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

Chest. 2019 Feb;155(2):364-374. doi: 10.1016/j.chest.2018.11.005. Epub 2018 Nov 22.


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:; No.: NCT02348619; URL:; EudraCT No.: 2014-005515-16.

Keywords: JZP-110; OSA; TONES 4; excessive sleepiness; obstructive sleep apnea; solriamfetol.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carbamates / therapeutic use*
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Middle Aged
  • Phenylalanine / analogs & derivatives
  • Sleep Apnea, Obstructive / complications*
  • Sleep Apnea, Obstructive / drug therapy*
  • Sleepiness*
  • Treatment Outcome
  • Wakefulness


  • Carbamates
  • Phenylalanine
  • solriamfetol

Associated data

  • EudraCT/2014-005515-16