0768 Time Course Of Improvement In Excessive Daytime Sleepiness And Cataplexy During Treatment With Pitolisant In Patients With Narcolepsy. (27th May 2020)

• Record Type: Journal Article
• Authors: Roy, A; Davis, C W; Vaughn, B; Dayno, J M; Dauvilliers, Y; Schwartz, J
• Is Part Of: Sleep. Volume 43(2020)Supplement 1
• Page Start: A291
• Page End: A292
• Publication Date: 2020-05-27
• Subjects: Sleep -- Physiological aspects -- Periodicals; Sleep disorders -- Periodicals; Sommeil -- Aspect physiologique -- Périodiques; Sommeil, Troubles du -- Périodiques; Sleep disorders; Sleep -- Physiological aspects; Sleep -- physiological aspects; Sleep Wake Disorders; Psychophysiology; Electronic journals; Periodicals; 616.8498
• DOI: 10.1093/sleep/zsaa056.764
• Languages: English
• ISSNs: 0161-8105

Abstract

Abstract: Introduction: This analysis evaluated the efficacy of pitolisant over time in three 7- to 8-week, randomized, placebo-controlled studies of adults with narcolepsy. Methods: Patients in all 3 studies (HARMONY-1, HARMONY-1bis, HARMONY-CTP) experienced excessive daytime sleepiness (EDS) at study baseline; patients in HARMONY-CTP also experienced ≥3 cataplexy attacks/week. Pitolisant was titrated to a maximum dose of 35.6 mg/day (HARMONY-1, HARMONY-CTP) or 17.8 mg/day (HARMONY-1bis). Change from baseline in mean Epworth Sleepiness Scale (ESS) score (3 studies) and mean weekly rate of cataplexy (WRC; 1 study) was compared for pitolisant versus placebo. Results: In the higher-dose 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 (LS mean difference, -2.8; P =0.015) and Week 3 (LS mean difference, -2.0; P =0.005), respectively. In the lower-dose HARMONY-1bis study (pitolisant, n=66; placebo, n=32), significant separation from placebo was first observed at Week 7 (LS mean difference, -2.3; P =0.044). At end-of-treatment, LS mean difference in ESS score change from baseline was -3.1 ( P =0.022) in HARMONY-1, -3.4 ( P <0.001) in HARMONY-CTP, and -2.2 ( P =0.030) in HARMONY-1bis. In HARMONY-CTP, LS mean WRC with pitolisant was 11.7 at baseline, 4.6 at end-of-treatment, and 5.1 after a 1-week, placebo-washout period. Improvement in WRC was significantly greater with pitolisant versus placebo beginning at Week 2 (LS mean difference, -5.3; P =0.004) and continued through end-of-treatment (LS mean difference, -6.2; P <0.001); there was no evidence of rebound cataplexy after placebo-washout (LS mean difference, -4.9; P =0.027). Conclusion: During pitolisant treatment, improvement in EDS occurred sooner (within first few weeks) and was more robust in studies that permitted titration to the maximum recommended dose (35.6 mg/day). The rate of cataplexy attacks decreased early during treatment, with no evidence of rebound when pitolisant was withdrawn. Support: Bioprojet Pharma and Harmony Biosciences, LLC.