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

• Sponsor: Sinphar Pharmaceutical Co., Ltd (Other)
• Overall Status: Completed
• CT.gov ID: NCT01239511
• Collaborator: (none)
• Enrollment: 186
• Locations: 5
• Arms: 4
• Duration (Months): 17
• Patients Per Site: 37.2
• Patients Per Site Per Month: 2.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Stable Angina	Drug: green tea polyphenols (STA-2)	Phase 2

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 186 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Study Start Date: Nov 1, 2010
• Actual Primary Completion Date: Apr 1, 2012
• Actual Study Completion Date: Apr 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo group placebo capsule 2# t.i.d./day	Drug: green tea polyphenols (STA-2); 2 capsules t.i.d., after meal
Experimental: Treatment Group A 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); 2 capsules t.i.d., after meal
Experimental: Treatment Group B 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); 2 capsules t.i.d., after meal
Experimental: Treatment Group C 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); 2 capsules t.i.d., after meal

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Change in Time to Onset of Angina From Baseline to the Final Visit [6 weeks]

2. Changes in Time to 1mm ST-segment Depression During ETT From Baseline to Final Visit [6 weeks]

3. Changes in Time to Maximum ST-segment Depression During ETT From Baseline to the Final Visit [6 weeks]

4. Changes in Angina Frequency in Subject's Diary From Baseline to All Visits [6 weeks]

5. Change in Consumption of Short-acting Nitrates From Baseline to All Visits [6 weeks]

6. Change in Pharmacological Parameters (Oxidized-LDL), Isoprostane and High-sensitivity Hs-CRP From Baseline to All Visits [6 weeks]

7. Change in Lipid Profiles (HDL-C, LDL-C, Total Cholesterol, Triglyceride) From Baseline to All Visits [6 weeks]

8. Dose-response Relationship of Three Different Dose Levels of STA-2 Versus Placebo Control in Change in Total Exercise Time. [6 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts 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;

1. Subject has received any investigational agent within 28 days prior to the first dose of investigational product;

2. Subjects who have had administered STA-2 in prior clinical trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung		Taiwan
2	Chi Mei Medical Center	Tainan		Taiwan
3	National Taiwan University Hospital	Taipei		Taiwan
4	Taipei Medical University-Shuang Ho Hospital	Taipei		Taiwan
5	Taipei Veterans General Hospital	Taipei		Taiwan

Sponsors and Collaborators

• Sinphar Pharmaceutical Co., Ltd

Investigators

• Principal Investigator: Chuen-Den Tseng, MD, Ph.D, Department of Cardiology National Taiwan University Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sinphar Pharmaceutical Co., Ltd
• ClinicalTrials.gov Identifier: NCT01239511
• Other Study ID Numbers: MCCD09004A
• First Posted: Nov 11, 2010
• Last Update Posted: Aug 27, 2014
• Last Verified: Aug 1, 2014

• Additional relevant MeSH terms: Angina Pectoris; Angina, Stable

Study Results

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 Detail	In order to ensure the consistency, the difference of total exercise time between V1 and V2 should be less than 20%.

Arm/Group Title	Placebo Group	Treatment Group A	Treatment Group B	Treatment Group C
Arm/Group Description	placebo capsule 2# t.i.d./day	150 mg STA-2, 2 capsules t.i.d., after meal (900 mg STA-2 total dose per day)	300 mg STA-2, 2 capsules t.i.d., after meal (1800 mg STA-2 total dose per day)	450 mg STA-2, 2 capsules t.i.d., after meal (2700 mg STA-2 total dose per day)
Period Title: Overall Study
STARTED	47	45	47	47
COMPLETED	46	40	43	38
NOT COMPLETED	1	5	4	9

Baseline Characteristics

Arm/Group Title	Placebo Group	Treatment Group A	Treatment Group B	Treatment Group C	Total
Arm/Group Description	placebo capsule 2# t.i.d./day	150 mg STA-2, 2 capsules t.i.d., after meal (900 mg STA-2 total dose per day)	300 mg STA-2, 2 capsules t.i.d., after meal (1800 mg STA-2 total dose per day)	450 mg STA-2, 2 capsules t.i.d., after meal (2700 mg STA-2 total dose per day)	Total of all reporting groups
Overall Participants	46	43	42	37	168
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	29 63%	24 55.8%	30 71.4%	23 62.2%	106 63.1%
>=65 years	17 37%	19 44.2%	12 28.6%	14 37.8%	62 36.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.6 (0.76)	62.1 (10.40)	61.4 (10.57)	59.6 (10.11)	61.0 (10.43)
Sex: Female, Male (Count of Participants)
Female	9 19.6%	7 16.3%	8 19%	4 10.8%	28 16.7%
Male	37 80.4%	36 83.7%	34 81%	33 89.2%	140 83.3%
Region of Enrollment (participants) [Number]
Taiwan	46 100%	43 100%	42 100%	37 100%	168 100%

Outcome Measures

1. Primary Outcome

Title	Change in Total Exercise Time (Seconds)
Description	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

Outcome Measure Data

Analysis Population Description

ITT (intend-to-treat) population will be used for analysis

Arm/Group Title	Placebo Group	Treatment Group A	Treatment Group B	Treatment Group C
Arm/Group Description	placebo capsule 2# t.i.d./day	150 mg STA-2, 2 capsules t.i.d., after meal (900 mg STA-2 total dose per day)	300 mg STA-2, 2 capsules t.i.d., after meal (1800 mg STA-2 total dose per day)	450 mg STA-2, 2 capsules t.i.d., after meal (2700 mg STA-2 total dose per day)
Measure Participants	46	43	42	37
Least Squares Mean (Standard Deviation) [second]	24.3 (8.73)	18.2 (8.95)	33.9 (9.03)	11.9 (9.69)

2. Secondary Outcome

Title	Change in Time to Onset of Angina From Baseline to the Final Visit
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Changes in Time to 1mm ST-segment Depression During ETT From Baseline to Final Visit
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Changes in Time to Maximum ST-segment Depression During ETT From Baseline to the Final Visit
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Changes in Angina Frequency in Subject's Diary From Baseline to All Visits
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Change in Consumption of Short-acting Nitrates From Baseline to All Visits
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Change in Pharmacological Parameters (Oxidized-LDL), Isoprostane and High-sensitivity Hs-CRP From Baseline to All Visits
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	Change in Lipid Profiles (HDL-C, LDL-C, Total Cholesterol, Triglyceride) From Baseline to All Visits
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Secondary Outcome

Title	Dose-response Relationship of Three Different Dose Levels of STA-2 Versus Placebo Control in Change in Total Exercise Time.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Placebo Group		Treatment Group A		Treatment Group B		Treatment Group C
Arm/Group Description	placebo capsule 2# t.i.d./day		150 mg STA-2, 2 capsules t.i.d., after meal (900 mg STA-2 total dose per day)		300 mg STA-2, 2 capsules t.i.d., after meal (1800 mg STA-2 total dose per day)		450 mg STA-2, 2 capsules t.i.d., after meal (2700 mg STA-2 total dose per day)
All Cause Mortality
	Placebo Group		Treatment Group A		Treatment Group B		Treatment Group C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo Group		Treatment Group A		Treatment Group B		Treatment Group C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/47 (0%)		0/45 (0%)		2/47 (4.3%)		1/47 (2.1%)
Cardiac disorders
Coronary artery disease	0/47 (0%)	0	0/45 (0%)	0	1/47 (2.1%)	1	0/47 (0%)	0
Angina Pectoris	0/47 (0%)	0	0/45 (0%)	0	0/47 (0%)	0	1/47 (2.1%)	1
Gastrointestinal disorders
gastrointestinal haemorrhage	0/47 (0%)	0	0/45 (0%)	0	1/47 (2.1%)	1	0/47 (0%)	0
General disorders
Pyrexia	0/47 (0%)	0	0/45 (0%)	0	1/47 (2.1%)	1	0/47 (0%)	0
Hepatobiliary disorders
Hepatitis acute	0/47 (0%)	0	0/45 (0%)	0	1/47 (2.1%)	1	0/47 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	0/47 (0%)	0	0/45 (0%)	0	1/47 (2.1%)	1	0/47 (0%)	0
Nervous system disorders
Headache	0/47 (0%)	0	0/45 (0%)	0	1/47 (2.1%)	1	0/47 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo Group		Treatment Group A		Treatment Group B		Treatment Group C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/47 (0%)		2/45 (4.4%)		2/47 (4.3%)		1/47 (2.1%)
Gastrointestinal disorders
Gastrointestinal haemorrhage	0/47 (0%)		1/45 (2.2%)		1/47 (2.1%)		0/47 (0%)
Abdominal pain upper	0/47 (0%)		0/45 (0%)		0/47 (0%)		1/47 (2.1%)
Psychiatric disorders
Insomnia	0/47 (0%)		0/45 (0%)		1/47 (2.1%)		0/47 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/47 (0%)		0/45 (0%)		0/47 (0%)		1/47 (2.1%)
Skin and subcutaneous tissue disorders
pruritus	0/47 (0%)		1/45 (2.2%)		0/47 (0%)		0/47 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.