Clinical trial NCT01659580: Phase III Trial of Dantonic® (T89) Capsule to Prevent and Treat Stable Angina
Official title: Phase III Confirmatory Trial to Confirm the Anti-anginal Effect of Dantonic® (T89) in Patients With Chronic Stable Angina
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Angina Pectoris
Keywords: Angina Pectoris Treatment Prevention
Lead sponsor: Tasly Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2012-08-08
Enrollment: 1004
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: The change of symptom-limited TED from baseline compared to placebo at the end of week 4.
timeFrame: 4 weeks
Secondary outcomes:
measure: The change of symptom-limited TED at trough drug levels at the end of the 2nd and 6th weeks
timeFrame: 2nd weeks and 6th weeks
measure: Frequency of weekly angina episodes
timeFrame: 6 weeks
Other outcomes:
measure: Time to onset of angina during Excise Tolerance Test (ETT);
timeFrame: 6 weeks
Locations:
city: Little Rock
country: United States
facility: Cardiology and Medicine Clinic
state: Arkansas
city: Banning
country: United States
facility: Beaver Medical Clinic
state: California
city: La Jolla
country: United States
facility: Foundation for Cardiovascular Medicine
state: California
city: National City
country: United States
facility: Precision Research Institute
state: California
city: Torrance
country: United States
facility: Paradigm Clinical Research Institute, Inc.
state: California
city: Torrance
country: United States
facility: Harbor-UCLA Medical Center
state: California
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Merritt
country: United States
facility: Brevard Cardiovascular Research Associates
state: Florida
city: Miami Beach
country: United States
facility: NewPhase Clinical Trials, Inc.
state: Florida
city: Miami
country: United States
facility: SouthCoast Research Center, Inc
state: Florida
city: Miami
country: United States
facility: Molecular Imaging Research and Clinical Trials
state: Florida
city: Miami
country: United States
facility: Integrity Clinical Trials
state: Florida
city: Ormond Beach
country: United States
facility: Peninsula Research, Inc.
state: Florida
city: Sarasota
country: United States
facility: Cardiovascular Center of Sarasota
state: Florida
city: Tampa
country: United States
facility: Jedidiah Clinical Research
state: Florida
city: Athens
country: United States
facility: Athens Heart Center
state: Georgia
city: Atlanta
country: United States
facility: Atlanta Clinical Research Center
state: Georgia
city: Atlanta
country: United States
facility: Ellipsis Research
state: Georgia
city: Campbellsville
country: United States
facility: Central Cardiology
state: Kentucky
city: Alexandria
country: United States
facility: Alexandria Cardiology Clinic
state: Louisiana
city: New Orleans
country: United States
facility: Tulane University Health Science Center, Tulane University Heart & Vascular Institute
state: Louisiana
city: New York
country: United States
facility: Manhattan Medical Research Practice
state: New York
city: Medina
country: United States
facility: Cleveland Clinic
state: Ohio
city: Hillsboro
country: United States
facility: Hillsboro Cardiology, PC
state: Oregon
city: Jackson
country: United States
facility: Kore CV Research
state: Tennessee
city: Tullahoma
country: United States
facility: Tennessee Center for Clinical Trials
state: Tennessee
city: Houston
country: United States
facility: Angiocardiac Care of Texas, PA
state: Texas
city: Houston
country: United States
facility: Northwest Houston Cardiology
state: Texas
city: Katy
country: United States
facility: Cardiology Center of Houston, PA
state: Texas
city: Tomball
country: United States
facility: Northwest Heart Center
state: Texas
city: Minsk
country: Belarus
facility: Minsk Regional Clinical Hospital
city: Kelowna
country: Canada
facility: Dr. Petr Polasek, MD, Office of
state: British Columbia
city: North Vancouver
country: Canada
facility: The Medical Arts Health Research Group
state: British Columbia
city: Victoria
country: Canada
facility: Victoria Heart Institute Foundation
state: British Columbia
city: Mississauga
country: Canada
facility: Dixie Medical Group
state: Ontario
city: Oshawa
country: Canada
facility: Bakbak Medicine Professional Corporation
state: Ontario
city: Oshawa
country: Canada
facility: Heart Care Research
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Brossard
country: Canada
facility: ViaCar Recherche Clinique Inc.
state: Quebec
city: Greenfield Park
country: Canada
facility: ViaCar Recherche Clinique Inc.
state: Quebec
city: Longueuil
country: Canada
facility: Centre Cardiovasculaire De La Rive-Sud (Ccrs)
state: Quebec
city: Montreal
country: Canada
facility: Montreal Heart Institute
state: Quebec
city: Montreal
country: Canada
facility: Clinique Sante Cardio MC
state: Quebec
city: Trois-Rivieres
country: Canada
facility: Centre de Sante et de Services Sociaux de Trois-Rivieres
state: Quebec
city: Quebec
country: Canada
facility: Institut Universitaire de Cardiologie et de Pneumologie de Quebec
city: Batumi
country: Georgia
facility: The "Unimed Ajara"
city: Tbilisi
country: Georgia
facility: Cardiological CLinic "Guli" Ltd
city: Tbilisi
country: Georgia
facility: Archangel St. Michael Multiprofile Clinical Hospital
city: Tbilisi
country: Georgia
facility: Cardio-Reanimation Centre
city: Tbilisi
country: Georgia
facility: Emergency Cardiology Center named by Academician G. Chapidze Ltd
city: Tbilisi
country: Georgia
facility: Tbilis Heart and vascular clinic Ltd.
city: Tbilisi
country: Georgia
facility: Center of Vascular and Heart Diseases Ltd.
city: Tbilisi
country: Georgia
facility: "Clinic L J" Ltd
city: Tijuana
country: Mexico
facility: Consultorio Medico de Especialidad
state: Baja California
city: Torreón
country: Mexico
facility: Centro para el Desarrollo de la Medicina y Asistencia Médica Especializada SC sede Torreon Coahuila
state: Coahuila
city: Guadalajara
country: Mexico
facility: Cardiocen de Guadalajara, S.C.
state: Jalisco
city: Morelia
country: Mexico
facility: Centro de Investigación Clínica Chapultepec
state: Michoacán
city: Culiacan
country: Mexico
facility: Centro para el Desarollo de la Medicina y de Asistencia Medica Esp. S.C.
state: Sinaloa
city: San Luis Potosí
country: Mexico
facility: Hospital Central "Dr. Ignacio Morones Prieto"
state: SLP
city: Aguascalientes
country: Mexico
facility: Hospital de Cardiología de Aguascalientes
city: Oaxaca
country: Mexico
facility: OSMO
city: Ivanovslaya
country: Russian Federation
facility: Regional Buegetary Healthcare Institution "Cardiological Dispensary"
state: Ivanovslaya Obl.
city: Novosibirsk
country: Russian Federation
facility: State Budgetary Healthcare Institution "State Novosibirsk Regional Clinical Hospital"
state: Russia
city: Volgograd
country: Russian Federation
facility: Regional Cardiology Center
state: Russia
city: Smolensk
country: Russian Federation
facility: Smolensk State Medical Academy Of Roszdrav
state: Smoleskaya oblast
city: Tomsk
country: Russian Federation
facility: Federal State Budgetary Institution Research Institution Of Cardiology Of Sibirsky
state: Tomskaya Obl.
city: Ekaterinburg
country: Russian Federation
facility: Ural Medical Academy
city: Kemerovo
country: Russian Federation
facility: Nonstate Healthcare Institution "Departmental Clinical Hospital on Kemerovo Station of Public Corporation "Russian Railroad"
city: Krasnodar
country: Russian Federation
facility: Krasnodar regional hospital #1 n.a. Prof. Ochapovskiy S.V.
city: Moscow
country: Russian Federation
facility: Moscow State Healthcare Institution, City Clinical Hospital #15
city: Moscow
country: Russian Federation
facility: First Moscow State Medical University
city: Saint-Petersburg
country: Russian Federation
facility: Almazov Federal Heart, Blood And Endocrinology Centre
city: St. Petersburg
country: Russian Federation
facility: City Polyclinic # 109
city: St. Petersburg
country: Russian Federation
facility: City Hospital #38 named after Semashko N.A.
city: St. Petersburg
country: Russian Federation
facility: Almazov Federal Heart, Blood And Endocrinology Centre
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg State Health Care, Institution Pokrovskaya City Hospital
city: Tyumen
country: Russian Federation
facility: Tyumen Cardiology Center
city: Vladimir
country: Russian Federation
facility: City Hospital #4
city: Yaroslavl
country: Russian Federation
facility: Clinical Hospital n.a. N.V. Solovyov
city: Zaporizhzhya
country: Ukraine
facility: Regional medical center of cardiovascular diseases
state: Zaporizhzhya region
city: Zaporizhzhya
country: Ukraine
facility: Department of internal diseases #2
state: Zaporizhzhya region
city: Ivano-Frankivsk
country: Ukraine
facility: Ivano-Frankivsk Regional Clinical Cardiology Dispensary, department of anesthesiology with intensive care unit
city: Kharkiv
country: Ukraine
facility: L.T. Malaya Therapy Institute of National Academy of Medical Sciences of Ukraine, Head of Cardiopulmonology Department Government Institution
city: Kharkiv
country: Ukraine
facility: L.T. Malaya Therapy Institute of National Academy of Medical Sciences of Ukraine
city: Kiev
country: Ukraine
facility: Institute Of Gerontology, Department Of Clinical Physiology And Pathology Of Internal Organs
city: Kiev
country: Ukraine
facility: Kyiv Oleksandrivska Clinical Hospital
city: Kiev
country: Ukraine
facility: Municipal Clinical Hospital #1
city: Kiev
country: Ukraine
facility: National medical university named after O.O.Bogomolets
city: Lviv
country: Ukraine
facility: Lviv Regional State Clinical Threatment-and-Diagnostic Cardiology Center
city: Odessa
country: Ukraine
facility: Department of Family Medicine and General Practice of Odessa National Medical University
city: Odessa
country: Ukraine
facility: City Clinical Hospital No. 3
city: Odessa
country: Ukraine
facility: Odessa regional cardiological dispensary
city: Uzhgorod
country: Ukraine
facility: District Clinical Hospital Of Station "Uzhgorod", Dgto "Lviv Railway Station" Therapeutic Department
city: Vinnitsa
country: Ukraine
facility: City Clinical Hospital # 1
city: Vinnytsya
country: Ukraine
facility: Vinnytsya Regional Specialized Center for Radiation Protection of People
Study officials:
affiliation: Tasly Group, Co. Ltd.
name: Henry He Sun, PhD
role: STUDY_DIRECTOR
References:
citation: 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.