A comparative pharmacokinetic study of DRL_BZ, a candidate biosimilar of bevacizumab, with Avastin® (EU and US) in healthy male subjects
| Autor: | Luis Lopez-Lazaro, Christian Schwabe, Sonica Sachdeva Batra, Chris Wynne, Suresh Kankanwadi |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Pharmacology medicine.medical_specialty Bevacizumab business.industry Cmax Serum concentration Bioequivalence Gastroenterology Confidence interval 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Pharmacokinetics 030220 oncology & carcinogenesis Internal medicine medicine Pharmacology (medical) Geometric mean Adverse effect business medicine.drug |
| Zdroj: | British Journal of Clinical Pharmacology. 84:2352-2364 |
| ISSN: | 0306-5251 |
| Popis: | 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 (Cmax ), 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. |
| Databáze: | OpenAIRE |
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