Journal ArticleDOI
Safety and efficacy of pitolisant on cataplexy in patients with narcolepsy: a randomised, double-blind, placebo-controlled trial.
Zoltan Szakacs,Yves Dauvilliers,Vladimir Mikhaylov,Irina Poverennova,Sergei Krylov,Slavko Jankovic,Karel Sonka,Philippe Lehert,Philippe Lehert,Isabelle Lecomte,Jeanne-Marie Lecomte,Jean-Charles Schwartz,Mikhail Poluektov,Eduard Yakupov,Alexander Kalinkin,Murat Aksu,Hikmet Yilmaz,Gulcin Benbir,Dorota Wolynczyk-Gmaj,Wojchiech Jernajczyk,Ivan Staykov,Arben N Tavarari +21 more
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TLDR
Pitolisant was well tolerated and efficacious in reducing cataplexy and might constitute a useful first-line therapy for catapLexy in patients with narcolepsy, for whom there are currently few therapeutic options.Abstract:
Summary Background Histaminergic neurons are crucial to maintain wakefulness, but their role in cataplexy is unknown. We assessed the safety and efficacy of pitolisant, a histamine H3 receptor inverse agonist, for treatment of cataplexy in patients with narcolepsy. Methods For this randomised, double-blind, placebo-controlled trial we recruited patients with narcolepsy from 16 sleep centres in nine countries (Bulgaria, Czech Republic, Hungary, Macedonia, Poland, Russia, Serbia, Turkey, and Ukraine). Patients were eligible if they were aged 18 years or older, diagnosed with narcolepsy with cataplexy according to version two of the International Classification of Sleep Disorders criteria, experienced at least three cataplexies per week, and had excessive daytime sleepiness (defined as an Epworth Sleepiness Scale score ≥12). We used a computer-generated sequence via an interactive web response system to randomly assign patients to receive either pitolisant or placebo once per day (1:1 ratio). Randomisation was done in blocks of four. Participants and investigators were masked to treatment allocation. Treatment lasted for 7 weeks: 3 weeks of flexible dosing decided by investigators according to efficacy and tolerance (5 mg, 10 mg, or 20 mg oral pitolisant), followed by 4 weeks of stable dosing (5 mg, 10 mg, 20 mg, or 40 mg). The primary endpoint was the change in the average number of cataplexy attacks per week as recorded in patient diaries (weekly cataplexy rate [WCR]) between the 2 weeks of baseline and the 4 weeks of stable dosing period. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01800045. Findings The trial was done between April 19, 2013, and Jan 28, 2015. We screened 117 patients, 106 of whom were randomly assigned to treatment (54 to pitolisant and 52 to placebo) and, after dropout, 54 patients from the pitolisant group and 51 from the placebo group were included in the intention-to-treat analysis. The WCR during the stable dosing period compared with baseline was decreased by 75% (WCR final =2·27; WCR baseline =9·15; WCR final/baseline =0·25) in patients who received pitolisant and 38% (WCR final =4·52; WCR baseline =7·31; WCR final/baseline =0·62) in patients who received placebo (rate ratio 0·512; 95% CI 0·43–0·60, p vs 6 [12%] of 51; p=0·048). There were no serious adverse events, but one case of severe nausea in the pitolisant group. The most frequent adverse events in the pitolisant group (headache, irritability, anxiety, and nausea) were mild or moderate except one case of severe nausea. No withdrawal syndrome was detected following pitolisant treatment; one case was detected in the placebo group. Interpretation Pitolisant was well tolerated and efficacious in reducing cataplexy. If confirmed in long-term studies, pitolisant might constitute a useful first-line therapy for cataplexy in patients with narcolepsy, for whom there are currently few therapeutic options. Funding Bioprojet, France.read more
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Journal ArticleDOI
Narcolepsy - clinical spectrum, aetiopathophysiology, diagnosis and treatment.
Claudio L. Bassetti,Antoine Roger Adamantidis,Denis Burdakov,Denis Burdakov,Denis Burdakov,Fang Han,Ulf Kallweit,Ramin Khatami,Frits Koning,Brigitte R. Kornum,Gert Jan Lammers,Roland S. Liblau,Pierre H. Luppi,Pierre H. Luppi,Geert Mayer,T. Pollmacher,Takeshi Sakurai,Federica Sallusto,Federica Sallusto,Thomas E. Scammell,Mehdi Tafti,Yves Dauvilliers,Yves Dauvilliers +22 more
TL;DR: Current understanding of how genetic, environmental and immune-related factors contribute to a prominent orexin signalling deficiency in patients with NT1 are focused on, along with uncertainties concerning the ‘narcoleptic borderland’, including narcolepsy type 2 (NT2).
Journal ArticleDOI
The clinical spectrum of childhood narcolepsy.
Emanuela Postiglione,Elena Antelmi,Fabio Pizza,Michel Lecendreux,Yves Dauvilliers,Giuseppe Plazzi +5 more
TL;DR: Spreading the awareness outside the sleep specialist community is necessary in order to reduce the diagnostic delay and to obtain prompt and multidisciplinary management of narcoleptic children.
Journal ArticleDOI
The European Medicines Agency review of pitolisant for treatment of narcolepsy: summary of the scientific assessment by the Committee for Medicinal Products for Human Use
Marta Kollb-Sielecka,Pierre Demolis,Joseph Emmerich,Greg Markey,Greg Markey,Tomas Salmonson,Tomas Salmonson,Manuel Haas +7 more
TL;DR: The main evidence of efficacy of pitolisant was based on two Phase III clinical trials and the most commonly reported adverse reactions were headache, insomnia and nausea.
Journal ArticleDOI
Pitolisant for Daytime Sleepiness in Patients with Obstructive Sleep Apnea Who Refuse Continuous Positive Airway Pressure Treatment. A Randomized Trial.
Yves Dauvilliers,Johan Verbraecken,Markku Partinen,Jan Hedner,Tarja Saaresranta,Tarja Saaresranta,Ognian Georgiev,Rumen Tiholov,Isabelle Lecomte,Renaud Tamisier,Patrick Levy,Catherine Scart-Grès,Jeanne-Marie Lecomte,Jean-Charles Schwartz,Jean-Louis Pépin +14 more
TL;DR: Pitolisant significantly reduced self-reported daytime sleepiness and fatigue and improved patient-reported outcomes and physician disease severity assessment in sleepy patients with obstructive sleep apnea refusing or nonadherent to continuous positive airway pressure.
Journal ArticleDOI
Histamine: neural circuits and new medications
TL;DR: A translational overview of the histamine system is provided, from basic research to new clinical trials demonstrating the usefulness of drugs that enhance histamine signaling, and clinical trials show that these medications reduce sleepiness and cataplexy in narcolepsy.
References
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Journal ArticleDOI
International classification of sleep disorders-third edition: highlights and modifications.
TL;DR: Significant modifications have been made to the nosology of insomnia, narcolepsy, and parasomnias in the recently released third edition of the International Classification of Sleep Disorders.
Journal ArticleDOI
Narcolepsy with cataplexy
TL;DR: Because narcolepsy is an under-recognised disease, it is important that general practitioners and other primary health-care workers identify abnormal daytime sleepiness early.
Journal ArticleDOI
Practice parameters for the treatment of narcolepsy and other hypersomnias of central origin.
Timothy I. Morgenthaler,Vishesh K. Kapur,Terry Brown,Todd J. Swick,Cathy A. Alessi,R. Nisha Aurora,Brian Boehlecke,Andrew L. Chesson,Leah Friedman,Rama Maganti,Judith A. Owens,Jeffrey Pancer,Rochelle S. Zak +12 more
TL;DR: These practice parameters serve as both an update of previous practice parameters for the therapy of narcolepsy and as the first practice parameters to address treatment of other hypersomnias of central origin, based on evidence analyzed in the accompanying review paper.
Journal ArticleDOI
Pitolisant versus placebo or modafinil in patients with narcolepsy : a double-blind, randomised trial
Yves Dauvilliers,Claudio L. Bassetti,Gert Jan Lammers,Isabelle Arnulf,Geert Mayer,Andrea Rodenbeck,Philippe Lehert,Philippe Lehert,Claire-Li Ding,Jeanne-Marie Lecomte,J C Schwartz +10 more
TL;DR: Pitolisant at doses up to 40 mg was efficacious on EDS compared with placebo and well tolerated compared with modafinil, and could offer a new treatment option for patients with narcolepsy.
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