Consistent efficacy of once-nightly sodium oxybate regardless of patient demographic and baseline disease characteristics
Recommended Citation
Thorpy MJ, Roth T, Kushida CA, Morse AM, Harsh J, Ortiz LE, Dubow J, Gudeman J, Dauvilliers Y. Consistent efficacy of once-nightly sodium oxybate regardless of patient demographic and baseline disease characteristics. Sleep Med 2024; 115:211.
Document Type
Conference Proceeding
Publication Date
2-1-2024
Publication Title
Sleep Med
Abstract
Introduction: Once-nightly formulation of sodium oxybate (ON-SXB; LUMRYZ™) was investigated in patients with narcolepsy in the phase 3 REST-ON trial; treatment with 6, 7.5, and 9 g resulted in significant improvements (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 attacks (NCA), and the secondary endpoint, Epworth Sleepiness Scale (ESS) score. ON-SXB was well tolerated; the most common adverse events were nausea, dizziness, headache, enuresis, and vomiting. As narcolepsy is a chronic disease with different phenotypes, this post hoc analysis assessed ON-SXB efficacy in various subgroups. Materials and methods: Participants in the REST-ON clinical trial (NCT02720744) were aged ≥16 years with narcolepsy type 1 (NT1) or 2 (NT2) and were randomized to ON-SXB (4.5 g for 1 week, 6 g for 2 weeks, 7.5 g for 5 weeks, and 9 g for 5 weeks) or matching placebo for 13 weeks. Differences in least squares mean (LSM) changes from baseline for ON-SXB vs placebo were compared for mean sleep latency on MWT, NCA (NT1 only), and ESS and odds ratios for “much”/“very much” improved on CGI-I among subgroups of baseline demographics (age [<35 y/≥35 y], sex, race [white/other], body mass index [BMI] category [underweight/normal; overweight/obese]) and narcolepsy disease characteristics (NT1/NT2; concomitant alerting agent use). Results: The modified intent-to-treat population included 190 participants (ON-SXB, n=97; placebo, n=93). LSM differences for ON-SXB 9 g vs placebo in change from baseline on the MWT in minutes at week 13 revealed significant improvements (P<0.05) for subgroups based on age (<35 years: 7.3; ≥35: 4.2), sex (female: 6.8; male: 5.3), race (white: 7.0; non-white: 4.8), BMI (low: 10.0; high: 4.0), narcolepsy type (NT1: 6.0; NT2: 6.3), and alerting agent/no alerting agent use (6.0 and 6.3, respectively). 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, and ranged from 3.3 (no alerting agent) to 7.1 (age <35); 3 subgroups (male, low BMI, and NT2) could not be calculated. LSM differences 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. Among the subgroups that were significant, reductions ranged from –5.5 to –7.6; for the non-white and male subgroups, reductions were –3.8 and –5.1, respectively. For the ESS, all subgroups exhibited significant improvements with ON-SXB 9 g vs placebo except NT2 ( LSM difference [95% CI]: –2.72 [–6.09, 0.65]); the largest reduction was in low BMI ( LSM difference [95% CI]: –6.25 [–8.83, –3.68]). Similar, albeit smaller, differences were found with lower doses. Conclusions: Post-hoc subgroup analyses demonstrate the robust efficacy of ON-SXB and provide further insight into its effectiveness in different demographic and clinical subgroups. Acknowledgements: This study was funded by Avadel Pharmaceuticals.
Volume
115
First Page
211
