Study of Cilostazol and Probucol Alone and in Combination on Atherosclerosis Related Biomarker---atherosclerosis Cerebral Infarction Patient as Study Subject

Study Overview
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Brief Summary
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Randomized, control, open label, multicentre clinical study. The patient who are in accordance with subject inclusion and exclusion criteria will be randomized to A group: Routine treatment B group: Routine treatment+ Cilostazol; C group : Routine treatment + Probucol; D group: Routine treatment+ Cilostazol+ Probucol .

Detailed Description
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Efficacy index: After 12 weeks of treatment, the change difference of arteriosclerosis related biomarker between 4 modality groups. Pharmacokinetics: After 12 weeks of treatment, the study medication plasma concentration including of Probucol ,Cilostazol , Cilostazol metabolism OPC-13015 and OPC-13213 will be measured. Safety evaluation: Analysis the abnormality of Adverse Event, Vital Sign, Physical Examination, 12-lead ECG, and Laboratory Tests (including blood routine examination, routine urine analysis, blood biochemistry examination, glycosylated hemoglobin) in 4 modality groups.

Official Title
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A Randomized, Control, Open Label, Multicentre Clinical Study to Evaluate the Efficacy and Safety of Cilostazol and Probucol Alone and in Combination on Atherosclerosis Related Biomarker---atherosclerosis Cerebral Infarction Patient as Study Subject

Conditions
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Atherosclerosis Cerebral Infarction

Intervention / Treatment
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* Drug: Cilostazol group
* Drug: Probucol group
* Drug: Cilostazol + Probucol group
* Drug: control group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 40～80-year-old male or female By brain CT or MRI result, cerebral infarction is clarified diagnosis within 1 year With atherosclerosis, atherosclerosis should meet at least one of the conditions as below: Clarified diagnosis of type 2 diabetes before Clarified diagnosis of primary hypertension before Clarified diagnosis of Atherosclerotic stenosis in any 2 or more than 2 regions as cerebral artery, carotid, extremity artery and coronary by conformation of ultrasonic or angiography result Has Aspirin regularly for more than 1 month before registration Informed Consent Form signature Exclusion criteria： Has an allergic history to study drugs( including of Probucol and Cilostazol) and Aspirin Had lipid-lowing agents within the last 3 months ( except Statins) Had antiplatelet or anticoagulation agents within the last 3 months (except Aspirin) Had acute cerebral infarction within the last 1 month Has cardiogenic cerebral embolism At the registration ,Modified Rankin Scale ≥ 4 Hemorrhagic tendency or hemorrhagic disease (such as cerebral hemorrhage, gastrointestinal tract hemorrhage, etc.) Had a myocardial infarction, angina pectoris within the last 3 months Congestive heart failure Is pregnant, is potentially pregnant, or is breastfeeding Severe hepatic inadequacy or severe renal inadequacy (AST or ALT is 2.5 times higher than the upper limit of the normal value range, or serum creatinine is 1.2 times higher than the upper limit of the normal value range) Persistent or hardly controlled hypertension (such as malignant hypertension, BP> 160/100 mmHg) Severe ventricular arrhythmia (such as multiple and multifocal premature ventricular contractions) Has a medical history that includes a cardiac syncope or a primary syncope Has a condition that may prolong QT interval (such as congenital long QT syndrome, taking drugs which prolong QT interval, hypokalemia or hypomagnesemia, etc.) Has severe diseases (such as, malignant tumor, severe anaemia, severe hematologic diabetes mellitus ketoacidosis, nonketotic hyperosmolar diabetic coma, etc.) Registered other clinical trails within the last 3 months Has vasculitis, moyamoya disease and other non-atherosclerosis vascular diseases Other conditions that could exclude the subject from this study by doctor's judgment

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 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: 1<br> | Drug: Cilostazol group<br>* Cilostazol: At first, 50 mg (1 tablets) Bid, PO after breakfast and dinner. After administration of study drug for 1 week, and if patient has no significant discomfort, the drug dosage will increase to 100mg（2 tablets）Bid.<br>* Other names: Pletaal;|
| Experimental: 2<br> | Drug: Probucol group<br>* Probucol: 250 mg (1 tablet) Bid, PO after breakfast and dinner<br>* Other names: Changtai;|
| Experimental: 3<br> | Drug: Cilostazol + Probucol group<br>* Cilostazol: At first, 50 mg (1 tablets) Bid, PO after breakfast and dinner. After administration of study drug for 1 week, and if patient has no significant discomfort, the drug dosage will increase to 100mg（2 tablets）Bid. Probucol: 250 mg (1 tablet) Bid, PO after breakfast and dinner<br>* Other names: Pletaal and Changtai;|
| Other: 4<br>Control Group | Drug: control group<br>* routine treatment<br>* Other names: Routine Treatment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| After 12 weeks of treatment, the change difference of arteriosclerosis related biomarker between 4 modality groups. |  | 12 week |