A randomised study in healthy volunteers to investigate the safety, tolerability and pharmacokinetics of idarucizumab, a specific antidote to dabigatran

Thrombosis and Haemostasis

Volumn 113, Issue 5, 2015, Pages 943-951

  Glund, Stephan ^a   Moschetti, Viktoria ^a   Norris, Stephen ^b   Stangier, Joachim ^a   Schmohl, Michael ^a   Van Ryn, Joanne ^a   Lang, Benjamin ^a   Ramael, Steven ^c   Reilly, Paul ^b  

^a BOEHRINGER INGELHEIM PHARMA GMBH AND CO KG   (Germany)

^b BOEHRINGER INGELHEIM PHARMACEUTICALS INC   (United States)

^c SGS Life Science Services   (Belgium)

Author keywords

Antidote; Dabigatran etexilate; Idarucizumab; Reversal agent; Safety

Indexed keywords

ANTIDOTE; DABIGATRAN; IDARUCIZUMAB; PLACEBO; ANTICOAGULANT AGENT; MONOCLONAL ANTIBODY;

ADULT; APPLICATION SITE PAIN; AREA UNDER THE CURVE; ARTICLE; BACKACHE; BLOOD CLOTTING; BLOOD CLOTTING TIME; CONTROLLED STUDY; DIARRHEA; DIZZINESS; DOUBLE BLIND PROCEDURE; DRUG DISTRIBUTION; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG SAFETY; DRUG TOLERABILITY; ERYTHEMA; HEADACHE; HUMAN; HUMAN EXPERIMENT; MALE; MAXIMUM PLASMA CONCENTRATION; MIGRAINE; MUSCULOSKELETAL STIFFNESS; NORMAL HUMAN; PRIORITY JOURNAL; RHINOPHARYNGITIS; SKIN IRRITATION; THROMBIN TIME; TIME TO MAXIMUM PLASMA CONCENTRATION; ADOLESCENT; ANTAGONISTS AND INHIBITORS; BLOOD CLOTTING TEST; CHEMISTRY; CLINICAL TRIAL; DOSE RESPONSE; INTRAVENOUS DRUG ADMINISTRATION; MIDDLE AGED; PHASE 1 CLINICAL TRIAL; RANDOMIZED CONTROLLED TRIAL; TIME; YOUNG ADULT;

ADOLESCENT; ADULT; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTICOAGULANTS; AREA UNDER CURVE; BLOOD COAGULATION; BLOOD COAGULATION TESTS; DABIGATRAN; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; HEALTHY VOLUNTEERS; HUMANS; INFUSIONS, INTRAVENOUS; MALE; MIDDLE AGED; TIME FACTORS; YOUNG ADULT;

EID: 84930965307     PISSN: 03406245     EISSN: None     Source Type: Journal    
DOI: 10.1160/TH14-12-1080     Document Type: Article

References (19)

1. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139–1151.
2. Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med 2009; 361: 2342–2352.
3. Schulman S, Kakkar AK, Goldhaber SZ, et al. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation 2014; 129: 764–772.
4. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Newly identified events in the RE-LY trial. N Engl J Med 2010; 363: 1875–1876.
5. Friedman RJ, Dahl OE, Rosencher N, et al. Dabigatran versus enoxaparin for prevention of venous thromboembolism after hip or knee arthroplasty: a pooled analysis of three trials. Thromb Res 2010; 126: 175–182.
6. Majeed A, Hwang HG, Connolly SJ, et al. Management and outcomes of major bleeding during treatment with dabigatran or warfarin. Circulation 2013; 128: 2325–2332.
7. Heidbuchel H, Verhamme P, Alings M, et al. EHRA practical guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation: executive summary. Eur Heart J 2013; 34: 2094–2106.
8. Bauer KA. Reversal of antithrombotic agents. Am J Hematol 2012; 87 (Suppl 1): S119-S126.
9. van Ryn J, Stangier J, Haertter S, et al. Dabigatran etexilate–a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost 2010; 103: 1116–1127.
10. Schiele F, van Ryn J, Canada K, et al. A specific antidote for dabigatran: functional and structural characterization. Blood 2013; 121: 3554–3562.
11. van Ryn J, Litzenburger T, Schurer J. Reversal of anticoagulant activity of dabigatran and dabigatran-induced bleeding in rats by a specific antidote (antibody fragment). Circulation 2012; 126: A9928.
12. Grottke O, Honickel M, van Ryn J, et al. A specific antidote to dabigatran reduces blood loss in dabigatran- and trauma-induced bleeding in pigs. J Am Coll Cardiol 2014; 63 (12_S).
13. Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet 2008; 47: 285–295.
14. Stangier J, Feuring M. Using the HEMOCLOT direct thrombin inhibitor assay to determine plasma concentrations of dabigatran. Blood Coagul Fibrinolysis 2012; 23: 138–143.
15. Meibohm B, Zhou H. Characterizing the impact of renal impairment on the clinical pharmacology of biologics. J Clin Pharmacol 2012; 52: 54S-62S.
16. Christensen EI, Birn H, Storm T, et al. Endocytic receptors in the renal proximal tubule. Physiology 2012; 27: 223–236.
17. Behr TM, Sharkey RM, Juweid ME, et al. Reduction of the renal uptake of radiolabeled monoclonal antibody fragments by cationic amino acids and their derivatives. Cancer Res 1995; 55: 3825–3834.
18. Behr TM, Becker WS, Sharkey RM, et al. Reduction of renal uptake of monoclonal antibody fragments by amino acid infusion. J Nucl Med 1996; 37: 829–833.
19. Reilly PA, Lehr T, Haertter S, et al. The effect of dabigatran plasma concentrations and patient characteristics on the frequency of ischemic stroke and major bleeding in atrial fibrillation patients: the RE-LY Trial (Randomized Evaluation of Long-Term Anticoagulation Therapy). J Am Coll Cardiol 2014; 63: 321–328.