0650 Safety and Efficacy of KP1077 in a Phase 2, Double-Blind, Randomized Trial in Patients with Idiopathic Hypersomnia

Abstract Introduction KP1077 is under development as an oral medication for the treatment of rare sleep disorders with Excessive Daytime Sleepiness (EDS), including idiopathic hypersomnia (IH). The active ingredient in KP1077 is serdexmethylphenidate (SDX), a prodrug of d-methylphenidate. The objectives of the study were to assess the safety (primary endpoint) and efficacy of KP1077 in patients with IH. Methods Adult patients with IH began KP1077 treatment in a 5-week open-label (OL) titration period. Possible dose levels were 80, 160, 240 and 320 mg/day SDX. Patients were randomized to receive their daily dose either once per day (just before going to sleep), or twice per day (half the daily dose just before going to sleep and half shortly after awakening). After the titration period, patients in each treatment group were randomized to placebo or continued KP1077 (optimized dose) during a 2-week double-blind (DB) withdrawal period. Assessments of safety were based on adverse events (AEs), physical examinations, clinical laboratory tests, vital signs, electrocardiograms, sleep quality, and suicidal ideation. Efficacy assessments included the Epworth Sleepiness Scale (ESS) and Idiopathic Hypersomnia Severity Scale (IHSS). Patients rated their difficulty of waking up in the morning with the Sleep Inertia Visual Analog Scale (SI-VAS) and brain fog throughout the day with an exploratory Brain Fog Scale (BFS). Results Safety and efficacy in the OL titration phase were evaluated in an interim analysis when 22 patients completed the study (target: ≥48 completers). KP1077 was well-tolerated for both treatments and all dose levels, with most frequent AEs of insomnia, headache, and nausea. Most AEs were mild, not leading to early discontinuation. Meaningful clinical improvements in scores of ESS, IHSS, SI-VAS, and BFS were observed in both treatment groups. Mean total ESS scores decreased by >9 points after 5 weeks of OL treatment. Results from all patients in the both the OL titration and DB withdrawal periods will be presented. Conclusion KP1077 was well-tolerated in patients with IH with AEs typical for a central nervous system stimulant. Meaningful clinical improvements of EDS, sleep inertia and brain fog were observed after 5 weeks of OL KP1077. Support (if any) Zevra Therapeutics