Composite Response With Once-Nightly Sodium Oxybate: Symptom Improvement in Participants With Narcolepsy Type 1 in REST-ON

Introduction: In the phase 3 REST-ON trial (NCT02720744), once-nightly sodium oxybate (ON-SXB) treatment in participants with narcolepsy type 1 (NT1) and 2 (NT2) resulted in statistically significant improvements vs placebo across the coprimary endpoints (change from baseline in mean sleep latency on the Maintenance of Wakefulness test [MWT], Clinical Global Impression-Improvement [CGI-I] rating, and weekly cataplexy episodes), and the secondary endpoint Epworth Sleepiness Scale (ESS) score. This post hoc analysis assessed the proportion of participants with NT1 achieving clinically significant improvement on a composite of these endpoints.

Methods: Participants (aged ≥16 years with NT1 or NT2) with excessive daytime sleepiness (sleep latency < 11 min on the MWT, ESS score >10) and cataplexy (average of 8 episodes/week) were randomized 1:1 to ON-SXB (4.5 g week 1; 6 g weeks 2−3; 7.5 g weeks 4−8; 9 g weeks 9−13) or placebo. Clinically significant improvement thresholds (per 2021 AASM Clinical Practice Guidelines) were defined as: MWT (2-min improvement), CGI-I (1-point improvement), cataplexy (25% decrease), and ESS (2-point improvement).

Results: The modified intent-to-treat population included 145 participants with NT1 (ON-SXB, n=73; placebo, n=72; mean age, 32.1 years; 72.8% female; 76.5% white). At week 13 (9 g), more ON-SXB–treated participants had clinically significant improvements vs placebo in ≥2 endpoints (87.3% vs 62.9%; P < 0.01), ≥3 endpoints (76.4% vs 43.5%; P < 0.001), and in all 4 endpoints (47.3% vs 14.5%; P < 0.001). Similar results were observed at all doses.

Conclusions: These data support the robust clinical efficacy of ON-SXB for treating cataplexy or EDS in adults with narcolepsy.