Once-Nightly Sodium Oxybate Improves Sleepiness, Sleep Disruption in Narcolepsy

Extended-release once-nightly sodium oxybate (ON-SXB) improves sleepiness during the day and sleep disruption at night in patients with narcolepsy, according to a post hoc analysis published in the journal Sleep.

The presence of catalepsy, or sudden muscle weakness, distinguishes narcolepsy type 1 (NT1) from narcolepsy type 2 (NT2). Few previous studies in patients with NT2 have evaluated the benefits of bedtime extended-release oxybate, which is the only once-nightly treatment option for patients with either type of narcolepsy. For the current study, researchers sought to evaluate the efficacy of ON-SXB vs placebo for daytime sleepiness and disrupted nighttime sleep in NT1 and 2.

In REST-ON (ClinicalTrials.gov Identifier: NCT02720744), a 13-week, multicenter, phase 3 trial that evaluated ON-SXB efficacy and safety in treating narcolepsy, patients were divided into subgroups by narcolepsy type and randomly assigned to receive either placebo or a weekly dose of drug that gradually increased from 4.5 g to 9 g.

The post hoc analysis analyzed the data collected on the study’s modified intent-to-treat population, which included 145 patients with NT1 and 45 patients with NT2. Those in the NT1 subgroup were somewhat older than those in the NT2 subgroup (32.1 years vs. 28.3 years). Both subgroups had a higher proportion of women (NT1: 72.8%; NT2: 52.0%, respectively) than men, and most of the patients in each subgroup were White (NT1: 76.5%; NT2: 72%).

The researchers assessed patients for mean sleep latency, determined by using changes observed from baseline to study end in ratings on the Maintenance of Wakefulness Test and on an investigator-rated improvement scale, the Clinical Global Impression-Improvement (CGI-I). These 2 ratings were the study’s coprimary endpoints. Assessments also included daytime sleepiness (determined by Epworth Sleepiness Scale score), sleep stage shifts, nocturnal arousals, and patient reports of sleep quality and how refreshing the sleep was. These 5 assessments were the study’s secondary endpoints.

Since the REST-ON trial was not sufficiently powerful to enable subgroup analysis, the post hoc analysis used a mixed-effects model for repeated measures to determine the change from baseline in mean sleep latency and in the secondary endpoints for each study subgroup. The analysis used another mixed-effects model for binomial data to analyze responses of very much or much improved on the CGI-I.

These methods of analysis revealed clinically meaningful improvements in sleep latency for active treatment vs placebo for both subgroups. These improvements were significant at all doses in the NT1 subgroup (P =.001) and at the 6 g and 9 g doses in the NT2 subgroup (P =.05). In both subgroups, more patients who received ON-SXB than patients who received placebo were rated as very much or much improved, and sleep stage shifts and sleep quality improved significantly (P =.001).

The researchers noted that a single bedtime dose of ON-SXB, across all doses evaluated, has shown clinically meaningful improvements in excessive daytime sleepiness and disrupted nighttime sleep and overall condition in both types of narcolepsies.

“ON-SXB does not disrupt or fragment sleep, and is less burdensome for patients as they can avoid the middle-of-the-night dose, which is particularly relevant given the potential chronic need for pharmacotherapy,” the researchers wrote.

Regarding study limitations, the researchers commented that, although the sample size prevented them from making statistical comparisons between subgroups, their significant findings support the efficacy of ON-SXB in patients with NT1 or NT2 and augment the limited data available on treatments for NT2.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.