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

BACKGROUND: Solriamfetol, a dopamine-norepinephrine reuptake inhibitor, is approved in the United States to improve wakefulness in adults with excessive daytime sleepiness (EDS) associated with 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 use? 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 end points were week 12 change from baseline in 40-min Maintenance of Wakefulness Test (MWT) and Epworth Sleepiness Scale (ESS) in the modified intention-to-treat population. Primary OSA therapy use (hours per night, % nights) and safety were evaluated. RESULTS: At baseline, 324 participants (70.6%) adhered to OSA therapy (positive airway pressure use ≥ 4 h/night on ≥ 70% nights, surgical intervention, or oral appliance use on ≥ 70% nights) and 135 participants (29.4%) did not adhere. Least squares (LS) mean differences from placebo in MWT sleep latency (minutes) in the 37.5-, 75-, 150-, and 300-mg/d groups among adherent participants were 4.8 (95% CI, 0.6-9.0), 8.4 (95% CI, 4.3-12.5), 10.2 (95% CI, 6.8-13.6), and 12.5 (95% CI, 9.0-15.9) and among nonadherent participants were 3.7 (95% CI, –2.0 to 9.4), 9.9 (95% CI, 4.4-15.4), 11.9 (95% CI, 7.5-16.3), and 13.5 (95% CI, 8.8-18.3). On ESS, LS mean differences from placebo in the 37.5-, 75-, 150-, and 300-mg/d groups among adherent participants were –2.4 (95% CI, –4.2 to –0.5), –1.3 (95% CI, –3.1 to 0.5), –4.2 (95% CI, –5.7 to –2.7), and –4.7 (95% CI, –6.1 to –3.2) and among nonadherent participants were –0.7 (95% CI, –3.5 to 2.1), –2.6 (95% CI, –5.4 to 0.1), –5.0 (95% CI, –7.2 to –2.9), and –4.6 (95% CI, –7.0 to –2.3). Common adverse events included headache, nausea, anxiety, decreased appetite, nasopharyngitis, and 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. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02348606; URL: www.clinicaltrials.gov; EU Clinical Trials Register; No.: EudraCT2014-005514-31; URL: www.clinicaltrialsregister.eu