title: Idarucizumab does not have procoagulant effects: Assessment of thrombosis biomarkers in healthy volunteers.
abstract: Idarucizumab, a humanised monoclonal antibody fragment, binds dabigatran with high affinity and immediately, completely and sustainably reverses dabigatran-induced changes on blood coagulation. The present analysis focuses on the evaluation of potential procoagulant properties of idarucizumab when administered in the absence of dabigatran. As part of two Phase I studies conducted in healthy Caucasian and Japanese male volunteers, the effect of idarucizumab (8 g as a 1-hour [h] infusion and 4 g as a 5-minute [min] infusion) and placebo on calibrated automated thrombography (CAT) was assessed using platelet-poor plasma samples. Measures were made before and 15 min after the end of infusion in Caucasian subjects, as well as pre-dose, 15 min, 4 h and 8 h in Japanese subjects. The levels of the thrombosis markers D-dimer and prothrombin fragment 1 + 2 (F1.2) were assessed over time in plasma samples up to 72 h after the end of infusion of idarucizumab and placebo. Idarucizumab had no apparent effect on endogenous thrombin formation as measured by CAT. D-dimer and F1.2 levels were highly variable in all dose groups but did not increase when compared with placebo or pre-dose levels. In conclusion, idarucizumab had no effect on endogenous thrombin generation. Additional markers of thrombosis, F1.2 and D-dimer, did not differ between placebo and idarucizumab, indicating a lack of procoagulant properties of idarucizumab.
authors.forename: Michael
authors.initials: M
authors.lastname: Schmohl
authors.forename: Stephan
authors.initials: S
authors.lastname: Glund
authors.forename: Akiko
authors.initials: A
authors.lastname: Harada
authors.forename: Susumu
authors.initials: S
authors.lastname: Imazu
authors.forename: Marina
authors.initials: M
authors.lastname: De Smet
authors.forename: Viktoria
authors.initials: V
authors.lastname: Moschetti
authors.forename: Steven
authors.initials: S
authors.lastname: Ramael
authors.forename: Ippei
authors.initials: I
authors.lastname: Ikushima
authors.forename: Fredrik
authors.initials: F
authors.lastname: Grünenfelder
authors.forename: Paul
authors.initials: P
authors.lastname: Reilly
authors.affiliation: Dr. Joachim Stangier, Boehringer Ingelheim Pharma GmbH & Co. KG, Translational Medicine & Clinical Pharmacology, Birkendorfer Strasse 65, 88397 Biberach an der Riß, Germany, Tel.: +49 7351 548443, Fax: +49 7351 838443, E-mail: joachim.stangier@boehringer-ingelheim.com.
authors.forename: Joachim
authors.initials: J
authors.lastname: Stangier
mesh_terms: D000293:Adolescent; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects*; D044466:Asian People; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D004311:Double-Blind Method; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D064368:Healthy Volunteers; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D011516:Prothrombin; D018570:Risk Assessment; D012307:Risk Factors; D013917:Thrombin / Q000378:metabolism; D013927:Thrombosis / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis / Q000208:ethnology; D013997:Time Factors; D044465:White People; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; C036309:fibrin fragment D; C045879:prothrombin fragment 1.2; D011516:Prothrombin; C000594745:idarucizumab; D013917:Thrombin
keywords: Idarucizumab; calibrated automated thrombography; coagulation biomarker; dabigatran