-blind treatment were performed using a linear regression and a two-stage meta-analysis approach. Efficacy endpoints were polysomnography-derived wake after sleep onset, latency to persistent sleep (LPS), self-reported total sleep time and the Insomnia Daytime Symptoms and Impacts Questionnaire total score (only Phase 3 data for the latter). Safety endpoints were the incidence of total adverse events (AEs) and AEs corresponding to somnolence/fatigue.

RESULTS:

Dose-responses for all efficacy endpoints were significant in the observed dose range (both statistical approaches, p < 0.01). All dose-response relationships were linear except for LPS (two-stage meta-analysis) which showed a change in slope above 10 mg without reaching a plateau. No significant dose-response was observed for any AE (both approaches, p > 0.05). The incidence of AEs corresponding to somnolence/fatigue was low at all doses and, without linear assumption (two-stage meta-analysis) there was no dose-dependency (p = 0.369).

CONCLUSIONS:

The data support the use of 50 mg as the preferred daridorexant dose in patients with insomnia disorder to provide the greatest opportunity for efficacy with no increased risk for AEs, including somnolence/fatigue, compared to lower doses.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Relación Dosis-Respuesta a Droga / Trastornos del Inicio y del Mantenimiento del Sueño Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Sleep Med Asunto de la revista: NEUROLOGIA / PSICOFISIOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Relación Dosis-Respuesta a Droga / Trastornos del Inicio y del Mantenimiento del Sueño Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Sleep Med Asunto de la revista: NEUROLOGIA / PSICOFISIOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos