Effects of solriamfetol on cognition in participants with cognitive impairment associated with excessive daytime sleepiness in obstructive sleep apnea: SHARP study results

Document Type

Conference Proceeding

Publication Date

2-1-2024

Publication Title

Sleep Med

Abstract

Introduction: The SHARP study evaluated whether solriamfetol improves cognitive function in patients with obstructive sleep apnea (OSA) experiencing excessive daytime sleepiness (EDS) and extant impaired cognition. OSA is characterized by repeated intermittent airway collapse resulting in disrupted sleep and excessive daytime sleepiness (EDS). EDS often persists even with Positive Airway Pressure (PAP) therapy. Cognitive impairment is a burdensome symptom in many patients with OSA and EDS, leading to occupational and social dysfunction and degraded quality of life. Solriamfetol (Sunosi®) is approved in the U.S., Canada, and Europe to improve wakefulness in adults with OSA and EDS; its effect on cognitive impairment was not previously assessed. Methods: SHARP (NCT04789174) was a randomized, double-blind, placebo-controlled, crossover trial in 59 patients with OSA and EDS and concurrent cognitive impairment. All patients received solriamfetol (75 mg for 3 days followed by 150 mg/day) for 2 weeks, and placebo for 2 weeks, with treatment periods separated by a 1-week washout. The primary endpoint was the score on the Coding Subtest (a variation of the Digit Symbol Substitution Test) of the Repeatable Battery for the Assessment of Neuropsychological Status (DSST RBANS) at the end of each treatment period, averaged across 2, 4, 6, and 8 hour time points post-dose. Secondary endpoints included DSST RBANS scores at each of the individual time points, as well as scores on the British Columbia Cognitive Complaints Inventory (BC-CCI), the Epworth Sleepiness Scale (ESS), and a Patient Global Impression of Severity (PGI-S) scale measuring perceived symptom severity. All endpoints were expressed relative to baseline. Results: The study completion rate was 96.7%. Solriamfetol treatment improved performance on the DSST RBANS compared to placebo (6.49 vs. 4.75, p=0.009), with an effect size (Cohen’s d) of 0.36. Across individual time points, solriamfetol yielded DSST-RBANS score improvements (solriamfetol–placebo difference) at 2 hours (1.91, p=0.033), 4 hours (1.38, p=0.089; not significant), 6 hours (2.33, p=0.004), and 8 hours (1.58, p=0.022) post-dose. There were improvements in self-reported cognitive complaints and daytime sleepiness in the solriamfetol group compared to the placebo group, as measured by the BC-CCI (-4.70 vs -3.11, d=0.43, p=0.002) and the ESS (-4.41 vs -2.31, d=0.50, p=0.004), respectively. Scores on the PGI-S improved with solriamfetol compared to placebo (-0.90 vs -0.61, p=0.034). The most common adverse events with solriamfetol were nausea (6.9%) and anxiety (3.4%). Conclusions: Solriamfetol (150 mg/day) improved objective and subjective measures of cognitive function in patients with impaired cognition associated with OSA and EDS and exhibited sustained effects over an 8-hour period while reducing perceived symptom severity. The adverse events profile and high study completion rate suggest solriamfetol was well tolerated. These findings support the use of solriamfetol to improve cognitive performance and daytime sleepiness through the day in patients with cognitive impairment associated with OSA and EDS. Support, Axsome Therapeutics and Jazz Pharmaceuticals

Volume

115

First Page

75

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