Weight loss combination shows efficacy in phase 3 trial

June 7, 2009

A combination of naltrexone and bupropion produces a significant, 4.7% greater weight loss than placebo when combined with behavior modification, according to phase 3 study results.

A combination of naltrexone and bupropion produces a significant, 4.7% greater weight loss than placebo when combined with behavior modification, according to phase 3 study results presented by Thomas Wadden, MD, director, Center for Weight and Eating Disorders, University of Pennsylvania, Philadelphia. "This is the first phase 3 trial to evaluate the safety and efficacy of naltrexone-bupropion for body weight loss in obese patients," he reports.

Overall, patients taking the combination lost an average of 20.3 to 25.0 pounds over 56 weeks, amounting to a loss of 9.3% to 11.5% of body weight. Patients taking placebo lost 11.0 to 16.0 pounds, for a loss of 5.1% to 7.3% of body weight. "The combination produces weight loss in the same neighborhood as orlistat and sibutramine," says Dr. Wadden.

He adds that previous trials showed that the combination has superior efficacy to monotherapy with either naltrexone or bupropion, which produced weight loss of 1.2% and 2.7%, respectively.

The trial included 793 patients with a body mass index (BMI) of 27 to 45 kg/m² randomized to receive the sustained-release combination of 32 mg naltrexone and 360 mg bupropion (n=482) or placebo (n=193) for 56 weeks. Average patient age was 46 years, and 90% of patients were women. Average baseline BMI was 36.5 kg/m², and average body weight was 101 kg at baseline. All patients also received 28 group sessions of intensive behavior modification including diet and exercise counseling.

The primary endpoints were percentage change in body weight and percentage of patients losing at least 5% of body weight. After 56 weeks, the mean change in body weight from baseline was –9.29% among those receiving active treatment and –5.08% among patients taking placebo (p

Dr. Wadden says that more patients receiving the naltrexone-bupropion combination achieved a statistically significant (ppp

Patient responses on the Control of Eating visual analog scale indicated that those taking the combination treatment had significant improvement from baseline in terms of appetite control (pCombination naltrexone and bupropion was generally well tolerated, with the most frequent adverse event being nausea, which occurred in 34.1% of patients on active treatment versus 10.5% of patients on placebo. Nausea was the most frequent cause of adverse event-related study discontinuation (4.6%).

Other frequent side effects were headache (23.8% of treated patients and 17.5% of patients taking placebo) and constipation (24.1% and 14.0% of patients, respectively). Some patients also reported dizziness, Dr. Wadden says. These adverse events were mild to moderate and occurred early in the 56-week study period.

Psychiatric adverse events occurred in fewer patients and included insomnia (8.7% vs 6.0%), anxiety (5.1% vs 3.5%), other sleep disorder (2.4% vs 3.0%), and depression (1.9% vs 4.0%).

Two cases of cholecystitis occurred with rapid significant weight loss and may be related to treatment with naltrexone-bupropion, says Dr. Wadden.

Results of three other phase 3 trials of the combination therapy are expected to be available later this year.