Evaluation of the Fixed-dose Combination of Irbesartan/Atorvastatin in Type 2 Diabetic Patients Diagnosed With Hyperlipidemia and Hypertension

Study Overview
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Brief Summary
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Primary Objective: To evaluate the effect of irbesartan/atorvastatin fixed-dose combination comparing to each irbesartan and atorvastatin on flow mediated dilation change in type 2 diabetic patients diagnosed with hyperlipidemia, hypertension. Secondary Objective: To evaluate efficacy of blood pressure and hyperlipidemic factors of irbesartan/atorvastatin fixed-dose combination in type 2 diabetic patients diagnosed with hyperlipidemia and hypertension, with adequately controlled blood glucose levels in groups.

Detailed Description
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The total study duration per patient is up to maximum of 7 weeks.

Official Title
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Efficacy Evaluation of Metabolic, Anti-inflammatory, and Antioxidative Factors of Irbesartan/Atorvastatin Fixed-dose Combination in Type 2 Diabetic Patients Diagnosed With Hyperlipidemia and Hypertension, With Adequately Controlled Blood Glucose Levels

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Irbesartan/atorvastatin fixed dose combination
* Drug: Irbesartan SR47436
* Drug: Atorvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients aged ≥19 years to <75 years. Patients without medication history of hyperlipidemia and hypertension within 3 months following registration, among type 2 diabetic patients diagnosed with hyperlipidemia and stage I hypertension (systolic blood pressure: ≥140mmHg, ≤159 mmHg or diastolic blood pressure: ≥90 mmHg, ≤99mmHg), with adequately controlled hemoglobin levels. Patients who signed a written consent to data utilization. Diagnosis of diabetes: HemoglobinA1c ≥6.5% or; Fasting plasma glucose level above 8 hour ≥126 mg/dL or; Plasma glucose ≥200 mg/dL ( 11.1 mmol/l) 2 hours after a 75g glucose load or; Symptoms (such as polyuria, polydipsia, unexplained weight loss) and a random plasma glucose ≥200 mg/dL (11.1 mmol/L). Exclusion criteria: Patients indicated as contraindication in the approved labeling of Rovelito. Pregnant/nursing women. Patients with difference in blood pressure systolic blood pressure ≥20 mmHg or diastolic blood pressure ≥10mmHg in the arm selected during screening at Visit 1. Patients who were administered Angiotensin II receptor blockers, angiotensin converting enzyme inhibitors, or HMG-CoA reductase inhibitors in 2 months. Patients who had taken antidiabetics in the past. Patients who have to or may take any drug suggested in the prohibited concomitant medications during the study period. Patients with tolerance or hypersensitivity to angiotensin II receptor blocker or HMGCoA reductase inhibitor, or an ingredient of this drug, or with history of multi-drug allergy. Patients with genetic angioedema, or medical history of angioedema when treating with angiotensin converting enzyme inhibitor or angiotensin II receptor antagonist Patients who have suffered from fibromyalgia, myopathy, rhabdomyolysis, or sudden arthralgia, or adverse events while taking statins in the past. Creatine phosphokinase (CPK) >5 times of the upper limit of normal (ULN). Patients diagnosed with secondary hypertension or suspected of secondary hypertension by the Investigator (coarctation of aorta, primary aldosteronism, renal artery stenosis, renal hypertension, pheochromocytoma, Cushing syndrome, etc.). Patients with poorly controlled hypothyroidism despite treatment Type 1 diabetic patients or poorly controlled type 2 diabetic patients (HemoglobinA1c ≥7.5%) Patients with arrhythmia requiring separate treatment. Patients with the following past history: Severe cerebrovascular disease (cerebral infarction, cerebral hemorrhage, etc.), hypertensive encephalopathy, transient ischemic attack (TIA), which occurred in the recent 6 months. Severe heart disease (NYHA class III-IV heart failure), clinically significant valvular disease of the heart, myocardial infarction and unstable angina in the recent 6 months. Angioplasty or coronary artery bypass graft (CABG) surgery. If patients have clinically significant renal or hepatic diseases , or significant hematologic test findings at screening (serum creatinine ≥ 2mg/dL, AST or ALT [aspartate transaminase or alanine transaminase] ≥3 times of the ULN). Patients suspected of pancreatitis or active gall bladder disease by the Investigator. Surgical or internal disease likely to significantly change absorption, distribution, metabolism, and elimination of drug, which falls under one of the followings (but not limited to): Major gastrointestinal surgical history such as gastrectomy, gastro-enterostomy or bowel resection, gastric bypass, gastrointestinal stapling, or gastrointestinal banding, medical history of active inflammatory bowel syndrome at present or in the past 12 months, current active gastritis, ulcer, gastrointestinal/rectal hemorrhage, or urinary tract obstruction that is deemed clinically significant by the Investigator. Patients with volume depletion, as clinically judged by the Investigator, using vital signs, skin turgor pressure, mucous membrane wettability, and laboratory values. All chronic inflammatory patients requiring chronic inflammatory treatment. Patients with past history of autoimmune disease, such as chronic rheumatoid arthritis, systemic lupus erythematosus, etc. Patients with past clinical history of alcohol or drug abuse. Patients with history of malignant tumors including leukemia and lymphoma in the past 5 years. Patients who have been administered another investigational product within 30 days prior to participation in this clinical study (from the time when they signed the informed consent form). Patients who may not be measured for flow mediated dilatation in Investigator's judgment for a congenital or secondary reason in the bilateral brachial artery. Patients who are deemed ineligible as subject in Investigator's judgment for other reasons. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 19 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: Rovelito<br>Fixed-dose combination of irbesartan/atorvastatin will be given orally daily for 28 days | Drug: Irbesartan/atorvastatin fixed dose combination<br>* Pharmaceutical form:Tablet Route of administration: Oral<br>* Other names: Rovelito;|
| Active Comparator: Irbesartan<br>Irbesartan will be given orally daily for 28 days | Drug: Irbesartan SR47436<br>* Pharmaceutical form:Tablet Route of administration: Oral<br>* Other names: Aprovel;|
| Active Comparator: Atorvastatin<br>Atorvastatin will be given orally daily for 28 days | Drug: Atorvastatin<br>* Pharmaceutical form:Tablet Route of administration: Oral<br>* Other names: Newvast;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in flow mediated dilatation |  | 4 weeks, up to maximum 5 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of change from baseline in nytrotyrosine marker |  | 4 weeks, up to maximum 5 weeks | 
| Rate of change from baseline in Intercellular Adhesion Molecule-1 |  | 4 weeks, up to maximum 5 weeks | 
| Rate of change from baseline in Interleukin-6 |  | 4 weeks, up to maximum 5 weeks | 
| Rate of change from baseline in C-reactive protein |  | 4 weeks, up to maximum 5 weeks | 
| Change from baseline in blood pressure (irbesartan/atorvastatin fixed-dose combination group and irbesartan group) |  | 4 weeks, up to maximum 5 weeks | 
| Change from baseline in low density lipoprotein-C (irbesartan/atorvastatin fixed-dose combination group and atorvastatin group) |  | 4 weeks, up to maximum 5 weeks | 
| Change from baseline in total cholesterol (irbesartan/atorvastatin fixed-dose combination group and atorvastatin group) |  | 4 weeks, up to maximum 5 weeks | 
| Change from baseline in high density lipoprotein-C (irbesartan/atorvastatin fixed-dose combination group and atorvastatin group) |  | 4 weeks, up to maximum 5 weeks | 
| Change from baseline in triglycerides (irbesartan/atorvastatin fixed-dose combination group and atorvastatin group) |  | 4 weeks, up to maximum 5 weeks | 
| Change from baseline in apolipoprotein-A1 (irbesartan/atorvastatin fixed-dose combination group and atorvastatin group) |  | 4 weeks, up to maximum 5 weeks | 
| Change from baseline in apolipoprotein-B (irbesartan/atorvastatin fixed-dose combination group and atorvastatin group) - Time Frame: 4 weeks, up to maximum 5 weeks |  | 4 weeks, up to maximum 5 weeks | 
| Percentage of participants with decreased level of blood pressure (irbesartan/atorvastatin fixed-dose combination group and irbesartan group) |  | 4 weeks, up to maximum 5 weeks | 
| Rate of change from baseline in immunosenescence T cell fractionation |  | 4 weeks, up to maximum 5 weeks | 
| Rate of change from baseline in T-cell induced inflammatory factors |  | 4 weeks, up to maximum 5 weeks |