Résumé
Introduction Once-nightly sodium oxybate (ON-SXB; LUMRYZ™) was investigated in patients with narcolepsy type 1 (NT1) or 2 (NT2) in the phase 3 REST-ON trial; treatment with 6, 7.5, and 9 g demonstrated significant improvements vs placebo (all P< 0.001) for the coprimary endpoints of change from baseline in mean sleep latency on the Maintenance of Wakefulness Test (MWT), Clinical Global Impression-Improvement (CGI-I) rating, and weekly number of cataplexy episodes (NCA), and the secondary endpoint Epworth Sleepiness Scale (ESS) score. This post-hoc analysis assessed ON-SXB efficacy in various subgroups. Methods REST-ON (NCT02720744) participants aged ≥16 years with NT1 or NT2 were randomized 1:1 to ON-SXB (4.5 g, 1 week; 6 g, 2 weeks; 7.5 g, 5 weeks; 9 g, 5 weeks) or placebo for 13 weeks. Least squares mean differences (LSMDs) in changes from baseline for ON-SXB vs placebo for mean sleep latency on MWT, NCA (NT1 only), and ESS, and odds ratios for “much”/“very much” improved on CGI-I, were compared among baseline demographic (age, sex, race, body mass index [BMI] category) and narcolepsy disease characteristic (NT1/NT2; concomitant alerting agent use) subgroups. Results The modified intent-to-treat population included 190 participants (ON-SXB, n=97; placebo, n=93). LSMDs for ON-SXB 9 g vs placebo in change from baseline on the MWT at week 13 revealed significant improvements (P< 0.05) for subgroups based on age, sex, race, BMI, narcolepsy type, and alerting agent/no alerting agent use. Odds ratios were significant in favor of ON-SXB 9 g vs placebo for “much” or “very much” improved on CGI-I at week 13 (P< 0.05) for both low/high age, female sex, white/non-white, high BMI, NT1, and alerting agent/no alerting agent use. LSMDs were significant in favor of ON-SXB 9 g vs placebo for change from baseline in NCA (P< 0.05) in all subgroups, except non-white and male. For the ESS, all subgroups exhibited significant improvements (P< 0.05) with ON-SXB 9 g vs placebo, except NT2. Comparable differences were found with the 6-g dose at Week 3 and the 7.5-g dose at Week 8. Conclusion Post-hoc subgroup analyses demonstrate the robust efficacy of ON-SXB across demographic and clinical subgroups. Support (if any) Avadel Pharmaceuticals