PMID- 36897521 OWN - NLM STAT- MEDLINE DCOM- 20230517 LR - 20230822 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 40 IP - 5 DP - 2023 May TI - A Bioequivalence Study of Ezetimibe/Rosuvastatin Fixed Dose Combination (10 mg/10 mg) Versus the Individual Formulations Taken Concomitantly. PG - 2205-2216 LID - 10.1007/s12325-023-02439-8 [doi] AB - 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(max), AUC(0-t), and AUC(0-infinity) 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(max), AUC(0-t), and AUC(0-infinity) 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. CI - (c) 2023. The Author(s). FAU - Di, Yujing AU - Di Y AD - Department of Medical Affairs, Phase I Center, Peking University (PKU) Care, Luzhong Hospital, No. 65, Taigong Road, Linzi District, Zibo, Shandong, China. FAU - Wang, Zhaojun AU - Wang Z AD - Department of Medical Affairs, Phase I Center, Peking University (PKU) Care, Luzhong Hospital, No. 65, Taigong Road, Linzi District, Zibo, Shandong, China. FAU - Jia, Chuandong AU - Jia C AD - Department of Medical Affairs, Phase I Center, Peking University (PKU) Care, Luzhong Hospital, No. 65, Taigong Road, Linzi District, Zibo, Shandong, China. FAU - Xie, Xin AU - Xie X AD - Department of Medical Affairs, Phase I Center, Peking University (PKU) Care, Luzhong Hospital, No. 65, Taigong Road, Linzi District, Zibo, Shandong, China. FAU - Yang, Shanshan AU - Yang S AD - Department of Medical Affairs, Phase I Center, Peking University (PKU) Care, Luzhong Hospital, No. 65, Taigong Road, Linzi District, Zibo, Shandong, China. FAU - Wang, Wenhua AU - Wang W AD - Department of Medical Affairs, Phase I Center, Peking University (PKU) Care, Luzhong Hospital, No. 65, Taigong Road, Linzi District, Zibo, Shandong, China. FAU - Xie, Xiaochuan AU - Xie X AD - Department of Medical Affairs, Sanofi, Beijing, China. FAU - Wang, Qian AU - Wang Q AD - Department of Medical Affairs, Sanofi, Shanghai, China. FAU - Hu, Chanyan AU - Hu C AD - Department of Medical Affairs, Sanofi, Shanghai, China. FAU - Xie, Fang AU - Xie F AD - Department of Medical Affairs, Sanofi, Shanghai, China. FAU - Abdel-Moneim, Mohamed AU - Abdel-Moneim M AD - Department of Medical Affairs, Sanofi, Dubai, United Arab Emirates. FAU - Hovsepian, Lionel AU - Hovsepian L AD - Department of Medical Affairs, Sanofi, Paris, France. FAU - Wu, Yanzhen AU - Wu Y AD - Department of Research and Development (R&D), Sanofi, Beijing, China. FAU - Yang, Na AU - Yang N AD - Department of Research and Development (R&D), Sanofi, Beijing, China. FAU - Hou, Jie AU - Hou J AD - Department of Medical Affairs, Phase I Center, Peking University (PKU) Care, Luzhong Hospital, No. 65, Taigong Road, Linzi District, Zibo, Shandong, China. jie.hou@gohealtharo.com. LA - eng PT - Clinical Trial, Phase I PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20230310 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 83MVU38M7Q (Rosuvastatin Calcium) RN - EOR26LQQ24 (Ezetimibe) RN - 0 (Tablets) MH - Humans MH - *Rosuvastatin Calcium/adverse effects MH - Therapeutic Equivalency MH - Cross-Over Studies MH - Area Under Curve MH - Ezetimibe/adverse effects MH - Tablets PMC - PMC10129950 OTO - NOTNLM OT - Bioequivalence OT - Ezetimibe OT - Fixed-dose combination OT - Pharmacokinetics OT - Rosuvastatin COIS- Xiaochuan Xie, Qian Wang, Chanyan Hu, Fang Xie, Mohamed Abdel-Moneim, Lionel Hovsepian, Yanzhen Wu and Na Yang are employees of Sanofi and may hold shares and/or stock options in the company for the Sanofi employees. Yujing Di, Zhaojun Wang, Chuandong Jia, Xin Xie, Shanshan Yang, Wenhua Wang, and Jie Hou have no conflict of interests. EDAT- 2023/03/11 06:00 MHDA- 2023/05/17 06:42 PMCR- 2023/03/10 CRDT- 2023/03/10 11:23 PHST- 2022/12/07 00:00 [received] PHST- 2023/01/17 00:00 [accepted] PHST- 2023/05/17 06:42 [medline] PHST- 2023/03/11 06:00 [pubmed] PHST- 2023/03/10 11:23 [entrez] PHST- 2023/03/10 00:00 [pmc-release] AID - 10.1007/s12325-023-02439-8 [pii] AID - 2439 [pii] AID - 10.1007/s12325-023-02439-8 [doi] PST - ppublish SO - Adv Ther. 2023 May;40(5):2205-2216. doi: 10.1007/s12325-023-02439-8. Epub 2023 Mar 10.