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

Primary Purpose

Peripheral Artery Disease

Status

Completed

Phase

Phase 2

Locations

Korea, Republic of

Study Type

Interventional

Intervention

Cilostazol, Probucol

About this trial

This is an interventional treatment trial for Peripheral Artery Disease focused on measuring Biomarker, Endothelial Function, Peripheral Artery Disease, Coronary Artery Disease, Flow Mediated Dilation, Cilostazol, Probucol

Eligibility Criteria

40 Years - 79 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

New diagnosis of PAD within 3 months.
Currently taking cilostazol or has taken cilostazol
Currently taking probucol or has taken probucol within the last 3 months
Critical limb ischemia (CLI)
Congestive heart failure
Transient ischemic attack (TIA)
Endovascular peripheral or coronary revascularization procedure within 3 months
Coronary artery bypass graft (CABG) or major cardiovascular surgical procedures within 6 months
Major surgical procedures within 3 months
Uncontrolled hypertension
Type 1 diabetes mellitus or poorly controlled type 2 diabetes mellitus
Diabetic complications of severe peripheral neuropathy or active retinopathy.
Inflammatory bowel disease.
Unstable angina
QT prolongation
Severe or life threatening ventricular arrhythmias
History of syncope
Serum creatinine > 2.5 mg/dL, Creatinine Clearance ≤25ml/min or renal failure requiring dialysis.
History or evidence of any hematological or clotting disorder.
Hematocrit ≤ 28% or ≥ 55%.
AST or ALT > 3 times the upper limit of normal (ULN).
Any form of chronic anticoagulation.
Coagulopathies defined as an INR > 1.5
History of malignant disease within 5 years.
Acute or chronic hepatitis.
Hemophilia or known increased risk of hemorrhage.
Other clinically significant disorders resulting in a remaining life expectancy less than one year.
Current alcohol or drug abuse.
If female, the subject cannot be pregnant or breastfeeding and must be of non-childbearing potential

Sites / Locations

Asan Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Cilostazol

Probucol

Cilostazol + Probucol

Arm Description

Placebo

cilostazol

probucol

cilostazol and probucol

Outcomes

Primary Outcome Measures

On the 12-week change in FMD / Safety

To evaluate the effect of concomitant administration of cilostazol and probucol on the 12-week change To assess the safety of concomitant administration of cilostazol and probucol

Secondary Outcome Measures

Changes in the biomarker and FMD

To evaluate the effect of cilostazol and probucol administered concomitantly and as individual drugs, compared with control, on changes in FMD To evaluate the effect of cilostazol and probucol administered concomitantly and as individual drugs, compared with control on biomarkers To evaluate the effect of cilostazol and probucol administered concomitantly and as individual drugs, compared with control, on the time course To assess the effect of drug withdrawal To explore the relationship between changes in FMD and changes in the biomarker levels

Full Information

NCT ID

NCT01142284

First Posted

June 10, 2010

Last Updated

July 14, 2022

Sponsor

Korea Otsuka Pharmaceutical Co., Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT01142284

Brief Title

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

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.

Study Type

Interventional

2. Study Status

Record Verification Date

July 2022

Overall Recruitment Status

Completed

Study Start Date

May 19, 2010 (Actual)

Primary Completion Date

November 29, 2012 (Actual)

Study Completion Date

December 18, 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Korea Otsuka Pharmaceutical Co., Ltd.

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

Detailed Description

Primary: 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. 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: 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. 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. 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. To assess the effect of drug withdrawal on these endpoints at follow-up (from Week 12 to Week 16). To explore the relationship between changes in FMD and changes in the biomarker levels at Week 12.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Peripheral Artery Disease

Keywords

Biomarker, Endothelial Function, Peripheral Artery Disease, Coronary Artery Disease, Flow Mediated Dilation, Cilostazol, Probucol

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

80 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo

Arm Title

Cilostazol

Arm Type

Experimental

Arm Description

cilostazol

Arm Title

Probucol

Arm Type

Experimental

Arm Description

probucol

Arm Title

Cilostazol + Probucol

Arm Type

Experimental

Arm Description

cilostazol and probucol

Intervention Type

Drug

Intervention Name(s)

Cilostazol, Probucol

Intervention Description

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

Primary Outcome Measure Information:

Title

On the 12-week change in FMD / Safety

Description

To evaluate the effect of concomitant administration of cilostazol and probucol on the 12-week change To assess the safety of concomitant administration of cilostazol and probucol

Time Frame

12 weeks

Secondary Outcome Measure Information:

Title

Changes in the biomarker and FMD

Description

Time Frame

12 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

40 Years

Maximum Age & Unit of Time

79 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age is ≥ 40 and <80 years at Screening. The subject has a diagnosis of PAD The subject has a diagnosis of CAD Stable background medical therapy over the past 3 months Taking 100mg/day of aspirin or 75mg/day of clopidogrel over the past 3 months Hyperlipidemia defined as a LDL cholesterol concentration > 70 mg/dL The subject is willing to participate in this study as documented by written informed consent Exclusion Criteria: New diagnosis of PAD within 3 months. Currently taking cilostazol or has taken cilostazol Currently taking probucol or has taken probucol within the last 3 months Critical limb ischemia (CLI) Congestive heart failure Transient ischemic attack (TIA) Endovascular peripheral or coronary revascularization procedure within 3 months Coronary artery bypass graft (CABG) or major cardiovascular surgical procedures within 6 months Major surgical procedures within 3 months Uncontrolled hypertension Type 1 diabetes mellitus or poorly controlled type 2 diabetes mellitus Diabetic complications of severe peripheral neuropathy or active retinopathy. Inflammatory bowel disease. Unstable angina QT prolongation Severe or life threatening ventricular arrhythmias History of syncope Serum creatinine > 2.5 mg/dL, Creatinine Clearance ≤25ml/min or renal failure requiring dialysis. History or evidence of any hematological or clotting disorder. Hematocrit ≤ 28% or ≥ 55%. AST or ALT > 3 times the upper limit of normal (ULN). Any form of chronic anticoagulation. Coagulopathies defined as an INR > 1.5 History of malignant disease within 5 years. Acute or chronic hepatitis. Hemophilia or known increased risk of hemorrhage. Other clinically significant disorders resulting in a remaining life expectancy less than one year. Current alcohol or drug abuse. If female, the subject cannot be pregnant or breastfeeding and must be of non-childbearing potential

Facility Information:

Facility Name

Asan Medical Center

City

Seoul

Country

Korea, Republic of

12. IPD Sharing Statement

Learn more about this trial

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

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