title: A randomised, single-blind, single-dose, three-arm, parallel-group study in healthy subjects to demonstrate pharmacokinetic equivalence of ABP 501 and adalimumab.
abstract: OBJECTIVE
  To demonstrate pharmacokinetic (PK) similarity of biosimilar candidate ABP 501 relative to adalimumab reference product from the USA and European Union (EU) and evaluate safety, tolerability and immunogenicity of ABP 501.
  
  
  METHODS
  Randomised, single-blind, single-dose, three-arm, parallel-group study; healthy subjects were randomised to receive ABP 501 (n=67), adalimumab (USA) (n=69) or adalimumab (EU) (n=67) 40 mg subcutaneously. Primary end points were area under the serum concentration-time curve from time 0 extrapolated to infinity (AUCinf) and the maximum observed concentration (Cmax). Secondary end points included safety and immunogenicity.
  
  
  RESULTS
  AUCinfand Cmaxwere similar across the three groups. Geometrical mean ratio (GMR) of AUCinfwas 1.11 between ABP 501 and adalimumab (USA), and 1.04 between ABP 501 and adalimumab (EU). GMR of Cmaxwas 1.04 between ABP 501 and adalimumab (USA) and 0.96 between ABP 501 and adalimumab (EU). The 90% CIs for the GMRs of AUCinfand Cmaxwere within the prespecified standard PK equivalence criteria of 0.80 to 1.25. Treatment-related adverse events were mild to moderate and were reported for 35.8%, 24.6% and 41.8% of subjects in the ABP 501, adalimumab (USA) and adalimumab (EU) groups; incidence of antidrug antibodies (ADAbs) was similar among the study groups.
  
  
  CONCLUSIONS
  Results of this study demonstrated PK similarity of ABP 501 with adalimumab (USA) and adalimumab (EU) after a single 40-mg subcutaneous injection. No new safety signals with ABP 501 were identified. The safety and tolerability of ABP 501 was similar to the reference products, and similar ADAb rates were observed across the three groups.
  
  
  BACKGROUND
  EudraCT number 2012-000785-37; Results.
authors.affiliation: Biosimilars Development, Amgen Inc., Thousand Oaks, California, USA.
authors.forename: Primal
authors.initials: P
authors.lastname: Kaur
authors.affiliation: Clinical Pharmacology, Modeling and Simulation, Amgen Inc., Thousand Oaks, California, USA.
authors.forename: Vincent
authors.initials: V
authors.lastname: Chow
authors.affiliation: Biosimilars Development, Amgen Inc., Thousand Oaks, California, USA.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Clinical Immunology, Amgen Inc., Thousand Oaks, California, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Moxness
authors.affiliation: Clinical Immunology, Amgen Inc., Thousand Oaks, California, USA.
authors.forename: Arunan
authors.initials: A
authors.lastname: Kaliyaperumal
authors.affiliation: Biosimilars Development, Amgen Inc., Thousand Oaks, California, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Markus
mesh_terms: D000068879:Adalimumab / Q000009:adverse effects / Q000097:blood / Q000276:immunology / Q000494:pharmacology*; D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000097:blood; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000097:blood / Q000276:immunology / Q000493:pharmacokinetics*; D019540:Area Under Curve; D059451:Biosimilar Pharmaceuticals / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D005060:Europe; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D016037:Single-Blind Method; D013810:Therapeutic Equivalency; D014481:United States; D055815:Young Adult
chemical_list: D000906:Antibodies; D018501:Antirheumatic Agents; D059451:Biosimilar Pharmaceuticals; D000068879:Adalimumab
keywords: Anti-TNF; Pharmacokinetics; TNF-alpha