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薬理と治療
Abstract
Background Filgrastim is used for medical treatment of neutropenia and for hematopoietic stem cell mobilization. Three pharmacokinetic(PK)studies were conducted to compare the PK and pharmacodynamic(PD)profiles of TKN732, a filgrastim biosimilar, with filgrastim Gran, marketed in Japan. TKN732 is manufactured from the same active pharmaceutical ingredient as XM02 which is approved by EMA and FDA. Methods The PK studies were randomized, single-dose, two-period crossover, two-arm studies with a three-week wash-out period. In total, 80 healthy male subjects were enrolled, 30 in each of two subcutaneous administration studies and 20 in an intravenous administration study. Subjects were randomized and received a single dose of the test drug(TKN732)or the reference drug(Gran syringe, Kyowa Hakko Kirin Co., Ltd.), with subsequent crossover. The serum rhG-CSF concentrations were measured by enzyme-linked immunosorbent assay(ELISA)for 48 hours after injection. The absolute neutrophil counts(ANC)were determined with a Coulter automated hematology analyzer. The primary PK(AUC0-48h and Cmax)variables were considered equivalent if the 90% confidence intervals were in the range of 80-125%. Equivalence of the secondary PD(ANC AUEC0-96h and ANCmax)variables was evaluated on the basis of the 95% CIs. Results Seventy-six subjects completed the studies. Statistic equivalence between the two products was demonstrated for both the PK and PD parameters in each study. The incidence of adverse events was the same with the two drugs, and they were both well tolerated. Conclusion The study results demonstrated the equivalence of TKN732 and the reference drug, Gran, with respect to their PK, PD and safety profiles.
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