Pharmacokinetics and pharmacodynamics of FSK0808 and Gran after single intravenous drip administration or single subcutaneous administration: comparative study in healthy Japanese adult male subjects

Abstract

FSK0808 is a recombinant human granulocyte colony-stimulating factor developed by Fuji Pharma Co., Ltd and Mochida Pharmaceutical Co., Ltd. as a biosimilar product of Gran®. We verified the pharmacokinetic/pharmacodynamic equivalence of FSK0808 and commercially available Gran® by a randomized crossover study of single intravenous dose (200 µg/m²) and single subcutaneous dose (400 µg/m²) in healthy Japanese adult male subjects. According to the bioequivalence guidelines, the area under the blood concentration – time curve by 48 hours after administration (AUC_0–48) in a single intravenous drip (IVD) study, and AUC_0–48 and maximum blood concentration (C_max) in a single subcutaneous (SC) dose study were used as primary endpoints, and the pharmacodynamic parameters including absolute neutrophil count (ANC) or number of CD34 positive cells (CD34⁺ cells) as secondary endpoints. The safety was evaluated based on the characteristics and incidence of adverse reactions. As a result, the 90% confidence interval (CI) of the difference in mean value for AUC_0–48 among drugs ranged from log(0.8) to log(1.25), in the IVD study, and those for C_max and AUC_0–48 were within the range of log(0.8)–log(1.25) in the SC study. Those for secondary endpoints were all within the range of log(0.8)–log(1.25). Thus, the pharmacokinetics/pharmacodynamics of both drugs were considered equivalent for all routes of administration, and the profiles of adverse reactions were also very similar.

• Biosimilar
• clinical trial
• filgrastim
• G-CSF
• pharmacodynamics
• pharmacokinetics

Declaration of interest

Financial supports for these studies were provided by Fuji Pharma Co., Ltd and Mochida Pharmaceutical Co., Ltd. One author, Daiki Kaneko was an employee in Fuji Pharma Co., Ltd and the other authors have no conflicts of interest.