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A comparative pharmacokinetic study of DRL_BZ, a candidate biosimilar of bevacizumab, with Avastin ® (EU and US) in healthy male subjects
Author(s) -
Wynne Chris,
Schwabe Christian,
Batra Sonica Sachdeva,
LopezLazaro Luis,
Kankanwadi Suresh
Publication year - 2018
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.13691
Subject(s) - medicine , adverse effect , pharmacokinetics , confidence interval , biosimilar , clinical endpoint , bevacizumab , randomized controlled trial , area under the curve , pharmacology , chemotherapy
Aim The aim of this study was to compare the pharmacokinetics (PK) of DRL_BZ with that of EU‐approved (reference medicinal product; RMP) and US‐licensed (reference product; RP) bevacizumab (Avastin ® ) in healthy male subjects. Methods In this double‐blind, parallel‐group, Phase 1 study (BZ‐01‐001), men aged 20–45 years were randomized 1:1:1 to receive a single intravenous infusion of 1 mg kg −1 of bevacizumab as DRL_BZ, RMP or RP. A total of 149 subjects were randomized (DRL_BZ, 50; RMP, 50; RP, 49). Primary endpoints included maximum observed serum concentration ( C max ), area under the concentration–time curve from time zero (pre‐dose) extrapolated to infinity (AUC (0–∞) ), and area under the concentration–time curve from time zero (pre‐dose) to last quantifiable concentration (AUC (0– t ) ). Secondary objectives were to compare the safety and immunogenicity of DRL_BZ with those of the reference products. Results Primary PK parameters were comparable across groups, and 90% confidence intervals for the geometric mean ratios of the primary PK endpoints were within the pre‐specified equivalence margins (80–125%) for all pairwise comparisons (DRL_BZ vs . RMP, DRL_BZ vs . RP and RMP vs . RP). No deaths or serious adverse events were reported. Similar numbers of subjects reported similar numbers of treatment‐emergent adverse events in the three treatment groups. One subject who received DRL_BZ had anti‐drug antibodies at the Day 85 visit; however, no anti‐drug antibodies were detected in this subject at the 12‐month follow‐up visit. Conclusions PK, safety and immunogenicity of DRL_BZ were comparable to EU‐approved and US‐licensed bevacizumab in healthy male subjects.