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

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 .

Study Overview

• Status: Completed
• Conditions: Atherosclerosis Cerebral Infarction
• Intervention / Treatment: Drug: Cilostazol group; Drug: Probucol group; Drug: Cilostazol + Probucol group; Drug: control group

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • First Affliate Hospital of Beijing University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1	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.; Other Names: Pletaal
EXPERIMENTAL: 2	Drug: Probucol group; Probucol: 250 mg (1 tablet) Bid, PO after breakfast and dinner; Other Names: Changtai
EXPERIMENTAL: 3	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; Other Names: Pletaal and Changtai
OTHER: 4; Control Group	Drug: control group; routine treatment; Other Names: Routine Treatment

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Otsuka Beijing Research Institute

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (ACTUAL): December 1, 2009
• Study Completion (ACTUAL): July 1, 2010

Study Registration Dates

• First Submitted: January 15, 2009
• First Submitted That Met QC Criteria: January 15, 2009
• First Posted (ESTIMATE): January 16, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): December 1, 2010
• Last Update Submitted That Met QC Criteria: November 30, 2010
• Last Verified: January 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Brain Ischemia; Stroke; Brain Infarction; Intracranial Arterial Diseases; Infarction; Cerebral Infarction; Atherosclerosis; Intracranial Arteriosclerosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Antimetabolites; Neuroprotective Agents; Protective Agents; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Antioxidants; Phosphodiesterase Inhibitors; Phosphodiesterase 3 Inhibitors; Cilostazol; Probucol
• Other Study ID Numbers: 260-08-803-01