Chronic Stable Angina
Conditions
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
Interventions
DRUGgreen tea polyphenols (STA-2)
2 capsules t.i.d., after meal
Sponsors
Sinphar Pharmaceutical Co., Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female aged ≧ 20 years; 2. Subjects weight \> 50 kg 3. subjects who had more than 50% coronary stenosis documented by catheterization or ever received coronary intervention; 4. 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; 5. The difference in exercise duration between screening (Visit 1) and baseline (Visit 2) do not exceed 20% of the longer test; 6. Able to provide written informed consent.
Exclusion criteria
1. Subjects with pacemaker rhythm, unstable angina or myocardial infarction within the preceding 3 months; 2. Subjects with heart failure (New York Heart Association class III or IV), uncorrected valvular or congenital heart disease, subjects who need digoxin or digitalis; 3. Subjects with any resting EKG abnormalities preventing the interpretation of ischemia as judged by the investigator; 4. Subjects with COPD requiring bronchodilators; 5. 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; 6. Subjects with documented evidence of gastroduodenal ulcer disease, gastrointestinal bleeding or other gastrointestinal disease within the preceding 3 months as judged by investigator; 7. 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; 8. Subject with any conditions that could interfere the performance of exercise tolerance test as judged by investigator (e.g., knee/ankle arthropathy, Parkinsonism, stoke); 9. Female subjects of childbearing potential who: * are lactating; * have positive pregnancy test (urine) at V1; 10. Subject has received any investigational agent within 28 days prior to the first dose of investigational product; 11. Subjects who have had administered STA-2 in prior clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Total Exercise Time (Seconds) | 6 weeks after the first exercise tolerance testing is conducted | the time difference of total exercise time from V2 to V5 compare to placebo |
Secondary
| Measure | Time frame |
|---|---|
| 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 Time to Onset of Angina From Baseline to the Final Visit | 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 |
| Change in Consumption of Short-acting Nitrates From Baseline to All Visits | 6 weeks |
Countries
Taiwan
Participant flow
Recruitment details
The recruitment period was from Nov. 2010 through Apr. 2012. There are 5 study sites participated in this study, including National Taiwan University Hospita, Chi Mei Medical Center, Taipei Veterans General Hospital, Taipei Medical University-Shuang Ho Hospital and Kaohsiung Medical University Chung-Ho emorial Hospital.
Pre-assignment details
In order to ensure the consistency, the difference of total exercise time between V1 and V2 should be less than 20%.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Group placebo capsule 2# t.i.d./day | 46 |
| Treatment Group A 150 mg STA-2, 2 capsules t.i.d., after meal (900 mg STA-2 total dose per day) | 43 |
| Treatment Group B 300 mg STA-2, 2 capsules t.i.d., after meal (1800 mg STA-2 total dose per day) | 42 |
| Treatment Group C 450 mg STA-2, 2 capsules t.i.d., after meal (2700 mg STA-2 total dose per day) | 37 |
| Total | 168 |
Baseline characteristics
| Characteristic | Treatment Group A | Treatment Group B | Placebo Group | Treatment Group C | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 19 Participants | 12 Participants | 17 Participants | 14 Participants | 62 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants | 30 Participants | 29 Participants | 23 Participants | 106 Participants |
| Age, Continuous | 62.1 years STANDARD_DEVIATION 10.4 | 61.4 years STANDARD_DEVIATION 10.57 | 60.6 years STANDARD_DEVIATION 0.76 | 59.6 years STANDARD_DEVIATION 10.11 | 61.0 years STANDARD_DEVIATION 10.43 |
| Region of Enrollment Taiwan | 43 participants | 42 participants | 46 participants | 37 participants | 168 participants |
| Sex: Female, Male Female | 7 Participants | 8 Participants | 9 Participants | 4 Participants | 28 Participants |
| Sex: Female, Male Male | 36 Participants | 34 Participants | 37 Participants | 33 Participants | 140 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 47 | 2 / 45 | 2 / 47 | 1 / 47 |
| serious Total, serious adverse events | 0 / 47 | 0 / 45 | 2 / 47 | 1 / 47 |
Outcome results
Primary
Change in Total Exercise Time (Seconds)
the time difference of total exercise time from V2 to V5 compare to placebo
Time frame: 6 weeks after the first exercise tolerance testing is conducted
Population: ITT (intend-to-treat) population will be used for analysis
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Group | Change in Total Exercise Time (Seconds) | 24.3 second | Standard Deviation 8.73 |
| Treatment Group A | Change in Total Exercise Time (Seconds) | 18.2 second | Standard Deviation 8.95 |
| Treatment Group B | Change in Total Exercise Time (Seconds) | 33.9 second | Standard Deviation 9.03 |
| Treatment Group C | Change in Total Exercise Time (Seconds) | 11.9 second | Standard Deviation 9.69 |
Secondary
Change in Consumption of Short-acting Nitrates From Baseline to All Visits
Time frame: 6 weeks
Secondary
Change in Lipid Profiles (HDL-C, LDL-C, Total Cholesterol, Triglyceride) From Baseline to All Visits
Time frame: 6 weeks
Secondary
Change in Pharmacological Parameters (Oxidized-LDL), Isoprostane and High-sensitivity Hs-CRP From Baseline to All Visits
Time frame: 6 weeks
Secondary
Change in Time to Onset of Angina From Baseline to the Final Visit
Time frame: 6 weeks
Secondary
Changes in Angina Frequency in Subject's Diary From Baseline to All Visits
Time frame: 6 weeks
Secondary
Changes in Time to 1mm ST-segment Depression During ETT From Baseline to Final Visit
Time frame: 6 weeks
Secondary
Changes in Time to Maximum ST-segment Depression During ETT From Baseline to the Final Visit
Time frame: 6 weeks
Secondary
Dose-response Relationship of Three Different Dose Levels of STA-2 Versus Placebo Control in Change in Total Exercise Time.
Time frame: 6 weeks