{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:45:38Z","timestamp":1792802738399,"version":"4.5.0"},"reference-count":17,"publisher":"American Medical Association (AMA)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2023,10,1]]},"abstract":"\n Importance<\/jats:title>\n Levodopa has a short half-life and a limited window of opportunity for absorption in the proximal small intestine. IPX203 is an oral, extended-release formulation of carbidopa-levodopa developed to address these limitations.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To assess the efficacy and safety of IPX203 vs immediate-release carbidopa-levodopa in patients with Parkinson disease who are experiencing motor fluctuations.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n RISE-PD was a 20-week, randomized, double-blind, double-dummy, active-controlled, phase 3 clinical trial. The study was conducted between November 6, 2018, and June 15, 2021, at 105 academic and clinical centers in the US and Europe. Patients with Parkinson disease taking a total daily dose of 400 mg or more of levodopa and experiencing an average of 2.5 hours or more daily off-time were included in the study. A total of 770 patients were screened, 140 were excluded (those taking controlled-release carbidopa-levodopa apart from a single daily bedtime dose, Rytary (Amneal Pharmaceuticals), additional carbidopa or benserazide, or catechol O-methyl transferase inhibitors or who had a history of psychosis within the past 10 years), and 630 were enrolled in the trial.<\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n Following open-label immediate-release carbidopa-levodopa dose adjustment (3 weeks) and conversion to IPX203 (4 weeks), patients were randomized in a 1:1 ratio to double-blind, double-dummy treatment with immediate-release carbidopa-levodopa or IPX203 for 13 weeks.<\/jats:p>\n <\/jats:sec>\n \n Main Outcome and Measures<\/jats:title>\n The primary end point was mean change in daily good on-time (ie, on-time without troublesome dyskinesia) from baseline to the end of the double-blind treatment period.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 630 patients (mean [SD] age, 66.5 [8.95] years; 396 [62.9%] men) were enrolled, and 506 patients were randomly assigned to receive IPX203 (n\u2009=\u2009256) or immediate-release carbidopa-levodopa (n\u2009=\u2009250). The study met its primary end point, demonstrating statistically significant improvement in daily good on-time for IPX203 compared to immediate-release carbidopa-levodopa (least squares mean, 0.53 hours; 95% CI, 0.09-0.97;\n P<\/jats:italic>\n \u2009=\u2009.02), with IPX203 dosed a mean 3 times per day vs 5 times per day for immediate-release carbidopa-levodopa. Good on-time per dose increased by 1.55 hours with IPX203 compared to immediate-release carbidopa-levodopa (95% CI, 1.37-1.73;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001). IPX203 was well tolerated. The most common adverse events in the double-blind phase (IPX203 vs immediate-release carbidopa-levodopa) were nausea (4.3% vs 0.8%) and anxiety (2.7% vs 0.0%).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this study, IPX203 provided more hours of good on-time per day than immediate-release carbidopa-levodopa, even as IPX203 was dosed less frequently.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT03670953<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaneurol.2023.2679","type":"journal-article","created":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T11:00:59Z","timestamp":1692010859000},"page":"1062","source":"Crossref","is-referenced-by-count":51,"title":["IPX203 vs Immediate-Release Carbidopa-Levodopa for the Treatment of Motor Fluctuations in Parkinson Disease"],"prefix":"10.1001","volume":"80","author":[{"given":"Robert A.","family":"Hauser","sequence":"first","affiliation":[{"name":"University of South Florida Parkinson\u2019s Disease and Movement Disorders Center\/Parkinson Foundation Center of Excellence, Tampa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto J.","family":"Espay","sequence":"additional","affiliation":[{"name":"James J. and Joan A. Gardner Center for Parkinson\u2019s Disease and Movement Disorders, University of Cincinnati, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron L.","family":"Ellenbogen","sequence":"additional","affiliation":[{"name":"Quest Research Institute\/Michigan Institute for Neurological Disorders, Farmington Hills"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hubert H.","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Center for Neurological Restoration, Neurological Institute, Cleveland Clinic, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart H.","family":"Isaacson","sequence":"additional","affiliation":[{"name":"Parkinson\u2019s Disease and Movement Disorders Center of Boca Raton, Boca Raton, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"LeWitt","sequence":"additional","affiliation":[{"name":"Wayne State University School of Medicine and Henry Ford Hospital, Detroit, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William G.","family":"Ondo","sequence":"additional","affiliation":[{"name":"Methodist Hospital and Weill Cornell Medical School, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh","family":"Pahwa","sequence":"additional","affiliation":[{"name":"University of Kansas Medical Center, Kansas City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Geriatric Hospital Haag and Technical University of Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Stocchi","sequence":"additional","affiliation":[{"name":"Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Pisana, Department of Neurology, Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonid","family":"Zeitlin","sequence":"additional","affiliation":[{"name":"Quartesian, Princeton, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghazal","family":"Banisadr","sequence":"additional","affiliation":[{"name":"Amneal Pharmaceuticals, Bridgewater, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley","family":"Fisher","sequence":"additional","affiliation":[{"name":"Amneal Pharmaceuticals, Bridgewater, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hester","family":"Visser","sequence":"additional","affiliation":[{"name":"Amneal Pharmaceuticals, Bridgewater, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"D\u2019Souza","sequence":"additional","affiliation":[{"name":"Amneal Pharmaceuticals, Bridgewater, New 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