Yujing Di

and 15 more

Purpose This study aimed at evaluating 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 A phase I, randomized, open-label, 2-treatment, 2-period, 2-sequence, crossover study was conducted in healthy Chinese participants under fasting condition. 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. Findings 68 subjects were enrolled, and 67 were treated. Systemic exposure to rosuvastatin based on Cmax, AUC0-t and AUC0-∞ were 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 were 4.14 ng/ml, 89.7 ng·h/mL and 102 ng·h/mL for 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 were 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 estimate for rosuvastatin, unconjugated ezetimibe and total ezetimibe were in the acceptable range of 0.80-1.25. No deaths, serious adverse events (SAE) were reported. Conclusions Fixed dose combination of ezetimibe/rosuvastatin (10mg/10mg) achieved bioequivalence with reference to commercial tablets.