AzTrials
AzTrials

Essential HypertensionPhase 3NCT00846365

Efficacy and Safety of Azilsartan Medoxomil Plus Chlorthalidone in Participants With Moderate to Severe Hypertension

A Phase 3 study testing Azilsartan medoxomil and chlorthalidone and Olmesartan medoxomil-hydrochlorothiazide in people with Essential Hypertension, run by Takeda at 80 sites in 3 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 determine the efficacy and safety of azilsartan medoxomil combined with chlorthalidone, once daily (QD), in participants with moderate to severe essential hypertension. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Essential Hypertension
What is being tested?
Azilsartan medoxomil and chlorthalidone and Olmesartan medoxomil-hydrochlorothiazide
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,085 participants
Where
80 sitesin 3 countries
Study dates
Mar 2009to Jun 2010
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

  • 190 mm Hg on Day -1 or if the participant has not received antihypertensive treatment within 28 days before screening and has a mean sitting clinic systolic blood pressure greater than or equal to 160 and less than or equal to 190 mm Hg at the Screening Visit and on Day -1.
  • 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.
  • Has clinical laboratory test results within the reference range for the testing laboratory or the investigator does not consider the results to be clinically significant.
  • Is willing to discontinue current antihypertensive medications on Day -21 or on Day -28 if is on amlodipine or chlorthalidone.

Who cannot join

  • Has a mean sitting clinic diastolic blood pressure greater than 119 mm Hg.
  • Has a baseline 24-hour ambulatory blood pressure monitoring reading of insufficient quality.
  • Works a night (third) shift (from 11 PM [2300] to 7 AM [0700]).
  • Has an upper arm circumference less than 24 cm or greater than 42 cm.
  • Is noncompliant with study medication during the placebo run-in period.
  • Has secondary hypertension of any etiology.
Show all 20Show fewer
  • Has a recent history of myocardial infarction, heart failure, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebrovascular accident or transient ischemic attack.
  • Has a clinically significant cardiac conduction.
  • Has hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease.
  • Has severe renal dysfunction or disease.
  • Has a known or suspected unilateral or bilateral renal artery stenosis.
  • Has a history of cancer that has not been in remission for at least 5 years prior to the first dose of study drug.
  • Has poorly controlled type 1 or type 2 diabetes mellitus.
  • Has hypokalemia or hyperkalemia.
  • Has an alanine aminotransferase or aspartate aminotransferase level of greater than 2.5 times the upper limit of normal, active liver disease or jaundice.
  • Has any other known serious disease or condition that would compromise safety, might affect life expectancy or make it difficult to successfully manage and follow the participant according to the protocol.
  • Has a known hypersensitivity to angiotensin II receptor blockers or thiazide-type diuretics or other sulfonamide-derived compounds.
  • Has been randomized in a previous Azilsartan Medoxomil study.
  • Is currently participating in another investigational study or has participated in an investigational study or is receiving or has received any investigational compound within 30 days prior to Randomization.
  • Has a history of drug abuse or a history of alcohol abuse within the past 2 years.

Trial locations and contacts

80 sites in 3 countries.

80 sites in 3 countries

United States70 sites

  • Study site

    Akron, Ohio

  • Study site

    Arlington, Virginia

  • Study site

    Arlington Heights, Illinois

  • Study site

    Auburn, Maine

  • Study site

    Austin, Texas

  • Study site

    Avon, Indiana

  • Study site

    Baltimore, Maryland

  • Study site

    Bensalem, Pennsylvania

  • Study site

    Bingham Farms, Michigan

  • Study site

    Birmingham, Alabama

  • Study site

    Brockton, Massachusetts

  • Study site

    Burke, Virginia

  • Study site

    Burlington, North Carolina

  • Study site

    Charlotte, North Carolina

  • Study site

    Charlottesville, Virginia

  • Study site

    Chicago, Illinois

  • Study site

    Clearwater, Florida

  • Study site

    Cleveland, Ohio

  • Study site

    Columbus, Ohio

  • Study site

    Corpus Christi, Texas

  • Study site

    Cranston, Rhode Island

  • Study site

    Cumberland, Rhode Island

  • Study site

    Dallas, Texas

  • Study site

    Erie, Pennsylvania

  • Study site

    Green Valley, Arizona

  • Study site

    Gurnee, Illinois

  • Study site

    Haleyville, Alabama

  • Study site

    Haverhill, Massachusetts

  • Study site

    Hickory, North Carolina

  • Study site

    Houston, Texas

  • Study site

    Hueytown, Alabama

  • Study site

    Jackson, Tennessee

  • Study site

    Jacksonville, Florida

  • Study site

    Jasper, Alabama

  • Study site

    Jupiter, Florida

  • Study site

    Kansas City, Missouri

  • Study site

    Kingsport, Tennessee

  • Study site

    Lakewood, Washington

  • Study site

    Long Beach, California

  • Study site

    Louisville, Kentucky

  • Study site

    Manassas, Virginia

  • Study site

    Marion, Ohio

  • Study site

    Menomonee Falls, Wisconsin

  • Study site

    Miami, Florida

  • Study site

    Middleburg Heights, Ohio

  • Study site

    Milan, Tennessee

  • Study site

    National City, California

  • Study site

    New York, New York

  • Study site

    Newark, Delaware

  • Study site

    Norman, Oklahoma

  • Study site

    North Charleston, South Carolina

  • Study site

    North Dartmouth, Massachusetts

  • Study site

    Ocala, Florida

  • Study site

    Olive Branch, Mississippi

  • Study site

    Pembroke Pines, Florida

  • Study site

    Phoenix, Arizona

  • Study site

    Plant City, Florida

  • Study site

    Port Orchard, Washington

  • Study site

    Reading, Pennsylvania

  • Study site

    Roseville, California

  • Study site

    Salt Lake City, Utah

  • Study site

    San Antonio, Texas

  • Study site

    San Francisco, California

  • Study site

    San Jose, California

  • Study site

    Shelby, North Carolina

  • Study site

    Stevensville, Michigan

  • Study site

    Tallahassee, Florida

  • Study site

    Tallassee, Alabama

  • Study site

    Wichita, Kansas

  • Study site

    Willoughby Hills, Ohio

Other trials in United States

Chile5 sites

  • Study site

    La Serena, Elqui

  • Study site

    Osorno, Osorno

  • Study site

    Santiago, Santiago Metropolitan

  • Study site

    Temuco, Cautín

  • Study site

    Viña del Mar, Valparaiso

Other trials in Chile

Mexico5 sites

  • Study site

    Chihuahua City, Chihuahua

  • Study site

    Guadalajara, Jalisco

  • Study site

    León, Guanajuato

  • Study site

    San Luis Potosí City, San Luis Potosí

  • Study site

    Tijuana, Estado de Baja California

Other trials in Mexico

About this study

Official title: A Phase 3, Double-Blind, Randomized, Efficacy and Safety Study Comparing the TAK-491 Plus Chlorthalidone Fixed-Dose Combination vs Benicar HCT® (Olmesartan Medoxomil-Hydrochlorothiazide) in Subjects With Moderate to Severe Essential Hypertension

The purpose of this study is to determine the efficacy and safety of azilsartan medoxomil combined with chlorthalidone, once daily (QD), in participants with moderate to severe essential hypertension.

Read the detailed description

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. As the population ages, the prevalence of hypertension will continue to increase if broad and effective preventive measures are not implemented. Despite the availability of antihypertensive agents, hypertension remains inadequately controlled; only about one-third of patients continue to maintain control successfully.

Although most antihypertensive agents are effective at the appropriate dose, the majority have side effects that limit their use. As a class, angiotensin II receptor blockers generally are considered more tolerable than other classes of antihypertensive agents. TAK-491 (azilsartan medoxomil) is an angiotensin II receptor blocker being evaluated by Takeda to treat essential hypertension.

Treatments for essential hypertension commonly include use of a thiazide-like diuretic, either alone or as part of combination treatment. Although chlorthalidone was commonly prescribed in the past, its use has widely been replaced with hydrochlorothiazide, presumably due to a lack of available combination products containing chlorthalidone, the assumption that hydrochlorothiazide and chlorthalidone have similar antihypertensive effects and cardiovascular benefits, and the perception that chlorthalidone use is associated with a greater frequency of hypokalemia. However, the frequency of hypokalemia with chlorthalidone use is relatively low in the dose range of 12.5 to 25 mg and these doses have been shown to be associated with potent blood pressure reduction. Several long-term outcomes trials have shown that blood pressure reductions associated with chlorthalidone treatment reduce risk of cardiovascular morbidity and mortality.

Most hypertensive patients require two or more agents to achieve target blood pressure and diuretics are commonly used in combination with other antihypertensive agents.

Participants in this study will be randomized to receive one of 3 possible dosing combinations of azilsartan medoxomil with either chlorthalidone or olmesartan medoxomil-hydrochlorothiazide over 8 weeks. The total duration of the study is approximately 13 weeks. Participants will make a total of 11 visits to the clinic, and will be required to participate in a follow-up telephone call 14 days after last dose of the study drug for adverse event assessment.

Being tested
Azilsartan medoxomil and chlorthalidone, Olmesartan medoxomil-hydrochlorothiazide
Keywords
Essential Hypertension, Hypertensive, Blood Pressure, High, Vascular Disease, Cardiovascular Disease, Drug Therapy
Medical subject headings
Essential Hypertension, Hypertension, Vascular Diseases, Cardiovascular Diseases

What participants receive

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

  • Azilsartan medoxomil and chlorthalidoneDrug

    Also called azilsartan medoxomil, chlorthalidone, TAK-491, TAK-491CLD

    Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

    If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

  • Azilsartan medoxomil and chlorthalidoneDrug

    Also called azilsartan medoxomil, chlorthalidone, TAK-491, TAK-491CLD

    Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

    If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

  • Olmesartan medoxomil-hydrochlorothiazideDrug

    Also called Benicar HCT®

    Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks.

    If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Study groups in NCT00846365
Study groupRoleWhat they receive
Azilsartan Medoxomil 20-40mg plus Chlorthalidone 12.5-25 mg QDExperimental(dependant on blood pressure)
Receives: Drug: Azilsartan medoxomil and chlorthalidone
Azilsartan Medoxomil 40-80mg plus Chlorthalidone 12.5-25 mg QDExperimental(dependant on blood pressure)
Receives: Drug: Azilsartan medoxomil and chlorthalidone
Olmesartan medoxomil 20-40mg/hydrochlorothiazide 12.5-25mg QDActive comparator(dependant on blood pressure)
Receives: Drug: Olmesartan medoxomil-hydrochlorothiazide

What is being measured

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

  1. Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure.

    The change in trough systolic blood pressure measured at week 8 or final visit relative to baseline. Systolic blood pressure is the average of the 3 serial trough sitting systolic blood pressure measurements.

    Measured: Baseline and Week 8.

Secondary outcomes (15)

  1. Change From Baseline to Week 4 in Trough, Sitting, Clinic Systolic Blood Pressure.

    The change in trough systolic blood pressure measured at week 4 relative to baseline. Systolic blood pressure is the average of the 3 serial trough sitting systolic blood pressure measurements.

    Measured: Baseline and Week 4.

  2. Change From Baseline in Trough, Sitting, Clinic Diastolic Blood Pressure

    The change in trough diastolic blood pressure measured at week 4 and week 8 relative to baseline. Diastolic blood pressure is the average of the 3 serial trough sitting diastolic blood pressure measurements.

    Measured: Baseline, Week 4 and Week 8.

  3. Change From Baseline in Trough Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

    The change in trough systolic blood pressure measured at week 4 and week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Trough is the average of all measurements recorded from 22 to 24 hours after dosing.

    Measured: Baseline, Week 4 and Week 8.

  4. Change From Baseline in Trough Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

    The change in trough systolic blood pressure measured at week 4 and week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Trough is the average of all measurements recorded from 22 to 24 hours after dosing.

    Measured: Baseline, Week 4 and Week 8.

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

    The change in the 24-hour mean systolic blood pressure at week4 and week 8 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, Week 4 and Week 8.

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

    The change in the 0 to 24-hours-after-dosing mean diastolic blood pressure measured at Week 4 and Week 8 relative to baseline. . Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The mean consists of the average of measurements collected over the subsequent 24 hours.

    Measured: Baseline, Week 4 and Week 8.

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

    The change in the daytime, while awake (6am to 10pm) mean systolic blood pressure measured at Week 4 and Week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night Daytime mean is the average of measurements recorded between the hours of 6 AM (inclusive) and 10 PM (exclusive) included in the 24-hour mean calculations.

    Measured: Baseline, Week 4 and Week 8.

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

    The change in the daytime, while awake (6am to 10pm) mean diastolic blood pressure measured at Week 4 and Week 8relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of measurements recorded between the hours of 6 AM (inclusive) and 10 PM (exclusive) included in the 24-hour mean calculations.

    Measured: Baseline, Week 4 and Week 8.

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

    The change in the nighttime, while asleep (12am to 6am) mean systolic blood pressure measured at Week 4 and Week 8 to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of measurements recorded between the hours of 12 AM (inclusive) and 6 AM (exclusive) included in the 24-hour mean calculations.

    Measured: Baseline, Week 4 and Week 8.

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

    The change in the nighttime, while asleep (12am to 6am) mean diastolic blood pressure measured at Week 4 and Week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average (arithmetic mean) of measurements recorded between the hours of 12 AM (inclusive) and 6 AM (exclusive) included in the 24-hour mean calculations.

    Measured: Baseline, Week 4 and Week 8.

  11. Change From Baseline in 12-hr Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

    The change in the 0 to 12 hours-after-dosing mean Systolic Blood Pressure measured at Week 4 and Week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night The mean consists of the average (arithmetic mean) of measurements collected at each time frame and includes all observations recorded over the subsequent 12 hours.

    Measured: Baseline, Week 4 and Week 8.

  12. Change From Baseline in 12-hr Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.

    The change in the 0 to 12 hours-after-dosing mean diastolic blood pressure measured at Week 4 and Week 8 to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The mean consists of the average (arithmetic mean) of measurements collected at each time frame and includes all observations recorded over the subsequent 12 hours.

    Measured: Baseline, Week 4 and Week 8.

  13. Percentage of Participants Who Achieve a Clinic Systolic Blood Pressure Response, Defined as <140 mm Hg for Participants Without Diabetes or CKD or <130 mm Hg for Participants With Diabetes or CKD

    Percentage of participants who achieve a clinic systolic blood pressure response, defined as <140 mm Hg for participants without diabetes or CKD or <130 mm Hg for participants with diabetes or CKD at each time frame relative to baseline.

    Measured: Baseline, Week 2, Week 4, Week 6 and Week 8.

  14. Percentage of Participants Who Achieve a Clinic Diastolic Blood Pressure Response, Defined as Defined as <90 mm Hg for Participants Without Diabetes or CKD or <80 mm Hg for Participants With Diabetes or CKD

    Percentage of participants who achieve a clinic diastolic blood pressure response, defined as defined as <90 mm Hg for participants without diabetes or CKD or <80 mm Hg for participants with diabetes or CKD at each time frame relative to baseline.

    Measured: Baseline, Week 2, Week 4, Week 6 and Week 8.

  15. Percentage of Participants Who Achieve a Clinic Diastolic AND Systolic Blood Pressure Response, Defined as <140/90 mm Hg for Participants Without Diabetes or Chronic Kidney Disease (CKD) or <130/80 mm Hg for Participants With Diabetes or CKD

    Percentage of participants who achieve both a clinic diastolic blood pressure response, defined as <140/90 mm Hg for participants without diabetes or chronic kidney disease (CKD) or <130/80 mm Hg for participants with diabetes or CKD at each time frame relative to baseline.

    Measured: Baseline, Week 2, Week 4, Week 6 and Week 8.

Timeline

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

  1. First posted18 Feb 2009 (estimated)
  2. Study startMar 2009
  3. Primary completionJun 2010
  4. Study completionJun 2010

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
1,085 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00846365
Sponsor's protocol ID
TAK-491CLD_301
Other IDs
U1111-1112-4287
Status last verified
Feb 2012
First submitted
13 Feb 2009
Last updated
13 Mar 2012
Data monitoring committee
No

Publications

  • Cushman WC, Bakris GL, White WB, Weber MA, Sica D, Roberts A, Lloyd E, Kupfer S. A randomized titrate-to-target study comparing fixed-dose combinations of azilsartan medoxomil and chlorthalidone with olmesartan and hydrochlorothiazide in stage-2 systolic hypertension. J Hypertens. 2018 Apr;36(4):947-956. doi: 10.1097/HJH.0000000000001647.

    PubMed 29334491

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Azilsartan medoxomil and chlorthalidone and Olmesartan medoxomil-hydrochlorothiazide in people with Essential Hypertension, run by Takeda at 80 sites in 3 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 4 inclusion and 20 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 13 Mar 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 80 sites in United States, Chile, Mexico. 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. 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 13 Mar 2012). 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 to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure. (time frame: Baseline and Week 8.). 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 NCT00846365, 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 13 Mar 2012.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in