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

Document Type

Article

Publication Date

8-25-2025

Publication Title

Journal of sleep research

Abstract

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).

Medical Subject Headings

FT218; LUMRYZ; MCID; clinical improvement cutoff; excessive daytime sleepiness; minimal clinically important difference

PubMed ID

40851446

ePublication

ePub ahead of print

First Page

e70189

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