The Influence of Febuxostat on Coronary Artery Endothelial Dysfunction in Participants With Chronic Stable Angina

Inclusion Criteria

• In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
• The participant signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
• Has a serum urate ≥4.0 mg/dL.
• Has a history of coronary artery disease, defined as:
• ≥50 % stenosis of ≥1 major coronary artery confirmed by angiography; OR
• Documented prior myocardial infarction (MI) by enzymes/electrocardiogram (ECG) changes; OR
• Documented prior exercise or pharmacologic stress/echo myocardial imaging study positive for ischemia.
• Has estimated glomerular filtration rate (eGFR) ≥30 mL/min by Modification of Diet in Renal Disease (MDRD) at the screening visit.
• Has a change in coronary artery flow from rest to isometric handgrip exercise of less than + 10 mL/min.
• Is male or female and aged 18 to 85 years, inclusive.
• A female of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study.
• Is on stable (30 days prior to Screening Day-21) medication doses prescribed for any underlying medical condition (ie, hypertension, angina) and is expected to remain on stable doses throughout the study duration.
• Is able to take nitroglycerin for anginal symptoms during study procedures.

Exclusion Criteria

• Has received any investigational compound within 30 days prior to Screening.
• Has received allopurinol or febuxostat in a previous clinical study or as a therapeutic agent with-in 6 months of randomization.
• Has gout or secondary hyperuricemia (eg, due to myeloproliferative disorder, or organ transplant) or has experienced a gout flare.
• Has a history of xanthinuria.
• Has known contraindication to magnetic resonance imaging (MRI) scanning
• Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.
• Has a history of hypersensitivity or allergies to febuxostat or nitroglycerin.
• Has hemoglobin <10 g/L at Screening.
• Has a history or clinical manifestations of a significant medical condition that might affect his/her ability to complete the study.
• Has any of the following during Screening:
• New York Heart Association Class III or IV heart failure.
• Acute coronary syndrome or a coronary revascularization procedure within 2 months of Screening.
• Wolff-Parkinson-White syndrome.
• Pacemaker or implantable cardioverter defibrillator.
• Arrhythmias (ie, supraventricular tachycardia (SVT), atrial fibrillation/flutter, or ventricular tachycardia (VT) during Screening).
• Has a recent history (within the last 2 months prior to Screening) of acute coronary syndrome or a coronary revascularization procedure, MI, heart failure, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebrovascular accident, or transient ischemic attack.
• Has a contraindication for using nitrates (severe anemia, increased intracranial pressure, and those with a known sensitivity or hypersensitivity to nitroglycerin or its ingredients, or other nitrates or nitrites; concomitant use either regularly and/or intermittently, with phosphodiesterase type 5 (PDE5) inhibitors).
• Has unstable angina that:
• Occurs when the patient is at rest.
• Is prolonged, usually greater than 20 minutes.
• Occurs with increasing in intensity, duration, and/or frequency.
• Responds poorly to nitroglycerin (ie, does not go away after three doses of nitroglycerin or returns after the nitroglycerin helped at first).
• Is unable to exercise sufficiently to complete exercise treadmill test (ETT) due to leg claudication, arthritis, deconditioning, or associated pulmonary diseas