title: Efficacy and safety of CP-945,598, a selective cannabinoid CB1 receptor antagonist, on weight loss and maintenance.
abstract: Three double-blind, placebo-controlled, three-parallel-group, multicenter phase 3 trials were conducted to assess the efficacy and safety of CP-945,598 for weight loss and weight-loss maintenance. Two trials were designed to be 2 years in duration (in obese and overweight patients) and one as a 1-year study (in obese and overweight patients with type 2 diabetes). However, the 2-year trials and the CP-945,598 development program were terminated before completion due to changing regulatory perspectives of CB1 receptor-related drugs. In total, 1,253 and 2,536 participants in the two 2-year multinational and North American studies were randomized to 10-mg CP-945,598 (n = 360; 718); 20-mg CP-945,598 (n = 534, 1,084) and placebo (n = 359, 734), respectively; and 975 participants were randomized to 10-mg CP-945,598 (n = 318); 20-mg CP-945,598 (n = 320); and placebo (n = 337) in the 1-year multinational diabetes trial. Baseline demographics were similar between treatment groups within each trial. One year of treatment with CP-945,598 resulted in a dose-related mean percentage reduction from baseline body-weight in all trials. A significant proportion of all participants also achieved 5% and 10% weight loss after 1 year. In participants with mainly well-controlled type 2 diabetes, the combination of lifestyle and CP-945,598 induced substantial improvements in glycemic control. The most frequent adverse events (AEs) for CP-945,598 were: diarrhea, nausea, nasopharyngitis, and headache. Self-reported experiences of anxiety and suicidal thoughts were higher with CP-945,598 than placebo, as were the incidence of depression and depressed mood. However, the reported increases in psychiatric symptoms were not consistently dose dependent.
authors.affiliation: Weill Cornell Medical College, Cornell University, New York, New York, USA.
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Aronne
authors.forename: Nick
authors.initials: N
authors.lastname: Finer
authors.forename: Priscilla A
authors.initials: PA
authors.lastname: Hollander
authors.forename: Richard D
authors.initials: RD
authors.lastname: England
authors.forename: Solomon S
authors.initials: SS
authors.lastname: Klioze
authors.forename: Robert D
authors.initials: RD
authors.lastname: Chew
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fountaine
authors.forename: Coralie M
authors.initials: CM
authors.lastname: Powell
authors.forename: John D
authors.initials: JD
authors.lastname: Obourn
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019440:Anti-Obesity Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015507:Drugs, Investigational / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D057239:Early Termination of Clinical Trials; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000188:drug therapy* / Q000517:prevention & control / Q000628:therapy; D050177:Overweight / Q000150:complications / Q000188:drug therapy* / Q000517:prevention & control / Q000628:therapy; D010352:Patient Dropouts; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D011687:Purines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*; D055502:Secondary Prevention; D015431:Weight Loss / Q000187:drug effects*; D055815:Young Adult
chemical_list: C535235:1-(9-(4-chlorophenyl)-8-(2-chlorophenyl)-9H-purin-6-yl)-4-ethylaminopiperidine-4-carboxylic acid amide; D019440:Anti-Obesity Agents; D015507:Drugs, Investigational; D010880:Piperidines; D011687:Purines; D043884:Receptor, Cannabinoid, CB1