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AIMS: JNJ-64179375 (hereafter JNJ-9375) is a first-in-class, highly specific, large molecule, exosite 1 thrombin inhibitor. In preclinical studies, JNJ-9375 demonstrated robust antithrombotic protection with a wider therapeutic index when compared to apixaban. The purpose of the present study was to examine for the first time the antiplatelet, anticoagulant and antithrombotic effects of JNJ-9375 in a translational model of ex vivo human thrombosis. METHODS AND RESULTS: Fifteen healthy volunteers participated in a double-blind randomized crossover study of JNJ-9375 (2.5, 25, and 250 μg/mL), bivalirudin (6 μg/mL; positive control), and matched placebo. Coagulation, platelet activation, and thrombus formation were determined using coagulation assays, flow cytometry, and an ex vivo perfusion chamber, respectively.JNJ-9375 caused concentration-dependent prolongation of all measures of blood coagulation (prothrombin time, activated partial thromboplastin time, and thrombin time; P 

Original publication

DOI

10.1093/cvr/cvy227

Type

Journal article

Journal

Cardiovasc res

Publication Date

01/03/2019

Volume

115

Pages

669 - 677

Keywords

Anticoagulant, Exosite 1 thrombin, JNJ-9375, Novel, Thrombosis, Adult, Antithrombins, Biomarkers, Blood Coagulation, Blood Coagulation Tests, Blood Platelets, Cross-Over Studies, Dose-Response Relationship, Drug, Double-Blind Method, Female, Fibrin, Healthy Volunteers, Hirudins, Humans, Male, P-Selectin, Peptide Fragments, Platelet Activation, Recombinant Proteins, Scotland, Thrombosis, Young Adult