Intermittent Claudication

Peripheral arterial disease (PAD) results in decrease in arterial blood flow to the lower extremities with symptoms that may include pain at rest, numbing sensation in limbs or feet, limited ability to walk before pain occurs, and inhibited ability of ulcer healing in the lower extremity. Intermittent claudication (IC) is the most common debilitating symptom of PAD. The study is designed to compare the efficacy and safety of once daily PMR treatment with twice daily Pletaal® treatment in patients with IC caused by PAD and are currently treated with cilostazol of any strength and any dosing frequency.

PMR

Cilostazol

Modified Release Tablet

200mg

Primary Efficacy Endpoint
The Primary efficacy outcome in this study is the geometric mean percent change in ICD
over the 24-week treatment period compared to baseline.

Inclusion Criteria:
Potential subjects are required to meet all of the following criteria for enrollment into the
study and subsequent randomization.
1. Must be 20 years of age or older.
2. Stable use of Cilostazol of any strength and any dosing frequency for at least 3 months
prior to screening, for the treatment of PAD*.
* History** of or current PAD is defined as a resting ankle-brachial index (ABI) of ≤
0.90 and a post-exercise drop in ankle artery blood pressure of ≥ 10 mmHg measured
immediately after the onset of ACD, or those with a resting ABI of ≤ 0.90 and
stenosis proven by imaging studies such as angiography or pulse volume recordings
(PVR).
** Data within 6 months prior to screening will be acceptable.
3. ICD ≥ 30 meters at the constant workload treadmill test.
4. Subjects should be able to understand, communicate, and willing to conform to the study
procedures, including but not limited to treadmill tests, and visits; subjects must sign an
IRB/IEC approved Informed Consent Form before screening procedures are undertaken.

Exclusion Criteria:
Potential subjects meeting any of the following criteria will be excluded from enrollment and
subsequent randomization.
1. Presence of limb-threatening chronic limb ischemia, manifested by ischemic rest pain*,
ulceration or gangrene**.
* Defined as persistent recurrent pain at rest requiring analgesics for more than 2
weeks.
** Defined as persistent, non-healing ulceration or gangrene.
2. History of lower-extremity surgical or endovascular arterial reconstructions or
sympathectomy within 3 months prior to screening.
3. Presence of illness(es) (such as angina pectoris, respiratory disease, orthopaedic disease,
or neurological disorders, except the study disease) limiting the exercise capacity.
4. Presence of uncontrolled hypertension (based on physician's judgment) or other unstable
cardiovascular disease such as congestive heart failure of any severity and myocardial
infarction within 6 months prior to screening.
5. History of coronary artery bypass graft (CABG) or major cardiovascular surgical
procedures within 6 months prior to screening.
6. History of Buerger’s disease or deep vein thrombosis within 3 months prior to screening.
7. Presence of haemostatic disorders or active pathologic bleeding, such as bleeding
peptic ulcer and intracranial bleeding.
8. Presence or history of ventricular tachycardia, ventricular fibrillation or multifocal
ventricular tachycardia with or without adequate treatment, QTc prolongation associated
with cardiac disorders, or severe tachyarrhythmia within 6 months prior to screening,
which is considered not suitable for this study by Investigator.
9. History of type 1 diabetes mellitus or poorly controlled type 2 diabetes mellitus*.
* Poorly controlled type 2 diabetes mellitus is defined as Hemoglobin A1c (HbA1c) >
10%.
10. History of malignancy, except in situ of the cervix or adequately treated basal cell or
squamous cell skin carcinoma, within 5 years prior to screening.
11. Gross obesity defined as body mass index (BMI) > 40 kg/m2
.
12. Patient with any of the following laboratory parameters at screening:
a) AST or ALT > 3 times the upper limit of normal (ULN)
b) Coagulopathies defined as an INR > 1.5
c) eGFR < 30 mL/min
13. Use of anticoagulant agent(s) within 6 months prior to screening.
14. Use of two or more than two anti-platelet agents within 3 months prior to screening.
15. Intermittent or unstable use of nonsteroidal anti-inflammatory drug(s) (NSAIDs), anti-platelet, hemorrheologic, vasodilating or other hemodilution/rheological agent(s) within 3
months prior to screening.
16. Use or anticipated use of the prohibited medication during the Treatment Phase of the
study.
17. Patient on any investigational drug(s) or therapeutic device(s) within 30 days preceding
screening; or patient or physician anticipates use of any of these therapies by the patient
during the course of the study.
18. Previous participation in the Treatment Phase of this Protocol.
19. History of substance abuse, such as alcohol, intravenous drugs and inhaled drugs, within
1 year prior to screening.
20. Known history of having acquired immunodeficiency syndrome (AIDS) or with a history
known to be infected with human immunodeficiency virus (HIV).
21. Women who are pregnant, breast feeding, or of child-bearing potential not using an
effective birth control method. Women of child-bearing potential are defined as women
physiologically capable of becoming pregnant, UNLESS they meet the following criteria:
a) Post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of
spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels >
40mIU/mL, OR;
b) 6 weeks post surgical bilateral oophorectomy with or without hysterectomy, OR;
c) Are using one or more of the following acceptable methods of contraception:
surgical sterilization (e.g. bilateral tubal ligation), hormonal contraception
(implantable, patch, and oral), and double-barrier methods. Reliable
contraception should be maintained throughout the study and for 7 days after
study discontinuation.
22. Patient with any medical or psychiatric condition, including the presence of significant
abnormal laboratory values, which is considered not suitable for this study by
Investigator.
23. Known or suspected hypersensitivity to any ingredient of study drug(s), or known
intolerance to lactose.