Efficacy and Safety of Azilsartan Medoxomil and Chlorthalidone in Participants With Moderate to Severe Hypertension

• Status: Completed
• Trial end date: 2009-11-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Takeda
• Treatments: Azilsartan medoxomil; Chlorthalidone; Hydrochlorothiazide

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.