title: Bioavailability, safety and immunogenicity of biosimilar infliximab (BOW015) compared to reference infliximab.
abstract: OBJECTIVE
  To compare the single-dose pharmacokinetics (PK), safety, and immunogenicity of the biosimilar infliximab (BOW015) to reference infliximab (rIFX) in healthy volunteers and to establish bioequivalence.
  
  
  METHODS
  In this randomized, double-blind, parallel-group, single-dose study, subjects received either BOW015 or rIFX. Both drugs were administered as a single IV 5 mg/kg dose over 2 hours on day 1. PK sampling occurred 10 times over 3 days and during safety and immunogenicity follow-up on day 4 and 1, 2, 3, 5, 7, 9, and 12 weeks after the infusion.
  
  
  RESULTS
  Of the 84 healthy male Caucasian subjects randomized, 43 received BOW015 and 41 received rIFX. PK parameters (geometric mean) for BOW015 vs. rIFX were as follows; C(max) 142.47 vs. 126.74 μg/mL, AUC(0-t) 36,211 vs. 34,304 h×μg/mL, and AUC(0-inf) 36,775 vs. 34,801 h×μg/mL. The point estimates of the BOW015/rIFX geometric mean ratios (90% CI) were; C(max) 1.13 (1.07 - 1.18), AUC(0-t) 1.06 (0.98 - 1.14), and AUC(0-inf) 1.06 (0.98 - 1.15). Overall, anti-drug antibodies were detected in 18.6% of BOW015-treated subjects and 24.4% of rIFX-treated subjects. A total of 26 (60.5%) subjects in the BOW015 group reported 50 treatment-emergent adverse events (TEAEs) and 27 (65.9%) subjects in the rIFX group reported 54 TEAEs.
  
  
  CONCLUSIONS
  Bioequivalence of BOW015 to rIFX is demonstrated as 90% CIs for the study drug mean ratios of C(max), AUC(0-t), and AUC(0-inf) were within the log-transformed ± 20% equivalence range of 0.80 - 1.25. Safety and immunogenicity were also comparable.
authors.forename: John
authors.initials: J
authors.lastname: Lambert
authors.forename: Michael
authors.initials: M
authors.lastname: Wyand
authors.forename: Cheryl
authors.initials: C
authors.lastname: Lassen
authors.forename: Lucy
authors.initials: L
authors.lastname: Shneyer
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Thomson
authors.forename: Alastair
authors.initials: A
authors.lastname: Knight
authors.forename: Joerg
authors.initials: J
authors.lastname: Willers
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kay
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D059451:Biosimilar Pharmaceuticals / Q000009:adverse effects / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D006801:Humans; D000069285:Infliximab / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D013810:Therapeutic Equivalency
chemical_list: D059451:Biosimilar Pharmaceuticals; D000069285:Infliximab