Inclusion Criteria:

• Is treated with antihypertensive therapy and has a post-washout mean sitting clinic systolic blood pressure greater than or equal to 160 and less than or equal to 190 mm Hg on Day -1 or the subject is treatment naïve and has a mean sitting clinic systolic blood pressure greater than or equal to 160 and less than or equal to 190 mm Hg at the Screening Visit and on Day -1.
• Females of childbearing potential who are sexually active agree to routinely use adequate contraception from Screening through 30 days after the last administered study drug dose.
• Has clinical laboratory test results (clinical chemistry, hematology, and complete urinalysis) within the reference range for the testing laboratory or the investigator does not consider the results to be clinically significant.
• Is willing to discontinue current antihypertensive medications on Day -21 or Day -28 if the subject is on amlodipine or chlorthalidone.

Exclusion Criteria:

• Has a mean sitting clinic diastolic blood pressure greater than 119 mm Hg on Day -1.
• Has a baseline 24-hour ambulatory blood pressure monitoring reading of insufficient quality.
• Works a night (third) shift (defined as 11 PM [2300] to 7 AM [0700]).
• Has an upper arm circumference less than 24 cm or greater than 42 cm.
• Is noncompliant (less than 70% or greater than 130%) with study medication during the placebo run-in period.
• Has secondary hypertension of any etiology (eg, renovascular disease, pheochromocytoma, Cushing's syndrome).
• 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.
• Has clinically significant cardiac conduction defects (ie, third-degree atrioventricular block, sick sinus syndrome, atrial fibrillation, or atrial flutter).
• Has hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease.
• Has severe renal dysfunction or disease [based on estimated glomerular filtration rate less than 30 mL/min/1.73m2 at Screening].
• Has known or suspected unilateral or bilateral renal artery stenosis.
• 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 subjects with basal cell or stage I squamous cell carcinoma of the skin).
• Has type 1 or poorly-controlled type 2 diabetes mellitus (hemoglobin A1c greater than 8.0%) at Screening.
• Has hypokalemia or hyperkalemia (defined as serum potassium outside of the normal reference range of the central laboratory).
• Has an alanine aminotransferase or aspartate aminotransferase level of greater than 2.5 times the upper limit of normal, active liver disease, or jaundice.
• 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 subject according to the protocol.
• Has known hypersensitivity to angiotensin II receptor blockers or thiazide-type diuretics or other sulfonamide-derived compounds.
• Has been randomized in a previous TAK-491 study.
• Is currently participating in another investigational study or has participated in an investigational study within 30 days prior to Randomization.
• Has a history of drug abuse or a history of alcohol abuse within the past 2 years.

• Is required to take or intends to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:

  • Antihypertensive agents, including those used for treatment of other conditions, such as benign prostatic hyperplasia (a-blockers) or edema (diuretics).
  • Insulin.

  • Other agents that alter blood pressure, including:

    • Tricyclic antidepressants.
    • Monoamine oxidase inhibitors.
    • Central nervous system stimulants.
    • Amphetamines or their derivatives.
    • Dopamine agonists.
    • Atypical antipsychotic agents.
    • Opiates
    • Muscle relaxants.
    • Trazodone.
    • Lithium.
    • Phosphodiesterase type 5 inhibitors.
    • Diet medications.
    • Nitrates.
    • Chronically used common cold medications with pseudoephedrine or nonsteroidal anti-inflammatory drugs, including aspirin more than 325 mg/day or cyclooxygenase-2 inhibitors.
    • Systemic use of corticosteroids.
    • Thiazolidinediones.
  • Medications for treatment of insomnia are limited to no more than once a week on average and are prohibited on ambulatory blood pressure monitoring days.