Characterization of patients who had ≥5% weight loss with once-nightly sodium oxybate: post hoc analysis from REST-ON
Recommended Citation
Roth T, Morse AM, Bogan R, Roy A, Dubow J, Gudeman J, Dauvilliers Y. Characterization of patients who had ≥5% weight loss with once-nightly sodium oxybate: post hoc analysis from REST-ON. Sleep Med 2024; 115:209.
Document Type
Conference Proceeding
Publication Date
2-1-2024
Publication Title
Sleep Med
Abstract
Introduction: Narcolepsy, particularly type 1 (NT1), is often comorbid with obesity. Efficacy and safety of a once-at-bedtime oxybate (LUMRYZ™, sodium oxybate for extended-release oral suspension, CIII [FT218; once-nightly sodium oxybate (ON-SXB)]), were shown in the phase 3 REST-ON clinical trial (NCT02720744). Materials and Methods: REST-ON was a 13-week, randomized (1:1), double-blind, placebo-controlled multicenter study in patients ≥16 years old with NT1/NT2. ON-SXB doses were 4.5 g for 1 week, 6 g for 2 weeks, 7.5 g for 5 weeks, and 9 g for 5 weeks. Stable concomitant stimulant use was permitted. A post hoc analysis to further characterize participants in the ON-SXB group experiencing ≥5% weight loss (weight-loss group) in REST-ON was conducted. Results: In REST-ON (n=212), mean participant age was 31.2 years (range, 16–72), 67.9% were female, 75.5% were white, 76.4% had NT1, mean baseline BMI was 28.1 kg/m2 (range, 16.9–71.9), and 61.3% were taking stimulants. At the end of the study, mean (SD) weight had decreased by 1.3 (3.6) kg in the ON-SXB and had increased by 0.2 (2.6) kg in the placebo group; least squares mean (LSM; SE) change from baseline was ‒0.51 (0.13) kg/m2 with ON-SXB and 0.08 (0.13) kg/m2 with placebo (LSM difference [95% CI], ‒0.59 [‒0.95 to ‒0.23] kg/m2; P=0.001). At week 13, 17.8% (19/107) of participants receiving ON-SXB experienced ≥5% weight loss vs 3.8% (4/105) of participants receiving placebo (P<0.001). Compared to the REST-ON population without weight loss, the weight-loss group had similar age and proportion of NT1 diagnosis, a smaller proportion was female, and a higher proportion was white and was taking stimulants. At baseline, mean BMI was 25.6 kg/m2 (range, 20.3–34.0) in the weight-loss group, 47.4% (9/19) were overweight (BMI 25.0–29.9kg/m2) or obese (BMI >30kg/m2); none were underweight (BMI <18.5kg/m2). At week 13, 31.6% (6/19) remained overweight or obese; none were underweight. Excessive daytime sleepiness was significantly improved from baseline to week 13 (ON-SXB 9 g) in the weight-loss group vs the group without weight loss (Maintenance of Wakefulness test, P<0.05; Epworth Sleepiness Scale score, P<0.001). On the Clinical Global Impression of Improvement, 84.6% of participants in the weight loss group were classified as “much” or “very much improved” at week 13 vs 69.8% in the group without weight loss (odds ratio, 2.4; 95% CI, 0.5–10.7). Adverse events of nausea and vomiting were more frequent in the weight-loss group (42.1%) vs the group without weight loss (19.7%); however, rate of discontinuations owing to AEs in the weight-loss group was half that of the ON-SXB group without weight loss (10.5% vs 21.1%, respectively). Conclusions: These data expand the body of knowledge regarding weight loss during treatment with sodium oxybate. Given the high proportion of comorbid obesity among people with narcolepsy, the additional benefit of potential weight loss with sodium oxybate may further inform treatment selection. Efficacy of ON-SXB for treatment of narcolepsy symptoms was demonstrated overall; further exploration of possible increased pharmacologic response in certain subgroups should be evaluated. Acknowledgements: Funded by Avadel Pharmaceuticals.
Volume
115
First Page
209
