CONTRAVE®





Acronyms



DRUGS IN CLASS



MECHANISM OF ACTION



FDA-APPROVED INDICATION



WEIGHT LOSS


RCT
COR I trial - Contrave vs Placebo for Weight Loss in Overweight Adults, Lancet (2010) [PubMed abstract]
  • The COR I trial enrolled 1742 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
  • History of bariatric surgery or device
Baseline characteristics
  • Average age 44 years
  • Female sex - 85%
  • Average baseline weight - 219 pounds (99.6 kg)
  • Average baseline BMI - 36
  • Hypertension - 21%
  • High cholesterol - 50%
Randomized treatment groups
  • Group 1 (581 patients) - Placebo
  • Group 2 (578 patients) - Naltrexone-bupropion 8/180 mg twice daily (NB16)
  • Group 2 (583 patients) - Naltrexone-bupropion 16/180 mg twice daily (NB32)
  • Medications were titrated over 4 weeks
  • All participants received instructions on a hypocaloric diet and exercise
Primary outcomes:
  • 1. Percent change in bodyweight at 56 weeks
  • 2. Proportion of patients achieving ≥ 5% weight loss at week 56
Results

Duration: 56 weeks
Outcome Placebo NB16 NB32 Comparisons
Percent decrease in bodyweight 1.3% 5% 6.1% p<0.0001 vs placebo
≥ 5% weight loss 16% 39% 48% p<0.0001 vs placebo
Weight loss 3 lbs (1.4 kg) 10.8 lbs (4.9 kg) 13.4 lbs (6.1 kg) N/A
Nausea 5.3% 27.2% 29.8% p<0.05
Headache 9.3% 16% 13.8% p<0.05
Constipation 5.6% 15.8% 15.7% p<0.05
Dizziness 2.6% 7.7% 9.4% p<0.05
Vomiting 2.5% 6.3% 9.8% p<0.05
Dry mouth 1.9% 7.4% 7.5% p<0.05
Dropouts 50% 49% 51% N/A

Findings: A sustained-release combination of naltrexone plus bupropion could be a useful therapeutic option for treatment of obesity




SIDE EFFECTS

  • Only side effects that occurred in > 4% of patients or at a difference of ≥ 3% compared to placebo are presented
  • Reference [2]
Common side effects
Side effect Contrave 16/180 mg twice a day
(N=2545)
Placebo
(N=1515)
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%







CONTRAINDICATIONS



PRECAUTIONS












DRUG INTERACTIONS





DOSING


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





LONG-TERM SAFETY



BIBLIOGRAPHY