Intervention: Ranolazine
Trial phase: Phase 4
ATC code: C01EB18
SMILES: COc1ccccc1OCC(O)CN1CCN(CC(=O)Nc2c(C)cccc2C)CC1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 470
Group description: Qualifying phase: Participants entered a 2-week washout period if needed to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period were randomized to the treatment period.

Treatment period: Ranolazine tablets (Day 1: 1 × 500 tablet in the evening; Days 2-7: 1 × 500 mg twice daily; 2 × 500 mg twice daily thereafter) for up to 8 weeks.
Eligibility criteria:
Inclusion Criteria:

Written informed consent
Males and females aged at least 18 years
At least a 3-month history of chronic stable angina triggered by physical effort and relieved by rest and/or sublingual nitroglycerin

CAD documented by one or more of the following:

Angiographic evidence of ≥ 50% stenosis of one or more major coronary arteries
History of myocardial infarction (MI) documented by positive myocardial muscle creatine kinase (CK-MB) enzymes, troponins, or electrocardiogram (ECG) changes
Cardiac imaging study or exercise test diagnostic for CAD
Treatment with up to 2 antianginal therapies at a stable dose for at least 2 weeks prior to the Qualifying Period.
Documented history of T2DM
Willing to maintain stable tobacco usage habits throughout the study
Willing to maintain stable activity levels throughout the study
Females of childbearing potential must agree to utilize highly effective contraception methods from Screening throughout the duration of study treatment and for 14 days following the last dose of study drug.

Exclusion Criteria:

New York Heart Association (NYHA) Class III and IV
Acute coronary syndrome in the prior 2 months or planned coronary revascularization during the study period
Stroke or transient ischemic attack within 6 months prior to Screening
QTc > 500 milliseconds
Uncontrolled hypertension (seated systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg)
Systolic blood pressure < 100 mmHg
Clinically significant hepatic impairment
Prior treatment with ranolazine, or known hypersensitivity or intolerance to ranolazine
Females who are breastfeeding
Positive serum pregnancy test
Participation in another investigational drug or device study within 1 month prior to Screening
Current treatment with trimetazidine, ivabradine, or nicorandil. Subjects will need to discontinue these medications 2 weeks prior to the Qualifying Period.
Current treatment with potent inhibitors of cytochrome (CYP)3A (eg, ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir)
Current treatment with CYP3A and P glycoprotein (Pgp) inducers (eg, rifampicin/rifampin, carbamazepine, and St. John's wort [Hypericum perforatum])
Current treatment with CYP3A4 substrates with a narrow therapeutic range (eg, cyclosporine, tacrolimus, and sirolimus)
Subjects taking simvastatin who cannot reduce the dose to 20 mg once daily or who cannot switch to another statin
Current treatment with Class I or III antiarrhythmic medications
History of illicit drug use or alcohol abuse within 1 year of Screening
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