Abstract

Objective: To compare the steady-state pharmacokinetics and pharmacodynamics following multiple subcutaneous administration of a new erythropoiesis stimulating agent (HX575, Binocrit^®, Sandoz GmbH, Holzkirchen, Germany) with that of epoetin beta (NeoRecormon^®, Roche Ltd., Welwyn Garden City, UK). Methods: An open, randomized, parallel group study was conducted in 80 healthy adult males. Subjects were randomized to multiple subcutaneous doses of 100 IU/kg body weight of HX575 or epoetin beta three-times-weekly for 4 weeks. Serum epoetin concentrations were measured using an enzyme-linked immunosorbent assay (ELISA) and pharmacokinetic parameters for the two treatments were compared. The time course and area under the effect curve ratios of hematological characteristics were used as surrogate parameters for efficacy evaluation. Results: The pharmacokinetic profiles after multiple doses were similar for both treatments. HX575 was bioequivalent to epoetin beta with respect to the rate and extent of exposure of exogenous epoetin, as indicated by the ratios (90% confidence intervals) of AUC_tau (96.1 (86.4 – 106.9)) and C_max,ss (98.5 (85.2 – 113.9)). The hematological profiles of both treatments were similar as determined from the population mean curves and the AUEC_Hb ratio (90% confidence interval] (99.2 (97.7 – 100.7)), the primary endpoint of this study. Study medication was well tolerated with no clinically relevant differences between safety profiles of the treatments. Anti-epoetin antibodies were not detected at any time. Conclusions: HX575 and epoetin beta were bioequivalent with respect to their steady-state pharmacokinetic profile and pharmacodynamic action. These results support the conclusion that HX575 and epoetin beta will be equally efficacious and may be interchangeable as therapy.

Author Details

Authors

• F. Sörgel¹
• U. Thyroff-Friesinger²
• A. Vetter²
• B. Vens-Cappell³
• M. Kinzig¹

Departments

• ¹ IBMP-Institute for Biomedical and Pharmaceutical Research, Nürnberg-Heroldsberg,
• ² Clinical Research, Hexal AG, Holzkirchen, and
• ³ Scope International, Hamburg, Germany

Address

Prof. F. Sörgel
Department of Research
IBMP-Institute for Biomedical and Pharmaceutical Research
Paul-Ehrlich-Straße 19
90562 Nürnberg-Heroldsberg, Germany
Email: [email protected]

Citation