A Clinical Trial to Compare the Efficacy and Safety of a Combination Therapy of Ezetimibe and Rosuvastatin Versus Monotherapy of Rosuvastatin in Hypercholesterolemia Patients (I-ROSETTE Study)

Study Overview
=================
Brief Summary
-----------------
A phase Ⅲ, multi-center, randomized, double-blinded, active comparator, factorial design clinical trial to compare the efficacy and safety of a combination therapy of ezetimibe and rosuvastatin versus monotherapy of rosuvastatin in hypercholesterolemia patients.

Conditions
-----------------
Hypercholesterolemia

Intervention / Treatment
-----------------
* Drug: Rosuvastatin
* Drug: Ezetimibe


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 19   79 years old Patients who confirmed hypercholesterolemia. Patients who requiring drug therapy according to NCEP ATP(National Cholesterol Education Program Adult Treatment Panel) III Guideline at Visit2. Patients with Triglyceride< 400 at Visit 2. Patients who have a wash-out period over 4 weeks for other drugs that can affect lipid profile.(Patients who have lipid regulators should have washout period over six weeks) Patients who agreed to participate in the trial Exclusion Criteria: Patients who have a history of myopathy or rhabdomyolysis by statin treatment or hypersensitivity to statin HMG CoA(3-hydroxy-3-methylglutaryl-coenzyme) reductase inhibitors) or ezetimibe. A heavy alcohol consumer. (alcohol > 25 units/week) Patients with severe renal disease. (creatinine ≥ 2.0 mg/dL) Patients with active liver disease and AST(aspartate transaminase) or ALT(alanine transaminase) > 2 times of upper limit of normal range. Patients with CPK(creatine phosphokinase) > 2 x upper limit of normal range. Patients who have a endocrine or metabolic diseases known to affect the serum phospholipid or lipoprotein. Patients with HIV(human immunodeficiency virus positive. Patients who have a acute arteriopathy. Patients with uncontrolled hypertension. Patients who have hereditary problems such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption. Patients who have a drugs absorption disorder by gastrointestinal surgery or gastrointestinal disorder. Patients with tumor. Patients who have hormonal therapy. Pregnancy or breastfeeding patients who don't agree to use adequate contraception. Patients who are judged unsuitable to participate in this study by investigator. Patients taking other clinical trial drugs within 30 days from the time of visit for screening.

Ages Eligible for Study
-----------------
Minimum Age: 19 Years
Maximum Age: 79 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: R5<br>Rosuvastatin 5mg | Drug: Rosuvastatin<br> <br> |
| Active Comparator: R10<br>Rosuvastatin 10mg | Drug: Rosuvastatin<br> <br> |
| Active Comparator: R20<br>Rosuvastatin 20mg | Drug: Rosuvastatin<br> <br> |
| Experimental: R5/E10<br>Rosuvastatin 5mg/Ezetimibe 10mg | Drug: Rosuvastatin<br> <br> Drug: Ezetimibe<br> <br> |
| Experimental: R10/E10<br>Rosuvastatin 10mg/Ezetimibe 10mg | Drug: Rosuvastatin<br> <br> Drug: Ezetimibe<br> <br> |
| Experimental: R20/E10<br>Rosuvastatin 20mg/Ezetimibe 10mg | Drug: Rosuvastatin<br> <br> Drug: Ezetimibe<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change from baseline to 8 week in LDL-Cholesterol |  | baseline and 8 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change from baseline to 4 and 8 week in Total Cholesterol |  | baseline to 4 and 8 week | 
| Percent change from baseline to 4 and 8 week in Triglyceride |  | baseline to 4 and 8 week | 
| Percent change from baseline to 4 and 8 week in HDL-Cholesterol |  | baseline to 4 and 8 week | 
| Percent change from baseline to 4 and 8 week in non-HDL-Cholesterol |  | baseline to 4 and 8 week | 
| Percent change from baseline to 4 and 8 week in Apolipoprotein B |  | baseline to 4 and 8 week | 
| Percent change from baseline to 4 and 8 week in Apolipoprotein A1 |  | baseline to 4 and 8 week | 
| Percent change from baseline to 4 week in LDL-Cholesterol |  | baseline to 4 week | 
| Percent change from baseline to 4 and 8 week in hs-CRP(high-sensitivity C-reactive protein) |  | baseline to 4 and 8 | 
| The change of LDL-Cholesterol/HDL-Cholesterol ratio |  | baseline to 4 and 8 week | 
| The change of Total Cholesterol/HDL-Cholesterol ratio |  | baseline to 4 and 8 week | 
| The change of non-HDL-Cholesterol/HDL-Cholesterol ratio |  | baseline to 4 and 8 week | 
| The change of Apolipoprotein B/Apolipoprotein A1 ratio |  | baseline to 4 and 8 week | 
| The ratio of subjects who reach the goal of LDL-Cholesterol according to NCEP(National Cholesterol Education Program Adult Treatment Panel) III Guideline |  | baseline to 4 and 8 week |