Efficacy and Safety of Azilsartan Medoxomil and Chlorthalidone Compared to Olmesartan Medoxomil and Hydrochlorothiazide in Participants With Moderate to Severe Hypertension.

NCT ID: NCT01033071

Last Updated: 2012-02-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1071 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-31
• Study Completion Date: 2010-11-30

Brief Summary

The purpose of this study is to compare the antihypertensive effect of azilsartan medoxomil plus chlorthalidone, once daily (QD), to olmesartan medoxomil plus hydrochlorothiazide in participants with moderate to severe hypertension.

Detailed Description

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. As the population ages, the prevalence of hypertension will continue to increase if broad and effective preventive measures are not implemented. Despite the availability of antihypertensive agents, hypertension remains inadequately controlled; only about one third of patients continue to maintain control successfully.

Treatment algorithms for essential hypertension commonly include thiazides or thiazide-like diuretics, either alone or as part of combination treatment. Chlorthalidone is a commercially available, orally administered thiazide-type diuretic agent.

TAK-491 (azilsartan medoxomil) is an angiotensin II receptor blocker developed by Takeda to treat participants with essential hypertension.

This study will compare the safety and tolerability of azilsartan medoxomil plus chlorthalidone (TAK-491CLD) fixed-dose combination to olmesartan medoxomil plus hydrochlorothiazide fixed-dose combination.

Conditions

Essential Hypertension

Study Design

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

Study Groups

Azilsartan Medoxomil 20-40mg/Chlorthalidone 12.5-25mg QD

Group Type: EXPERIMENTAL

Azilsartan medoxomil and chlorthalidone

Intervention Type: DRUG

Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks.

Participants will be force titrated at Week 4 to azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks.

Participants will then be force titrated at Week 8 to azilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks.

Azilsartan Medoxomil 40-80mg/Chlorthalidone 12.5-25mg QD

Group Type: EXPERIMENTAL

Azilsartan medoxomil and chlorthalidone

Intervention Type: DRUG

Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks.

Participants will be force titrated at Week 4 to azilsartan medoxomil 80 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks.

Participants will then be force titrated at Week 8 to azilsartan medoxomil 80 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks.

Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD

Group Type: ACTIVE_COMPARATOR

Olmesartan medoxomil and hydrochlorothiazide

Intervention Type: DRUG

Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily and azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for up to 4 weeks.

Participants will be force titrated at Week 4 to olmesartan medoxomil 40 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily for the next 4 weeks.

Participants will then be force titrated at Week 8 to olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg combination tablets, orally, once daily for the next 4 weeks.

Interventions

Azilsartan medoxomil and chlorthalidone

Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks.

Participants will be force titrated at Week 4 to azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks.

Participants will then be force titrated at Week 8 to azilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks.

Intervention Type: DRUG

Azilsartan medoxomil and chlorthalidone

Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks.

Participants will be force titrated at Week 4 to azilsartan medoxomil 80 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks.

Participants will then be force titrated at Week 8 to azilsartan medoxomil 80 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks.

Intervention Type: DRUG

Olmesartan medoxomil and hydrochlorothiazide

Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily and azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for up to 4 weeks.

Participants will be force titrated at Week 4 to olmesartan medoxomil 40 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily for the next 4 weeks.

Participants will then be force titrated at Week 8 to olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg combination tablets, orally, once daily for the next 4 weeks.

Intervention Type: DRUG

Other Intervention Names

azilsartan medoxomil plus chlorthalidone; TAK-491CLD; azilsartan medoxomil plus chlorthalidone; TAK-491CLD; Benicar HCT®

Eligibility Criteria

Inclusion Criteria

1. Has a mean sitting clinic systolic blood pressure greater than or equal to 160 and less than or equal to 190 mm Hg.

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 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.

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

5. Has secondary hypertension of any etiology.

6. 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.

7. Has clinically significant cardiac conduction defects.

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

9. Has severe renal dysfunction or disease.

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

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

12. Has poorly-controlled diabetes mellitus at Screening.

13. Has hypokalemia or hyperkalemia.

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

15. 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.

16. Has known hypersensitivity to angiotensin II receptor blockers or thiazide-type diuretics or other sulfonamide-derived compounds.

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

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

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sr VP Clinical Science

Role: STUDY_DIRECTOR

Takeda

Locations

Gulf Shores, Alabama, United States

Litchfield Park, Arizona, United States

Mesa, Arizona, United States

Scottsdale, Arizona, United States

Tucson, Arizona, United States

Buena Park, California, United States

Carmichael, California, United States

Greenbrae, California, United States

Irvine, California, United States

Paramount, California, United States

Sacramento, California, United States

San Diego, California, United States

San Francisco, California, United States

Spring Valley, California, United States

Wildomar, California, United States

Colorado Springs, Colorado, United States

Milford, Connecticut, United States

Waterbury, Connecticut, United States

Newark, Delaware, United States

Aventura, Florida, United States

Clearwater, Florida, United States

DeLand, Florida, United States

Fort Lauderdale, Florida, United States

Miami, Florida, United States

Ocala, Florida, United States

Plant City, Florida, United States

Tallahassee, Florida, United States

Tampa, Florida, United States

West Palm Beach, Florida, United States

Winter Haven, Florida, United States

Dunwoody, Georgia, United States

Roswell, Georgia, United States

Suwanee, Georgia, United States

Chicago, Illinois, United States

Melrose Park, Illinois, United States

Naperville, Illinois, United States

Avon, Indiana, United States

Indianapolis, Indiana, United States

Valparaiso, Indiana, United States

Crestview Hills, Kentucky, United States

Lexington, Kentucky, United States

Auburn, Maine, United States

Brockton, Massachusetts, United States

Hyannis, Massachusetts, United States

West Yarmouth, Massachusetts, United States

Ann Arbor, Michigan, United States

City of Saint Peters, Missouri, United States

St Louis, Missouri, United States

Henderson, Nevada, United States

Margate City, New Jersey, United States

Wildwood Crest, New Jersey, United States

Albuquerque, New Mexico, United States

Glens Falls, New York, United States

Boiling Springs, North Carolina, United States

Raleigh, North Carolina, United States

Salisbury, North Carolina, United States

Cincinnati, Ohio, United States

Columbus, Ohio, United States

Willoughby Hills, Ohio, United States

Oklahoma City, Oklahoma, United States

Yukon, Oklahoma, United States

Ashland, Oregon, United States

Portland, Oregon, United States

Bensalem, Pennsylvania, United States

Feasterville, Pennsylvania, United States

Lansdale, Pennsylvania, United States

Pittsburgh, Pennsylvania, United States

Reading, Pennsylvania, United States

Tipton, Pennsylvania, United States

Cranston, Rhode Island, United States

Cumberland, Rhode Island, United States

Mt. Pleasant, South Carolina, United States

Simpsonville, South Carolina, United States

Beaumont, Texas, United States

Dallas, Texas, United States

Houston, Texas, United States

North Richland Hills, Texas, United States

San Antonio, Texas, United States

Magna, Utah, United States

Manassas, Virginia, United States

Lakewood, Washington, United States

Port Orchard, Washington, United States

Madison, Wisconsin, United States

Menomonee Falls, Wisconsin, United States

Abbotsford, British Columbia, Canada

Powell River, British Columbia, Canada

Mount Pearl, Newfoundland and Labrador, Canada

Halifax, Nova Scotia, Canada

London, Ontario, Canada

Ottawa, Ontario, Canada

Sarnia, Ontario, Canada

Vaughan, Ontario, Canada

Whitby, Ontario, Canada

Woodstock, Ontario, Canada

Countries

United States; Canada

References

Cushman WC, Bakris GL, White WB, Weber MA, Sica D, Roberts A, Lloyd E, Kupfer S. Azilsartan medoxomil plus chlorthalidone reduces blood pressure more effectively than olmesartan plus hydrochlorothiazide in stage 2 systolic hypertension. Hypertension. 2012 Aug;60(2):310-8. doi: 10.1161/HYPERTENSIONAHA.111.188284. Epub 2012 Jun 18.

Reference Type: DERIVED

PMID: 22710649 (View on PubMed)

Other Identifiers

U1111-1112-4298

Identifier Type: REGISTRY

Identifier Source: secondary_id

TAK-491CLD_303

Identifier Type: -

Identifier Source: org_study_id