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Abstract Introduction Low-sodium oxybate (LXB; Xywav®) is approved by the US Food and Drug Administration to treat excessive daytime sleepiness or cataplexy in patients ≥7 years of age with narcolepsy, and idiopathic hypersomnia in adults. LXB contains the same active moiety as high-sodium oxybates (sodium oxybate SXB, Xyrem® and fixed-dose SXB Lumryz™) but with 92% less sodium. Previous studies have reported increased cardiovascular (CV) and cardiometabolic (CM) comorbidities in people with narcolepsy. This post-hoc analysis of a phase 3 trial assessed LXB efficacy and safety in participants with narcolepsy with and without CV/CM comorbidities. Methods Participants 18–70 years of age with narcolepsy with cataplexy optimized/titrated their LXB dose (up to 12 weeks) before entering a 2-week stable-dose period (SDP) (NCT03030599). Following SDP, participants withdrew to placebo or continued LXB during a 2-week double-blind randomized-withdrawal period (DBRWP). Epworth Sleepiness Scale (ESS) scores, cataplexy (average N/week), Patient Global Impression of Change (PGIc) scores, and treatment-emergent adverse events (TEAEs) were assessed in participants with and without CV/CM comorbidities, per medical history. Results Of 201 participants, 69 reported CV/CM comorbidities at baseline (most commonly hypertension and obesity). Participants with and without CV/CM comorbidities, respectively, had mean (SD) BMI of 31.6 (6.4) and 27.2 (5.3); mean age was 43.4 (12.0) and 33.9 (11.0) years; 66.7% and 57.6% were female. Participants randomized to placebo in the DBRWP in both subgroups showed worsening (increases) in ESS scores compared with those randomized to LXB (least squares mean differences, LXB vs placebo 95% CI, with CV/CM comorbidities: −2.6 −4.5, −0.70, P=0.0077; without CV/CM comorbidities: −2.7 −4.2, −1.2, P=0.0004; subgroup interaction, P=0.95). Participants without CV/CM comorbidities randomized to placebo had increased cataplexy attacks compared with those taking LXB (median, placebo, 3.0; LXB, 0.0; P 0.0001); those with CV/CM comorbidities had similar efficacy (placebo, 1.9; LXB, 0.0; P=0.0745). PGIc scores showed worsening in participants randomized to placebo vs LXB in both subgroups (P 0.0001 for both). Serious TEAEs were reported by 3% of participants with CV/CM comorbidities and 2% of those without. Conclusion In this post-hoc analysis, the efficacy and safety of LXB were similar in participants with narcolepsy with and without CV/CM comorbidities. Support (if any) Jazz Pharmaceuticals
Corser et al. (Sat,) studied this question.