A study in healthy volunteers investigating the reversal of the anticoagulant effect of dabigatran etexilate (Pradaxa, Boehringer Ingelheim) by its specific agent idarucizumab has shown the antidote led to immediate, complete and sustained reversal of the anticoagulant effect. Results were recently published in The Lancet.
The study authored by Stephan Glund and others and funded by Boehringer Ingelheim, demonstrated that idarucizumab was well tolerated with no unexpected or clinically relevant safety concerns in healthy men.
The data support the specific reversal agent as a highly-targeted treatment option if reversal of the anticoagulant effect is needed, eg. for urgent interventions. Idarucizumab was granted breakthrough therapy designation by the US Food and Drug Administration (FDA) and has recently been submitted for approval to the FDA, European Medicines Agency and Health Canada. Boehringer Ingelheim pursues accelerated procedures with all three regulatory authorities.
The randomised, placebo-controlled, double-blind, prof-of-concept phase I study enrolled 47 healthy men aged 18-45 years. Patients were randomly assigned within groups in a 3:1 ratio to idarucizumab or placebo. All participants first received dabigatran etexilate 220mg twice daily for three days and a final dose on day four. The specific reversal agent was given two hours after the last dose of dabigatran, when the anticoagulant concentrations were at peak levels. After a five-minute infusion of idarucizumab, anticoagulation was immediately reversed back to baseline levels. The reversal effect was sustained for more than 24 hours for all doses of 2g and above.
Similar results were also seen in elderly and renally impaired volunteers in a study presented at the Annual Meeting & Exposition of the American Society for Hematology (5–8 December 2014, Orlando, USA). Boehringer Ingelheim is now evaluating idarucizumab in the RE-VERSE AD study, the first study to investigate a reversal agent to a non-vitamin K antagonist oral anticoagulant in patients.
