BIOEQUIVALENCE EVALUATION OF TWO EDOXABAN 60 MG TABLET FORMULATIONS IN HEALTHY INDIAN SUBJECTS: AN OPEN-LABEL, RANDOMIZED, TWO-PERIOD, SINGLE DOSE, CROSSOVER STUDY

Dr. Bhupesh Dewan*, Mr. Siddheshwar Shinde, Ms. Alisha Dabade

ABSTRACT

Objective: To evaluate the bioequivalence of two oral tablet formulations of edoxaban 60 mg in healthy Indian adults. Method and material: An open-label, randomized, two-treatment, two-sequence, two-period, single-dose crossover study was conducted under fasting conditions. Eligible subjects received a single 60 mg tablet of edoxaban, either the test formulation (Supexa-ODTM from Zuventus Healthcare Limited, India) or the reference formulation (Lixiana® from Daiichi Sankyo Europe GmbH, Germany). The two doses were separated by a 7-day washout period. Blood samples were collected up to 72 hours post-dose, and the plasma concentrations of edoxaban were detected using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The pharmacokinetic parameters Cmax, AUC0-t, AUC0-inf, Tmax, t1/2, and Kel were determined. Bioequivalence was assessed by calculating the geometric least square (LS) mean ratios and corresponding 90% confidence intervals (CIs) for these parameters. Safety was evaluated by monitoring adverse events. Results: Forty subjects were randomized and completed the study. The pharmacokinetic parameters of the test formulation were similar to those of the reference. The 90% CIs of the geometric LS mean ratios of the test to reference for Cmax (86.53-114.53%), AUC0-t (100.87-115.43%), and AUC0-inf (100.38-113.31) fell within the acceptable range of 80.00–125.00%. Both formulations were well tolerated, with no serious adverse events reported. Conclusions: Both formulations of edoxaban 60 mg tablet were bioequivalent and well-tolerated in healthy Indian adults under fasting conditions. These findings support their interchangeability in clinical practice.

Keywords: Bioequivalence, Edoxaban, Factor Xa Inhibitors, Oral anticoagulant.