Efficacy and Safety of Azilsartan Medoxomil Plus Chlorthalidone 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-hydrochlorothiazide
Intervention description: Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.
If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.; Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.
If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.; Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks.
If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 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: 1085.0
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 determine the efficacy and safety of azilsartan medoxomil
      combined with chlorthalidone, once daily (QD), in participants with moderate to severe
      essential hypertension.
    

Eligibility criteria:

        Inclusion Criteria:

          1. 190 mm Hg on Day -1 or if the participant has not received antihypertensive treatment
             within 28 days before 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.

          2. Females of childbearing potential who are sexually active must agree to use adequate
             contraception, and can neither be pregnant nor lactating from Screening throughout the
             duration of the study.

          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 on Day
             -28 if is on amlodipine or chlorthalidone.

        Exclusion Criteria:

          1. Has a mean sitting clinic diastolic blood pressure greater than 119 mm Hg.

          2. Has a baseline 24-hour ambulatory blood pressure monitoring reading of insufficient
             quality.

          3. Works a night (third) shift (from 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 with study medication during the placebo run-in period.

          6. Has secondary hypertension of any etiology.

          7. 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.

          8. Has a clinically significant cardiac conduction.

          9. Has hemodynamically significant left ventricular outflow obstruction due to aortic
             valvular disease.

         10. Has severe renal dysfunction or disease.

         11. Has a 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.

         13. Has poorly controlled type 1 or type 2 diabetes mellitus.

         14. Has hypokalemia or hyperkalemia.

         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 a 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. Is currently participating in another investigational study or has participated in an
             investigational study or is receiving or has received any investigational compound
             within 30 days prior to Randomization.

         20. Has a history of drug abuse or a history of alcohol abuse within the past 2 years.