PMID- 21293451
OWN - NLM
STAT- MEDLINE
DCOM- 20111108
LR  - 20141120
IS  - 1930-739X (Electronic)
IS  - 1930-7381 (Linking)
VI  - 19
IP  - 7
DP  - 2011 Jul
TI  - Efficacy and safety of CP-945,598, a selective cannabinoid CB1 receptor 
      antagonist, on weight loss and maintenance.
PG  - 1404-14
LID - 10.1038/oby.2010.352 [doi]
AB  - 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.
FAU - Aronne, Louis J
AU  - Aronne LJ
AD  - Weill Cornell Medical College, Cornell University, New York, New York, USA.
FAU - Finer, Nick
AU  - Finer N
FAU - Hollander, Priscilla A
AU  - Hollander PA
FAU - England, Richard D
AU  - England RD
FAU - Klioze, Solomon S
AU  - Klioze SS
FAU - Chew, Robert D
AU  - Chew RD
FAU - Fountaine, Robert J
AU  - Fountaine RJ
FAU - Powell, Coralie M
AU  - Powell CM
FAU - Obourn, John D
AU  - Obourn JD
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20110203
PL  - United States
TA  - Obesity (Silver Spring)
JT  - Obesity (Silver Spring, Md.)
JID - 101264860
RN  - 0 
      (1-(9-(4-chlorophenyl)-8-(2-chlorophenyl)-9H-purin-6-yl)-4-ethylaminopiperidine-4-carboxylic 
      acid amide)
RN  - 0 (Anti-Obesity Agents)
RN  - 0 (Drugs, Investigational)
RN  - 0 (Piperidines)
RN  - 0 (Purines)
RN  - 0 (Receptor, Cannabinoid, CB1)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Anti-Obesity Agents/administration & dosage/*adverse effects/therapeutic use
MH  - Diabetes Mellitus, Type 2/complications
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drugs, Investigational/administration & dosage/*adverse effects/therapeutic use
MH  - Early Termination of Clinical Trials
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Obesity/complications/*drug therapy/prevention & control/therapy
MH  - Overweight/complications/*drug therapy/prevention & control/therapy
MH  - Patient Dropouts
MH  - Piperidines/administration & dosage/*adverse effects/therapeutic use
MH  - Purines/administration & dosage/*adverse effects/therapeutic use
MH  - Receptor, Cannabinoid, CB1/*antagonists & inhibitors
MH  - Secondary Prevention
MH  - Weight Loss/*drug effects
MH  - Young Adult
EDAT- 2011/02/05 06:00
MHDA- 2011/11/09 06:00
CRDT- 2011/02/05 06:00
PHST- 2011/02/05 06:00 [entrez]
PHST- 2011/02/05 06:00 [pubmed]
PHST- 2011/11/09 06:00 [medline]
AID - oby2010352 [pii]
AID - 10.1038/oby.2010.352 [doi]
PST - ppublish
SO  - Obesity (Silver Spring). 2011 Jul;19(7):1404-14. doi: 10.1038/oby.2010.352. Epub 
      2011 Feb 3.