Effects of Solriamfetol on Cognitive Function in Participants with Cognitive Impairment Associated with Excessive Daytime Sleepiness in Obstructive Sleep Apnea: Results of the SHARP Study
Hans Van Dongen1, Eileen Leary2, Christopher Drake3, Richard Bogan4, Judith Jaeger5, Russell Rosenberg6, Caroline Streicher7, Hannah Kwak7, Jay Bates7, Herriot Tabuteau7
1Translational Medicine and Physiology; Sleep and Performance Research Center, Washington State University, 2Jazz Pharmaceuticals, 3Henry Ford Health System, 4SleepMed, 5CognitionMetrics, 6Neurotrials Research, 7Axsome Therapeutics
Objective:
The SHARP study evaluated whether solriamfetol improves cognitive function in patients with excessive daytime sleepiness (EDS) associated with obstructive sleep apnea (OSA) and extant impaired cognition.
Background:
OSA is a common disorder characterized by repeated intermittent hypoxic events resulting in disrupted sleep and EDS. Positive Airway Pressure (PAP) reduces hypoxic events and mitigates sleep disruption, but EDS often persists. Cognitive impairment is a burdensome symptom in many patients with EDS associated with OSA, which leads to occupational and social dysfunction and degrades quality of life. Solriamfetol (Sunosi®) is approved to improve wakefulness in adults with EDS associated with OSA. In nonclinical pharmacology studies, solriamfetol inhibited dopamine/norepinephrine reuptake and activated trace amine-associated receptor 1 (TAAR1), potentially benefiting cognition.
Design/Methods:
SHARP was a randomized, double-blind, placebo-controlled, crossover trial in 59 patients with EDS associated with OSA and demonstrated cognitive impairment. All patients received solriamfetol (75mg for 3 days followed by 150mg/day) for 2 weeks, and placebo for 2 weeks, with treatment periods separated by a 1-week washout. The primary endpoint was change from baseline on the Digit Symbol Substitution Test equivalent of the Repeatable Battery for the Assessment of Neuropsychological Status (DSST-RBANS). Secondary endpoints included change from baseline on the British Columbia Cognitive Complaints Inventory (BC-CCI) and the Epworth Sleepiness Scale (ESS).
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. Solriamfetol treatment also yielded improvements on the BC-CCI (-4.70 vs -3.11, p=0.002; d =0.43) and the ESS (-4.41 vs -2.31, p=0.004; d = 0.50). The most common adverse events with solriamfetol treatment (incidence ≥3%) were nausea (6.9%) and anxiety (3.4%).
Conclusions:
Solriamfetol (150mg/day) improved both objective and subjective measures of cognitive function in patients with EDS associated with OSA and impaired cognition.