Bioequivalence assessment of two Ticagrelor formulations under fasting condition in healthy Pakistani subjects.

Abstract

To investigate the Bioequivalence of Anplag® 90mg (Ticagrelor) tablet and Brilinta® 90 mg (Ticagrelor) tablet under fasting conditions in healthy Pakistani subjects. This was an open-label, cross-over, randomized, single-dose, two-period, single-center Bioequivalence Study conducted at Center of Bioequivalence Studies and Clinical Research (CBSCR), ICCBS, University of Karachi, Karachi, Pakistan from September 2020 to January 2021. This was an open-label, randomized, single-dose, two-period, cross-over Bioequivalence Study. After randomization, a single dose of Ticagrelor 90mg tablet (test or reference drug) were administered orally in 1:1 ratio to each subject under fasting conditions. Seven days washout period was kept between the two periods in order to avoid carry over. Blood samples were then taken up to 48th hours post-dose. Point estimates and 90% confidence intervals (CI) for the ratio of the log-transformed values were calculated. Bioequivalence assessment of both, the reference and the test drugs were based on the primary Pharmacokinetic PK metrics including peak maximum concentration (Cmax), area under the curve (AUC) from zero to last quantifiable concentration (AUClast), and AUC from zero to infinity (AUCtotal) after log-transformation of data with ANOVA. In this bioequivalence study, the primary pharmacokinetic parameters were assessed for both Ticagrelor and its Active Metabolite (AR-C124910XX). Safety endpoints were evaluated by monitoring adverse events (AEs). The 90% Confidence Intervals (CIs) of the Geometric Mean Ratio for primary PK parameters including Cmax, AUClast, and AUCtotal all were within the accepted bioequivalence range of 80%- 125%. In the current study, no serious adverse events were reported. Our results showed that the two tested formulations of Ticagrelor tablets were bioequivalent and well tolerated.Trial Registration: ClinicalTrials.gov Identifier: NCT04941196.