Effects of Solriamfetol on Cognition in Participants with Cognitive Impairment Associated with Excessive Daytime Sleepiness in Obstructive Sleep Apnea: SHARP Study Results

This work was sponsored by Axsome Therapeutics and Jazz Pharmaceuticals Purpose: SHARP evaluated the effects of solriamfetol on cognitive function in patients with cognitive impairment associated with obstructive sleep apnea (OSA)and excessive daytime sleepiness (EDS). Solriamfetol (Sunosi®) is currently indicated to improve wakefulness in adults with EDS and OSA. Methods: SHARP was a randomized, double-blind, placebo-controlled, crossover trial in 59 patients with cognitive impairment associated OSA-and EDS. Patients received solriamfetol (150mg/day) for 2 weeks, and placebo for 2 weeks, with a 1-week washout. Efficacy was evaluated using the Coding subtest, a version of the Digit Symbol Substitution Test in the Repeatable Battery for the Assessment of Neuropsychological Status (DSST RBANS), the British Columbia Cognitive Complaints Inventory (BC-CCI), and Patient Global Impression of Severity (PGI-S). The Epworth Sleepiness Scale (ESS) was used to measure sleepiness. The primary endpoint was change from baseline in average post-dose DSST RBANS scores. Key secondary endpoints were change from baseline in BC-CCI, PGI-S, and ESS scores. Safety was also monitored. Results: Solriamfetol improved DSST RBANS scores compared to placebo (6.49 vs. 4.75, p=0.009), with an effect size (Cohen’s d) of 0.36. During solriamfetol treatment, there were significant improvements in BC-CCI (P=0.002; d=0.45), PGI-S (P=0.034; d=0.29), and ESS (P=0.004; d=0.40) compared with placebo. Conclusions: Solriamfetol (150mg/day) improved objective and subjective measures of cognition in patients with cognitive impairment associated with OSA and EDS. The adverse events profile and high completion rate suggest solriamfetol was well tolerated. These findings support the use of solriamfetol to improve cognitive performance in patients with cognitive impairment associated with OSA and EDS.