A Randomized, Double-blind, Three-arm, Parallel Group, Single-dose Study to Compare the Pharmacokinetics, Safety, and Tolerability of Three Formulations of Infliximab (CT-P13, EU-sourced Infliximab and US-sourced Infliximab) in Healthy Volunteers

초록

Background: CT-P13 has been approved as the first biosimilar to innovator infliximab sourced from European Union (EU INX) in Sep 2013. Even if it has been concluded as equivalent or comparable to EU INX through pivotal studies and switching studies, it was questioned about the comparability between reference products with different origins1,2,3,4. This study was designed to demonstrate comparability among CT P13, EU-INX and US-sourced infliximab (US-INX) in healthy volunteers and to conclude examine whether CT-P13, EU-INX and US-INX three biologic infliximabs from the different manufacturing source are comparable each other primarily in pharmacokinetics. Methods: In this double blind, randomized, parallel group, single-dose study, a total of 213 healthy volunteers were randomized 1:1:1 to receive a single dose (5 mg/kg) of CT P13, EU-INX or US-INX by intravenous infusion on Day 1 followed for 8 weeks. The primary endpoints were maximum serum concentration (Cmax), area under the concentration-time curve from time zero to the last quantifiable concentration (AUClast) and area under the concentration-time curve from time zero to infinity (AUCinf) of CT-P13, EU-INX and US-INX. A total of 11 serum blood samples were obtained for the primary PK analysis, and safety and tolerability were also evaluated up to 8 weeks. Similarity of systemic exposure (Cmax, AUClast and AUCinf) was considered to be demonstrated if the 90% confidence interval (CI) for the ratio of geometric means was within the acceptance interval of 0.8 to 1.25 for the following comparisons: CT-P13 versus EU-INX, CT-P13 versus US-INX, and EU-INX versus US-INX. Results: The baseline demographics for 213 subjects among 3 treatment groups were highly similar. The PK parameters in 3 treatment groups were highly similar (Table 1). The 90% CI for the ratios of Cmax, AUClast and AUCinf were within the acceptance interval of 0.8 to 1.25 for the comparisons of CT-P13 to EU-INX, CT-P13 to US-INX and EU-INX to U