Long-term Efficacy and Safety of Low-Sodium Oxybate in an Open-Label Extension Period of a Placebo-Controlled, Double-Blind, Randomized Withdrawal Study in Adults with Idiopathic Hypersomnia

STUDY OBJECTIVES To evaluate 6-month efficacy and safety of low-sodium oxybate (LXB) in people with idiopathic hypersomnia during an open-label extension period (OLE) of a phase 3 clinical trial. METHODS Efficacy measures included the Epworth Sleepiness Scale (ESS), Idiopathic Hypersomnia Severity Scale (IHSS), Patient Global Impression of Change (PGIc), Functional Outcomes of Sleep Questionnaire, short version (FOSQ-10), and Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP). Treatment-emergent adverse events (TEAEs) were collected throughout the OLE. RESULTS The OLE population included 106 participants. Most were female (71%) and White (83%), and the mean (SD) age was 41.0 (13.8) years. ESS scores decreased (improved) during OLE (mean [SD], study baseline: 16.3 [2.8]; OLE week (W)2: 6.7 [4.7]; OLE end: 5.3 [3.7]), and IHSS total scores trended toward a decrease (study baseline: 32.6 [7.3]; OLE W2: 16.2 [8.9]; OLE end: 14.8 [8.6]. Median (min, max) paired differences from OLE W2 to OLE end were ESS, -1.0 (-20, 7), nominal P=0.012; IHSS, -1.0 (-31, 19), nominal P=0.086). The proportion of participants reporting PGIc ratings of "very much improved" increased from 36.7% at OLE W2 to 53.8% at OLE end. FOSQ-10 and WPAI:SHP scores remained stable during OLE. The incidence of newly reported TEAEs decreased over the duration of OLE. CONCLUSIONS Efficacy and safety of LXB were maintained or improved during the 6-month OLE, supporting long-term treatment with LXB in adults with idiopathic hypersomnia. CLINICAL TRIAL REGISTRATION Registry: ClinicalTrials.gov; Identifier: NCT03533114 and Registry: EU Clinical Trials; Identifier: 2018-001311-79.