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A4396 - Excessive Sleepiness Treated with Solriamfetol in a Phase 3 Study of Participants with Obstructive Sleep Apnea: Stratification by Adherence or Nonadherence to Primary Obstructive Sleep Apnea Therapy
Author Block: P. Schweitzer1, R. Rosenberg2, A. Malhotra3, G. Zammit4, M. H. Gotfried5, D. Chen6, J. Li6, L. Carter7, J. Black8, R. Ryan6, K. P. Strohl9; 1Sleep Medicine and Research Center, St. Luke’s Hospital, Chesterfield, MO, United States, 2NeuroTrials Research and Atlanta School of Sleep Medicine, Atlanta, GA, United States, 3Univeristy of California, San Diego, CA, United States, 4Clinilabs, Inc.; Icahn School of Medicine at Mount Sinai, New York, NY, United States, 5Pulmonary Associates, PA, Phoenix, AZ, United States, 6Jazz Pharmaceuticals, Palo Alto, CA, United States, 7Jazz Pharmaceuticals; University of Arkansas for Medical Sciences, Palo Alto, CA, United States, 8Jazz Pharmaceuticals; Stanford Center for Sleep Sciences and Medicine, Palo Alto, CA, United States, 9Case Western Reserve University, Cleveland, OH, United States.
Rationale: Excessive sleepiness (ES) is common in obstructive sleep apnea (OSA) despite the use of primary OSA therapy. Solriamfetol is a dopamine/norepinephrine reuptake inhibitor with wake-promoting effects in narcolepsy and OSA. This analysis evaluated solriamfetol treatment in participants with OSA stratified by adherence or nonadherence to primary OSA therapy.
Methods: Participants with OSA and ES randomized to 12 weeks of treatment with placebo or solriamfetol 37.5-mg, 75-mg, 150-mg, or 300-mg once daily were stratified according to adherence/nonadherence to primary OSA therapy (continuous positive airway pressure, oral appliance, oral pressure therapy, or surgical intervention for obstruction). Adherence was defined as use ≥4 hours/night on >70% of nights for devices with downloadable data and >70% of nights for devices without downloadable data. Primary endpoints: change from baseline to week 12 in Maintenance of Wakefulness Test (40-minute MWT) and Epworth Sleepiness Scale (ESS); secondary endpoint: improvement at week 12 in Patient Global Impression of Change (PGI-C); additional secondary endpoints: change from baseline to week 12 in Functional Outcomes of Sleep Questionnaire short version (FOSQ-10), and primary OSA therapy adherence (number of hours per night and percentage of nights used from baseline to week 12).
Results: At study entry, 324 (70.6%) participants were adherent and 135 (29.4%) were nonadherent with primary OSA therapy. At baseline, there were no clinically meaningful differences in age, sex, body mass index, or ESS scores in adherent/nonadherent subgroups across treatment. The nonadherent group had slightly shorter baseline MWT sleep latency across treatment groups (10.31-11.19 minutes) compared to the adherent group (12.78-14.91 minutes). In both subgroups, solriamfetol was shown to have robust wake-promoting effects with dose-dependent increases in MWT, PGI-C, and FOSQ-10 scores, and dose-dependent decreases in ESS scores from baseline to week 12. Responses to solriamfetol were numerically similar between the adherent and nonadherent subgroups. As in previous studies, the most common treatment-emergent adverse events observed with solriamfetol were nausea, decreased appetite, headache, and anxiety in both adherent and nonadherent subgroups. There were no major changes in adherence to OSA therapy from baseline to week 12 in either subgroup.
Conclusions: Solriamfetol was effective in the treatment of ES in OSA regardless of adherence or nonadherence to OSA therapy. The safety and tolerability of solriamfetol were consistent with previously reported studies and were similar in both subgroups. Solriamfetol did not adversely affect adherence to OSA therapy across the 12 weeks of this study.