A comparative pharmacokinetic and pharmacodynamic study of FSK0808 versus reference filgrastim after repeated subcutaneous administration in healthy Japanese men

• Published in: Clinical pharmacology in drug development 2015-03, Vol.4 (2), p.99-104
• Main Authors: Matsuguma, Kyoko, Matsuki, Shunji, Sakamoto, Kei, Shiramoto, Masanari, Nakagawa, Misato, Kimura, Miyuki, Irie, Shin, Kaneko, Daiki, Ohnishi, Akihiro
• Format: Article
• Language: English
• Subjects: Adult; Antigens, CD34 - blood; Area Under Curve; Asian Continental Ancestry Group; Biomarkers - blood; Biosimilar Pharmaceuticals - administration & dosage; Biosimilar Pharmaceuticals - adverse effects; Biosimilar Pharmaceuticals - blood; Biosimilar Pharmaceuticals - pharmacokinetics; Cross-Over Studies; Double-Blind Method; Filgrastim - administration & dosage; Filgrastim - adverse effects; Filgrastim - pharmacokinetics; Granulocyte Colony-Stimulating Factor - administration & dosage; Granulocyte Colony-Stimulating Factor - adverse effects; Granulocyte Colony-Stimulating Factor - blood; Granulocyte Colony-Stimulating Factor - pharmacokinetics; Healthy Volunteers; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - metabolism; Humans; Japan; Male; Therapeutic Equivalency; Treatment Outcome; Young Adult
• ISSN: 2160-763X; 2160-7648
• DOI: 10.1002/cpdd.178

FSK0808, a biosimilar of filgrastim, is a recombinant human granulocyte colony‐stimulating factor developed by Fuji Pharmaceuticals and Mochida Pharmaceutical Co., Ltd. We conducted a double‐blind, randomized, crossover study in healthy Japanese men, comparing the number of CD34‐positive cells (CD34+ cells) after repeated subcutaneous administration of either FSK0808 or the reference filgrastim (Gran®). As primary endpoints, we compared the maximum number of CD34+ cells (CD34+ Cmax) and the time to reach CD34+ Cmax (CD34+ tmax). As secondary endpoints, we compared the area under the curve for the number of CD34+ cells over time at the 410 hours time point (CD34+ AUC0–410), the parameters used to calculate the pharmacodynamic index of the absolute neutrophil count, and the pharmacokinetic parameters. Regarding the CD34+ Cmax and the CD34+ AUC0–410 values, the 95% confidence interval (CI) of the differences between the mean values for each drug was within the range of log(0.8)–log(1.25). With respect to the differences in the median values between drugs, the ratio against the reference filgrastim median value in the 95% CI was within the range of ± 0.2 for the CD34+ tmax value. From these results, we considered that these drugs display equivalent pharmacodynamic and pharmacokinetic properties.