Edoxaban was safe and well tolerated up to 150 mg in healthy males, with predictable pharmacokinetics including a terminal elimination half-life of 5.8 to 10.7 hours.
RCT (n=121)
Single-blind
Does edoxaban demonstrate safety, tolerability, and predictable pharmacokinetics/pharmacodynamics in healthy males?
Single and multiple doses of the novel factor Xa inhibitor edoxaban up to 150 mg are safe and well tolerated in healthy males, with predictable pharmacokinetic and pharmacodynamic profiles.
This is a clinical safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) study of a single ascending dose (SAD) and a multiple ascending dose (MAD) of the oral direct factor Xa inhibitor edoxaban in healthy males. The placebo-controlled, single-blind, randomized, 2-part study consists of a SAD arm with 85 subjects (10, 30, 60, 90, 120, 150 mg) and a MAD arm with 36 subjects (90 mg daily, 60 mg twice daily, 120 mg daily). Effects of food and formulation (tablet vs solution) are assessed in a crossover substudy. In the SAD, doses are well tolerated up to 150 mg. Exposure is proportional to dose. PK profiles are consistent across dose with rapid absorption, biphasic elimination, and terminal elimination half-life of 5.8 to 10.7 hours. In the MAD, mean accumulation after daily dosing is 1.10 to 1.13 and consistent with elimination half-life of 8.75 to 10.4 hours. Intrasubject variability ranges from 12% to 17% for area under the curve. In general, plasma edoxaban concentrations are linearly correlated with coagulation parameters. Edoxaban is safe and well tolerated with no dose-dependent increases in adverse events. It is concluded that single and multiple doses of edoxaban are safe and well tolerated up to 150 mg with predictable PK and PD profiles.
Ogata et al. (Sat,) conducted a rct in Healthy volunteers (n=121). Edoxaban vs. Placebo was evaluated on Safety, tolerability, pharmacokinetics, and pharmacodynamics. Edoxaban was safe and well tolerated up to 150 mg in healthy males, with predictable pharmacokinetics including a terminal elimination half-life of 5.8 to 10.7 hours.