Dataset Information

A comparative pharmacokinetic study of DRL_BZ, a candidate biosimilar of bevacizumab, with Avastin^® (EU and US) in healthy male subjects.

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 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.

SUBMITTER: Wynne C

PROVIDER: S-EPMC6138499 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Publications

A comparative pharmacokinetic study of DRL_BZ, a candidate biosimilar of bevacizumab, with Avastin<sup>®</sup> (EU and US) in healthy male subjects.

Wynne Chris C Schwabe Christian C Batra Sonica Sachdeva SS Lopez-Lazaro Luis L Kankanwadi Suresh S

British journal of clinical pharmacology 20180726 10

<h4>Aim</h4>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<sup>®</sup> ) in healthy male subjects.<h4>Methods</h4>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<sup>-1</sup> of bevacizumab as DRL_BZ, RMP or RP. A total of 149 subjects were ...[more]

PMID: 29943831

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Project description:PurposeBevacizumab is a recombinant humanized monoclonal antibody that inhibits vascular endothelial growth factor-specific angiogenesis in some cancers. MYL-1402O is a proposed bevacizumab biosimilar.MethodsThe primary objective of this single-center, randomized, double-blind, three-arm, parallel-group, phase 1 study in healthy male volunteers was to evaluate bioequivalence of MYL-1402O to EU and US-reference bevacizumab, and EU-reference bevacizumab to US-reference bevacizumab. The primary pharmacokinetic parameter was area under the serum concentration-time curve from 0 extrapolated to infinity (AUC0-∞). Pharmacokinetic parameters were analyzed using general linear models of analysis of variance. Secondary endpoints included safety and tolerability.ResultsOf 111 enrolled subjects, 110 were included in the pharmacokinetic analysis (MYL-1402O, n = 37; EU-reference bevacizumab, n = 36; US-reference bevacizumab, n = 37). Bioequivalence was demonstrated between MYL-1402O and EU-reference bevacizumab, MYL-1402O and US-reference bevacizumab, and between EU- and US-reference bevacizumab where least squares mean ratios of AUC0-∞ were close to 1, and 90% CIs were within the equivalence range (0.80-1.25). Secondary pharmacokinetic parameters (AUC from 0 to time of last quantifiable concentration [AUC0-t], peak serum concentration [Cmax], time to Cmax, elimination rate constant, and elimination half-life) were also comparable, with 90% CIs for ratios of AUC0-t and Cmax within 80-125%. Treatment-emergent adverse events were similar across all three treatment groups and were consistent with clinical data for bevacizumab.ConclusionMYL-1402O was well tolerated and demonstrated pharmacokinetic and safety profiles similar to EU-reference bevacizumab and US-reference bevacizumab in healthy male volunteers. No new significant safety issues emerged (ClinicalTrials.gov, NCT02469987; ClinicalTrialsRegister.eu EudraCT, 2014-005621-12; June 12, 2015).

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Dataset Information

A comparative pharmacokinetic study of DRL_BZ, a candidate biosimilar of bevacizumab, with Avastin^® (EU and US) in healthy male subjects.

Aim

Methods

Results

Conclusions

Publications

A comparative pharmacokinetic study of DRL_BZ, a candidate biosimilar of bevacizumab, with Avastin<sup>®</sup> (EU and US) in healthy male subjects.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

A comparative pharmacokinetic study of DRL_BZ, a candidate biosimilar of bevacizumab, with Avastin® (EU and US) in healthy male subjects.

Aim

Methods

Results

Conclusions

Publications

A comparative pharmacokinetic study of DRL_BZ, a candidate biosimilar of bevacizumab, with Avastin<sup>®</sup> (EU and US) in healthy male subjects.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

A comparative pharmacokinetic study of DRL_BZ, a candidate biosimilar of bevacizumab, with Avastin^® (EU and US) in healthy male subjects.