A comparative pharmacokinetic study of DRL_BZ, a candidate biosimilar of bevacizumab, with Avastin® (EU and US) in healthy male subjects.
Br J Clin Pharmacol
; 84(10): 2352-2364, 2018 10.
Article
em En
| MEDLINE
| ID: mdl-29943831
ABSTRACT
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 111 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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Medicamentos Biossimilares
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Bevacizumab
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Antineoplásicos Imunológicos
Tipo de estudo:
Clinical_trials
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Observational_studies
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Prognostic_studies
Limite:
Adult
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Humans
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Male
Idioma:
En
Revista:
Br J Clin Pharmacol
Ano de publicação:
2018
Tipo de documento:
Article