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

Official Title: “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”

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 .

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.

Intervention(s) in this Clinical Trial

• Drug: Cilostazol group
  • 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.
• Drug: Probucol group
  • Probucol: 250 mg (1 tablet) Bid, PO after breakfast and dinner
• Drug: Cilostazol + Probucol group
  • 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
• Drug: control group
  • routine treatment

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
• Experimental: 2
• Experimental: 3
• Other: 4
  • Control Group

Primary Measures

• After 12 weeks of treatment, the change difference of arteriosclerosis related biomarker between 4 modality groups.
  • Time Frame: 12 week
    Safety Issue?: No

Inclusion Criteria:

• 1. 40～80-year-old male or female
• 2. By brain CT or MRI result, cerebral infarction is clarified diagnosis within 1 year
• 3. 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
• 4. Has Aspirin regularly for more than 1 month before registration
• 5. Informed Consent Form signature
• Exclusion criteria：
• 1. Has an allergic history to study drugs( including of Probucol and Cilostazol) and Aspirin
• 2. Had lipid-lowing agents within the last 3 months ( except Statins)
• 3. Had antiplatelet or anticoagulation agents within the last 3 months (except Aspirin)
• 4. Had acute cerebral infarction within the last 1 month
• 5. Has cardiogenic cerebral embolism
• 6. At the registration ,Modified Rankin Scale ≥ 4
• 7. Hemorrhagic tendency or hemorrhagic disease (such as cerebral hemorrhage, gastrointestinal tract hemorrhage, etc.)
• 8. Had a myocardial infarction, angina pectoris within the last 3 months
• 9. Congestive heart failure
• 10. Is pregnant, is potentially pregnant, or is breastfeeding
• 11. 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)
• 12. Persistent or hardly controlled hypertension (such as malignant hypertension, BP>
• 160/100 mmHg)
• 13. Severe ventricular arrhythmia (such as multiple and multifocal premature ventricular contractions)
• 14. Has a medical history that includes a cardiac syncope or a primary syncope
• 15. Has a condition that may prolong QT interval (such as congenital long QT syndrome, taking drugs which prolong QT interval, hypokalemia or hypomagnesemia, etc.)
• 16. Has severe diseases (such as, malignant tumor, severe anaemia, severe hematologic diabetes mellitus ketoacidosis, nonketotic hyperosmolar diabetic coma, etc.)
• 17. Registered other clinical trails within the last 3 months
• 18. Has vasculitis, moyamoya disease and other non-atherosclerosis vascular diseases
• 19. Other conditions that could exclude the subject from this study by doctor's judgment

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 40 Years

Maximum Age for this Clinical Trial: 80 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Otsuka Beijing Research Institute Industry

Overall Clinical Trial Officials and Contacts

Yining Huang, M.D. Principal Investigator Peking University First Hospital  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00823875

Study ID Number: 260-08-803-01

ClinicalTrials.gov Identifier: NCT00823875

Health Authority: China: State Food and Drug Administration