A phase I, randomized, double-blinded, single-dose study evaluating the pharmacokinetic equivalence of the biosimilar IBI305 and bevacizumab in healthy male subjects

Int J Clin Pharmacol Ther. 2019 Mar;57(3):167-174. doi: 10.5414/CP203349.

Abstract

Objective: To compare the pharmacokinetic (PK) profiles, immunogenicity, and safety of the proposed biosimilar IBI305 with those of bevacizumab in healthy male subjects.

Design: A phase I, randomized, double-blinded, two-arm, parallel-group study.

Settings: The study was conducted in The First Hospital of Jilin University, Changchun, China, from March 2017 to November 2017.

Participants: A total of 100 healthy male subjects were enrolled, with 48 in the IBI305 group and 50 in bevacizumab group included in the final analysis.

Intervention: In a 16-week study course, participants were randomized at a 1:1 ratio to receive intravenous administration of either a single dose of 3 mg/kg IBI305 (n = 50) or bevacizumab (n = 50).

Outcome measures: The primary endpoints were area under the concentration-time curve from zero to the time of the last measurable concentration (AUC0-t) and AUC curve from zero to infinity (AUC0-∞). The secondary endpoints include the other PK parameters, immunogenicity, and safety measurements.

Results: AUC0-t, AUC0-∞, maximum concentration observed (Cmax), half-life (T1/2), drug clearance, and volume of distribution were similar between IBI305- and bevacizumab-treated subjects. For AUC0-∞, AUC0-t, and Cmax, the 90% confidence intervals for the ratios of geometric means were fully within the range 0.80 - 1.25, confirming the bioequivalence of the two investigational agents. Furthermore, no apparent difference in adverse events was found between the two groups.

Conclusion: This study demonstrated the similarity of PK, immunogenicity, and safety profiles of IBI305 to those of bevacizumab.

Publication types

  • Clinical Trial, Phase I
  • Equivalence Trial

MeSH terms

  • Area Under Curve
  • Bevacizumab / pharmacokinetics*
  • Biosimilar Pharmaceuticals / pharmacokinetics*
  • China
  • Cross-Over Studies
  • Healthy Volunteers
  • Humans
  • Male
  • Therapeutic Equivalency

Substances

  • Biosimilar Pharmaceuticals
  • Bevacizumab