Abstract
Background and objective: The aim of this randomized, single dose, two-period crossover study with two weeks wash-out period was the demonstration of bioequivalence of two recombinant human granulocyte colony-stimulating factor (rG-CSF) formulations after subcutaneous administration of 300 μg comparing their pharmacokinetic (primary endpoints AUC0–24, AUC0–∞ and Cmax) and pharmacodynamic (primary endpoints ANC AUC0–72, ANC AUC0–∞ and ANCmax) profiles in healthy male subjects.
Materials and methods: A total of 36 (23.0 ± 6.0 years, 76.6 ± 7.2 kg) healthy subjects were recruited. Using a 1:1 randomization ratio, subjects were randomly assigned to one of two possible treatment-sequence groups to receive the single dose of test formulation (Gp-02) and reference product (NeupogenTM) concentrations were measured by enzyme-linked immunosorbent assay (ELISA) up to 24 h and the Absolute Neutrophil Count (ANC) was determined using hematology analyzer Coulter STKSTM (Beckman Coulter) up to 72 h after injection. The geometric mean of primary pharmacokinetic and pharmacodynamic variables were considered bioequivalent if the 90% confidence intervals (CI) would fall in the bioequivalence range of 80%–125%.
Results: AUC0–24 (ratio of means 103.4, 90% CI: 95.6–111.9), AUC0–∞ (103.4, 90% CI: 95.7–111.7), Cmax (99.6, 90% CI: 89.0–111.4), ANC AUC0–72 (100.0, 90% CI: 96.6–103.5), ANC AUC0–∞ (100.8, 90% CI: 96.5–105.3), and ANCmax (100.2, 90% CI: 95.4–105.1) were determined. Single doses of test and reference formulations were well tolerated. The incidence of AEs was equally distributed across treatment groups with the most frequent AEs being headache, fever, and back pain.
Conclusions: The study results demonstrated the bioequivalence of Gp-02, a new formulation of filgrastim, and the reference product NeupogenTM.
Materials and methods: A total of 36 (23.0 ± 6.0 years, 76.6 ± 7.2 kg) healthy subjects were recruited. Using a 1:1 randomization ratio, subjects were randomly assigned to one of two possible treatment-sequence groups to receive the single dose of test formulation (Gp-02) and reference product (NeupogenTM) concentrations were measured by enzyme-linked immunosorbent assay (ELISA) up to 24 h and the Absolute Neutrophil Count (ANC) was determined using hematology analyzer Coulter STKSTM (Beckman Coulter) up to 72 h after injection. The geometric mean of primary pharmacokinetic and pharmacodynamic variables were considered bioequivalent if the 90% confidence intervals (CI) would fall in the bioequivalence range of 80%–125%.
Results: AUC0–24 (ratio of means 103.4, 90% CI: 95.6–111.9), AUC0–∞ (103.4, 90% CI: 95.7–111.7), Cmax (99.6, 90% CI: 89.0–111.4), ANC AUC0–72 (100.0, 90% CI: 96.6–103.5), ANC AUC0–∞ (100.8, 90% CI: 96.5–105.3), and ANCmax (100.2, 90% CI: 95.4–105.1) were determined. Single doses of test and reference formulations were well tolerated. The incidence of AEs was equally distributed across treatment groups with the most frequent AEs being headache, fever, and back pain.
Conclusions: The study results demonstrated the bioequivalence of Gp-02, a new formulation of filgrastim, and the reference product NeupogenTM.