Boehringer Ingelheim has reported positive Phase I results which showed that a five-minute infusion of the investigational specific antidote idarucizumab led to immediate, complete and sustained reversal of the anticoagulant effect of Pradaxa (dabigatran etexilate).
The randomised, double-blind, placebo-controlled cross-over trial included 46 male and female volunteers ranging from 45 to 80 years of age.
All doses of idarucizumab, a humanised antibody fragment (Fab), were found to be well tolerated in healthy volunteers who were middle-aged (45-64 years) or elderly (65-80 years), or volunteers with mild or moderate kidney impairment.
In addition, anticoagulation was restored when volunteers were re-dosed with dabigatran 24 hours after idarucizumab was administered.
The company said that a second administration of idarucizumab also showed that anticoagulation reversal was comparable to the results observed in the first administration.
For three days, the volunteers aged 45-80 years were given a high dose of dabigatran 220mg twice daily, and 150mg twice daily to those with mild or moderate kidney impairment, with one final dose given on the fourth day.
Boehringer Ingelheim vice-president Medicine Therapeutic Area Cardiovascular professor Jörg Kreuzer said: "These results showed that idarucizumab consistently reversed the anticoagulant effects of dabigatran in adults independent of gender, age and kidney function, complementing data previously reported from younger, healthy male volunteers.
"Our findings show that the antidote’s effects remain consistent following a second administration and also that anticoagulation from dabigatran can be successfully restored 24 hours after idarucizumab is given."
The company is developing idarucizumab as a highly specific and selective antidote to Pradaxa to add a reversal option for physicians.
In June, the US Food and Drug Administration (FDA) granted breakthrough therapy designation to idarucizumab.
Currently, the company is evaluating idarucizumab in RE-VERSE AD, a Phase III global trial investigating idarucizumab in actual clinical settings where Pradaxa patients may require emergency intervention or experience an uncontrolled or life-threatening bleeding event.