Angina

This is a double-blind, randomized, placebo-controlled, and parallel study. The study is comprised of three main phases: a single-blind placebo run-in qualifying phase lasting about 14 days, a double-blind treatment phase of 12 weeks, and a 2-week follow-up phase. Approximately 18 patients will be enrolled and randomly assigned to receive placebo or 1,000 mg of extended-release Ranolazine twice-daily for 12 weeks to reach 14 evaluable patients at the end of the study.

Ranolazine

Ranolazine

Tablet

500

Primary efficacy endpoint:
 To compare the change from baseline of ETT performing duration between
add-on Ranolazine and placebo at trough (12 hours after dosing) at Week 12.

Main inclusion criteria:
(1) Male or female patients aged ≥ 20 years old.
(2) A minimum 3-month history of stable angina.
(3) Patients with diagnosis of coronary artery disease (CAD) via at least one of
the following criteria:
o Angiographic evidence of ≥ 50% stenosis of ≥ 1 major coronary artery;
o CT angiographic evidence of ≥ 50% stenosis of ≥ 1 major coronary artery;
o History of previous myocardial infarction (MI)*;
*Previous MI history of patients has to be occurred and diagnosed at least 2
months prior entering this study.
o A stress-induced reversible perfusion defect identified by radionuclide or
echocardiographic imaging.
(4) Patients present with the symptoms of stable angina after withdrawn from
other antianginal drugs and given the required background therapy for at least
5 days will be qualified for entering this study and performing 1st ETT qualifying
test.
(5) Patients developed exercise-induced ECG ischemiai
during two qualifying
exercise treadmill testsii. The difference between twoiii tests should be ≤ 20%of the longer test or ≤ 1 minute.
i. ECG ischemia is defined as ST-segment depression ≥ 1mm below the
resting values or ST-segment elevation ≥ 0.5mm above the resting values; if
patients with ST depression at rest (<1mm), qualifying ST segment
depression is defined as additional ST depression of at least 1 mm below
the resting value or additional ST segment elevation of at least 0.5 mm
above the resting value.
ii. Exercise treadmill test (ETT) will be performed by Modified Bruce Protocol.
iii. Two qualifying tests will be conducted 1 week apart, a 3rd ETT test will be
performed ≤ 3 days when differences between previous two qualifying ETTs
>20% of the longer test or >1 minute.
(6) Willing and able to provide a written informed consent.

Main exclusion criteria:
(1) Factors that might compromise ECG or ETT interpretation.
o Patients with resting ST-segment depression ≥ 1mm in any lead.
o Left bundle-branch block.
o Patients implanted with pacemaker.
o Patients under Digitalis therapy.
(2) Patients with family history of (or congenital) long QT syndrome.
(3) Patients with congenital heart disease.
(4) Patients with uncorrected valvular heart disease.
(5) Patients with unstable angina, or MI, or coronary revascularization procedure ≤
2 months prior enter this study.
(6) Female who is pregnant/lactating or planning to be pregnant, or female of
childbearing potential* who is not using medically recognized method of
contraception.
*Other than those who have been surgically sterilized (defined as having
undergone hysterectomy or bilateral oophorectomy or bilateral salpingectomy;
tubal ligation alone is not considered sufficient) or one year post-menopausal.
(7) Patients are under any one of the following conditions:
o New York Heart Association (NYHA) Class III or Class IV congestive heart
failure (CHF);
o QTc > 450 msec at screening;
o Active myocarditis, pericarditis, hypertrophic cardiomyopathy;
o Uncontrolled hypertension (defined as SBP > 180 mmHg).
Voltage criteria for left ventricular hypertrophy in the absence of repolarization
abnormalities will not be exclusion criteria.
(8) Use of any investigational product ≤ 4 weeks prior to screening.
(9) Patients with severe hepatic disease (e.g., liver cirrhosis).
(10) Patients with impaired renal function (defined as serum Cr >1.5 mg/dl).
(11) Patients with any condition or disease which is considered not suitable for this
study by investigator.