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

Phase 2

Completed

• Conditions: Variant Angina
• Interventions: Drug: Placebo

• Registration Number: NCT01444885
• Lead Sponsor: Korea Otsuka Pharmaceutical Co., Ltd.

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2011-09-27
• Study First Submitted QC: 2011-09-30
• Study Start: 2011-10
• Study First Posted: 2011-10-03
• Status Verified: 2012-07
• Primary Completion: 2012-07
• Study Completion: 2012-07
• Last Update Submitted: 2012-07-13
• Last Update Posted: 2012-07-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1. Male or female over the age of 20 and under the age of 80
2. Diagnosis of vasospastic angina
3. At least one episode of chest pain weekly during the Amlodipine run in period for 2 weeks

Exclusion Criteria

1. Currently taking or has taken Cilostazol within the last 3 month before the screening.

2. Taking oral antiplatelet agents such as Aspirin, Clopidogrel after Amlodipine run-in period.

3. Oral anticoagulants such as Warfarin within the last a month before the screening.

4. 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

5. History of Myocardial infarction or Myocardial infarction by vasospastic angina at screening

6. History of life threatening vasospastic events such as ventricular tachycardia , ventricular fibrillation, or syncope

7. History of stroke, intracranial hemorrhage, or Transient Ischemic Attack(TIA)

8. 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)

9. History of clinically significant hypersensitivity to the substances of Cilostazol, Amlodipine, Nitroglycerin or dihydropyridine

10. Patients with severe aortic valvular stenosis

11. History of shock

12. Hypotension of diastolic pressure < 90 mmHg at screening

13. History of clinically significant hypersensitivity to the substances of Nitrates

14. Patients with severe anemia of Hemoglobin ≤ 6.5 g/dl at screening

15. History of glaucoma

16. Electrocardiogram(ECG) abnormality precluding interpretation of ST change at screening

17. Congestive heart failure with less than 40% of left ventricular ejection fraction within the last 3 month before the screening or screening period

18. Atrial fibrillation or valvular heart disease, more than moderate severity

19. Suspected or identified spasm of left main coronary artery, result of coronary angiography or coronary angiography in the ergonovine induced coronary spasm provocation test

20. History of Coronary artery bypass graft(CABG) or percutaneous coronary intervention(PCI)

21. Tachycardia; Heart rate > 100 bpm, at Screening

22. Uncontrolled hypertension, defined as ≥ 160 mmHg systolic or ≥ 100 mmHg diastolic at Screening

23. Creatinine ≥ 1.5 mg/dL at screening

24. Aspartate transaminase (AST) or alanine transaminase (ALT) > 3 times the upper limit of normal (ULN) at screening

25. Platelet < 100,000 mm3 at screening

26. QT prolongation defined as baseline QTc > 450 msec for males or > 470 msec for females at Screening.

27. Women who have the possible of pregnancy, or positive urine or blood pregnancy test at screening

28. Women who are not using a reliable method of birth control, who are pregnant, or who are breast-feeding

29. Drug compliance of Amlodipine < 80% during the Amlodipine run in period for 2 weeks

30. Otherwise judged by the investigator to be inappropriate for inclusion in the trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cilostazol	Placebo	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).

Primary Outcome Measures

Name	Time	Method
Percent change of the chest pain frequency	A week before IP dosing and the final a week after IP dosing (average 6weeks)	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.

Secondary Outcome Measures

Name	Time	Method
The chest pain frequency, the pain intensity, nitroglycerin consumption of the final a week after IP dosing from a week before IP dosing	A week before IP dosing and the final a week after IP dosing (average 6weeks)	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.

Trial Locations

Locations (10)

Ajou University Hospital; 🇰🇷 Suwon, Korea, Republic of

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

ChungNam Univ. Hospital; 🇰🇷 DaeJeon, Korea, Republic of

Pusan National University Yansan Hospital; 🇰🇷 Pusan, Korea, Republic of

Gangneung Asan Hospital; 🇰🇷 Gangneung, Korea, Republic of

Dong-A University Hospital; 🇰🇷 Pusan, Korea, Republic of

Keimyung University Dongsan Medical Center; 🇰🇷 Daegu, Korea, Republic of

Ulsan University Hospital; 🇰🇷 Ulsan, Korea, Republic of

Chonnam National University Hospital; 🇰🇷 Gwangju, Korea, Republic of

Gyongsang National University Hospital; 🇰🇷 Jinjoo, Korea, Republic of