This study aimed to assess and compare the pharmacokinetic (PK) and pharmacodynamic (PD) properties following a single subcutaneous injection of epoetin alfa (Eporon ®) with those of the comparator (Eprex ®) in healthy male subjects.
A randomized, double-blind, two-sequence, crossover study was conducted. Subjects were randomly assigned to receive a single dose, that is, 4,000 IU, of the test or comparator epoetin alfa. After 4 weeks, all subjects received the alternative formulation. The primary PK parameters, maximum observed concentration (C max) and area under the curve extrapolated to infinity (AUC inf), were calculated with the serum erythropoietin (EPO) concentrations from blood samples collected for 144 h after dosing. The reticulocyte, hematocrit, hemoglobin and red blood cell counts were measured up to 312 h as PD markers. The primary PD parameters, maximum observed effect (E max) and area under the effect curve (AUEC), were obtained from the baseline-corrected reticulocyte count. The serum EPO concentration and the reticulocyte count were used to assess the concentration–response relationship. The tolerability and immunogenicity profiles were assessed together.
Forty-two subjects completed the study. The mean EPO concentration–time profiles were comparable between the two formulations. The geometric mean ratios (90% CI) of the C max and AUC inf were 0.908 (0.843–0.978) and 1.049 (0.999–1.101), respectively, both of which were within the regulatory range of 0.80–1.25. Additionally, the PD and tolerability profiles were similar between the two formulations. The time-matched serum EPO concentration and PD markers presented a counterclockwise hysteresis, suggesting a time delay between the measured concentration and the response. Both formulations were well tolerated, and production of anti-drug antibodies was not observed.