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

Objective: To evaluate the efficacy, safety and tolerability of taranabant in obese and overweight patients. Design: Double-blind, randomized, placebo-controlled study. Subjects: Patients were >= 18 years old, with body mass index of 27-43 kg m(-2),and 51% with metabolic syndrome (MS) randomized to placebo (N=417) or taranabant 2mg (N=414), 4mg (N=415) or 6mg (N=1256) for 104 weeks. Measurements: Key efficacy measurements included body weight, waist circumference (WC), lipid and glycemic end points. Results: On the basis of risk/benefit assessments, the 6-mg dose was discontinued during year 1 (patients on 6 mg were down-dosed to 2mg or placebo) and the 4-mg dose was discontinued during year 2 (patients on 4mg were down-dosed to 2 mg). Changes from baseline in body weight at week 52 (all-patients-treated population, last observation carried forward analysis) were -2.6, -6.6 and -8.1 kg, respectively, for placebo and taranabant 2 and 4mg (both doses P < 0.001 vs placebo). For patients who completed year 1, changes from baseline in body weight at week 104 were -1.4, -6.4 and -7.6 kg for placebo and taranabant 2 and 4 mg, respectively (both doses P < 0.001 vs placebo). The proportions of patients at weeks 52 and 104 who lost at least 5 and 10% of their baseline body weight were significantly higher and the proportions of patients who met criteria for MS were significantly lower for taranabant 2 and 4mg vs placebo. The incidence of adverse experiences classified in the gastrointestinal, nervous, psychiatric, cutaneous and vascular organ systems were generally observed to be dose related with taranabant vs placebo. Conclusion: Taranabant at the 2- and 4-mg dose was effective in achieving clinically significant weight loss over 2 years and was associated with dose-related increases in adverse experiences. On the basis of these and other data, an assessment was made that the overall safety and efficacy profile of taranabant did not support its further development for the treatment of obesity. International Journal of Obesity (2010) 34, 919-935; doi: 10.1038/ijo.2010.21; published online 16 February 2010