Pegnivacogin results in near complete FIX inhibition in acute coronary syndrome patients

RADAR pharmacokinetic and pharmacodynamic substudy

Thomas J. Povsic, William A. Wargin, John H. Alexander, Joshua Krasnow, Merill Krolick, Mauricio G Cohen, Roxana Mehran, Christopher E. Buller, Christoph Bode, Steven L. Zelenkofske, Christopher P. Rusconi, Richard C. Becker

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2412-2419
Number of pages8
JournalEuropean Heart Journal
Volume32
Issue number19
DOIs
StatePublished - Oct 1 2011

Fingerprint

Factor IX
Acute Coronary Syndrome
Pharmacokinetics
Partial Thromboplastin Time
Cardiac Catheterization
Factor IXa
Nucleotide Aptamers
Health Services Needs and Demand
Catheterization
Heparin
RB 006
Clinical Trials
Weights and Measures
Pharmaceutical Preparations

Keywords

  • Acute coronary syndrome
  • Anivamersen
  • Factor IX inhibition
  • Pegnivacogin
  • Pharmacodynamic
  • Pharmacokinetic

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Pegnivacogin results in near complete FIX inhibition in acute coronary syndrome patients : RADAR pharmacokinetic and pharmacodynamic substudy. / Povsic, Thomas J.; Wargin, William A.; Alexander, John H.; Krasnow, Joshua; Krolick, Merill; Cohen, Mauricio G; Mehran, Roxana; Buller, Christopher E.; Bode, Christoph; Zelenkofske, Steven L.; Rusconi, Christopher P.; Becker, Richard C.

In: European Heart Journal, Vol. 32, No. 19, 01.10.2011, p. 2412-2419.

Research output: Contribution to journalArticle

Povsic, TJ, Wargin, WA, Alexander, JH, Krasnow, J, Krolick, M, Cohen, MG, Mehran, R, Buller, CE, Bode, C, Zelenkofske, SL, Rusconi, CP & Becker, RC 2011, 'Pegnivacogin results in near complete FIX inhibition in acute coronary syndrome patients: RADAR pharmacokinetic and pharmacodynamic substudy', European Heart Journal, vol. 32, no. 19, pp. 2412-2419. https://doi.org/10.1093/eurheartj/ehr179
Povsic, Thomas J. ; Wargin, William A. ; Alexander, John H. ; Krasnow, Joshua ; Krolick, Merill ; Cohen, Mauricio G ; Mehran, Roxana ; Buller, Christopher E. ; Bode, Christoph ; Zelenkofske, Steven L. ; Rusconi, Christopher P. ; Becker, Richard C. / Pegnivacogin results in near complete FIX inhibition in acute coronary syndrome patients : RADAR pharmacokinetic and pharmacodynamic substudy. In: European Heart Journal. 2011 ; Vol. 32, No. 19. pp. 2412-2419.
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abstract = "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.",
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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.

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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.

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KW - Anivamersen

KW - Factor IX inhibition

KW - Pegnivacogin

KW - Pharmacodynamic

KW - Pharmacokinetic

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