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

International Journal of Obesity volume 34, pages 919–935 (2010)Cite this article

Subjects

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 ⩾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 2 mg (N=414), 4 mg (N=415) or 6 mg (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 2 mg or placebo) and the 4-mg dose was discontinued during year 2 (patients on 4 mg 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 4 mg (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 4 mg 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.

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Acknowledgements

We thank the staff and patients at the 72 clinical sites who participated in the clinical trial (see Supplementary Information). We thank Dr Barry Gumbiner and Dr Bret Musser for their contribution to the design of this study and Dr Kenneth Cheung (Biostatistics, MSPH, Columbia University, New York, NY, USA) for his independent verification of the study results database. We extend our appreciation to the Data Safety and Monitoring Committee members, Drs Julie Buring, Daniel Heijtan, Edward Horton (Chair), Robert Josse and Robert Spitzer. We thank Catherine Phillips of Merck Medical Communications Department for assistance in the preparation of this manuscript.

Author information

Authors and Affiliations

  1. Weill Cornell Medical College, New York, NY, USA

    L J Aronne

  2. Ullevaal University Hospital, Oslo, Norway

    S Tonstad

  3. Pontificia Universidad Católica de Chile, Santiago, Chile

    M Moreno

  4. Merck Research Laboratories, Rahway, NJ, USA

    I Gantz, N Erondu, S Suryawanshi, C Molony, S Sieberts, J Nayee, A G Meehan, D Shapiro, S B Heymsfield, K D Kaufman & J M Amatruda

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  1. L J Aronne
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  2. S Tonstad
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Corresponding author

Correspondence to L J Aronne.

Ethics declarations

Competing interests

The study was funded by Merck & Co. The authors IG, NE, SS, CM, SS, JN, AGM, DS, SBH, KDK and JMA are or were employees of Merck & Co., Inc. and may hold stock in that company. LA and ST are members of a Merck Diabetes and Obesity Advisory Committee.

Additional information

Supplementary Information accompanies the paper on International Journal of Obesity website

Supplementary information

Appendix

Appendix

Study sites

Louis J Aronne, Comprehensive Weight Control Program, New York, NY; Stephen Louis Aronoff, Research Institute of Dallas, Dallas, TX; Harold E Bays, Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY; Robert J Bielski, Summit Research Network, Farmington Hills, MI; Bruce Taylor Bowling, Regional Clinical Research, Inc., Endwell, NY; George August Bray, Pennington Biomedical Research Center, Baton Rouge, LA; Cynthia C Brinson, Central Texas Clinical Research, Austin, TX; Mary E Bartz, Central Texas Clinical Research, Austin, TX; Richard O Butcher, Careview Medical Group, Inc., San Diego, CA; Rodney G Hood, Careview Medical Group, Inc., San Diego, CA; Robert S Call, Commonwealth Clinical Research Specialists, Richmond, VA; Antonio Caos, Central Florida Clinical Studies, Ocoee, FL; Christopher M Chappel, FPA Clinical Research, Kissimmee, FL; Harry Collins, Anderson and Collins Clinical Research, Inc., Edison, NJ; Martin J Conway, Lovelace Scientific Resources, Inc., Albuquerque, NM; Michael H Davidson, Radiant Research, Chicago, IL; Mark A Deeg, Richard L Roudebush Veterans Affairs Medical Center, Indianapolis, IN; Marian Sue Kirkman, Richard L Roudebush Veterans Affairs Medical Center, Indianapolis, IN; John Howard Pratt, Richard L Roudebush Veterans Affairs Medical Center, Indianapolis, IN; Eleuterio P Delfin, Jr., Center for Clinical Trials, LLC; Paramount, CA; Samuel S Engel, Soundview Research Associates; Norwalk, CT; Mindy J Sotsky, Soundview Research Associates, Norwalk, CT; James Mecham Ferguson, Radiant Research; Salt Lake City, UT; Fares J Arguello, Radiant Research, Salt Lake City, UT; Harold J Fields, Village Family Practice Clinic, Houston, TX; Chester L Fisher, Jr., Health Research of Hampton Roads; Newport News, VA; Alan Duane Forker, Saint Luke's Hospital, Lipid and Diabetes Research Center, Kansas City, MO; Neil J Fraser, Troy Internal Medicine Research; Troy, MI; Ken Fujioka, Scripps Clinic and Research Foundation; San Diego, CA; Geoffrey S Gladstein, Stamford Therapeutics Consortium, Stamford, CT; David M Radin, Stamford Therapeutics Consortium; Stamford, CT; Forrest Anthony Hanke, Trover Clinic, Madisonville, KY; Lisa M Harris, Chase Wellness Center; Virginia Beach, VA; David R Hassman, Comprehensive Clinical Research, Berlin, NJ; David Keith Helton, Southeastern Clinical Research, Chattanooga, TN; Priscilla L Hollander, Baylor University Medical Center, Baylor Endocrine Center, Dallas, TX; William P Jennings, Radiant Research, San Antonio, TX; Norman J Kakos, QUEST Research Institute, Bingham Farms, MI; Adam D Karns, Lovelace Scientific Resources, Inc., Beverly Hills, CA; Alan J. Kivitz, Altoona Center for Clinical Research, Duncansville, PA; Eric J Klein, Capital Clinical Research Center, Olympia, WA; Samuel Klein, Washington University School of Medicine, Center for Human Nutrition, Saint Louis, MO; Dominic Reeds, Washington University School of Medicine, Center for Human Nutrition, Saint Louis, MO; Diane Rachel Krieger, Miami Research Associates, Inc., Miami, FL; Wayne E Larson, Radiant Research, Lakewood, WA; Frank P Maggiacomo, New England Center for Clinical Research, Cranston, RI; Dennis C McCluskey, Radiant Research, Mogadore, OH; Harris Hugh McIlwain, Tampa Medical Group, Tampa, FL; James McKenney, National Clinical Research, Inc., Richmond, VA; Alan Brad Miller, Atlanta Pharmaceutical Research Center, Inc., Dunwoody, GA; Richard E Mills, Palmetto Medical Research, Mount Pleasant, SC; Leslie Penny Moldauer, Radiant Research, Denver, CO; Arthur J Mollen, Mollen Clinic, Phoenix, AZ; David J Morin, Tri-Cities Medical Research, Bristol, TN; Bryan C Pogue, Radiant Research, Boise, ID; Terry L Poling, Heartland Research Associates, LLC, Wichita, KS; Jane L Rohlf, Premier Research, Trenton, NJ; Domenica Marie Rubino, Weight Management Program, Washington DC; Richard D Wasnich, Covance, Inc., Honolulu, HI; Jon Leslie Ruckle, Covance, Inc., Honolulu, HI; Gary E. Ruoff, Westside Family Medical Center, Kalamazoo, MI; Randall J Severance, Radiant Research, Chandler, AZ; Stephan C Sharp, Clinical Research Associates, Inc., Nashville, TN; Norman G Soler, Springfield Diabetes and Endocrine Center, Springfield, IL; Joseph Soufer, Chase Medical Research, Waterbury, CT; Mark Allen Stich, Jacksonville Center for Clinical Research, Jacksonville, FL; Phillip D Toth, Midwest Institute for Clinical Research, Indianapolis, IN; David J Turk, Madrona Medical Group, Bellingham, WA; Thomas A Wadden, University of Pennsylvania, Weight & Eating Disorder Program, Philadelphia, PA; Mervyn Upali Weerasinghe, Rochester Clinical Research, Inc., Rochester, NY; Frederick C Whittier, Clinical Research Limited, Canton, OH; Michael Paul Wiggins, Big Thompson Medical Group, PC, Loveland, CO; Troy Williams, Pivotal Research Centers, Peoria, AZ; Louise A Taber, Pivotal Research Centers, Peoria, AZ; James H Zavoral, Radiant Research, Edina, MN; Karl-Michael Derwahl, St Hedwig-Krankenhaus, Institut fur Klinische Foschung und Entwicklung GmbH, Berlin, Germany; Hans-Michael Foerster,Grafschafter Str., Baerl/Ndrhn, Germany; Andreas Hamann, Diabetes Klinik Bad Nauheim GmbH, FA fur Innere Medizin, Bad Nauheim, Germany; Alberto Allemant, Hospital Nacional ‘Hipolito Unanue’, Lima, Peru; Cesar Butron Delgado, Centro Endocrionologico, Arequipa, Peru; Luis H Zapata-Rincon, Casa De Diabetes Y Nutricion, Lima, Peru; Soren Toubro, Hvidovre Hospital, Hvidovre, Denmark; Arya Sharma, Hamilton Hospital General Division, Hamilton, Ontario, Canada; Paul F Whitsitt, Paradigm Clinical Trials, Inc., Oshawa, Ontario, Canada; Michelle Tolszczuk, Q et T Recherche Inc., Sherbrooke, Quebec, Canada; Ronald Girard, Q et T Recherche Inc., Sherbrooke, Quebec, Canada; Markolf Hanefeld, Gesellschaft fur Wissens-und Technologietransfer der TU Dresden GmbH, Zentrum fur Klinische Studien Forschungsbereich Endokrinologie und Stoffwechsel, Dresden, Germany; Peter Kindermann, Internistische Praxis, Riesa, Germany; Peter Marcinowski, H-Arzt Torenstr. Meersburg, Germany; Erik-Delf Schulze, Hauptstr. Berlin, Germany; Thomas Zoeller, Klinische Forschung Berlin, Berlin, Germany; Francis CC Chow, Prince of Wales Hospital, Shatin, Hong Kong; Karen Siu Ling Lam, Queen Mary Hospital, Hong Kong, Hong Kong; Eduardo Garcia Garcia, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico; Jose Geraldo Gonzalez, Hospital Universitario de Monterrey, Mexico City, Nuevo Leon, Mexico; Bernhard Paulweber, St Johanns-Spital, Landesklinik fur Innere Medizin I, Salzburg, Austria; Hermann Toplak, University of Graz, Medical University Clinic, Ambulanz fur Diabetes und Stoffwechsel, Graz, Austria; Christa Firbas, Allgemeines Krankenhaus (AKH) Wien, Klinische Pharmakologie, Wien, Austria; Gerfried Hans Karl Nell, ClinPharm International GmbH & Co KG, Vienna, Austria; Rudolf Prager, Krankenhaus Lainz, Wein, Austria; Miguel Angel Rubio Herrara, Hospital Clinico San Carlos, Madrid, Spain; Xavier Formiguera Sala, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain; Olga Gonzalez-Albarran, Hospital Ramon y Cajal, Madrid, Spain; Barbara C Biedermann, Kantonsspital Bruderholz, Bruderholz, Switzerland; Bernhard H Lauterberg, Inselspital, Bern, Switzerland; Roger Darioli, CHUV Policlinique Medicale Universitaire, Lausanne, Switzerland; Alain Golay, Hopitaux Universitaires de Geneve, Division d’Enseignement/Therapeutique pour Maladies Chroniques, Geneva, Switzerland; Jocelyne Rachelle Benatar, Green Lane Hospital, Green Lane Clinical Centre Cardiovascular Research Unit, Auckland, New Zealand; Ajith Munasinghe Dissanayake, Middlemore Hospital, Centre for Clinical Research and Effective Practice, Auckland, New Zealand; Siew Pheng Chan, University Malaya Medical Centre, Jalan University, Kuala Lumpur, Malaysia; Chii-Min Hwu, Taipei Veterans General Hospital, Taipei, Taiwan; Wayne Huey-Herng Sheu, Taichung Veterans General Hospital, Taichung, Taiwan; Wei-Shiung Yang, National Taiwan University, University Hospital, Taipei, Taiwan; Jeff Karrasch, Peninsula Specialist Centre, Kipparing, Queensland, Australia; Robert Moses, Clinical Trials and Research Unit, Wollongong, New South Wales, Australia; Boyd Strauss, Monash Medical Centre, Body Composition Laboratory, Clayton, Victoria, Australia; Joseph Proietto, Austin & Repatriation Medical Centre, Heidelberg, Victoria, Australia; Ian Caterson, Royal Prince Alfred Hospital, Metabolish & Obesity Research Group, Camperdon, New South Wales, Australia; Milan Kvapil, ResTrial Outpatient Office of Diabetology, Prague, Czech Republic; Vojtech Hainer, Institute of Endocrinology, Prague, Czech Republic; Pavol Hlubik, University of Defence, Faculty of Military Health Sciences, Department of Preventive Medicine, Hradec Kralova, Czech Republic; Gerrit H de Groot, Nederlandse Obesitas Kliniek, Hilversum, Netherlands; Elisabeth M Mathuss-Vliegen, Academisch Medisch Centrum, Amsterdam, Netherlands; Manuel Ignacio Moreno, Av. Portugal, Santiago, Chile; Victor Saavedra, NovAdilap Servicios Medicos Ltda, Santiago, Chile; Verner Codoceo, FACH Hospital, Tratamiento Intermedio Medico (TIM), Santiago, Chile; Aila Marjatta Rissanen, Lihavuustutkimusyksikko, Helsinki, Finland; Markku Savolainen, Oulun Yliopisto, Sairaala Sisatautien Kilinkka, Oulu, Finland; Manuel Borrell Munoz, Centres d’Assistencia Primeria Sarria, Barcelona, Spain; Albert Ledesma-Castelltort, CAP Remei, Barcelona, Spain; Serena Tonstad, Ullevaal Hospital, Ulleval universitetssykehus HF, Oslo, Norway; Hans Olav Hoivik, Hedmark Medisinske Senter AS, Hamar, Norway; Bard Eirik Kulseng, Sankt Olavs Hospital, Trondheim, Norway.

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Aronne, L., Tonstad, S., Moreno, M. et al. A clinical trial assessing the safety and efficacy of taranabant, a CB1R inverse agonist, in obese and overweight patients: a high-dose study. Int J Obes 34, 919–935 (2010). https://doi.org/10.1038/ijo.2010.21

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