Azilsartan Medoxomil (TAK-491) Compared to Valsartan in Chinese Participants With Hypertension
Condition: Essential Hypertension
MeSH terms: Hypertension; Essential Hypertension
Intervention: Azilsartan medoxomil; Valsartan; Azilsartan medoxomil Placebo; Valsartan Placebo
Intervention description: Azilsartan medoxomil tablets; Valsartan 80 mg capsules; Azilsartan medoxomil placebo-matching tablets; Valsartan placebo-matching capsules
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: 612.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Drug therapy

Summary:

      The purpose of this study is to evaluate the antihypertensive effect of azilsartan medoxomil
      compared with valsartan in Chinese participants with essential hypertension.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Is treated with antihypertensive therapy and has a post-washout mean sitting clinic
             systolic blood pressure (SBP) ≥150 and ≤180 mm Hg on Day 1; or the participant has not
             received antihypertensive treatment within 28 days prior to Screening and has a mean
             sitting clinic SBP ≥150 and ≤180 mm Hg at the Screening Visit and on Day 1.

          2. Is a man or woman aged 18 years or older.

          3. In the opinion of the investigator, the participant is capable of understanding and
             complying with protocol requirements.

          4. 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.

          5. A female participant of childbearing potential who is sexually active with a
             nonsterilized male partner agrees to use routinely adequate contraception from signing
             of informed consent through 30 days after last study drug dose.

          6. 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.

          7. Is willing to discontinue current antihypertensive medications on Day -21 or on Day
             -28 if the participant is on amlodipine or chlorthalidone.

        Exclusion Criteria:

          1. Has a mean, sitting clinic diastolic blood pressure (DBP) greater than 110 mm Hg at
             Day 1 (after placebo run in).

          2. Is non-compliant (less than 70% or greater than 130%) with study medication during
             placebo run-in period.

          3. Has secondary hypertension of any etiology (eg, renovascular disease documented as the
             cause of hypertension, pheochromocytoma, Cushing's syndrome).

          4. Has a history of myocardial infarction, heart failure, unstable angina, coronary
             artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy,
             cerebrovascular accident, or transient ischemic attack.

          5. Has clinically significant cardiac conduction defects (eg, third-degree
             atrioventricular block, sick sinus syndrome).

          6. Has hemodynamically significant left ventricular outflow obstruction due to aortic
             valvular disease and hypertrophic obstructive cardiomyopathy (HOCM).

          7. Has severe renal dysfunction or disease (based on estimated glomerular filtration rate
             [GFR] <30 mL/min/1.73 m^2) at Screening.

          8. Has known or suspected unilateral or bilateral renal artery stenosis.

          9. 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 1 squamous cell carcinoma of the skin).

         10. Has type 1 or poorly controlled type 2 diabetes mellitus (hemoglobin A1c [HbA1c]
             >8.5%) at Screening.

         11. Has hyperkalemia (defined as serum potassium above the normal reference range of the
             central laboratory) at Screening.

         12. Has an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level of
             greater than 2.5 times the upper limit of normal (ULN), active liver disease, or
             jaundice at Screening.

         13. Has any other known serious disease or condition at Screening (or Randomization) that
             would compromise participant safety, might affect life expectancy, or make it
             difficult to successfully manage and follow the participant according to the protocol.

         14. Has a history of hypersensitivity or allergies to TAK-491 (azilsartan medoxomil), any
             of its excipients or other angiotension II (AII) receptor blockers (ARBs).

         15. 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.

         16. Is currently participating in another investigational study or is receiving or has
             received any investigational compound within 30 days prior to the first dose of study
             medication.

             Note: This criterion does not apply to participants who participated in observational
             studies that lacked an intervention or invasive procedure.

         17. Is an immediate family member, study site employee, or is in a dependant relationship
             with a study site employee who is involved in conduct of this study (eg, spouse,
             parent, child, sibling) or may consent under duress.

         18. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol
             abuse within the past 2 years.

         19. Is taking or expected to take an excluded medication.

         20. Works a night (third) shift (defined as 11 PM [2300] to 7 AM [0700]). (Only for
             participants with ambulatory blood pressure monitoring [ABPM].)

         21. Has an upper arm circumference <24 cm or >42 cm. (Only for participants with ABPM.)