J. Park,1 S. Rhee,1 S. Kim,1 Y. Koh,2 T. Koo,2 J. Sohn,2 J. Kim,2 I. Jang,1 S. Shin,1 K. Yu,1 H. Lee1; 1Seoul National University, Seoul, Korea, Republic of, 2Chong Kun Dang Pharmaceutical Corp. Yongin, Seoul, Korea, Republic of
BACKGROUND: CKD-11101, a biosimilar to NESP® (Darbepoetin alfa, manufactured by kyowa-Hakko-Kirin, Japan) under development, is expected to have a sustained erythropoietic activity because its half-life is longer than conventional recombinant human erythropoietin. The purpose of this study was to compare the pharmacokinetic (PK), pharmacodynamic (PD), and tolerability profiles of CKD-11101 with those of NESP® after a single subcutaneous (SC) injection in healthy male volunteers.
METHODS: A randomized, double-blind, two-sequence, two-period, two-way crossover study was conducted in 34 subjects, who randomly received a single SC injection of CKD-11101 and NESP®, both at 60 μg, one in period 1 and the other in period 2 with a 3-week washout. PK and PD parameters were calculated using the non-compartmental technique. Tolerability was assessed based on vital signs, adverse events (AE), clinical laboratory tests, electrocardiography, and immunogenicity.
RESULTS: CKD-11101 showed comparable PK and PD profiles to those of NESP®. The geometric mean ratios (90% confidence interval) of CKD-11101 to NESP® for the Cmax, AUClast were 1.06 (0.97-1.16) and 1.09 (1.03-1.15), respectively. No statistically significant difference was found between CKD-11101 and NESP® in the maximum change in reticulocyte counts from baseline (p=0.435) or the area under the change from baseline in reticulocyte counts-time curve (p=0.199). There was no significant difference in the frequency of drug-related AEs between CKD-11101 and NESP®. Antidrug antibodies were not detected in either treatment.
CONCLUSION: There were no significant differences in the PK, PD, tolerability profiles between CKD-11101 and NESP® after a single SC injection in healthy males. Both CKD-11101 and NESP® were well tolerated.