title: A phase I pharmacokinetics study comparing PF-06439535 (a potential biosimilar) with bevacizumab in healthy male volunteers.
abstract: OBJECTIVE
  This study compared the pharmacokinetics of PF-06439535, a potential bevacizumab biosimilar, to bevacizumab sourced from the European Union (bevacizumab-EU) and USA (bevacizumab-US), and of bevacizumab-EU to bevacizumab-US.
  
  
  METHODS
  In this double-blind study, 102 healthy males, aged 21-55 years, were randomized 1:1:1 to receive a single 5 mg/kg intravenous dose of PF-06439535, bevacizumab-EU, or bevacizumab-US. Pharmacokinetic assessments were conducted for 71 days, with additional safety and immunogenicity assessments until day 100. Pharmacokinetic similarity was achieved if 90 % confidence intervals (CIs) for the test-to-reference ratios of the maximum serum concentration (C max), area under the serum concentration-time curve from zero to infinity (AUC0-∞), and from zero to time of last quantifiable concentration (AUC0-t ) were within the 80.00-125.00 % bioequivalence acceptance window.
  
  
  RESULTS
  The three study drugs exhibited similar pharmacokinetic properties. For the comparisons of PF-06439535 to bevacizumab-EU or bevacizumab-US, and of bevacizumab-EU to bevacizumab-US, the 90 % CIs for the ratios of C max, AUC0-t , and AUC0-∞ were all within 80.00-125.00 %. Two, one, and two subjects treated with PF-06439535, bevacizumab-EU, and bevacizumab-US, respectively, tested positive for antidrug antibodies, none of whom tested positive for neutralizing antibodies. Treatment-related adverse events were reported in 15.2, 25.7, and 18.2 % of subjects in the PF-06439535, bevacizumab-EU, and bevacizumab-US treatment arms, respectively.
  
  
  CONCLUSIONS
  This study demonstrated the pharmacokinetic similarity of PF-06439535 to both bevacizumab-EU and bevacizumab-US, and of bevacizumab-EU to bevacizumab-US. The safety profile (including immunogenicity) was similar in the three treatment groups, with no significant safety findings reported.
authors.affiliation: Clinical Pharmacology, Pfizer Inc, 10555 Science Center Drive, San Diego, CA, 92121, USA. Beverly.Knight@pfizer.com.
authors.forename: Beverly
authors.initials: B
authors.lastname: Knight
authors.affiliation: Biosimilars Clinical Development, Pfizer Inc, San Diego, CA, USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Rassam
authors.affiliation: Clinical Statistics, Pfizer Inc, Shanghai, People's Republic of China.
authors.forename: Shanmei
authors.initials: S
authors.lastname: Liao
authors.affiliation: Biosimilars Clinical Development, Pfizer Inc, Cambridge, MA, USA.
authors.forename: Reginald
authors.initials: R
authors.lastname: Ewesuedo
mesh_terms: D000328:Adult; D000068258:Bevacizumab / Q000009:adverse effects / Q000493:pharmacokinetics*; D059451:Biosimilar Pharmaceuticals / Q000009:adverse effects / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D059451:Biosimilar Pharmaceuticals; D000068258:Bevacizumab
keywords: Bevacizumab; Biosimilar; Immunogenicity; PF-06439535; Pharmacokinetics