1. ^*Department of Human Nutrition, University of Copenhagen, Frederiksberg, Denmark
2. ^†Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana
3. ^‡Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, University of California-Los Angeles, Los Angeles, California
4. ^§Schering-Plough Research Institute, Kenilworth, New Jersey

Correspondence: Arne Astrup Department of Human Nutrition, Faculty of Life Sciences, University of Copenhagen, 30 Rolighedsvej, 1958 Frederiksberg C, Denmark. E-mail: ast@life.ku.dk

^*The costs of publication of this article were defrayed, in part, by the payment of page charges. This article must, therefore, be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 24 April 2006; Revised  0000; Accepted 5 January 2007.

Abstract

Objective: To evaluate the efficacy and safety of the selective dopamine D1/D5 antagonist ecopipam for the treatment of obesity.

Research Methods and Procedures: 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 5% weight loss from baseline at 12 weeks (Phase 2) or the distribution of percentage weight loss from baseline at 52 weeks (Phase 3).

Results: In the Phase 2 study, 26% of subjects administered ecopipam 100 mg vs. 6% of placebo subjects achieved 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.

Discussion: 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.