• Open Access

A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II)

Authors

  • Caroline M. Apovian,

    1. Section of Endocrinology, Diabetes and Nutrition, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA
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    • Disclosure: C.M.A has participated on advisory boards for Allergan, Amylin, Orexigen, Merck, Johnson and Johnson, Abbott, Arena, Zafgen, Novo Nordisk, and Sanofi-Aventis, and has received research funding from Lilly, Amylin, Pfizer, Sanofi-Aventis, Orexigen, MetaProteomics, and the Dr. Robert C. and Veronica Atkins Foundation. L.J.A. has participated in advisory boards/acted as a consultant for Amylin Pharmaceuticals, Inc., Ethicon Endo-Surgery, Inc., GlaxoSmithKline Consumer Healthcare LP, Novo Nordisk, Orexigen Therapeutics, Inc., VIVUS, Inc., Takeda Pharmaceuticals, and Zafgen, Inc. L.J.A has also performed contracted research for Amylin Pharmaceuticals, Inc., High Point Pharmaceuticals LLC, Medical University of South Carolina (MUSC), and Novo Nordisk, and has ownership interest in Cardiometabolic Support Network, LLC, and Myos Corporation. D.M.R. has served as a clinical investigator in clinical drug trials of obesity therapeutics for Orexigen; D.M.R. has not received any financial support as a consultant for Orexigen. C.D.S. has participated on advisory boards for Allergan, and Ethicon-Endosurgery. C.D.S. has also received research funding from Ethicon Endo-Surgery Arena and Orexigen Pharmaceuticals. H.W. received has served as an advisor for Orexigen Pharmaceuticals, Arena Pharmaceuticals, Wellspring Camps, and Eisai, Inc. H.W. receives royalties from Up to Date and has received grant funding from the NIH, Orexigen, and Novo Nordisk. H.W. has ownership interests in Active Planet LLC and has co-ownership on a patent for a weight loss maintenance strategy. C.B. is an employee at Orexigen. D.D.K. and E.D. are former employees at Orexigen; D.D.K. is currently employed at Zafgen, Inc., and has acted as a consultant for Orexigen; E.D. is currently an employee of Amgen, Inc.

  • Louis Aronne,

    1. Weill Cornell Medical College, New York, New York, USA
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  • Domenica Rubino,

    1. Washington Center for Weight Management, Arlington, Virginia, USA
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  • Christopher Still,

    1. Geisinger Health Care System, Danville, Pennsylvania, USA
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  • Holly Wyatt,

    1. University of Colorado Denver, Denver, Colorado, USA
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  • Colleen Burns,

    1. Orexigen Therapeutics, Inc., La Jolla, California, USA
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  • Dennis Kim,

    1. Orexigen Therapeutics, Inc., La Jolla, California, USA
    Current affiliation:
    1. Dr Kim is currently affiliated with Zafgen, Inc., Cambridge, Massachusetts, USA
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  • Eduardo Dunayevich,

    Current affiliation:
    1. Dr Dunayevich is currently affiliated with Amgen, Inc., Thousand Oaks, California, USA
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  • for the COR-II Study Group


  • Funding agencies: Orexigen Therapeutics, Inc., provided study drug and collaborated with the investigators in the design of the study; interpretation of the data; and the preparation, review, and approval of the manuscript. Metropolitan Research Associates (New York, New York, USA) was responsible for study conduct and monitoring, and inVentiv Clinical Solutions (Hunt Valley, Maryland, USA) was responsible for collection, management, and analysis of the data. The dataset is available at Orexigen Therapeutics, Inc.

  • *Members listed at end of report.

Abstract

Objective:

To examine the effects of naltrexone/bupropion (NB) combination therapy on weight and weight-related risk factors in overweight and obese participants.

Design and Methods:

CONTRAVE Obesity Research-II (COR-II) was a double-blind, placebo-controlled study of 1,496 obese (BMI 30-45 kg/m2) or overweight (27-45 kg/m2 with dyslipidemia and/or hypertension) participants randomized 2:1 to combined naltrexone sustained-release (SR) (32 mg/day) plus bupropion SR (360 mg/day) (NB32) or placebo for up to 56 weeks. The co-primary endpoints were percent weight change and proportion achieving ≥5% weight loss at week 28.

Results:

Significantly (P < 0.001) greater weight loss was observed with NB32 versus placebo at week 28 (−6.5% vs. −1.9%) and week 56 (−6.4% vs. −1.2%). More NB32-treated participants (P < 0.001) experienced ≥5% weight loss versus placebo at week 28 (55.6% vs. 17.5%) and week 56 (50.5% vs. 17.1%). NB32 produced greater improvements in various cardiometabolic risk markers, participant-reported weight-related quality of life, and control of eating. The most common adverse event with NB was nausea, which was generally mild to moderate and transient. NB was not associated with increased events of depression or suicidality versus placebo.

Conclusion:

NB represents a novel pharmacological approach to the treatment of obesity, and may become a valuable new therapeutic option.

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