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Clinical Trial
. 2013 May;21(5):935-43.
doi: 10.1002/oby.20309.

A Randomized, Phase 3 Trial of Naltrexone SR/bupropion SR on Weight and Obesity-Related Risk Factors (COR-II)

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Clinical Trial

A Randomized, Phase 3 Trial of Naltrexone SR/bupropion SR on Weight and Obesity-Related Risk Factors (COR-II)

Caroline M Apovian et al. Obesity (Silver Spring). .
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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.


Following screening, participants were randomized via a centrally administered interactive voice response system in a 2:1 ratio, stratified by study site, to receive a combined oral formulation of 32 mg/day naltrexone SR + 360 mg/day bupropion SR (NB32) or matching placebo, administered in divided doses twice daily. Naltrexone was initiated at one-eighth or one-quarter of the maintenance dose and bupropion was initiated at one-quarter of the maintenance dose; doses were escalated linearly over the first 3-4 weeks, and the maintenance dose was reached by the start of week 5. To evaluate the efficacy and safety of a dose increase in participants with suboptimal response, NB32 participants with <5% weight loss at visits between weeks 28 and 44 inclusive were re-randomized (double-blind, 1:1 ratio) to continue receiving NB32 or escalate to NB48 (48 mg/day naltrexone SR + 360 mg/day bupropion SR) for the remainder of the study. Study visits occurred at baseline (week 0) and every 4 weeks thereafter.
Participant flow chart.
A) Percent weight loss (observed; LS mean ± SE) by visit in the week 28 and 56 completers populations (NB32 data are weighted for weeks 32-56), and percent weight loss for the week 28 and 56 mITT-LOCF populations. ***P < 0.001 for NB32 vs. Placebo. B) Categorical weight loss in week 28 and 56 mITT-LOCF and Completers populations. ***P < 0.001 for NB32 vs. Placebo. In both panels, week 56 data for NB32 are weighted as described in the Statistical analyses section.

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    1. Hedley AA, Ogden CL, Johnson CL, Carroll MD, Curtin LR, Flegal KM. Prevalence of overweight and obesity among US children, adolescents, and adults, 1999-2002. JAMA. 2004;291:2847–28s50. - PubMed
    1. Olshansky SJ, Passaro DJ, Hershow RC, et al. A potential decline in life expectancy in the United States in the 21st century. N Engl J Med. 2005;352:1138–1145. - PubMed
    1. NHLBI/NIDDK. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: the evidence report. Bethesda: National Institutes of Health; 1998. - PubMed
    1. Grodstein F, Levine R, Troy L, Spencer T, Colditz GA, Stampfer MJ. Three-year follow-up of participants in a commercial weight loss program. Can you keep it off? Arch Intern Med. 1996;156:1302–1306. - PubMed
    1. Riddle M. Combining sulfonylureas and other oral agents. Am J Med. 2000;108(Suppl 6a):15S–22S. - PubMed

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