title: A randomized phase 1 pharmacokinetic trial comparing the potential biosimilar PF-05280014 with trastuzumab in healthy volunteers (REFLECTIONS B327-01).
abstract: OBJECTIVE
  The pharmacokinetic (PK) similarity between PF-05280014, a proposed trastuzumab biosimilar, trastuzumab sourced from European Union (trastuzumab-EU) or from United States (trastuzumab-US) was evaluated. Safety and immunogenicity were also assessed.
  
  
  METHODS
  In this phase 1, double-blind trial (NCT01603264), 105 healthy male volunteers were randomized 1:1:1 to receive a single 6 mg kg(-1) intravenous dose of PF-05280014, trastuzumab-EU, or trastuzumab-US, and evaluated for 70 days. Drug concentration-time data were analyzed by non-compartmental methods. PK similarity for the comparisons of PF-05280014 to each of trastuzumab-EU and trastuzumab-US, and trastuzumab-EU to trastuzumab-US were determined using the standard 80.00% to 125.00% bioequivalence criteria.
  
  
  RESULTS
  Baseline demographics for the 101 subjects evaluable for PK were similar across all arms. The three products exhibited similar PK profiles with target-mediated disposition. The 90% CIs for the ratios of Cmax , AUC (0 , t last) and AUC(0,∞) were within 80.00% to 125.00% for all three pairwise comparisons. Adverse events (AEs) were similar across all arms with treatment-related AEs reported by 71.4%, 68.6% and 65.7% subjects in the PF-05280014, trastuzumab-EU, and trastuzumab-US arms, respectively. The most common AEs were infusion-related reactions, headache, chills, pyrexia and nausea. The AE term 'pyrexia' was numerically greater in the PF-05280014 arm. All post-dose samples, except 1, tested negative for anti-drug antibodies (ADA).
  
  
  CONCLUSIONS
  This study demonstrates PK similarity among PF-05280014, trastuzumab-EU and trastuzumab-US. The safety and immunogenicity profiles observed for the three products in this study are consistent with previous reports for trastuzumab.
authors.affiliation: Clinical Pharmacology, 10777 Science Center Drive, CB1, Pfizer Inc, San Diego, CA, 92121.
authors.forename: Donghua
authors.initials: D
authors.lastname: Yin
authors.forename: Kerry B
authors.initials: KB
authors.lastname: Barker
authors.forename: Ruifeng
authors.initials: R
authors.lastname: Li
authors.forename: Xu
authors.initials: X
authors.lastname: Meng
authors.forename: Steven D
authors.initials: SD
authors.lastname: Reich
authors.forename: Alejandro D
authors.initials: AD
authors.lastname: Ricart
authors.forename: Dan
authors.initials: D
authors.lastname: Rudin
authors.forename: Carrie T
authors.initials: CT
authors.lastname: Taylor
authors.forename: Charles M
authors.initials: CM
authors.lastname: Zacharchuk
authors.forename: Arne G
authors.initials: AG
authors.lastname: Hansson
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004311:Double-Blind Method; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C000598430:PF-05280014; D000068878:Trastuzumab
keywords: PF-05280014; biosimilar; immunogenicity; pharmacokinetics; safety; trastuzumab