Orexigen® Therapeutics, Inc. (Nasdaq: OREX) announced that results from its COR-I trial of Contrave® were published online today in the journal Lancet. COR-I was the largest of the four, 56-week, Phase 3 trials supporting the New Drug Application for Contrave, currently under review by the U.S. Food and Drug Administration. Results show that patients taking Contrave were two to three times more likely to lose at least 5% or 10% of their body weight compared to those taking placebo, on both an intent-to-treat (ITT) and completers basis.
Many patients with obesity are at higher risk for diabetes and cardiovascular disease, so evaluating the impact of weight loss on markers of cardiovascular and metabolic risk was a key objective of the COR (Contrave Obesity Research) Phase 3 program. Results from COR-I showed that treatment with Contrave resulted in significant improvements over placebo in waist circumference, insulin resistance, HDL cholesterol, triglycerides, and hsCRP, which are well-known and accepted measures of cardiometabolic risk. Patients taking Contrave also showed significant improvements in patient-reported control of eating, including reduced food cravings and reduced difficulty resisting food cravings.
"The secondary health benefits of weight loss are critical to understanding the potential role of pharmacotherapy in managing overweight and obese patients," said Frank Greenway, M.D., Medical Director at the Pennington Center Outpatient Research Clinic and lead investigator for the study. "This study showed that treatment with Contrave has meaningful impact on markers of cardiometabolic risk, demonstrating its potential to be an important new approach to the treatment of obesity."
Additional findings from patients on Contrave32 (32mg naltrexone sustained release (SR)/360mg bupropion SR):
- 34% of patients completing the study lost at least 10% of their body weight as compared to 11% on placebo (p<0.0001).
- Patients taking Contrave showed significant improvements in important secondary endpoints: waist circumference (-6.2 cm on Contrave32 vs. -2.5 cm on placebo), insulin resistance (-20.2% vs. -5.9%), HDL cholesterol (+8.0% vs. +0.8%), triglycerides (-12.7% vs. -3.1%) and hsCRP (-29.0% vs. -16.7%) compared to patients taking placebo on an ITT basis.
The most frequently observed treatment-emergent adverse events in COR-I included nausea, headache, constipation and upper respiratory tract infection. Adverse events in the Contrave groups were generally mild to moderate in intensity, transient, and did not result in discontinuation for most patients. Mean systolic blood pressure decreased from baseline to endpoint by 1.6 mmHg for patients taking Contrave32 and 2.8 mmHg for patients on placebo. As expected, greater weight loss was associated with greater reductions in blood pressure.
"As a clinician, I was comforted to see that the safety findings from the largest of the Phase 3 studies of Contrave were consistent with the known effects of its constituent components," said Ken Fujioka, M.D., Director of Nutrition and Metabolic Research at Scripps Clinic and investigator in this study. "When studying a combination therapy, a primary goal is making sure that the combination does not result in a different safety profile from what is already known about the constituent components. Contrave achieved that goal: the adverse event profile was consistent with the 20-year history of use of these products."
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