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HypertensionPhase 3NCT00591773

Efficacy and Safety of Azilsartan Medoxomil Co-Administered With Chlorthalidone in Participants With Essential Hypertension

A Phase 3 study testing Azilsartan medoxomil and chlorthalidone and Chlorthalidone in people with Hypertension, run by Takeda at 46 sites in United States.

Completed

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

Official record
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Trial summary

The purpose of this study is to evaluate the efficacy and safety of azilsartan medoxomil, once daily (QD), co-administered with chlorthalidone in treating individuals with essential hypertension, compared to treatment with chlorthalidone alone. 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 and chlorthalidone and Chlorthalidone
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
551 participants
Where
46 sitesUnited States
Study dates
Sep 2007to Mar 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

  • Has essential hypertension (defined as sitting trough clinic systolic blood pressure between 160 and 190 mm Hg inclusive at Day minus 1 and 24-hour mean systolic blood pressure greater than or equal to 140 mm Hg and ≤ 180 mm Hg at 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 evaluations (including clinical chemistry, hematology, and complete urinalysis) within the reference range for the testing laboratory or results that are deemed not clinically significant for inclusion into this study by the investigator.
  • 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.

Who cannot join

  • Has sitting trough clinic diastolic blood pressure greater than 119 mmHg at Day minus 1.
  • Has a baseline 24 hour ambulatory blood pressure monitor reading of insufficient quality.
  • 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.
  • 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.
  • Clinically significant cardiac conduction defects (for example, 3rd degree atrioventricular block, left bundle branch block, sick sinus syndrome, atrial fibrillation).
  • Hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease.
Show all 22Show fewer
  • The subject has secondary hypertension of any etiology.
  • Non-compliant (less than 70% or greater than 130%) with study medication
  • during the placebo run- in period.
  • Severe renal dysfunction or disease (based on calculated creatinine clearance less than 30 mL/min/1.73 m2) at Screening.
  • Known or suspected unilateral or bilateral renal artery stenosis.
  • 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.
  • 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.)
  • Type 1 or poorly controlled type 2 diabetes mellitus (glycosylated hemoglobin greater than 8.0%).
  • Hypo- or hyperkalemia (defined as serum potassium outside of the normal reference range of the central laboratory).
  • Alanine aminotransferase level of greater than 2.5 times the upper limit of normal, active liver disease, or jaundice.
  • Upper arm circumference less than 24 cm or greater than 42 cm.
  • Works night (3rd) shift (defined as 11PM [2300] to 7AM [0700]).
  • Currently is participating in another investigational study or has participated in an investigational study within 30 days prior to randomization.
  • Study site employee, or is an immediate family member ( ie, spouse, parent, child, sibling) of a study site employee who is involved in conduct of this study.
  • 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.
  • Randomized in a previous azilsartan medoxomil study.

Trial locations and contacts

46 sites in 1 country.

46 sites in 1 country

United States46 sites
  • Study site

    Akron, Ohio

  • Study site

    Arlington, Virginia

  • Study site

    Auburn, Maine

  • Study site

    Bensalem, Pennsylvania

  • Study site

    Bingham Farms, Michigan

  • Study site

    Buena Park, California

  • Study site

    Burke, Virginia

  • Study site

    Centerville, Ohio

  • Study site

    Charlotte, North Carolina

  • Study site

    Cincinnati, Ohio

  • Study site

    Coral Gables, Florida

  • Study site

    Corpus Christi, Texas

  • Study site

    Cranston, Rhode Island

  • Study site

    DeLand, Florida

  • Study site

    Eugene, Oregon

  • Study site

    Feasterville, Pennsylvania

  • Study site

    Fort Lauderdale, Florida

  • Study site

    Hollywood, Florida

  • Study site

    Houston, Texas

  • Study site

    Huntersville, North Carolina

  • Study site

    Huntington Beach, California

  • Study site

    Huntsville, Alabama

  • Study site

    Kingsport, Tennessee

  • Study site

    Lakewood, Washington

  • Study site

    Long Beach, California

  • Study site

    Miami, Florida

  • Study site

    Mission Viejo, California

  • Study site

    Montgomery, Alabama

  • Study site

    Norman, Oklahoma

  • Study site

    Oklahoma City, Oklahoma

  • Study site

    Olympia, Washington

  • Study site

    Pearland, Texas

  • Study site

    Port Orchard, Washington

  • Study site

    Portland, Oregon

  • Study site

    Richmond, Virginia

  • Study site

    Roseville, California

  • Study site

    Sacramento, California

  • Study site

    Salt Lake City, Utah

  • Study site

    San Antonio, Texas

  • Study site

    Shelby, North Carolina

  • Study site

    Simpsonville, South Carolina

  • Study site

    Troy, Michigan

  • Study site

    Tualatin, Oregon

  • Study site

    Westlake Village, California

  • Study site

    Willoughby Hills, Ohio

  • Study site

    Zanesville, Ohio

Other trials in United States

About this study

Official title: A Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of TAK-491 When Co-administered With Chlorthalidone in Subjects With Essential Hypertension

The purpose of this study is to evaluate the efficacy and safety of azilsartan medoxomil, once daily (QD), co-administered with chlorthalidone in treating individuals with essential hypertension, compared to treatment with chlorthalidone alone.

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 continue to maintain control successfully.

TAK-491 (azilsartan medoxomil) is an angiotensin II receptor blocker that was shown to be a orally active antihypertensive agent with a prolonged duration of activity and good safety tolerability in a recent clinical study. Chlorthalidone is a thiazide-like diuretic that reduces blood pressure by decreasing intravascular volume through urinary salt and water excretion. By combining this action with azilsartan medoxomil, a greater reduction in blood pressure is expected than with either agent alone. For subjects requiring combination therapy, azilsartan medoxomil plus chlorthalidone offers a novel combination that may provide a more potent and safe combination for blood pressure reduction.

This study is being conducted to determine whether administration of azilsartan medoxomil in combination with chlorthalidone to subjects with uncontrolled hypertension is more effective in reducing blood pressure than chlorthalidone alone. This study is also being conducted to evaluate the safety and tolerability of azilsartan medoxomil combined with chlorthalidone.

Individuals who want to participate in this study will be required to provide written informed consent. Study participation is anticipated to be about 10 Weeks. Multiple procedures will occur at each visit which may include fasting, blood collection, urine collection, vital signs including sitting and standing blood pressure and pulse, body height and weight, physical examinations, electrocardiogram. Outside of the study center, participants will be required to wear an ambulatory blood pressure monitoring device at 24 hour intervals.

Conditions
Hypertension
Being tested
Azilsartan medoxomil and chlorthalidone, Chlorthalidone
Keywords
Blood pressure, Blood pressure monitoring, ambulatory
Medical subject headings
Hypertension

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 TAK-491, Edarbi

    Azilsartan medoxomil 40 mg, tablets, orally, once daily; azilsartan medoxomil 80 mg placebo-matching tablets, orally, once daily; and chlorthalidone 25 mg, tablets, orally, once daily for up to 6 weeks.

  • Azilsartan medoxomil and chlorthalidoneDrug

    Also called TAK-491, Edarbi

    Azilsartan medoxomil 80 mg, tablets, orally, once daily; azilsartan medoxomil 40 mg placebo-matching tablets, orally, once daily and chlorthalidone 25 mg, tablets, orally, once daily for up to 6 weeks.

  • ChlorthalidoneDrug

    Also called Thalitone

    Chlorthalidone 25 mg, tablets, orally, once daily; azilsartan medoxomil 80 mg placebo-matching tablets, orally, once daily and azilsartan medoxomil 40 mg placebo-matching tablets, orally, once daily for up to 6 weeks.

Study groups in NCT00591773
Study groupRoleWhat they receive
Azilsartan Medoxomil 40 mg QD and Chlorthalidone 25 mg QDExperimentalNot described
Receives: Drug: Azilsartan medoxomil and chlorthalidone
Azilsartan Medoxomil 80 mg QD and Chlorthalidone 25 mg QDExperimentalNot described
Receives: Drug: Azilsartan medoxomil and chlorthalidone
Chlorthalidone 25 mg QDActive comparatorNot described
Receives: Drug: Chlorthalidone

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. Systolic blood pressure is the arithmetic mean of the 3 trough sitting systolic blood pressure measurements.

    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 diastolic blood pressure measured at final visit or week 6 relative to baseline. Diastolic blood pressure is the arithmetic mean of the 3 trough sitting diastolic blood pressure measurements.

    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 posted11 Jan 2008 (estimated)
  2. Study startSep 2007
  3. Primary completionMar 2009
  4. Study completionMar 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
551 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00591773
Sponsor's protocol ID
01-05-TL-491-009
Other IDs
U1111-1113-9040
Status last verified
Mar 2011
First submitted
27 Dec 2007
Last updated
19 Apr 2011
Data monitoring committee
No

Publications

  • Weber MA, Sever P, Juhasz A, Roberts A, Cao C. A randomized trial of the efficacy and safety of azilsartan medoxomil combined with chlorthalidone. J Renin Angiotensin Aldosterone Syst. 2018 Jul-Sep;19(3):1470320318795000. doi: 10.1177/1470320318795000.

    PubMed 30175930

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Azilsartan medoxomil and chlorthalidone and Chlorthalidone in people with Hypertension, run by Takeda at 46 sites in United States.

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 22 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 46 sites in United States. 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 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 NCT00591773, 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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