A clinical trial assessing the safety and efficacy of the CB1R inverse agonist taranabant in obese and overweight patients: low-dose study.

Abstract

OBJECTIVE:

To evaluate the weight loss efficacy, safety and tolerability of taranabant, a CB1R inverse agonist, in obese and overweight patients.

DESIGN:

Multicenter, double-blind, randomized, placebo-controlled study.

SUBJECTS:

Patients >or=18 years old, BMI 27-43 kg m(-2), were randomized to placebo (n=209) or taranabant 0.5 mg (n=207), 1 mg (n=208) or 2 mg given orally once daily (n=417) for 52 weeks.

MEASUREMENTS:

Key efficacy measurements included body weight (BW), waist circumference (WC), lipid endpoints and glycemic endpoints.

RESULTS:

Based on a last observation carried forward analysis of the all-patients-treated population, mean change in BW for taranabant 0.5, 1, and 2 mg and placebo was -5.4, -5.3, -6.7 and -1.7 kg, respectively (P<0.001 for all doses vs placebo). The proportions of patients who lost at least 5 and 10% of their baseline BW at week 52 were significantly higher for all taranabant doses vs placebo (P<0.001 for all doses). Reductions in WC, percentage of body fat, and triglycerides were significant for taranabant 2 mg and in triglycerides for taranabant 1 mg vs placebo. There was no effect of taranabant vs placebo on other lipid or glucose-related endpoints. Incidences of adverse experiences classified in the gastrointestinal (diarrhea and nausea), nervous system (dizziness/dizziness postural), psychiatric-related (irritability and anger/aggression) and vascular (flushing/hot flush) organ systems were higher and statistically significant in the taranabant 2-mg group compared with the placebo group. Irritability was higher and statistically significant in all taranabant groups compared with the placebo group.

CONCLUSION:

All three doses of taranabant-induced clinically meaningful and statistically significant weight loss. Incidences of adverse experiences in organ systems known to express CB1R were higher in taranabant groups.

• Authors: J Proietto, A Rissanen, J B Harp, N Erondu, Q Yu, S Suryawanshi, M E Jones, A O Johnson-Levonas, S B Heymsfield, K D Kaufman, J M Amatruda
• Journal: International journal of obesity (2005) (Int J Obes (Lond)) Vol. 34 Issue 8 Pg. 1243-54 (Aug 2010) ISSN: 1476-5497 [Electronic] England
• PMID: 20212496 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Amides
• Anti-Obesity Agents
• Pyridines
• Receptor, Cannabinoid, CB1
• N-(3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl)-2-methyl-2-((5-(trifluoromethyl)pyridin-2-yl)oxy)propanamide

Topics

• Administration, Oral
• Adult
• Aged
• Aged, 80 and over
• Amides (administration & dosage)
• Anti-Obesity Agents (administration & dosage)
• Body Weight (drug effects)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Humans
• Male
• Middle Aged
• Obesity (drug therapy)
• Pyridines (administration & dosage)
• Receptor, Cannabinoid, CB1 (antagonists & inhibitors)
• Surveys and Questionnaires
• Weight Loss
• Young Adult