Clinical trial NCT00696436: An Efficacy and Safety Study of Azilsartan Medoxomil Compared to Valsartan and Olmesartan in Participants With Essential Hypertension.
Official title: A Double-Blind, Randomized, Placebo-Controlled, 5-Arm Titration Study to Evaluate the Efficacy and Safety of TAK-491 When Compared With Valsartan and Olmesartan in Subjects With Essential Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypertension
Keywords: Essential Hypertension
Cardiovascular Disease
High Blood Pressure
Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2008-06-12
Enrollment: 1291
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 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.

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.

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-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
timeFrame: Baseline and Week 6.
measure: Change From Baseline in the 12-hour 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: Ozark
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state: Alabama
city: Green Valley
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state: Arizona
city: Litchfield Park
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state: Arizona
city: Mesa
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state: Arizona
city: Tempe
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state: Arizona
city: Carmichael
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state: California
city: Chula Vista
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state: California
city: Lincoln
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state: California
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state: California
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city: San Diego
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city: San Dimas
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state: California
city: San Fransisco
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city: San Ramon
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city: Santa Ana
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state: California
city: Vista
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state: California
city: Colorado Springs
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state: Colorado
city: Denver
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state: Colorado
city: Littleton
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state: Colorado
city: Longmont
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state: Colorado
city: Cape Coral
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state: Florida
city: Clearwater
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state: Florida
city: Largo
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state: Florida
city: Miami
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city: New Port Richey
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state: Florida
city: New Smyrna Beach
country: United States
state: Florida
city: Palm Harbor
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state: Florida
city: Tallahassee
country: United States
state: Florida
city: Dunwoody
country: United States
state: Georgia
city: Roswell
country: United States
state: Georgia
city: Arlington Heights
country: United States
state: Illinois
city: Belleville
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state: Illinois
city: Champaign
country: United States
state: Illinois
city: Chicago
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state: Illinois
city: Peoria
country: United States
state: Illinois
city: Vernon Hills
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state: Illinois
city: Evansville
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state: Indiana
city: Indianapolis
country: United States
state: Indiana
city: Terre Haute
country: United States
state: Indiana
city: Kansas City
country: United States
state: Kansas
city: Overland Park
country: United States
state: Kansas
city: Shawnee
country: United States
state: Kansas
city: Biddeford
country: United States
state: Maine
city: Norwood
country: United States
state: Maine
city: Baltimore
country: United States
state: Maryland
city: Towson
country: United States
state: Maryland
city: Brooklyn Center
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state: Minnesota
city: Chesterfield
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state: Missouri
city: Jefferson City
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state: Missouri
city: Kansas City
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state: Missouri
city: St Louis
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state: Missouri
city: Billings
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state: Montana
city: Las Vegas
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state: Nevada
city: Margate
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state: New Jersey
city: Glens Falls
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state: New York
city: Great Neck
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state: New York
city: New Hyde Park
country: United States
state: New York
city: New Windsor
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state: New York
city: New York
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state: New York
city: Charlotte
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state: North Carolina
city: Raleigh
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state: North Carolina
city: Columbus
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state: Ohio
city: Norman
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state: Oklahoma
city: Tulsa
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state: Oklahoma
city: Yukon
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state: Oklahoma
city: Ashland
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state: Oregon
city: Eugene
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state: Oregon
city: Medford
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state: Oregon
city: Portland
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state: Oregon
city: Pittsburgh
country: United States
state: Pennsylvania
city: Tipton
country: United States
state: Pennsylvania
city: Charleston
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state: South Carolina
city: Murrells Inlet
country: United States
state: South Carolina
city: North Charleston
country: United States
state: South Carolina
city: Cleveland
country: United States
state: Tennessee
city: Bedford
country: United States
state: Texas
city: Dallas
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state: Texas
city: Houston
country: United States
state: Texas
city: Missouri City
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Sugarland
country: United States
state: Texas
city: Tacoma
country: United States
state: Washington
city: Carlos Paz
country: Argentina
state: Córdoba
city: Guaymayen
country: Argentina
state: Mendoza
city: Bahía Blanca
country: Argentina
city: Berazategui
country: Argentina
city: Buenos Aires
country: Argentina
city: Corrientes
country: Argentina
city: Córdoba
country: Argentina
city: Haedo Pcia. de Buenos Aires
country: Argentina
city: Jujuy
country: Argentina
city: La Plata
country: Argentina
city: Ramos Mejía Pcia. de Buenos Aires
country: Argentina
city: Rosario
country: Argentina
city: Salta
country: Argentina
city: San Miguel de Tucumán
country: Argentina
city: Belo Horizonte
country: Brazil
city: Campinas
country: Brazil
city: Fortaleza
country: Brazil
city: Goiaenia
country: Brazil
city: Joildille
country: Brazil
city: Porto Alegre
country: Brazil
city: Rio Janeiro
country: Brazil
city: Sao Paulo
country: Brazil
city: Sorocava
country: Brazil
city: Tijuana
country: Mexico
state: Baja California
city: León
country: Mexico
state: Guanajuato
city: Guadalajara
country: Mexico
state: Jalapa
city: Monterrey
country: Mexico
state: Nuevo Leon
city: Xalapa
country: Mexico
state: Veracruz
city: Aguascalientes
country: Mexico
city: Chihuahua
country: Mexico
city: Mexico City
country: Mexico
city: Querètaro
country: Mexico
city: San Luis Potosí
country: Mexico
city: Arequipa
country: Peru
city: Cusco
country: Peru
city: Huaura
country: Peru
city: Ica
country: Peru
city: Lima
country: Peru
city: Trujillo
country: Peru
city: Aguas Buenas
country: Puerto Rico
city: Carolina
country: Puerto Rico
city: Jardines de Loiza
country: Puerto Rico
city: Orocovis
country: Puerto Rico
city: Ponce
country: Puerto Rico
city: San Juan
country: Puerto Rico
Study officials:
affiliation: Takeda
name: Executive Medical Director Clinical Science
role: STUDY_DIRECTOR
References:
citation: 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.