0639 Long-term Safety and Timing of Adverse Events with Low-Sodium Oxybate in a Phase 3 Idiopathic Hypersomnia Study

Abstract Introduction Low-sodium oxybate (LXB; Xywav®) is approved by the US Food and Drug Administration for the treatment of idiopathic hypersomnia in adults. To examine the long-term safety of LXB in this population, this post hoc analysis evaluated treatment-emergent adverse events (TEAEs) over time in a phase 3, double-blind, placebo-controlled, randomized withdrawal trial (NCT03533114), including its open-label extension period. Methods Participants were adults with idiopathic hypersomnia. TEAEs were analyzed across all study periods (open-label titration,10–14 weeks; stable-dose, 2 weeks; double-blind randomized withdrawal, 2 weeks; open-label extension, 24 weeks; safety follow-up, 2 weeks) in the analysis population (oxybate-naive participants who took ≥1 dose of study drug; N=148). Onset and duration of common TEAEs (≥5% of participants) were reported in the total population and by baseline medication group (treatment-naive, n=66; taking alerting agents stimulants or wake-promoting agents, n=82). Duration was defined as the time from when a TEAE started until it was reported as ended. Results are presented using descriptive statistics. Results The majority of the most frequently reported TEAEs occurred within the first 5 weeks after study onset. In treatment-naive participants, the most common TEAEs (incidence; median duration) were nausea (n=13 19.7%; 7.5 days), headache (n=12 18.2%; 3.0 days), dizziness (n=11 16.7%; 4.0 days), anxiety (n=7 10.6%; 9.0 days), and decreased appetite (n=7 10.6%; 15.0 days). In participants taking alerting agents, the most common TEAEs were nausea (n=21 25.6%; 7.5 days), headache (n=15 18.3%; 2.0 days), vomiting (n=14 17.1%; 1.5 days), anxiety (n=10 12.2%; 28.0 days), insomnia (n=9 11.0%; 7.0 days), and tremor (n=9 11.0%; 11.0 days). Common TEAEs were of mild or moderate severity and infrequently led to study discontinuation (≤3.7% of participants each). Nine serious TEAEs occurred in 4/148 (2.7%) participants; none were considered related to study drug or led to study discontinuation. Conclusion In this study of LXB in participants with idiopathic hypersomnia, the common TEAEs (≥5% of participants) were consistent with the known safety profile of oxybate, peaked early (generally within 5 weeks), and were mild to moderate in severity, in both treatment-naive participants and participants taking alerting agents. Support (if any) Jazz Pharmaceuticals