Tavapadon as Adjunctive Treatment for Parkinson Disease

作者：Hubert H. Fernandez, S. H. Isaacson, Robert A. Hauser, Pinky Agarwal, William Ondo, Ariane Park, D. Kremens, Matthew Leoni, Sridhar Reddy Duvvuri, Cari Combs, E. Koenig, Ih Chang, Gina Pastino, Stacey Tringali, Nicole Golonski, Raymond Sanchez, Linda Harmer, Joey Boiser, Cindy Zadikoff, Zoltan Mari · 发表于：JAMA Neurology · 年份：2026 · DOI：10.1001/jamaneurol.2026.0577 · 被引用次数：8 · 研究领域：Parkinson's Disease Mechanisms and Treatments、Parkinson's Disease and Spinal Disorders、Neurological disorders and treatments

Importance: 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. Objective: To evaluate the efficacy, safety, and tolerability of tavapadon as adjunctive therapy to oral levodopa in adults with PD experiencing motor fluctuations. Design, Setting, and Participants: 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 (≥400 mg daily). Interventions: Participants were randomized 1:1 to flexible-dose tavapadon (5-15 mg once daily) or placebo adjunctive to oral levodopa for 27 weeks. Main Outcomes and Measures: 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 good-on-time). The key secondary end point was chan...