{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T01:45:11Z","timestamp":1790646311120,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100030995","name":"Bioprojet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100030995","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Sleep Research"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Obstructive sleep apnea (OSA) syndrome commonly leads to excessive daytime sleepiness (EDS). Pitolisant, a selective histamine\u20103 receptor antagonist, is efficacious at doses up to 20\u2009mg 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\u2009mg once daily in patients with moderate to severe OSA treated or not with CPAP therapy. In this phase 3, multicentre, randomised, double\u2010blind, placebo\u2010controlled clinical trial, patients with OSA were assigned 2:1 to receive pitolisant (according to an individual up\u2010titration scheme, 10, 20 or 40\u2009mg once daily) or placebo for 12\u2009weeks. 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\u2010C), and Patient's Global Opinion of the Effect (PGOE) of study treatment. Overall, 361 patients (mean age 52.4\u2009years, 77.3% male; mean apnea\u2010hypopnea index [AHI] 27.0 events\/h) were randomised to receive pitolisant (<jats:italic>n<\/jats:italic>\u2009=\u2009242; 50% received CPAP) or placebo (<jats:italic>n<\/jats:italic>\u2009=\u2009119; 48.7% CPAP). After the dose\u2010adjustment phase (week 3), 88.8% of patients received pitolisant 40\u2009mg. Compared with placebo, pitolisant produced a significant reduction in the ESS score at week 12 (least square mean difference \u22122.6 (95% CI: \u22123.4; \u22121.8; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001)) irrespective of CPAP use; and improved the reaction time on OSleR, CGI\u2010C, and PGOE at week 12. Pitolisant was well tolerated; no new safety signals were identified. In conclusion, pitolisant up to 40\u2009mg once daily was an effective treatment for EDS in patients with moderate to severe OSA irrespective of CPAP use.<\/jats:p>","DOI":"10.1111\/jsr.14373","type":"journal-article","created":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T16:45:29Z","timestamp":1728405929000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Pitolisant 40\u2009mg for excessive daytime sleepiness in obstructive sleep apnea patients treated or not by <scp>CPAP<\/scp>: Randomised phase 3 study"],"prefix":"10.1111","volume":"34","author":[{"given":"Yves","family":"Dauvilliers","sequence":"first","affiliation":[{"name":"Centre National de R\u00e9f\u00e9rence Narcolepsie, Unit\u00e9 du Sommeil, CHU Montpellier, H\u00f4pital Gui\u2010de\u2010Chauliac Service de Neurologie, Universit\u00e9 de Montpellier, INSERM INM  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonya Elizabeth","family":"Craig","sequence":"additional","affiliation":[{"name":"Liverpool Sleep and Ventilation Centre, University Hospital Aintree Liverpool University Foundation Trust  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria R.","family":"Bonsignore","sequence":"additional","affiliation":[{"name":"PROMISE Department University of Palermo, Institute for Biomedical Research and Innovation (IRIB), National Research Council (CNR)  Palermo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferran","family":"Barb\u00e9","sequence":"additional","affiliation":[{"name":"Respiratory Department Institut Ricerca Biomedica de Vilanova  Lleida Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Verbraecken","sequence":"additional","affiliation":[{"name":"Multidisciplinary Sleep Disorders Centre Antwerp University Hospital and University of Antwerp  Edegem\u2010Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerryl","family":"Asin","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Centre for Sleep Medicine Amphia Hospital  Breda The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ognian","family":"Georgiev","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Pulmonology Alexandrovska Hospital Medical University  Sofia Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rumen","family":"Tiholov","sequence":"additional","affiliation":[{"name":"Department of Internal Diseases Sv. Ivan Rilski Multiprofile Hospital for Active Treatment  Kozloduy Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Causs\u00e9","sequence":"additional","affiliation":[{"name":"Bioprojet Pharma  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanne\u2010Marie","family":"Lecomte","sequence":"additional","affiliation":[{"name":"Bioprojet Pharma  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Charles","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Bioprojet Pharma  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Lehert","sequence":"additional","affiliation":[{"name":"Faculty of Economics University Louvain  Ottignies\u2010Louvain\u2010la\u2010Neuve Belgium"},{"name":"Faculty of Medicine University of Melbourne  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winfried","family":"Randerath","sequence":"additional","affiliation":[{"name":"Bethanien Hospital, Institute of Pneumonology University of Cologne  Solingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Louis","family":"P\u00e9pin","sequence":"additional","affiliation":[{"name":"HP2 Laboratory INSERM U1300 University Grenoble Alpes  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the HAROSA III Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.5664\/jcsm.4104"},{"key":"e_1_2_10_3_1","first-page":"ICSD\u20102","volume-title":"International classification of sleep disorders: Diagnostic and coding manual","author":"American Academy of Sleep Medicine","year":"2005"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/jsr.13387"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(19)30198-5"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2869.1997.00039.x"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2018-211959"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsz174"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70225-4"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201907-1284OC"},{"key":"e_1_2_10_11_1","unstructured":"European Medicines Agency. 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