Solriamfetol for the Treatment of Excessive Sleepiness in OSA: A Placebo-Controlled Randomized Withdrawal Study.
Strollo, Patrick J. Jr. MD a, *; Hedner, Jan MD b; Collop, Nancy MD c; Lorch, Daniel G. Jr. MD d; Chen, Dan MD, PhD e; Carter, Lawrence P. PhD e, f; Lu, Yuan MS e; Lee, Lawrence PhD e; Black, Jed MD e, g; Pepin, Jean-Louis MD h; Redline, Susan MD, MPH i; Tones 4 Study Investigators; Partinen, Markku MD; Polo, Olli MD; Saaresranta, Tarja MD; Paschen, Christine MD; Leissner, Lena MD; Block, Bradley MD; Collop, Nancy MD; Doekel, Robert MD; Duntley, Stephen MD; Giangreco, Guillermo MD; Givelber, Rachel MD; Krystal, Andrew MD; Lal, Chitra MD; Lee, Mitchell MD; Maynard, James MD; Norman, Daniel MD; Redline, Susan MD; Rosenberg, Russell PhD; Rowe, Vernon MD; Sarmiento, Kathleen MD; Schreiber, Andrew MD; Schwab, Richard MD; Seiden, David MD; Shamsnia, Morteza MD; Ware, Catesby J. PhD
[Article]
Chest.
155(2):364-374, February 2019.
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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
(C) 2019Elsevier, Inc.
