Randomized controlled trials of the D1/D5 antagonist ecopipam for weight loss in obese subjects.

Abstract

To evaluate the efficacy and safety of the selective dopamine D1/D5 antagonist ecopipam for the treatment of obesity. Four randomized, double-blind, multicenter trials compared ecopipam (n=1667) and placebo (n=1118) in obese subjects including type 2 diabetic subjects. Subjects received oral ecopipam 10, 30, or 100 mg daily for 12 weeks (Phase 2) or 50 or 100 mg daily for 52 weeks (Phase 3) combined with a weight loss program. Primary efficacy variables were the proportion of subjects with>or=5% weight loss from baseline at 12 weeks (Phase 2) or the distribution of percentage weight loss from baseline at 52 weeks (Phase 3). In the Phase 2 study, 26% of subjects administered ecopipam 100 mg vs. 6% of placebo subjects achieved>or=5% weight loss after 12 weeks (p<0.01). In the Phase 3 studies, ecopipam 100 mg produced a 3.1% to 4.3% greater weight loss than placebo at 52 weeks. More subjects administered ecopipam vs. placebo achieved a 5% to 10% or >10% weight loss in two non-diabetic phase 3 trials. Ecopipam-treated subjects also maintained more weight loss compared with placebo subjects at 52 weeks. Phase 3 studies were discontinued because of unexpected psychiatric adverse events (ecopipam 31% vs. placebo 15%), including depression, anxiety, and suicidal ideation. Ecopipam was effective for achieving and maintaining weight loss in obese subjects, including type 2 diabetic subjects; however, the adverse effects on mood observed in the Phase 3 studies exclude its projected use in weight management.