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. 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.
Results: 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 12.4 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.
Keywords: Bioequivalence; Ezetimibe; Fixed-dose combination; Pharmacokinetics; Rosuvastatin.
© 2023. The Author(s).