Efficacy and Safety of Azilsartan Medoxomil and Chlorthalidone in Participants With Moderate to Severe Hypertension
Condition: Essential Hypertension
MeSH terms: Hypertension; Essential Hypertension
Intervention: Azilsartan medoxomil and chlorthalidone; Azilsartan medoxomil and hydrochlorothiazide
Intervention description: Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablet, orally, once daily and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 10 weeks.
For participants who do not achieve target blood pressure by Week 6, the dose of chlorthalidone will be increased for the remaining 4 weeks of treatment.; Azilsartan medoxomil 40 mg, tablets, orally, once daily and hydrochlorothiazide 12.5 mg, tablets, orally, once daily for up to 10 weeks.
For participants who do not achieve target blood pressure by Week 6, the dose of hydrochlorothiazide will be increased for the remaining 4 weeks of treatment.
Intervention MeSH terms: Hydrochlorothiazide; 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: 609.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Essential Hypertension; Hypertensive; Blood Pressure, High; Vascular Disease; Cardiovascular Disease; Drug Therapy

Summary:

      The purpose of this study is to compare the antihypertensive effect of chlorthalidone vs
      hydrochlorothiazide when each is used with azilsartan medoxomil, once daily (QD), in
      participants with moderate to severe essential hypertension.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Is treated with antihypertensive therapy and has a post-washout mean sitting clinic
             SBP greater than or equal to 160 and less than or equal to 190 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 greater than or equal to 160 and less than
             or equal to 190 mm Hg at the Screening Visit and on Day -1.

          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 (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.

          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 (defined as 11 PM [2300] to 7 AM [0700]).

          4. Has an upper arm circumference less than 24 cm or greater than 42 cm.

          5. Is noncompliant (less than 70% or greater than 130%) with study medication during the
             placebo run-in period.

          6. Has secondary hypertension of any etiology (eg, renovascular disease,
             pheochromocytoma, Cushing's syndrome).

          7. 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.

          8. Has clinically significant cardiac conduction defects (ie, third-degree
             atrioventricular block, sick sinus syndrome, atrial fibrillation, or atrial flutter).

          9. Has hemodynamically significant left ventricular outflow obstruction due to aortic
             valvular disease.

         10. Has severe renal dysfunction or disease [based on estimated glomerular filtration rate
             less than 30 mL/min/1.73m2 at Screening].

         11. Has known or suspected unilateral or bilateral renal artery stenosis.

         12. 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 I squamous cell carcinoma of the skin).

         13. Has poorly-controlled type 1 or type 2 diabetes mellitus at Screening.

         14. Has hypokalemia or hyperkalemia (defined as serum potassium outside of the normal
             reference range of the central laboratory).

         15. Has an alanine aminotransferase or aspartate aminotransferase level of greater than
             2.5 times the upper limit of normal, active liver disease, or jaundice.

         16. 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.

         17. Has known hypersensitivity to angiotensin II receptor blockers or thiazide-type
             diuretics or other sulfonamide-derived compounds.

         18. Has been randomized in a previous azilsartan medoxomil study.

         19. Currently participating in another investigational study or is receiving or has
             received any investigational compound within 30 days prior to Screening.

         20. Has a history of drug abuse or a history of alcohol abuse within the past 2 years.