2025 American Academy of Neurology Abstract Website

Objective:

This post hoc analysis of REST-ON evaluates the effect of once-nightly sodium oxybate (ON-SXB) compared to placebo on apnea hypopnea index (AHI) in individuals with narcolepsy with either no sleep apnea or mild sleep apnea.

Background:

Registrational trials of SXB, a central nervous system depressant used to treat narcolepsy, have generally excluded patients with respiratory depression, including those with an AHI >15.

Design/Methods:

In the phase 3, double-blind REST-ON (NCT02720744) trial, participants (age ≥16 years) with narcolepsy and AHI <15 were randomized 1:1 to ON-SXB (week 1, 4.5 g; weeks 2–3, 6 g; weeks 4–8, 7.5 g; weeks 9–13, 9 g) or placebo. AHI was measured using polysomnography at baseline and weeks 3, 8, and 13, and analyzed post hoc. Adverse drug reactions (ADRs) were assessed.

Results:

Respective mean (min, max) AHI values were similar for the ON-SXB (n=97) and placebo groups (n=93) at baseline (2.7 [0, 15] and 2.8 [0, 13]), week 3 (0.1 [0, 5] and 0.1 [0, 2]), and week 8 (0 [0, 0] and 0 [0, 0]). At week 13, mean (min, max) AHI was 0 (0, 0) and 0.2 (0, 10) in the ON-SXB and placebo groups, respectively. Least squares mean differences (95% CI) in change from baseline in AHI with ON-SXB and placebo were –0.11 (–0.46 to 0.24; P=0.522) at week 3, –0.11 (–0.46 to 0.23; P=0.518) at week 8, and –0.12 (–0.46 to 0.23; P=0.515) at week 13. One (0.9%) and 1 (1.0%) participant in the ON-SXB and placebo arms, respectively, experienced ADRs of sleep apnea, and 1 (0.9%) participant receiving ON-SXB reported snoring; all were mild or moderate in severity.

Conclusions:

Treatment with ON-SXB was not associated with worsened AHI at any tested dose. ON-SXB was well-tolerated, as reported respiratory-related ADRs were minimal, and mild or moderate in severity.