Objective: The objective of the study was the demonstration of bioequivalence of two recombinant human granulocyte colony-stimulating factor (G-CSF) formulations after subcutaneous administration of 5 microg/kg and 10 microg/kg comparing their pharmacokinetic and pharmacodynamic profiles in healthy subjects.
Methods: This was a randomized, single dose, two-period cross-over, two-arm study with a 14 days wash-out period. In total 56 subjects were included, 28 in each dosage cohort (5 microg/kg and 10 microg/kg). Using a 1 : 1 : 1 : 1 randomization ratio, subjects were randomly assigned to one of four possible treatment-sequence groups. A single dose of test formulation (XM02) and reference product (Neupogen, F. Hoffmann - La Roche, Ltd.) were injected. The serum G-CSF concentrations were measured by enzyme-linked immunosorbent assay (ELISA) during 48 hours after injection. The absolute Neutrophil Count (ANC) was determined by automated hematology analyzer Coulter STKSTM (Beckman Coulter, Inc.) up to 96 hours after injection. The primary pharmacokinetic (AUC0-48, AUC0- yen and Cmax) and pharmacodynamic (ANC AUC0-96, ANC AUC0- yen and ANCmax) variables were considered bioequivalent if the 90% confidence intervals (CI) were in the bioequivalence range of 80 - 125%.
Results: 50 subjects completed the study: 24 subjects in 5 microg/kg and 26 in 10 microg/kg dosage groups. The pharmacokinetic and pharmacodynamic parameters in 5 mg/kg and 10 mg/kg group for both formulations were very close to each other. Single doses of test and reference formulations were well tolerated. The most frequent AEs were: headache, erythrocyturia and myalgia. The incidence of AEs was equally distributed across dosage and treatment groups.
Conclusion: The study results demonstrated the bioequivalence of two body weight-dependent doses of XM02, a new formulation of filgrastim, and the reference product Neupogen after administration of a 5 microg/kg b.w. and 10 microg/kg b.w. with respect to pharmacokinetic, pharmacodynamic and safety profiles.