Safety and Efficacy of Mevidalen in Lewy Body Dementia: A Phase 2, Randomized, Placebo‐Controlled Trial

Background Mevidalen is a selective positive allosteric modulator (PAM) of the dopamine D1 receptor subtype. Objective To assess the safety and efficacy of mevidalen for treatment of cognition in patients with Lewy body dementia (LBD). Methods PRESENCE was a phase 2, 12‐week study in participants with LBD (N = 344) randomly assigned (1:1:1:1) to daily doses of mevidalen (10, 30, or 75 mg) or placebo. The primary outcome measure was change from baseline on Cognitive Drug Research Continuity of Attention (CoA) composite score. Secondary outcomes included Alzheimer's Disease Assessment Scale‐Cognitive Subscale 13 (ADAS‐cog13), Movement Disorder Society‐Unified Parkinson's Disease Rating Scale (MDS‐UPDRS), and Alzheimer's Disease Cooperative Study‐Clinical Global Impression of Change (ADCS‐CGIC). Numerous safety measures were collected. Results Mevidalen failed to meet primary or secondary cognition endpoints. Mevidalen resulted in significant, dose‐dependent improvements of MDS‐UPDRS total score (sum of Parts I−III, 10 mg P