Pharmacokinetic and Safety Comparison of 2 Afatinib Dimaleate Tablets in Healthy Chinese Volunteers Under Fasted Conditions: A Randomized, Open-Label, 2-Period, Single-Dose Crossover Study.

Abstract

In this bioequivalence study, we aimed to evaluate the bioequivalence of test (T) and reference (R) afatinib dimaleate tablets in healthy Chinese subjects under fasted conditions. This was a randomized, open-label, 2-period, single-dose, crossover study. A total of 60 healthy subjects were included in the study according to the screening criteria, and the subjects were randomly divided into the T/R and R/T groups. All subjects were administrated a single 40-mg oral dose of the test or reference formulation, separated by a 14-day washout period in the crossover manner. The pharmacokinetic parameters, including maximum concentration (Cmax ), area under the concentration-time curve (AUC) from time 0 to the last measurable concentration and AUC from time 0 to infinity were assessed for bioequivalence. The plasma concentrations of afatinib dimaleate were analyzed by liquid chromatography-tandem mass spectrometry. In addition, adverse events were monitored and recorded on the basis of patient interviews and physical examinations to assess the safety of the 2 formulations. There were 4 subjects who withdrew before the dosing of period 2. The 90%CIs of geometric mean ratios of Cmax , AUC from time 0 to the last measurable concentration, and AUC from time 0 to infinity were 95.9% to 104.1%, 98.8 % to 104.1%, and 98.9% to 104.0%, respectively, all of which were within the bioequivalence range of 80.0% to 125.0%. This randomized study demonstrated that the test formulation of afatinib was bioequivalent to the reference formulation in healthy Chinese subjects under fasted conditions. Both formulations were well tolerated, and no serious adverse events were observed during the study.