Clinical trial NCT00591578: Efficacy and Safety Comparison of Azilsartan Medoxomil to Valsartan in Participants With Essential Hypertension
Official title: A Double-Blind, Randomized, Parallel-Group Study to Compare the Efficacy and Safety of TAK-491 With Valsartan in Subjects With Essential Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypertension
Keywords: Blood pressure
blood pressure monitoring, ambulatory
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2008-01-11
Enrollment: 984
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 compare the efficacy and safety of TAK-491 (azilsartan medoxomil), once daily (QD), to valsartan 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 (WHO), 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.

This study is being conducted to determine whether administration of azilsartan medoxomil in subjects with essential hypertension is more efficacious in reducing systolic blood pressure than valsartan.

Study participation is anticipated to be approximately 7 months. Outside of the study center, participants will be required to wear an ambulatory blood pressure monitoring device at 24 hour intervals.

Following completion of the 6-month double-blind treatment period, all available subjects will be offered the option to continue in a 28-week extension study with open-label azilsartan medoxomil 40 mg.

For the extension study, participants will take azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 28 weeks. Hydrochlorothiazide 12.5 mg or 25 mg or any other antihypertensive (except angiotensin II receptor blockers) may be added in a step-wise fashion to maintain blood pressure within target \<140/90 mmHg for non-diabetic subjects and \<130/80 mmHg for diabetic subjects

Eligibility criteria: Inclusion Criteria

1. 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 between 130 and 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 (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. 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. The subject has a baseline 24-hour ambulatory blood pressure monitor reading of insufficient quality.
3. 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.
4. Hypersensitive to angiotensin II receptor blockers.
5. Recent history (within the last 6 months) 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 (eg, 3rd degree atrioventricular block, left bundle branch block, sick sinus syndrome, atrial fibrillation or flutter).
7. Hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease.
8. Secondary hypertension of any etiology.
9. Non-compliant (less than 70% or greater than 130%) with study medication during placebo run-in period.
10. Severe renal dysfunction or disease (based on calculated creatinine clearance less than 30 mL per min/1.73m2) at Screening.
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 subjects with basal cell or Stage 1 squamous cell carcinoma of the skin).
14. Type 1 or poorly controlled type 2 diabetes mellitus (glycosylated hemoglobin greater than 8.0%) at Screening.
15. Hyperkalemia as defined by the central laboratory normal reference range at Screening.
16. Upper arm circumference less than 24 cm or greater than 42 cm.
17. Works night (3rd) shift (defined as 11PM to 7AM).
18. Alanine aminotransferase level of greater than 2.5 times the upper limit of normal, active liver disease, or jaundice at Screening.
19. Currently is participating in another investigational study or has participated in an investigational study within 30 days prior to randomization.
20. 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.
21. Randomized in a previous azilsartan medoxomil study.

Primary outcomes:
measure: Change From Baseline in 24-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
timeFrame: Baseline and Week 24.
Secondary outcomes:
measure: Change From Baseline in Mean Trough Clinic Sitting Systolic Blood Pressure.
timeFrame: Baseline and Week 24.
measure: Change From Baseline in the 24-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
timeFrame: Baseline and Week 24.
measure: Change From Baseline in Mean Trough Clinic Sitting Diastolic Blood Pressure
timeFrame: Baseline and Week 24.
measure: Change From Baseline in Daytime (6am to 10 pm) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
timeFrame: Baseline and Week 24.
measure: Change From Baseline in Daytime (6am to 10 pm) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
timeFrame: Baseline and Week 24.
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 24.
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 24.
measure: Change From Baseline in the 12-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
timeFrame: Baseline and Week 24.
measure: Change From Baseline in the 12-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
timeFrame: Baseline and Week 24.
measure: Change From Baseline in the Trough (22-24-hr) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
timeFrame: Baseline and Week 24.
measure: Change From Baseline in the Trough (22-24-hr) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
timeFrame: Baseline and Week 24.
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 24.
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 24.
measure: Percentage of Participants Who Achieve Both a Clinic Diastolic and Systolic Blood Pressure Response.
timeFrame: Baseline and Week 24.
Other outcomes:
Locations:
city: Huntsville
country: United States
state: Alabama
city: Glendale
country: United States
state: Arizona
city: Phoenix
country: United States
state: Arizona
city: Scottsdale
country: United States
state: Arizona
city: Tuscon
country: United States
state: Arizona
city: Beverly Hills
country: United States
state: California
city: Burbank
country: United States
state: California
city: La Jolla
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Paramount
country: United States
state: California
city: San Diego
country: United States
state: California
city: Santa Monica
country: United States
state: California
city: Spring Valley
country: United States
state: California
city: Tustin
country: United States
state: California
city: Vista
country: United States
state: California
city: Westlake Village
country: United States
state: California
city: Ridgefield
country: United States
state: Connecticut
city: Newark
country: United States
state: Delaware
city: Washington
country: United States
state: District of Columbia
city: DeLand
country: United States
state: Florida
city: Fort Lauderdale
country: United States
state: Florida
city: Hollywood
country: United States
state: Florida
city: Inverness
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Boise
country: United States
state: Idaho
city: Chicago
country: United States
state: Illinois
city: Gurnee
country: United States
state: Illinois
city: Morton
country: United States
state: Illinois
city: Park Ridge
country: United States
state: Illinois
city: Avon
country: United States
state: Indiana
city: Bloomington
country: United States
state: Indiana
city: Crestview Hills
country: United States
state: Kentucky
city: Baltimore
country: United States
state: Maryland
city: Columbia
country: United States
state: Maryland
city: Brockton
country: United States
state: Massachusetts
city: West Yarmouth
country: United States
state: Massachusetts
city: Ann Arbor
country: United States
state: Michigan
city: Florissant
country: United States
state: Missouri
city: Kansas City
country: United States
state: Missouri
city: St. Peters
country: United States
state: Missouri
city: Washington
country: United States
state: Missouri
city: Wentzville
country: United States
state: Missouri
city: Charlotte
country: United States
state: North Carolina
city: Salisbury
country: United States
state: North Carolina
city: Shelby
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Delaware
country: United States
state: Ohio
city: Mogadore
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: Eugene
country: United States
state: Oregon
city: Portland
country: United States
state: Oregon
city: Bridgeville
country: United States
state: Pennsylvania
city: Downingtown
country: United States
state: Pennsylvania
city: Jenkintown
country: United States
state: Pennsylvania
city: Lansdale
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Spartanburg
country: United States
state: South Carolina
city: Kingsport
country: United States
state: Tennessee
city: Austin
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Fort Worth
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Pearland
country: United States
state: Texas
city: Rosenberg
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Riverton
country: United States
state: Utah
city: Salt Lake City
country: United States
state: Utah
city: West Jordan
country: United States
state: Utah
city: Arlington
country: United States
state: Virginia
city: Burke
country: United States
state: Virginia
city: Norfolk
country: United States
state: Virginia
city: Lakewood
country: United States
state: Washington
city: Port Richard
country: United States
state: Washington
city: Menomonee Falls
country: United States
state: Wisconsin
city: Santiago
country: Chile
city: Temuco
country: Chile
city: Cabo San Lucas
country: Mexico
city: Colonia Escandon
country: Mexico
city: Culiacan
country: Mexico
city: Mexico City
country: Mexico
city: Monterrey Nuevo Leon
country: Mexico
city: Morelia
country: Mexico
city: Queretaro
country: Mexico
city: Chiclayo
country: Peru
city: Lima
country: Peru
Study officials:
affiliation: Takeda
name: Executive Medical Director Clinical Science
role: STUDY_DIRECTOR
References:
citation: Sica D, White WB, Weber MA, Bakris GL, Perez A, Cao C, Handley A, Kupfer S. Comparison of the novel angiotensin II receptor blocker azilsartan medoxomil vs valsartan by ambulatory blood pressure monitoring. J Clin Hypertens (Greenwich). 2011 Jul;13(7):467-72. doi: 10.1111/j.1751-7176.2011.00482.x. Epub 2011 Jun 20.