Back to Search
Start Over
A phase I, single and fractionated, ascending-dose study evaluating the safety, pharmacokinetics, pharmacodynamics, and immunogenicity of an erythropoietin mimetic antibody fusion protein (CNTO 528) in healthy male subjects.
- Source :
-
Journal of clinical pharmacology [J Clin Pharmacol] 2008 Oct; Vol. 48 (10), pp. 1197-207. - Publication Year :
- 2008
-
Abstract
- The erythropoietin mimetic antibody fusion protein CNTO 528 was developed as a novel antibody fusion protein by constructing an active hematopoietic peptide onto an IgG1-based scaffold. This resulted in a molecule with a long circulating half-life and a prolonged effect of stimulating reticulocyte production and hemoglobin (Hgb) synthesis. To assess the safety, pharmacokinetics, and pharmacodynamics of CNTO 528, the authors gave 44 adult healthy male subjects single or fractionated doses of intravenous CNTO 528 or placebo. CNTO 528 was generally well tolerated. The maximum observed concentration (Cmax) and the area under the concentration versus time curve (AUC) increased in an approximately dose-dependent manner between the 0.09-mg/kg and 0.9-mg/kg doses. The maximum effect on the reticulocyte response occurred approximately 8 to 9 days after administration. A median increase in Hgb (> or =1 g/dL above baseline) was achieved 9 to 10 days after administration, with a maximum effect between 19 and 26 days. Two subjects in the 0.9-mg/kg dose group had elevated Hgb concentrations requiring phlebotomy. In this first-in-human study, CNTO 528 was well tolerated and effective in elevating and maintaining Hgb by at least 1 g/dL following a single intravenous administration, which suggests that an erythropoietin mimetic molecule, such as CNTO 528, may be an effective therapy for patients with anemia.
- Subjects :
- Adolescent
Adult
Anemia drug therapy
Antibodies, Monoclonal adverse effects
Antibodies, Monoclonal immunology
Antibodies, Monoclonal pharmacokinetics
Area Under Curve
Dose-Response Relationship, Drug
Follow-Up Studies
Hemoglobins metabolism
Humans
Injections, Intravenous
Male
Middle Aged
Phlebotomy
Reticulocytes metabolism
Single-Blind Method
Time Factors
Young Adult
Antibodies, Monoclonal administration & dosage
Hemoglobins drug effects
Reticulocytes drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0091-2700
- Volume :
- 48
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Journal of clinical pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 18812609
- Full Text :
- https://doi.org/10.1177/0091270008322907