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

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)

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

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

• ≥ 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