Solriamfetol for the Treatment of Excessive Sleepiness in OSA: A Placebo-Controlled Randomized Withdrawal Study

[摘要] Background Excessive sleepiness (ES) is a common symptom of OSA, which often persists despite primary OSA therapy. This phase III randomized withdrawal trial evaluated solriamfetol (JZP-110) for the treatment of ES in adults with OSA. Methods After 2 weeks of clinical titration (n = 174) and 2 weeks of stable dose administration (n = 148), participants who reported improvement on the Patient Global Impression of Change (PGI-C) and had numerical improvements on the Maintenance of Wakefulness Test (MWT) and Epworth Sleepiness Scale (ESS) were randomly assigned to placebo (n = 62) or solriamfetol (n = 62) for 2 additional weeks. Coprimary end points were change from weeks 4 to 6 in MWT and ESS. Results In the modified intention-to-treat population (n = 122), MWT mean sleep latencies and ESS scores improved from baseline to week 4 (from 12.3-13.1 to 29.0-31.7 minutes and from 15.3-16.0 to 5.9-6.4, respectively). From weeks 4 to 6, participants treated with solriamfetol maintained improvements (least squares [LS] mean [SE] changes of −1.0 [1.4] minutes on MWT and −0.1 [0.7] on ESS), whereas participants treated with placebo worsened (LS mean [SE] change of −12.1 [1.3] minutes on MWT and 4.5 [0.7] on ESS); LS mean differences between treatments were 11.2 minutes (95% CI, 7.8-14.6) and −4.6 (95% CI, −6.4 to −2.8) on MWT and ESS, respectively. Fewer participants treated with solriamfetol reported worsening on the PGI-C from weeks 4 to 6 (20% vs 50%; P = .0005). Common adverse events included headache, dry mouth, nausea, dizziness, and insomnia. Conclusions This study demonstrated maintenance of solriamfetol efficacy and safety over 6 weeks. Trial Registry ClinicalTrials.gov; No.: NCT02348619; URL: www.clinicaltrials.gov; EudraCT No.: 2014-005515-16

[学科分类] 呼吸医学

[关键词] excessive sleepiness;JZP-110;obstructive sleep apnea;OSA;solriamfetol;TONES 4;CGI-C;Clinical Global Impression of Change;ES;excessive sleepiness;ESS;Epworth Sleepiness Scale;FOSQ-10;10-item Functional Outcomes of Sleep Questionnaire;LS;least squares;mITT;modified intention to treat;MWT;Maintenance of Wakefulness Test;PGI-C;Patient Global Impression of Change