Safety and Efficacy of Solriamfetol for the Treatment of Excessive Daytime Sleepiness in Parkinson’s Disease in a Four-Week Double-blind, Placebo-controlled Randomized Crossover Study (P3.8-036)

Objective: To evaluate the safety (primary objective) and efficacy of solriamfetol for the treatment of excessive daytime sleepiness (EDS) in participants with Parkinson’s Disease (PD). Background: EDS affects up to 50% of PD patients. Solriamfetol, a selective dopamine and norepinephrine reuptake inhibitor, significantly reduced EDS in Phase 3 clinical studies of narcolepsy and obstructive sleep apnea patients, and has not been studied in PD. Design/Methods: This is a phase 2 double-blind, placebo-controlled, randomized, crossover clinical trial of participants 35–80 years of age, diagnosed with idiopathic PD according to the UK PDS Brain Bank Criteria, Hoehn and Yahr stage ≤3, on a stable PD treatment regimen, and with an Epworth Sleepiness Scale (ESS) score >10. Participants were randomized (3:3:1) to three sequence groups (A, B, and C) for a four-week treatment period. Participants assigned to sequence A or B received one week of placebo and solriamfetol 75 mg, 150 mg, and 300 mg; those in sequence C received placebo all four weeks. The primary objective of the study was to assess safety and tolerability by adverse events, physical exams, electrocardiograms, laboratory tests, vital signs and Columbia-Suicide Severity Rating Scale (C-SSRS). The key efficacy endpoint was change in ESS score. Exploratory endpoints included MDS-UPDRS Parts III and IV, Global Impression of Change, and scales for apathy, fatigue severity (FSS), and Cognition (SCOPA-Cog). Results: Sixty-six participants were randomized (mean [SD] age, 64.6 [8.5]; 68.2% male). Mean (SD) duration of PD was 6.4 (4.4) years. At baseline, 75.8% of participants were Hoehn and Yahr stage 2 and 19.7% were stage 3, and mean (SD) ESS total score was 16.1 (2.9). Completion of this study occurred in August 2018. Conclusions: Study participants had mild-moderate PD with moderate to severe EDS. Final safety and efficacy data will be available for presentation at the 2019 annual AAN meeting. Disclosure: Dr. Videnovic has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Pfizer, Acorda, and Wilsons Therapeutics. Dr. Amara has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Jazz Pharmaceuticals and Grey Matter Technologies. Dr. Amara has received research support from Parkinson’s Disease Foundation and serves as site investigator for studies sponsored by the Michael J. Fox Foundation for Parkinson’s Research, Abbvie, Axovant Neurological Solutions, and Jazz Pharmaceuticals. Dr. Comella has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merz Pharmaceutical, Revance Therapeutic, Retrophin Therapeutic. Dr. Comella receives compensation for services as a consultant or an advisory committee member: Acorda Therapeutics, Allergan, Inc; Lundbeck Ltd.; Medtronic Inc.; Merz Pharmaceuticals; Acadia Pharmaceuticals; Jazz Pharmaceuticals, Neurocrine Biosciences Inc., Revance Therapeutic. Dr. Comella receives royalties from Cambridge, Wolters Kluwer. Dr. Comella has received research support from Acorda, Revance, Merz, Eisai, Jazz Pharmacuetical, Parkinson’s Foundation. Dr. Schweitzer has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Jazz Pharmaceuticals. Dr. Schweitzer has received research support from Jazz Pharmaceuticals, NightBalance, Balance Therapeutics, and Flamel/Avadel Pharmaceuticals. Dr. Emsellem has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Jazz Pharmaceuticals, Harmony Bioscience and Vanda Pharmaceuticals. Dr. Emsellem has received compensation for serving on the Board of Directors of National Sleep Foundation. Dr. Emsellem has received research support from Jazz Pharmaceuticals, Vanda Pharmaceuticals, NightBalance, Harmony Bioscience, Eisai Pharmaceuticals, Flamel/Avadel Pharmaceuticals, Idorsia Pharmaceuticals, Balance Pharmaceuticals, Novartis Pharmaceuticals and Philips Respironics. Dr. Liu has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with employed by Jazz Pharmaceuticals. Dr. Liu holds stock and/or stock options in Jazz Pharmaceuticals which sponsored research in which Dr. Liu was involved as an investigator. . Dr. Sterkel has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Jazz Pharmaceuticals. Dr. Sterkel holds stock and/or stock options in Jazz Pharmaceuticals which sponsored research in which Dr. Sterkel was involved as an investigator. . Dr. Gottwald has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Jazz Pharmaceuticals. Dr. Gottwald holds stock and/or stock options in Jazz Pharmaceuticals. Dr. Steinerman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Jazz Pharmaceuticals. Dr. Steinerman holds stock and/or stock options in Jazz Pharmaceuticals which sponsored research in which Dr. Steinerman was involved as an investigator. Dr. Jochelson has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Jazz Pharmaceuticals. Dr. Jochelson holds stock and/or stock options in Jazz Pharmaceuticals which sponsored research in which Dr. Jochelson was involved as an investigator. Dr. Hauser has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AbbVie Inc., Acorda Therapeutics, Academy for Continued Healthcare Learning, Acadia Pharmaceuticals, Inc., Adamas Pharmaceuticals, AstraZeneca, ApoPharma, Back Bay Life Science, Biotie Therapies, Bracket, Cerecor, Inc., ClearView Healthcare Partners, ClinicalMind Medical and Therapeutic Communications, CNS Ratings, LLC., Cowen and Company, Cynapsus Therapeutics, DDB Health LLC, Decision Resources Group (DRG), Eli Lilly & Company, eResearch Technology, Inc., Expert Connect, Extera Partners, GE Healthcare, Health Advances, HealthLogix, Health and Wellness Partners, Huron Consulting Group, Impax Laboratories, Impel Neuropharma, Intec Pharma Ltd., Jazz Pharmaceuticals, Kashiv Pharma LLC, Kyowa Kirin Pharmaceutical Development, Ltd., LCN Consulting, LifeMax, Life Sciences, Lundbeck LLC, The Lockwood Group, MEDACorp, Medscape, Medtronic, Michael J. Fox Foundation, Mitsubishi Tanabe Pharmaceuticals, Movement Disorder Society, National Institutes of Health (NIH), Neurocea LLC, Neurocrine Biosciences, Neuroderm, Neuropore Therapies, Orbes Medical Group, Outcomes Insights, Parkinson Study Group, Peerview Press, Pennside Partners, Pfizer, Inc., Pharma Two B, Ltd, Phase Five Communications, Prescott Medical Group, Prexton Therapeutics, Prilenia Development Ltd., Projects in Knowledge, Putnam Associates, Quintiles, RMEI Medical Education for Better Outcomes, SAI Med Partners LLC, Sarepta Therapeutics, Schlesinger Associates, Scion Neurostim, LLC, Seagrove Partners, LLC, Slingshot Insights, Sunovion Pharmaceuticals, Inc., Sun Pharma, Teva Pharmaceutical Industries, US WorldMeds, Vista Research, WebMD, Windrose Consulting Group. Dr. Hauser has received royalty, license fees, or contractual rights payments from the University of South Florida. Dr. Hauser has received research support from AbbVie Inc., Acorda Therapeutics, AstraZeneca, Axovant Sciences , Biogen Inc., Cavion, Enterin Inc., Impax Laboratories, LLC., Intec Pharma Ltd, Jazz Pharmaceuticals, NeuroDerm Ltd., Lundbeck, Michael J Fox Foundation for Parkinson’s Research, F. Hoffman-La Roche, Dart NeuroScience LLC, Prexton Therapeutics, Revance Therapeutics Inc., Sunovion Pharmaceuticals.