Efficacy of pitolisant in patients with high burden of narcolepsy symptoms: pooled analysis of short-term, placebo-controlled studies.

Abstract

STUDY OBJECTIVE\nTo evaluate the efficacy of pitolisant, a histamine 3 (H3)-receptor antagonist/inverse agonist, in adult patients with high burden of narcolepsy symptoms.\n\n\nMETHODS\nData were pooled from two randomized, placebo-controlled, 7- or 8-week studies of pitolisant (titrated to a potential maximum dose of 35.6\xa0mg/day) in adults with narcolepsy. Analyses included three independent patient subgroups: Epworth Sleepiness Scale (ESS) baseline score ≥16, Maintenance of Wakefulness Test (MWT) sleep latency ≤8\xa0min, and ≥15 cataplexy attacks per week.\n\n\nRESULTS\nThe analysis populations included 118 patients for ESS (pitolisant, n\xa0=\xa060; placebo, n\xa0=\xa058), 105 for MWT (pitolisant, n\xa0=\xa059; placebo, n\xa0=\xa046), and 31 for cataplexy (pitolisant, n\xa0=\xa020; placebo, n\xa0=\xa011). On the ESS, least-squares mean change from baseline was significantly greater for pitolisant (-6.1) compared with placebo (-2.3; P\xa0<\xa00.001). Significantly more pitolisant-treated patients were classified as treatment responders: ESS score reduction ≥3, 69.0% in the pitolisant group versus 35.1% in the placebo group (P\xa0=\xa00.001); final ESS score ≤10, 36.2% versus 10.5%, respectively (P\xa0=\xa00.005). On the MWT, mean sleep latency increased from 3.5\xa0min to 10.4\xa0min with pitolisant and from 3.4\xa0min to 6.8\xa0min with placebo (P\xa0=\xa00.017). Least-squares mean change in the weekly rate of cataplexy was significantly greater for pitolisant (-14.5; baseline, 23.9; final, 9.4) compared with placebo (-0.1; baseline, 23.1; final, 23.0; P\xa0=\xa00.004). Headache was the most common adverse event with pitolisant.\n\n\nCONCLUSIONS\nPitolisant, at once-daily doses up to 35.6\xa0mg, was efficacious for reducing excessive daytime sleepiness and cataplexy in patients with severe narcolepsy symptom burden.