0644 A PHASE 3, PLACEBO-CONTROLLED, RANDOMIZED-WITHDRAWAL, DOUBLE-BLIND, 6-WEEK MULTICENTER STUDY OF THE SAFETY AND EFFICACY OF JZP-110 FOR THE TREATMENT OF EXCESSIVE SLEEPINESS IN PARTICIPANTS WITH OBSTRUCTIVE SLEEP APNEA

• Published in: Sleep (New York, N.Y.) Vol. 40; no. suppl_1; p. A238
• Main Authors: Strollo, PJ, Redline, S, Hedner, H, Collop, N, Lorch, DG, Chen, D, Li, J, Carter, LP, Lu, Y, Black, J, Pepin, JL
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 28.04.2017
• Subjects: Double-blind studies; Sleep apnea; Standard deviation
• ISSN: 0161-8105; 1550-9109
• DOI: 10.1093/sleepj/zsx050.643

Abstract Introduction: Patients with obstructive sleep apnea (OSA) may experience excessive sleepiness (ES) despite use of a primary OSA therapy. JZP-110 is a selective dopamine and norepinephrine reuptake inhibitor with wake-promoting effects. This phase 3 study assessed the safety and efficacy of JZP-110 for treatment of ES in adults with OSA. Methods: Eligibility criteria for this study included a diagnosis of OSA per International Classification of Sleep Disorders-3 criteria; Epworth Sleepiness Scale (ESS) score ≥10; mean sleep latency <30 minutes on the first 4 trials of a 5-trial, 40-minute Maintenance of Wakefulness Test (MWT); and current/past use of a primary OSA therapy. Participants were initiated on once-daily 75-mg JZP-110 and titrated open-label to a maximum tolerated once-daily dose of 75mg, 150mg, or 300mg (weeks 1–2), which was continued for the subsequent 2 weeks. At week 4, participants who reported “much” or “very much” improvement on the Patient Global Impression of Change (PGI-C) scale and improvement on MWT and ESS were randomized 1:1 to placebo or the same dose of JZP-110 for 2 weeks. Co-primary endpoints were the change from week 4 to 6 in MWT mean sleep latency and ESS score; PGI-C was a key secondary endpoint. Safety and tolerability were also evaluated. Results: Preliminary demographics for the 162 (of 176 enrolled) participants were 59.3% male, 78.4% white, and age 55.7 ± 10.7 years (mean±standard deviation). Baseline mean±standard deviation MWT and ESS scores were 12.2 ± 6.7 minutes and 15.5 ± 3.4, respectively; 126 of 176 participants met improvement criteria at week 4 and advanced to the randomized withdrawal period. Enrollment was completed by September 2016 and data are being analyzed. Conclusion: Seventy-two percent of OSA participants in this study had numerical improvement (as measured by PGI-C, MWT, and ESS) after 4 weeks of open-label treatment with JZP-110. Support (If Any): Jazz Pharmaceuticals