An Efficacy and Safety Study of Azilsartan Medoxomil Compared to Valsartan and Olmesartan in Participants With Essential Hypertension.

NCT ID: NCT00696436

Last Updated: 2011-04-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1291 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-04-30
• Study Completion Date: 2009-08-31

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of azilsartan medoxomil, once daily (QD), compared to placebo, valsartan 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 successfully maintain control.

A major component of blood pressure regulation is the renin-angiotensin-aldosterone system. This is a system of hormone-mediated feedback interactions that result 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 and has multiple effects on the cardiovascular system and on electrolyte homeostasis.

TAK-491 (azilsartan medoxomil) is an angiotensin II type 1 receptor antagonist currently being tested as a treatment for essential hypertension.

Study participation is anticipated to be about 10 weeks. Multiple procedures will occur at each visit which may include fasting, blood collection, urine collection, physical examinations, electrocardiograms and ambulatory blood pressure monitoring. Outside of the study center, participants will be required wear an ambulatory blood pressure monitoring device at 24 hour intervals.

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 20 mg, tablets and matching placebo comparator orally once daily for two weeks.

Increased to azilsartan medoxomil 40 mg tablets and matching placebo comparator orally, once daily for up to four weeks.

Azilsartan Medoxomil 80 mg QD

Group Type: EXPERIMENTAL

Azilsartan medoxomil

Intervention Type: DRUG

Azilsartan medoxomil 40 mg, tablets and matching placebo comparator orally, once daily for two weeks.

Increased to Azilsartan medoxomil 80 mg, tablets and matching placebo comparator orally, once daily for up to four weeks.

Valsartan 320 mg QD

Group Type: ACTIVE_COMPARATOR

Valsartan

Intervention Type: DRUG

Valsartan 160 mg, tablets, and matching placebo comparator orally, once daily for two weeks.

Increased to Valsartan 320 mg, tablets, and matching placebo comparator, orally, once daily for up to four weeks.

Olmesartan 40 mg QD

Group Type: ACTIVE_COMPARATOR

Olmesartan

Intervention Type: DRUG

Olmesartan 20 mg, tablets and matching placebo comparator, orally, once daily for two weeks.

Increased to Olmesartan 40 mg, tablets and matching placebo comparator, orally, once daily for up to four weeks.

Placebo QD

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching placebo, orally, once daily for up to six weeks.

Interventions

Azilsartan medoxomil

Azilsartan medoxomil 20 mg, tablets and matching placebo comparator orally once daily for two weeks.

Increased to azilsartan medoxomil 40 mg tablets and matching placebo comparator orally, once daily for up to four weeks.

Intervention Type: DRUG

Azilsartan medoxomil

Azilsartan medoxomil 40 mg, tablets and matching placebo comparator orally, once daily for two weeks.

Increased to Azilsartan medoxomil 80 mg, tablets and matching placebo comparator orally, once daily for up to four weeks.

Intervention Type: DRUG

Valsartan

Valsartan 160 mg, tablets, and matching placebo comparator orally, once daily for two weeks.

Increased to Valsartan 320 mg, tablets, and matching placebo comparator, orally, once daily for up to four weeks.

Intervention Type: DRUG

Olmesartan

Olmesartan 20 mg, tablets and matching placebo comparator, orally, once daily for two weeks.

Increased to Olmesartan 40 mg, tablets and matching placebo comparator, orally, once daily for up to four weeks.

Intervention Type: DRUG

Placebo

Matching placebo, orally, once daily for up to six weeks.

Intervention Type: DRUG

Other Intervention Names

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

Eligibility Criteria

Inclusion Criteria

1. Essential hypertension (sitting systolic blood pressure between 150 and 180 mm Hg, inclusive, at Day -1 and 24-hour mean systolic blood pressure between 130 and 170 mm Hg, inclusive, at Day 1).

2. Capable of understanding and complying with protocol requirements.

3. 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

4. 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.

5. Willing to discontinue current antihypertensive medications at Screening Day 21 visit. If the participant is on amlodipine prior to Screening, the participant is willing to discontinue this medication at Screening Day -28.

Exclusion Criteria

1. Sitting diastolic blood pressure greater than 114 mm Hg at Day -1 (day prior to Randomization).

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

3. Taking or expected to take an excluded medication as described in the Excluded Medications.

4. Hypersensitive to angiotensin II receptor blockers.

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

6. Clinically significant cardiac conduction defects.

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

8. Secondary hypertension of any etiology.

9. Noncompliant (less than 70% or greater than 130%) with study medication during run-in period.

10. Moderate to severe renal dysfunction or disease.

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

12. History of drug or alcohol abuse 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 participants with basal cell or stage I squamous cell carcinoma of the skin).

14. Type 1 or poorly-controlled type 2 diabetes mellitus (glycosylate hemoglobin greater than 8.0%) at Screening.

15. Hyperkalemia as defined by the central laboratory normal reference range at Screening.

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

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

18. Works night (3rd) shift (defined as 11 PM [2300] to 7 AM [0700]).

19. Unwilling or unable to comply with the protocol or scheduled appointments.

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

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

22. Has been randomized in a previous azilsartan medoxomil study.

23. 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

Ozark, Alabama, United States

Green Valley, Arizona, United States

Litchfield Park, Arizona, United States

Mesa, Arizona, United States

Tempe, Arizona, United States

Carmichael, California, United States

Chula Vista, California, United States

Lincoln, California, United States

Mission Viejo, California, United States

National City, California, United States

Pasadena, California, United States

Riverside, California, United States

Sacramento, California, United States

San Diego, California, United States

San Dimas, California, United States

San Francisco, California, United States

San Ramon, California, United States

Santa Ana, California, United States

Vista, California, United States

Colorado Springs, Colorado, United States

Denver, Colorado, United States

Littleton, Colorado, United States

Longmont, Colorado, United States

Cape Coral, Florida, United States

Clearwater, Florida, United States

Largo, Florida, United States

Miami, Florida, United States

New Port Richey, Florida, United States

New Smyrna Beach, Florida, United States

Palm Harbor, Florida, United States

Tallahassee, Florida, United States

Dunwoody, Georgia, United States

Roswell, Georgia, United States

Arlington Heights, Illinois, United States

Belleville, Illinois, United States

Champaign, Illinois, United States

Chicago, Illinois, United States

Peoria, Illinois, United States

Vernon Hills, Illinois, United States

Evansville, Indiana, United States

Indianapolis, Indiana, United States

Terre Haute, Indiana, United States

Kansas City, Kansas, United States

Overland Park, Kansas, United States

Shawnee, Kansas, United States

Biddeford, Maine, United States

Norwood, Maine, United States

Baltimore, Maryland, United States

Towson, Maryland, United States

Brooklyn Center, Minnesota, United States

Chesterfield, Missouri, United States

Jefferson City, Missouri, United States

Kansas City, Missouri, United States

St Louis, Missouri, United States

Billings, Montana, United States

Las Vegas, Nevada, United States

Margate City, New Jersey, United States

Glens Falls, New York, United States

Great Neck, New York, United States

New Hyde Park, New York, United States

New Windsor, New York, United States

New York, New York, United States

Charlotte, North Carolina, United States

Raleigh, North Carolina, United States

Columbus, Ohio, United States

Norman, Oklahoma, United States

Tulsa, Oklahoma, United States

Yukon, Oklahoma, United States

Ashland, Oregon, United States

Eugene, Oregon, United States

Medford, Oregon, United States

Portland, Oregon, United States

Pittsburgh, Pennsylvania, United States

Tipton, Pennsylvania, United States

Charleston, South Carolina, United States

Murrells Inlet, South Carolina, United States

North Charleston, South Carolina, United States

Cleveland, Tennessee, United States

Bedford, Texas, United States

Dallas, Texas, United States

Houston, Texas, United States

Missouri City, Texas, United States

San Antonio, Texas, United States

Sugarland, Texas, United States

Tacoma, Washington, United States

Carlos Paz, Córdoba Province, Argentina

Córdoba, Córdoba Province, Argentina

Guaymayen, Mendoza Province, Argentina

Bahía Blanca, , Argentina

Berazategui, , Argentina

Buenos Aires, , Argentina

Corrientes, , Argentina

Haedo Pcia. de Buenos Aires, , Argentina

La Plata, , Argentina

Ramos Mejía Pcia. de Buenos Aires, , Argentina

Rosario, , Argentina

Salta, , Argentina

San Miguel de Tucumán, , Argentina

San Salvador de Jujuy, , Argentina

Belo Horizonte, , Brazil

Campinas, , Brazil

Fortaleza, , Brazil

Goiaenia, , Brazil

Joildille, , Brazil

Porto Alegre, , Brazil

Rio Janeiro, , Brazil

São Paulo, , Brazil

Sorocava, , Brazil

Aguascalientes, Aguascalientes, Mexico

Chihuahua City, Chihuahua, Mexico

Tijuana, Estado de Baja California, Mexico

León, Guanajuato, Mexico

Guadalajara, Jalapa, Mexico

Monterrey, Nuevo León, Mexico

San Luis Potosí City, San Luis Potosí, Mexico

Xalapa, Veracruz, Mexico

Mexico City, , Mexico

Querètaro, , Mexico

Arequipa, , Peru

Cusco, , Peru

Huaura, , Peru

Ica, , Peru

Lima, , Peru

Trujillo, , Peru

Aguas Buenas, , Puerto Rico

Carolina, , Puerto Rico

Jardines de Loiza, , Puerto Rico

Orocovis, , Puerto Rico

Ponce, , Puerto Rico

San Juan, , Puerto Rico

Countries

United States; Argentina; Brazil; Mexico; Peru; Puerto Rico

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)

Other Identifiers

U1111-1113-9161

Identifier Type: REGISTRY

Identifier Source: secondary_id

01-06-TL-491-019

Identifier Type: -

Identifier Source: org_study_id