Phase III Confirmatory Trial to Confirm the Anti-anginal Effect of Dantonic® (T89) in Patients With Chronic Stable Angina
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,004
- 试验地点
- 93
- 主要终点
- The change of symptom-limited TED from baseline compared to placebo at the end of week 4.
研究概览
简要总结
This phase III study is designed as a double blind, randomized, multi-nation, multi-center, placebo controlled clinical research, which aims to evaluate the safety and efficacy of Dantonic® (T89) in patients with chronic stable angina pectoris.
详细描述
Dantonic® (T89) is a botanical drug consists of extracts of Danshen (Radix Salviae Miltiorrhizae) and Sanqi (Radix Notoginseng) with borneol in a capsule form. The drug is currently approved in 26 countries outside the USA for the treatment and prevention of chronic stable angina pectoris and other cardiovascular disease related conditions. This pivotal confirmative Phase III clinical trial is to confirm the efficacy and safety of the drug at 150mg and 225mg doses in the prevention and treatment of angina pectoris in patients with Chronic Stable Angina. The contribution of the main herb Danshen to, and the difference of various production batches in, the overall efficacy and safety profiles will also be explored. Patients will take a morning and an evening dose orally (every 12 hours) for 6 weeks while stop taking any long-acting nitroglycerin, ranolazine, and/or multiple beta-blockers or beta blocker(s) with calcium channel blocker during the trial. Single beta-blocker and/or on-demand short acting nitroglycerin to relief angina pectoris is allowed during the trial. After physical exams and if eligible to participation, patients will stop taking other drugs, and undergo two baseline screen Exercise Treadmill Tests (ETT) on Standard Bruce Protocol in the clinic one week before and right before starting the drug treatment. Patients will perform three more ETTs before the morning dose at the end of week 2, 4 and 6 after receiving the drug treatment. The primary efficiency endpoint is the change of symptom-limited Total Exercise Duration of the ETT at the end of the 4th week of treatment from the average of the two screening baselines compared with that of placebo treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 20 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent.
- •Males and females between the ages of 20 and 80 years.
- •Females of childbearing potential must have a negative pregnancy test, not be breast feeding and established on a method of contraception that in the investigator's opinion is acceptable. Females must agree to remain on their established method of contraception through their participation in the study and for 14 days following the last dose of study drug.
- •Evidence of coronary artery disease that consists of a well-documented medical history (over 3 months prior to the enrolment) of myocardial infarction or significant coronary artery disease with noninvasive or angiographic confirmation.
- •Symptoms that support the diagnosis of chronic angina and/or a history of an abnormal exercise response limited by angina and/or electrocardiograph (ECG) changes.
- •Moderate angina pectoris (Class II or III, Grading of Angina Pectoris by the Canadian Cardiovascular Society Classification System).
- •Patient whose symptom-limited Total Exercise Duration (TED) is between 3 to 7 minutes in Exercise Tolerance Test (ETT) on Standard Bruce Protocol, and symptom-limited TED on two screen examinations (Day -7 and 0) in which the shorter is within 85% of the longer .
- •Patient has been on one beta-blocker or on one calcium-channel blocker for at least 14 days prior to dosing of study medication and can remain on this treatment throughout the study as background anti-anginal treatment. Short-acting nitroglycerin for on-demand use is allowed for all eligible patients.
- •Understand and be willing, able and likely to comply with all study procedures and restrictions and comprehends the verbal rating scales and diary cards.
排除标准
- •With contraindication to, unable to, or with other co-morbidities that may prevent or interfere with the ability to perform treadmill ETT (including, but not limited to: pulmonary hypertension, functionally limiting COPD (chronic obstructive pulmonary disease), history of pulmonary tuberculosis, prior hospitalization for acute exacerbation of chronic lung disease, home oxygen use, chronic oral steroid therapy that can limit exercise capacity, functionally limiting peripheral artery disease, etc.).
- •Presence of electrocardiographic or other abnormalities/factors that could interfere with exercise electrocardiograph interpretation or may lead to a false positive stress test (e.g., pre-exercise horizontal or down-sloping ST segment depression in any standard lead, cardiac glycoside therapy, Lown-Ganong-Levine Syndrome, Wolff-Parkinson-White syndrome (WPW), left bundle branch block, left ventricular hypertrophy with repolarization abnormality, implanted pacemaker, etc.).
- •Clinically significant arrhythmias or atrioventricular conduction block greater than first degree, decompensated heart failure, atrial fibrillation, hypertrophic cardiomyopathy.
- •Acute coronary syndrome (acute myocardial infarction or unstable angina) in the prior 2 months or coronary revascularization within the prior 6 months or planned coronary revascularization during the study period.
- •Congenital cardiac defects, ongoing history of decompensated congestive heart failure, severe valvular disease, severe uncontrolled hypertension (seated systolic blood pressure > 180 mm Hg or diastolic blood pressure > 110 mm Hg), severe anemia, suspected or known dissecting aortic aneurysm, acute myocarditis or pericarditis, thrombophlebitis or pulmonary embolism.
- •History of bleeding diathesis, cerebral hemorrhage, or seizure disorders that required anticonvulsant medication.
- •Patients requiring the use of long-acting nitroglycerin, ranolazine, and/or multiple anti-anginal drugs.
- •Aspirin and/or statins started less than 14 days prior to the signing of informed consent.
- •Pregnancy or lactation.
- •Clinical trials/experimental medication 1) Participation in any other clinical trial or receipt of an investigational drug within 30 days prior to the initial visit.
- •Previous participation in the studies of T
- •Substance abuse. Patients with a recent history (within the last 2 years) of alcoholism or known drug dependence.
- •Is a family member or relative of the study site staff.
- •Any other conditions that, in the opinion of the investigator, are likely to prevent compliance with the study protocol or pose a safety concern if the subject participates in the study.
研究组 & 干预措施
T89 high dose
T89 225mg bid
干预措施: T89 high dose (Drug)
T89 low dose
T89 150mg bid
干预措施: T89 Low dose (Drug)
Sanqi+Bingpian
225mg bid
干预措施: Sanqi+Bingpian (Drug)
Placebo
225mg bid
干预措施: Placebo (Drug)
结局指标
主要结局
The change of symptom-limited TED from baseline compared to placebo at the end of week 4.
时间窗: 4 weeks
The change of symptom-limited Total Exercise Duration (TED) at trough drug levels at the end of the 4th week of treatment from screen baseline on Standard Bruce Protocol compared with placebo.
次要结局
- The change of symptom-limited TED at trough drug levels at the end of the 2nd and 6th weeks(2nd weeks and 6th weeks)
- Frequency of weekly angina episodes(6 weeks)