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

  • STATUS
    Recruiting
  • End date
    Sep 1, 2023
  • participants needed
    765
  • sponsor
    Tasly Pharmaceuticals, Inc.
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Updated on 4 March 2022
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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.

Description

After signing the consent, patients will enter the single blind qualifying run-in period for 3 weeks. All prophylactic anti-anginal medications will be withdrawn except no more than one beta blocker or one calcium channel blocker (CCB) to remain. If patients can tolerate the withdrawal of the multiple anti-anginal medications, the dose of the remained one beta blocker or one CCB will be kept unchanged until the double-blind treatment period ends. In this study period, patients will have two exercise tolerance tests (ETTs) on standard Bruce protocol, conducted one week apart. Sublingual nitroglycerin is allowed for symptomatic relief of angina attack.

After screening, eligible patients will be randomly assigned to receive one of the three double-blind treatments: high dose T89 of 300 mg, bid, low dose T89 of 225 mg, bid, or placebo, in a 1:1:1 ratio. Each patient will be instructed to administer assigned treatment twice daily for 8 weeks. ETTs will be performed at the end of week 6 and 8 of treatment, or end of treatment (EOT) if study patient discontinues study prematurely.

Seattle Angina Questionnaire (SAQ) will be used to record patients' quality of life. Clinical evaluations and adverse event monitoring will be assessed throughout the study. Laboratory tests will be performed at screening and the designated visits.

Once the treatment period is completed, patients will enter the extended open label safety assessment period for a further 44 weeks. During this period, all patients will receive T89 at a daily dose of 600 mg, and they can resume their original anti-anginal medications as needed.

Details
Condition Chronic Stable Angina Pectoris
Treatment Placebo Capsule, T89 capsule
Clinical Study IdentifierNCT03789552
SponsorTasly Pharmaceuticals, Inc.
Last Modified on4 March 2022

Eligibility

 Yes No Not Sure

Inclusion Criteria

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
1) For patients who have to modify their anti-anginal treatment regimen to
\. Documented history of coronary artery disease with one or more of the
meet the above qualification criteria, health care provider who is responsible
following
for the patient's cardiac care (if this is not the study doctor) must provide
conditions
a form of agreement (verbal conversation, phone call, in writing or shown as
referral) to the PI before the treatment modification
2) 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
\. Understand and be willing, able and likely to comply with all study
procedures and restrictions and comprehends the Seattle Angina Questionnaire
1) History of previous myocardial infarction (previous MI that occurred and
rating scales and diary cards
was diagnosed at least 3 months prior to start of screening)
\. Women of child bearing potential: Female patients of child-bearing
2) Ischemic heart disease determined by stress myocardial imaging
potential or male patients with partners of child-bearing potential must use
examination (including nuclear stress test, cardiac stress MRI and
appropriate birth control from the start of screening, until 3 months after
echocardiography stress test)
the last dose of study medication. Female patients of child bearing potential
3) Clinically significant coronary stenosis 50% in any vessel detected by
must have negative pregnancy tests at screening visit [Day -21, quantitative
coronary angiography (or coronary CT angiography)
serum human chorionic gonadotropin (-hCG test)] and randomization visit (Day
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
ETTs must meet the positive ETT criteria
Total exercise duration (TED) of the positive ETT is between 3-12 minutes of exercise
The difference in TED between the two ETTs must not exceed 15% of the longer one
For the qualifying ETTs, in patients with permitted baseline ST-segment depression at rest (<1 mm at 80 msec after the J point), qualifying ST-segment depression during ETT will be defined as additional ST-segment depression 1 mm (at 80 msec after the J point) below the resting value

Exclusion Criteria

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
Left ventricular hypertrophy (LVH) without repolarization abnormalities is not considered an exclusion criterion
\. Patients with history of any coronary revascularization procedure (e.g
PCI or CABG) within 2 months prior to the start of screening
prior to the start of screening
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 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 ongoing myocarditis, pericarditis, thrombophlebitis or
\. Patients with rapid atrial fibrillation at screening (rest heart rate
pulmonary embolism or who have recovered from these conditions <1 month prior
>120/min) or any time prior to randomization from Day -21
pulmonary embolism or thrombophlebitis will not be subject to the one-month
restriction
to screening. Note: Patients who are on anticoagulant prophylaxis just for a
\. 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
\. Patients with hemoglobin (HGB) <10 g/dL, aspartate aminotransferase (AST)
with severe congenital cardiac defects, severe valvular disease, suspected or
or alanine aminotransferase (ALT) >2upper limit of normal (ULN), hemoglobin
known dissecting aortic aneurysm and hypertrophic cardiomyopathy should be
excluded
\. Patient with history of bleeding diathesis or cerebral hemorrhage or
seizure disorder that need anticonvulsant
A1C (HbA1C) >10%, or glomerular filtration rate (GFR) <30cc/min, in any of the
\. Patients who have to be on ranolazine, ivabradine or calcium channel
single blind qualifying lab tests
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
\. Clinical trials/experimental medication: participation in any other
clinical trial or receipt of an investigational drug or device within 30 days
\. Female patients with known, suspected or planned pregnancy, or lactation
\. Patients with a recent (within the last 2 years) history of substance
abuse (alcohol, marijuana, or known drug dependence). Or patients who have a
positive urine substance screening test at the Day -21 initial visit
\. Any family member or relative of the study site staff, sponsor or CRO
\. Patients with any other severe or serious condition that, in the opinion
of the investigator is likely to prevent compliance with the study protocol or
pose a safety concern if the patient participates in the study
\. Patients whose QTcF (Fridericia's method corrected QT interval) is >460
ms in male and >470 ms in female during supine 12-lead ECG at rest at
screening or any time prior to randomization from Day -21. And patients who
are currently taking any medication that are known to prolong the QTcF
interval at screening or any time prior to randomization from Day -21
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