Summary of bioequivalence study for EXIB, film-coated tablets (etoricoxib)
Purpose. To prove the bioequivalence (BE) of the test investigational medicinal product (IMP) EXIB, 120 mg etoricoxib film-coated tablets, manufactured by PrJSC “Pharmaceutical Firm “Darnitsa” to the reference IMP ARCOXIA®, 120 mg etoricoxib film-coated tablets, manufactured by Merck Sharp & Dohme B.V. in a randomized, open-label, single-dose, two-sequence, two-period, crossover, comparative, oral bioequivalence study in 28 healthy male volunteers under fasting conditions.
Objects and methods of the study. Blood samples were collected within 72 hours in healthy male volunteers after a single oral dose of IMPs at a dose level of 120 mg etoricoxib in each period (i.e., 240 mg of etoricoxib throughout the study) under fasting conditions. Etoricoxib was determined in plasma using a validated bioanalytical method of liquid chromatography with tandem mass spectrometry (LC/MS/MS).
Results. All 28 randomized subjects completed the study, and their data were included in pharmacokinetic analysis. Due to two subjects showed plasma concentrations of etoricoxib below LLOQ (Lower Limit of Quantification) at 72 hours post-dose, area under the plasma concentration curve from administration to last observed concentration at time t (AUC0-t) was calculated for all volunteers instead of area under the plasma concentration curve from administration to last observed concentration at 72 hours (AUC0-72h).
Pharmacokinetic results demonstrate that etoricoxib geometric least squares means ratios and corresponding 90% confidence intervals (CIs) of maximum plasma concentration Cmax and AUC0-t were 102.15% (94.54 – 110.37) and 99.23% (96.97 – 101.54), respectively. The criteria used to assess bioequivalence between the Test and Reference IMPs were all fulfilled since the Test to Reference ratio of geometric least squares means and corresponding 90% CI for Cmax and AUC0-t were all within the acceptance range of 80.00 to 125.00%.
The drugs tested were safe and well tolerated by healthy volunteers included in this study.
Conclusions. The bioequivalence of the test IMP (EXIB, 120 mg etoricoxib film-coated tablets) to the reference IMP (ARCOXIA®, 120 mg etoricoxib film-coated tablets) was demonstrated in this study.
The Sponsor of the study, PrJSC “Pharmaceutical Firm “Darnitsa”, expresses its gratitude to the employees of global contract research organization (CRO) Anapharm Europe S.L.U. (Barcelona, Spain) and Clinical Unit (CU) of Erciyes University Hakan Cetinsaya GCP and Research Center (Kayseri, Turkey) for conducting the research and processing its results.