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.
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 All prophylactic anti-anginal medications will be withdrawn except no more than one beta blocker or one calcium channel blocker (CCB) to remain.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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
765
T89 capsules (75mg)
Placebo capsules (0mg)
Southwest Florida Research LLC
Naples, Florida, United States
RECRUITINGChange 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.
Time frame: Day 57 (post drug administration from randomization)
The trend of TED changes over time (Slop) from Day 1 to Day 57
The trend of TED changes from Day 1 to Day 57 double-blind treatment period will be compared among high dose group, low dose group and placebo group.
Time frame: 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]
A Wearable Cardiac Monitor (WCM) is a device similar to a Holter but quite smaller in size. This is a FDA-approved device used for recording the ECG up to for 7 days when patients may suffer from transient symptoms such as palpitations, dizziness, anxiety, fatigue, syncope, pre-syncope, light-headedness, shortness of breath. The WCM device is safe and easy for patients to use even when they are taking a short shower. Angina episodes during the past 7 days will be mainly collected from this device and recorded by site staff at due visit until Day 57. And 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 \[Day 43 to 57\] in high-dose and low-dose groups will be compared with that in placebo group.
Time frame: 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].
The amount of used short-acting nitroglycerin since last visit will be counted and recorded at each visit (except for the first visit), and 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 \[Day 43 to 57\] in high-dose and low-dose groups will be compared with that in placebo group.
Time frame: 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
The TED at each ETT will be collected and recorded as primary parameter, and change in symptom-limited total exercise duration (TED) at trough drug levels on standard Bruce protocol from baseline to Day 43 in high-dose and low-dose groups will be compared with that in placebo group.
Time frame: 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]
A Wearable Cardiac Monitor (WCM) is a device similar to a Holter but quite smaller in size. This is a FDA-approved device used for recording the ECG up to for 7 days when patients may suffer from transient symptoms such as palpitations, dizziness, anxiety, fatigue, syncope, pre-syncope, light-headedness, shortness of breath. The WCM device is safe and easy for patients to use even when they are taking a short shower. Angina episodes during the past 7 days will be mainly collected from this device and recorded by site staff at due visit until Day 57. And 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 \[Day 29 to 43\] in high-dose and low-dose groups will be compared with that in placebo group.
Time frame: Day 43 (post drug administration from randomization)
Change in time to onset of angina during ETT from baseline to Day 57
Commonly, exercise will make heart pump harder and faster, and further cause angina event during ETT as a result of myocardial ischemia. The time from the beginning of ETT to onset of angina during ETT will be collected and recorded at each ETT, and change in time to onset of angina during ETT from baseline to Day 57 in high-dose and low-dose groups will be compared with that in placebo group.
Time frame: Day 57 (post drug administration from randomization)
Change in time to 1 mm ST depression during ETT from baseline to Day 57
Commonly, exercise will make heart pump harder and faster, and further cause angina event during ETT as a result of myocardial ischemia, sometimes accompanied by horizontal or down-slopping ST segment depression in electrocardiograph (ECG) in some patients with stable angina. The time from the beginning of ETT to onset of at least of 1 millimeter (mm) horizontal or down-slopping ST segment depression during ETT will be collected and recorded at each ETT, and the change in time to onset of at least of 1 mm horizontal or down-slopping ST segment depression during ETT from baseline to Day 57 of treatment in high-dose and low-dose groups will be compared with that in placebo group.
Time frame: Day 57 (post drug administration from randomization)
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