A Phase I study to determine safety, pharmacokinetics, and pharmacodynamics of ANF-RHO™, a novel PEGylated granulocyte colony-stimulating factor, in healthy volunteers
Autor: | Hemant Misra, John Berryman, Abraham Abuchowski, Ronald G. Jubin |
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Rok vydání: | 2017 |
Předmět: |
Adult
Male Neutrophils Pain Neutropenia Pharmacology Polyethylene Glycols Leukocyte Count Young Adult 03 medical and health sciences 0302 clinical medicine Double-Blind Method Pharmacokinetics Granulocyte Colony-Stimulating Factor Humans Medicine Pharmacology (medical) 030212 general & internal medicine Bone pain business.industry Middle Aged medicine.disease Healthy Volunteers Recombinant Proteins Granulocyte colony-stimulating factor Oncology Tolerability 030220 oncology & carcinogenesis Pharmacodynamics Absolute neutrophil count Female medicine.symptom business Pegfilgrastim medicine.drug |
Zdroj: | Investigational New Drugs. 36:75-84 |
ISSN: | 1573-0646 0167-6997 |
Popis: | Patients receiving pegfilgrastim (Neulasta®) for the treatment of neutropenia can experience bone pain following the injections required to achieve effective neutrophil levels. The safety, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of ANF-RHO™, a novel pegylated granulocyte colony stimulating factor, were assessed in a randomized, controlled, double-blind Phase 1 clinical study in healthy volunteers. Subjects received a single subcutaneous dose of ANF-RHO over a range of 6 doses (5-50 μg/kg), placebo (saline), or the recommended clinical dose of pegfilgrastim administered at the labeled fixed 6 mg dosage (equivalent to 80-100 μg/kg). The primary outcome measure was safety and tolerability. Secondary outcomes included PK and PD effects on absolute neutrophil count (ANC) and number of CD34+ progenitor cells. Severity of bone pain was also assessed. In healthy volunteers, ANF-RHO was administered at ascending doses up to 50 μg/kg without significant adverse effects; appeared to be better (5 to 30 μg/kg) or equally well (50 μg/kg) tolerated, and had lower mean bone pain scores as compared to pegfilgrastim. ANF-RHO achieved CD34+ and ANC numbers at significantly lower doses, and had a significantly longer circulating half-life than pegfilgrastim. These results suggest that ANF-RHO can be provided less frequently, at a lower dose, and with fewer side effects. ANF-RHO had unique, prolonged PK/PD attributes as compared to marketed pegfilgrastim, suggesting that it may provide an improved clinical benefit in further clinical studies in patients with chemotherapy-induced or chronic idiopathic neutropenia. |
Databáze: | OpenAIRE |
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