Abstract 17322: Heparin-Antagonist PMX-60056 Rapidly and Completely Reverses Heparin Anticoagulation in Man
PMX-60056 is a new small-molecule chemical entity developed from first principle to antagonize the anticoagulant effect of heparin. In vitro and ex-vivo testing in human blood has previously demonstrated efficacy. Six normal male subjects provided informed consent for inclusion in this double-blind placebo-controlled crossover trial. All were confined for the duration of the study. Each subject received 70U/kg unfractionated heparin as an intravenous bolus; and 20 minutes later, each received either PMX-60056 or placebo as a ten-minute intravenous infusion. Coagulation was assessed by activated clotting time (ACT) and activated partial thromboplastin time (aPTT). There was a 2-day washout period between doses. The ACT (bedside) measurements used finger-stick samples and showed variability; but the results were completely conclusive. The aPTT assays occurred under controlled and validated laboratory conditions. The accompanying graphs indicate the actual aPTT data for every individual subject. As seen, in no case did any subject lack complete reversal of anticoagulation after PMX-60056, while in no case did any subject have reversal after saline placebo. Furthermore, the reversal was complete before the end of the infusion, suggesting that less than 0.3mg/kg was required to neutralize 70U/kg of heparin. Equally important is the observation that the reversal after PMX-60056 was permanent. The placebo data indicate that heparin was eliminated over a 4-hour period, as expected from known pharmacokinetics; and the PMX-60056 data show that restoration of anticoagulation did not occur at any time -- there was no dissociation of PMX-60056 from heparin. PMX-60056, a new small molecule designed to reverse heparin and LMWH anticoagulation by binding to the consensus pentasaccharide group, rapidly and permanently reverses the effects of prophylactic doses of heparin in healthy male subjects.
- © 2010 by American Heart Association, Inc.