Efficacy and Safety of Azilsartan Medoxomil in Participants With Essential Hypertension

NCT ID: NCT00696241

Last Updated: 2011-07-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1275 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-06-30
• Study Completion Date: 2008-10-31

Brief Summary

The purpose of this study is to determine the safety and efficacy of azilsartan medoxomil, once daily (QD), compared to placebo and olmesartan in 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.

TAK-491 (azilsartan medoxomil) is an angiotensin II receptor blocker and this study is being conducted to evaluate the efficacy and safety of oral azilsartan medoxomil compared to placebo and olmesartan in subjects with essential hypertension.

Individuals who want to participate in this study will be required to provide written informed consent. Study participation is anticipated to be about 11 weeks. Multiple procedures will occur at each visit which may include fasting, blood collection, urine collection, vital signs including sitting blood pressure and pulse, body height and weight, physical examinations and electrocardiograms. Outside of the study center, participants will be required to wear an ambulatory blood pressure monitoring device at 24 hour intervals.

Conditions

Hypertension

Keywords

Essential Hypertension; Cardiovascular Disease; High Blood Pressure; Drug Therapy

Study Design

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

Study Groups

Azilsartan Medoxomil 20 mg QD

Group Type: EXPERIMENTAL

Azilsartan medoxomil and olmesartan

Intervention Type: DRUG

Azilsartan medoxomil 20 mg, tablets, azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets and olmesartan 40 mg placebo-matching tablets, orally, for up to 6 weeks.

Azilsartan Medoxomil 40 mg QD

Group Type: EXPERIMENTAL

Azilsartan medoxomil and olmesartan

Intervention Type: DRUG

Azilsartan medoxomil 40 mg, tablets, azilsartan medoxomil 20 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets and olmesartan 40 mg placebo-matching tablets, orally, for up to 6 weeks.

Azilsartan Medoxomil 80 mg QD

Group Type: EXPERIMENTAL

Azilsartan medoxomil and olmesartan

Intervention Type: DRUG

Azilsartan medoxomil 80 mg, tablets, azilsartan medoxomil 20 mg placebo-matching tablets, azilsartan medoxomil 40 mg placebo-matching tablets and olmesartan 40 mg placebo-matching tablets, orally, once daily for up to 6 weeks.

Olmesartan 40 mg QD

Group Type: ACTIVE_COMPARATOR

Olmesartan

Intervention Type: DRUG

Olmesartan 40 mg, tablets, azilsartan medoxomil 20 mg placebo-matching tablets, azilsartan medoxomil 40 mg placebo-matching tablets and azilsartan medoxomil 80 mg placebo-matching tablets, orally, once daily for up to 6 weeks.

Placebo QD

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Azilsartan medoxomil 20 mg placebo-matching tablets, azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and olmesartan 40 mg placebo- matching tablets, orally, once daily for up to 6 weeks.

Interventions

Azilsartan medoxomil and olmesartan

Azilsartan medoxomil 20 mg, tablets, azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets and olmesartan 40 mg placebo-matching tablets, orally, for up to 6 weeks.

Intervention Type: DRUG

Azilsartan medoxomil and olmesartan

Azilsartan medoxomil 40 mg, tablets, azilsartan medoxomil 20 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets and olmesartan 40 mg placebo-matching tablets, orally, for up to 6 weeks.

Intervention Type: DRUG

Azilsartan medoxomil and olmesartan

Azilsartan medoxomil 80 mg, tablets, azilsartan medoxomil 20 mg placebo-matching tablets, azilsartan medoxomil 40 mg placebo-matching tablets and olmesartan 40 mg placebo-matching tablets, orally, once daily for up to 6 weeks.

Intervention Type: DRUG

Olmesartan

Olmesartan 40 mg, tablets, azilsartan medoxomil 20 mg placebo-matching tablets, azilsartan medoxomil 40 mg placebo-matching tablets and azilsartan medoxomil 80 mg placebo-matching tablets, orally, once daily for up to 6 weeks.

Intervention Type: DRUG

Placebo

Azilsartan medoxomil 20 mg placebo-matching tablets, azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and olmesartan 40 mg placebo- matching tablets, orally, once daily for up to 6 weeks.

Intervention Type: DRUG

Other Intervention Names

TAK-491; Edarbi; TAK-491; Edarbi; TAK-491; Edarbi; Benicar®

Eligibility Criteria

Inclusion Criteria

1. Has essential hypertension (defined as sitting trough clinic systolic blood pressure between 150 and 180 mm Hg, inclusive at Day minus 1) and 24-hour mean systolic blood pressure greater than or equal to 130 mm Hg and less than or equal to 170 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. Clinical laboratory evaluations (including clinical chemistry, hematology, and complete urinalysis) 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. The subject is 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. Sitting trough clinic diastolic blood pressure greater than 114 mm Hg at Day minus 1.

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

3. History of myocardial infarction, heart failure, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebrovascular accident, or transient ischemic attack.

4. Clinically significant cardiac conduction defects (eg, third degree atrioventricular block, left bundle branch block, sick sinus syndrome, atrial fibrillation or atrial flutter).

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

6. Secondary hypertension of any etiology.

7. Is noncompliant (less than 70% or greater than 130%) with study medication during Placebo Run-In Period.

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

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

10. 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.

11. 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 I squamous cell carcinoma of the skin).

12. Type 1 or poorly controlled type 2 diabetes mellitus (glycosylated hemoglobin greater than 8.0%) at Screening.

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

14. Hyperkalemia (defined as serum potassium greater than the upper limit of normal per the central laboratory) at Screening.

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

16. Works night (3rd) shift (defined as 11 PM to 7 AM).

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

18. 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.

19. Randomized in a previous azilsartan medoxomil study.

• 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

VP Clinical Science Strategy

Role: STUDY_DIRECTOR

Takeda

Locations

Birmingham, Alabama, United States

Huntsville, Alabama, United States

Mesa, Arizona, United States

Phoenix, Arizona, United States

Tempe, Arizona, United States

Little Rock, Arkansas, United States

Tempe, Arkansas, United States

Beverly Hills, California, United States

Carmichael, California, United States

Fountain Valley, California, United States

Long Beach, California, United States

Los Gatos, California, United States

Orangevale, California, United States

Sacramento, California, United States

Santa Ana, California, United States

Spring Valley, California, United States

Tustin, California, United States

Westlake Village, California, United States

Colorado Springs, Colorado, United States

Farmington, Connecticut, United States

Hollywood, Florida, United States

Jacksonville, Florida, United States

Jupiter, Florida, United States

Melbourne, Florida, United States

Miami, Florida, United States

Naples, Florida, United States

Ocala, Florida, United States

Pembroke Pines, Florida, United States

Sarasota, Florida, United States

St. Petersburg, Florida, United States

Augusta, Georgia, United States

Lawrenceville, Georgia, United States

Chicago, Illinois, United States

Melrose Park, Illinois, United States

Naperville, Illinois, United States

Round Lake Beach, Illinois, United States

Valparaiso, Indiana, United States

Wichita, Kansas, United States

Erlanger, Kentucky, United States

Lexington, Kentucky, United States

Auburn, Maine, United States

West Yarmouth, Massachusetts, United States

Benzonia, Michigan, United States

Chelsea, Michigan, United States

Omaha, Nebraska, United States

Trenton, New Jersey, United States

Wildwood Crest, New Jersey, United States

Albuquerque, New Mexico, United States

Brooklyn, New York, United States

Orangevale, New York, United States

Rochester, New York, United States

Burlington, North Carolina, United States

Charlotte, North Carolina, United States

Raleigh, North Carolina, United States

Salisbury, North Carolina, United States

Statesville, North Carolina, United States

Wilmington, North Carolina, United States

Winston-Salem, North Carolina, United States

Kettering, Ohio, United States

Lyndhurst, Ohio, United States

Marion, Ohio, United States

Norman, Oklahoma, United States

Oklahoma City, Oklahoma, United States

Altoona, Pennsylvania, United States

Reading, Pennsylvania, United States

Mt. Pleasant, South Carolina, United States

Simpsonville, South Carolina, United States

Taylors, South Carolina, United States

Nashville, Tennessee, United States

New Tazewell, Tennessee, United States

Dallas, Texas, United States

Houston, Texas, United States

Lake Jackson, Texas, United States

North Richland Hills, Texas, United States

San Antonio, Texas, United States

Draper, Utah, United States

Burke, Virginia, United States

Norfolk, Virginia, United States

Tacoma, Washington, United States

Madison, Wisconsin, United States

Provincia de Buenos Aires, , Argentina

Provincia de Cordoba, , Argentina

Aguascalientes, , Mexico

Mexico City, , Mexico

San Luis Potosí City, , Mexico

Countries

United States; Argentina; Mexico

References

White WB, Weber MA, Sica D, Bakris GL, Perez A, Cao C, Kupfer S. Effects of the angiotensin receptor blocker azilsartan medoxomil versus olmesartan and valsartan on ambulatory and clinic blood pressure in patients with stages 1 and 2 hypertension. Hypertension. 2011 Mar;57(3):413-20. doi: 10.1161/HYPERTENSIONAHA.110.163402. Epub 2011 Jan 31.

Reference Type: RESULT

PMID: 21282560 (View on PubMed)

Bakris GL, Sica D, Weber M, White WB, Roberts A, Perez A, Cao C, Kupfer S. The comparative effects of azilsartan medoxomil and olmesartan on ambulatory and clinic blood pressure. J Clin Hypertens (Greenwich). 2011 Feb;13(2):81-8. doi: 10.1111/j.1751-7176.2010.00425.x.

Reference Type: RESULT

PMID: 21272195 (View on PubMed)

Other Identifiers

U1111-1113-8905

Identifier Type: REGISTRY

Identifier Source: secondary_id

01-05-TL-491-008

Identifier Type: -

Identifier Source: org_study_id