HypertensionPhase 3NCT00847626
Efficacy and Safety of Azilsartan Medoxomil Combined With Chlorthalidone in Participants With Moderate to Severe Hypertension
A Phase 3 study testing Azilsartan medoxomil and chlorthalidone, Chlorthalidone and Azilsartan medoxomil in people with Hypertension, run by Takeda at 99 sites in 5 countries.
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 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 and chlorthalidone, Chlorthalidone and Azilsartan medoxomil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,711 participants
- Where
- 99 sitesin 5 countries
- Study dates
- Jan 2009to Jul 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
- Is treated with antihypertensive therapy and has a post-washout mean sitting clinic systolic blood pressure greater than or equal to 160 and less than or equal to 190 mm Hg on the day prior to randomization, or the participant has not received antihypertensive treatment within 28 days prior to 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 the day prior to randomization.
- 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 on amlodipine or chlorthalidone.
Who cannot join
- Has a mean sitting clinic diastolic blood pressure greater than 119 mm Hg on the day prior to randomization.
- Has a baseline 24-hour ambulatory blood pressure measurement reading of insufficient quality.
- Has works a night (third) shift (defined as 11 PM [2300] to 7 AM [0700]).
- Has an upper arm circumference less than 24 cm or greater than 42 cm.
- Has is noncompliant with study medication during the placebo run-in period.
- Has secondary hypertension of any etiology.
Show all 20Show fewer
- Has 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 clinically significant cardiac conduction defects.
- Has hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease.
- Has severe renal dysfunction or disease.
- Has 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 at Screening.
- 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 Has according to the protocol.
- Has known hypersensitivity to angiotensin II receptor blockers, 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 is receiving or has received any investigational compound within 30 days prior to Screening.
- Has a history of drug abuse or a history of alcohol abuse within the past 2 years.
Trial locations and contacts
99 sites in 5 countries.
99 sites in 5 countries
United States84 sites
Study site
Albuquerque, New Mexico
Study site
Altoona, Pennsylvania
Study site
Ann Arbor, Michigan
Study site
Arlington, Virginia
Study site
Ashland, Oregon
Study site
Atlanta, Georgia
Study site
Austin, Texas
Study site
Bellaire, Texas
Study site
Bensalem, Pennsylvania
Study site
Birmingham, Alabama
Study site
Bradenton, Florida
Study site
Brick, New Jersey
Study site
Buena Park, California
Study site
Buffalo Grove, Illinois
Study site
Carmichael, California
Study site
Cary, North Carolina
Study site
Chandler, Arizona
Study site
Charleston, South Carolina
Study site
Chesterfield, Michigan
Study site
Cincinnati, Ohio
Study site
Clarksville, Tennessee
Study site
Cleveland, Ohio
Study site
Columbiana, Alabama
Study site
Columbus, Ohio
Study site
Costa Mesa, California
Study site
Dallas, Texas
Study site
Dayton, Ohio
Study site
Deerfield Beach, Florida
Study site
Endwell, New York
Study site
Erlanger, Kentucky
Study site
Feasterville, Pennsylvania
Study site
Fishers, Indiana
Study site
Florence, South Carolina
Study site
Fort Lauderdale, Florida
Study site
Hallandale, Florida
Study site
Henderson, Nevada
Study site
Hialeah, Florida
Study site
Houston, Texas
Study site
Indianapolis, Indiana
Study site
Irvine, California
Study site
Jacksonville, Florida
Study site
Jenkintown, Pennsylvania
Study site
Libertyville, Illinois
Study site
Little Rock, Arkansas
Study site
Longwood, Florida
Study site
Lyndhurst, Ohio
Study site
Madisonville, Kentucky
Study site
Magna, Utah
Study site
Margate City, New Jersey
Study site
McKinney, Texas
Study site
Melrose Park, Illinois
Study site
Miami, Florida
Study site
Middletown, Delaware
Study site
Murrells Inlet, South Carolina
Study site
New Tazewell, Tennessee
Study site
Ocala, Florida
Study site
Oklahoma City, Oklahoma
Study site
Omaha, Nebraska
Study site
Oregon, Wisconsin
Study site
Ormond Beach, Florida
Study site
Paducah, Kentucky
Study site
Palm Springs, California
Study site
Phoenix, Arizona
Study site
Richardson, Texas
Study site
Riverside, California
Study site
Rockville, Maryland
Study site
Sacramento, California
Study site
San Antonio, Texas
Study site
San Diego, California
Study site
Scottsdale, Arizona
Study site
Sellersville, Pennsylvania
Study site
Simpsonville, South Carolina
Study site
Spartanburg, South Carolina
Study site
St Louis, Missouri
Study site
St. Petersburg, Florida
Study site
Tucson, Arizona
Study site
Tuscaloosa, Alabama
Study site
Virginia Beach, Virginia
Study site
Vista, California
Study site
Walnut Creek, California
Study site
Warminster, Pennsylvania
Study site
West Jordan, Utah
Study site
Willoughby Hills, Ohio
Study site
Winston-Salem, North Carolina
Peru8 sites
Study site
Bellavista
Study site
Chiclayo
Study site
Jesus Maria
Study site
Miraflores
Study site
San Borja
Study site
San Martín de Porres
Study site
Trujillo
Study site
Umacollo
About this study
Official title: A Phase 3, Double-Blind, Randomized, Factorial, Efficacy and Safety Study of TAK 491 Plus Chlorthalidone Fixed-Dose Combination in Participants With Moderate to Severe 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 hypertension.
Read the detailed description
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. 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 that is 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.
This study is designed to compare the antihypertensive effect and the safety and tolerability of the azilsartan medoxomil plus chlorthalidone fixed-dose combination product (TAK 491CLD FDC) with azilsartan monotherapy and chlorthalidone monotherapy during 8 weeks of treatment.
Participants in this study will be randomized to receive one of 11 possible dosing combinations of azilsartan medoxomil , chlorthalidone and placebo over an 8 week period. The total duration of the study will be approximately 13 weeks. Participants will make 12 visits to the clinic. Each participant will also be contacted by telephone 14 days after last dose of study drug for a follow-up assessment.
- Conditions
- Hypertension
- Being tested
- Azilsartan medoxomil and chlorthalidone, Chlorthalidone, Azilsartan medoxomil
- Keywords
- Hypertensive, Blood Pressure, High, Vascular Disease, Cardiovascular Disease, Drug Therapy
- Medical subject headings
- 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 TAK-491CLD
Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for up to 8 weeks
Azilsartan medoxomil and chlorthalidoneDrug
Also called TAK-491CLD
Azilsartan medoxomil 20 mg and chlorthalidone 25 mg combination tablets, orally, once daily for up to 8 weeks
Azilsartan medoxomil and chlorthalidoneDrug
Also called TAK-491CLD
Azilsartan 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for up to 8 weeks
Azilsartan medoxomil and chlorthalidoneDrug
Also called TAK-491CLD
Azilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for up to 8 weeks
Azilsartan medoxomil and chlorthalidoneDrug
Also called TAK-491CLD
Azilsartan 80 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for up to 8 weeks
Azilsartan medoxomil and chlorthalidoneDrug
Also called TAK-491CLD
Azilsartan medoxomil 80 mg and chlorthalidone 25 mg combination tablets, orally, once daily for up to 8 weeks
ChlorthalidoneDrug
Azilsartan medoxomil placebo and chlorthalidone 12.5 mg combination tablets, orally, once daily for up to 8 weeks
ChlorthalidoneDrug
Azilsartan medoxomil placebo and chlorthalidone 25 mg combination tablets, orally, once daily for up to 8 weeks
Azilsartan medoxomilDrug
Also called TAK-491CLD
Azilsartan medoxomil 20 mg and chlorthalidone placebo combination tablets, orally, once daily for up to 8 weeks
Azilsartan medoxomilDrug
Also called TAK-491CLD
Azilsartan medoxomil 40 mg and chlorthalidone placebo combination tablets, orally, once daily for up to 8 weeks
Azilsartan medoxomilDrug
Also called TAK-491CLD
Azilsartan medoxomil 80 mg and chlorthalidone placebo combination tablets, orally, once daily for up to 8 weeks
| Study group | Role | What they receive |
|---|---|---|
| Azilsartan medoxomil 20 mg/chlorthalidone 12.5 mg QD | Experimental | Not described Receives: Drug: Azilsartan medoxomil and chlorthalidone |
| Azilsartan medoxomil 20 mg/chlorthalidone 25 mg QD | Experimental | Not described Receives: Drug: Azilsartan medoxomil and chlorthalidone |
| Azilsartan medoxomil 40 mg/chlorthalidone 12.5 mg QD | Experimental | Not described Receives: Drug: Azilsartan medoxomil and chlorthalidone |
| Azilsartan medoxomil 40 mg/chlorthalidone 25 mg QD | Experimental | Not described Receives: Drug: Azilsartan medoxomil and chlorthalidone |
| Azilsartan medoxomil 80 mg/chlorthalidone 12.5 mg QD | Experimental | Not described Receives: Drug: Azilsartan medoxomil and chlorthalidone |
| Azilsartan medoxomil 80 mg/chlorthalidone 25 mg QD | Experimental | Not described Receives: Drug: Azilsartan medoxomil and chlorthalidone |
| Chlorthalidone 12.5 mg QD | Active comparator | Not described Receives: Drug: Chlorthalidone |
| Chlorthalidone 25 mg QD | Active comparator | Not described Receives: Drug: Chlorthalidone |
| Azilsartan medoxomil 20 mg QD | Experimental | Not described Receives: Drug: Azilsartan medoxomil |
| Azilsartan medoxomil 40 mg QD | Experimental | Not described Receives: Drug: Azilsartan medoxomil |
| Azilsartan medoxomil 80 mg QD | Experimental | Not described Receives: Drug: Azilsartan medoxomil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline to Week 8 in Trough, Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring (Pooled Analysis)
The change in trough systolic blood pressure measured at final visit or week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough is the average of all measurements recorded from 22 to 24 hours after dosing.
Measured: Baseline and Week 8.
Change From Baseline to Week 8 in Trough, Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring (Pairwise Analysis)
The change in trough systolic blood pressure measured at final visit or week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough is the average of all measurements recorded from 22 to 24 hours after dosing.
Measured: Baseline and Week 8.
Secondary outcomes (16)
Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure
The change in trough systolic blood pressure measured at final visit or week 8 relative to baseline. Systolic blood pressure is the arithmetic mean of the 3 serial trough sitting systolic blood pressure measurements.
Measured: Baseline and Week 8
Change From Baseline to Week 8 in Trough Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring in Black Participants (Pooled Analysis)
The change in trough systolic blood pressure in black subjects measured at final visit or week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough is the average of all measurements recorded from 22 to 24 hours after dosing.
Measured: Baseline and Week 8.
Change From Baseline to Week 8 in Trough Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring in Black Participants (Pairwise Analysis)
The change in trough systolic blood pressure in black participants as measured at final visit or week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough is the average of all measurements recorded from 22 to 24 hours after dosing.
Measured: Baseline and Week 8.
Change From Baseline to Week 8 in Trough, Sitting, Clinic Diastolic Blood Pressure
The change in trough diastolic blood pressure measured at final visit or week 8 relative to baseline. Diastolic blood pressure is the average of the 3 serial trough clinic sitting diastolic blood pressure measurements.
Measured: Baseline and Week 8.
Change From Baseline to Week 8 in the Mean Trough Diastolic Blood Pressure (22 to 24 Hours After Dosing), as Measured by Ambulatory Blood Pressure Monitoring.
The change in trough diastolic blood pressure measured at final visit or week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough is the average of all measurements recorded from 22 to 24 hours after dosing.
Measured: Baseline and Week 8.
Change From Baseline to Week 8 in the 24-hour Mean Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring
The change in 24-hour mean systolic blood pressure measured at final visit or 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 and Week 8.
Change From Baseline to Week 8 in the 24-hour Mean Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring
The change in 24-hour mean diastolic blood pressure measured at final visit or 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 and Week 8.
Change From Baseline to Week 8 in the Mean Daytime (6 AM to 10 PM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring.
The change in daytime (6am to 10pm) mean systolic blood pressure measured at final visit or 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 all measurements recorded between the hours of 6 am and 10 pm.
Measured: Baseline and Week 8.
Change From Baseline to Week 8 in the Mean Daytime (6 AM to 10 PM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring.
The change in daytime (6am to 10pm) mean diastolic blood pressure measured at final visit or 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 all measurements recorded between the hours of 6 am and 10 pm.
Measured: Baseline and Week 8.
Change From Baseline to Week 8 in the Mean Nighttime (12 AM to 6 AM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring.
The change in nighttime (12am to 6am) mean systolic blood pressure measured at final visit or 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 of all measurements recorded between the hours of 12 am and 6 am.
Measured: Baseline and Week 8.
Change From Baseline to Week 8 in the Mean Nighttime (12 AM to 6 AM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring.
The change in nighttime (12am to 6am) mean diastolic blood pressure measured at final visit or 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 of all measurements recorded between the hours of 12 am and 6 am.
Measured: Baseline and Week 8.
Change From Baseline to Week 8 in the Mean Systolic Blood Pressure at 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring.
The change in the 12-hour mean systolic blood pressure measured at final visit or week 8 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 8
Change From Baseline to Week 8 in the Mean Diastolic Blood Pressure at 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring.
The change in the 12-hour mean diastolic blood pressure measured at final visit or week 8 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 8.
Percentage of Participants Who Achieve a Clinic Systolic Blood Pressure Response at Week 8, as Defined by Clinic Systolic Blood Pressure <140 mm Hg and/or a Reduction of ≥20 mm Hg From Baseline.
Percentage of participants who achieve a clinic systolic blood pressure response measured at week 8, 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 average of the 3 serial trough sitting clinic systolic blood pressure measurements.
Measured: Baseline and Week 8
Percentage of Participants Who Achieve a Clinic Diastolic Blood Pressure Response at Week 8, Defined as Clinic Diastolic Blood Pressure <90 mm Hg and/or a Reduction of ≥10 mm Hg From Baseline.
Percentage of participants who achieve a clinic diastolic blood pressure response measured at week 8, 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 average of the 3 serial trough sitting clinic diastolic blood pressure measurements.
Measured: Baseline and Week 8.
Percentage of Participants Who Achieve Both a Clinic Systolic and Diastolic Blood Pressure Response at Week 8.
Percentage of participants who achieve both a clinic systolic and diastolic blood pressure response measured at week 8, defined as systolic blood pressure less than 140 mm Hg and/or reduction from baseline of greater than or equal to 20 mm Hg AND diastolic blood pressure less than 90 mm Hg and/or reduction from baseline of greater than or equal to 10 mm Hg . Systolic/diastolic blood pressure is based on the average of the 3 serial trough clinic sitting systolic/diastolic blood pressure measurements.
Measured: Baseline and Week 8.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2009 (estimated)
- Study startJan 2009
- Primary completionMay 2010
- Study completionJul 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HypertensionStudies of the same condition, open and under way.
- More trials run by TakedaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Factorial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,711 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Executive Medical Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00847626
- Sponsor's protocol ID
- TAK-491CLD_302
- Other IDs
- 2008-004218-28, U1111-1113-8735, 2008
- Status last verified
- Jan 2012
- First submitted
- 18 Feb 2009
- Last updated
- 7 Feb 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Double-Blind, Randomized, Factorial, Efficacy and Safety Study of TAK 491 Plus Chlorthalidone Fixed-Dose Combination in Participants With Moderate to Severe Hypertension
- ClinicalTrials.gov ID
- NCT00847626
- Acronym / sponsor ID
- TAK-491CLD_302
- Conditions
- Hypertension
- Keywords
- Hypertensive, Blood Pressure, High, Vascular Disease, Cardiovascular Disease, Drug Therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,711 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- Jan 2009
- Primary completion
- May 2010 (actual)
- Study completion
- Jul 2010 (actual)
- First posted
- 19 Feb 2009 (estimated)
- Results
- Posted 7 Feb 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 hypertension.
Detailed description
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. 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 that is 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.
This study is designed to compare the antihypertensive effect and the safety and tolerability of the azilsartan medoxomil plus chlorthalidone fixed-dose combination product (TAK 491CLD FDC) with azilsartan monotherapy and chlorthalidone monotherapy during 8 weeks of treatment.
Participants in this study will be randomized to receive one of 11 possible dosing combinations of azilsartan medoxomil , chlorthalidone and placebo over an 8 week period. The total duration of the study will be approximately 13 weeks. Participants will make 12 visits to the clinic. Each participant will also be contacted by telephone 14 days after last dose of study drug for a follow-up assessment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 11
| Arm | Type | Receives |
|---|---|---|
| Azilsartan medoxomil 20 mg/chlorthalidone 12.5 mg QD | Experimental | Drug: Azilsartan medoxomil and chlorthalidone |
| Azilsartan medoxomil 20 mg/chlorthalidone 25 mg QD | Experimental | Drug: Azilsartan medoxomil and chlorthalidone |
| Azilsartan medoxomil 40 mg/chlorthalidone 12.5 mg QD | Experimental | Drug: Azilsartan medoxomil and chlorthalidone |
| Azilsartan medoxomil 40 mg/chlorthalidone 25 mg QD | Experimental | Drug: Azilsartan medoxomil and chlorthalidone |
| Azilsartan medoxomil 80 mg/chlorthalidone 12.5 mg QD | Experimental | Drug: Azilsartan medoxomil and chlorthalidone |
| Azilsartan medoxomil 80 mg/chlorthalidone 25 mg QD | Experimental | Drug: Azilsartan medoxomil and chlorthalidone |
| Chlorthalidone 12.5 mg QD | Active comparator | Drug: Chlorthalidone |
| Chlorthalidone 25 mg QD | Active comparator | Drug: Chlorthalidone |
| Azilsartan medoxomil 20 mg QD | Experimental | Drug: Azilsartan medoxomil |
| Azilsartan medoxomil 40 mg QD | Experimental | Drug: Azilsartan medoxomil |
| Azilsartan medoxomil 80 mg QD | Experimental | Drug: Azilsartan medoxomil |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Is treated with antihypertensive therapy and has a post-washout mean sitting clinic systolic blood pressure greater than or equal to 160 and less than or equal to 190 mm Hg on the day prior to randomization, or the participant has not received antihypertensive treatment within 28 days prior to 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 the day prior to randomization.
- 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 on amlodipine or chlorthalidone.
Key exclusion criteria (20 listed)
- Has a mean sitting clinic diastolic blood pressure greater than 119 mm Hg on the day prior to randomization.
- Has a baseline 24-hour ambulatory blood pressure measurement reading of insufficient quality.
- Has works a night (third) shift (defined as 11 PM [2300] to 7 AM [0700]).
- Has an upper arm circumference less than 24 cm or greater than 42 cm.
- Has is noncompliant with study medication during the placebo run-in period.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Azilsartan medoxomil and chlorthalidoneAlso: TAK-491CLDAzilsartan medoxomil 20 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for up to 8 weeks | Drug | Azilsartan medoxomil 20 mg/chlorthalidone 12.5 mg QD |
| Azilsartan medoxomil and chlorthalidoneAlso: TAK-491CLDAzilsartan medoxomil 20 mg and chlorthalidone 25 mg combination tablets, orally, once daily for up to 8 weeks | Drug | Azilsartan medoxomil 20 mg/chlorthalidone 25 mg QD |
| Azilsartan medoxomil and chlorthalidoneAlso: TAK-491CLDAzilsartan 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for up to 8 weeks | Drug | Azilsartan medoxomil 40 mg/chlorthalidone 12.5 mg QD |
| Azilsartan medoxomil and chlorthalidoneAlso: TAK-491CLDAzilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for up to 8 weeks | Drug | Azilsartan medoxomil 40 mg/chlorthalidone 25 mg QD |
| Azilsartan medoxomil and chlorthalidoneAlso: TAK-491CLDAzilsartan 80 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for up to 8 weeks | Drug | Azilsartan medoxomil 80 mg/chlorthalidone 12.5 mg QD |
| Azilsartan medoxomil and chlorthalidoneAlso: TAK-491CLDAzilsartan medoxomil 80 mg and chlorthalidone 25 mg combination tablets, orally, once daily for up to 8 weeks | Drug | Azilsartan medoxomil 80 mg/chlorthalidone 25 mg QD |
| ChlorthalidoneAzilsartan medoxomil placebo and chlorthalidone 12.5 mg combination tablets, orally, once daily for up to 8 weeks | Drug | Chlorthalidone 12.5 mg QD |
| ChlorthalidoneAzilsartan medoxomil placebo and chlorthalidone 25 mg combination tablets, orally, once daily for up to 8 weeks | Drug | Chlorthalidone 25 mg QD |
| Azilsartan medoxomilAlso: TAK-491CLDAzilsartan medoxomil 20 mg and chlorthalidone placebo combination tablets, orally, once daily for up to 8 weeks | Drug | Azilsartan medoxomil 20 mg QD |
| Azilsartan medoxomilAlso: TAK-491CLDAzilsartan medoxomil 40 mg and chlorthalidone placebo combination tablets, orally, once daily for up to 8 weeks | Drug | Azilsartan medoxomil 40 mg QD |
| Azilsartan medoxomilAlso: TAK-491CLDAzilsartan medoxomil 80 mg and chlorthalidone placebo combination tablets, orally, once daily for up to 8 weeks | Drug | Azilsartan medoxomil 80 mg QD |
Primary outcome
Change From Baseline to Week 8 in Trough, Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring (Pooled Analysis)
Time frame: Baseline and Week 8.
The change in trough systolic blood pressure measured at final visit or week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough is the average of all measurements recorded from 22 to 24 hours after dosing.
Change From Baseline to Week 8 in Trough, Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring (Pairwise Analysis)
Time frame: Baseline and Week 8.
The change in trough systolic blood pressure measured at final visit or week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough is the average of all measurements recorded from 22 to 24 hours after dosing.
16 secondary outcomes
Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure
Time frame: Baseline and Week 8
Change From Baseline to Week 8 in Trough Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring in Black Participants (Pooled Analysis)
Time frame: Baseline and Week 8.
Change From Baseline to Week 8 in Trough Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring in Black Participants (Pairwise Analysis)
Time frame: Baseline and Week 8.
Change From Baseline to Week 8 in Trough, Sitting, Clinic Diastolic Blood Pressure
Time frame: Baseline and Week 8.
Change From Baseline to Week 8 in the Mean Trough Diastolic Blood Pressure (22 to 24 Hours After Dosing), as Measured by Ambulatory Blood Pressure Monitoring.
Time frame: Baseline and Week 8.
Change From Baseline to Week 8 in the 24-hour Mean Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring
Time frame: Baseline and Week 8.
Change From Baseline to Week 8 in the 24-hour Mean Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring
Time frame: Baseline and Week 8.
Change From Baseline to Week 8 in the Mean Daytime (6 AM to 10 PM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring.
Time frame: Baseline and Week 8.
Change From Baseline to Week 8 in the Mean Daytime (6 AM to 10 PM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring.
Time frame: Baseline and Week 8.
Change From Baseline to Week 8 in the Mean Nighttime (12 AM to 6 AM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring.
Time frame: Baseline and Week 8.
Change From Baseline to Week 8 in the Mean Nighttime (12 AM to 6 AM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring.
Time frame: Baseline and Week 8.
Change From Baseline to Week 8 in the Mean Systolic Blood Pressure at 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring.
Time frame: Baseline and Week 8
Change From Baseline to Week 8 in the Mean Diastolic Blood Pressure at 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring.
Time frame: Baseline and Week 8.
Percentage of Participants Who Achieve a Clinic Systolic Blood Pressure Response at Week 8, as Defined by Clinic Systolic Blood Pressure <140 mm Hg and/or a Reduction of ≥20 mm Hg From Baseline.
Time frame: Baseline and Week 8
Percentage of Participants Who Achieve a Clinic Diastolic Blood Pressure Response at Week 8, Defined as Clinic Diastolic Blood Pressure <90 mm Hg and/or a Reduction of ≥10 mm Hg From Baseline.
Time frame: Baseline and Week 8.
Percentage of Participants Who Achieve Both a Clinic Systolic and Diastolic Blood Pressure Response at Week 8.
Time frame: Baseline and Week 8.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Executive Medical Director study director
Takeda
99 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Azilsartan medoxomil and chlorthalidone, Chlorthalidone and Azilsartan medoxomil in people with Hypertension, run by Takeda at 99 sites in 5 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 7 Feb 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 99 sites in United States, Peru, Mexico, Chile, Russia. 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 7 Feb 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, Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring (Pooled Analysis) (time frame: Baseline and Week 8.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Feb 2012.