Contrave
Encyclopedia
Bupropion/naltrexone 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 is 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:
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.
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
in phase III clinical trials. Currently being developed by Orexigen in a sustained-release formulation, it is a combination of two approved drugs, bupropion
Bupropion
Bupropion is an atypical antidepressant and smoking cessation aid. The drug is a non-tricyclic antidepressant and differs from most commonly prescribed antidepressants such as SSRIs, as its primary pharmacological action is thought to be norepinephrine-dopamine reuptake inhibition...
and naltrexone
Naltrexone
Naltrexone is an opioid receptor antagonist used primarily in the management of alcohol dependence and opioid dependence. It is marketed in generic form as its hydrochloride salt, naltrexone hydrochloride, and marketed under the trade names Revia and Depade...
. 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 is 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
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
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.