Phase II Study of STA-2 in Patients With Chronic Stable Angina

A Double-blind, Randomized, Placebo-controlled Study to Evaluate the Efficacy and Safety of STA-2 in Patients With Chronic Stable Angina

The objectives of this study are to evaluate the efficacy, pharmacological activities and safety of STA-2 in the treatment of chronic stable angina.

The primary objective of this study was to evaluate the efficacy of STA-2 in the management of chronic stable angina. The secondary objectives of this study were to evaluate the safety and pharmacological activities of STA-2 in the management of chronic stable angina. This was a multi-center, double-blind, randomized, parallel-group, placebo-controlled study of STA-2 in the management of chronic stable angina. The study period for each patient was approximately 7 weeks, during which the patient undergone one-week screening and washout period, followed by 6 weeks of treatment. Each patient was required to make a total of 5 visits. Primary Efficacy Endpoint: Change in total exercise time.

After washout, patients who met the inclusion and exclusion criteria were randomly assigned either to the treatment or control group. The respective regimens were:

Treatment group:

STA-2 250 mg capsule, each containing 100 mg green tea polyphenols, 2 capsules ter in die (t.i.d.=three times daily) for 6 weeks, to be administered in a non-fasting state.

Control group:

Placebo 250 mg capsule, 2 capsules t.i.d. (three times daily) for 6 weeks, to be administered in a non-fasting state.

Inclusion criteria:

1. Male or female aged > 20;

2. Patients who had effort-induced angina which was relieved by rest or nitroglycerin, or who had catheterization-documented coronary artery disease or previous myocardial infarction ≥ 3 months before screening;

3. Patients who manifested positive ETT (exercise tolerance testing) (defined as ST-segment depression ≥ 1 mm compared with at rest, with or without limiting angina) at screening (Day -7);

4. Patients who manifested positive ETT (exercise tolerance testing) (defined as ST-segment depression ≥ 1 mm compared with at rest, with or without limiting angina) on the day of enrollment (Day 0). ETT performance between Day -7 and Day 0 were required not differ by >20% in total exercise time;

5. Female patient who was in the post-menopausal stage or of childbearing potential who:

   • used adequate contraception since last menstruation and no plan for conception during the study;
   • was non-lactating;
   • had negative pregnancy test (urine) within 14 days prior to the study;

6. Able to provide written informed consent.

Exclusion criteria:

1. Patients with pre-excitation, conduction abnormalities, pacemaker rhythm, unstable angina or myocardial infarction within the preceding 3 months;
2. Patients with heart failure (New York Heart Association class III or IV), uncorrected valvular or congenital heart disease, patients who needed digoxin, isosorbide mononitrate, nitroglycerin sustained release preparation, theophylline, class I antiarrhythmic agents, digitalis, or monoamine oxidase inhibitors, as judged by the investigator;
3. Patients with any EKG abnormalities preventing the interpretation of ischemia (complete left bundle branch block);
4. Patients with Chronic Obstructive Pulmonary Disease (COPD) requiring bronchodilators;
5. Patients with hepatic failure (defined as aspartate transaminase (AST) and/or alanine transaminase (ALT) > 3X the upper limit of normal values), and/or renal failure (defined as serum creatinine > 3 mg/dL);
6. Patients with severe gastrointestinal illness as judged by the investigator;
7. Patient with any conditions that interfered the performance of exercise tolerance test as judged by investigator (e.g., knee/ankle arthropathy, Parkinsonism, stroke).