1007 Solriamfetol on Cognition in Obstructive Sleep Apnea with Excessive Daytime Sleepiness and Impaired Cognition

Abstract Introduction Cognitive impairment is a burdensome symptom in many patients with excessive daytime sleepiness (EDS) associated with obstructive sleep apnea (OSA). Solriamfetol (Sunosi®) is a dopamine/norepinephrine reuptake inhibitor, with agonistic properties at TAAR1 and serotonin 1A receptors, approved to treat EDS associated with OSA (37.5–150 mg/day). We evaluated the effect of solriamfetol on subjective cognitive function by examining overall scores and individual cognitive complaint and functional items of the British Columbia-Cognitive Complaints Inventory (BC-CCI). Methods SHARP was a randomized, double-blind, placebo-controlled, crossover trial in participants with impaired cognition associated with OSA and EDS. Participants received solriamfetol for 2 weeks (75 mg for 3 days, then 150 mg/day), and placebo for 2 weeks, separated by a 1-week wash out. Items of the BC-CCI included forgetfulness/memory problems, slow thinking speed, trouble expressing thoughts, trouble finding the right word, poor concentration, trouble figuring things out, and vocational, family/friends, and social/recreational functioning. Mixed models with repeated measures were used to examine differences in changes from baseline between placebo and solriamfetol. Results The SHARP study enrolled 59 participants (ages 52.2±10.7y; 36% female). Baseline overall BC-CCI scores were 11.4±2.5 (mean±SD); scores were comparable in participants randomized to the solriamfetol/placebo (n=30; mean=11.4) versus placebo/solriamfetol (n=29; mean=11.4) crossover sequences. Overall BC-CCI scores showed greater reduction from baseline (ie, more improvement in subjective cognitive function) after solriamfetol compared with place bo (P=0.002; Cohen’s d=0.45). Baseline scores on individual BC-CCI items were generally similar for participants randomized to solriamfetol/placebo versus placebo/solriamfetol. Solriamfetol led to greater reductions from baseline compared with placebo in poor concentration (P=0.007; d=0.37), slow thinking speed (P=0.009; d=0.36), trouble finding the right word (P=0.042; d=0.28), trouble figuring things out (P=0.030; d=0.30), and forgetfulness/memory problems (P=0.013; d=0.34). Trouble expressing thoughts approached significance (P=0.077; d=0.24). No significant differences were found for vocational, family/friends, and social/recreational functioning (P>0.05). Conclusion Consistent with previous reports showing improvement on objective cognitive measures, solriamfetol led to significant subjective improvements overall, and particularly in subjective cognitive domains that may be related to memory, executive functioning, and processing speed. Solriamfetol can improve subjective cognitive functioning in participants with impaired cognition associated with OSA and EDS. Support (if any) Axsome Therapeutics, Jazz Pharmaceuticals