Safety and Efficacy of Low-Sodium Oxybate in Participants With Narcolepsy With and Without Psychiatric Comorbidities: Subgroup Analysis of a Phase 3 Clinical Trial

This work was sponsored by Jazz Pharmaceuticals Introduction: Low-sodium oxybate (LXB; Xywav®) is approved by the US FDA for treating cataplexy or excessive daytime sleepiness in patients aged ≥7 years with narcolepsy. Narcolepsy and psychiatric comorbidities (PC) appear remarkably intertwined. This analysis assessed LXB safety and efficacy in participants with and without PC. Methods: Participants 18–70 years of age with narcolepsy with cataplexy were enrolled (NCT03030599). Participants optimized/titrated their LXB dose (12 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) and Patient Health Questionnaire-9 (PHQ-9) scores and treatment-emergent adverse events (TEAEs) were assessed in participants with or without PC (based on medical history). Results: Of 201 participants, 50 had past or concurrent PC, most commonly depression (n=26) and anxiety (n=22). Demographic/baseline characteristics were generally similar between subgroups; 78.0% with PC and 55.0% without PC were female. After open-label stabilization, participants randomized to placebo in both subgroups showed worsening (increases) in ESS scores from end of SDP to end of DBRWP compared with those randomized to LXB (least squares mean differences, LXB vs placebo [95% CI], with PC: −4.5 [−6.9, −2.1], 𝘗=0.0003; without PC: −2.2 [−3.5, −0.9], 𝘗=0.0012). PHQ-9 scores remained stable in both subgroups. Three participants with PC (6.0%) and 4 without (2.6%) discontinued due to psychiatric-related TEAEs. Conclusion: The safety and efficacy of low-sodium oxybate were similar in participants with and without PC. There were no signals for the occurrence of new psychiatric disorders in either subgroup.