EFFICACY OF FT218, A ONCE-NIGHTLY SODIUM OXYBATE FORMULATION, IN PATIENTS WITH NARCOLEPSY: POST-HOC SENSITIVITY ANALYSES FROM THE REST-ON TRIAL

Document Type

Conference Proceeding

Publication Date

5-25-2022

Publication Title

Sleep

Abstract

Introduction: In REST-ON, once-nightly sodium oxybate (ON-SXB; FT218) achieved significant improvement (P<0.001) vs placebo for all coprimary endpoints: Maintenance of Wakefulness test (MWT) mean sleep latency, Clinical Global Impression of Improvement (CGI-I) rating, and weekly number of cataplexy attacks (NCA). Methods: Individuals aged ≥16 years 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. Post-hoc sensitivity analyses were conducted with methods to handle missing data: completer population; placebobased multiple imputation (MI) with missing not at random assumption; analysis of covariance (ANCOVA); and tipping pointbased MI of worsening values until P>0.05. Results: Completers (ON-SXB, n=69; placebo, n=79) showed significant improvement (P<0.001) with 6, 7.5, and 9 g ON-SXB vs placebo on all coprimary endpoints; with 9-g dose, mean (95% CI) differences vs placebo were 6.0 min (3.38.7) on MWT and 6.6 (9.6 to 3.6) in NCA; 72.3% and 31.6%, respectively (odds ratio [OR], 5.7 [95% CI: 2.811.6]), were CGI-I responders. All ON-SXB doses achieved significant improvement (P<0.001) vs placebo on all coprimary endpoints with placebo-based MI and ANCOVA. With placebo-based MI, mean (95% CI) differences vs placebo (9-g dose) were 5.4 min (2.88.0) on MWT and 6.4 (11.3 to 3.7) in NCA; 63.0% and 28.5%, respectively (OR, 4.3 [95% CI: 2.38.0]), were CGI-I responders. With ANCOVA, mean (95% CI) differences vs placebo (9-g dose) were 6.0 min (3.68.5) on MWT and 6.4 (9.0 to 3.8) in NCA; CGI-I rating difference was 1.0 (1.3 to 0.7). With MWT tipping point MI, between-treatment differences lost significance with worsening of 7.0, 5.2, and 4.3 min from baseline for 6, 7.5, and 9 g, respectively (implausible for 7.5- and 9-g doses). When withdrawals from ON-SXB were imputed as not improved, CGI-I remained significant (all 3 doses, P<0.001). Mean NCA remained significant for all 3 doses vs placebo with worsening trajectories imputed; positive results were not tipped over with plausible values. Conclusion: These results support the robustness of the primary efficacy data for ON-SXB for narcolepsy treatment.

Volume

45

Issue

SUPPL 1

First Page

A180

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