Effect of Febuxostat on Blood Pressure

1. The participant has documented hypertension, defined as average clinic systolic blood pressure (SBP) of ≥145 mm Hg and ≤165 mm Hg or average clinic diastolic blood pressure (DBP) of ≥90 mm Hg and ≤105 mm Hg at the Day -21 Screening Visit; the average BP measurement at two of the three Placebo Run-in Visits (Day -14, Day -7 and Day -1) must also meet the above criteria for hypertension.
2. The participant has a serum uric acid (sUA) level ≥7.0 mg/dL not associated with gout, at the Day -21 Screening Visit.
3. The participant has a 24-hour mean ambulatory SBP of ≥130 mm Hg and \< 165 mm Hg at the Baseline (Day 1) Visit.
4. At the initial Screening Visit (Day -21), the maximum number of antihypertensive medications the participant is taking is ≤ 2 (fixed-dose combination medications are considered 2 medications, including diuretics), and the participant has been on a stable dose of this medication for at least1 month prior to start of the initial Screening Visit (Day -21).

5. The participant is male and at least 18 years of age, or a female who is:

   • Surgically sterilized (hysterectomy, bilateral oophorectomy or tubal ligation), OR
   • Postmenopausal (defined as at least 1 year since last regular menses with an follicle-stimulating hormone (FSH) >40 IU/L, or at least 5 years since last regular menses), OR
   • On hormone replacement therapy and ≥ 55 years of age.
6. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
7. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.

Exclusion Criteria:

1. The participant has received any investigational compound within 30 days, or within 5 half-lives of the compound (whichever is longer) prior to the Screening Visit.
2. The participant has received febuxostat or any urate-lowering therapy (ULT) in a previous clinical study or as a therapeutic agent.
3. The participant has gout, history of gout, or gout flares.
4. The participant has secondary hyperuricemia (HPU) (e.g., due to myeloproliferative disorder, or organ transplant).
5. The participant has known secondary hypertension of any etiology (e.g., renovascular disease, primary hyperaldosteronism, Cushing syndrome).
6. The participant has a history, within the 6 months prior to screening, of myocardial infarction, heart failure, unstable angina, coronary artery bypass graft, or percutaneous coronary intervention.
7. The participant has an irregular cardiac rhythm (e.g., atrial fibrillation, multifocal premature atrial contractions) which leads to difficulty with interpretation of ambulatory blood pressure monitoring (ABPM).
8. The participant has a history of congestive heart failure, hypertensive encephalopathy, cerebrovascular accident, or transient ischemic attack.
9. The participant has type 1 or poorly controlled type 2 diabetes mellitus (glycosylated hemoglobin [HbA1c] >8.0%) at Screening.
10. The participant has a history of infection with hepatitis B, hepatitis C, or human immunodeficiency virus.
11. The participant has an average clinic SBP >165 mm Hg or DBP >105 mm Hg at 1 or more visits during the Placebo Run-in Period.
12. The participant's average clinic SBP or DBP measurement that increases or decreases by >10 mm Hg between Placebo Run-in visits (Day -14 to Day -7, or Day -7 to Day -1, or Day -14 to Day -1).
13. The participant 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 (e.g., spouse, parent, child, sibling) or may consent under duress.
14. The participant has an alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) values greater than 2.0 times the upper limit of normal (ULN).
15. The participant has a significant medical condition and/or conditions that would interfere with the treatment, safety or compliance with the protocol.
16. The participant has a history of alcoholism or illicit drug abuse within 5 years prior to the Screening Visit or is currently consuming >14 alcoholic drinks per week.
17. The participant has a known hypersensitivity or allergies to febuxostat or any components of the formulations of this compound.
18. The participant is taking or expected to take a medication as described in the excluded medication section.
19. The participant has a history of cancer that has not been in remission for at least 5 years prior to the first dose of study drug. This criterion does not apply to those participants with successfully resected basal cell or stage I squamous cell carcinoma of the skin.
20. The participant's estimated glomerular filtration rate (eGFR) is \<30 mL/min/1.73m3, where eGFR is calculated by the Central Laboratory using the Modification of Diet in Renal Disease (MDRD) formula at the Day -21 Screening Visit.
21. The participant is noncompliant (\<80% or >120%) with study medication during Placebo Run-In Period.
22. The participant has an upper arm circumference less than 24 cm or greater than 42 cm.
23. The participant's work shift includes any hour between 11 PM (2300) to 7 AM (0700).
24. The participant has a baseline 24-hour ABPM reading of insufficient quality (as described in Appendix F of the protocol).