Efficacy and Safety of Azilsartan Medoxomil, Once Daily (QD), Co-Administered With Amlodipine in Participants With Essential Hypertension

NCT ID: NCT00591266

Last Updated: 2011-07-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 566 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 efficacy and safety of azilsartan medoxomil, once daily (QD), co-administered with amlodipine in treating individuals with essential hypertension, compared to treatment with amlodipine alone.

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.

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, azilsartan, which is a selective antagonist of the angiotensin II type 1 receptor subtype.

Amlodipine is a slow-channel blocker that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. It is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure.

This study is being conducted to determine whether administration of azilsartan medoxomil in combination with amlodipine in participants with uncontrolled hypertension is more efficacious in reducing systolic blood pressure than amlodipine alone. 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 and Amlodipine 5 mg QD

Group Type: EXPERIMENTAL

Azilsartan Medoxomil and amlodipine

Intervention Type: DRUG

Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.

Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD

Group Type: EXPERIMENTAL

Azilsartan Medoxomil and amlodipine

Intervention Type: DRUG

Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.

Amlodipine 5 mg QD

Group Type: ACTIVE_COMPARATOR

Amlodipine

Intervention Type: DRUG

Azilsartan medoxomil placebo-matching tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.

Interventions

Azilsartan Medoxomil and amlodipine

Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.

Intervention Type: DRUG

Azilsartan Medoxomil and amlodipine

Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.

Intervention Type: DRUG

Amlodipine

Azilsartan medoxomil placebo-matching tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.

Intervention Type: DRUG

Other Intervention Names

Norvasc; TAK-491; Edarbi; Norvasc; TAK-491; Edarbi; Norvasc

Eligibility Criteria

Inclusion Criteria

1. Has essential hypertension and 24-hour mean systolic blood pressure greater than or equal to 140 mm Hg and less than or equal to 180 mm Hg.

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 within the reference range for the testing laboratory or the results are deemed not clinically significant for inclusion into this study by the investigator.

4. Is willing to discontinue current antihypertensive medications.

Exclusion Criteria

1. Has sitting trough clinic diastolic blood pressure greater than 119 mm Hg.

2. Has a baseline 24 hour ambulatory blood pressure monitoring reading of insufficient quality.

3. The subject is hypersensitive to angiotensin II receptor blockers or calcium channel blockers.

4. 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.

5. Has clinically significant cardiac conduction defects.

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

7. Has secondary hypertension of any etiology

8. Is non-compliant with study medication during placebo run-in period.

9. Has severe renal dysfunction or disease.

10. Has known or suspected unilateral or bilateral renal artery stenosis.

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

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

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

14. Has hyperkalemia as defined by the central laboratory normal reference range,

15. Has an alanine aminotransferase level of greater than 2.5 times the upper limit of normal, active liver disease or jaundice.

16. Has an upper arm circumference less than 24 cm or greater than 42 cm.

17. Works night (3rd) shift.

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

19. Has any other serious disease or condition that would compromise subject safety or make it difficult to successfully manage and follow the subject according to the protocol.

20. Has been randomized in a previous TAK-491 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

Mesa, Arizona, United States

Phoenix, Arizona, United States

Anaheim, California, United States

Beverly Hills, California, United States

Burbank, California, United States

Burlingame, California, United States

La Jolla, California, United States

Orange, California, United States

Roseville, California, United States

Tustin, California, United States

Wheat Ridge, Colorado, United States

Newark, Delaware, United States

Washington D.C., District of Columbia, United States

Hialeah, Florida, United States

Longwood, Florida, United States

Tampa, Florida, United States

Honolulu, Hawaii, United States

Boise, Idaho, United States

Chicago, Illinois, United States

Gurnee, Illinois, United States

Peoria, Illinois, United States

Elkhart, Indiana, United States

Crestview Hills, Kentucky, United States

Lexington, Kentucky, United States

Riverdale, Maryland, United States

Brockton, Massachusetts, United States

Haverhill, Massachusetts, United States

North Dartmouth, Massachusetts, United States

Kansas City, Missouri, United States

Omaha, Nebraska, United States

Raleigh, North Carolina, United States

Akron, Ohio, United States

Canton, Ohio, United States

Cincinnati, Ohio, United States

Mogadore, Ohio, United States

Norman, Oklahoma, United States

Tulsa, Oklahoma, United States

Warminster, Pennsylvania, United States

Cumberland, Rhode Island, United States

Arlington, Texas, United States

Austin, Texas, United States

Carrollton, Texas, United States

Dallas, Texas, United States

Houston, Texas, United States

Irvine, Texas, United States

Lake Jackson, Texas, United States

North Richland Hills, Texas, United States

Manassas, Virginia, United States

Renton, Washington, United States

Menomonee Falls, Wisconsin, United States

Countries

United States

Other Identifiers

U1111-1113-9132

Identifier Type: REGISTRY

Identifier Source: secondary_id

01-05-TL-491-010

Identifier Type: -

Identifier Source: org_study_id