Efficacy and Safety of Low-Sodium Oxybate in Participants With Idiopathic Hypersomnia With and Without Psychiatric Comorbidities
Introduction: Psychiatric comorbidities (PC) are common in patients with idiopathic hypersomnia (IH). Low-sodium oxybate (LXB; Xywav®) is approved by the US FDA for the treatment of IH in adults. This post-hoc analysis of a phase 3 trial (NCT03533114) assessed efficacy and safety of LXB in participants with IH with and without PC.
Methods: Adults with IH had their LXB dose optimized/titrated (10–14 weeks), entered a 2-week stable-dose period (SDP), then withdrew to placebo or continued LXB during a 2-week, double-blind, randomized-withdrawal period (DBRWP). Epworth Sleepiness Scale (ESS), Idiopathic Hypersomnia Severity Scale (IHSS), and Visual Analog Scale–Sleep Inertia (VAS-SI) scores were assessed in participants with and without PC (per medical history). Participants with past/present bipolar, schizophrenia, or other psychotic disorders were excluded.
Results: Of 154 enrolled participants, 68 had a past/concurrent PC, most commonly anxiety (n=35) and depression (n=35). Participants randomized to placebo in both subgroups showed worsening (increases) in ESS scores from end of SDP to end of DBRWP compared with those continuing LXB. Least squares mean differences (LXB vs placebo) [95% CI] were: ESS scores—with PC: −7.5 [−9.7, −5.4], without PC: −5.8 [−7.9, −3.8]; IHSS scores—with PC: −12.9 [−16.6, −9.2], without PC: −11.1 [−14.6, −7.6]; VAS-SI—with PC: −31.2 [−41.9, −20.5], without PC: −14.4 [−24.4, −4.4]. TEAEs were similar between subgroups. Limitations include the small sample size and post-hoc nature, which may affect generalizability.
Conclusion: Efficacy and safety of LXB were similar in IH participants with and without past/concurrent PC.
