CLINICAL EVIDENCE:

PRAXBIND—Immediate, Complete, and Long-lasting Effect over 24 Hours1,2,3*

Results in a phase 1 trial in healthy volunteers

  • Immediately after the administration of 5 g PRAXBIND, dabigatran plasma concentrations were reduced to below the lower limit of quantification, and subjects' coagulation parameters (dTT, ECT, aPTT, TT, ACT) returned to baseline levels
  • Reduction observed over the entire observation period of ≥24 hours
  • In a limited number of patients, re‑distribution of dabigatran from the periphery to plasma led to re‑elevation of dTT, ECT, aPTT, and TT

Change of ECT From Baseline
in the Representative Group of Healthy Volunteers

Clinical study results depicting the role of PRAXBIND in the reversal of dabigatran-induced clotting determined by ECT in healthy volunteers
  • PRAXBIND has shown no procoagulant effect
    • Measured as ETP
  • Comparable rate of adverse reactions overall (25%) in healthy volunteers who received PRAXBIND (55/224) vs placebo (26/105)
  • The most frequent (≥5%) adverse reaction reported was headache at 5%

In an interim analysis of an ongoing trial in actively treated patients of RE-VERSE AD™

PRAXBIND rapidly reversed the anticoagulant activity of dabigatran

  • Median maximum reversal was 100% in the first 4 hours (primary endpoint; n=90), based on determination of DTT or ECT3
  • 9 out of 10 patients achieved complete reversal (n=90)3
  • In a limited number of patients, elevated coagulation parameters (e.g., aPPT or ECT) have been observed 12‑24 hours post-dose

Click here for Trial Design.

Change of ECT From Baseline
in PRADAXA-Treated Patients From RE-VERSE AD†§

Clinical study results depicting the role of PRAXBIND in the reversal of dabigatran-induced clotting determined by ECT (n-90)
  • Most frequently reported adverse reactions in ≥5% of patients were: hypokalemia, delirium, constipation, pyrexia, and pneumonia

PRAXBIND—Fast-acting reversal, sustained effect*

  • Reversal was evident seconds after administration
  • Effect was sustained for 24 hours4

Change of aPTT From Baseline
in PRADAXA-Treated Patients From RE-VERSE AD§

Clinical study results depicting the role of PRAXBIND in the reversal of dabigatran-induced clotting determined by aPTT (n=90)
  • 5 patients reported thrombotic events in RE-VERSE AD (5/123 patients)
    • 1 report was 2 days after PRAXBIND administration
    • 4 reports were ≥7 days after PRAXBIND administration
    • Events occurred in the absence of antithrombotic therapy and could be attributed to the patients' underlying medical condition

RE-VERSE AD™ Trial: Multicenter, multinational, single-cohort case series trial for the reversal of PRADAXA3

Primary Endpoint: To determine the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours after the administration of PRAXBIND (based on central laboratory determination of dTT or ECT) in patients who presented with Pradaxa® (dabigatran etexilate)-related life‑threatening or uncontrolled bleeding (Group A) or who required emergency surgery or urgent procedures (Group B).

Methodology: The interim analysis included data for 123 patients (66 patients in Group A and 57 patients in Group B) currently taking PRADAXA who were administered PRAXBIND 5 g. Results of central laboratory evaluations were available for a subset of 90 patients (51 patients in Group A and 39 patients in Group B). Median age was 77 years and median CrCl was 55 mL/min. Approximately 67% and 63% of the patients in groups A and B, respectively, had been treated with 110 mg of PRADAXA twice daily prior to PRAXBIND administration.

RE-VERSE AD™=A Study of the RE-VERSal Effects of Idarucizumab on Active Dabigatran.
Immediate reversal=effect of dabigatran reversed to below the ULN directly after infusion of PRAXBIND.2
Complete reversal=mean clotting time returned to below the ULN. Cases with partial reversal were identified with laboratory assessment.2

aPTT=activated partial thromboplastin time; ECT=ecarin clotting time; ETP=endogenous thrombin; ULN=upper limit of normal; dTT=dilute thrombin time; TT=thrombin time; ACT=activated clotting time.

*Determined by mean clotting time below the ULN as measured by ECT and aPTT.
Based on determination for dTT or ECT.
Plasma concentrations on unbound PRADAXA were reduced to below the lower limit of quantification immediately after the administration of PRAXBIND 5 g in healthy volunteers aged 45-64 years.
§Blood samples were obtained at baseline, after the first infusion, at 10-30 min after the second infusion, and at 1, 2, 4, 12, and 24 hours.3

References: 1. PRAXBIND [Prescribing Information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc. 2. Glund S, Stangier J, Schmohl M, et al. Safety, tolerability, and efficacy of idarucizumab for the reversal of the anticoagulant effect of dabigatran in healthy male volunteers: a randomised, placebo-controlled, double-blind phase 1 trial. Lancet. 2015;386(9994):680-690. 3. Pollack CV, Reilly PA, Eikelboom J, et al. Idarucizumab for dabigatran reversal. N Engl J Med. 2015;373:511-520; 1-19 [suppl appendix]. 4. Drug Trials Snapshot: PRAXBIND. Silver Spring, MD: U.S. Food and Drug Administration; November 10, 2015. http://www.fda.gov/drugs/informationondrugs/ucm470762.htm. Accessed on July 22, 2016.