Abstract 13255: RB006, a Direct Factor IX Inhibitor Results in Consistent and Near Complete Inhibition of Factor IX in Patients with Acute Coronary Syndromes: A RADAR Pharmacokinetic and Pharmacodynamic Substudy
Background: The REG1 system consists of RB006, a direct FIXa inhibitor, and RB007, its active control agent. RB006 produces consistent and near complete inhibition of factor IXa in healthy controls and patients with stable coronary artery disease. Its pharmacological characteristics among patients with acute coronary syndromes (ACS) have not yet been established.
Methods: RADAR is a phase IIb partially blinded study in patients with ACS undergoing planned early cardiac catheterization. Patients (n=800) are randomly allocated (4:1) to receive open-label RB006 or heparin. Thirty patients, 20 of whom had not received recent prior heparin, underwent thorough pharmacokinetic and pharmacodynamic assessment just prior to and 10 minutes after dosing with RB006, as well as prior to and after cardiac catheterization before RB007 dosing. All assessments were performed in a central core laboratory.
Results: Consistent with results from phase I and IIa in stable subjects (Figure 1A), administration of 1 mg/kg RB006 achieves rapid (< 10 min): [a] therapeutic RB006 concentrations (26.1 ± 4.6 mcg/ml), [b] elevation in aPTT (93.0 ± 9.5 s), and [c] near complete FIX inhibition as assessed by fold increase in aPTT (fold increase 2.9 ± 0.3, Figure 1B). These levels remained stable throughout catheterization and PCI.
Conclusions: As in stable patients, RB006 (1 mg/kg IV) results in consistent and near complete inhibition of FIX activity in patients with ACS and stable anti-coagulation during catheterization/PCI. These findings support the dosing of RB006 in ongoing and planned clinical trials.
- Acute coronary syndromes
- Percutaneous coronary intervention
- © 2010 by American Heart Association, Inc.