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

Angina Pectoris Clinical Trial

— CAESA  

Official title:

Phase III Confirmatory Trial to Confirm the Anti-anginal Effect of Dantonic® (T89) in Patients With Chronic Stable Angina

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01659580
• Other study ID #: T89-07-CAESA
• Secondary ID: T89-07-GL
• Status: Completed
• Phase: Phase 3
• First received: July 19, 2012
• Last updated: March 7, 2017
• Start date: August 2012
• Est. completion date: December 2016

Study information

• Verified date: March 2017
• Source: Tasly Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 1004
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Angina Pectoris
• Angina, Stable

Intervention

Drug:
• T89 high dose
225mg bid
• T89 Low dose
150mg bid
• Sanqi+Bingpian
225 mg bid
• Placebo
225mg bid

Locations

Country	Name	City	State
Belarus	Minsk Regional Clinical Hospital	Minsk
Canada	ViaCar Recherche Clinique Inc.	Brossard	Quebec
Canada	ViaCar Recherche Clinique Inc.	Greenfield Park	Quebec
Canada	Dr. Petr Polasek, MD, Office of	Kelowna	British Columbia
Canada	Centre Cardiovasculaire De La Rive-Sud (Ccrs)	Longueuil	Quebec
Canada	Dixie Medical Group	Mississauga	Ontario
Canada	Clinique Sante Cardio MC	Montreal	Quebec
Canada	Montreal Heart Institute	Montreal	Quebec
Canada	The Medical Arts Health Research Group	North Vancouver	British Columbia
Canada	Bakbak Medicine Professional Corporation	Oshawa	Ontario
Canada	Heart Care Research	Oshawa	Ontario
Canada	Institut Universitaire de Cardiologie et de Pneumologie de Quebec	Quebec
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	Centre de Sante et de Services Sociaux de Trois-Rivieres	Trois-Rivieres	Quebec
Canada	Victoria Heart Institute Foundation	Victoria	British Columbia
Georgia	The "Unimed Ajara"	Batumi
Georgia	"Clinic L J" Ltd	Tbilisi
Georgia	Archangel St. Michael Multiprofile Clinical Hospital	Tbilisi
Georgia	Cardio-Reanimation Centre	Tbilisi
Georgia	Cardiological CLinic "Guli" Ltd	Tbilisi
Georgia	Center of Vascular and Heart Diseases Ltd.	Tbilisi
Georgia	Emergency Cardiology Center named by Academician G. Chapidze Ltd	Tbilisi
Georgia	Tbilis Heart and vascular clinic Ltd.	Tbilisi
Mexico	Hospital de Cardiología de Aguascalientes	Aguascalientes
Mexico	Centro para el Desarollo de la Medicina y de Asistencia Medica Esp. S.C.	Culiacan	Sinaloa
Mexico	Cardiocen de Guadalajara, S.C.	Guadalajara	Jalisco
Mexico	Centro de Investigación Clínica Chapultepec	Morelia	Michoacán
Mexico	OSMO	Oaxaca
Mexico	Hospital Central "Dr. Ignacio Morones Prieto"	San Luis Potosí	SLP
Mexico	Consultorio Medico de Especialidad	Tijuana	Baja California
Mexico	Centro para el Desarrollo de la Medicina y Asistencia Médica Especializada SC sede Torreon Coahuila	Torreón	Coahuila
Russian Federation	Ural Medical Academy	Ekaterinburg
Russian Federation	Regional Buegetary Healthcare Institution "Cardiological Dispensary"	Ivanovslaya	Ivanovslaya Obl.
Russian Federation	Nonstate Healthcare Institution "Departmental Clinical Hospital on Kemerovo Station of Public Corporation "Russian Railroad"	Kemerovo
Russian Federation	Krasnodar regional hospital #1 n.a. Prof. Ochapovskiy S.V.	Krasnodar
Russian Federation	First Moscow State Medical University	Moscow
Russian Federation	Moscow State Healthcare Institution, City Clinical Hospital #15	Moscow
Russian Federation	State Budgetary Healthcare Institution "State Novosibirsk Regional Clinical Hospital"	Novosibirsk	Russia
Russian Federation	Almazov Federal Heart, Blood And Endocrinology Centre	Saint-Petersburg
Russian Federation	Smolensk State Medical Academy Of Roszdrav	Smolensk	Smoleskaya oblast
Russian Federation	Almazov Federal Heart, Blood And Endocrinology Centre	St. Petersburg
Russian Federation	City Hospital #38 named after Semashko N.A.	St. Petersburg
Russian Federation	City Polyclinic # 109	St. Petersburg
Russian Federation	St. Petersburg State Health Care, Institution Pokrovskaya City Hospital	St. Petersburg
Russian Federation	Federal State Budgetary Institution Research Institution Of Cardiology Of Sibirsky	Tomsk	Tomskaya Obl.
Russian Federation	Tyumen Cardiology Center	Tyumen
Russian Federation	City Hospital #4	Vladimir
Russian Federation	Regional Cardiology Center	Volgograd	Russia
Russian Federation	Clinical Hospital n.a. N.V. Solovyov	Yaroslavl
Ukraine	Ivano-Frankivsk Regional Clinical Cardiology Dispensary, department of anesthesiology with intensive care unit	Ivano-Frankivsk
Ukraine	L.T. Malaya Therapy Institute of National Academy of Medical Sciences of Ukraine	Kharkiv
Ukraine	L.T. Malaya Therapy Institute of National Academy of Medical Sciences of Ukraine, Head of Cardiopulmonology Department Government Institution	Kharkiv
Ukraine	Institute Of Gerontology, Department Of Clinical Physiology And Pathology Of Internal Organs	Kiev
Ukraine	Kyiv Oleksandrivska Clinical Hospital	Kiev
Ukraine	Municipal Clinical Hospital #1	Kiev
Ukraine	National medical university named after O.O.Bogomolets	Kiev
Ukraine	Lviv Regional State Clinical Threatment-and-Diagnostic Cardiology Center	Lviv
Ukraine	City Clinical Hospital No. 3	Odessa
Ukraine	Department of Family Medicine and General Practice of Odessa National Medical University	Odessa
Ukraine	Odessa regional cardiological dispensary	Odessa
Ukraine	District Clinical Hospital Of Station "Uzhgorod", Dgto "Lviv Railway Station" Therapeutic Department	Uzhgorod
Ukraine	City Clinical Hospital # 1	Vinnitsa
Ukraine	Vinnytsya Regional Specialized Center for Radiation Protection of People	Vinnytsya
Ukraine	Department of internal diseases #2	Zaporizhzhya	Zaporizhzhya region
Ukraine	Regional medical center of cardiovascular diseases	Zaporizhzhya	Zaporizhzhya region
United States	Alexandria Cardiology Clinic	Alexandria	Louisiana
United States	Athens Heart Center	Athens	Georgia
United States	Atlanta Clinical Research Center	Atlanta	Georgia
United States	Ellipsis Research	Atlanta	Georgia
United States	Beaver Medical Clinic	Banning	California
United States	Central Cardiology	Campbellsville	Kentucky
United States	Hillsboro Cardiology, PC	Hillsboro	Oregon
United States	Angiocardiac Care of Texas, PA	Houston	Texas
United States	Northwest Houston Cardiology	Houston	Texas
United States	Kore CV Research	Jackson	Tennessee
United States	Jacksonville Center for Clinical Research	Jacksonville	Florida
United States	Cardiology Center of Houston, PA	Katy	Texas
United States	Foundation for Cardiovascular Medicine	La Jolla	California
United States	Cardiology and Medicine Clinic	Little Rock	Arkansas
United States	Cleveland Clinic	Medina	Ohio
United States	Brevard Cardiovascular Research Associates	Merritt	Florida
United States	Integrity Clinical Trials	Miami	Florida
United States	Molecular Imaging Research and Clinical Trials	Miami	Florida
United States	SouthCoast Research Center, Inc	Miami	Florida
United States	NewPhase Clinical Trials, Inc.	Miami Beach	Florida
United States	Precision Research Institute	National City	California
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	Peninsula Research, Inc.	Ormond Beach	Florida
United States	Cardiovascular Center of Sarasota	Sarasota	Florida
United States	Jedidiah Clinical Research	Tampa	Florida
United States	Northwest Heart Center	Tomball	Texas
United States	Harbor-UCLA Medical Center	Torrance	California
United States	Paradigm Clinical Research Institute, Inc.	Torrance	California
United States	Tennessee Center for Clinical Trials	Tullahoma	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Tasly Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Belarus,  Canada,  Georgia,  Mexico,  Russian Federation,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Time to onset of angina during Excise Tolerance Test (ETT);	Time to onset of angina during ETT;	6 weeks
Primary	The change of symptom-limited TED from baseline compared to placebo at the end of week 4.	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.	4 weeks
Secondary	The change of symptom-limited TED at trough drug levels at the end of the 2nd 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;	2nd weeks and 6th weeks
Secondary	Frequency of weekly angina episodes	Frequency of weekly angina episodes	6 weeks

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