High-intensity Rosuvastatin vs. Moderate-intensity Rosuvastatin/Ezetimibe in High Atherosclerotic Cardiovascular Disease Risk Patients With Type 2 Diabetes

Study Overview
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Brief Summary
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To assess the efficacy and safety of moderate-intensity rosuvastatin/ezetimibe compared to high-intensity rosuvastatin in high atherosclerotic cardiovascular disease risk patients with type 2 diabetes

Detailed Description
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This study is to assess the efficacy and safety of Rosuvamibe® (rosuvastatin 10mg/ezetimibe 10mg) vs. rosuvastatin 20mg treated for 24 weeks in atherosclerotic cardiovascular disease risk (≥ 7.5%) patients with type 2 diabetes

Official Title
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A Randomized, Multicenter, Open, Parallel, Phase 4 Study to Compare the Efficacy and Safety Between High-intensity Rosuvastatin and Moderate-intensity Rosuvastatin/Ezetimibe in High ASCVD Risk Patients With Type 2 diabEtes (CREATE Study)

Conditions
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Atherosclerotic Cardiovascular Disease, Type 2 Diabetes

Intervention / Treatment
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* Drug: Rosuvamibe
* Drug: Monorova


Participation Criteria
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Eligibility Criteria
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≥ 40 and < 75 years of age at the time of informed consent Estimated 10-year ASCVD (atherosclerotic cardiovascular disease) risk ≥ 7.5% with type 2 diabetes according to the American Diabetes Association criteria in screening HbA1c ≥ 6% and < 10% in screening Body mass index (BMI) ≤ 35kg/m2 in screening Female of childbearing with a negative pregnancy test who must agree to use contraception (including those not medically pregnant) during the study period Written consent after being informed of the purpose and contents of the clinical trial and the characteristics and risks of IPs Exclusion Criteria: Type 1 diabetes Chronic hepatitis B or chronic hepatitis C, severe hepatic dysfunction (AST, ALT, ALP or CPK ≥ 3 x ULN) in screening Heavy drinking > 210g per week in screening Estimated GFR < 30mL/min/1.73m2 using the CKD-EPI formula in screening Undergoing renal replacement therapy (hemodialysis or peritoneal dialysis) in screening Having used other statin (HMG-CoA converting enzyme inhibitors) than Rosuvastatin or fibrate drugs in the last 3 months before screening Taking any medication (ex. Fenofibrate, Omega 3 fatty acid, etc.) that may affect LDL * Can be enrolled after 4 week-washout Having used thiazolidinedione drugs in the last 3 months before screening Taking cyclosporine concomitantly Positive HIV test in screening Pregnant, breastfeeding, or childbearing women who are not likely to use the appropriate contraceptive methods as judged by investigator Subjects with a medical history of myopathy and rhabdomyolysis due to use of statin Hypersensitive to statin and ezetimibe Having endocrine or metabolic disease known to affect serum lipids or lipoproteins Uncontrolled diabetes (HbA1c ≥ 10%) Uncontrolled thyroid dysfunction (TSH ≥ 3 x ULN) Subjects with a medical history of acute arterial diseases such as unstable angina, myocardial infarction, transient ischemic attack, cerebrovascular disease, coronary artery bypass graft or percutaneous coronary intervention in the last 6 months before screening Subjects with a surgical history of gastrointestine or drug absorption disorders due to gastrointestinal disorders Insulin-treated Taking other IPs in the last 30 days before screening Subjects who cannot discontinue contraindications that may affect the treatment of all types of diabetes and/or hypercholesterolemia during the study period Subjects with a significant or unstable medical or psychological condition that is judged by investigator to be detrimental to safety or to successful participation in the trial Other conditions than the above who is deemed to be ineligible to participate in the trial by investigator

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rosuvamibe ® Tab.<br>Rosuvastatin 10mg/Ezetimibe10mg | Drug: Rosuvamibe<br>* Rosuvastatin 10mg/Ezetimibe10mg qd for 24 weeks<br>|
| Active Comparator: Monorova ® Tab.<br>Rosuvastatin 20mg | Drug: Monorova<br>* Rosuvastatin 20mg qd for 24 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean percent change from baseline to week 24 in low-density lipoprotein cholesterol (LDL-C) |  | Up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects achieving < 7.5% 10-year ASCVD risk without withdrawn due to adverse events |  | Up to 24 weeks | 
| Mean change from baseline to week 12 and to week 24 in 10-year ASCVD risk |  | Up to 12 weeks, Up to 24 weeks | 
| Proportion of subjects achieving the comprehensive lipid target (LDL-C < 70mg/dL, Non-HDL-C < 100mg/dL, and Apolipoprotein B < 80mg/dL) without withdrawn due to adverse events |  | Up to 24 weeks | 
| Mean change from baseline to week 24 in calculated LDL cholesterol(mg/dL), HDL cholesterol(mg/dL), Triglyceride(mg/dL), non-HDL cholesterol(mg/dL), Apolipoprotein B(mg/dL), Apolipoprotein A1(mg/dL) |  | Up to 24 weeks | 
| Mean change from baseline to week 24 in Hepatic Steatosis Index (HSI) | hepatic steatosis index (HSI)= 8x(ALT/AST ratio)+BMI (+2, if female; +2, if diabetes mellitus) | Up to 24 weeks | 
| Mean change from baseline to week 24 in Fatty Liver Index (FLI) | FLI scores will be calculated based on triglycerides, BMI, r-GT and Waist circumference. BMI(kg/m^2) will be calculated based on height(m) and weight(kg). | Up to 24 weeks | 
| Mean change from baseline to week 24 in non-alcoholic fatty liver disease liver fat score (NAFLD-LFS) |  | Up to 24 weeks | 
| Mean change from baseline to week 24 in HbA1c |  | Up to 24 weeks | 
| Mean change from baseline to week 24 in fasting plasma glucose (FPG) |  | Up to 24 weeks | 
| Mean change from baseline to week 24 in sCD36 |  | Up to 24 weeks | 
| Mean change from baseline to week 24 in HOMA-IR |  | Up to 24 weeks | 
| Mean change from baseline to week 24 in HOMA-B |  | Up to 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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High ASCVD risk patients with type 2 diabetes