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

: Strollo PJ, Hedner J, Collop N, Lorch DG, Chen D, Carter LP, Lu Y, Lee L, Black J, Pepin JL, Redline S, Partinen M, Polo O, Saaresranta T, Paschen C, Leissner L, Block B, Doekel R, Duntley S, Giangreco G, Givelber R, Krystal A, Lal C, Lee M, Maynard J, Norman D, Rosenberg R, Rowe V, Sarmiento K, Schreiber A, Schwab R, Seiden D, Shamsnia M, Ware JC, Ware JC

Publisher: ELSEVIER SCIENCE BV

: 2019

: Chest

: CHEST

: 155

: 2

: 364

: 374

: 11

: 0012-3692

: 1931-3543

DOI: https://doi.org/10.1016/j.chest.2018.11.005

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.METHOD 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.RESULTF: 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.