BACKGROUND AND OBJECTIVES: Idarucizumab is an antibody fragment that 
specifically reverses dabigatran-mediated anticoagulation. Safety, 
pharmacokinetics and pharmacodynamics of idarucizumab were investigated in 
dabigatran-treated, middle-aged, elderly and renally impaired volunteers with 
characteristics similar to patients receiving anticoagulant therapy.
METHODS: In this randomized, double-blind, crossover study, 46 subjects (12 
middle-aged, 45-64 years; 16 elderly, 65-80 years; and 18 with mild or moderate 
renal impairment) received dabigatran etexilate (DE; 220 or 150 mg twice daily) 
for 4 days. Idarucizumab doses of 1, 2.5 and 5 g or 2 × 2.5 g 1 h apart, or 
placebo, were administered as a rapid (5 min) infusion ~2 h after DE at steady 
state.
RESULTS: Dabigatran-prolonged diluted thrombin time, ecarin clotting time and 
activated partial thromboplastin time were reversed to baseline immediately 
after idarucizumab infusion in all groups. Reversal was sustained with doses 
≥2.5 g. Idarucizumab was well tolerated under all conditions. No impact of age 
on idarucizumab pharmacokinetics was observed; however, subjects with mild or 
moderate renal impairment demonstrated increased exposure (up to 84 %), 
decreased clearance and prolonged (by up to 49 %) initial half-life of 
idarucizumab compared with healthy middle-aged subjects.
CONCLUSIONS: Impaired renal function was associated with increased exposure and 
decreased clearance of idarucizumab. Idarucizumab resulted in immediate, 
complete and sustained reversal of dabigatran anticoagulant activity, and was 
safe and well tolerated in middle-aged, elderly and renally impaired volunteers. 
The results support the clinical use of a 5 g dose of idarucizumab.
CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov . Unique identifier: 
NCT01955720.