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PI‐46
Author(s) -
Lambert J. R.,
Duliege A. M.,
Stead R.,
Wessels D. H.,
Pcikup E. M.,
Iwashita J.,
Leuther K.,
Woodburn K.,
Schatz P.,
Naso R.
Publication year - 2006
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2005.12.067
Subject(s) - erythropoietin , medicine , pharmacodynamics , erythropoiesis , pharmacology , cmax , epoetin alfa , pharmacokinetics , placebo , darbepoetin alfa , anemia , alternative medicine , pathology
BACKGROUND/AIM Hematide is a synthetic, PEGylated, peptidic ESA that binds to and activates the erythropoietin (EPO) receptor. Hematide has comparable in vitro activity to EPO and shows sustained plasma persistence in animal studies. A randomized double‐blind placebo controlled, intravenous single dose escalation study was conducted to assess the safety, PK and PD of Hematide in NHVs. METHODS Four cohorts, each with 7 NHVs (5 on active, 2 on placebo) received 0.025, 0.05 or 0.1mg/kg (two cohorts) of Hematide intravenously. Follow‐up was at least 28 days. Non‐compartmental PK parameters were calculated. RESULTS Hematide appeared to be safe and well tolerated. Reticulocyte increases were dose proportional (p<0.0001). The 0.1 mg/kg dose produced a clinically and statistically significant increase in hemoglobin (Hgb) from baseline that was sustained for > 1 month. Changes in all other PD parameters were consistent with stimulation of erythropoiesis. Mean C max ranged from 585 to 2868 ng/mL and the mean half‐life ranged from 19 to 23.5 hours (per dose group). First order kinetics were observed at lower drug concentrations only, suggesting saturation of metabolic/elimination processes at higher doses. CONCLUSION A single IV injection of Hematide in NHVs was well tolerated and demonstrated potent and sustained dose dependent erythropoietic activity. The sustained increase in Hgb after a single injection support the hypothesis of infrequent administration of Hematide in patients. Clinical Pharmacology & Therapeutics (2005) 79 , P19–P19; doi: 10.1016/j.clpt.2005.12.067