{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T21:27:26Z","timestamp":1791840446328,"version":"4.3.4"},"reference-count":33,"publisher":"American Medical Association (AMA)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2026,5,1]]},"abstract":"\n Importance<\/jats:title>\n Development of motor fluctuations is common in people with Parkinson disease (PD) treated with oral levodopa, and currently available dopamine (D) agonists adjunctive to levodopa offer additional motor control but may increase risk of adverse events (AEs) via preferential activation of D2\/D3 receptors. Tavapadon is a novel, investigational, oral, once-daily, selective D1\/D5 agonist that may improve motor control while minimizing AEs commonly associated with D2\/D3 receptor activation.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To evaluate the efficacy, safety, and tolerability of tavapadon as adjunctive therapy to oral levodopa in adults with PD experiencing motor fluctuations.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This was a phase 3, double-blind, placebo-controlled randomized clinical trial conducted between September 2020 and February 2024 with a 4-week safety follow-up. Participants were recruited from 148 sites across 14 countries. Participants were enrolled after screening adults with PD who were experiencing fluctuations while receiving stable oral levodopa (\u2265400 mg daily).<\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n Participants were randomized 1:1 to flexible-dose tavapadon (5-15 mg once daily) or placebo adjunctive to oral levodopa for 27 weeks.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n \n The primary end point was change from baseline to week 26 in total daily on-time (ie, good mobility, smoother movement, fewer motor\/nonmotor symptoms) without troublesome dyskinesia (referred to as\n good-on-time<\/jats:italic>\n ). The key secondary end point was change from baseline in total daily off-time (ie, return\/worsening of motor\/nonmotor symptoms often experienced between medication doses).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n After screening 824 adults with PD, 507 participants (mean [SD] age, 64.9 [8.5] years; 321 male [63%]; mean [SD] disease duration, 6.7 [4.5] years; mean [SD] baseline daily off-time, 5.5 [2.4] hours) were enrolled and received tavapadon (n\u2009=\u2009252) or placebo (n\u2009=\u2009255). Tavapadon significantly increased daily good-on-time by 1.10 hours compared with placebo (1.70 vs 0.60 hours; 95% CI, 0.60-1.70;\n P<\/jats:italic>\n \u2009&amp;lt;.001). Daily off-time was significantly reduced from baseline with tavapadon vs placebo (\u22121.88 vs \u22120.93 hours; difference, \u22120.94 hours; 95% CI, \u22121.48 to \u22120.41];\n P<\/jats:italic>\n \u2009&amp;lt; .001). Tavapadon had a favorable safety profile; although more AEs occurred with tavapadon vs placebo (180 participants [71.7%] vs 140 participants [55.1%]), most were nonserious (93.2%) and mild to moderate in severity. Common AEs with tavapadon (\u22655% of participants) were nausea (14.3%), dyskinesia (10.0%), and dizziness (7.6%).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n Findings of this randomized clinical trial demonstrate the efficacy, tolerability, and safety profile of tavapadon adjunctive to levodopa for off fluctuations.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT04542499<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaneurol.2026.0577","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T15:30:19Z","timestamp":1774020619000},"page":"442","source":"Crossref","is-referenced-by-count":14,"title":["Tavapadon as Adjunctive Treatment for Parkinson Disease"],"prefix":"10.1001","volume":"83","author":[{"given":"Hubert H.","family":"Fernandez","sequence":"first","affiliation":[{"name":"Center for Neurological Restoration, Cleveland Clinic, Cleveland, 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