Clinical trial NCT00591253: Efficacy and Safety of Azilsartan Medoxomil in African American Participants With Essential Hypertension
Official title: A Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of TAK-491 in Black Subjects With Essential Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypertension
Keywords: Blood pressure
blood pressure monitoring ambulatory
Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2008-01-11
Enrollment: 413
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change From Baseline in the 24-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
timeFrame: Baseline and Week 6.
Secondary outcomes:
measure: Change From Baseline in Mean Trough Clinic Sitting Systolic Blood Pressure
timeFrame: Baseline and Week 6.
measure: Change From Baseline in the 24-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
timeFrame: Baseline and Week 6.
measure: Change From Baseline in Mean Trough Clinic Sitting Diastolic Blood Pressure
timeFrame: Baseline and Week 6.
measure: Change From Baseline in Daytime (6am to 10 pm) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
timeFrame: Baseline and Week 6.
measure: Change From Baseline in Daytime (6am to 10 pm) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
timeFrame: Baseline and Week 6.
measure: Change From Baseline in the Nighttime (12 am to 6 am) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
timeFrame: Baseline and Week 6.
measure: Change From Baseline in the Nighttime (12 am to 6 am) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
timeFrame: Baseline and Week 6.
measure: Change From Baseline in the 12-hr Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
timeFrame: Baseline and Week 6.
measure: Change From Baseline in the 12-hr Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
timeFrame: Baseline and Week 6.
measure: Change From Baseline in the Trough (22-24-hr) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
timeFrame: Baseline and Week 6.
measure: Change From Baseline in the Trough (22-24-hr) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
timeFrame: Baseline and Week 6.
measure: Percentage of Participants Who Achieve a Clinic Systolic Blood Pressure Response, Defined as < 140 mm Hg and/or Reduction From Baseline ≥ 20 mm Hg
timeFrame: Baseline and Week 6.
measure: Percentage of Participants Who Achieve a Clinic Diastolic Blood Pressure Response, Defined as < 90 mm Hg and/or Reduction From Baseline ≥ 10 mm Hg
timeFrame: Baseline and Week 6.
measure: Percentage of Participants Who Achieve Both a Clinic Diastolic and Systolic Blood Pressure Response
timeFrame: Baseline and Week 6.
Other outcomes:
Locations:
city: Alabaster
country: United States
state: Alabama
city: Huntsville
country: United States
state: Alabama
city: Tempe
country: United States
state: Arizona
city: Freemont
country: United States
state: California
city: Garden Grove
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Riverside
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Diego
country: United States
state: California
city: Whittier
country: United States
state: California
city: Newark
country: United States
state: Delaware
city: Hialeah
country: United States
state: Florida
city: Hollywood
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Pembroke Pines
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Waycross
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Avon
country: United States
state: Indiana
city: Elkhart
country: United States
state: Indiana
city: Indianapolis
country: United States
state: Indiana
city: Lexington
country: United States
state: Kentucky
city: Baltimore
country: United States
state: Maryland
city: Ann Arbor
country: United States
state: Michigan
city: Bingham Farms
country: United States
state: Michigan
city: Southfield
country: United States
state: Michigan
city: Florissant
country: United States
state: Missouri
city: Brooklyn
country: United States
state: New York
city: Hickory
country: United States
state: North Carolina
city: Raleigh
country: United States
state: North Carolina
city: Salisbury
country: United States
state: North Carolina
city: Shelby
country: United States
state: North Carolina
city: Akron
country: United States
state: Ohio
city: Centerville
country: United States
state: Ohio
city: Cincinnati
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Willoughby Hills
country: United States
state: Ohio
city: Zanesville
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Downingtown
country: United States
state: Pennsylvania
city: Jenkintown
country: United States
state: Pennsylvania
city: Anderson
country: United States
state: South Carolina
city: Charleston
country: United States
state: South Carolina
city: Simpsonville
country: United States
state: South Carolina
city: Spartanburg
country: United States
state: South Carolina
city: Dallas
country: United States
state: Texas
city: Friendswood
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Irving
country: United States
state: Texas
city: Katy
country: United States
state: Texas
city: Missouri City
country: United States
state: Texas
city: North Richland Hills
country: United States
state: Texas
city: Pearland
country: United States
state: Texas
city: Sugarland
country: United States
state: Texas
city: Riverton
country: United States
state: Utah
city: Salt Lake City
country: United States
state: Utah
city: Arlington
country: United States
state: Virginia
city: Burke
country: United States
state: Virginia
city: Manassas
country: United States
state: Virginia
city: Port Orchard
country: United States
state: Washington
city: Aguas Buenas
country: Puerto Rico
city: Aibonito
country: Puerto Rico
city: Loiza
country: Puerto Rico
city: San Juan
country: Puerto Rico
Study officials:
affiliation: Takeda
name: Executive Medical Director Clinical Science
role: STUDY_DIRECTOR
References: