Clinical trial NCT00696241: Efficacy and Safety of Azilsartan Medoxomil in Participants With Essential Hypertension
Official title: A Phase 3, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of TAK-491 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: 1275
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 determine the safety and efficacy of azilsartan medoxomil, once daily (QD), compared to placebo 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 continue to maintain control successfully.

TAK-491 (azilsartan medoxomil) is an angiotensin II receptor blocker and this study is being conducted to evaluate the efficacy and safety of oral azilsartan medoxomil compared to placebo and olmesartan in subjects with essential hypertension.

Individuals who want to participate in this study will be required to provide written informed consent. Study participation is anticipated to be about 11 weeks. Multiple procedures will occur at each visit which may include fasting, blood collection, urine collection, vital signs including sitting blood pressure and pulse, body height and weight, physical examinations and electrocardiograms. Outside of the study center, participants will be required to wear an ambulatory blood pressure monitoring device at 24 hour intervals.

Eligibility criteria: Inclusion Criteria

1. Has 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 greater than or equal to 130 mm Hg and less than or equal to 170 mm Hg 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. The subject is 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. Baseline 24-hour ambulatory blood pressure monitor reading of insufficient quality.
3. History of myocardial infarction, heart failure, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebrovascular accident, or transient ischemic attack.
4. Clinically significant cardiac conduction defects (eg, third degree atrioventricular block, left bundle branch block, sick sinus syndrome, atrial fibrillation or atrial flutter).
5. Hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease.
6. Secondary hypertension of any etiology.
7. Is noncompliant (less than 70% or greater than 130%) with study medication during Placebo Run-In Period.
8. Severe renal dysfunction or disease (based on calculated creatinine clearance less than 30 mL/min/1.73 m2) at Screening.
9. Known or suspected unilateral or bilateral renal artery stenosis.
10. History of drug abuse (defined as illicit drug use) or a history of alcohol abuse (defined as regular or daily consumption of more than 2 alcoholic drinks per day) within the past 2 years.
11. 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 I squamous cell carcinoma of the skin).
12. Type 1 or poorly controlled type 2 diabetes mellitus (glycosylated hemoglobin greater than 8.0%) at Screening.
13. Alanine aminotransferase level greater than 2.5 times the upper limit of normal, active liver disease, or jaundice at Screening.
14. Hyperkalemia (defined as serum potassium greater than the upper limit of normal per the central laboratory) at Screening.
15. Upper arm circumference less than 24 cm or greater than 42 cm.
16. Works night (3rd) shift (defined as 11 PM to 7 AM).
17. Currently participating in another investigational study or has participated in an investigational study within 30 days prior to Screening.
18. 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.
19. Randomized in a previous azilsartan medoxomil study.

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: Birmingham
country: United States
state: Alabama
city: Huntsville
country: United States
state: Alabama
city: Mesa
country: United States
state: Arizona
city: Phoenix
country: United States
state: Arizona
city: Tempe
country: United States
state: Arizona
city: Little Rock
country: United States
state: Arkansas
city: Tempe
country: United States
state: Arkansas
city: Beverly Hills
country: United States
state: California
city: Carmichael
country: United States
state: California
city: Fountain Valley
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Los Gatos
country: United States
state: California
city: Orangevale
country: United States
state: California
city: Sacramento
country: United States
state: California
city: Santa Ana
country: United States
state: California
city: Spring Valley
country: United States
state: California
city: Tustin
country: United States
state: California
city: Westlake Village
country: United States
state: California
city: Colorado Springs
country: United States
state: Colorado
city: Farmington
country: United States
state: Connecticut
city: Hollywood
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Jupiter
country: United States
state: Florida
city: Melbourne
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Naples
country: United States
state: Florida
city: Ocala
country: United States
state: Florida
city: Pembroke Pines
country: United States
state: Florida
city: Sarasota
country: United States
state: Florida
city: St. Petersburg
country: United States
state: Florida
city: Augusta
country: United States
state: Georgia
city: Lawrenceville
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Melrose Park
country: United States
state: Illinois
city: Naperville
country: United States
state: Illinois
city: Round Lake Beach
country: United States
state: Illinois
city: Valparaiso
country: United States
state: Indiana
city: Wichita
country: United States
state: Kansas
city: Erlanger
country: United States
state: Kentucky
city: Lexington
country: United States
state: Kentucky
city: Auburn
country: United States
state: Maine
city: West Yarmouth
country: United States
state: Massachusetts
city: Benzonia
country: United States
state: Michigan
city: Chelsea
country: United States
state: Michigan
city: Omaha
country: United States
state: Nebraska
city: Trenton
country: United States
state: New Jersey
city: Wildwood Crest
country: United States
state: New Jersey
city: Albuquerque
country: United States
state: New Mexico
city: Brooklyn
country: United States
state: New York
city: Orangevale
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Burlington
country: United States
state: North Carolina
city: Charlotte
country: United States
state: North Carolina
city: Raleigh
country: United States
state: North Carolina
city: Salisbury
country: United States
state: North Carolina
city: Statesville
country: United States
state: North Carolina
city: Wilmington
country: United States
state: North Carolina
city: Winston-Salem
country: United States
state: North Carolina
city: Kettering
country: United States
state: Ohio
city: Lyndhurst
country: United States
state: Ohio
city: Marion
country: United States
state: Ohio
city: Norman
country: United States
state: Oklahoma
city: Oklahoma City
country: United States
state: Oklahoma
city: Altoona
country: United States
state: Pennsylvania
city: Reading
country: United States
state: Pennsylvania
city: Mt. Pleasant
country: United States
state: South Carolina
city: Simpsonville
country: United States
state: South Carolina
city: Taylors
country: United States
state: South Carolina
city: Nashville
country: United States
state: Tennessee
city: New Tazewell
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Lake Jackson
country: United States
state: Texas
city: North Richland Hills
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Draper
country: United States
state: Utah
city: Burke
country: United States
state: Virginia
city: Norfolk
country: United States
state: Virginia
city: Tacoma
country: United States
state: Washington
city: Madison
country: United States
state: Wisconsin
city: Provincia de Buenos Aires
country: Argentina
city: Provincia de Cordoba
country: Argentina
city: Aguascalientes,
country: Mexico
city: Mexico DF
country: Mexico
city: San Luis Potosi
country: Mexico
Study officials:
affiliation: Takeda
name: VP Clinical Science Strategy
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.
citation: Bakris GL, Sica D, Weber M, White WB, Roberts A, Perez A, Cao C, Kupfer S. The comparative effects of azilsartan medoxomil and olmesartan on ambulatory and clinic blood pressure. J Clin Hypertens (Greenwich). 2011 Feb;13(2):81-8. doi: 10.1111/j.1751-7176.2010.00425.x.