Boehringer Ingelheim Pharmaceuticals, Inc. today announced results showing that its investigational fully humanized antibody fragment (Fab) rapidly reversed the anticoagulation effect of dabigatran in healthy male volunteers. These results, presented today during the American Heart Association's Scientific Sessions 2013, represent the first clinical data involving the compound, which was discovered and developed by the company (ClinicalTrials.gov Identifier: NCT01955720).

In this randomized, double-blind, placebo-controlled study of 145 healthy male volunteers, investigators evaluated the safety, tolerability, pharmacokinetics and pharmacodynamics of the Fab. In part one of the study, subjects received single, progressively increasing intravenous doses of up to 8 g of the Fab. In part two, the potential for reversal of dabigatran-induced anticoagulation was evaluated, with 5-minute intravenous infusions using doses of 1 g, 2 g and 4 g following pre-treatment with dabigatran (220 mg twice-daily for 3 days). The anticoagulant effect of dabigatran and its reversal were assessed using diluted thrombin time (Hemoclot® DTI assay), thrombin time (TT), activated partial thromboplastin time (aPTT), ecarin clotting time (ECT) and activated clotting time (ACT). Dabigatran prolonged clotting times of all coagulation markers.

Results of the study showed:

• The on-set of action of the antidote was detected immediately following a 5-minute infusion
• Thrombin time, which is a measurement of the time it takes for a clot to form in a blood sample and the most sensitive indicator of dabigatran's anticoagulant effect, was reversed with the Fab
• With this assay, reversal of the anticoagulation effect was complete and sustained in 7 of 9 subjects who received the 2 g dose and in 8 out of 8 subjects who received the 4 g dose
• The 1 g dose resulted in complete reversal of anticoagulation effect; however, after approximately 30 minutes there was some return of the anticoagulation effects of dabigatran
• All Fab-related adverse events (AEs) were of mild intensity:
• In part I of the study, 5 of 110 subjects experienced a total of 6 AEs considered as drug-related, of which 3 occurred after receiving the Fab: headache, erythema and migraine
• In part II, 5 of 35 subjects experienced a total of 6 AEs considered as drug-related, of which 2 occurred after the Fab: feeling hot and erythema

"Boehringer Ingelheim was the leader in bringing the first novel, oral anticoagulant treatment to reduce the risk of stroke in patients with non-valvular atrial fibrillation. Through our commitment to scientific innovation, our scientists continue to lead research which may further improve outcomes in patients treated with PRADAXA whose bleeding event may not be adequately managed by standard measures alone," said Sabine Luik, M.D., senior vice president, Medicine & Regulatory Affairs, U.S. Regional Medical Director, Boehringer Ingelheim Pharmaceuticals, Inc. "Even in the absence of a specific antidote, PRADAXA's stroke risk reduction is well-documented through the pivotal RE-LY® trial. These new findings represent an important step in the development of a specific antidote for PRADAXA."

Currently, no specific antidotes for new oral anticoagulants (NOACs) are available to complement the existing range of bleed management options during critical care situations. In the absence of approved antidotes for NOACs, standard clinical support for bleeding is similar for anticoagulant treatments, and may include applying direct pressure to the site of the bleeding, administering fluids and/or blood products (e.g., blood transfusions or plasma-derived clotting factor therapies) as needed, or stopping the bleeding through surgery.