Bioequivalence study of two formulations of teriflunomide tablets in a healthy Chinese population under fasting and fed conditions.

Abstract

Aims: The aims of this study were to evaluate and compare the pharmacokinetic profiles and establish bioequivalence of test and reference teriflunomide tablets (Aubagio) in healthy Chinese male subjects under fasting and fed conditions.

Materials and methods: Subjects were randomly assigned to either the fasting or the fed group and also to one of the two treatment sequences (test-reference or reference-test), according to which they received a single 14-mg dose of the test or reference teriflunomide tablet in the study periods. During each period, blood samples were collected at pre-dose and at intervals up to 72 hours after dosing. After 72 hours post dose, an accelerated elimination procedure using cholestyramine 4 g t.i.d. PO was done. Plasma concentrations of teriflunomide were determined by liquid chromatography-tandem mass spectrometry. The safety of both tablets was monitored throughout the study.

Results: 48 subjects were enrolled, and all completed the study, with 24 participants each in the fasting and fed groups. In both groups, the 90% confidence intervals for AUC_0-72h and C_max were within the acceptable bioequivalence range (80 - 125%). There were no significant differences in adverse event (AE) reporting between the subjects receiving test or reference tablet. No serious AEs occurred during the study period.

Conclusion: The test teriflunomide tablet was pharmacokinetic bioequivalent to the reference teriflunomide tablet (Aubagio) in healthy Chinese male subjects under both fasting and fed conditions. Both formulations were well tolerated by all study participants.