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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

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Abstract

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.

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Acknowledgments

Sponsored by Dong-A Pharmaceutical Co., Seoul, Republic of Korea, this study was designed and performed by qualified investigators of the Department of Clinical Pharmacology and Therapeutics of Seoul National University Hospital. None of the authors have any conflicts of interest to disclose regarding the content of this article. Li Young Ahn, Kwang-Hee Shin, and Hyewon Jeon received training program grants from the Korea Healthcare Technology R&D Project, Ministry for Health and Welfare, Republic of Korea (A070001, Korea National Enterprise for Clinical Trials).

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Author notes

  1. Kwang-Hee Shin

    Present address: College of Pharmacy, Kyungpook National University, Daegu, Republic of Korea

Authors and Affiliations

  1. Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 101 Daehak-ro, Jongno-gu, 110-744, Seoul, Republic of Korea

    Li Young Ahn, Kwang-Hee Shin, Kyoung Soo Lim, Tae-Eun Kim, Hyewon Jeon, Seo Hyun Yoon, Joo-Youn Cho, Sang-Goo Shin, In-Jin Jang & Kyung-Sang Yu

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  1. Li Young Ahn
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Corresponding author

Correspondence to Kyung-Sang Yu.

Additional information

Trial registration: ClinicalTrials.gov identifier: NCT00959777.

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Ahn, L.Y., Shin, KH., Lim, K.S. et al. 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. Clin Drug Investig 33, 817–824 (2013). https://doi.org/10.1007/s40261-013-0130-9

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