Patrick J Strollo1, Jan Hedner2, Nancy Collop3, Daniel G Lorch4, Dan Chen5, Lawrence P Carter6, Yuan Lu5, Lawrence Lee5, Jed Black7, Jean-Louis Pépin8, Susan Redline9. 1. From the University of Pittsburgh/Veterans Administration Pittsburgh Health System, Pittsburgh, PA. Electronic address: strollopj@upmc.edu. 2. Sahlgrenska University Hospital, Gothenberg University, Gothenberg, Sweden. 3. Emory Sleep Center, Emory University, Atlanta, GA. 4. PAB Clinical Research/Florida Sleep Disorder Center, Brandon, FL. 5. Jazz Pharmaceuticals plc, Palo Alto, CA. 6. Jazz Pharmaceuticals plc, Palo Alto, CA; University of Arkansas for Medical Sciences, Little Rock, AR. 7. Jazz Pharmaceuticals plc, Palo Alto, CA; Stanford University Center for Sleep Sciences and Medicine, Redwood City, CA. 8. INSERM U1042, Grenoble Alpes University Hospital, Grenoble, France. 9. Brigham and Women's Hospital and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
Abstract
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.
RCT Entities:
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.
Authors: Winfried Randerath; Jan de Lange; Jan Hedner; Jean Pierre T F Ho; Marie Marklund; Sofia Schiza; Jörg Steier; Johan Verbraecken Journal: ERJ Open Res Date: 2022-06-27
Authors: Russell Rosenberg; Michael J Thorpy; Yves Dauvilliers; Paula K Schweitzer; Gary Zammit; Mark Gotfried; Shay Bujanover; Brian Scheckner; Atul Malhotra Journal: J Clin Sleep Med Date: 2022-01-01 Impact factor: 4.062
Authors: Paula K Schweitzer; Kingman P Strohl; Geert Mayer; Russell Rosenberg; Patricia Chandler; Michelle Baladi; Lawrence Lee; Atul Malhotra Journal: J Clin Sleep Med Date: 2021-04-01 Impact factor: 4.062