Open Access Highly Accessed Research article

Comparison of two recombinant erythropoietin formulations in patients with anemia due to end-stage renal disease on hemodialysis: A parallel, randomized, double blind study

Jorge F Pérez-Oliva1, Martha Casanova-González2, Idrian García-García3*, Pedro J Porrero-Martín3, Carmen M Valenzuela-Silva3, Tairí Hernández-Montero4, Marcia Lagarde-Ampudia4, Yuri Casanova-Kutsareva3, Yisel Ávila-Albuerne5, Alicia Vargas-Batista5, Hailen Bobillo-López3, Raúl Herrera-Valdés1, Pedro A López-Saura3 and the Bioequivalence Study of Erythropoietin Group

Author Affiliations

1 Hemodialysis Department, National Institute of Nephrology, Havana, Cuba

2 Nephrology Department, "Gustavo Aldereguía Lima" Hospital, Cienfuegos, Cuba

3 Clinical Trials Division, Center for Biological Research, Havana, Cuba

4 Clinical Laboratory Department, National Institute of Nephrology, Havana, Cuba

5 Clinical Trials Department, National Center of Clinical Trials, Havana, Cuba

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BMC Nephrology 2005, 6:5  doi:10.1186/1471-2369-6-5

Published: 23 May 2005

Abstract

Background

Recombinant human erythropoietin (EPO) is used for the treatment of last stage renal anemia. A new EPO preparation was obtained in Cuba in order to make this treatment fully nationally available. The aim of this study was to compare the pharmacokinetic, pharmacodynamic and safety properties of two recombinant EPO formulations in patients with anemia due to end-stage renal disease on hemodialysis.

Methods

A parallel, randomized, double blind study was performed. A single 100 IU/Kg EPO dose was administered subcutaneously. Heberitro (Heber Biotec, Havana, formulation A), a newly developed product and Eprex (CILAG AG, Switzerland, formulation B), as reference treatment were compared. Thirty-four patients with anemia due to end-stage renal disease on hemodialysis were included. Patients had not received EPO previously. Serum EPO level was measured by enzyme immunoassay (EIA) during 120 hours after administration. Clinical and laboratory variables were determined as pharmacodynamic and safety criteria until 216 hours.

Results

Both groups of patients were similar regarding all demographic and baseline characteristics. EPO kinetics profiles were similar for both formulations; the pharmacokinetic parameters were very close (i.e., AUC: 4667 vs. 4918 mIU.h/mL; Cmax: 119.1 vs. 119.7 mIU/mL; Tmax: 13.9 vs. 18.1 h; half-life, 20.0 vs. 22.5 h for formulations A and B, respectively). The 90% confidence intervals for the ratio between both products regarding these metrics were close to the 0.8 – 1.25 range, considered necessary for bioequivalence. Differences did not reach 20% in any case and were not determined by a formulation effect, but probably by a patients' variability effect. Concerning pharmacodynamic features, a high similitude in reticulocyte counts increments until 216 hours and the percentage decrease in serum iron until 120 hours was observed. There were no differences between formulations regarding the adverse events and their intensity. The more frequent events were pain at injection site (35.3%) and hypertension (29%). Additionally, further treatment of the patients with the study product yielded satisfactory increases in hemoglobin and hematocrit values.

Conclusion

The formulations are comparable. The newly developed product should be acceptable for long-term application.