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

Study Overview
=================
Brief Summary
-----------------
The objective of this study is to evaluate the dose-response of three different dose levels of STA-2 (900 mg daily, 1800 mg daily and 2700 mg daily for 42 days) versus placebo in patients with chronic stable angina.

Detailed Description
-----------------
The objective of this study is to evaluate the dose-response of three different dose levels of STA-2 (900 mg daily, 1800 mg daily and 2700 mg daily for 42 days) versus placebo in patients with chronic stable angina. Treatment Group A: 150 mg STA-2, 2 capsules t.i.d., after meal (900 mg STA-2 total dose per day) Treatment Group B: 300 mg STA-2, 2 capsules t.i.d., after meal (1800 mg STA-2 total dose per day) Treatment Group C: 450 mg STA-2, 2 capsules t.i.d., after meal (2700 mg STA-2 total dose per day) Placebo Group: Placebo capsule, 2 capsules t.i.d., after meal

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

Conditions
-----------------
Chronic Stable Angina

Intervention / Treatment
-----------------
* Drug: green tea polyphenols (STA-2)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female aged ≧ 20 years; Subjects weight > 50 kg subjects who had more than 50% coronary stenosis documented by catheterization or ever received coronary intervention; The two ETT results at screening (Visit 1) and baseline (Visit 2) show greater than or equal to 1 mm ST-segment depression within exercise duration; The difference in exercise duration between screening (Visit 1) and baseline (Visit 2) do not exceed 20% of the longer test; Able to provide written informed consent. Exclusion Criteria: Subjects with pacemaker rhythm, unstable angina or myocardial infarction within the preceding 3 months; Subjects with heart failure (New York Heart Association class III or IV), uncorrected valvular or congenital heart disease, subjects who need digoxin or digitalis; Subjects with any resting EKG abnormalities preventing the interpretation of ischemia as judged by the investigator; Subjects with COPD requiring bronchodilators; Subjects with impaired hepatic function (defined as AST or ALT > 2X the upper limit of normal values), or impaired renal function (defined as serum creatinine > 1.5 mg/dL), or diagnosis of any chronic renal/hepatic disease; Subjects with documented evidence of gastroduodenal ulcer disease, gastrointestinal bleeding or other gastrointestinal disease within the preceding 3 months as judged by investigator; Subjects who have a history or evidence of a medical condition that would expose them to an undue risk of a significant adverse event or interfere with safety assessments during the course of the trial, including but not limited to hepatic, renal, respiratory, cardiovascular, endocrine, immune, neurological, or hematological disease as determined by the clinical judgment of the investigator; Subject with any conditions that could interfere the performance of exercise tolerance test as judged by investigator (e.g., knee/ankle arthropathy, Parkinsonism, stoke); Female subjects of childbearing potential who: are lactating; have positive pregnancy test (urine) at V1; Subject has received any investigational agent within 28 days prior to the first dose of investigational product; Subjects who have had administered STA-2 in prior clinical trial.

Ages Eligible for Study
-----------------
Minimum Age: 20 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo group<br>placebo capsule 2# t.i.d./day | Drug: green tea polyphenols (STA-2)<br>* 2 capsules t.i.d., after meal<br>|
| Experimental: Treatment Group A<br>150 mg STA-2, 2 capsules t.i.d., after meal (900 mg STA-2 total dose per day) | Drug: green tea polyphenols (STA-2)<br>* 2 capsules t.i.d., after meal<br>|
| Experimental: Treatment Group B<br>300 mg STA-2, 2 capsules t.i.d., after meal (1800 mg STA-2 total dose per day) | Drug: green tea polyphenols (STA-2)<br>* 2 capsules t.i.d., after meal<br>|
| Experimental: Treatment Group C<br>450 mg STA-2, 2 capsules t.i.d., after meal (2700 mg STA-2 total dose per day) | Drug: green tea polyphenols (STA-2)<br>* 2 capsules t.i.d., after meal<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Total Exercise Time (Seconds) | the time difference of total exercise time from V2 to V5 compare to placebo | 6 weeks after the first exercise tolerance testing is conducted | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Time to Onset of Angina From Baseline to the Final Visit |  | 6 weeks | 
| Changes in Time to 1mm ST-segment Depression During ETT From Baseline to Final Visit |  | 6 weeks | 
| Changes in Time to Maximum ST-segment Depression During ETT From Baseline to the Final Visit |  | 6 weeks | 
| Changes in Angina Frequency in Subject's Diary From Baseline to All Visits |  | 6 weeks | 
| Change in Consumption of Short-acting Nitrates From Baseline to All Visits |  | 6 weeks | 
| Change in Pharmacological Parameters (Oxidized-LDL), Isoprostane and High-sensitivity Hs-CRP From Baseline to All Visits |  | 6 weeks | 
| Change in Lipid Profiles (HDL-C, LDL-C, Total Cholesterol, Triglyceride) From Baseline to All Visits |  | 6 weeks | 
| Dose-response Relationship of Three Different Dose Levels of STA-2 Versus Placebo Control in Change in Total Exercise Time. |  | 6 weeks |