Title: Safety and efficacy of pitolisant on cataplexy in patients with narcolepsy: a randomised, double-blind, placebo-controlled trial

Authors: Szakacs, Zoltan et al.


What You Need to Know:

Treatment with pitolisant, a first-in-class, highly-selective, histamine H3 receptor inverse agonist, significantly reduced cataplexy in patients with severe nacrolepsy. Pitolisant reduced the frequency of attacks per week and significantly improved excessive daytime sleepiness (EDS).

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Trial Design:

  • HARMONY CTP was a Phase 3, multicenter, randomized, prospective, double blind, placebo-controlled study evaluating the efficacy and safety of pitolisant (5mg–40mg individual dose titration) vs. placebo 
  • Study period: April 19, 2013 to January 28, 2015 
  • 105 patients; pitolisant (n=54) and placebo (n=51) 
  • Enrolled patients had a high frequency of cataplexy (7–9 attacks per week), a high level of diurnal somnolence, or associated symptoms like hallucinations 
  • The primary endpoint was the change in the average number of cataplexy attacks per week as recorded in patient diaries between the 2 weeks of baseline and the 4 weeks of stable dosing period

Key Outcomes:

  • Pitolisant significantly reduced cataplexy when given once daily for 2 months in severely affected patients
  • Frequency of attacks per week decreased by 75% (from 9.15 to 2.27) with pitolisant vs. 38% (from 7.31 to 4.52) with placebo (P<0.0001)
  • Excessive Daytime Sleepiness (EDS) was also significantly improved with pitolisant therapy, as well as hallucinations and patient’s quality of life
  • Most frequent side effects: headache, nausea, and anxiety, irritability