Safety and efficacy of pitolisant on cataplexy in patients with narcolepsy: a randomised, double-blind, placebo-controlled trial
Abstract
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).
This trial is registered with ClinicalTrials.gov, number NCT01800045. The WCR during the stable dosing period compared with baseline was decreased by 75% (WCRfinal=2.27; WCRbaseline=9.15; WCRfinal/baseline=0.25) in patients who received pitolisant and 38% (WCRfinal=4.52; WCRbaseline =7.31; WCRfinal/baseline=0.62) in patients who received placebo (rate ratio 0.512; 95% CI 0.43-0 60, p<0.0001).
Treatment-related adverse events were significantly more common in the pitolisant group than in the placebo group (15 [28%] of 54 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.