Original Article

International Journal of Obesity (2010) 34, 919–935; doi:10.1038/ijo.2010.21; published online 16 February 2010

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

L J Aronne1, S Tonstad2, M Moreno3, I Gantz4, N Erondu4, S Suryawanshi4, C Molony4, S Sieberts4, J Nayee4, A G Meehan4, D Shapiro4, S B Heymsfield4, K D Kaufman4 and J M Amatruda4

  1. 1Weill Cornell Medical College, New York, NY, USA
  2. 2Ullevaal University Hospital, Oslo, Norway
  3. 3Pontificia Universidad Católica de Chile, Santiago, Chile
  4. 4Merck Research Laboratories, Rahway, NJ, USA

Correspondence: Dr LJ Aronne, Weill Medical College of Cornell University, 1165 York Avenue, New York, NY 10021-7917, USA. E-mail: ljaronne@med.cornell.edu

Received 12 July 2009; Revised 22 November 2009; Accepted 2 January 2010; Published online 16 February 2010.

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Abstract

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 greater than or equal to18 years old, with body mass index of 27–43kgm–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 6mg were down-dosed to 2mg or placebo) and the 4-mg dose was discontinued during year 2 (patients on 4mg were down-dosed to 2mg). Changes from baseline in body weight at week 52 (all-patients-treated population, last observation carried forward analysis) were −2.6, −6.6 and −8.1kg, 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 −7.6kg for placebo and taranabant 2 and 4mg, 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.

Keywords:

randomized clinical trial; cannabinoid-1 receptor; endocannabinoid

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