Pitolisant 40 mg for excessive daytime sleepiness in obstructive sleep apnea patients treated or not by CPAP: Randomised phase 3 study.
continuous positive airway pressure
excessive daytime sleepiness
obstructive sleep apnea
pitolisant
Journal
Journal of sleep research
ISSN: 1365-2869
Titre abrégé: J Sleep Res
Pays: England
ID NLM: 9214441
Informations de publication
Date de publication:
08 Oct 2024
08 Oct 2024
Historique:
revised:
16
09
2024
received:
27
05
2024
accepted:
17
09
2024
medline:
8
10
2024
pubmed:
8
10
2024
entrez:
8
10
2024
Statut:
aheadofprint
Résumé
Obstructive sleep apnea (OSA) syndrome commonly leads to excessive daytime sleepiness (EDS). Pitolisant, a selective histamine-3 receptor antagonist, is efficacious at doses up to 20 mg once daily in OSA treated or not with continuous positive airway pressure (CPAP). We assessed the efficacy and safety of pitolisant at doses up to 40 mg once daily in patients with moderate to severe OSA treated or not with CPAP therapy. In this phase 3, multicentre, randomised, double-blind, placebo-controlled clinical trial, patients with OSA were assigned 2:1 to receive pitolisant (according to an individual up-titration scheme, 10, 20 or 40 mg once daily) or placebo for 12 weeks. The primary endpoint was a change in the Epworth Sleepiness Scale (ESS) score from baseline to week 12. Secondary endpoints included a change in reaction time using the Oxford Sleep Resistance test (OSleR), Clinical Global Impression of Change (CGI-C), and Patient's Global Opinion of the Effect (PGOE) of study treatment. Overall, 361 patients (mean age 52.4 years, 77.3% male; mean apnea-hypopnea index [AHI] 27.0 events/h) were randomised to receive pitolisant (n = 242; 50% received CPAP) or placebo (n = 119; 48.7% CPAP). After the dose-adjustment phase (week 3), 88.8% of patients received pitolisant 40 mg. Compared with placebo, pitolisant produced a significant reduction in the ESS score at week 12 (least square mean difference -2.6 (95% CI: -3.4; -1.8; p < 0.001)) irrespective of CPAP use; and improved the reaction time on OSleR, CGI-C, and PGOE at week 12. Pitolisant was well tolerated; no new safety signals were identified. In conclusion, pitolisant up to 40 mg once daily was an effective treatment for EDS in patients with moderate to severe OSA irrespective of CPAP use.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e14373Subventions
Organisme : Bioprojet Pharma
Investigateurs
Dejan Dokic
(D)
Hristo Metev
(H)
Iliev Kartev
(I)
Zdravka Karamyan
(Z)
Ventsislav Nozharov
(V)
Daniel Petkov
(D)
Informations de copyright
© 2024 The Author(s). Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.
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