Study the Effects of Ranolazine on Myocardial Perfusion Assessed by Serial Quantitative Exercise SPECT Imaging

To evaluate the effect of ranolazine 1000 mg administered twice daily compared to placebo on
exercise-induced myocardial perfusion defect size (PDS) and total perfusion deficit (TPD),
assessed by gated single photon emission computed tomography (SPECT) myocardial perfusion
imaging (MPI) in subjects with documented exercise induced myocardial ischemia at baseline.

Key Inclusion Criteria:

- Exercise SPECT MPI study (stress and rest) showing at least 10% reversible myocardial
ischemia (as confirmed by the core nuclear laboratory) performed not more than 12
weeks prior to Screening, OR

- Exercise SPECT MPI study (stress and rest) conducted during screening (after
consultation with the Medical Monitor and after informed consent has been obtained)
showing at least 10% reversible myocardial ischemia (as confirmed by the core nuclear
laboratory)

- Stable antianginal medical therapy (excluding short-acting nitroglycerin)

Key Exclusion Criteria:

- Left bundle branch block

- Automated implantable defibrillator and/or pacemaker (selected subjects with
permanent pacemakers who have an intact sinus mechanism may be included following
consultation with the Medical Monitor)

- Intervening coronary revascularization between the time of qualifying exercise SPECT
MPI study and Randomization

- Acute myocardial infarction within 60 days prior to Screening or at any time after
the qualifying exercise SPECT MPI study, or MI undergoing staged intervention during
a subject's participation in the trial

- Unstable angina within 30 days prior to Screening, or at any time after the
qualifying exercise SPECT MPI study

- Coronary artery bypass graft (CABG) surgery within 60 days prior to Screening or at
any time after the qualifying exercise SPECT MPI study, or percutaneous coronary
intervention (PCI) within 30 days prior to Screening or at any time after the
qualifying exercise SPECT MPI study

- Anticipated coronary revascularization during the trial period

- Cerebrovascular Attack (CVA) or Transient Ischemic Attack (TIA) within 90 days prior
to Screening

- History of serious arrhythmias

- Currently in atrial fibrillation or atrial flutter

- QTc interval > 500 milliseconds

- Diagnosed as having New York Heart Association (NYHA) Class III or IV heart failure

- Inability to exercise or exercise limitation due to other co morbidities that may
interfere with ability to perform required exercise SPECT MPI study

- Body Mass Index (BMI) greater than or equal to 38 kg/m2 (may be up to 40 kg/m2 after
consultation with the Medical Monitor)

- Any absolute contraindications to exercise stress testing