A randomized, single-blind, single-dose study to assess the pharmacokinetic equivalence of the biosimilar ABP 215 and bevacizumab in healthy Japanese male subjects

Abstract

PurposeAnalytic, pharmacokinetic (PK), and clinical similarity between the biosimilar ABP 215 and bevacizumab has previously been demonstrated in global studies. Here we present a phase 1 study in healthy adult Japanese men.MethodsThis study was a randomized, single-blind, single-dose, parallel-group study comparing PK parameters of ABP 215 versus EU-authorized bevacizumab in healthy Japanese men. Primary endpoints were maximum observed serum concentration (Cmax) and area under the serum concentration—time curve from time 0 to infinity (AUCinf). Secondary endpoints included AUC from time 0 to time of last quantifiable concentration (AUClast), safety, tolerability, and immunogenicity.ResultsBaseline characteristics were similar among study subjects (n = 24/group). After a 3-mg/kg intravenous infusion, the geometric means (GMs) of Cmax, AUCinf, and AUClast were 71.2 µg/mL, 25,259 µg h/mL, and 22,499.3 µg h/mL, respectively, for ABP 215 and 70.16 µg/mL, 25,801 µg h/mL, and 22,604.6 µg h/mL, respectively, for bevacizumab. The GM ratios (90% confidence interval; CI) for Cmax, AUCinf, and AUClast were 1.015 (0.946–1.088), 0.979 (0.914–1.049), and 0.995 (0.941–1.053) for ABP 215 versus bevacizumab. All CIs fell within the prespecified bioequivalence margin (0.80–1.25). Adverse events (AEs) occurred in 2/24 subjects receiving ABP 215 and 1/24 receiving bevacizumab. There were no deaths or AEs leading to study discontinuation; no subject was positive for binding anti-drug antibodies (ADAs).ConclusionsABP 215 and bevacizumab showed PK similarity in Japanese men. Safety profiles were comparable between the two groups. The pharmacokinetics in Japanese subjects were consistent with those in a previous global PK equivalence study.