Bupropion/naltrexone (proposed trade name Contrave) is an experimental treatment for obesity in phase III clinical trials. Currently being developed by Orexigen in a sustained-release formulation, it is a combination of two approved drugs, bupropion and naltrexone. Both drugs have individually shown some evidence of effectiveness in weight loss, and the combination is expected to have a synergistic effect. In clinical trials, patients taking Contrave combined with diet and exercise lost more weight than patients taking a placebo and following the same diet and exercise program. On 31 March 2010, Orexigen submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for this drug combination. On 7 December 2010, an FDA Advisory Committee voted 13-7 for the approval of Contrave, and voted 11-8 for the conduct of a post-marketing cardiovascular outcomes study. Contrave's PDUFA date was 31 January 2011. Subsequently, on 2 February 2011, the FDA rejected the drug and it was decided that an extremely large-scale study of the long-term cardiovascular effects of Contrave would be needed, before approval could be considered. The recommended daily dose of Contrave is two (8 mg naltrexone/90 mg bupropion) tablets taken twice daily (4 tablets total - 32 mg naltrexone, 360 mg bupropion). Upon initiation, the drug will be started with a quarter-dose (or one tablet) for one week and a pill will be added to the regimen each week until the full recommended dose is reached on Week 4.
During phase 2 testing, different dosages were used in a once daily formula. These include:
- 16 mg naltrexone - 400 mg bupropion
- 32 mg naltrexone - 400 mg bupropion
- 48 mg naltrexone - 400 mg bupropion
The second dosage (32 mg-400 mg) on average showed the best benefit-to-risk ratio.
Treatment is designed to influence the hypothalamus in order to decrease food intake over an extended period of time. Studies of almost 700 patients, 90% female, ran up to 56 weeks. The control group, overall, lost 5% of their initial body weight, or 11-16 lbs. The experimental (medicated) group lost 20-23 lbs during the same amount of time. The average starting weight for participants was 223 lbs. Current medical weight loss medications average 5-22 lbs lost in 6 months.[unreliable source?]