Published in:
01-11-2013 | Original Research Article
Relationship Between Absolute Neutrophil Count Profiles and Pharmacokinetics of DA-3031, a Pegylated Granulocyte Colony-Stimulating Factor (Pegylated-G-CSF): A Dose Block-Randomized, Double-Blind, Dose-Escalation Study in Healthy Subjects
Published in: Clinical Drug Investigation | Issue 11/2013
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Background
DA-3031 is a newly developed pegylated filgrastim, a recombinant human granulocyte colony-stimulating factor, that is expected to have an extended duration of action compared with non-modified filgrastim.
Objective
This study evaluated the tolerability, pharmacokinetics, and pharmacodynamics of DA-3031 in humans, and compared them with filgrastim.
Methods
The study was conducted in 48 healthy male Korean subjects. Forty subjects received subcutaneous single doses of 1.8, 3.6, 6, or 18 mg of DA-3031 or placebo in a dose block-randomized, double-blind, dose-escalation design. The remaining eight subjects were given subcutaneous doses of 100 μg/m2 of filgrastim daily for 5 days. Serial blood samples were collected for pharmacokinetic and pharmacodynamic analyses up to 312 h after the administration of DA-3031 and up to 264 h following the first administration of filgrastim.
Results
DA-3031 reached its peak plasma concentration at 6.0–48.0 h and was eliminated mono-exponentially. The pharmacokinetic parameters of DA-3031 increased with dose in a non-linear fashion. Absolute neutrophil count (ANC) levels increased with the dose of DA-3031, although the extent of the increase in ANC decreased at higher dose levels. DA-3031 resulted in similar ANC changes in the 3.6 to 6 mg dose range as 100 μg/m2 of filgrastim. The most frequent adverse event was back pain, which was observed after both DA-3031 and filgrastim administration.
Conclusions
DA-3031 showed non-linear pharmacodynamic and pharmacokinetic profiles and an extended duration of action compared with non-modified filgrastim, without unexpected toxicities in healthy subjects.