Exploration of the Effect and Pharmacokinetics of Intracvenous and Subcutaneous GC1113, a Novel Erythropoiesis-Stimulating Agent

Abstract

Introduction: GC1113, a hybrid Fc fused erythropoietin, is a novel erythropoiesis-stimulating agent which is expected to have an extended duration of action. The preclinical data showed that the hemoglobin increase lasted longer following GC1113 administration than it did following the administration of NESP®(Darbepoetin alfa). This study aimed to investigate the pharmacodynamic (PD), pharmacokinetic (PK) characteristics and tolerability profiles of GC1113 in humans after single intravenous (IV) or subcutaneous (SC) administration and to compare the results with those for NESP®. Methods: A dose-block randomized, placebo- and active- controlled, dose-escalation, phase 1 clinical trial was conducted with 96 healthy volunteers. Blood samples were collected before and up to 672 hours after drug administration and the erythropoietin concentration following the GC1113 or NESP® administration was measured by an enzyme-linked immunosorbent assay (ELISA). PK and PD parameters were determined using noncompartmental methods. Tolerability including immunogenicity evaluation was monitored during hospitalization and until the end of the study. Results: The reticulocyte count-time profiles in the IV GC1113 3–5 μg/kg groups were comparable with those of the NESP® 30 μg. After subcutaneous administration of GC1113, reticulocyte count peaked later and decreased more slowly than it did following NESP® administration. For pharmacokinetics, GC1113 showed faster elimination and slower absorption through subcutaneous administration than NESP®. The GC1113 (0.3–5 μg/kg for IV, 1–8 μg/kg SC) was well tolerated in the volunteers, and no immunogenicity was observed. Conclusions: GC1113 showed erythropoietic activity in healthy volunteers. Intravenous GC1113 showed comparable erythropoietic activity to NESP®, and following subcutaneous administration, the reticulocyte count increase lasted longer for GC1113 than for NESP®. GC1113 was tolerated and effective in the studied dose range

these findings could be applied to further clinical studies with patients.