LIpid Lowering With Highly Potent Statins in Hyperlipidaemia With Type 2 Diabetes patiENts

Study Overview
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Brief Summary
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The purpose of this study is to compare the effect of rosuvastatin and atorvastatin on lipid lowering effect and glucose metabolism in hypercholesterolemia patients with diabetes mellitus.

Official Title
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Study on Effect of Highly Potent Statins on Lipid Lowering Effect and Glucose Metabolism in Hypercholesterolemia Patients With Diabetes Mellitus

Conditions
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Hypercholesterolemia With Concomitant Type 2 Diabetes

Intervention / Treatment
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* Drug: Atorvastatin
* Drug: Rosuvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hypercholesterolemia patients • Patients who have not achieved the target control levels of LDL-C in the Japan Atherosclerosis Society Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2007 Type 2 diabetes patients Patients diagnosed with type 2 diabetes and receiving diet therapy, exercise therapy, or medication Patients who received constant therapy for three months before registration and have no plan for therapy change Patients with kept HbA1c level (Japan Diabetes Society [JDS] level) of less than 7.0% (or, National Glycohemoglobin Standardization Program [NGSP] level of less than 7.4%) within three months before registration Patients receiving or not receiving medication at present Patients giving voluntary written consent to participate in the study Male or female patients at 20 years or older Exclusion Criteria: Patients who administered rosuvastatin, atorvastatin or ezetimibe within three month at the registration Patients with severe hypertension (systolic blood pressure [SBP] ≥ 180 mmHg or diastolic blood pressure [DBP] ≥ 110 mmHg) Patients with type 1 diabetes Patients judged to have familial hypercholesterolemia Patients with a serum triglyceride level of ≥ 400 mg/dL Patients who had the onset of cardiovascular or cerebrovascular disease within three months Patients with serious heart failure (NYHA classification III - IV) Patients with a history of hypersensitivity to statins Patients with a history of drug-induced myopathy Patients with severe complication of diabetes Patients receiving insulin Patients with serious liver or kidney disease Patients with serious concurrent disease such as malignancy, or patients with severely limited lifespan Patients who are or may be pregnant Patients judged by the investigators to be ineligible for participation in the study for any other reason

Ages Eligible for Study
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Minimum Age: 20 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: Atorvastatin administration group<br> | Drug: Atorvastatin<br>* Atorvastatin 10 mg (atorvastatin 10 mg tablet x 1 or atorvastatin 5 mg tablet x 2), orally,once daily for 12 months. (When not reach the LDL-C level of target in the Japan Atherosclerosis Society [JAS] Guidelines [GL] after 3 months, had the atorvastatin [ATV] dose of 20 mg.)<br>* Other names: Lipitor;|
| Experimental: Rosuvastatin administration group<br> | Drug: Rosuvastatin<br>* Rosuvastatin 5 mg (rosuvastatin 5 mg tablet x1 or rosuvastatin 2.5 mg tablet x 2), orally, once daily for 12 months. (When not reach the LDL-C level of target in JAS GL after 3 months, had the rosuvastatin [RSV] dose of 10 mg.)<br>* Other names: Crestor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Non-high-density Lipoprotein Cholesterol (HDL-C) Level |  | Baseline, and 12 months after administration | 
| Change in HbA1c Level |  | Baseline, 12 months after administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of Deterioration of Diabetic Treatment Status | Deterioration of diabetic treatment status is defined as addition of new drug, increase in dosage, drug changes (therapy intensification), and deterioration in HbA1c of > 0.5%. | Baseline, 12 months after administration | 
| Number of Participants Stratified by Time to the Occurrence of Deterioration of Diabetic Treatment Status | Deterioration of diabetic treatment status is defined as addition of new drug, increase in dosage, drug changes (therapy intensification), and deterioration in HbA1c of > 0.5%. | Baseline, 3, 6, 12 months after administration | 
| Percent Change in 1,5-AG Level | An inverse relationship exists between mean change in 1,5-AG level and the mean rate of change when the degree of standard deviation is large, wherein the mean change is negative although the mean rate of change is positive or vice versa | Baseline, 3, 6, 12 months after administration and the end of study treatment（or at the occurrence of deterioration of diabetic treatment status） | 
| Change in HbA1c Level |  | Baseline, 3, 6 months after administration and the end of study treatment （or at the occurrence of deterioration of diabetic treatment status） | 
| Percent Change in Blood Glucose Level (Fasting) |  | Baseline, 3, 6, 12 months after administration and the end of study treatment（or at the occurrence of deterioration of diabetic treatment status） | 
| Change in Blood Glucose Level (Fasting) |  | Baseline, 3, 6, 12 months after administration and the end of study treatment（or at the occurrence of deterioration of diabetic treatment status） | 
| Percent Change in Insulin Level | An inverse relationship exists between mean change in insulin level and the mean rate of change when the degree of standard deviation is large, wherein the mean change is negative although the mean rate of change is positive or vice versa. | Baseline, 3, 6, 12 months after administration and the end of study treatment （or at the occurrence of deterioration of diabetic treatment status） | 
| Change From Baseline in Insulin Level | An inverse relationship exists between mean change in insulin level and the mean rate of change when the degree of standard deviation is large, wherein the mean change is negative although the mean rate of change is positive or vice versa | Baseline, 3, 6, 12 months after administration and the end of study treatment （or at the occurrence of deterioration of diabetic treatment status） | 
| Frequency of Cardiovascular Events (Coronary Artery Disease, Heart Failure, Cerebrovascular Disease, Peripheral Artery Disease and Aortic Disease) |  | From the start of the treatment to the end of study treatment | 
| Frequency of Serious Adverse Events (SAE) |  | Up to 12 months | 
| Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA) |  | Baseline, 3, 6, 12 months after administration, the end of starting dose and the end of study treatment | 
| Percent Change in Non-HDL-C Level |  | Baseline, 3 and 6 months after administration, the end of starting dose and the end of study treatment | 
| Percent Changes in Lipids and Inflammatory Marker (Hs-CRP) and Their Correlation | Correlation between percent changes in lipids (LDL-C, HDL-C, non-HDL-C, TG, non-HDL-C/HDL-C ratio, LDL-C/HDL-C ratio, TC and FFA) and inflammatory marker (hs-CRP) | Baseline, 3, 6, 12 months after administration, the end of starting dose and the end of study treatment | 
| Rate of Patients Who Have Reached the Target LDL-C Level Specified in Japan Atherosclerosis Society Guidelines (JASGL) 2007 | Percentage of participants achieving the target LDL-C levels <100 mg/dL for participants with history of coronary artery diseases (CAD) and <120 mg/dL for participants without history of CAD are presented. | 3 months after administration, the end of starting dose and the end of study treatment | 
| Change From Baseline in 1,5-AG Level | An inverse relationship exists between mean change in 1,5-AG level and the mean rate of change when the degree of standard deviation is large, wherein the mean change is negative although the mean rate of change is positive or vice versa | Baseline, 3, 6, 12 months after administration and the end of study treatment（or at the occurrence of deterioration of diabetic treatment status） |