Drug Design, Development and Therapy (Apr 2021)
Comparison of Pharmacokinetic, Pharmacodynamic and Tolerability Profiles of CKD-11101, Darbepoetin Alfa (NESP®) Biosimilar, to Those of NESP® After a Single Subcutaneous or Intravenous Administration to Healthy Subjects
Abstract
Inseung Jeon,1,* Jaeseong Oh,1,* Yu-Kyung Kwon,2 Seo Hyun Yoon,1 Joo-Youn Cho,1 In-Jin Jang,1 Kyung-Sang Yu,1 SeungHwan Lee1 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea; 2Department of Clinical Research, Chong Kun Dang, Seoul, Republic of Korea*These authors contributed equally to this workCorrespondence: SeungHwan LeeDepartment of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of KoreaTel +82 2 2072 2343Fax +82 2 742 9252Email [email protected]: Darbepoetin alfa (NESP® and ARANESP®) has a sustained erythropoietic activity with a longer half-life than conventional recombinant human erythropoietin. CKD-11101 is under clinical development as a biosimilar of darbepoetin alfa. The purpose of this study was to compare the pharmacokinetic (PK), pharmacodynamic (PD), and tolerability profiles of CKD-11101 with those of reference drug in healthy subjects.Methods: This study was performed in two parts for healthy subjects. In each period, CKD-11101 and reference, both at 60 μg, were administered via intravenous (IV) or subcutaneous (SC) route of administration.Results: After both IV or SC dose, the geometric mean ratio (GMR) of CKD-11101 to reference drug and its 90% confidence intervals (CIs) for Cmax, AUC0–last and AUC0–∞ were all within 0.8– 1.25. No statistically significant differences were noted in the maximum baseline adjusted reticulocyte count or the area under the baseline adjusted reticulocyte count-time between the CKD-11101 and reference drug after IV or SC dose (all p-value> 0.05). Both CKD-11101 and reference drug were generally well tolerated.Discussion: After a single IV or SC dose, the CKD-11101 was well tolerated and showed comparable PK and PD characteristics with reference drug.Keywords: pharmacokinetics, pharmacodynamics, biosimilar, darbepoetin alfa