"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."
Study Design
COR-I was a 56-week placebo-controlled, double-blind randomized trial enrolling patients whose body-mass index (BMI) was between 30-45 kg/m(2) for patients with uncomplicated obesity, or BMI 27-45 kg/m(2) with controlled hypertension or dyslipidemia, or both. 1742 patients were randomized to receive either Contrave32, Contrave16 (16mg naltrexone SR/360mg bupropion SR), or placebo in a 1:1:1 ratio. Thirty-four sites in the United States participated in the study.
About Contrave
Contrave is an investigational combination therapy believed to address both physiological and behavioral drivers of obesity. The two components of this combination therapy act in a complementary manner in the central nervous system. The central pathways targeted by this treatment are involved in controlling the balance of food intake and metabolism, and regulating reward-based eating behavior. In clinical trials, Contrave was shown to help obese patients initiate and sustain significant weight loss, improve important markers of cardiometabolic risk and increase ability to control eating. The U.S. Food and Drug Administration (FDA) has tentatively scheduled a Division of Metabolic and Endocrine Drug Products Advisory Committee meeting on December 7, 2010 and the Prescription Drug User Fee Act (PDUFA) action date has been set for January 31, 2011.
About the Contrave Clinical Development Program
All four trials in the COR Phase 3 program (COR-I, COR-II, COR-BMOD and COR-Diabetes) were randomized, double-blind, placebo-controlled trials. The co-primary endpoints were the proportion of patients achieving at least 5% weight loss and percent change in body weight compared to placebo. Secondary endpoints included multiple measures of cardiometabolic risk, quality of life, control of eating, and glycemic control. Contrave was generally well tolerated. The safety and tolerability profile of Contrave in the clinical development program was consistent with the safety profile of the constituent components, which have been in use for other indications for over 20 years. The most frequent treatment-emergent adverse events in patients treated with Contrave were nausea, constipation, headache, vomiting, and dizziness. Treatment with Contrave was not associated with increases in adverse event reports of depression or suicidal ideation compared to placebo. Mean blood pressure with Contrave was generally unchanged from baseline to endpoint. Placebo patients experienced decreases in blood pressure from baseline to endpoint of approximately 2mmHg. Greater weight loss correlated with greater reductions in blood pressure in both Contrave and placebo patients, suggesting that the expected relationship between weight loss and blood pressure was maintained. Importantly, normal circadian blood pressure patterns were preserved with Contrave. There was an increase in pulse of about one beat per minute in patients taking Contrave. Serious events were reported infrequently and included events of cholecystitis (Contrave 0.2%, PBO <0.1%), seizure (<0.1%, 0%) and major cardiovascular events (<0.1%, <0.1%).