A phase I pharmacokinetics study comparing PF-06439535 (a potential biosimilar) with bevacizumab in healthy male volunteers

A phase I pharmacokinetics study comparing PF-06439535 (a potential biosimilar) with bevacizumab in healthy male volunteers

Purpose 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 ye...

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Bibliographic Details
Published in:Cancer chemotherapy and pharmacology Vol. 77; no. 4; pp. 839 - 846
Main Authors: Knight, Beverly, Rassam, Danielle, Liao, Shanmei, Ewesuedo, Reginald
Format: Journal Article
Language:English
Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-04-2016
Springer Nature B.V
Subjects:
Adult
Bevacizumab - adverse effects
Bevacizumab - pharmacokinetics
Biosimilar Pharmaceuticals - adverse effects
Biosimilar Pharmaceuticals - pharmacokinetics
Cancer Research
Double-Blind Method
Healthy Volunteers
Humans
Male
Medicine
Medicine & Public Health
Middle Aged
Oncology
Original
Original Article
Pharmacology/Toxicology
PF-06439535
Immunogenicity
Pharmacokinetics
Biosimilar
Bevacizumab
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Summary:Purpose 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 (AUC 0–∞ ), and from zero to time of last quantifiable concentration (AUC 0– 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 , AUC 0– t , and AUC 0–∞ 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.
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ISSN:0344-5704
1432-0843
DOI:10.1007/s00280-016-3001-2