Efficacy and Safety Study of Azilsartan Medoxomil Compared to Ramipril for Treating Essential Hypertension
Condition: Hypertension
MeSH terms: Hypertension; Essential Hypertension
Intervention: Azilsartan medoxomil; Azilsartan medoxomil; Ramipril
Intervention description: Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 40 mg, tablets, orally, once daily for up to 22 weeks.; Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 80 mg, tablets, orally, once daily for up to 22 weeks.; Ramipril 2.5 mg, tablets, orally, once daily for two weeks; then increased to 10 mg, tablets, orally, once daily for up to 22 weeks.
Intervention MeSH terms: Ramipril; 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: 885.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Essential Hypertension; Hypertension; Drug Therapy; Blood Pressure, High; Vascular Disease; Cardiovascular Disease

Summary:

      The purpose of this study is to determine the efficacy and safety of azilsartan medoxomil,
      once daily (QD), compared to ramipril for treating Essential Hypertension.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Essential hypertension (sitting systolic blood pressure between 150 and 180 mm Hg,
             inclusive).

          2. A female participant of childbearing potential who is sexually active agrees to use
             adequate contraception from screening throughout the duration of the study, and cannot
             be pregnant.

          3. Has clinical laboratory evaluations (including clinical chemistry, hematology, and
             complete urinalysis) within the reference range for the testing laboratory at
             Screening or the results are deemed not clinically significant for inclusion into this
             study by the investigator.

          4. Is willing to discontinue current antihypertensive medications at Screening Day -21.
             If the participant is on amlodipine prior to screening, the participant is willing to
             discontinue this medication at Screening Day -28.

        Exclusion Criteria:

          1. Has an systolic blood pressure greater than 180 mmHg or diastolic blood pressure
             greater than 114 mmHg at Randomization.

          2. Is taking or expected to take an excluded medication including antihypertensive
             agents, insulin or other agents that alter blood pressure.

          3. Is hypersensitive to angiotensin II receptor blockers and/or angiotensin-converting
             enzyme inhibitors.

          4. 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.

          5. Has clinically significant cardiac conduction defects (eg, third-degree
             atrioventricular block, left bundle branch block, sick sinus syndrome, atrial
             fibrillation or flutter).

          6. Has hemodynamically significant left ventricular outflow obstruction due to aortic
             valvular disease.

          7. Has secondary hypertension of any etiology (eg, renovascular disease,
             pheochromocytoma, Cushing's syndrome).

          8. Is noncompliant (less than 70% or greater than 130%) with study medication during
             placebo run-in period.

          9. Has severe renal dysfunction or disease (based on calculated creatinine clearance less
             than 30 mL/min/1.73 m² at Screening).

         10. Has known or suspected unilateral or bilateral renal artery stenosis.

         11. Has a history of drug or alcohol abuse within the past 2 years.

         12. Has a 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).

         13. Has type 1 or poorly controlled type 2 diabetes mellitus (hemoglobin A1c greater than
             8.0%) or is taking insulin.

         14. Has hyperkalemia as defined by the central laboratory normal reference range at
             Screening.

         15. Has an upper arm circumference less than 24 cm or greater than 42 cm.

         16. Works night (third) shift (defined as 11 PM to 7 AM).

         17. Has an alanine aminotransferase level at Screening of greater than 2.5 times the upper
             limit of normal, active liver disease, or jaundice.

         18. Is currently participating in another investigational study or has participated in an
             investigational study within 30 days prior to Screening.

         19. Has 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 participant according to the protocol.

         20. Has been randomized in a previous azilsartan medoxomil study.