Results of the SHARP Study: A Randomized, Placebo-Controlled, Double-Blind, Repeated-Measures, Crossover, Phase IV Clinical Trial of the Effect of the Wake-Promoting Agent Solriamfetol on Cognitive Function in OSA With Excessive Daytime Sleepiness and Cognitive Impairment.

Abstract

Background: OSA causes episodes of fragmented sleep and intermittent hypoxia and leads to excessive daytime sleepiness (EDS). Deficits in cognitive function are a troublesome symptom in patients with OSA and EDS.

Research question: How does solriamfetol affect cognitive function in patients with cognitive impairment associated with OSA and EDS?.

Study design and methods: Solriamfetol's Effect on Cognitive Health in Apnea Participants During a Randomized Placebo-controlled Study (SHARP) was a phase IV, randomized, double-blind, placebo-controlled, crossover trial. Participants (N = 59) were randomized to receive placebo or solriamfetol (75 mg/d for 3 days, then 150 mg/d) for 2 weeks, with crossover separated by a 1-week washout period. Efficacy measures included the Coding subtest, comparable to the Digit Symbol Substitution Test (DSST), of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), the British Columbia Cognitive Complaints Inventory (BC-CCI), Patient Global Impression of Severity (PGI-S), and the Epworth Sleepiness Scale (ESS). The primary end point was change from baseline in average postdose DSST RBANS scores. Secondary end points were changes from baseline in BC-CCI, PGI-S, ESS, and DSST RBANS scores at 2, 4, 6, and 8 hours' postdose. Safety was monitored by assessment of treatment-emergent adverse events.

Results: Solriamfetol significantly improved postdose average DSST RBANS scores compared with placebo (P = .009; effect size [Cohen's d], 0.37). When evaluated at each 2-hour time point, cognitive function was significantly improved at 2, 6, and 8 hours after dosing (all, P < .05). During solriamfetol treatment, there were significant improvements in BC-CCI (P = .002; d = 0.45), PGI-S (P = 0.0mixed; d = 0.29), and ESS (P = .004; d = 0.40) compared with placebo. The most common treatment-emergent adverse events were nausea (7%) and anxiety (3%).

Interpretation: SHARP showed that solriamfetol can improve objective and subjective measures of cognitive function in patients with cognitive impairment associated with OSA and EDS.

Clinical trial registration: ClinicalTrials.gov; No.: NCT04789174; ;URL: www.

Clinicaltrials: gov and EudraCT; No.: 2020-004243-92; URL: https://eudract.ema.europa.eu.