Effects of Low-Sodium Oxybate on 24-Hour Total Sleep Time: Data From a Phase 3 Clinical Study in Adults With Idiopathic Hypersomnia (P5-13.001)

Abstract

<h3>Objective:</h3> Evaluate the effects of lower-sodium oxybate (LXB; Xywav^®) on total sleep time (TST) in idiopathic hypersomnia. <h3>Background:</h3> Idiopathic hypersomnia is a debilitating central hypersomnolence disorder. Efficacy and safety of LXB for idiopathic hypersomnia in adults were established in a double-blind randomized withdrawal study (NCT03533114). <h3>Design/Methods:</h3> Participants began LXB treatment in an open-label titration and optimization period (10–14 weeks), followed by a 2-week, open-label, stable-dose period (SDP), then were randomized to placebo or continued LXB during a 2-week, double-blind, randomized withdrawal period (DBRWP). Participant-recorded daily sleep diaries from week 2 of the screening and SDP periods were analyzed. Results are reported by baseline TST in groups with &lt;8, ≥8 to &lt;9, or ≥9 hours of sleep per 24 hours and by treatment at study entry (treatment naive or taking alerting agents [AAs; stimulants or wake-promoting agents]). <h3>Results:</h3> There were 154 participants (mean±SD age, 40±14 years; 68% female). From baseline to end of SDP, estimated median reductions were observed in participants with ≥8 hours of reported baseline sleep in 24-hour TST (≥8 to &lt;9 hours=42 minutes; ≥9 hours=115 minutes), nocturnal TST (≥8 to &lt;9 hours=15 minutes; ≥9 hours=81 minutes), and nap duration (≥8 to &lt;9 hours=2.5 minutes; ≥9 hours=45.2 minutes). Minimal changes were observed in 24-hour TST, nocturnal TST, and nap duration in participants with &lt;8 hours of TST at baseline (1, 0, and 1.0 minutes, respectively). Reductions in TST were observed regardless of taking concomitant AAs in 24-hour TST (without AAs=61 minutes; with AAs=28 minutes), nocturnal TST (without AAs=32 minutes; with AAs=23 minutes), and nap duration (without AAs=11.3 minutes; with AAs=8.4 minutes). Common treatment-emergent adverse events (excluding placebo data) were nausea, headache, dizziness, anxiety, and vomiting. <h3>Conclusions:</h3> Open-label LXB treatment reduced TST and nap duration in participants with ≥8 hours of TST at baseline, and regardless of taking concomitant AAs. <b>Disclosure:</b> The institution of Dr. Morse has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Jazz Pharmaceuticals, Harmony Biosciences, Avadel Pharmaceuticals, Takeda Pharmaceuticals, Alkermes, National Institute for Health, and Geisinger Health Plan. The institution of Dr. Morse has received research support from Harmony Biosciences, Avadel Pharmaceuticals, Takeda Pharmaceuticals, Alkermes, National Institute for Health, and Geisinger Health Plan. Ms. Chen has received personal compensation for serving as an employee of Jazz Pharmaceuticals. Ms. Chen has received stock or an ownership interest from Jazz Pharmaceuticals. Teresa Steininger has received personal compensation for serving as an employee of Jazz Pharmaceuticals. Teresa Steininger has stock in Jazz Pharmaceuticals. Dr. Macfadden has received personal compensation for serving as an employee of Jazz pharma. Dr. Macfadden has stock in Jazz pharma.