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A Bioequivalence Study of Ezetimibe/Rosuvastatin Fixed Dose Combination (10 mg/10 mg) Versus the Individual Formulations Taken Concomitantly
  • +13
  • Yujing Di,
  • Zhaojun Wang,
  • Chuandong Jia,
  • Xin Xie ,
  • Shanshan Yang,
  • Wenhua Wang,
  • Xiaochuan Xie,
  • Qian Wang,
  • Chanyan Hu,
  • Fang Xie,
  • Mohamed Abdel-Moneim,
  • Lionel Hovsepian,
  • Yanzhen Wu,
  • Na Yang,
  • Jie Hou,
  • Shifang Mei
Zhaojun Wang
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Chuandong Jia
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Shanshan Yang
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Wenhua Wang
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Xiaochuan Xie
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Chanyan Hu
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Mohamed Abdel-Moneim
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Lionel Hovsepian
Sanofi SA
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Yanzhen Wu
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Jie Hou
Peking University (PKU) Care

Corresponding Author:[email protected]

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Shifang Mei
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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.