Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina
Condition: Angina Pectoris; Coronary Artery Disease; Type 2 Diabetes Mellitus
MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Angina Pectoris; Angina, Stable; Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Ranolazine; Ranolazine placebo
Intervention MeSH terms: Ranolazine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 949.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Chronic angina; Angina pectoris; Coronary artery disease; Type 2 Diabetes Mellitus

Summary:

      This study will evaluate the effect of ranolazine compared to placebo on the average weekly
      angina frequency in subjects with chronic stable angina and coronary artery disease (CAD) who
      have a history of type 2 diabetes mellitus (T2DM), and whether ranolazine can reduce the
      frequency of angina (chest pain) attacks, compared to a placebo. Subjects will be asked to
      record their daily angina episodes in a diary at the end of each study day. Ranolazine is
      approved for the treatment of chronic angina, and is not approved for the treatment of T2DM.
    

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:

               1. Angiographic evidence of ≥ 50% stenosis of one or more major coronary arteries

               2. History of myocardial infarction (MI) documented by positive myocardial muscle
                  creatine kinase (CK-MB) enzymes, troponins, or electrocardiogram (ECG) changes

               3. 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