Two phase 3 studies have found that a combination of naltrexone SR/bupropion SR can produce significant weight loss in overweight and obese women, regardless of menopausal status.…
La Jolla, California-based Orexigen is developing the two-drug formulation as the experimental anti-obesity drug Contrave. Bupropion, a norepinephrine/dopamine reuptake inhibitor, and naltrexone, an opioid receptor antagonist, have been on the market for several years for treating depression and alcohol or opioid dependence, respectively.
This past February, in a major setback for Contrave, the FDA declined to approve the drug. The FDA said it wants Orexigen to conduct a long-term clinical trial to show that treatment would not raise the risk of heart attacks.
That trial — bound to be very costly — would come on top of the already-completed studies presented this week at the American College of Obstetrics and Gynecology’s annual clinical meeting in Washington, DC.
The larger of the two, reported by Dr. Daphne Y. LaCoursiere from the University of California, San Diego, compared two formulations of the drug to placebo in 1,482 women. Just under half of the women in each treatment group completed the 56-week study.
Intent-to-treat analysis found women given 32 mg naltrexone plus 360 mg bupropion lost 6.2% of their body weight, on average, compared to 5.3% for women on the lower-dose formulation (16 mg naltrexone plus 360 mg bupropion). Women in the placebo group lost 1.2%.
Dr. LaCoursiere stated that, “The women who received Contrave had improved responsiveness to their food cravings and had an easier time controlling what they were eating. A per protocol analysis showed that women in the treatment groups lost 7 to 8% of their body weight.”
“It’s clear from the data that either of the two combinations resulted in significantly more weight loss in women,” Dr. LaCoursiere said. “This is another possible tool to help our patients lose weight.”
The other study, presented by Dr. Sandra Ann Carson of Brown University in Providence, Rhode Island, compared the 32 mg naltrexone/360 mg bupropion formulation to placebo in 713 women, all of whom also received 28 group sessions of counseling on diet, exercise and behavior.
Fifty-eight percent of the women completed the study. At 56 weeks, the women in the treatment group had lost 9.8% of their body weight, on average, compared to 5.7% for women in the placebo group.
In both studies, the most frequent side effects were nausea, headache and gastrointestinal side effects. But Contrave has also been reported to raise pulse rates and blood pressure slightly, which is what makes the FDA nervous.
Both studies reported this week also found significantly greater improvements in weight-related quality of life for the women in the treatment groups than for women on placebo. All effects were similar for pre- and peri- and postmenopausal women.