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

Sponsor

Korea Otsuka Pharmaceutical Co., Ltd. (Industry)

Overall Status

Completed

CT.gov ID

NCT01142284

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Months)

2.6

Patients Per Site Per Month

Study Details

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.

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

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
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.

Study Design

Study Type:

Interventional

Actual Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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.

Actual Study Start Date :

May 19, 2010

Actual Primary Completion Date :

Nov 29, 2012

Actual Study Completion Date :

Dec 18, 2012

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

On the 12-week change in FMD / Safety [12 weeks]
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 [12 weeks]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 79 Years

Sexes Eligible for Study:

All

Accepts 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