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

NCT ID: NCT01659580

Last Updated: 2017-03-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1004 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-08-31
• Study Completion Date: 2016-12-31

Brief Summary

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.

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.

Conditions

Angina Pectoris

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

T89 high dose

T89 225mg bid

Group Type: EXPERIMENTAL

T89 high dose

Intervention Type: DRUG

225mg bid

T89 low dose

T89 150mg bid

Group Type: EXPERIMENTAL

T89 Low dose

Intervention Type: DRUG

150mg bid

Sanqi+Bingpian

225mg bid

Group Type: EXPERIMENTAL

Sanqi+Bingpian

Intervention Type: DRUG

225 mg bid

Placebo

225mg bid

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

225mg bid

Interventions

T89 high dose

225mg bid

Intervention Type: DRUG

T89 Low dose

150mg bid

Intervention Type: DRUG

Sanqi+Bingpian

225 mg bid

Intervention Type: DRUG

Placebo

225mg bid

Intervention Type: DRUG

Other Intervention Names

Dantonic®; Compound Danshen Dripping Pills; Salvtonic®; Dantonic®; Salvtonic®; Compound Danshen Dripping Pill

Eligibility 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 III, Grading of Angina Pectoris by the Canadian Cardiovascular Society Classification System).

7. 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 .

8. 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.

9. 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 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.).

2. 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.).

3. Clinically significant arrhythmias or atrioventricular conduction block greater than first degree, decompensated heart failure, atrial fibrillation, hypertrophic cardiomyopathy.

4. 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.

5. 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.

6. History of bleeding diathesis, cerebral hemorrhage, or seizure disorders that required anticonvulsant medication.

7. Patients requiring the use of long-acting nitroglycerin, ranolazine, and/or multiple anti-anginal drugs.

8. Aspirin and/or statins started less than 14 days prior to the signing of informed consent.

9. Pregnancy or lactation.

10. 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.

2) Previous participation in the studies of T89. 11. Substance abuse. Patients with a recent history (within the last 2 years) of alcoholism or known drug dependence.

12. Is a family member or relative of the study site staff. 13. 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.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tasly Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Henry He Sun, PhD

Role: STUDY_DIRECTOR

Tasly Group, Co. Ltd.

Locations

Cardiology and Medicine Clinic

Little Rock, Arkansas, United States

Beaver Medical Clinic

Banning, California, United States

Foundation for Cardiovascular Medicine

La Jolla, California, United States

Precision Research Institute

National City, California, United States

Paradigm Clinical Research Institute, Inc.

Torrance, California, United States

Harbor-UCLA Medical Center

Torrance, California, United States

Jacksonville Center for Clinical Research

Jacksonville, Florida, United States

Brevard Cardiovascular Research Associates

Merritt, Florida, United States

SouthCoast Research Center, Inc

Miami, Florida, United States

Molecular Imaging Research and Clinical Trials

Miami, Florida, United States

Integrity Clinical Trials

Miami, Florida, United States

NewPhase Clinical Trials, Inc.

Miami Beach, Florida, United States

Peninsula Research, Inc.

Ormond Beach, Florida, United States

Cardiovascular Center of Sarasota

Sarasota, Florida, United States

Jedidiah Clinical Research

Tampa, Florida, United States

Athens Heart Center

Athens, Georgia, United States

Atlanta Clinical Research Center

Atlanta, Georgia, United States

Ellipsis Research

Atlanta, Georgia, United States

Central Cardiology

Campbellsville, Kentucky, United States

Alexandria Cardiology Clinic

Alexandria, Louisiana, United States

Tulane University Health Science Center, Tulane University Heart & Vascular Institute

New Orleans, Louisiana, United States

Manhattan Medical Research Practice

New York, New York, United States

Cleveland Clinic

Medina, Ohio, United States

Hillsboro Cardiology, PC

Hillsboro, Oregon, United States

Kore CV Research

Jackson, Tennessee, United States

Tennessee Center for Clinical Trials

Tullahoma, Tennessee, United States

Angiocardiac Care of Texas, PA

Houston, Texas, United States

Northwest Houston Cardiology

Houston, Texas, United States

Cardiology Center of Houston, PA

Katy, Texas, United States

Northwest Heart Center

Tomball, Texas, United States

Minsk Regional Clinical Hospital

Minsk, Belarus, Belarus

Dr. Petr Polasek, MD, Office of

Kelowna, British Columbia, Canada

The Medical Arts Health Research Group

North Vancouver, British Columbia, Canada

Victoria Heart Institute Foundation

Victoria, British Columbia, Canada

Dixie Medical Group

Mississauga, Ontario, Canada

Bakbak Medicine Professional Corporation

Oshawa, Ontario, Canada

Heart Care Research

Oshawa, Ontario, Canada

St. Michael's Hospital

Toronto, Ontario, Canada

ViaCar Recherche Clinique Inc.

Brossard, Quebec, Canada

ViaCar Recherche Clinique Inc.

Greenfield Park, Quebec, Canada

Centre Cardiovasculaire De La Rive-Sud (Ccrs)

Longueuil, Quebec, Canada

Montreal Heart Institute

Montreal, Quebec, Canada

Clinique Sante Cardio MC

Montreal, Quebec, Canada

Institut Universitaire de Cardiologie et de Pneumologie de Quebec

Québec, Quebec, Canada

Centre de Sante et de Services Sociaux de Trois-Rivieres

Trois-Rivières, Quebec, Canada

The "Unimed Ajara"

Batumi, Georgia, Georgia

Cardiological CLinic "Guli" Ltd

Tbilisi, Georgia, Georgia

Archangel St. Michael Multiprofile Clinical Hospital

Tbilisi, Georgia, Georgia

Cardio-Reanimation Centre

Tbilisi, Georgia, Georgia

Emergency Cardiology Center named by Academician G. Chapidze Ltd

Tbilisi, Georgia, Georgia

Tbilis Heart and vascular clinic Ltd.

Tbilisi, Georgia, Georgia

Center of Vascular and Heart Diseases Ltd.

Tbilisi, Georgia, Georgia

"Clinic L J" Ltd

Tbilisi, Georgia, Georgia

Hospital de Cardiología de Aguascalientes

Aguascalientes, Aguascalientes, Mexico

Centro para el Desarrollo de la Medicina y Asistencia Médica Especializada SC sede Torreon Coahuila

Torreón, Coahuila, Mexico

Consultorio Medico de Especialidad

Tijuana, Estado de Baja California, Mexico

Cardiocen de Guadalajara, S.C.

Guadalajara, Jalisco, Mexico

Centro de Investigación Clínica Chapultepec

Morelia, Michoacán, Mexico

OSMO

Oaxaca City, Oaxaca, Mexico

Hospital Central "Dr. Ignacio Morones Prieto"

San Luis Potosí City, San Luis Potosí, Mexico

Centro para el Desarollo de la Medicina y de Asistencia Medica Esp. S.C.

Culiacán, Sinaloa, Mexico

Regional Buegetary Healthcare Institution "Cardiological Dispensary"

Ivanovslaya, Ivanovslaya Obl., Russia

Nonstate Healthcare Institution "Departmental Clinical Hospital on Kemerovo Station of Public Corporation "Russian Railroad"

Kemerovo, Russian Federation, Russia

Krasnodar regional hospital #1 n.a. Prof. Ochapovskiy S.V.

Krasnodar, Russian Federation, Russia

Moscow State Healthcare Institution, City Clinical Hospital #15

Moscow, Russian Federation, Russia

First Moscow State Medical University

Moscow, Russian Federation, Russia

City Polyclinic # 109

Saint Petersburg, Russian Federation, Russia

City Hospital #38 named after Semashko N.A.

Saint Petersburg, Russian Federation, Russia

Almazov Federal Heart, Blood And Endocrinology Centre

Saint Petersburg, Russian Federation, Russia

St. Petersburg State Health Care, Institution Pokrovskaya City Hospital

Saint Petersburg, Russian Federation, Russia

Tyumen Cardiology Center

Tyumen, Russian Federation, Russia

City Hospital #4

Vladimir, Russian Federation, Russia

Clinical Hospital n.a. N.V. Solovyov

Yaroslavl, Russian Federation, Russia

Ural Medical Academy

Yekaterinburg, Russian Federation, Russia

State Budgetary Healthcare Institution "State Novosibirsk Regional Clinical Hospital"

Novosibirsk, Russia, Russia

Regional Cardiology Center

Volgograd, Russia, Russia

Smolensk State Medical Academy Of Roszdrav

Smolensk, Smoleskaya Oblast, Russia

Federal State Budgetary Institution Research Institution Of Cardiology Of Sibirsky

Tomsk, Tomskaya Obl., Russia

Ivano-Frankivsk Regional Clinical Cardiology Dispensary, department of anesthesiology with intensive care unit

Ivano-Frankivsk, Ukraine, Ukraine

L.T. Malaya Therapy Institute of National Academy of Medical Sciences of Ukraine, Head of Cardiopulmonology Department Government Institution

Kharkiv, Ukraine, Ukraine

L.T. Malaya Therapy Institute of National Academy of Medical Sciences of Ukraine

Kharkiv, Ukraine, Ukraine

Institute Of Gerontology, Department Of Clinical Physiology And Pathology Of Internal Organs

Kiev, Ukraine, Ukraine

Kyiv Oleksandrivska Clinical Hospital

Kiev, Ukraine, Ukraine

Municipal Clinical Hospital #1

Kiev, Ukraine, Ukraine

National medical university named after O.O.Bogomolets

Kiev, Ukraine, Ukraine

Lviv Regional State Clinical Threatment-and-Diagnostic Cardiology Center

Lviv, Ukraine, Ukraine

Department of Family Medicine and General Practice of Odessa National Medical University

Odesa, Ukraine, Ukraine

City Clinical Hospital No. 3

Odesa, Ukraine, Ukraine

Odessa regional cardiological dispensary

Odesa, Ukraine, Ukraine

District Clinical Hospital Of Station "Uzhgorod", Dgto "Lviv Railway Station" Therapeutic Department

Uzhhorod, Ukraine, Ukraine

City Clinical Hospital # 1

Vinnitsa, Ukraine, Ukraine

Vinnytsya Regional Specialized Center for Radiation Protection of People

Vinnytsia, Ukraine, Ukraine

Regional medical center of cardiovascular diseases

Zaporizhzhya, Zaporizhzhia Oblast, Ukraine

Department of internal diseases #2

Zaporizhzhya, Zaporizhzhia Oblast, Ukraine

Countries

United States; Belarus; Canada; Georgia; Mexico; Russia; Ukraine

References

Shi Y, Liu D, Yuan J, Yan L, Zhan Z, Pan D, Lin L, Mu B. Compound Danshen Dripping Pills Prevented Leptin Deficiency-Induced Hepatic ER Stress, Stimulated Autophagy, and Improved Insulin Resistance of ob/ob Mice. Evid Based Complement Alternat Med. 2020 Jul 3;2020:5368657. doi: 10.1155/2020/5368657. eCollection 2020.

Reference Type: DERIVED

PMID: 32714408 (View on PubMed)

Related Links

http://www.tasly.com

manufacture and sponsor

Other Identifiers

T89-07-GL

Identifier Type: OTHER

Identifier Source: secondary_id

T89-07-CAESA

Identifier Type: -

Identifier Source: org_study_id