{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T12:34:31Z","timestamp":1792586071914,"version":"4.5.0"},"reference-count":22,"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 Tavapadon is an oral, once-daily, selective D1\/D5 agonist that may improve Parkinson disease (PD) motor symptoms while minimizing adverse events (AEs) 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 in adults with early PD.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n TEMPO-1 was a phase 3, double-blind, placebo-controlled randomized clinical trial conducted at 102 sites across 12 countries between December 2019 and June 2024. Adults with early PD (&amp;lt;3 years\u2019 disease duration) who were treatment naive or had less than 3 months of prior dopaminergic treatment were eligible for enrollment. Data analysis was completed from July 2024 to May 2025.<\/jats:p>\n <\/jats:sec>\n \n Intervention<\/jats:title>\n Participants were randomized 1:1:1 to receive 1 of 2 fixed doses of tavapadon (5 or 15 mg once daily) or placebo for 27 weeks, followed by a 4-week safety follow-up period.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary end point was least-squares mean (LSM) change from baseline to week 26 in Movement Disorder Society\u2013Unified Parkinson\u2019s Disease Rating Scale (MDS-UPDRS) parts II and III combined score. Key secondary end points were LSM change from baseline to week 26 in MDS-UPDRS part II scores and the proportion of participants with a score of \u201cmuch improved\u201d or \u201cvery much improved\u201d on the Patient Global Impression of Change.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Overall, 751 adults with early PD who were treatment naive or had less than 3 months of prior dopaminergic treatment were screened, and 529 participants were enrolled (187 female participants [35.3%]; mean [SD] age, 63.7 [9.6] years; mean [SD] disease duration, 0.7 [0.8] years) and randomized to receive tavapadon, 5 mg (n\u2009=\u2009177), tavapadon, 15 mg (n\u2009=\u2009177), or placebo (n\u2009=\u2009175). The change from baseline to week 26 in the MDS-UPDRS parts II and III combined score was significantly improved in participants treated with both the 5-mg dose of tavapadon (9.7-point decrease vs 1.8-point increase with placebo; treatment difference, \u221211.5 points; 95% CI, \u221213.8 to \u22129.2;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001;\n d<\/jats:italic>\n \u2009=\u20091.14) and 15-mg dose of tavapadon (10.2-point decrease vs 1.8-point increase with placebo; treatment difference, \u221212.1 points; 95% CI, \u221214.4 to \u22129.8;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001;\n d<\/jats:italic>\n \u2009=\u20091.20). Tavapadon had a favorable safety profile; most AEs were nonserious and mild to moderate in severity. Common AEs with tavapadon were nausea (90 of 354 with tavapadon [25.4%]), headache (59 of 354 [16.7%]), and dizziness (45 of 354 [12.7%]).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In the TEMPO-1 randomized clinical trial, tavapadon improved motor function in participants with early PD and was well tolerated with a favorable safety profile.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT04201093<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaneurol.2026.0590","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T15:30:20Z","timestamp":1774020620000},"page":"452","source":"Crossref","is-referenced-by-count":16,"title":["Fixed-Dose Tavapadon for Early Parkinson Disease"],"prefix":"10.1001","volume":"83","author":[{"given":"Rajesh","family":"Pahwa","sequence":"first","affiliation":[{"name":"University of Kansas Medical Center, Kansas 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