PMID- 30506495
OWN - NLM
STAT- MEDLINE
DCOM- 20190716
LR  - 20200225
IS  - 1179-190X (Electronic)
IS  - 1173-8804 (Print)
IS  - 1173-8804 (Linking)
VI  - 33
IP  - 1
DP  - 2019 Feb
TI  - Comparison of the Pharmacokinetic-Pharmacodynamic Relationships of Two 
      Darbepoetin Alfa Formulations in Healthy Male Volunteers.
PG  - 101-112
LID - 10.1007/s40259-018-0323-0 [doi]
AB  - OBJECTIVE: This study compared the pharmacokinetic (PK), pharmacodynamic (PD), 
      and safety properties of the test (CJ-40001) and reference (NESP((R))) 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.
FAU - Kim, Seokuee
AU  - Kim S
AD  - Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, 
      Seoul, Republic of Korea.
FAU - Hong, Taegon
AU  - Hong T
AD  - Department of Clinical Pharmacology, Severance Hospital, Yonsei University 
      College of Medicine, Seoul, Republic of Korea.
FAU - Ko, Jae-Wook
AU  - Ko JW
AD  - Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, 
      Seoul, Republic of Korea.
FAU - Huh, Wooseong
AU  - Huh W
AD  - Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, 
      Seoul, Republic of Korea. wooseong.huh@samsung.com.
AD  - Division of Nephrology, Department of Medicine, Samsung Medical Center, 
      Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 
      wooseong.huh@samsung.com.
FAU - Kim, Jung-Ryul
AU  - Kim JR
AUID- ORCID: 0000-0002-1638-3574
AD  - Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, 
      Seoul, Republic of Korea. jungryul.kim@samsung.com.
AD  - Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan 
      University, Seoul, Republic of Korea. jungryul.kim@samsung.com.
LA  - eng
SI  - ClinicalTrials.gov/NCT03542916
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - New Zealand
TA  - BioDrugs
JT  - BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy
JID - 9705305
RN  - 0 (Biosimilar Pharmaceuticals)
RN  - 0 (Hemoglobins)
RN  - 15UQ94PT4P (Darbepoetin alfa)
SB  - IM
MH  - Adult
MH  - Biosimilar Pharmaceuticals/adverse 
      effects/chemistry/*pharmacokinetics/*pharmacology
MH  - Darbepoetin alfa/adverse effects/chemistry/*pharmacokinetics/*pharmacology
MH  - Erythrocyte Count
MH  - Hematocrit
MH  - Hemoglobins/metabolism
MH  - Humans
MH  - Injections, Intravenous
MH  - Injections, Subcutaneous
MH  - Male
MH  - Middle Aged
MH  - Reticulocytes/drug effects
MH  - Single-Blind Method
MH  - Young Adult
PMC - PMC6373390
COIS- CONFLICT OF INTEREST: Seokuee Kim, Taegon Hong, Jae-Wook Ko, Wooseong Huh, and 
      Jung-Ryul Kim declare that they have no conflict of interest. ETHICAL APPROVAL: 
      The study protocol was reviewed and approved by the health authorities from the 
      Ministry of Food and Drug Safety of South Korea and the Institutional Review 
      Board of Samsung Medical Center. Written informed consents were obtained from all 
      subjects included in this study.
EDAT- 2018/12/07 06:00
MHDA- 2019/07/17 06:00
PMCR- 2018/12/01
CRDT- 2018/12/04 06:00
PHST- 2018/12/07 06:00 [pubmed]
PHST- 2019/07/17 06:00 [medline]
PHST- 2018/12/04 06:00 [entrez]
PHST- 2018/12/01 00:00 [pmc-release]
AID - 10.1007/s40259-018-0323-0 [pii]
AID - 323 [pii]
AID - 10.1007/s40259-018-0323-0 [doi]
PST - ppublish
SO  - BioDrugs. 2019 Feb;33(1):101-112. doi: 10.1007/s40259-018-0323-0.