Phase III Trial of Dantonic® (T89) Capsule to Prevent and Treat Stable Angina (CAESA)

This study is currently recruiting participants.
Verified June 2013 by Tasly Pharmaceuticals, Inc.
Sponsor:
Information provided by (Responsible Party):
Tasly Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01659580
First received: July 19, 2012
Last updated: June 26, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Angina Pectoris
Drug: T89
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase III Confirmatory Trial to Confirm the Anti-anginal Effect of Dantonic® (T89) in Patients With Chronic Stable Angina

Resource links provided by NLM:


Further study details as provided by Tasly Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • The change of symptom-limited TED from baseline compared to placebo at the end of week 4. [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • The change of symptom-limited TED at trough drug levels at the end of the 2nd and 6th weeks [ Time Frame: 2nd weeks and 6th weeks ] [ Designated as safety issue: No ]
    The change of symptom-limited TED at trough drug levels at the end of the 2nd and 6th weeks of treatment from screen baseline on Standard Bruce Protocol compared with placebo;

  • Frequency of weekly angina episodes [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Frequency of weekly angina episodes


Other Outcome Measures:
  • Time to onset of angina during Excise Tolerance Test (ETT); [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Time to onset of angina during ETT;


Estimated Enrollment: 960
Study Start Date: August 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A: T89 High dose treatment
Drug to be given as 3x75mg capsule, twice a day.
Drug: T89
A botanical drug
Other Names:
  • Dantonic®
  • Dantonic® dripping pill
  • Cardiotonic® pill
Experimental: Group B: T89 Low dose treatment.
Drug to be given as 2x75mg plus one placebo capsule, twice a day. The daily dose is 300 mg.
Drug: T89
A botanical drug
Other Names:
  • Dantonic®
  • Dantonic® dripping pill
  • Cardiotonic® pill
Experimental: Group C: Exploratory base treatment
Drug to be given as 3 capsules contains herbal extract of Sanqi and Borneol that matchs 75 mg T89 capsule. twice a day.
Drug: T89
A botanical drug
Other Names:
  • Dantonic®
  • Dantonic® dripping pill
  • Cardiotonic® pill
Placebo Comparator: Group D: Placebo
Drug to be given as 3 placebo capsules, twice a day. The daily dose is 0 mg.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   20 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent.
  2. Males and females between the ages of 20 and 80 years.
  3. 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.
  4. 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.
  5. 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.
  6. Moderate angina pectoris (Class II or Class III).
  7. Patient whose symptom-limited Total Exercise Duration (TED) is between 3 to 7 minutes in ETT on Standard Bruce Protocol, and symptom-limited TED on two screen examinations (Day -7 and Day 0) in which the shorter is within 85% of the longer.
  8. Naïve patients not willing to take any anti-anginals as background treatment. Short-acting nitroglycerin for on-demand use is allowed for all eligible patients.
  9. Patient has been on one of the following anti-anginal medications for at least 14 days prior to T89 dosing on Day 0 and can remain this treatment throughout the study as background anti-anginal treatment:1) beta-blocker, or 2) dihydropyridine calcium-channel blocker, or 3) non-dihydropyridine calcium-channel blocker.
  10. Willingness to discontinue, or not to take, other anti-anginals such as long-acting nitroglycerin, or/and ranolazine after the initial visit. Short-acting nitroglycerin for on-demand use is allowed for all eligible patients.
  11. Understand and be willing, able and likely to comply with all study procedures and restrictions and comprehends the verbal rating scales and diary cards.

Exclusion Criteria:

  1. With contraindication, unable to, or with other co-morbidities that may prevent or interfere with the ability to perform treadmill Exercise Tolerance Test (ETT).
  2. Presence of electrocardiographic or other abnormalities/factors that could interfere with exercise electrocardiograph interpretation or may lead to a false positive stress test.
  3. Clinically significant arrhythmias or atrioventricular conduction block greater than first degree, decompensated heart failure, atrial fibrillation,hypertrophic cardiomyopathy.
  4. Acute coronary syndrome in the prior 2 months or coronary revascularization within the prior 6 months or planned coronary revascularization during the study period.
  5. Congenital cardiac defects, ongoing history of congestive heart failure, unstable angina, severe valvular disease, severe uncontrolled hypertension, severe anemia, suspected or known dissecting aneurysm, acute myocarditis or pericarditis, thrombophlebitis or pulmonary embolism or recent myocardial infarction within three months of study entry.
  6. History of bleeding diathesis, cerebral hemorrhage, or seizure disorders that required anticonvulsant medication.
  7. Aspirin and/or statins started less than 14 days prior to the signing of informed consent.
  8. Pregnancy or lactation.
  9. Clinical trials/experimental medication1) Participation in any other clinical trial or receipt of an investigational drug within 30 days prior to the initial visit.2) Previous participation in the studies of T89.
  10. Substance abuse. Patients with a recent history (within the last 2 years) of alcoholism or known drug dependence.
  11. Is a family member or relative of the study site staff.
  12. 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01659580

Contacts
Contact: Jennifer Pietrowski, PhD +1 215-616-6895 Jennifer.Pietrowski@iconplc.com
Contact: Jason Zhixin Guo, MD +1 301-216-3838 Jzxguo@gmail.com

Locations
United States, New York
Under contracting Recruiting
Multiple Cities, New York, United States
Australia
Under Contracting Active, not recruiting
Multiple Citis, Australia
Canada
Under Contracting Active, not recruiting
Multiple Citis, Canada
Japan
Under Contracting Active, not recruiting
Multiple Citis, Japan
Sponsors and Collaborators
Tasly Pharmaceuticals, Inc.
Investigators
Study Director: Henry He Sun, PhD Tasly Group, Co. Ltd.
  More Information

Additional Information:
No publications provided

Responsible Party: Tasly Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01659580     History of Changes
Other Study ID Numbers: T89-07-CAESA, T89-07-GL
Study First Received: July 19, 2012
Last Updated: June 26, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Tasly Pharmaceuticals, Inc.:
Angina Pectoris Treatment Prevention

Additional relevant MeSH terms:
Angina Pectoris
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Chest Pain
Pain
Signs and Symptoms
Cardiotonic Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 22, 2014