BACKGROUND AND OBJECTIVES:GC1113, a hybrid Fc-fused erythropoietin, is a novel erythropoiesis-stimulating agent that 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 darbepoetin alfa (NESP®). This study aimed to investigate the pharmacodynamic and pharmacokinetic characteristics and tolerability profiles of GC1113 in humans after single intravenous or subcutaneous administration and to compare the results with those for darbepoetin alfa. METHODS: A dose-block randomized, placebo- and active-controlled, dose-escalation phase I clinical trial was conducted in 96 healthy volunteers. Blood samples were collected before and up to 672 h after drug administration and the serum erythropoietin concentration following the GC1113 or darbepoetin alfa administration was measured by an ELISA. The reticulocyte counts were measured for pharmacodynamic assessments. Pharmacokinetic and pharmacodynamic parameters were determined using non-compartmental methods. RESULTS: The reticulocyte count-time profiles in the intravenous GC1113 3-5 μg/kg groups were comparable with those of the darbepoetin alfa 30 μg group. After subcutaneous administration of GC1113, reticulocyte count peaked later and decreased more slowly than it did following darbepoetin alfa administration. GC1113 (0.3-5 μg/kg intravenous, 1-8 μg/kg subcutaneous) was well-tolerated in the volunteers, and no immunogenicity was observed. CONCLUSION:GC1113 was tolerated and effective in the studied dose range; these findings could be applied to further clinical studies with patients.
RCT Entities:
BACKGROUND AND OBJECTIVES: GC1113, a hybrid Fc-fused erythropoietin, is a novel erythropoiesis-stimulating agent that 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 darbepoetin alfa (NESP®). This study aimed to investigate the pharmacodynamic and pharmacokinetic characteristics and tolerability profiles of GC1113 in humans after single intravenous or subcutaneous administration and to compare the results with those for darbepoetin alfa. METHODS: A dose-block randomized, placebo- and active-controlled, dose-escalation phase I clinical trial was conducted in 96 healthy volunteers. Blood samples were collected before and up to 672 h after drug administration and the serum erythropoietin concentration following the GC1113 or darbepoetin alfa administration was measured by an ELISA. The reticulocyte counts were measured for pharmacodynamic assessments. Pharmacokinetic and pharmacodynamic parameters were determined using non-compartmental methods. RESULTS: The reticulocyte count-time profiles in the intravenous GC1113 3-5 μg/kg groups were comparable with those of the darbepoetin alfa 30 μg group. After subcutaneous administration of GC1113, reticulocyte count peaked later and decreased more slowly than it did following darbepoetin alfa administration. GC1113 (0.3-5 μg/kg intravenous, 1-8 μg/kg subcutaneous) was well-tolerated in the volunteers, and no immunogenicity was observed. CONCLUSION: GC1113 was tolerated and effective in the studied dose range; these findings could be applied to further clinical studies with patients.
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