Safety and Tolerability of Azilsartan Medoxomil Plus Chlorthalidone Compared to Olmesartan Medoxomil Plus Hydrochlorothiazide in Participants With Essential Hypertension
Condition: Essential Hypertension
MeSH terms: Hypertension; Essential Hypertension
Intervention: Azilsartan medoxomil and chlorthalidone; Olmesartan medoxomil and hydrochlorothiazide
Intervention description: Combination tablet.; Combination tablet.
Intervention MeSH terms: Hydrochlorothiazide; Olmesartan; Olmesartan Medoxomil; Chlorthalidone; Azilsartan medoxomil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 837.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Hypertensive; Blood Pressure, High; Cardiovascular disease; Vascular Disease; Drug Therapy

Summary:

      The purpose of this study is to compare the safety and tolerability of azilsartan medoxomil
      plus chlorthalidone, once daily (QD), versus olmesartan medoxomil-hydrochlorothiazide in
      adults with essential hypertension.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Is treated with antihypertensive therapy and has a post-washout mean sitting clinic
             systolic blood pressure greater than or equal to 160 and less than or equal to 190 mm
             Hg on Day, or has not received antihypertensive treatment within 14 days prior to
             Screening and has a mean sitting clinic systolic blood pressure greater than or equal
             to 160 and less than or equal to 190 mm Hg at the Screening Visit and on Day 1.

          -  Females of childbearing potential who are sexually active agree to routinely use
             adequate contraception, and can neither be pregnant nor lactating from before study
             participation to Screening to 30 days after the last study drug dose.

          -  Has clinical laboratory test results within the reference range for the testing
             laboratory or the investigator does not consider the results to be clinically
             significant.

          -  Is willing to discontinue current antihypertensive medications up to 3 weeks before
             enrollment.

        Exclusion Criteria:

          -  Has a mean clinic diastolic blood pressure (sitting, trough) greater than 119 mm Hg on
             Day 1.

          -  Has secondary hypertension of any etiology (eg, renovascular disease,
             pheochromocytoma, Cushing's syndrome).

          -  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.

          -  Has clinically significant cardiac conduction defects (ie, third-degree
             atrioventricular block, sick sinus syndrome).

          -  Has hemodynamically significant left ventricular outflow obstruction due to aortic
             valvular disease.

          -  Has severe renal dysfunction or disease.

          -  Has known or suspected unilateral or bilateral renal artery stenosis.

          -  Has a history of cancer that has not been in remission for at least 5 years prior to
             the first dose of study drug.

          -  Has poorly-controlled type 1 or 2 diabetes mellitus at Screening.

          -  Has hypokalemia or hyperkalemia at Screening.

          -  Has an alanine aminotransferase or aspartate aminotransferase level of greater than
             2.5 times the upper limit of normal, active liver disease, or jaundice at Screening.

          -  Has any other known serious disease or condition that would compromise safety, might
             affect life expectancy, or make it difficult to successfully manage and follow
             according to the protocol.

          -  Has known hypersensitivity to angiotensin II receptor blockers or thiazide-type
             diuretics or other sulfonamide-derived compounds.

          -  Has been randomized/enrolled in a previous azilsartan or azilsartan medoxomil plus
             chlorthalidone study.

          -  Currently is participating in another investigational study or has received any
             investigational compound within 30 days prior to Screening.

          -  Has a history of drug abuse or a history of alcohol abuse within the past 2 years.

          -  Is taking or expected to take any excluded medication, including:

               -  Antihypertensive medications must be discontinued completely by Day -14, except
                  antihypertensive medications used in the open-label treatment period in
                  accordance with the titration-to-target blood pressure titration.

               -  Angiotensin II receptor blockers or thiazide-type diuretics other than study
                  medication.

               -  Over-the-counter products not permitted by investigator.