Androgen receptor inhibitors (ARIs) are approved for the treatment of advanced prostate cancer; however, some patients may experience symptoms and side effects that hinder their physical functioning. The Timed Up and Go (TUG) and Short Physical Performance Battery (SPPB) tests are used to assess physical functioning in older adults and are recommended assessments for patients with prostate cancer, despite lacking validation in this setting. DaroAct (NCT04157088) was an open-label, multicenter, phase 2b study designed to evaluate the effects of the ARI darolutamide (lead-in phase) and darolutamide vs enzalutamide (randomized phase) on physical functioning in men with castration-resistant prostate cancer (CRPC). Only the lead-in phase, in which participants received darolutamide 600mg twice daily, was completed. The TUG and SPPB tests were used to assess physical functioning. The lead-in phase enrolled 30 participants. During 24 weeks of treatment, 8 (32.0%) of 25 evaluable participants exhibited clinically meaningful worsening in TUG from baseline (primary endpoint). At the week 24 visit, 5 (21.7%) of 23 participants had worsening in TUG time, and 8 (33.3%) of 24 participants had worsening in SPPB score. Because only 48% of participants had the same outcome on the TUG and SPPB tests, the study was terminated without initiating the randomized comparison. Most participants showed no clinically meaningful worsening in physical functioning after 24 weeks of darolutamide treatment, but poor agreement between tests was observed. Tools to accurately and consistently measure the impact of ARIs on physical functioning in patients with CRPC are needed.