Randomized Controlled Trial of Solriamfetol for Excessive Daytime Sleepiness in Obstructive Sleep Apnea: An Analysis of Subgroups Adherent or Nonadherent to Obstructive Sleep Apnea Treatment

ABSTRACT Background Solriamfetol, a dopamine-norepinephrine reuptake inhibitor, is approved in the USA to improve wakefulness in adults with excessive daytime sleepiness (EDS) associated with obstructive sleep apnea (OSA) (37.5-150 mg/d). Research Question Does solriamfetol have differential effects on EDS based on adherence to primary OSA therapy and does solriamfetol affect primary OSA therapy usage? Study Design and Methods Participants were randomized to 12 weeks of placebo or solriamfetol 37.5, 75, 150, or 300 mg/d (stratified by primary OSA therapy adherence). Coprimary endpoints: week-12 change from baseline in Maintenance of Wakefulness Test (40-minute MWT) and Epworth Sleepiness Scale (ESS) in the modified intent-to-treat population. Primary OSA therapy use (hours/night, % nights) and safety were evaluated. Results At baseline, 324 (70.6%) participants were adherent (positive airway pressure use ≥4 hours/night on ≥70% nights, surgical intervention, or oral appliance use on ≥70% nights) and 135 (29.4%) nonadherent. Least squares (LS) mean differences (95% CI) from placebo in MWT sleep latency (minutes) in the 37.5-, 75-, 150-, and 300-mg groups among adherent participants were 4.8 (0.6, 9.0), 8.4 (4.3, 12.5), 10.2 (6.8, 13.6), 12.5 (9.0, 15.9) and among nonadherent participants were 3.7 (-2.0, 9.4), 9.9 (4.4, 15.4), 11.9 (7.5, 16.3), 13.5 (8.8, 18.3). On ESS, LS mean differences (95% CI) from placebo in the 37.5-, 75-, 150-, and 300-mg groups among adherent participants were -2.4 (-4.2, -0.5), -1.3 (-3.1, 0.5), -4.2 (-5.7, -2.7), -4.7 (-6.1, -3.2) and among nonadherent participants were -0.7 (-3.5, 2.1), -2.6 (-5.4, 0.1), -5.0 (-7.2, -2.9), -4.6 (-7.0, -2.3). Common adverse events: headache, nausea, anxiety, decreased appetite, nasopharyngitis, diarrhea. No clinically meaningful changes were seen in primary OSA therapy use with solriamfetol. Interpretation Solriamfetol improved EDS in OSA regardless of primary OSA therapy adherence. Primary OSA therapy use was unaffected with solriamfetol.