A Bioequivalence Study of Ezetimibe/Rosuvastatin Fixed Dose Combination (10mg/10mg) Versus the Individual Formulations Taken Concomitantly.

Abstract

This study evaluated the bioequivalence of ezetimibe/rosuvastatin fixed dose combination compared to the concomitant administration of individual formulations (ezetimibe and rosuvastatin) in Chinese healthy subjects under fasting conditions. This was a phaseI, randomized, open-label, two-treatment, two-period, two-sequence, crossover study conducted in healthy Chinese participants under fasting conditions. Cmax, AUC0-t, and AUC0-∞ from test and individual reference formulations were evaluated to assess bioequivalence. The safety assessments included adverse events (AEs)/treatment-emergent adverse events (TEAEs), potential clinically significant abnormalities (PCSAs) in vital signs, 12-lead electrocardiogram (12-ECG), and clinical laboratory parameters. Of the 68 subjects enrolled, 67 were treated. Systemic exposure to rosuvastatin based on Cmax, AUC0-t, and AUC0-∞ was similar in both treatments, with respective arithmetic values 12.4ng/ml, 117ng·h/mL, and 120ng·h/mL for test formulation and 12.7ng/ml, 120ng·h/mL, and 123ng·h/mL for reference formulations. Similarly, systemic exposure to unconjugated ezetimibe was 4.14ng/ml, 89.7ng·h/mL, and 102ng·h/mL for the test formulation and 3.80ng/ml, 89.7ng·h/mL, and 102ng·h/mL for reference formulations. Systemic exposure to total ezetimibe was 70.5ng/ml, 664ng·h/mL, and 718ng·h/mL for test formulation and 60.2ng/ml, 648ng·h/mL, and 702ng·h/mL for reference formulations. The point estimates for rosuvastatin unconjugated ezetimibe and total ezetimibe were in the acceptable range of 0.80-1.25. No deaths or serious adverse events were reported. Fixed dose combination of ezetimibe/rosuvastatin (10mg/10mg) achieved bioequivalence with reference to commercial tablets. CTR20202108.