A phase I dose-escalation and bioequivalence study of a trastuzumab biosimilar in healthy male volunteers.
Clin Drug Investig
; 34(12): 887-94, 2014 Dec.
Article
em En
| MEDLINE
| ID: mdl-25377592
ABSTRACT
BACKGROUND:
Trastuzumab (Herceptin(®)) is a humanized monoclonal antibody targeting the human epidermal growth factor receptor 2 (HER2) and is used in the treatment of HER2-overexpressing breast and gastric cancer. FTMB is being developed as a biosimilar of trastuzumab.OBJECTIVE:
In this combined dose-escalation and bioequivalence study of parallel design, the pharmacokinetic profile of FTMB was compared with Herceptin(®).METHODS:
Healthy male volunteers received single doses of 0.5, 1.5, 3.0 or 6.0 mg/kg FTMB, or placebo, in consecutive dose-escalation cohorts to assess the safety profile. Thereafter, the 6 mg/kg cohort was expanded to establish bioequivalence between FTMB (Test) and Herceptin(®) (Reference) based on an acceptance interval of 80.0-125.0 %. In total, 118 subjects were enrolled in the study.RESULT:
The mean area under the concentration-time curve from time zero to infinity (AUC∞) was 1,609 µg·day/mL (Test) and 1,330 µg·day/mL (Reference). The log-transformed geometric mean Test/Reference (T/R) ratio for AUC∞ was 89.6 % (90 % confidence interval [CI] 85.1-94.4), demonstrating bioequivalence. For the secondary endpoint, the maximum concentration observed (Cmax), the geometric mean T/R ratio was 89.4 % (90 % CI 83.4-95.9). Non-linear, target-mediated pharmacokinetics were also observed. Adverse events other than the documented side effects of Herceptin(®) (fever, influenza-like illness, and fatigue) did not occur. No signs of cardiotoxicity were observed.CONCLUSIONS:
This bioequivalence study with a trastuzumab biosimilar in healthy male volunteers demonstrated bioequivalence of FTMB with Herceptin(®). FTMB was well tolerated in doses up to 6 mg/kg. Non-linear target elimination was also observed in the pharmacokinetic profile of trastuzumab.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Anticorpos Monoclonais Humanizados
/
Medicamentos Biossimilares
Tipo de estudo:
Clinical_trials
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Etiology_studies
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Incidence_studies
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Observational_studies
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Risk_factors_studies
Limite:
Adult
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Humans
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Male
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article