title: A randomized phase l pharmacokinetic study comparing SB4 and etanercept reference product (Enbrel®) in healthy subjects.
abstract: SB4 has been developed as a biosimilar of etanercept. The primary objective of the present study was to demonstrate the pharmacokinetic (PK) equivalence between SB4 and European Union -sourced etanercept (EU-ETN), SB4 and United States-sourced etanercept (US-ETN), and EU-ETN and US-ETN. The safety and immunogenicity were also compared between the treatments.
  
  
  
  This was a single-blind, three-part, crossover study in 138 healthy male subjects. In each part, 46 subjects were randomized at a 1:1 ratio to receive a single 50 mg subcutaneous dose of the treatments (part A: SB4 or EU-ETN; part B: SB4 or US-ETN; and part C: EU-ETN or US-ETN) in period 1, followed by the crossover treatment in period 2 according to their assigned sequences. PK equivalence between the treatments was determined using the standard equivalence margin of 80-125%.
  
  
  
  The geometric least squares means ratios of AUCinf , AUClast and Cmax were 99.04%, 98.62% and 103.71% (part A: SB4 vs. EU-ETN); 101.09%, 100.96% and 104.36% (part B: SB4 vs. US-ETN); and 100.51%, 101.27% and 103.29% (part C: EU-ETN vs. US-ETN), respectively, and the corresponding 90% confidence intervals were completely contained within the limits of 80-125 %. The incidence of treatment-emergent adverse events was comparable, and the incidence of the antidrug antibodies was lower in SB4 compared with the reference products.
  
  
  
  The present study demonstrated PK equivalence between SB4 and EU-ETN, SB4 and US-ETN, and EU-ETN and US-ETN in healthy male subjects. SB4 was well tolerated, with a lower immunogenicity profile and similar safety profile compared with those of the reference products.
authors.affiliation: Samsung Bioepis Co., Ltd., Incheon, Republic of Korea.
authors.forename: Yoon Jung
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Samsung Bioepis Co., Ltd., Incheon, Republic of Korea.
authors.forename: Donghoon
authors.initials: D
authors.lastname: Shin
authors.affiliation: Samsung Bioepis Co., Ltd., Incheon, Republic of Korea.
authors.forename: Youngdoe
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Samsung Bioepis Co., Ltd., Incheon, Republic of Korea.
authors.forename: Jungwon
authors.initials: J
authors.lastname: Kang
authors.affiliation: PAREXEL International Early Phase Clinical Unit, Berlin, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Gauliard
authors.affiliation: PAREXEL International Early Phase Clinical Unit, Berlin, Germany.
authors.forename: Rainard
authors.initials: R
authors.lastname: Fuhr
mesh_terms: D000328:Adult; D000906:Antibodies / Q000276:immunology; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D019540:Area Under Curve; D059451:Biosimilar Pharmaceuticals / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D000068800:Etanercept / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D005062:European Union; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D008875:Middle Aged; D016037:Single-Blind Method; D013810:Therapeutic Equivalency; D014481:United States
chemical_list: D000906:Antibodies; D018501:Antirheumatic Agents; D059451:Biosimilar Pharmaceuticals; D000068800:Etanercept
keywords: SB4; biosimilar; etanercept; immunogenicity; pharmacokinetics; safety