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