TY - JOUR
T1 - Pegnivacogin results in near complete FIX inhibition in acute coronary syndrome patients
T2 - RADAR pharmacokinetic and pharmacodynamic substudy
AU - Povsic, Thomas J.
AU - Wargin, William A.
AU - Alexander, John H.
AU - Krasnow, Joshua
AU - Krolick, Merill
AU - Cohen, Mauricio G.
AU - Mehran, Roxana
AU - Buller, Christopher E.
AU - Bode, Christoph
AU - Zelenkofske, Steven L.
AU - Rusconi, Christopher P.
AU - Becker, Richard C.
N1 - Funding Information:
This work was supported by Regado Biosciences.
Funding Information:
Conflict of interest: T.J.P.: employee of the Duke Clinical Research Institute, which has received funding from REGADO Biosciences. W.A.W.: consultant for REGADO Biosciences. J.H.A.: consulting fees and research support from REGADO Biosciences; employee of the Duke Clinical Research Institute, which has received funding from REGADO Biosciences. J.K.: none to report. M.K.: none to report. M.G.C.: research funding from REGADO Biosciences. R.M.: medical board advisory member and modest consulting and speaking fees from REGADO Biosciences. C.E.B.: none to report. C.B.: none to report. S.T.Z.: Employee and stockholder in REGADO Biosciences.C.P.R.: founder, employee, and stockholder in REGADO Biosciences. R.C.B.: medical advisory board member for REGADO Biosciences; employee of the Duke Clinical Research Institute, which has received funding from REGADO Biosciences to conduct clinical research.
PY - 2011/10
Y1 - 2011/10
N2 - Aim s Establishing factor IX inhibition in patients with acute coronary syndrome/non-ST-elevation myocardial infarction (ACS/NSTEMI), a setting characterized by increased factor IX activity, is critical to investigate the REG1 system in this target population. The REG1 system (Regado Biosciences, Basking Ridge, NJ) consists of pegnivacogin (RB006), an RNA aptamer that directly inhibits factor IXa, and anivamersen (RB007), its complementary control agent. Methods and resultsRADAR is a Phase 2b study investigating the use of pegnivacogin in patients (n 800) with ACS undergoing planned early cardiac catheterization. To validate dose selection and stability of anticoagulation throughout the time of cardiac catheterization at an early stage of the clinical trial, 33 patients, 22 of whom had not received recent prior heparin, underwent thorough pharmacokinetic and pharmacodynamic assessment. Fold prolongation of activated partial thromboplastin time (aPTT) was used to impute factor IX inhibition. Pegnivacogin 1 mg/kg rapidly achieved a high pegnivacogin plasma concentration (26.1 ± 4.6 g/mL), prolonged the aPTT (mean aPTT 93.0 ± 9.5 s), and approached near complete factor IX inhibition (mean fold increase from baseline 2.9 ± 0.3). These levels remained stable from the time of drug administration through completion of the catheterization. ConclusionPegnivacogin administered at a weight-adjusted dose of 1 mg/kg consistently achieves a high level of factor IX activity inhibition among patients with ACS and provides stable anticoagulation during cardiac catheterization. These findings support the dose of pegnivacogin selected for the RADAR study.
AB - Aim s Establishing factor IX inhibition in patients with acute coronary syndrome/non-ST-elevation myocardial infarction (ACS/NSTEMI), a setting characterized by increased factor IX activity, is critical to investigate the REG1 system in this target population. The REG1 system (Regado Biosciences, Basking Ridge, NJ) consists of pegnivacogin (RB006), an RNA aptamer that directly inhibits factor IXa, and anivamersen (RB007), its complementary control agent. Methods and resultsRADAR is a Phase 2b study investigating the use of pegnivacogin in patients (n 800) with ACS undergoing planned early cardiac catheterization. To validate dose selection and stability of anticoagulation throughout the time of cardiac catheterization at an early stage of the clinical trial, 33 patients, 22 of whom had not received recent prior heparin, underwent thorough pharmacokinetic and pharmacodynamic assessment. Fold prolongation of activated partial thromboplastin time (aPTT) was used to impute factor IX inhibition. Pegnivacogin 1 mg/kg rapidly achieved a high pegnivacogin plasma concentration (26.1 ± 4.6 g/mL), prolonged the aPTT (mean aPTT 93.0 ± 9.5 s), and approached near complete factor IX inhibition (mean fold increase from baseline 2.9 ± 0.3). These levels remained stable from the time of drug administration through completion of the catheterization. ConclusionPegnivacogin administered at a weight-adjusted dose of 1 mg/kg consistently achieves a high level of factor IX activity inhibition among patients with ACS and provides stable anticoagulation during cardiac catheterization. These findings support the dose of pegnivacogin selected for the RADAR study.
KW - Acute coronary syndrome
KW - Anivamersen
KW - Factor IX inhibition
KW - Pegnivacogin
KW - Pharmacodynamic
KW - Pharmacokinetic
UR - https://www.scopus.com/pages/publications/80054052562
U2 - 10.1093/eurheartj/ehr179
DO - 10.1093/eurheartj/ehr179
M3 - Article
C2 - 21724623
AN - SCOPUS:80054052562
SN - 0195-668X
VL - 32
SP - 2412
EP - 2419
JO - European Heart Journal
JF - European Heart Journal
IS - 19
ER -