Efficacy and Safety Comparison of Azilsartan Medoxomil to Valsartan in Participants With Essential Hypertension
Condition: Hypertension
MeSH terms: Hypertension; Essential Hypertension
Intervention: Azilsartan Medoxomil; Azilsartan Medoxomil; Valsartan
Intervention description: Azilsartan Medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks.; Azilsartan Medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks.; Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.
Intervention MeSH terms: Valsartan; 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: 984.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Blood pressure; blood pressure monitoring, ambulatory

Summary:

      The purpose of this study is to compare the efficacy and safety of TAK-491 (azilsartan
      medoxomil), once daily (QD), to valsartan in participants with essential hypertension.
    

Eligibility criteria:

        Inclusion Criteria

          1. 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).

          2. 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.

          3. 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.

          4. 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

          1. Sitting trough clinic diastolic blood pressure greater than 114 mm Hg at Day minus 1.

          2. The subject has a baseline 24-hour ambulatory blood pressure monitor reading of
             insufficient quality.

          3. 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.

          4. Hypersensitive to angiotensin II receptor blockers.

          5. 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.

          6. Clinically significant cardiac conduction defects (eg, 3rd degree atrioventricular
             block, left bundle branch block, sick sinus syndrome, atrial fibrillation or flutter).

          7. Hemodynamically significant left ventricular outflow obstruction due to aortic
             valvular disease.

          8. Secondary hypertension of any etiology.

          9. Non-compliant (less than 70% or greater than 130%) with study medication during
             placebo run-in period.

         10. Severe renal dysfunction or disease (based on calculated creatinine clearance less
             than 30 mL per min/1.73m2) at Screening.

         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 subjects with
             basal cell or Stage 1 squamous cell carcinoma of the skin).

         14. Type 1 or poorly controlled type 2 diabetes mellitus (glycosylated hemoglobin greater
             than 8.0%) at Screening.

         15. Hyperkalemia as defined by the central laboratory normal reference range at Screening.

         16. Upper arm circumference less than 24 cm or greater than 42 cm.

         17. Works night (3rd) shift (defined as 11PM to 7AM).

         18. Alanine aminotransferase level of greater than 2.5 times the upper limit of normal,
             active liver disease, or jaundice at Screening.

         19. Currently is participating in another investigational study or has participated in an
             investigational study within 30 days prior to randomization.

         20. 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.

         21. Randomized in a previous azilsartan medoxomil study.