0734 Effect of Pitolisant on Sleep Patterns in Idiopathic Hypersomnia: Analysis of Phase 3 Trial Sleep Diary Data

Abstract Introduction Idiopathic hypersomnia (IH) is a rare neurological disorder with symptoms including excessive daytime sleepiness (EDS), sleep inertia, excessive sleep duration, and daytime naps that typically are not refreshing. Pitolisant has been shown to reduce EDS; however, its impact on napping and sleep duration, quality, and continuity in patients with IH is unknown. Methods The present analyses focused on an eight-week open-label period (OLP) that was part of a twelve-week double-blind, placebo-controlled, randomized withdrawal phase 3 clinical trial to evaluate the safety and efficacy of pitolisant in adult patients with IH (NCT05156047). During the OLP, eligible participants were titrated with pitolisant for three weeks (8.9, 17.8, or 35.6 mg) and continued taking open-label pitolisant for five additional weeks. Patients completed the Consensus Sleep Diary for seven days at two timepoints: 1) prior to receiving pitolisant (screening), and 2) at the end of the eight-week OLP. These ad hoc analyses explored the potential effects of pitolisant and concomitant use of other wake-promoting medications on sleep patterns in patients with IH. Results One hundred and seventy-six patients (mean±SD age; 40.1±13.0 years; 77.8% female) completed sleep diaries at both screening and end of the OLP, and were thus included in these analyses. All nighttime sleep patterns remained stable between screening and end of the OLP, respectively (data expressed as mean±SD): nocturnal sleep duration (482.3±56.2 vs 482.9±67.1 min, P=0.91); sleep quality (3.5±0.8 vs 3.5±0.9 5-point Likert scale, higher is better, P=0.22); nighttime awakening frequency (1.6±1.1 vs 1.6±1.2 per night, P=0.99); and nighttime awakening duration (16.2±16.2 vs 16.2±17.1 min, P=0.43). Daytime nap frequency and nap duration decreased between screening and end of the OLP, respectively: nap frequency (0.8±0.6 vs 0.5±0.5 per day, P 0.0001); and nap duration (65.0±38.4 vs 55.7±41.5 min, P=0.02). Concomitant use of other prescribed wake-promoting medications did not influence any sleep pattern outcomes. Conclusion During eight weeks of open-label pitolisant administration, patients experienced stable nocturnal sleep duration, quality, and continuity, as well as a decreased number and duration of daytime naps. These data suggest that eight-week open-label pitolisant administration did not adversely affect sleep patterns in patients with IH. Support (if any) Harmony Biosciences