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

Otsuka

Status and phase: Completed; Phase 2

Conditions: Peripheral Artery Disease

Treatments: Drug: Cilostazol, Probucol

Study type: Interventional

Funder types: Industry

Identifiers

NCT01142284

021-KOA-0901i

Details and patient eligibility

About

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.

Full 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.

Enrollment: 80 patients

Sex: All

Ages: 40 to 79 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

80 participants in 4 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Placebo

Treatment:

Drug: Cilostazol, Probucol

Cilostazol

Experimental group

Description:

cilostazol

Treatment:

Drug: Cilostazol, Probucol

Probucol

Experimental group

Description:

probucol

Treatment:

Drug: Cilostazol, Probucol

Cilostazol + Probucol

Experimental group

Description:

cilostazol and probucol

Treatment:

Drug: Cilostazol, Probucol