Efficacy and Safety of Azilsartan Medoxomil in African American Participants With Essential Hypertension

NCT ID: NCT00591253

Last Updated: 2011-04-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 413 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-10-31
• Study Completion Date: 2009-04-30

Brief Summary

The purpose of this study is to evaluate the effectiveness and safety of azilsartan medoxomil compared to placebo, once daily (QD), in African-American participants with essential hypertension.

Detailed Description

Hypertension affects approximately 50 million individuals in the United States. As the population ages, the prevalence of hypertension will continue to increase if broad and effective preventive measures are not implemented. According to the World Health Organization, hypertension is the most common attributable cause of preventable death in developed nations, as uncontrolled hypertension greatly increases the risk of cardiovascular disease, cerebrovascular disease, and renal failure. Despite the availability of antihypertensive treatments, hypertension remains inadequately controlled; only about one third of patients continue to maintain control successfully.

A major component of blood pressure regulation is the renin-angiotensin-aldosterone system, a system of hormone-mediated feedback interactions that results in the relaxation or constriction of blood vessels in response to various stimuli. Angiotensin II, a polypeptide hormone, is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme as part of the renin-angiotensin-aldosterone system. Angiotensin II is the principal pressor agent of the renin-angiotensin-aldosterone system with a myriad of effects on the cardiovascular system and on electrolyte homeostasis.

In the United States, a disproportionate number of African-Americans have hypertension compared to age-matched non-Hispanic Caucasians and Mexican Americans. Earlier onset and greater severity of hypertension in African-Americans contribute to greater target organ damage and may be a factor in shorter life expectancy in this population compared to Caucasian-Americans. Although genetic factors have been invoked to explain these racial differences, environmental factors probably play a more important role. Improved management of hypertension through both lifestyle intervention and pharmacotherapy, including combination therapy, are necessary to achieve target blood pressure in African Americans.

Takeda Global Research & Development Center, Inc. is developing TAK-491 (azilsartan medoxomil) to treat patients with essential hypertension. Azilsartan medoxomil is a prodrug that is hydrolyzed to the active moiety, TAK-536 (azilsartan), which is a selective antagonist of the angiotensin II type 1 receptor subtype.

This study is being conducted to evaluate the effectiveness and safety of oral azilsartan medoxomil compared with placebo in African-American participants with essential hypertension. Participation in this study is anticipated to be approximately 10 weeks.

Conditions

Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Azilsartan Medoxomil 40 mg QD

Group Type: EXPERIMENTAL

Azilsartan medoxomil

Intervention Type: DRUG

Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 6 weeks.

Azilsartan Medoxomil 80 mg QD

Group Type: EXPERIMENTAL

Azilsartan medoxomil

Intervention Type: DRUG

Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 6 weeks.

Placebo QD

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 6 weeks.

Interventions

Azilsartan medoxomil

Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 6 weeks.

Intervention Type: DRUG

Azilsartan medoxomil

Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 6 weeks.

Intervention Type: DRUG

Placebo

Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 6 weeks.

Intervention Type: DRUG

Other Intervention Names

TAK-491; Edarbi; TAK-491; Edarbi

Eligibility Criteria

Inclusion Criteria

1. The participant has essential hypertension (defined as sitting trough clinic systolic blood pressure between 150 and 180 mm Hg, inclusive at Day -1) and 24-hour mean systolic blood pressure 130-170 mm Hg, inclusive, 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. Clinical laboratory evaluations within the reference range for the testing laboratory unless the results are deemed not clinically significant for inclusion into this study by the investigator.

4. Willing to discontinue current antihypertensive medication.

Exclusion Criteria

1. Has sitting trough clinic diastolic blood pressure greater than 114 mm Hg.

2. Baseline 24 hour ambulatory blood pressure monitor reading of insufficient quality.

3. Hypersensitive to angiotensin II receptor blockers.

4. History 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.

6. Hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease.

7. Secondary hypertension of any etiology.

8. Non-compliant with study medication during run-in period.

9. Severe renal dysfunction or disease (based on calculated creatinine clearance less than 30 mL/min/1.73 m2) at Screening.

10. Known or suspected unilateral or bilateral renal artery stenosis.

11. History of drug abuse or a history of alcohol abuse within the past 2 years.

12. Previous history of cancer that has not been in remission for at least 5 years prior to the first dose of study drug.

13. Type 1 or poorly controlled type 2 diabetes mellitus.

14. Alanine aminotransferase level of greater than 2.5 times the upper limit of normal, active liver disease, or jaundice.

15. Hyperkalemia.

16. Upper arm circumference less than 24 cm or greater than 42 cm.

17. Works night (3rd) shift.

18. Currently is participating in another investigational study or has participated in an investigational study within 30 days prior to randomization.

19. Any other serious disease or condition at Screening (or Randomization) that would compromise participant safety, might affect life expectancy, or make it difficult to successfully manage and follow the participant according to the protocol.

20. Randomized in a previous azilsartan medoxomil study.

21. 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Takeda Global Research & Development Center, Inc.

Principal Investigators

Executive Medical Director Clinical Science

Role: STUDY_DIRECTOR

Takeda

Locations

Alabaster, Alabama, United States

Huntsville, Alabama, United States

Tempe, Arizona, United States

Freemont, California, United States

Garden Grove, California, United States

Long Beach, California, United States

Riverside, California, United States

Sacramento, California, United States

San Diego, California, United States

Whittier, California, United States

Newark, Delaware, United States

Hialeah, Florida, United States

Hollywood, Florida, United States

Miami, Florida, United States

Pembroke Pines, Florida, United States

Atlanta, Georgia, United States

Waycross, Georgia, United States

Chicago, Illinois, United States

Avon, Indiana, United States

Elkhart, Indiana, United States

Indianapolis, Indiana, United States

Lexington, Kentucky, United States

Baltimore, Maryland, United States

Ann Arbor, Michigan, United States

Bingham Farms, Michigan, United States

Southfield, Michigan, United States

Florissant, Missouri, United States

Brooklyn, New York, United States

Hickory, North Carolina, United States

Raleigh, North Carolina, United States

Salisbury, North Carolina, United States

Shelby, North Carolina, United States

Akron, Ohio, United States

Centerville, Ohio, United States

Cincinnati, Ohio, United States

Columbus, Ohio, United States

Willoughby Hills, Ohio, United States

Zanesville, Ohio, United States

Oklahoma City, Oklahoma, United States

Downingtown, Pennsylvania, United States

Jenkintown, Pennsylvania, United States

Anderson, South Carolina, United States

Charleston, South Carolina, United States

Simpsonville, South Carolina, United States

Spartanburg, South Carolina, United States

Dallas, Texas, United States

Friendswood, Texas, United States

Houston, Texas, United States

Irving, Texas, United States

Katy, Texas, United States

Missouri City, Texas, United States

North Richland Hills, Texas, United States

Pearland, Texas, United States

Sugarland, Texas, United States

Riverton, Utah, United States

Salt Lake City, Utah, United States

Arlington, Virginia, United States

Burke, Virginia, United States

Manassas, Virginia, United States

Port Orchard, Washington, United States

Aguas Buenas, , Puerto Rico

Aibonito, , Puerto Rico

Loíza, , Puerto Rico

San Juan, , Puerto Rico

Countries

United States; Puerto Rico

Other Identifiers

U1111-1113-8925

Identifier Type: REGISTRY

Identifier Source: secondary_id

01-06-TL-491-011

Identifier Type: -

Identifier Source: org_study_id