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Tolerance, variability, and pharmacokinetics of bevacizumab biosimilars in Chinese healthy male subjects.
- Source :
-
Cancer chemotherapy and pharmacology [Cancer Chemother Pharmacol] 2018 Oct; Vol. 82 (4), pp. 615-623. Date of Electronic Publication: 2018 Jul 24. - Publication Year :
- 2018
-
Abstract
- Objective: The aim of this study was to explore the tolerance, variability, and pharmacokinetics (PK) of bevacizumab biosimilars (MIL60, BAT1706, IBI305) in Chinese healthy male subjects.<br />Methods: This randomized, double-blind, two-arm, parallel studies included three separate investigations, which were conducted by three sponsors to investigate the bioequivalence of bevacizumab biosimilars (MIL60, BAT1706, IBI305) with that of bevacizumab-EU as a reference drug. Subjects received a single-dose of 1 or 3 mg/kg of the bevacizumab biosimilars or bevacizumab-EU and were followed up for 70-99 days. Serum concentrations of bevacizumab, antidrug antibody (ADA), and neutralizing antibody (NAb) were measured using electrochemiluminescence. In addition, the PK parameters were determined using non-compartmental methods. The safety assessments included adverse events, hematology tests, and biochemistry tests.<br />Results: The three bevacizumab biosimilars exhibited similar PK properties to that of bevacizumab-EU. Bevacizumab demonstrated linear PK properties and a concentration-dependent disposition. When comparing the three biosimilars with bevacizumab-EU, the 90% CIs of the ratios for C <subscript>max</subscript> , AUC <subscript>0-t</subscript> , and AUC <subscript>0-∞</subscript> were within 80-125%. The inter-CV ranged from 12.6 to 23.3%. Three subjects in the biosimilar groups and bevacizumab-EU were positive for the ADA and negative for the NAb. Treatment-related mild or moderate adverse events were reported in 56-80 and 36-80% of subjects in the biosimilar and bevacizumab treatment arms, respectively.<br />Conclusions: The bevacizumab biosimilars exhibit similar PK characteristics to that of the reference product bevacizumab-EU. The inter-CV is moderate and less than 25% in all cases. The safety profile was similar among bevacizumab biosimilars and bevacizumab-EU with significant adverse events.
- Subjects :
- Adult
Antineoplastic Agents, Immunological administration & dosage
Antineoplastic Agents, Immunological adverse effects
Antineoplastic Agents, Immunological pharmacokinetics
Area Under Curve
Asian People
Double-Blind Method
Drug Monitoring methods
Electrochemical Techniques methods
Healthy Volunteers
Hematologic Tests methods
Humans
Male
Therapeutic Equivalency
Bevacizumab administration & dosage
Bevacizumab adverse effects
Bevacizumab pharmacokinetics
Biosimilar Pharmaceuticals administration & dosage
Biosimilar Pharmaceuticals adverse effects
Biosimilar Pharmaceuticals pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1432-0843
- Volume :
- 82
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cancer chemotherapy and pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 30043208
- Full Text :
- https://doi.org/10.1007/s00280-018-3645-1