Evaluate the Efficacy and Safety of Pletaal (Cilostazol) in Subjects With Vasospastic Angina

Study Overview
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Brief Summary
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The objective of this study is to investigate the efficacy and safety of Pletaal (Cilostazol) in comparison with placebo for 4 weeks in vasospastic angina patients who have an insufficient response to Amlodipine (Calcium channel blocker).

Detailed Description
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A Multicenter, Randomized, Double-Blind, Placebo-controlled, Parallel group, Therapeutic exploratory Study. The subject who has at least an episode of chest pain weekly despite Amlodipine 5mg once a day (qd) taking during 2 weeks will have treatment of Pletaal (Cilostazol) or Placebo for 4 weeks. Pletaal (Cilostazol) is taken 100mg oral tablets two times a day (bid) during 2 weeks after dosing of Pletaal (Cilostazol) 50mg oral tablets bid during 2 weeks. Placebo of Pletaal (Cilostazol) is used as the control medication.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Therapeutic Exploratory Study to Evaluate the Efficacy and Safety of PletaalÒ(Cilostazol) in Subjects With Vasospastic Angina (STELLA)

Conditions
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Variant Angina

Intervention / Treatment
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* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female over the age of 20 and under the age of 80 Diagnosis of vasospastic angina At least one episode of chest pain weekly during the Amlodipine run in period for 2 weeks Exclusion Criteria: Currently taking or has taken Cilostazol within the last 3 month before the screening. Taking oral antiplatelet agents such as Aspirin, Clopidogrel after Amlodipine run-in period. Oral anticoagulants such as Warfarin within the last a month before the screening. Currently taking any of the following medications or has taken any of the following medications within the last a week before the screening: Other Calcium channel blockers than Amlodipine Beta-blocker, or Alpha-blocker Oral Nitrate, Nicorandil, except sublingual Nitroglycerin as required(PRN) Vitamin E preparations Estrogens History of Myocardial infarction or Myocardial infarction by vasospastic angina at screening History of life threatening vasospastic events such as ventricular tachycardia , ventricular fibrillation, or syncope History of stroke, intracranial hemorrhage, or Transient Ischemic Attack(TIA) Hemorrhage (hemophilia, capillary fragility, intracranial hemorrhage, upper gastrointestinal hemorrhage, urinary hemorrhage, hemoptysis, vitreous hemorrhage, etc.) or such tendency (active peptic ulcer, hemorrhagic stroke within past 6 months, a case hemorrhage is suspected by wound for surgery within 3 months, proliferative diabetic retinopathy and uncontrolled hypertension) History of clinically significant hypersensitivity to the substances of Cilostazol, Amlodipine, Nitroglycerin or dihydropyridine Patients with severe aortic valvular stenosis History of shock Hypotension of diastolic pressure < 90 mmHg at screening History of clinically significant hypersensitivity to the substances of Nitrates Patients with severe anemia of Hemoglobin ≤ 6.5 g/dl at screening History of glaucoma Electrocardiogram(ECG) abnormality precluding interpretation of ST change at screening Congestive heart failure with less than 40% of left ventricular ejection fraction within the last 3 month before the screening or screening period Atrial fibrillation or valvular heart disease, more than moderate severity Suspected or identified spasm of left main coronary artery, result of coronary angiography or coronary angiography in the ergonovine induced coronary spasm provocation test History of Coronary artery bypass graft(CABG) or percutaneous coronary intervention(PCI) Tachycardia; Heart rate > 100 bpm, at Screening Uncontrolled hypertension, defined as ≥ 160 mmHg systolic or ≥ 100 mmHg diastolic at Screening Creatinine ≥ 1.5 mg/dL at screening Aspartate transaminase (AST) or alanine transaminase (ALT) > 3 times the upper limit of normal (ULN) at screening Platelet < 100,000 mm3 at screening QT prolongation defined as baseline QTc > 450 msec for males or > 470 msec for females at Screening. Women who have the possible of pregnancy, or positive urine or blood pregnancy test at screening Women who are not using a reliable method of birth control, who are pregnant, or who are breast-feeding Drug compliance of Amlodipine < 80% during the Amlodipine run in period for 2 weeks Otherwise judged by the investigator to be inappropriate for inclusion in the trial.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cilostazol<br>To investigate the efficacy and safety of Pletaal(Cilostazol) in comparison with placebo for 4 weeks in vasospastic angina patients who have an insufficient response to Amlodipine (Calcium channel blocker). | Drug: Placebo<br>* 2 weeks treatment of Cilostazol 100mg, or placebo oral tablets bid after 2 weeks treatment of Cilostazol 50mg, or placebo oral tablets bid (Total 4 weeks)<br>* Other names: Nitroglycerin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change of the chest pain frequency | Collect the chest pain frequency data related with vasospastic angina episodes by subject diaries. Descriptive statistics (N, mean, standard deviation, minimum, median and maximum) will be presented by treatment group. ANCOVA will be performed between the treatment groups using the baseline (a week before IP dosing) as covariate. | A week before IP dosing and the final a week after IP dosing (average 6weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The chest pain frequency, the pain intensity, nitroglycerin consumption of the final a week after IP dosing from a week before IP dosing | Descriptive statistics (N, mean, standard deviation, minimum, median and maximum) will be presented by treatment group. ANCOVA will be performed between the treatment groups using the baseline (a week before IP dosing) as covariate. The subject who has no chest pain will be regarded as the total pain intensity and the average pain intensity are '0'. The subject who has taken no nitroglycerin will be regarded as taking '0' tablet. | A week before IP dosing and the final a week after IP dosing (average 6weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Variant angina, Cilostazol