Efficacy and Safety of Azilsartan Medoxomil Combined With Chlorthalidone in Participants With Moderate to Severe Hypertension
Condition: Hypertension
MeSH terms: Hypertension
Intervention: Azilsartan medoxomil and chlorthalidone; Azilsartan medoxomil and chlorthalidone; Azilsartan medoxomil and chlorthalidone; Azilsartan medoxomil and chlorthalidone; Azilsartan medoxomil and chlorthalidone; Azilsartan medoxomil and chlorthalidone; Chlorthalidone; Chlorthalidone; Azilsartan medoxomil; Azilsartan medoxomil; Azilsartan medoxomil
Intervention description: Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for up to 8 weeks; Azilsartan medoxomil 20 mg and chlorthalidone 25 mg combination tablets, orally, once daily for up to 8 weeks; Azilsartan 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for up to 8 weeks; Azilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for up to 8 weeks; Azilsartan 80 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for up to 8 weeks; Azilsartan medoxomil 80 mg and chlorthalidone 25 mg combination tablets, orally, once daily for up to 8 weeks; Azilsartan medoxomil placebo and chlorthalidone 12.5 mg combination tablets, orally, once daily for up to 8 weeks; Azilsartan medoxomil placebo and chlorthalidone 25 mg combination tablets, orally, once daily for up to 8 weeks; Azilsartan medoxomil 20 mg and chlorthalidone placebo combination tablets, orally, once daily for up to 8 weeks; Azilsartan medoxomil 40 mg and chlorthalidone placebo combination tablets, orally, once daily for up to 8 weeks; Azilsartan medoxomil 80 mg and chlorthalidone placebo combination tablets, orally, once daily for up to 8 weeks
Intervention MeSH terms: Chlorthalidone; Azilsartan medoxomil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1711.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: 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
      hypertension.
    

Eligibility criteria:

        Inclusion Criteria:

          1. 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 the day prior to randomization, or the participant has not received
             antihypertensive treatment within 28 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 the day prior to randomization.

          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 on amlodipine or chlorthalidone.

        Exclusion Criteria:

          1. Has a mean sitting clinic diastolic blood pressure greater than 119 mm Hg on the day
             prior to randomization.

          2. Has a baseline 24-hour ambulatory blood pressure measurement reading of insufficient
             quality.

          3. Has 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. Has is noncompliant with study medication during the placebo run-in period.

          6. Has secondary hypertension of any etiology.

          7. Has 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 clinically significant cardiac conduction defects.

          9. Has hemodynamically significant left ventricular outflow obstruction due to aortic
             valvular disease.

         10. Has severe renal dysfunction or disease.

         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.

         13. Has poorly controlled type 1 or type 2 diabetes mellitus at Screening.

         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 Has
             according to the protocol.

         17. Has known hypersensitivity to angiotensin II receptor blockers, 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 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.