Comparison of the Pharmacokinetic-Pharmacodynamic Relationships of Two Darbepoetin Alfa Formulations in Healthy Male Volunteers.

OBJECTIVE: This study compared the pharmacokinetic (PK), pharmacodynamic (PD), and safety properties of the test (CJ-40001) and reference (NESP(®)) versions of darbepoetin alfa following a single subcutaneous (SC) or intravenous (IV) administration in healthy male subjects. METHODS: A single-blind, randomized, single-dose, two-period, two-intervention crossover study was conducted, with two separate parts consisting of SC or IV administration. In each period, either a test or reference product was administered via the SC or IV route. Serial blood samples for PK analysis and the reticulocyte, hematocrit, hemoglobin, and red blood cell counts for PD analysis were collected for up to 360 or 264 h after SC or IV administration, respectively. The PK and PD parameters were calculated using non-compartmental methods. The 90% confidence intervals of the geometric mean ratios for the PK and PD parameters between the two interventions were estimated. Safety and anti-drug antibody profile assessments were performed. RESULTS: The mean darbepoetin alfa concentration-time profiles were comparable between the two products for SC and IV administration. Additionally, the PD and safety profiles were similar between the two products. Anti-drug antibody reactivity was negative for all samples from both intervention groups for SC and IV administration. The time-matched serum darbepoetin alfa concentration and the PD markers presented a counter-clockwise hysteresis, which suggests a time delay between the exposure and response. CONCLUSION: The test and reference darbepoetin alfa formulations had similar PK, PD, and safety profiles. Thus, it is expected that the two formulations are able to be used interchangeably in clinical settings. ClinicalTrials.gov Identifier: NCT03542916.