1. Randomized Controlled Trial of Solriamfetol for Excessive Daytime Sleepiness in OSA
- Author
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Paula K. Schweitzer, Atul Malhotra, Mark H. Gotfried, Russell Rosenberg, Geert Mayer, Kingman P. Strohl, Gary Zammit, Patricia Chandler, and Michelle G. Baladi
- Subjects
Male ,Health Status ,Excessive daytime sleepiness ,mITT, modified intention-to-treat ,Critical Care and Intensive Care Medicine ,law.invention ,Randomized controlled trial ,law ,Medicine ,Sleep Apnea, Obstructive ,education.field_of_study ,Epworth Sleepiness Scale ,EDS, excessive daytime sleepiness ,Sleep apnea ,Middle Aged ,sleep apnea ,JZP-110 ,Female ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,AE, adverse event ,Adult ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Adolescent ,Phenylalanine ,Oral appliance ,Population ,Disorders of Excessive Somnolence ,Placebo ,ESS, Epworth Sleepiness Scale ,MWT, Maintenance of Wakefulness Test ,Young Adult ,Double-Blind Method ,Internal medicine ,FOSQ-10, Functional Outcomes of Sleep Questionnaire short version ,Sleep: Original Research ,Humans ,Wakefulness ,education ,Aged ,Intention-to-treat analysis ,business.industry ,medicine.disease ,obstructive sleep apnea syndromes ,Patient Compliance ,Carbamates ,Sleep ,business ,PAP, positive airway pressure ,PGI-C, Patient Global Impression of Change - Abstract
Background Solriamfetol, a dopamine-norepinephrine reuptake inhibitor, is approved in the United States to improve wakefulness in adults with excessive daytime sleepiness (EDS) associated with OSA (37.5-150 mg/d). Research Question Does solriamfetol have differential effects on EDS based on adherence to primary OSA therapy and does solriamfetol affect primary OSA therapy use? Study Design and Methods Participants were randomized to 12 weeks of placebo or solriamfetol 37.5, 75, 150, or 300 mg/d (stratified by primary OSA therapy adherence). Coprimary end points were week 12 change from baseline in 40-min Maintenance of Wakefulness Test (MWT) and Epworth Sleepiness Scale (ESS) in the modified intention-to-treat population. Primary OSA therapy use (hours per night, % nights) and safety were evaluated. Results At baseline, 324 participants (70.6%) adhered to OSA therapy (positive airway pressure use ≥ 4 h/night on ≥ 70% nights, surgical intervention, or oral appliance use on ≥ 70% nights) and 135 participants (29.4%) did not adhere. Least squares (LS) mean differences from placebo in MWT sleep latency (minutes) in the 37.5-, 75-, 150-, and 300-mg/d groups among adherent participants were 4.8 (95% CI, 0.6-9.0), 8.4 (95% CI, 4.3-12.5), 10.2 (95% CI, 6.8-13.6), and 12.5 (95% CI, 9.0-15.9) and among nonadherent participants were 3.7 (95% CI, –2.0 to 9.4), 9.9 (95% CI, 4.4-15.4), 11.9 (95% CI, 7.5-16.3), and 13.5 (95% CI, 8.8-18.3). On ESS, LS mean differences from placebo in the 37.5-, 75-, 150-, and 300-mg/d groups among adherent participants were –2.4 (95% CI, –4.2 to –0.5), –1.3 (95% CI, –3.1 to 0.5), –4.2 (95% CI, –5.7 to –2.7), and –4.7 (95% CI, –6.1 to –3.2) and among nonadherent participants were –0.7 (95% CI, –3.5 to 2.1), –2.6 (95% CI, –5.4 to 0.1), –5.0 (95% CI, –7.2 to –2.9), and –4.6 (95% CI, –7.0 to –2.3). Common adverse events included headache, nausea, anxiety, decreased appetite, nasopharyngitis, and diarrhea. No clinically meaningful changes were seen in primary OSA therapy use with solriamfetol. Interpretation Solriamfetol improved EDS in OSA regardless of primary OSA therapy adherence. Primary OSA therapy use was unaffected with solriamfetol. Trial Registry ClinicalTrials.gov; No.: NCT02348606; URL: www.clinicaltrials.gov; EU Clinical Trials Register; No.: EudraCT2014-005514-31; URL: www.clinicaltrialsregister.eu, Graphical abstract
- Published
- 2021
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