The nonreceptor Abelson (Abl) tyrosine kinases have been implicated as key drivers of initiation and progression in Parkinson's disease (PD). Risvodetinib, a potent, brain-penetrant, selective inhibitor of the nonreceptor Abl kinases c-Abl1 and c-Abl2/Arg (collectively, c-Abl), was evaluated in a randomized, double-blind, placebo-controlled phase 2a trial ('the 201 Trial') using once-daily 50 mg, 100 mg, 200 mg or placebo in 137 participants with early, untreated PD. The primary end points in safety and tolerability were met, with 95% of enrolled participants completing the 12-week dosing regimen and a 2-week safety follow-up. Both the average number of adverse events per person and the fraction of participants experiencing at least one treatment-emergent adverse event were similar between risvodetinib and placebo treatment groups, indicating that risvodetinib was safe and well tolerated. Although the trial was not powered to measure efficacy, 14 secondary end points evaluated motor and nonmotor features of disease in hierarchical order. The primary hierarchical secondary end point of the Movement Disorder Society revision to the Unified PD Rating Scale sum of Parts II + III did not reach statistical significance. The study findings indicate that risvodetinib is safe and well tolerated. Longer duration trials are needed to evaluate its potential clinical efficacy. ClinicalTrials.gov registration: NCT05424276 .