Outcome Research to Confirm the Anti-anginal Effect of T89 in Patients With Stable Angina

NCT03789552 | Recruiting Phase 3 FDA Drug

• 1 other identifier: T89-08-ORESA
• Study Type: interventional
• Target: 765
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multi-center, double-blind, randomized, placebo-controlled, parallel-group phase 3 clinical study to confirm the safety and efficacy of T89 in patients with stable angina pectoris, with an extended open-label period to evaluate the long-term safety of T89. This study includes three main periods: the first study period is a 3-week single-blind qualifying run-in period to screen eligible stable angina patients by exercise tolerance test (ETT). The second study period is a 8-week double-blind treatment period to evaluate the efficacy and safety of T89 in patients with stable angina by ETT. And, the last study period is a 44-week open-label period to observe long-term use safety of T89.

Conditions

Chronic Stable Angina Pectoris

Keywords

angina pectoris

Outcome Measures

Primary Outcomes (1)

• Change in symptom-limited total exercise duration (TED) at trough drug levels on standard Bruce protocol from baseline to Day 57

  Exercise, a common physiological stress, can elicit cardiovascular abnormalities that are not present at rest, and it can be used to determine the adequacy of cardiac function. Clinical exercise tolerance test (ETT) is an established non-invasive procedure that provides diagnostic and prognostic information for the evaluation of several pathologies, the most common of which is coronary heart disease. Total exercise duration (TED) is the time from starting ETT to terminating ETT, usually presented by minutes and seconds. Standard Bruce protocol, one of the protocols used for the conduction of an ETT as a pre-defined speed and gradient in different time interval, will be applied in this study. The TED at each ETT will be collected and recorded as primary parameter, and the change from baseline of symptom-limited TED at trough drug levels on standard Bruce protocol to Day 57 of treatment in high-dose and low-dose groups will be compared with that in placebo group.

  Day 57 (post drug administration from randomization)

Secondary Outcomes (7)

• The trend of TED changes over time (Slop) from Day 1 to Day 57

  Day 57 (post drug administration from randomization)

• Percent change in the average frequency of angina episodes (average over 14 days) from baseline [Day -14 to 1] to end of double-blind treatment period [Day 43 to 57]

  Day 57 (post drug administration from randomization)

• Percent change in the average on-demand consumption of short-acting nitroglycerin (average over 14 days) from baseline [Day -14 to 1] to end of double-blind treatment period [Day 43 to 57].

  Day 57 (post drug administration from randomization)

• Change in symptom-limited total exercise duration (TED) at trough drug levels on standard Bruce protocol from baseline to Day 43

  Day 43(post drug administration from randomization)

• Percent change in the average frequency of angina episodes (average over 14 days) from baseline [Day -14 to 1] to Week-6 visit of double-blind treatment period [Day 29 to 43]

  Day 43 (post drug administration from randomization)

Other Outcomes (2)

• Frequency and severity of adverse events and serious adverse events

  Day 57 (post drug administration from randomization)

• Notable laboratory abnormalities which are treatment-emergent

  Day 57 (post drug administration from randomization)

Study Arms (3)

T89 low-dose group

EXPERIMENTAL

T89 capsule is a botanical drug containing 75mg active substance which is the water extract of Danshen and Sanqi. Placebo capsule does not contain any amount of active substance. Subjects in this group will use three T89 capsules and one Placebo capsule each time by oral administration twice daily for 8 weeks.

Drug: T89 capsule; Drug: Placebo capsule

T89 high-dose group

EXPERIMENTAL

T89 capsule is a botanical drug containing 75mg active substance which is the water extract of Danshen and Sanqi. Subjects in this group will use four T89 capsules each time by oral administration twice daily for 8 weeks.

Drug: T89 capsule

Placebo group

PLACEBO COMPARATOR

Placebo capsule does not contain any amount of active substance. Subjects in this group will use four Placebo capsules each time by oral administration twice daily for 8 weeks.

Drug: Placebo capsule

Interventions

T89 capsule DRUG

T89 capsules (75mg)

T89 high-dose group; T89 low-dose group

Placebo capsule DRUG

Placebo capsules (0mg)

Placebo group; T89 low-dose group

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing to participate and sign a written informed consent
• Males and females ≥ 18 and ≤90 years old.
• Medical history of chronic stable angina triggered by physical effort and relieved by rest or sublingual nitroglycerin.
• Patients who agree and in the opinion of the investigator are able to withdraw all non-beta blocker and all non-calcium channel blocker anti-anginal medications. For those subjects who are on beta blockers and/or calcium channel blockers, they are able to keep only one beta blocker or one calcium channel blocker (acceptable calcium channel blocker: amlodipine, diltiazem, verapamil or nicardipine), but not both, and subjects agree and are expected to be able to remain on this treatment regimen from Day -21 until the completion of the double-blind period in the opinion of the investigator.
• ) For patients who have to modify their anti-anginal treatment regimen to meet the above qualification criteria, health care provider who is responsible for the patient's cardiac care (if this is not the study doctor) must provide a form of agreement (verbal conversation, phone call, in writing or shown as referral) to the PI before the treatment modification.
• ) For patients who are not on beta blocker or calcium channel blocker or other antianginal medications, there is no requirement to start on antianginal medication.
• \*nitroglycerin tablets, only those provided by sponsor, are allowed to be used for on-demand symptomatic relief of angina during the qualifying and treatment periods to ensure an accurate calculation of consumption.
• Documented history of coronary artery disease with one or more of the following conditions:
• ) History of previous myocardial infarction (previous MI that occurred and was diagnosed at least 3 months prior to start of screening).
• ) Ischemic heart disease determined by stress myocardial imaging examination (including nuclear stress test, cardiac stress MRI and echocardiography stress test).
• ) Clinically significant coronary stenosis ≥50% in any vessel detected by coronary angiography (or coronary CT angiography).
• Understand and be willing, able and likely to comply with all study procedures and restrictions and comprehends the Seattle Angina Questionnaire rating scales and diary cards.
• Women of child bearing potential: Female patients of child-bearing potential or male patients with partners of child-bearing potential must use appropriate birth control from the start of screening, until 3 months after the last dose of study medication. Female patients of child bearing potential must have negative pregnancy tests at screening visit \[Day -21, quantitative serum human chorionic gonadotropin (β-hCG test)\] and randomization visit (Day 1, urine pregnancy test).
• Patient must experience two or more angina episodes from Day-14 to Day 1, as the baseline frequency of angina. At least two of the angina episodes must be recorded by WCM (Other written forms of recording/reporting angina episodes may be acceptable only in situations and times that recording by WCM is impractical. In addition, patients are allowed to use short acting nitroglycerin for relief of angina).
• To be qualified, patients must have two qualifying ETTs on standard Bruce protocol on Day- 7 and Day 1. The qualifying ETTs are:

You may not qualify if:

• Patients with only non-cardiac chest pain or cardiac chest pain not related to angina.
• Patients with contraindication to, unable to, or with other co-morbidities that may prevent or interfere with the ability to perform ETT, in the opinion of investigator, including but not limited to: hospitalization for acute exacerbation of chronic lung disease within 4 weeks prior to the start of screening, current home oxygen use, needs for cardiac glycoside therapy, functionally limiting peripheral arterial disease, physical disability or other intercurrent illness such as acute respiratory infection/illness that, in the opinion of the Investigator or Sub-investigator, may interfere with the ability to perform ETT.
• Patients with presence of electrographic or other abnormalities/factors that could interfere with exercise ECG interpretation or may lead to a false positive stress test (including but not limited to, Lown-Ganong-Levine Syndrome (LGL), Wolff-Parkinson-White Syndrome (WPW), left bundle branch block, ≥1 mm ST segment depression at rest, pacemaker rhythm etc.).
• Patients with history of any coronary revascularization procedure (e.g. PCI or CABG) within 2 months prior to the start of screening.
• Patients who had unstable angina, or myocardial infarction within the recent 3 months prior to the start of screening.
• Patients with ongoing NYHA Classes III-IV congestive heart failure.
• Patients with angina pectoris at rest at screening.
• Patients with rapid atrial fibrillation at screening (rest heart rate \>120/min) or any time prior to randomization from Day -21.
• Patients with ongoing myocarditis, pericarditis, thrombophlebitis or pulmonary embolism or who have recovered from these conditions \<1 month prior to screening. Note: Patients who are on anticoagulant prophylaxis just for a pulmonary embolism or thrombophlebitis will not be subject to the one-month restriction.
• Patient with uncontrolled hypertension characterized by seated systolic blood pressure \>180mm Hg or diastolic blood pressure \>100mm Hg, within 2 months prior to, or during, the Single Blind Qualifying Period. Or patients with severe congenital cardiac defects, severe valvular disease, suspected or known dissecting aortic aneurysm and hypertrophic cardiomyopathy should be excluded.
• Patients with hemoglobin (HGB) \<10 g/dL, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>2×upper limit of normal (ULN), hemoglobin A1C (HbA1C) \>10%, or glomerular filtration rate (GFR) \<30cc/min, in any of the single blind qualifying lab tests.
• Patient with history of bleeding diathesis or cerebral hemorrhage or seizure disorder that need anticonvulsant.
• Patients who have to be on ranolazine, ivabradine or calcium channel blockers other than, amlodipine, verapamil, nicardipine or diltiazem, and patients who have to be on more than one beta blockers and/or calcium channel blockers, or other anti-anginal agent other than only sublingual nitroglycerin for on-demand angina relief.
• Patients who have to be on digoxin, digitalis, or other herbal products containing Danshen (Radix Salviae Miltiorrhizae, RSM), Sanqi (Radix Notoginseng, RN) or Ginkgo biloba during the single-blind screening and/or double-blind treatment period.
• Patients on antiplatelet drugs (except aspirin or clopidogrel), statins, ACE inhibitor, angiotensin II receptor blocker (ARB), warfarin or other direct acting oral anticoagulants (DOACs) need to be stable at current dose for at least 2 weeks prior to the start of screening.

Sponsors & Collaborators

• Tasly Pharmaceuticals, Inc.: lead

Study Sites (1)

Southwest Florida Research LLC

Naples, Florida, 34102, United States

RECRUITING

MeSH Terms

Conditions

Angina Pectoris

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Henry H Sun, PhD, MD

  Tasly Pharmaceuticals, Inc.

  STUDY CHAIR

Central Study Contacts

Henry H Sun, PhD, MD

CONTACT

301-978-3905; HSun@taslyUS.com

Ruoling Guo, PhD

CONTACT

RGuo@taslyUS.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 25, 2018
• First Posted: December 28, 2018
• Study Start: August 1, 2019
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: April 9, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)