Efficacy of Once-Nightly Sodium Oxybate (ONSXB; FT218) by Narcolepsy Type: Post-Hoc Analyses from the REST-ON Trial

Document Type

Conference Proceeding

Publication Date

10-14-2022

Publication Title

Ann Neurol

Abstract

Once-nightly sodium oxybate (ON-SXB; FT218) was evaluated for treatment of narcolepsy in the phase 3 REST-ON trial (NCT02720744). Significant improvement was shown for the three coprimary endpoints: mean sleep latency on the Maintenance of Wakefulness test (MWT), Clinical Global Impression of Improvement (CGI-I) rating, and weekly number of cataplexy episodes overall (all P<0.001 vs placebo); and in post-hoc analyses by narcolepsy type (NT1/NT2) for MWT and CGI-I (all P<0.05). Post-hoc efficacy analyses of objective and subjective measures of disrupted nighttime sleep (DNS) and daytime sleepiness by narcolepsy type were conducted. Participants 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. Mixed-effects models for repeated measures were used to calculate P values for change from baseline (least-squares mean difference [LSMD]) vs placebo at weeks 3 (6 g), 8 (7.5 g), and 13 (9 g) for secondary REST-ON endpoints of sleep stage shifts (ie, number of shifts from stages N1, N2, N3 and rapid eye movement [REM] sleep to Wake and from N2, N3 and REM sleep to N1), nocturnal arousals (NA), patient-reported sleep quality and refreshing nature of sleep (100-point visual analog scale), and Epworth sleepiness scale (ESS) score. Of 190 participants, 145 had NT1 (ON-SXB, n=73; placebo, n=72) and 45 had NT2 (ON-SXB, n=24; placebo, n=21). Improvements with ON-SXB 9 g vs placebo were reported for shifts to a lighter stage of sleep (LSMD, NT1: -22.0, P<0.001; NT2: -25.0, P<0.001), NA (LSMD, NT1: -22.8, P<0.01; NT2: -20.5, P<0.05), and sleep quality (LSMD, NT1: 11.2, P<0.001; NT2: 10.4, P<0.05). For the 6-g and 7.5-g dose, improvements with ON-SXB were also reported for shifts to a lighter stage of sleep (NT1: both P<0.001; NT2: both P<0.05), NA (NT1: 6 g, P<0.05; 7.5 g, P<0.01; NT2: 6 g, directional improvement; 7.5 g, P<0.05), and sleep quality (NT1: both P<0.001; NT2: both P<0.05). Significant improvements in refreshing nature of sleep and ESS for ON-SXB vs placebo were reported for NT1 (all doses, P≤0.001) with directional improvements observed for the NT2 subgroup. Results of these subgroup analyses are generally consistent with previously reported REST-ON endpoints and support efficacy of ON-SXB for DNS, as well as daytime sleepiness, with a single bedtime dose in adults with either NT1 or NT2.

Volume

92

First Page

S222

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