Randomized controlled trials of the D1/D5 antagonist ecopipam for weight loss in obese subjects.
OBJECTIVE
To evaluate the efficacy and safety of the selective dopamine D1/D5 antagonist ecopipam for the treatment of obesity.


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Astrup
Arne
A
Department of Human Nutrition, Faculty of Life Sciences, University of Copenhagen, 30 Rolighedsvej, 1958 Frederiksberg C, Denmark. ast@life.ku.dk
Greenway
Frank L
FL
Ling
Walter
W
Pedicone
Lisa
L
Lachowicz
Jean
J
Strader
Catherine D
CD
Kwan
Rudolf
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D001552:Benzazepines / Q000627:therapeutic use* / Q000633:toxicity; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy; D018492:Dopamine Antagonists / Q000627:therapeutic use* / Q000633:toxicity; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy*; D018579:Patient Selection; D010919:Placebos; D015431:Weight Loss / Q000187:drug effects*
D001552:Benzazepines; D018492:Dopamine Antagonists; D010919:Placebos; C058081:ecopipam