Efficacy of FT218, a Once-Nightly Sodium Oxybate Formulation, in Patients With Narcolepsy: Post-hoc Sensitivity Analyses From the REST-ON Trial
Recommended Citation
Kushida C, Roth T, Thorpy M, Seiden D, Dubow J, Gudeman J. Efficacy of FT218, a Once-Nightly Sodium Oxybate Formulation, in Patients With Narcolepsy: Post-hoc Sensitivity Analyses From the REST-ON Trial. Sleep Med 2022; 100:S156-S157.
Document Type
Conference Proceeding
Publication Date
12-1-2022
Publication Title
Sleep Med
Abstract
Introduction: In REST-ON (NCT02720744), once-nightly sodium oxybate (ON-SXB; FT218) treatment resulted in significant improvement vs placebo for coprimary endpoints mean sleep latency on the Maintenance of Wakefulness test (MWT), Clinical Global Impression of Improvement (CGI-I) rating of “much” or “very much” improved, and weekly number of cataplexy attacks (NCA) (all P<0.001). Post-hoc sensitivity analyses using different methods to handle missing data were conducted to support the robustness of the primary data. Materials and Methods: Individuals aged ≥16 years with narcolepsy type 1 or 2 were randomized 1:1 to receive ON-SXB (1 week, 4.5 g; 2 weeks, 6 g; 5 weeks, 7.5 g; 5 weeks, 9 g) or placebo. Sensitivity analyses included completer population; placebo-based multiple imputation (MI) with missing not at random assumption (missing values in both arms imputed from observed placebo-arm values); analysis of covariance (ANCOVA); and tipping point-based MI of worsening values until P>0.05. For MWT and NCA, mean differences and P values were calculated. For CGI-I, odds ratios (OR) and P values were calculated for completers; mean differences (1–7-points; lower values indicate greater improvement) and P values were calculated using ANCOVA. Results: For completers (ON-SXB, n=69; placebo, n=79), significant improvement was observed with 6, 7.5, and 9 g ON-SXB vs placebo on all coprimary endpoints (all P<0.001); with 9-g dose, mean difference vs placebo on MWT was 6.0 min (95% CI: 3.3–8.7), CGI-I responder proportions for ON-SXB and placebo were 72.3% and 31.6% (OR, 5.7 [95% CI: 2.8–11.6]), and mean difference in NCA was –6.6 (95% CI: –9.6 to –3.6). With placebo-based MI, all ON-SXB doses were associated with significant improvement vs placebo on all coprimary endpoints (all P<0.001); with 9-g dose, mean difference vs placebo on MWT was 5.4 min (95% CI: 2.8–8.0), CGI-I responder proportions for ON-SXB and placebo were 63.0% and 28.5% (OR, 4.3 [95% CI: 2.3–8.0]), and mean difference in NCA was –6.4 (95% CI: –11.3 to –3.7). With ANCOVA, all ON-SXB doses were associated with significant improvement vs placebo on all coprimary endpoints (all P<0.001); for the 9-g dose, mean difference vs placebo on the MWT was 6.0 min (95% CI: 3.6–8.5), CGI-I rating difference was –1.0 (95% CI: –1.3 to –0.7), and mean NCA was –6.4 (95% CI: –9.0 to –3.8). With MWT tipping point MI, differences between ON-SXB and placebo lost significance with worsening of 7.0, 5.2, and 4.3 min from baseline for 6, 7.5, and 9 g, respectively, which was implausible for the 7.5- and 9-g doses as baseline MWT was 5 min. When participants who withdrew from the ON-SXB arm were imputed as “not improved,” CGI-I remained significant in favor of ON-SXB (all 3 doses, P<0.001). Mean NCA remained significant for all 3 ON-SXB doses vs placebo with worsening trajectories imputed; positive results could not be tipped over with plausible values. Conclusions: These post-hoc results are consistent with the coprimary endpoints and further confirm the efficacy of ON-SXB as a treatment for narcolepsy symptoms. Acknowledgements: This study was funded by Avadel Pharmaceuticals.
Volume
100
First Page
S156
Last Page
S157
