title: Pegnivacogin results in near complete FIX inhibition in acute coronary syndrome patients: RADAR pharmacokinetic and pharmacodynamic substudy.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  RADAR 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 µg/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.
  
  
  CONCLUSIONS
  Pegnivacogin 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.
authors: Department of Medicine, Division of Cardiology, Duke Clinical Research Institute, Duke University Medical Center, Box 103208, Durham, NC 27710, USA. povsi001@mc.duke.edu
authors: Thomas J
authors: TJ
authors: Povsic
authors: William A
authors: WA
authors: Wargin
authors: John H
authors: JH
authors: Alexander
authors: Joshua
authors: J
authors: Krasnow
authors: Merill
authors: M
authors: Krolick
authors: Mauricio G
authors: MG
authors: Cohen
authors: Roxana
authors: R
authors: Mehran
authors: Christopher E
authors: CE
authors: Buller
authors: Christoph
authors: C
authors: Bode
authors: Steven L
authors: SL
authors: Zelenkofske
authors: Christopher P
authors: CP
authors: Rusconi
authors: Richard C
authors: RC
authors: Becker
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000188:drug therapy*; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D052157:Aptamers, Nucleotide / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D015949:Factor IXa / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy*; D010314:Partial Thromboplastin Time; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D052157:Aptamers, Nucleotide; C515724:RB 006; D015949:Factor IXa