Apixaban in End-stage Kidney Disease : A Pharmacokinetics Study
Status:
Completed
Trial end date:
2018-08-24
Target enrollment:
Participant gender:
Summary
Apixaban is a novel oral direct factor Xa inhibitor; In patients with atrial fibrillation,
apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less
bleeding, and resulted in lower mortality (the ARISTOTLE trial). Given its favorable outcome
profile compared to oral vitamin K antagonists in patients with normal kidney function and in
patients with mild to moderate kidney disease and given the potential serious side-effects of
oral vitamin K antagonists in end-stage kidney disease, apixaban may be an attractive
alternative for systemic anticoagulation in dialysis patients. The pharmacokinetics of
apixaban in end-stage renal disease is not well characterized.
The aim of the current study is to perform single dose pharmacokinetics / pharmacodynamics
studies in patients treated with end-stage renal disease. The primary aim is to determine
inter-dialytic pharmacokinetics of Apixaban, secondary aims are intra-dialytic
pharmacokinetics and dose finding. Two doses of drugs will be studies (2.5 mg and 5 mg).
Study drug will be administered at the end of a dialysis session (part A) and at the
beginning of a dialysis session (Part B). Six (n=6) patients are scheduled to be included for
each part and each dose.
Anti-Xa activity values (IIU/mL) will be converted to apixaban concentration data (ng/mL).
Apixaban concentration-time profiles will be generated and observed values for the
descriptive PK parameters Cmax (peak plasma concentration) and time to Cmax (Tmax) will be
determined directly from these profiles. PK profiles will be further analyzed with
non-compartmental analysis (NCA).