Inclusion Criteria

• Essential hypertension (defined as sitting trough clinic systolic blood pressure between 150 and 180 mm Hg inclusive at Day minus 1 and 24-hour mean systolic blood pressure between 130 and 170 mm Hg inclusive at Day 1).
• Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.
• Clinical laboratory evaluations (including clinical chemistry, hematology, and complete urinalysis) within the reference range for the testing laboratory or the results are deemed not clinically significant for inclusion into this study by the investigator.
• Willing to discontinue current antihypertensive medications at the Screening Day minus 21 visit. If the subject is on amlodipine prior to Screening, the subject is willing to discontinue this medication at Screening Day minus 28.

Exclusion Criteria

• Sitting trough clinic diastolic blood pressure greater than 114 mm Hg at Day minus 1.
• The subject has a baseline 24-hour ambulatory blood pressure monitor reading of insufficient quality.

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

  • Antihypertensive agents.
  • Insulin
  • Other agents that alter blood pressure, including:
  • tricyclic antidepressants
  • monoamine oxidase inhibitors
  • diuretics
  • lithium
  • atypical antipsychotics
  • Phosphodiesterase type 5 (PDE5) inhibitors
  • diet medications (including sibutramine)
  • amphetamines or their derivatives
  • chronically used common cold medications or nonsteroidal anti-inflammatory drugs, including aspirin greater than 325 mg per day or cyclooxygenase-2 inhibitors
  • systemic use of corticosteroids
  • thiazolidinediones
• Hypersensitive to angiotensin II receptor blockers.
• 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.
• Clinically significant cardiac conduction defects (eg, 3rd degree atrioventricular block, left bundle branch block, sick sinus syndrome, atrial fibrillation or flutter).
• Hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease.
• Secondary hypertension of any etiology.
• Non-compliant (less than 70% or greater than 130%) with study medication during placebo run-in period.
• Severe renal dysfunction or disease (based on calculated creatinine clearance less than 30 mL per min/1.73m2) at Screening.
• Known or suspected unilateral or bilateral renal artery stenosis.
• History of drug or alcohol abuse within the past 2 years.
• Previous 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 1 squamous cell carcinoma of the skin).
• Type 1 or poorly controlled type 2 diabetes mellitus (glycosylated hemoglobin greater than 8.0%) at Screening.
• Hyperkalemia as defined by the central laboratory normal reference range at Screening.
• Upper arm circumference less than 24 cm or greater than 42 cm.
• Works night (3rd) shift (defined as 11PM to 7AM).
• Alanine aminotransferase level of greater than 2.5 times the upper limit of normal, active liver disease, or jaundice at Screening.
• Currently is participating in another investigational study or has participated in an investigational study within 30 days prior to randomization.
• Any other serious disease or condition at Screening (or Randomization) that would compromise subject safety, might affect life expectancy, or make it difficult to successfully manage and follow the subject according to the protocol.
• Randomized in a previous TAK-491 study.