Evaluation of Concomitant Administration of Cilostazol and Probucol on Biomarkers, Endothelial Function and Safety

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2010 by Korea Otsuka Pharmaceutical Co.,Ltd..
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Korea Otsuka Pharmaceutical Co.,Ltd.
ClinicalTrials.gov Identifier:
NCT01142284
First received: June 10, 2010
Last updated: NA
Last verified: June 2010
History: No changes posted
  Purpose

Based upon evidence of efficacy and safety of both cilostazol and probucol administration in independent randomized controlled trials in PAD and CAD, the present trial seeks to investigate the effect of concomitant administration of cilostazol and probucol on FMD compared to each drug individually, as well as to evaluate biomarker measures and safety indices in this context.


Condition Intervention Phase
Peripheral Artery Disease
Drug: Cilostazol, Probucol
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Evaluation of Concomitant Administration of Cilostazol and Probucol on Biomarkers, Endothelial Function and Safety in Peripheral Artery Disease Subjects Complicated With Coronary Artery Disease.

Resource links provided by NLM:


Further study details as provided by Korea Otsuka Pharmaceutical Co.,Ltd.:

Primary Outcome Measures:
  • On the 12-week change in FMD / Safety [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    1. To evaluate the effect of concomitant administration of cilostazol and probucol on the 12-week change
    2. To assess the safety of concomitant administration of cilostazol and probucol


Secondary Outcome Measures:
  • Changes in the biomarker and FMD [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    1. To evaluate the effect of cilostazol and probucol administered concomitantly and as individual drugs, compared with control, on changes in FMD
    2. To evaluate the effect of cilostazol and probucol administered concomitantly and as individual drugs, compared with control on biomarkers
    3. To evaluate the effect of cilostazol and probucol administered concomitantly and as individual drugs, compared with control, on the time course
    4. To assess the effect of drug withdrawal
    5. To explore the relationship between changes in FMD and changes in the biomarker levels


Estimated Enrollment: 224
Study Start Date: April 2010
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo
Drug: Cilostazol, Probucol

Treatment Group 1 (control) No cilostazol or probucol

Treatment Group 2 (cilostazol alone) 1 tablet cilostazol 100 mg PO BID

Treatment Group 3 (probucol alone) 1 tablet probucol 250 mg PO BID

Treatment Group 4 (concomitant cilostazol and probucol) 1 tablet cilostazol 100 mg PO BID, and 1 tablet probucol 250 mg PO BID

Experimental: Cilostazol
cilostazol
Drug: Cilostazol, Probucol

Treatment Group 1 (control) No cilostazol or probucol

Treatment Group 2 (cilostazol alone) 1 tablet cilostazol 100 mg PO BID

Treatment Group 3 (probucol alone) 1 tablet probucol 250 mg PO BID

Treatment Group 4 (concomitant cilostazol and probucol) 1 tablet cilostazol 100 mg PO BID, and 1 tablet probucol 250 mg PO BID

Experimental: Probucol
probucol
Drug: Cilostazol, Probucol

Treatment Group 1 (control) No cilostazol or probucol

Treatment Group 2 (cilostazol alone) 1 tablet cilostazol 100 mg PO BID

Treatment Group 3 (probucol alone) 1 tablet probucol 250 mg PO BID

Treatment Group 4 (concomitant cilostazol and probucol) 1 tablet cilostazol 100 mg PO BID, and 1 tablet probucol 250 mg PO BID

Experimental: Cilostazol + Probucol
cilostazol and probucol
Drug: Cilostazol, Probucol

Treatment Group 1 (control) No cilostazol or probucol

Treatment Group 2 (cilostazol alone) 1 tablet cilostazol 100 mg PO BID

Treatment Group 3 (probucol alone) 1 tablet probucol 250 mg PO BID

Treatment Group 4 (concomitant cilostazol and probucol) 1 tablet cilostazol 100 mg PO BID, and 1 tablet probucol 250 mg PO BID


Detailed Description:

Primary:

  1. To evaluate the effect of concomitant administration of cilostazol and probucol on the 12-week change in FMD from baseline compared, with individual drugs alone.
  2. To assess the safety of concomitant administration of cilostazol and probucol in peripheral artery disease (PAD) subjects complicated with coronary artery disease (CAD) as determined by physical examination, vital signs, adverse events (AEs), laboratory tests, ECGs.

Secondary:

  1. To evaluate the effect of cilostazol and probucol administered concomitantly and as individual drugs, compared with control, on changes in FMD from baseline to Weeks 6 and 12.
  2. To evaluate the effect of cilostazol and probucol administered concomitantly and as individual drugs, compared with control, on changes in metabolic, inflammatory, oxidative, and platelet biomarkers from baseline to Weeks 6 and 12.
  3. To evaluate the effect of cilostazol and probucol administered concomitantly and as individual drugs, compared with control, on the time course (over the 12-week treatment period) of changes in FMD and biomarkers levels.
  4. To assess the effect of drug withdrawal on these endpoints at follow-up (from Week 12 to Week 16).
  5. To explore the relationship between changes in FMD and changes in the biomarker levels at Week 12.
  Eligibility

Ages Eligible for Study:   40 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age is ≥ 40 and <80 years at Screening.
  2. The subject has a diagnosis of PAD
  3. The subject has a diagnosis of CAD
  4. Stable background medical therapy over the past 3 months
  5. Taking 100mg/day of aspirin or 75mg/day of clopidogrel over the past 3 months
  6. Hyperlipidemia defined as a LDL cholesterol concentration > 70 mg/dL
  7. The subject is willing to participate in this study as documented by written informed consent

Exclusion Criteria:

  1. New diagnosis of PAD within 3 months.
  2. Currently taking cilostazol or has taken cilostazol
  3. Currently taking probucol or has taken probucol within the last 3 months
  4. Critical limb ischemia (CLI)
  5. Congestive heart failure
  6. Transient ischemic attack (TIA)
  7. Endovascular peripheral or coronary revascularization procedure within 3 months
  8. Coronary artery bypass graft (CABG) or major cardiovascular surgical procedures within 6 months
  9. Major surgical procedures within 3 months
  10. Uncontrolled hypertension
  11. Type 1 diabetes mellitus or poorly controlled type 2 diabetes mellitus
  12. Diabetic complications of severe peripheral neuropathy or active retinopathy.
  13. Inflammatory bowel disease.
  14. Unstable angina
  15. QT prolongation
  16. Severe or life threatening ventricular arrhythmias
  17. History of syncope
  18. Serum creatinine > 2.5 mg/dL, Creatinine Clearance ≤25ml/min or renal failure requiring dialysis.
  19. History or evidence of any hematological or clotting disorder.
  20. Hematocrit ≤ 28% or ≥ 55%.
  21. AST or ALT > 3 times the upper limit of normal (ULN).
  22. Any form of chronic anticoagulation.
  23. Coagulopathies defined as an INR > 1.5
  24. History of malignant disease within 5 years.
  25. Acute or chronic hepatitis.
  26. Hemophilia or known increased risk of hemorrhage.
  27. Other clinically significant disorders resulting in a remaining life expectancy less than one year.
  28. Current alcohol or drug abuse.
  29. If female, the subject cannot be pregnant or breastfeeding and must be of non-childbearing potential
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01142284

Contacts
Contact: SeungWhan Lee, MD.PhD. 02-3010-3170 seungwlee@amc.seoul.kr

Locations
Korea, Republic of
Asan Medical Center Recruiting
Seoul, Korea, Republic of
Contact: SeungWhan Lee, MD.PhD.    82-2-3010-3170    seungwlee@amc.seoul.kr   
Principal Investigator: SeungWhan Lee, MD.PhD.         
Sponsors and Collaborators
Korea Otsuka Pharmaceutical Co.,Ltd.
  More Information

No publications provided

Responsible Party: SW Hong/CTM, Korea Otsuka Pharmaceutical Co.,Ltd.
ClinicalTrials.gov Identifier: NCT01142284     History of Changes
Other Study ID Numbers: 021-KOA-0901i
Study First Received: June 10, 2010
Last Updated: June 10, 2010
Health Authority: Korea: Food and Drug Administration

Keywords provided by Korea Otsuka Pharmaceutical Co.,Ltd.:
Biomarker
Endothelial Function
Peripheral Artery Disease
Coronary Artery Disease
Flow Mediated Dilation
Cilostazol
Probucol

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Peripheral Arterial Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Atherosclerosis
Peripheral Vascular Diseases
Probucol
Cilostazol
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Antioxidants
Protective Agents
Physiological Effects of Drugs
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Fibrinolytic Agents
Fibrin Modulating Agents

ClinicalTrials.gov processed this record on August 20, 2014