Efficacy and Safety of Azilsartan Medoxomil and Chlorthalidone Compared to Olmesartan Medoxomil and Hydrochlorothiazide in Participants With Moderate to Severe Hypertension.
Condition: Essential Hypertension
MeSH terms: Hypertension; Essential Hypertension
Intervention: Azilsartan medoxomil and chlorthalidone; Azilsartan medoxomil and chlorthalidone; Olmesartan medoxomil and hydrochlorothiazide
Intervention description: Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks.
Participants will be force titrated at Week 4 to azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks.
Participants will then be force titrated at Week 8 to azilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks.; Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks.
Participants will be force titrated at Week 4 to azilsartan medoxomil 80 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks.
Participants will then be force titrated at Week 8 to azilsartan medoxomil 80 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks.; Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily and azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for up to 4 weeks.
Participants will be force titrated at Week 4 to olmesartan medoxomil 40 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily for the next 4 weeks.
Participants will then be force titrated at Week 8 to olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg combination tablets, orally, once daily for the next 4 weeks.
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: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1071.0
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 antihypertensive effect of azilsartan medoxomil
      plus chlorthalidone, once daily (QD), to olmesartan medoxomil plus hydrochlorothiazide in
      participants with moderate to severe hypertension.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Has a mean sitting clinic systolic blood pressure greater than or equal to 160 and
             less than or equal to 190 mm Hg.

          2. Females of childbearing potential who are sexually active agree to routinely use
             adequate contraception from Screening through 30 days after the last administered
             study drug dose.

          3. 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.

          4. Is willing to discontinue current antihypertensive medications on Day -21 or Day -28
             if the participant is on amlodipine or chlorthalidone.

        Exclusion Criteria:

          1. Has a mean sitting clinic diastolic blood pressure greater than 119 mm Hg on Day -1.

          2. Has a baseline 24-hour ambulatory blood pressure monitoring reading of insufficient
             quality.

          3. Works a night (third) shift.

          4. Has an upper arm circumference less than 24 cm or greater than 42 cm.

          5. Has secondary hypertension of any etiology.

          6. Has a recent history of myocardial infarction, heart failure, unstable angina,
             coronary artery bypass graft, percutaneous coronary intervention, hypertensive
             encephalopathy, cerebrovascular accident, or transient ischemic attack.

          7. Has clinically significant cardiac conduction defects.

          8. Has hemodynamically significant left ventricular outflow obstruction due to aortic
             valvular disease.

          9. Has severe renal dysfunction or disease.

         10. Has known or suspected unilateral or bilateral renal artery stenosis.

         11. Has a history of cancer that has not been in remission for at least 5 years prior to
             the first dose of study drug.

         12. Has poorly-controlled diabetes mellitus at Screening.

         13. Has hypokalemia or hyperkalemia.

         14. Has an alanine aminotransferase or aspartate aminotransferase level of greater than
             2.5 times the upper limit of normal, active liver disease, or jaundice.

         15. 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 the
             participant according to the protocol.

         16. Has known hypersensitivity to angiotensin II receptor blockers or thiazide-type
             diuretics or other sulfonamide-derived compounds.

         17. Has a history of drug abuse or a history of alcohol abuse within the past 2 years.