Dataset Information

A randomized phase 1 pharmacokinetic trial comparing the potential biosimilar PF-05280014 with trastuzumab in healthy volunteers (REFLECTIONS B327-01).

ABSTRACT:

Aims

The pharmacokinetic (PK) similarity between PF-05280014, a proposed trastuzumab biosimilar, trastuzumab sourced from European Union (trastuzumab-EU) or from United States (trastuzumab-US) was evaluated. Safety and immunogenicity were also assessed.

Methods

In this phase 1, double-blind trial (NCT01603264), 105 healthy male volunteers were randomized 1:1:1 to receive a single 6 mg kg(-1) intravenous dose of PF-05280014, trastuzumab-EU, or trastuzumab-US, and evaluated for 70 days. Drug concentration-time data were analyzed by non-compartmental methods. PK similarity for the comparisons of PF-05280014 to each of trastuzumab-EU and trastuzumab-US, and trastuzumab-EU to trastuzumab-US were determined using the standard 80.00% to 125.00% bioequivalence criteria.

Results

Baseline demographics for the 101 subjects evaluable for PK were similar across all arms. The three products exhibited similar PK profiles with target-mediated disposition. The 90% CIs for the ratios of Cmax , AUC (0 , t last) and AUC(0,∞) were within 80.00% to 125.00% for all three pairwise comparisons. Adverse events (AEs) were similar across all arms with treatment-related AEs reported by 71.4%, 68.6% and 65.7% subjects in the PF-05280014, trastuzumab-EU, and trastuzumab-US arms, respectively. The most common AEs were infusion-related reactions, headache, chills, pyrexia and nausea. The AE term 'pyrexia' was numerically greater in the PF-05280014 arm. All post-dose samples, except 1, tested negative for anti-drug antibodies (ADA).

Conclusions

This study demonstrates PK similarity among PF-05280014, trastuzumab-EU and trastuzumab-US. The safety and immunogenicity profiles observed for the three products in this study are consistent with previous reports for trastuzumab.

SUBMITTER: Yin D

PROVIDER: S-EPMC4256618 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Publications

A randomized phase 1 pharmacokinetic trial comparing the potential biosimilar PF-05280014 with trastuzumab in healthy volunteers (REFLECTIONS B327-01).

Yin Donghua D Barker Kerry B KB Li Ruifeng R Meng Xu X Reich Steven D SD Ricart Alejandro D AD Rudin Dan D Taylor Carrie T CT Zacharchuk Charles M CM Hansson Arne G AG

British journal of clinical pharmacology 20141201 6

<h4>Aims</h4>The pharmacokinetic (PK) similarity between PF-05280014, a proposed trastuzumab biosimilar, trastuzumab sourced from European Union (trastuzumab-EU) or from United States (trastuzumab-US) was evaluated. Safety and immunogenicity were also assessed.<h4>Methods</h4>In this phase 1, double-blind trial (NCT01603264), 105 healthy male volunteers were randomized 1:1:1 to receive a single 6 mg kg(-1) intravenous dose of PF-05280014, trastuzumab-EU, or trastuzumab-US, and evaluated for 70 d ...[more]

PMID: 25041377

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Dataset Information

A randomized phase 1 pharmacokinetic trial comparing the potential biosimilar PF-05280014 with trastuzumab in healthy volunteers (REFLECTIONS B327-01).

Aims

Methods

Results

Conclusions

Publications

A randomized phase 1 pharmacokinetic trial comparing the potential biosimilar PF-05280014 with trastuzumab in healthy volunteers (REFLECTIONS B327-01).

Similar Datasets

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