Efficacy and Safety of Azilsartan Medoxomil Co-Administered With Chlorthalidone in Participants With Essential Hypertension
Condition: Hypertension
MeSH terms: Hypertension; Essential Hypertension
Intervention: Azilsartan medoxomil and chlorthalidone; Azilsartan medoxomil and chlorthalidone; Chlorthalidone
Intervention description: Azilsartan medoxomil 40 mg, tablets, orally, once daily; azilsartan medoxomil 80 mg placebo-matching tablets, orally, once daily; and chlorthalidone 25 mg, tablets, orally, once daily for up to 6 weeks.; Azilsartan medoxomil 80 mg, tablets, orally, once daily; azilsartan medoxomil 40 mg placebo-matching tablets, orally, once daily and chlorthalidone 25 mg, tablets, orally, once daily for up to 6 weeks.; Chlorthalidone 25 mg, tablets, orally, once daily; azilsartan medoxomil 80 mg placebo-matching tablets, orally, once daily and azilsartan medoxomil 40 mg placebo-matching tablets, orally, once daily for up to 6 weeks.
Intervention MeSH terms: 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: 551.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Blood pressure; Blood pressure monitoring, ambulatory

Summary:

      The purpose of this study is to evaluate the efficacy and safety of azilsartan medoxomil,
      once daily (QD), co-administered with chlorthalidone in treating individuals with essential
      hypertension, compared to treatment with chlorthalidone alone.
    

Eligibility criteria:

        Inclusion Criteria

          1. Has essential hypertension (defined as sitting trough clinic systolic blood pressure
             between 160 and 190 mm Hg inclusive at Day minus 1 and 24-hour mean systolic blood
             pressure greater than or equal to 140 mm Hg and ≤ 180 mm Hg at 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 evaluations (including clinical chemistry, hematology, and
             complete urinalysis) within the reference range for the testing laboratory or results
             that are deemed not clinically significant for inclusion into this study by the
             investigator.

          4. Willing to discontinue current antihypertensive medications at the Screening Day minus
             21 visit. If the subject is on amlodipine prior to screening, the subject is willing
             to discontinue this medication at Screening Day minus 28.

        Exclusion Criteria

          1. Has sitting trough clinic diastolic blood pressure greater than 119 mmHg at Day minus
             1.

          2. Has a baseline 24 hour ambulatory blood pressure monitor reading of insufficient
             quality.

          3. Is required to take or continues taking any disallowed medication, prescription
             medication, herbal treatment or over-the counter medication that may interfere with
             evaluation of the study medication.

          4. 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.

          5. Clinically significant cardiac conduction defects (for example, 3rd degree
             atrioventricular block, left bundle branch block, sick sinus syndrome, atrial
             fibrillation).

          6. Hemodynamically significant left ventricular outflow obstruction due to aortic
             valvular disease.

          7. The subject has secondary hypertension of any etiology.

          8. Non-compliant (less than 70% or greater than 130%) with study medication

          9. during the placebo run- in period.

         10. Severe renal dysfunction or disease (based on calculated creatinine clearance less
             than 30 mL/min/1.73 m2) at Screening.

         11. Known or suspected unilateral or bilateral renal artery stenosis.

         12. History of drug abuse (defined as illicit drug use) or a history of alcohol abuse
             (defined as regular or daily consumption of more than 2 alcoholic drinks per day)
             within the past 2 years.

         13. Previous 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 subjects with
             basal cell or Stage 1 squamous cell carcinoma of the skin.)

         14. Type 1 or poorly controlled type 2 diabetes mellitus (glycosylated hemoglobin greater
             than 8.0%).

         15. Hypo- or hyperkalemia (defined as serum potassium outside of the normal reference
             range of the central laboratory).

         16. Alanine aminotransferase level of greater than 2.5 times the upper limit of normal,
             active liver disease, or jaundice.

         17. Upper arm circumference less than 24 cm or greater than 42 cm.

         18. Works night (3rd) shift (defined as 11PM [2300] to 7AM [0700]).

         19. Currently is participating in another investigational study or has participated in an
             investigational study within 30 days prior to randomization.

         20. Study site employee, or is an immediate family member ( ie, spouse, parent, child,
             sibling) of a study site employee who is involved in conduct of this study.

         21. Any other serious disease or condition at Screening (or Randomization) that would
             compromise subject safety, might affect life expectancy, or make it difficult to
             successfully manage and follow the subject according to the protocol.

         22. Randomized in a previous azilsartan medoxomil study.