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

Introduction: 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.

Methods: This was a phase I, randomized, open-label, two-treatment, two-period, two-sequence, crossover study conducted in healthy Chinese participants under fasting conditions. C, AUC, and AUC 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.

Results: Of the 68 subjects enrolled, 67 were treated. Systemic exposure to rosuvastatin based on C, AUC, and AUC was similar in both treatments, with respective arithmetic values 12.4 ng/ml, 117 ng·h/mL, and 120 ng·h/mL for test formulation and 12.7 ng/ml, 120 ng·h/mL, and 123 ng·h/mL for reference formulations. Similarly, systemic exposure to unconjugated ezetimibe was 4.14 ng/ml, 89.7 ng·h/mL, and 102 ng·h/mL for the test formulation and 3.80 ng/ml, 89.7 ng·h/mL, and 102 ng·h/mL for reference formulations. Systemic exposure to total ezetimibe was 70.5 ng/ml, 664 ng·h/mL, and 718 ng·h/mL for test formulation and 60.2 ng/ml, 648 ng·h/mL, and 702 ng·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.

Conclusions: Fixed dose combination of ezetimibe/rosuvastatin (10 mg/10 mg) achieved bioequivalence with reference to commercial tablets.

Trial Registration Number: CTR20202108.