An Efficacy and Safety Study of Azilsartan Medoxomil Compared to Valsartan and Olmesartan in Participants With Essential Hypertension.
Condition: Hypertension
MeSH terms: Hypertension; Essential Hypertension
Intervention: Azilsartan medoxomil; Azilsartan medoxomil; Valsartan; Olmesartan; Placebo
Intervention description: Azilsartan medoxomil 20 mg, tablets and matching placebo comparator orally once daily for two weeks.
Increased to azilsartan medoxomil 40 mg tablets and matching placebo comparator orally, once daily for up to four weeks.; Azilsartan medoxomil 40 mg, tablets and matching placebo comparator orally, once daily for two weeks.
Increased to Azilsartan medoxomil 80 mg, tablets and matching placebo comparator orally, once daily for up to four weeks.; Valsartan 160 mg, tablets, and matching placebo comparator orally, once daily for two weeks.
Increased to Valsartan 320 mg, tablets, and matching placebo comparator, orally, once daily for up to four weeks.; Olmesartan 20 mg, tablets and matching placebo comparator, orally, once daily for two weeks.
Increased to Olmesartan 40 mg, tablets and matching placebo comparator, orally, once daily for up to four weeks.; Matching placebo, orally, once daily for up to six weeks.
Intervention MeSH terms: Valsartan; Olmesartan; Azilsartan medoxomil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1291.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Essential Hypertension; Cardiovascular Disease; High Blood Pressure; Drug Therapy

Summary:

      The purpose of this study is to evaluate the efficacy and safety of azilsartan medoxomil,
      once daily (QD), compared to placebo, valsartan and olmesartan in participants with essential
      hypertension.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Essential hypertension (sitting systolic blood pressure between 150 and 180 mm Hg,
             inclusive, at Day -1 and 24-hour mean systolic blood pressure between 130 and 170 mm
             Hg, inclusive, at Day 1).

          2. Capable of understanding and complying with protocol requirements.

          3. 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

          4. Clinical laboratory evaluations within the reference range for the testing laboratory
             or the results are deemed not clinically significant for inclusion into this study by
             the investigator.

          5. Willing to discontinue current antihypertensive medications at Screening Day 21 visit.
             If the participant is on amlodipine prior to Screening, the participant is willing to
             discontinue this medication at Screening Day -28.

        Exclusion Criteria:

          1. Sitting diastolic blood pressure greater than 114 mm Hg at Day -1 (day prior to
             Randomization).

          2. Baseline 24-hour ambulatory blood pressure monitor reading of insufficient quality.

          3. Taking or expected to take an excluded medication as described in the Excluded
             Medications.

          4. Hypersensitive to angiotensin II receptor blockers.

          5. History of myocardial infarction, heart failure, unstable angina, coronary artery
             bypass graft, percutaneous coronary intervention, hypertensive encephalopathy,
             cerebrovascular accident, or transient ischemic attack.

          6. Clinically significant cardiac conduction defects.

          7. Hemodynamically significant left ventricular outflow obstruction due to aortic
             valvular disease.

          8. Secondary hypertension of any etiology.

          9. Noncompliant (less than 70% or greater than 130%) with study medication during run-in
             period.

         10. Moderate to severe renal dysfunction or disease.

         11. Known or suspected unilateral or bilateral renal artery stenosis.

         12. History of drug or alcohol abuse within the past 2 years.

         13. 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 participants
             with basal cell or stage I squamous cell carcinoma of the skin).

         14. Type 1 or poorly-controlled type 2 diabetes mellitus (glycosylate hemoglobin greater
             than 8.0%) at Screening.

         15. Hyperkalemia as defined by the central laboratory normal reference range at Screening.

         16. Alanine aminotransferase level of greater than 2.5 times the upper limit of normal,
             active liver disease, or jaundice at Screening.

         17. Upper arm circumference less than 24 cm or greater than 42 cm.

         18. Works night (3rd) shift (defined as 11 PM [2300] to 7 AM [0700]).

         19. Unwilling or unable to comply with the protocol or scheduled appointments.

         20. Currently is participating in another investigational study or has participated in an
             investigational study within 30 days prior to Randomization.

         21. Any other serious disease or condition at Screening or Randomization that would
             compromise participant's safety, might affect life expectancy, or make it difficult to
             successfully manage and follow the subject according to the protocol.

         22. Has been randomized in a previous azilsartan medoxomil study.

         23. 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.