CONTRAVE



















COR II trial - Contrave vs Placebo for Weight Loss in Overweight Adults, Obesity (2013) [PubMed abstract]
  • The COR II trial enrolled 1496 overweight adults
Main inclusion criteria
  • BMI 30 - 45 or BMI 27 - 45 + hypertension or high cholesterol
Main exclusion criteria
  • Diabetes
  • Significant vascular, hepatic, or renal disease
  • History of seizures or serious psychiatric illness
Baseline characteristics
  • Average age 44 years
  • Female sex - 85%
  • Average baseline weight - 220 pounds (100 kg)
  • Average baseline BMI - 36
  • Hypertension - 21%
  • High cholesterol - 54%
Randomized treatment groups
  • Group 1 (1001 patients) - Naltrexone-bupropion 16/180 mg twice daily
  • Group 2 (495 patients) - Placebo
  • After randomization, there was a titration period of 5 weeks to full dose
Primary outcomes:
  • 1. Percent weight change at 28 weeks
  • 2. Proportion of patients achieving ≥ 5% weight loss at week 28
Results

Duration: 28 weeks
Outcome Contrave Placebo Comparisons
Primary outcome (% weight loss at 28 weeks) 6.5% 1.9% p<0.001
Primary outcome (≥ 5% weight loss at 28 weeks) 55.6% 17.5% p<0.001
Weight loss at 28 weeks 13.8 lbs (6.3 kg) 4.4 lbs (2 kg) p<0.001
Nausea 29.2% 6.9% p<0.05
Constipation 19.1% 7.1% p<0.05
Headache 17.5% 8.7% p<0.05
Dry mouth 9.1% 2.6% p<0.05
Vomiting 8.5% 2% p<0.05
Dizziness 6.9% 3.7% p<0.05
Drug discontinuation 46% 46% N/A

Findings: Naltrexone/bupropion represents a novel pharmacological approach to the treatment of obesity, and may become a valuable new therapeutic option




  • Side effects presented are those that occurred in > 4% of patients or at a difference of ≥ 3% when compared to placebo
  • Reference [2]
Common side effects
Side effect Contrave 16/180 mg twice a day
(2545 patients)
Placebo
(1515 patients)
Nausea 32.5% 6.7%
Constipation 19.2% 7.2%
Headache 17.6% 10.4%
Vomiting 10.7% 2.9%
Dizziness 9.9% 3.4%
Insomnia 9.2% 5.9%
Dry mouth 8.1% 2.3%
Diarrhea 7.1% 5.2%
Anxiety 4.2% 2.8%
Hot flush 4.2% 1.2%
Fatigue 4.0% 3.4%
Tremor 4.0% 0.7%


























Contrave titration schedule
Morning dose Evening dose
Week 1 1 tablet None
Week 2 1 tablet 1 tablet
Week 3 2 tablets 1 tablet
Week 4 and on 2 tablets 2 tablets