• Audrius Sveikata, Gintautas Gumbrevičius, Kastytis Seštakauskas, Rima Kregždytė, Vytautas Janulionis, and Vidmantas Fokas.
• Institute of Physiology and Pharmacology, Medicial Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania. Electronic address: audrius.sveikata@lsmuni.lt.
• Medicina (Kaunas). 2014 Jan 1; 50 (3): 144149144-9.

Background And ObjectiveThe 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 300μg 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 MethodsA total of 36 (23.0±6.0 years, 76.6±7.2kg) 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 (Neupogen™) concentrations were measured by enzyme-linked immunosorbent assay (ELISA) up to 24h and the Absolute Neutrophil Count (ANC) was determined using hematology analyzer Coulter STKS™ (Beckman Coulter) up to 72h 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%.ResultsAUC0-24 (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.ConclusionsThe study results demonstrated the bioequivalence of Gp-02, a new formulation of filgrastim, and the reference product Neupogen™.Copyright © 2014 Lithuanian University of Health Sciences. Production and hosting by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

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