0739 Phase 3, Randomized, Double-Blind, Placebo-Controlled Studies of Pitolisant Delayed-Release HD Tablets for Narcolepsy and Idiopathic Hypersomnia

Abstract Introduction Pitolisant is a histamine 3 receptor antagonist/inverse agonist approved for treatment of excessive daytime sleepiness (EDS) or cataplexy in adult patients with narcolepsy and for EDS in pediatric patients aged ≥6 years with narcolepsy. HBS-301, an optimized pitolisant formulation, with a gastro-resistant coating, at a higher dose (up to 60 mg), has been developed to potentially provide an improved treatment option for patients with narcolepsy or idiopathic hypersomnia (IH). Methods HBS-301-CL-301 and HBS-301-CL-302 are two global phase 3, randomized, double-blind, parallel-group, placebo-controlled studies to examine the efficacy and safety of HBS-301 in patients with narcolepsy and IH, respectively. These studies will consist of a screening/baseline period, an 8-week double-blind treatment period (2-week titration week 1, 30 mg; week 2, 60 mg, 3-week flexible-dose, and 3-week stable-dose periods), an optional open-label extension period (1 year), and 30 days of safety follow-up. Results In HBS-301-CL-301, ~258 adult participants with narcolepsy (type 1 or 2) will be randomized to receive HBS-301 or placebo (1:1); ~50% of participants will have an average weekly rate of cataplexy ≥3 over 2 consecutive weeks during screening. The primary endpoint will be the change from baseline to Week 8 in EDS as measured by the Epworth Sleepiness Scale (ESS). Key secondary endpoints include MWT sleep onset latency, efficacy in treating cataplexy and fatigue, as well as the onset of efficacy in treating EDS and cataplexy. In HBS-301-CL-302, ~248 adult participants with IH will be randomized to receive HBS-301 or placebo (1:1). The primary endpoint will be the change from baseline to Week 8 in EDS as measured by the ESS. Secondary endpoints include severity of IH symptoms as measured by the IHSS, sleep inertia, and fatigue, as well as the onset of efficacy and IH symptoms. In both studies, safety and pharmacokinetic concentrations of pitolisant will be examined. Conclusion These studies will determine the efficacy and safety of HBS-301, an optimized pitolisant formulation, with a gastro-resistant coating, at a higher dose (up to 60 mg), in patient populations with narcolepsy or IH. Support (if any) Harmony Biosciences