Abstract Details

Title Time to Onset of Clinical Response During Treatment With Pitolisant

Topic Sleep

Presentation(s) Sleep Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 015

Background Time to onset of response was evaluated in two short-term studies to further elucidate clinical features of pitolisant.

Objective To evaluate the time to onset of clinical response during treatment with pitolisant for EDS and cataplexy in adults with narcolepsy.

Design/Methods

Patients in both studies (HARMONY-1, HARMONY-CTP) experienced excessive daytime sleepiness (EDS) at baseline; patients in HARMONY-CTP experienced ≥3 cataplexy attacks/week. Pitolisant was titrated to a maximum dose of 35.6mg/day in both clinical trials. Change from baseline in mean Epworth Sleepiness Scale (ESS) score (2 studies) and mean weekly rate of cataplexy (WRC; 1 study) was compared for pitolisant versus placebo.

Results In the HARMONY-1 (pitolisant, n=31; placebo, n=30) and HARMONY-CTP (pitolisant, n=54; placebo, n=51) studies, ESS score improvement was significantly greater with pitolisant versus placebo beginning at Week 2 (least squares mean (LSM) difference, -2.8; P=0.015) and Week 3 (LSM difference, -2.0; P=0.005), respectively. This greater improvement for pitolisant-treated patients was maintained through the end of both trials; final visit LSM differences of -3.2 (P=0.026) and -4.0 (P<0.001), respectively. In HARMONY-CTP, LSM weekly rate of cataplexy for pitolisant-treated patients was 11.7 at baseline, 4.6 at end-of-treatment, and 7.8 after a 1-week, placebo-washout period. Improvement in weekly rate of cataplexy was significantly greater with pitolisant versus placebo beginning at Week 2 (LSM difference, -5.3; P=0.004) and continued through end-of-treatment (LSM difference, -6.4; P<0.001); there was no evidence of rebound cataplexy after placebo-washout.

Conclusions During pitolisant treatment in which patients could be titrated to the maximum recommended dose of 35.6mg, improvement in EDS occurred within 2-3 weeks of treatment initiation when patients could be treated with up to 17.8mg daily. Improvement of cataplexy was seen at week two (treated with 8.9mg daily). No evidence of rebound was seen for either symptom when pitolisant was withdrawn.

Authors/Disclosures
Craig Davis, PhD (Harmony Biosciences) PRESENTER	Dr. Davis has received personal compensation for serving as an employee of Harmony Biosciences. Dr. Davis has received stock or an ownership interest from Harmony Biosciences.
Jeffrey M. Dayno, MD (Harmony Biosciences, LLC)	Dr. Dayno has received personal compensation for serving as an employee of Harmony Biosciences. Dr. Dayno has received stock or an ownership interest from Harmony Biosciences.
	No disclosure on file
Yves Dauvilliers, MD, PhD (Hopital Gui De Chaulliac)	Yves Dauvilliers, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for idorsia. Yves Dauvilliers, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for JAZZ. Yves Dauvilliers, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Takeda. Yves Dauvilliers, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avadel.