Phase III Trial of Dantonic® (T89) Capsule to Prevent and Treat Stable Angina
- Conditions
- Angina Pectoris
- Interventions
- Drug: T89 Low doseDrug: Sanqi+BingpianDrug: T89 high doseDrug: Placebo
- Registration Number
- NCT01659580
- Lead Sponsor
- Tasly Pharmaceuticals, Inc.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1004
- 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.
- 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 T89. 11. 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. 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description T89 low dose T89 Low dose T89 150mg bid Sanqi+Bingpian Sanqi+Bingpian 225mg bid T89 high dose T89 high dose T89 225mg bid Placebo Placebo 225mg bid
- Primary Outcome Measures
Name Time Method The change of symptom-limited TED from baseline compared to placebo at the end of week 4. 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.
- Secondary Outcome Measures
Name Time Method The change of symptom-limited TED at trough drug levels at the end of the 2nd and 6th weeks 2nd weeks and 6th weeks 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 6 weeks Frequency of weekly angina episodes
Trial Locations
- Locations (93)
St. Michael's Hospital
🇨🇦Toronto, Ontario, Canada
Beaver Medical Clinic
🇺🇸Banning, California, United States
NewPhase Clinical Trials, Inc.
🇺🇸Miami Beach, Florida, United States
Brevard Cardiovascular Research Associates
🇺🇸Merritt, Florida, United States
Manhattan Medical Research Practice
🇺🇸New York, New York, United States
Precision Research Institute
🇺🇸National City, California, United States
Foundation for Cardiovascular Medicine
🇺🇸La Jolla, California, United States
Tennessee Center for Clinical Trials
🇺🇸Tullahoma, Tennessee, United States
Montreal Heart Institute
🇨🇦Montreal, Quebec, Canada
Cardiological CLinic "Guli" Ltd
🇬🇪Tbilisi, Georgia
The "Unimed Ajara"
🇬🇪Batumi, Georgia
Institut Universitaire de Cardiologie et de Pneumologie de Quebec
🇨🇦Quebec, Canada
City Clinical Hospital No. 3
🇺🇦Odessa, Ukraine
Lviv Regional State Clinical Threatment-and-Diagnostic Cardiology Center
🇺🇦Lviv, Ukraine
Department of Family Medicine and General Practice of Odessa National Medical University
🇺🇦Odessa, Ukraine
Paradigm Clinical Research Institute, Inc.
🇺🇸Torrance, California, United States
Ellipsis Research
🇺🇸Atlanta, Georgia, United States
Harbor-UCLA Medical Center
🇺🇸Torrance, California, United States
Molecular Imaging Research and Clinical Trials
🇺🇸Miami, Florida, United States
Cardiovascular Center of Sarasota
🇺🇸Sarasota, Florida, United States
Angiocardiac Care of Texas, PA
🇺🇸Houston, Texas, United States
Atlanta Clinical Research Center
🇺🇸Atlanta, Georgia, United States
Northwest Heart Center
🇺🇸Tomball, Texas, United States
Dixie Medical Group
🇨🇦Mississauga, Ontario, Canada
Bakbak Medicine Professional Corporation
🇨🇦Oshawa, Ontario, Canada
Heart Care Research
🇨🇦Oshawa, Ontario, Canada
Centre Cardiovasculaire De La Rive-Sud (Ccrs)
🇨🇦Longueuil, Quebec, Canada
Centro para el Desarollo de la Medicina y de Asistencia Medica Esp. S.C.
🇲🇽Culiacan, Sinaloa, Mexico
Cardiology and Medicine Clinic
🇺🇸Little Rock, Arkansas, United States
Northwest Houston Cardiology
🇺🇸Houston, Texas, United States
Dr. Petr Polasek, MD, Office of
🇨🇦Kelowna, British Columbia, Canada
Center of Vascular and Heart Diseases Ltd.
🇬🇪Tbilisi, Georgia
Tbilis Heart and vascular clinic Ltd.
🇬🇪Tbilisi, Georgia
Regional Buegetary Healthcare Institution "Cardiological Dispensary"
🇷🇺Ivanovslaya, Ivanovslaya Obl., Russian Federation
State Budgetary Healthcare Institution "State Novosibirsk Regional Clinical Hospital"
🇷🇺Novosibirsk, Russia, Russian Federation
Institute Of Gerontology, Department Of Clinical Physiology And Pathology Of Internal Organs
🇺🇦Kiev, Ukraine
OSMO
🇲🇽Oaxaca, Mexico
Clinique Sante Cardio MC
🇨🇦Montreal, Quebec, Canada
Kore CV Research
🇺🇸Jackson, Tennessee, United States
Minsk Regional Clinical Hospital
🇧🇾Minsk, Belarus
Archangel St. Michael Multiprofile Clinical Hospital
🇬🇪Tbilisi, Georgia
"Clinic L J" Ltd
🇬🇪Tbilisi, Georgia
Centro de Investigación Clínica Chapultepec
🇲🇽Morelia, Michoacán, Mexico
Alexandria Cardiology Clinic
🇺🇸Alexandria, Louisiana, United States
Cardiocen de Guadalajara, S.C.
🇲🇽Guadalajara, Jalisco, Mexico
ViaCar Recherche Clinique Inc.
🇨🇦Greenfield Park, Quebec, Canada
The Medical Arts Health Research Group
🇨🇦North Vancouver, British Columbia, Canada
Cardio-Reanimation Centre
🇬🇪Tbilisi, Georgia
Victoria Heart Institute Foundation
🇨🇦Victoria, British Columbia, Canada
Hospital de Cardiología de Aguascalientes
🇲🇽Aguascalientes, Mexico
Consultorio Medico de Especialidad
🇲🇽Tijuana, Baja California, Mexico
Emergency Cardiology Center named by Academician G. Chapidze Ltd
🇬🇪Tbilisi, Georgia
Centre de Sante et de Services Sociaux de Trois-Rivieres
🇨🇦Trois-Rivieres, Quebec, Canada
Hospital Central "Dr. Ignacio Morones Prieto"
🇲🇽San Luis Potosí, SLP, Mexico
Nonstate Healthcare Institution "Departmental Clinical Hospital on Kemerovo Station of Public Corporation "Russian Railroad"
🇷🇺Kemerovo, Russian Federation
Smolensk State Medical Academy Of Roszdrav
🇷🇺Smolensk, Smoleskaya oblast, Russian Federation
Centro para el Desarrollo de la Medicina y Asistencia Médica Especializada SC sede Torreon Coahuila
🇲🇽Torreón, Coahuila, Mexico
City Hospital #38 named after Semashko N.A.
🇷🇺St. Petersburg, Russian Federation
St. Petersburg State Health Care, Institution Pokrovskaya City Hospital
🇷🇺St. Petersburg, Russian Federation
Clinical Hospital n.a. N.V. Solovyov
🇷🇺Yaroslavl, Russian Federation
Ivano-Frankivsk Regional Clinical Cardiology Dispensary, department of anesthesiology with intensive care unit
🇺🇦Ivano-Frankivsk, Ukraine
National medical university named after O.O.Bogomolets
🇺🇦Kiev, Ukraine
Regional Cardiology Center
🇷🇺Volgograd, Russia, Russian Federation
Ural Medical Academy
🇷🇺Ekaterinburg, Russian Federation
Almazov Federal Heart, Blood And Endocrinology Centre
🇷🇺St. Petersburg, Russian Federation
Kyiv Oleksandrivska Clinical Hospital
🇺🇦Kiev, Ukraine
Moscow State Healthcare Institution, City Clinical Hospital #15
🇷🇺Moscow, Russian Federation
Federal State Budgetary Institution Research Institution Of Cardiology Of Sibirsky
🇷🇺Tomsk, Tomskaya Obl., Russian Federation
Krasnodar regional hospital #1 n.a. Prof. Ochapovskiy S.V.
🇷🇺Krasnodar, Russian Federation
First Moscow State Medical University
🇷🇺Moscow, Russian Federation
City Polyclinic # 109
🇷🇺St. Petersburg, Russian Federation
Department of internal diseases #2
🇺🇦Zaporizhzhya, Zaporizhzhya region, Ukraine
Tyumen Cardiology Center
🇷🇺Tyumen, Russian Federation
City Hospital #4
🇷🇺Vladimir, Russian Federation
Municipal Clinical Hospital #1
🇺🇦Kiev, Ukraine
District Clinical Hospital Of Station "Uzhgorod", Dgto "Lviv Railway Station" Therapeutic Department
🇺🇦Uzhgorod, Ukraine
Regional medical center of cardiovascular diseases
🇺🇦Zaporizhzhya, Zaporizhzhya region, Ukraine
L.T. Malaya Therapy Institute of National Academy of Medical Sciences of Ukraine, Head of Cardiopulmonology Department Government Institution
🇺🇦Kharkiv, Ukraine
L.T. Malaya Therapy Institute of National Academy of Medical Sciences of Ukraine
🇺🇦Kharkiv, Ukraine
Vinnytsya Regional Specialized Center for Radiation Protection of People
🇺🇦Vinnytsya, Ukraine
Odessa regional cardiological dispensary
🇺🇦Odessa, Ukraine
City Clinical Hospital # 1
🇺🇦Vinnitsa, Ukraine
Jacksonville Center for Clinical Research
🇺🇸Jacksonville, Florida, United States
SouthCoast Research Center, Inc
🇺🇸Miami, Florida, United States
Integrity Clinical Trials
🇺🇸Miami, Florida, United States
Peninsula Research, Inc.
🇺🇸Ormond Beach, Florida, United States
Jedidiah Clinical Research
🇺🇸Tampa, Florida, United States
Cardiology Center of Houston, PA
🇺🇸Katy, Texas, United States
Athens Heart Center
🇺🇸Athens, Georgia, United States
Central Cardiology
🇺🇸Campbellsville, Kentucky, United States
Cleveland Clinic
🇺🇸Medina, Ohio, United States
Tulane University Health Science Center, Tulane University Heart & Vascular Institute
🇺🇸New Orleans, Louisiana, United States
Hillsboro Cardiology, PC
🇺🇸Hillsboro, Oregon, United States