0614 Safety and Tolerability of Pitolisant in the Treatment of Adults With Narcolepsy: Integrated Data From Clinical Studies

Abstract

Introduction: Pitolisant, a selective histamine 3 (H3) receptor antagonist/inverse agonist, has been investigated for treatment of excessive daytime sleepiness (EDS) and cataplexy in adult patients with narcolepsy. This analysis evaluates the integrated safety data from studies of pitolisant in adult patients with narcolepsy. Method(s): Data were pooled across 4 randomized, placebo-controlled, 7-8 week studies. Pitolisant was flexibly dosed to a maximum of 35.6 mg (3 studies) or 17.8 mg (1 study). Safety assessments included adverse events (AEs), vital signs, laboratory assessments, and electrocardiogram (ECG) measurements. Result(s): The analysis population consisted of 303 patients (pitolisant, n=172; placebo, n=131): 54.5% male; mean age, 39.2 years; and mean duration of narcolepsy, 11.3 years. The study completion rate was similar for pitolisant (94.2%) and placebo (94.7%). The maintenance dose of pitolisant was 35.6 mg in 39.5% of patients and 3% of pitolisant-treated patients) for pitolisant versus placebo were headache (18.0% vs 13.7%), nausea (5.2% vs 3.1%), insomnia (4.1% vs 2.3 %), upper respiratory tract infection (4.1% vs 0.8%), back pain (3.5% vs 0.8%), and dizziness (3.5% vs 2.3%). Serious AEs were reported in 2 (1.2%) pitolisant-treated patients (hemorrhoids, pyelonephritis) and 1 (0.8%) placebo-treated patient (biliary colic). AEs resulted in treatment discontinuation for 3.5% and 3.8% of patients in the pitolisant and placebo groups, respectively. No clinically relevant effects were observed in vital signs, laboratory findings, or ECG parameters. No new safety signals were identified from long-term, open-label studies in patients with narcolepsy. Conclusion(s): Integrated safety data from the clinical development program in adult patients with narcolepsy demonstrates that pitolisant was generally safe and well-tolerated. Considered together with the efficacy findings, pitolisant offers a favorable risk/ benefit profile and represents a potential advancement in the treatment of EDS and cataplexy in adult patients with narcolepsy.