Boehringer Ingelheim has announced results showing that its investigational fully humanized antibody fragment ( Fab ) rapidly reversed the anticoagulation effect of Dabigatran ( Pradaxa ) in healthy male volunteers.
These results were presented during the American Heart Association’s Scientific Sessions 2013.

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 were of mild intensity.

In part I of the study, 5 of 110 subjects experienced a total of 6 adverse events 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 adverse events considered as drug-related, of which 2 occurred after the Fab: feeling hot and erythema. ( Xagena )

Source: Boehringer Ingelheim, 2013

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