Pharmacokinetic and Pharmacodynamic Comparison of Two Recombinant Human Erythropoietin Formulations, PDA10 and Eprex, in Healthy Korean Male Volunteers: A Randomized, Double-Blinded, Single-Dose, Two-Period Crossover Study.

Abstract

BACKGROUND AND OBJECTIVES: A new biosimilar human recombinant epoetin alfa product (PDA10) has been developed by PanGen Biotech Inc., Korea. This study was planned to demonstrate the pharmacokinetic and pharmacodynamic comparability of PDA10 to an existing epoetin alfa (Eprex) after a single intravenous administration to healthy adult male volunteers.

METHODS: A randomized, double-blinded, single-dose, crossover study was conducted in 30 subjects. The subjects were assigned randomly to one of two sequence groups, and single doses of 100 IU/kg PDA10 or Eprex were administered intravenously on each of 2 treatment days separated by a 4-week washout period. Plasma erythropoietin concentrations were measured using an enzyme-linked immunosorbent assay and the pharmacokinetic parameters of the two treatments were compared. The time course and area under the effect curve (AUEC) of absolute reticulocyte counts were used as surrogate parameters for the pharmacodynamic evaluation. Adverse events (AEs) were recorded.

RESULTS: A total of 30 subjects were enrolled, and 27 completed the study. The geometric mean ratios (PDA10/Eprex) of erythropoietin for maximum plasma concentration (C max) and area under the plasma concentration-time curve to the last measurable concentration (AUC0-last) after intravenous administration of 100 IU/kg were 1.00 (90% confidence interval [CI] 0.96-1.05) and 0.96 (90% CI 0.93-1.00). The absolute reticulocyte counts of PDA10 and Eprex were similar, as determined from the maximum reticulocyte count and AUEC0-last values. Treatment-emergent AEs were mild and occurred in seven subjects.

CONCLUSION: PDA10 and Eprex met the regulatory criteria for bioequivalence with respect to their pharmacokinetic profiles and pharmacodynamic actions.