Once-Nightly Sodium Oxybate Meets American Academy of Sleep Medicine Criteria for Treatment of Narcolepsy.

Data from the REST-ON trial were not available before the 2021 American Academy of Sleep Medicine (AASM) clinical practice guideline update, which included a literature review through August 2020. This post hoc analysis from REST-ON assessed participants who achieved clinically significant improvements on individual AASM clinical significance thresholds (CSTs). Composites of the coprimary endpoints and a secondary endpoint were also analysed. Participants with narcolepsy aged ≥ 16 years were randomised 1:1 to once-nightly sodium oxybate (ON-SXB) or placebo for 13 weeks. Coprimary endpoints were mean sleep latency on the Maintenance of Wakefulness Test (MWT), Clinical Global Impression of Improvement (CGI-I) rating, and number of cataplexy episodes; secondary endpoints included the Epworth Sleepiness Scale (ESS) score. Outcomes with ON-SXB treatment compared with baseline were assessed according to the CSTs, and for those who met CSTs, the proportions of participants who experienced clinically significant improvements on a composite of ≥ 2, ≥ 3, or 4 endpoints were calculated. For improvements from baseline with ON-SXB at Week 13 (9-g dose), mean sleep latency on the MWT increased 10.8 min (CST, ≥ 2-min increase), 92.8% rated improvement on the CGI-I (CST, ≥ 33% of participants reporting improvement), reduction in number of cataplexy episodes was 60.8% reduction (CST, ≥ 25% reduction), and reduction in ESS score was -6.5 (CST, ≥ 2-point decrease). At Weeks 3, 8 and 13, significantly more participants treated with ON-SXB versus placebo experienced clinical improvements on ≥ 2, ≥ 3, or 4 endpoints (p ≤ 0.05). These data demonstrate the robust efficacy of ON-SXB across multiple clinically important narcolepsy symptoms per established CSTs, further supporting the use of ON-SXB in clinical practice. Trial Registration: This manuscript presents the results of a post hoc analysis from the REST-ON clinical trial (NCT02720744).