The Influence of Febuxostat on Coronary Artery Endothelial Dysfunction in Participants With Chronic Stable Angina
Condition: Coronary Artery Disease
MeSH terms: Coronary Artery Disease; Angina, Stable
Intervention: Febuxostat; Febuxostat placebo
Intervention description: Febuxostat capsules; Febuxostat placebo-matching capsules
Intervention MeSH terms: Febuxostat
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Drug therapy

Summary:

      The purpose of this study is to assess the effect of febuxostat on coronary artery flow in
      patients with coronary artery disease.
    

Eligibility criteria:

        Inclusion Criteria:

          1. In the opinion of the investigator, the participant is capable of understanding and
             complying with protocol requirements.

          2. The participant signs and dates a written, informed consent form and any required
             privacy authorization prior to the initiation of any study procedures.

          3. Has a serum urate ≥4.0 mg/dL.

          4. Has a history of coronary artery disease, defined as:

               1. ≥50 % stenosis of ≥1 major coronary artery confirmed by angiography; OR

               2. Documented prior myocardial infarction (MI) by enzymes/electrocardiogram (ECG)
                  changes; OR

               3. Documented prior exercise or pharmacologic stress/echo myocardial imaging study
                  positive for ischemia.

          5. Has estimated glomerular filtration rate (eGFR) ≥30 mL/min by Modification of Diet in
             Renal Disease (MDRD) at the screening visit.

          6. Has a change in coronary artery flow from rest to isometric handgrip exercise of less
             than + 10 mL/min.

          7. Is male or female and aged 18 to 85 years, inclusive.

          8. 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.

          9. 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.

         10. Is able to take nitroglycerin for anginal symptoms during study procedures.

        Exclusion Criteria:

          1. Has received any investigational compound within 30 days prior to Screening.

          2. Has received allopurinol or febuxostat in a previous clinical study or as a
             therapeutic agent with-in 6 months of randomization.

          3. Has gout or secondary hyperuricemia (eg, due to myeloproliferative disorder, or organ
             transplant) or has experienced a gout flare.

          4. Has a history of xanthinuria.

          5. Has known contraindication to magnetic resonance imaging (MRI) scanning

          6. 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.

          7. Has a history of hypersensitivity or allergies to febuxostat or nitroglycerin.

          8. Has hemoglobin <10 g/L at Screening.

          9. Has a history or clinical manifestations of a significant medical condition that might
             affect his/her ability to complete the study.

         10. Has any of the following during Screening:

               1. New York Heart Association Class III or IV heart failure.

               2. Acute coronary syndrome or a coronary revascularization procedure within 2 months
                  of Screening.

               3. Wolff-Parkinson-White syndrome.

               4. Pacemaker or implantable cardioverter defibrillator.

               5. Arrhythmias (ie, supraventricular tachycardia (SVT), atrial fibrillation/flutter,
                  or ventricular tachycardia (VT) during Screening).

         11. 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.

         12. 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).

         13. Has unstable angina that:

               1. Occurs when the patient is at rest.

               2. Is prolonged, usually greater than 20 minutes.

               3. Occurs with increasing in intensity, duration, and/or frequency.

               4. Responds poorly to nitroglycerin (ie, does not go away after three doses of
                  nitroglycerin or returns after the nitroglycerin helped at first).

         14. Is unable to exercise sufficiently to complete exercise treadmill test (ETT) due to
             leg claudication, arthritis, deconditioning, or associated pulmonary disease.

         15. Has severe or critical valvular disease documented by echocardiogram, or congenital
             heart disease.

         16. The subject has left ventricular ejection fraction (LVEF) less than 35%, as documented
             by echocardiogram, left ventriculogram, or gated blood pool scan..

         17. The subject has clinically significant cardiac conduction defects (ie, second- or
             third-degree atrioventricular block, or sick sinus syndrome) at Screening

         18. Has hypertrophic cardiomyopathy.

         19. Has an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level of
             greater than 2.0 times the upper limit of normal, has active liver disease, or
             jaundice.

         20. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol
             abuse within 5 years prior to the Screening Visit.

         21. Is required or expected to require excluded medications including digoxin or
             digoxin-containing compounds.

         22. If female, is pregnant or lactating or intending to become pregnant before, during, or
             within 1 month after participating in this study; or intending to donate ova during
             such time period.

         23. Has participated in another clinical trial within the past 30 days.