AzTrials
AzTrials

HypertensionPhase 3NCT00696436

An Efficacy and Safety Study of Azilsartan Medoxomil Compared to Valsartan and Olmesartan in Participants With Essential Hypertension.

A Phase 3 study testing Azilsartan medoxomil, Valsartan and Olmesartan in people with Hypertension, run by Takeda at 131 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hypertension
What is being tested?
Azilsartan medoxomil, Valsartan and Olmesartan
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1,291 participants
Where
131 sitesin 6 countries
Study dates
Apr 2008to Aug 2009
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
  • Capable of understanding and complying with protocol requirements.
  • 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
  • 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.
  • 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.

Who cannot join

  • Sitting diastolic blood pressure greater than 114 mm Hg at Day -1 (day prior to Randomization).
  • Baseline 24-hour ambulatory blood pressure monitor reading of insufficient quality.
  • Taking or expected to take an excluded medication as described in the Excluded Medications.
  • Hypersensitive to angiotensin II receptor blockers.
  • History of myocardial infarction, heart failure, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebrovascular accident, or transient ischemic attack.
  • Clinically significant cardiac conduction defects.
Show all 23Show fewer
  • Hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease.
  • Secondary hypertension of any etiology.
  • Noncompliant (less than 70% or greater than 130%) with study medication during run-in period.
  • Moderate to severe renal dysfunction or disease.
  • Known or suspected unilateral or bilateral renal artery stenosis.
  • History of drug or alcohol abuse within the past 2 years.
  • 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).
  • Type 1 or poorly-controlled type 2 diabetes mellitus (glycosylate hemoglobin greater than 8.0%) at Screening.
  • Hyperkalemia as defined by the central laboratory normal reference range at Screening.
  • Alanine aminotransferase level of greater than 2.5 times the upper limit of normal, active liver disease, or jaundice at Screening.
  • Upper arm circumference less than 24 cm or greater than 42 cm.
  • Works night (3rd) shift (defined as 11 PM [2300] to 7 AM [0700]).
  • Unwilling or unable to comply with the protocol or scheduled appointments.
  • Currently is participating in another investigational study or has participated in an investigational study within 30 days prior to Randomization.
  • 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.
  • Has been randomized in a previous azilsartan medoxomil study.
  • 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.

Trial locations and contacts

131 sites in 6 countries.

131 sites in 6 countries

United States86 sites

  • Study site

    Alabaster, Alabama

  • Study site

    Arlington Heights, Illinois

  • Study site

    Ashland, Oregon

  • Study site

    Baltimore, Maryland

  • Study site

    Bedford, Texas

  • Study site

    Belleville, Illinois

  • Study site

    Biddeford, Maine

  • Study site

    Billings, Montana

  • Study site

    Brooklyn Center, Minnesota

  • Study site

    Cape Coral, Florida

  • Study site

    Carmichael, California

  • Study site

    Champaign, Illinois

  • Study site

    Charleston, South Carolina

  • Study site

    Charlotte, North Carolina

  • Study site

    Chesterfield, Missouri

  • Study site

    Chicago, Illinois

  • Study site

    Chula Vista, California

  • Study site

    Clearwater, Florida

  • Study site

    Cleveland, Tennessee

  • Study site

    Colorado Springs, Colorado

  • Study site

    Columbus, Ohio

  • Study site

    Dallas, Texas

  • Study site

    Denver, Colorado

  • Study site

    Dunwoody, Georgia

  • Study site

    Eugene, Oregon

  • Study site

    Evansville, Indiana

  • Study site

    Glens Falls, New York

  • Study site

    Great Neck, New York

  • Study site

    Green Valley, Arizona

  • Study site

    Houston, Texas

  • Study site

    Indianapolis, Indiana

  • Study site

    Jefferson City, Missouri

  • Study site

    Kansas City, Kansas

  • Study site

    Kansas City, Missouri

  • Study site

    Largo, Florida

  • Study site

    Las Vegas, Nevada

  • Study site

    Lincoln, California

  • Study site

    Litchfield Park, Arizona

  • Study site

    Littleton, Colorado

  • Study site

    Longmont, Colorado

  • Study site

    Margate City, New Jersey

  • Study site

    Medford, Oregon

  • Study site

    Mesa, Arizona

  • Study site

    Miami, Florida

  • Study site

    Mission Viejo, California

  • Study site

    Missouri City, Texas

  • Study site

    Murrells Inlet, South Carolina

  • Study site

    National City, California

  • Study site

    New Hyde Park, New York

  • Study site

    New Port Richey, Florida

  • Study site

    New Smyrna Beach, Florida

  • Study site

    New Windsor, New York

  • Study site

    New York, New York

  • Study site

    Norman, Oklahoma

  • Study site

    North Charleston, South Carolina

  • Study site

    Norwood, Maine

  • Study site

    Overland Park, Kansas

  • Study site

    Ozark, Alabama

  • Study site

    Palm Harbor, Florida

  • Study site

    Pasadena, California

  • Study site

    Peoria, Illinois

  • Study site

    Pittsburgh, Pennsylvania

  • Study site

    Portland, Oregon

  • Study site

    Raleigh, North Carolina

  • Study site

    Riverside, California

  • Study site

    Roswell, Georgia

  • Study site

    Sacramento, California

  • Study site

    San Antonio, Texas

  • Study site

    San Diego, California

  • Study site

    San Dimas, California

  • Study site

    San Francisco, California

  • Study site

    San Ramon, California

  • Study site

    Santa Ana, California

  • Study site

    Shawnee, Kansas

  • Study site

    St Louis, Missouri

  • Study site

    Sugarland, Texas

  • Study site

    Tacoma, Washington

  • Study site

    Tallahassee, Florida

  • Study site

    Tempe, Arizona

  • Study site

    Terre Haute, Indiana

  • Study site

    Tipton, Pennsylvania

  • Study site

    Towson, Maryland

  • Study site

    Tulsa, Oklahoma

  • Study site

    Vernon Hills, Illinois

  • Study site

    Vista, California

  • Study site

    Yukon, Oklahoma

Other trials in United States

Argentina14 sites

  • Study site

    Bahía Blanca

  • Study site

    Berazategui

  • Study site

    Buenos Aires

  • Study site

    Carlos Paz, Córdoba Province

  • Study site

    Córdoba, Córdoba Province

  • Study site

    Corrientes

  • Study site

    Guaymayen, Mendoza Province

  • Study site

    Haedo Pcia. de Buenos Aires

  • Study site

    La Plata

  • Study site

    Ramos Mejía Pcia. de Buenos Aires

  • Study site

    Rosario

  • Study site

    Salta

  • Study site

    San Miguel de Tucumán

  • Study site

    San Salvador de Jujuy

Other trials in Argentina

Mexico10 sites

  • Study site

    Aguascalientes, Aguascalientes

  • Study site

    Chihuahua City, Chihuahua

  • Study site

    Guadalajara, Jalapa

  • Study site

    León, Guanajuato

  • Study site

    Mexico City

  • Study site

    Monterrey, Nuevo León

  • Study site

    Querètaro

  • Study site

    San Luis Potosí City, San Luis Potosí

  • Study site

    Tijuana, Estado de Baja California

  • Study site

    Xalapa, Veracruz

Other trials in Mexico

Brazil9 sites

  • Study site

    Belo Horizonte

  • Study site

    Campinas

  • Study site

    Fortaleza

  • Study site

    Goiaenia

  • Study site

    Joildille

  • Study site

    Porto Alegre

  • Study site

    Rio Janeiro

  • Study site

    São Paulo

  • Study site

    Sorocava

Other trials in Brazil

Peru6 sites

  • Study site

    Arequipa

  • Study site

    Cusco

  • Study site

    Huaura

  • Study site

    Ica

  • Study site

    Lima

  • Study site

    Trujillo

Other trials in Peru

Puerto Rico6 sites

  • Study site

    Aguas Buenas

  • Study site

    Carolina

  • Study site

    Jardines de Loiza

  • Study site

    Orocovis

  • Study site

    Ponce

  • Study site

    San Juan

Other trials in Puerto Rico

About this study

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

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.

Read the 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.

Conditions
Hypertension
Being tested
Azilsartan medoxomil, Valsartan, Olmesartan, Placebo
Keywords
Essential Hypertension, Cardiovascular Disease, High Blood Pressure, Drug Therapy
Medical subject headings
Hypertension, Essential Hypertension, Cardiovascular Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Azilsartan medoxomilDrug

    Also called TAK-491, Edarbi

    Azilsartan medoxomil 20 mg, tablets and matching placebo comparator orally once daily for two weeks.

    Increased to azilsartan medoxomil 40 mg tablets and matching placebo comparator orally, once daily for up to four weeks.

  • Azilsartan medoxomilDrug

    Also called TAK-491, Edarbi

    Azilsartan medoxomil 40 mg, tablets and matching placebo comparator orally, once daily for two weeks.

    Increased to Azilsartan medoxomil 80 mg, tablets and matching placebo comparator orally, once daily for up to four weeks.

  • ValsartanDrug

    Also called Diovan®

    Valsartan 160 mg, tablets, and matching placebo comparator orally, once daily for two weeks.

    Increased to Valsartan 320 mg, tablets, and matching placebo comparator, orally, once daily for up to four weeks.

  • OlmesartanDrug

    Also called Benicar®

    Olmesartan 20 mg, tablets and matching placebo comparator, orally, once daily for two weeks.

    Increased to Olmesartan 40 mg, tablets and matching placebo comparator, orally, once daily for up to four weeks.

  • PlaceboDrug

    Matching placebo, orally, once daily for up to six weeks.

Study groups in NCT00696436
Study groupRoleWhat they receive
Azilsartan Medoxomil 40 mg QDExperimentalNot described
Receives: Drug: Azilsartan medoxomil
Azilsartan Medoxomil 80 mg QDExperimentalNot described
Receives: Drug: Azilsartan medoxomil
Valsartan 320 mg QDActive comparatorNot described
Receives: Drug: Valsartan
Olmesartan 40 mg QDActive comparatorNot described
Receives: Drug: Olmesartan
Placebo QDPlacebo comparatorNot described
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change From Baseline in the 24-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

    The change in 24-hour mean systolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing.

    Measured: Baseline and Week 6.

Secondary outcomes (14)

  1. Change From Baseline in Mean Trough Clinic Sitting Systolic Blood Pressure.

    The change in mean trough clinic sitting systolic blood pressure measured at final visit or week 6 relative to baseline.

    Measured: Baseline and Week 6.

  2. Change From Baseline in the 24-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

    The change in 24-hour mean diastolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing.

    Measured: Baseline and Week 6.

  3. Change From Baseline in Mean Trough Clinic Sitting Diastolic Blood Pressure

    The change in mean trough clinic sitting systolic blood pressure measured at final visit or week 6 relative to baseline.

    Measured: Baseline and Week 6.

  4. Change From Baseline in Daytime (6am to 10 pm) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

    The change in daytime (6am to 10pm) mean systolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of all measurements recorded between the hours of 6 am and 10 pm.

    Measured: Baseline and Week 6.

  5. Change From Baseline in Daytime (6am to 10 pm) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

    The change in daytime (6am to 10pm) mean diastolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of all measurements recorded between the hours of 6 am and 10 pm.

    Measured: Baseline and Week 6.

  6. Change From Baseline in the Nighttime (12 am to 6 am) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

    The change in nighttime (12am to 6am) mean systolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of all measurements recorded between the hours of 12 am and 6 am.

    Measured: Baseline and Week 6.

  7. Change From Baseline in the Nighttime (12 am to 6 am) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

    The change in nighttime (12am to 6am) mean diastolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of all measurements recorded between the hours of 12 am and 6 am.

    Measured: Baseline and Week 6.

  8. Change From Baseline in the 12-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

    The change in the 12-hour mean systolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 12-hour mean is the average of all measurements recorded in the first 12 hours after dosing.

    Measured: Baseline and Week 6.

  9. Change From Baseline in the 12-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

    The change in the 12-hour mean diastolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 12-hour mean is the average of all measurements recorded in the first 12 hours after dosing.

    Measured: Baseline and Week 6.

  10. Change From Baseline in the Trough (22-24-hr) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

    The change in trough mean systolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough mean is the average of all measurements recorded from 22 to 24 hours after dosing.

    Measured: Baseline and Week 6.

  11. Change From Baseline in the Trough (22-24-hr) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

    The change in trough mean diastolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough mean is the average of all measurements recorded from 22 to 24 hours after dosing.

    Measured: Baseline and Week 6.

  12. Percentage of Participants Who Achieve a Clinic Systolic Blood Pressure Response, Defined as < 140 mm Hg and/or Reduction From Baseline ≥ 20 mm Hg

    Percentage of participants who achieve a clinic systolic blood pressure response measured at week 6, defined as less than 140 mm Hg and/or reduction from baseline of greater than or equal to 20 mm Hg. Systolic blood pressure is the arithmetic mean of the 3 trough sitting systolic blood pressure measurements.

    Measured: Baseline and Week 6.

  13. Percentage of Participants Who Achieve a Clinic Diastolic Blood Pressure Response, Defined as < 90 mm Hg and/or Reduction From Baseline ≥ 10 mm Hg

    Percentage of participants who achieve a clinic diastolic blood pressure response measured at week 6, defined as less than 90 mm Hg and/or reduction from baseline of greater than or equal to 10 mm Hg. Diastolic blood pressure is the arithmetic mean of the 3 trough sitting diastolic blood pressure measurements.

    Measured: Baseline and Week 6.

  14. Percentage of Participants Who Achieve Both a Clinic Diastolic and Systolic Blood Pressure Response

    Percentage of participants who achieve both a clinic diastolic and systolic blood pressure response measured at week 6, defined as less than 90 mm Hg and/or reduction from baseline of greater than or equal to 10 mm Hg AND less than 140 mm Hg and/or reduction from baseline of greater than or equal to 20 mm Hg. Diastolic and systolic blood pressure is based on the arithmetic mean of the 3 sitting blood pressure measurements.

    Measured: Baseline and Week 6.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jun 2008 (estimated)
  2. Study startApr 2008
  3. Primary completionAug 2009
  4. Study completionAug 2009

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
1,291 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00696436
Sponsor's protocol ID
01-06-TL-491-019
Other IDs
U1111-1113-9161
Status last verified
Mar 2011
First submitted
10 Jun 2008
Last updated
19 Apr 2011
Data monitoring committee
No

Publications

  • 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.

    PubMed 21282560

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Azilsartan medoxomil, Valsartan and Olmesartan in people with Hypertension, run by Takeda at 131 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Apr 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 131 sites in United States, Argentina, Mexico, Brazil, Peru and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Apr 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in the 24-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. (time frame: Baseline and Week 6.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00696436, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2011.

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