PMID- 22088414
OWN - NLM
STAT- MEDLINE
DCOM- 20120413
LR  - 20221207
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 33
IP  - 12
DP  - 2011 Dec
TI  - Comparative pharmacokinetics and tolerability of branded etanercept (25 mg) and 
      its biosimilar (25 mg): a randomized, open-label, single-dose, two-sequence, 
      crossover study in healthy Korean male volunteers.
PG  - 2029-37
LID - 10.1016/j.clinthera.2011.10.022 [doi]
AB  - BACKGROUND: The biosimilar is a recombinant dimeric tumor necrosis factor 
      receptor (TNFR) under development for the treatment of rheumatoid arthritis. 
      OBJECTIVE: The aim of this study was to compare the pharmacokinetics and/or 
      tolerability of branded etanercept and its biosimilar in healthy Korean men 
      before investigating the clinical efficacy of the biosimilar in subjects. 
      METHODS: Etanercept (reference, 25 mg) or its biosimilar (test, 25 mg) was 
      subcutaneously injected to the periumbilical area of healthy volunteers in a 
      randomized, open-label, single-dose, active-controlled, two-sequence, crossover 
      study. Plasma concentrations of TNFR in serial blood samples for 480 hours after 
      dosing were measured by ELISA. The primary outcome, pharmacokinetic 
      characteristics, was assessed via geometric mean ratios (GMRs) of the 
      log-transformed pharmacokinetic parameters. The second outcome, tolerability, was 
      evaluated using physical examinations, electrocardiograms, clinical laboratory 
      tests, vital sign measurements, and adverse events (AEs) by unmasked 
      investigators. RESULTS: Twenty-three men of mean age (%CV) 25.8 years (17.1%) and 
      weight 70.5 kg (12.8%) were administered study medication. Four subjects dropped 
      out after the first period; their data were included in the analysis. Both test 
      and reference drugs were absorbed with a median T(max) of 72 (range, 36-144) 
      hours and eliminated with mean (%CV) t((1/2)) of 92.7 (20.9%) and 87.4 (16.6%) hours, 
      respectively. The GMRs (90% CIs) of the test to reference drug for C(max), 
      AUC(0-t), and AUC(0-infinity) were 0.99 (0.83-1.17), 0.95 (0.79-1.13), and 0.95 
      (0.80-1.13), respectively. Eleven of 21 (52.4%) and 8 of 21 (38.1%) subjects 
      administered the test and reference drugs reported 22 and 21 AEs, respectively. 
      Common AEs were headache (14.3%), throat irritation (8.5%), and epistaxis (9.5%). 
      Three serious AEs related to a traffic accident (back, neck, and musculoskeletal 
      pain) were reported in a test drug-treated subject. CONCLUSIONS: In this select 
      group of Korean healthy male volunteers, the reference drug and the test 
      biosimilar met the standard criteria for assuming bioequivalence as defined by 
      Korean regulatory authorities. Because the reference drug is a biological 
      product, further trials for assessment of its efficacy are still required by 
      Korean authorities. World Health Organization International Clinical Trials 
      Registry Platform identifier: KCT0000118.
CI  - Copyright (c) 2011 Elsevier HS Journals, Inc. All rights reserved.
FAU - Gu, Namyi
AU  - Gu N
AD  - Department of Pharmacology and Clinical Pharmacology, Seoul National University 
      College of Medicine and Hospital, Seoul, Republic of Korea.
FAU - Yi, Sojeong
AU  - Yi S
FAU - Kim, Tae-Eun
AU  - Kim TE
FAU - Kim, Jaewoo
AU  - Kim J
FAU - Shin, Sang-Goo
AU  - Shin SG
FAU - Jang, In-Jin
AU  - Jang IJ
FAU - Yu, Kyung-Sang
AU  - Yu KS
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20111114
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Antirheumatic Agents)
RN  - 0 (Biosimilar Pharmaceuticals)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - OP401G7OJC (Etanercept)
SB  - IM
MH  - Adult
MH  - Antirheumatic Agents/administration & dosage/adverse 
      effects/blood/*pharmacokinetics
MH  - *Asian People
MH  - Biosimilar Pharmaceuticals/administration & dosage/adverse 
      effects/blood/*pharmacokinetics
MH  - Cross-Over Studies
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Etanercept
MH  - Humans
MH  - Immunoglobulin G/administration & dosage/adverse effects/blood/*metabolism
MH  - Injections, Subcutaneous
MH  - Male
MH  - Middle Aged
MH  - Models, Biological
MH  - Models, Statistical
MH  - Receptors, Tumor Necrosis Factor/administration & dosage/blood/*metabolism
MH  - Republic of Korea
MH  - Sex Factors
MH  - Therapeutic Equivalency
MH  - Young Adult
EDAT- 2011/11/18 06:00
MHDA- 2012/04/14 06:00
CRDT- 2011/11/18 06:00
PHST- 2011/10/24 00:00 [accepted]
PHST- 2011/11/18 06:00 [entrez]
PHST- 2011/11/18 06:00 [pubmed]
PHST- 2012/04/14 06:00 [medline]
AID - S0149-2918(11)00711-9 [pii]
AID - 10.1016/j.clinthera.2011.10.022 [doi]
PST - ppublish
SO  - Clin Ther. 2011 Dec;33(12):2029-37. doi: 10.1016/j.clinthera.2011.10.022. Epub 
      2011 Nov 14.