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

Obesity (Silver Spring). 2013 May;21(5):935-43. doi: 10.1002/oby.20309.

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/m(2) ) or overweight (27-45 kg/m(2) 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.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Obesity Agents / adverse effects
  • Anti-Obesity Agents / pharmacology
  • Anti-Obesity Agents / therapeutic use*
  • Bupropion / adverse effects
  • Bupropion / pharmacology
  • Bupropion / therapeutic use*
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / prevention & control*
  • Delayed-Action Preparations
  • Dopamine Uptake Inhibitors / adverse effects
  • Dopamine Uptake Inhibitors / pharmacology
  • Dopamine Uptake Inhibitors / therapeutic use
  • Double-Blind Method
  • Drug Therapy, Combination
  • Dyslipidemias / complications
  • Feeding Behavior / drug effects
  • Female
  • Humans
  • Hypertension / complications
  • Male
  • Middle Aged
  • Naltrexone / adverse effects
  • Naltrexone / pharmacology
  • Naltrexone / therapeutic use*
  • Narcotic Antagonists / adverse effects
  • Narcotic Antagonists / pharmacology
  • Narcotic Antagonists / therapeutic use
  • Nausea / etiology
  • Obesity / complications
  • Obesity / drug therapy*
  • Obesity / prevention & control
  • Overweight
  • Quality of Life
  • Risk Factors
  • Weight Loss / drug effects*

Substances

  • Anti-Obesity Agents
  • Delayed-Action Preparations
  • Dopamine Uptake Inhibitors
  • Narcotic Antagonists
  • Bupropion
  • Naltrexone