Cardiome Pharma Corp announced that its heart failure drug candidate oxypurinol met the primary endpoint in a recently completed clinical trial. Results from the study confirmed preclinical and clinical studies demonstrating the beneficial effects of oxypurinol on the endothelial dysfunction that often accompanies heart disease.
Results from the open-label, proof-of-concept EXOTIC study were presented at a satellite symposium to the Heart Failure Society of America's annual meeting. The satellite symposium, entitled "Xanthine Oxidase Inhibition for the Treatment of Congestive Heart Failure" was sponsored by Cardiome and focused on the benefit of using a well-known class of metabolism-modifying drugs upon heart disease.
The primary endpoint of the study was reversal of acetylcholine-mediated coronary vasoconstriction after intravenous administration of oxypurinol. Prof. Dr. Thomas Munzel and Dr. Stephan Baldus conducted the study at the Eppendorf Clinic at the University of Hamburg.
"Coronary endothelial dysfunction is a hallmark of coronary artery disease. Restoration of coronary vasomotor function by inhibition of xanthine oxidase as observed in this pilot study further points towards the significance of xanthine oxidase in contributing to the pathophysiology of coronary artery disease," said Dr. Stephan Baldus, co-investigator. "These results warrant the initiation of larger scale studies in order to evaluate whether oxypurinol can be beneficial to patients with coronary heart disease."
The study included 18 patients with coronary heart disease. The administration of intravenous oxypurinol (200mg) reduced xanthine oxidase activity by 65% (p (less than) 0.05) across the broad patient group. In the sub-set of 13 patients in whom acetylcholine challenge produced vasoconstriction, oxypurinol reduced the observed vasoconstriction by 33% (p (less than) 0.05), and increased coronary flow velocity by (greater than) 20% (p (less than) 0.05). These results indicate that oxypurinol, by inhibiting xanthine oxidase activity, improves the impaired endothelial function in patients with coronary artery disease.
The company intends to conduct a second trial in Hamburg designed to determine the effect of oxypurinol on left ventricular performance in patients with CHF of ischemic etiology. This study is an extension of the original clinical proof of concept study undertaken by Cappola et al. Another study, a phase II/III trial called OPT-CHF, is currently underway testing the impact of oxypurinol on clinical outcomes of 400 heart failure patients.