Long-Term Safety of Azilsartan Medoxomil and Chlorthalidone Compared to Olmesartan Medoxomil and Hydrochlorothiazide in Participants With Hypertension and Kidney Disease.

Inclusion Criteria:

1. The subject is treated with 2 or 3 antihypertensive medications and on stable therapy, defined as ≥6 weeks on medication, and has a mean sitting clinic systolic blood pressure ≥135 and ≤160 mm Hg at the Screening Visit and on Day 1.
2. The participant has an estimated glomerular filtration rate (eGFR) in the range of ≥30 to <60mL/min/1.73 m2 (Stage 3 chronic kidney disease) at the Screening Visit.
3. The participant is a man or woman and aged 18 years or older.
4. A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to routinely use adequate contraception from signing of the informed consent through 30 days after the last study drug dose.
5. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
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. The participant has clinical laboratory test results (clinical chemistry, hematology, and complete urinalysis) that the investigator does not consider to be clinically significant in this moderate renal impaired population.
8. The participant is willing to discontinue the current antihypertensive medications 2 days prior to randomization.

Exclusion Criteria:

1. The participant has received any investigational compound within 30 days prior to Screening or is currently participating in another investigational study.
2. The participant has been randomized/enrolled in a previous TAK-491 or TAK-491CLD study. NOTE: This criterion does not apply to participants who began participation in another TAK-491 or TAK-491CLD study but were not randomized/enrolled, nor does it apply to participants who participated in observational studies that lacked an intervention or invasive procedure.
3. The participant is receiving a combination of olmesartan and hydrochlorothiazide at the Screening Visit.
4. 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 (eg, spouse, parent, child, sibling) or may consent under duress.
5. The participant has a mean clinic diastolic (sitting, trough) >110 mm Hg on Day 1.
6. The participant has secondary hypertension of any etiology (eg, renovascular disease, pheochromocytoma, Cushing's syndrome).
7. The participant has a recent history (within the last 6 months) of myocardial infarction, heart failure, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebrovascular accident, or transient ischemic attack.
8. The participant has clinically significant cardiac conduction defects (ie, third-degree atrioventricular block, sick sinus syndrome).
9. The participant has hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease.
10. The participant has severe renal dysfunction or disease (based on eGFR <30 mL/min/1.73m2 at Screening) prior renal transplantation or nephrotic syndrome (defined as a urinary albumin/creatinine ratio >2000 mg/g at Screening).
11. Participant has known or suspected unilateral or bilateral renal artery stenosis.
12. 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 basal cell or stage I squamous cell carcinoma of the skin.)
13. The participant has poorly-controlled type 1 or 2 diabetes mellitus (glycosylated hemoglobin A [HbA1c] >8.5%) at Screening.
14. The participant has hypokalemia or hyperkalemia (defined as serum potassium outside of the normal reference range of the central laboratory).
15. The participant has an alanine aminotransferase or aspartate aminotransferase level of >2.5 times the upper limit of normal, active liver disease, or jaundice.
16. The participant has any other known serious disease or condition that would compromise safety, might affect life expectancy, or make it difficult to successfully manage and follow the participant according to the protocol.
17. The participant has a history of hypersensitivity or allergies to ARBs or thiazide-type diuretics or other sulfonamide-derived compounds.
18. The participant has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within the past 2 years.
19. The participant is required to take excluded medications.
20. If female, the participant is pregnant or lactating or intending to become pregnant before, during, or within 30 days after participating in this study; or intending to donate ova during such time period.