Essential HypertensionPhase 3NCT01033071
Efficacy and Safety of Azilsartan Medoxomil and Chlorthalidone Compared to Olmesartan Medoxomil and Hydrochlorothiazide in Participants With Moderate to Severe Hypertension.
A Phase 3 study testing Azilsartan medoxomil and chlorthalidone and Olmesartan medoxomil and hydrochlorothiazide in people with Essential Hypertension, run by Takeda at 94 sites in 2 countries.
Trial summary
The purpose of this study is to compare the antihypertensive effect of azilsartan medoxomil plus chlorthalidone, once daily (QD), to olmesartan medoxomil plus hydrochlorothiazide 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
- Essential Hypertension
- What is being tested?
- Azilsartan medoxomil and chlorthalidone and Olmesartan medoxomil and hydrochlorothiazide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,071 participants
- Where
- 94 sitesin 2 countries
- Study dates
- Jan 2010to Nov 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
- Has a mean sitting clinic systolic blood pressure greater than or equal to 160 and less than or equal to 190 mm Hg.
- Females of childbearing potential who are sexually active agree to routinely use adequate contraception from Screening through 30 days after the last administered study drug dose.
- 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 Day -28 if the participant is on amlodipine or chlorthalidone.
Who cannot join
- Has a mean sitting clinic diastolic blood pressure greater than 119 mm Hg on Day -1.
- Has a baseline 24-hour ambulatory blood pressure monitoring reading of insufficient quality.
- Works a night (third) shift.
- Has an upper arm circumference less than 24 cm or greater than 42 cm.
- Has secondary hypertension of any etiology.
- 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.
Show all 17Show fewer
- 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 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 the participant according to the protocol.
- Has known hypersensitivity to angiotensin II receptor blockers or thiazide-type diuretics or other sulfonamide-derived compounds.
- Has a history of drug abuse or a history of alcohol abuse within the past 2 years.
Trial locations and contacts
94 sites in 2 countries.
94 sites in 2 countries
United States84 sites
Study site
Albuquerque, New Mexico
Study site
Ann Arbor, Michigan
Study site
Ashland, Oregon
Study site
Auburn, Maine
Study site
Aventura, Florida
Study site
Avon, Indiana
Study site
Beaumont, Texas
Study site
Bensalem, Pennsylvania
Study site
Boiling Springs, North Carolina
Study site
Brockton, Massachusetts
Study site
Buena Park, California
Study site
Carmichael, California
Study site
Chicago, Illinois
Study site
Cincinnati, Ohio
Study site
City of Saint Peters, Missouri
Study site
Clearwater, Florida
Study site
Colorado Springs, Colorado
Study site
Columbus, Ohio
Study site
Cranston, Rhode Island
Study site
Crestview Hills, Kentucky
Study site
Cumberland, Rhode Island
Study site
Dallas, Texas
Study site
DeLand, Florida
Study site
Dunwoody, Georgia
Study site
Feasterville, Pennsylvania
Study site
Fort Lauderdale, Florida
Study site
Glens Falls, New York
Study site
Greenbrae, California
Study site
Gulf Shores, Alabama
Study site
Henderson, Nevada
Study site
Houston, Texas
Study site
Hyannis, Massachusetts
Study site
Indianapolis, Indiana
Study site
Irvine, California
Study site
Lakewood, Washington
Study site
Lansdale, Pennsylvania
Study site
Lexington, Kentucky
Study site
Litchfield Park, Arizona
Study site
Madison, Wisconsin
Study site
Magna, Utah
Study site
Manassas, Virginia
Study site
Margate City, New Jersey
Study site
Melrose Park, Illinois
Study site
Menomonee Falls, Wisconsin
Study site
Mesa, Arizona
Study site
Miami, Florida
Study site
Milford, Connecticut
Study site
Mt. Pleasant, South Carolina
Study site
Naperville, Illinois
Study site
Newark, Delaware
Study site
North Richland Hills, Texas
Study site
Ocala, Florida
Study site
Oklahoma City, Oklahoma
Study site
Paramount, California
Study site
Pittsburgh, Pennsylvania
Study site
Plant City, Florida
Study site
Port Orchard, Washington
Study site
Portland, Oregon
Study site
Raleigh, North Carolina
Study site
Reading, Pennsylvania
Study site
Roswell, Georgia
Study site
Sacramento, California
Study site
Salisbury, North Carolina
Study site
San Antonio, Texas
Study site
San Diego, California
Study site
San Francisco, California
Study site
Scottsdale, Arizona
Study site
Simpsonville, South Carolina
Study site
Spring Valley, California
Study site
St Louis, Missouri
Study site
Suwanee, Georgia
Study site
Tallahassee, Florida
Study site
Tampa, Florida
Study site
Tipton, Pennsylvania
Study site
Tucson, Arizona
Study site
Valparaiso, Indiana
Study site
Waterbury, Connecticut
Study site
West Palm Beach, Florida
Study site
West Yarmouth, Massachusetts
Study site
Wildomar, California
Study site
Wildwood Crest, New Jersey
Study site
Willoughby Hills, Ohio
Study site
Winter Haven, Florida
Study site
Yukon, Oklahoma
Canada10 sites
Study site
Abbotsford British Columbia, British Columbia
Study site
Halifax, Nova Scotia
Study site
London, Ontario
Study site
Mount Pearl, Newfoundland and Labrador
Study site
Ottawa, Ontario
Study site
Powell River, British Columbia
Study site
Sarnia, Ontario
Study site
Vaughan, Ontario
Study site
Whitby, Ontario
Study site
Woodstock, Ontario
About this study
Official title: A Phase 3b, Double-Blind, Randomized, 12-Week Efficacy and Safety Study Comparing the TAK-491 Plus Chlorthalidone Fixed-Dose Combination vs Olmesartan Medoxomil-Hydrochlorothiazide in Subjects With Moderate to Severe Hypertension
The purpose of this study is to compare the antihypertensive effect of azilsartan medoxomil plus chlorthalidone, once daily (QD), to olmesartan medoxomil plus hydrochlorothiazide in participants with moderate to severe 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.
Treatment algorithms for essential hypertension commonly include thiazides or thiazide-like diuretics, either alone or as part of combination treatment. Chlorthalidone is a commercially available, orally administered thiazide-type diuretic agent.
TAK-491 (azilsartan medoxomil) is an angiotensin II receptor blocker developed by Takeda to treat participants with essential hypertension.
This study will compare the safety and tolerability of azilsartan medoxomil plus chlorthalidone (TAK-491CLD) fixed-dose combination to olmesartan medoxomil plus hydrochlorothiazide fixed-dose combination.
- Conditions
- Essential Hypertension
- Being tested
- Azilsartan medoxomil and chlorthalidone, Olmesartan medoxomil and hydrochlorothiazide
- Keywords
- Hypertensive, Blood Pressure, High, Cardiovascular disease, Vascular Disease, Drug Therapy
- Medical subject headings
- Essential Hypertension, Hypertension, Cardiovascular Diseases, Vascular 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 plus chlorthalidone, TAK-491CLD
Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks.
Participants will be force titrated at Week 4 to azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks.
Participants will then be force titrated at Week 8 to azilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks.
Azilsartan medoxomil and chlorthalidoneDrug
Also called azilsartan medoxomil plus chlorthalidone, TAK-491CLD
Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks.
Participants will be force titrated at Week 4 to azilsartan medoxomil 80 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks.
Participants will then be force titrated at Week 8 to azilsartan medoxomil 80 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks.
Olmesartan medoxomil and hydrochlorothiazideDrug
Also called Benicar HCT®
Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily and azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for up to 4 weeks.
Participants will be force titrated at Week 4 to olmesartan medoxomil 40 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily for the next 4 weeks.
Participants will then be force titrated at Week 8 to olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg combination tablets, orally, once daily for the next 4 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Azilsartan Medoxomil 20-40mg/Chlorthalidone 12.5-25mg QD | Experimental | Not described Receives: Drug: Azilsartan medoxomil and chlorthalidone |
| Azilsartan Medoxomil 40-80mg/Chlorthalidone 12.5-25mg QD | Experimental | Not described Receives: Drug: Azilsartan medoxomil and chlorthalidone |
| Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD | Active comparator | Not described Receives: Drug: Olmesartan medoxomil and hydrochlorothiazide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Trough, Sitting, Clinic Systolic Blood Pressure.
The change in sitting trough clinic systolic blood pressure measured at week 12 or final visit relative to baseline. Trough blood pressure is the average of the non-missing values of the 3 serial trough sitting systolic blood pressure measurements.
Measured: Baseline and Week 12.
Secondary outcomes (17)
Change From Baseline in Trough, Sitting, Clinic Systolic Blood Pressure.
The change in sitting trough clinic systolic blood pressure measured at each week indicated relative to baseline. Trough blood pressure is the average of the non-missing values of the 3 serial trough sitting systolic blood pressure measurements.
Measured: Baseline, Week 4 and Week 8.
Change From Baseline in Trough, Sitting, Clinic Diastolic Blood Pressure.
The change in sitting trough clinic diastolic blood pressure measured at each week indicated relative to baseline. Trough blood pressure is the average (arithmetic mean) of the non-missing values of the 3 serial trough sitting systolic blood pressure measurements.
Measured: Baseline, Week 4, Week 8 and Week 12.
Change From Baseline in Mean Trough Systolic Blood Pressure by Ambulatory Blood Pressure Monitoring.
The change in trough systolic blood pressure measured at week 12 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 and Week 12.
Change From Baseline in Mean Trough Diastolic Blood Pressure by Ambulatory Blood Pressure Monitoring.
The change in trough diastolic blood pressure measured at week 12 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 and Week 12.
Change From Baseline in 24-hour Mean Systolic Blood Pressure by Ambulatory Blood Pressure Monitoring.
The change in 24-hour mean systolic blood pressure measured at week 12 or final visit 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 12.
Change From Baseline in 24-hour Mean Diastolic Blood Pressure by Ambulatory Blood Pressure Monitoring.
The change in 24-hour mean diastolic blood pressure measured at week 12 or final visit 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 12.
Change From Baseline in Mean Daytime (6 AM to 10 PM) Systolic Blood Pressure by Ambulatory Blood Pressure Monitoring.
The change in daytime (6am to 10pm) mean systolic blood pressure measured at week 12 or final visit 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 (inclusive) and 10 PM (exclusive).
Measured: Baseline and Week 12.
Change From Baseline in Mean Daytime (6 AM to 10 PM) Diastolic Blood Pressure by Ambulatory Blood Pressure Monitoring.
The change in daytime (6am to 10pm) mean diastolic blood pressure measured at week 12 or final visit 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 (inclusive) and 10 PM (exclusive).
Measured: Baseline and Week 12.
Change From Baseline in Mean Nighttime (12 AM to 6 AM) Systolic Blood Pressure by Ambulatory Blood Pressure Monitoring.
The change in the mean nighttime (12am to 6am) systolic blood pressure measured at week 12 or final visit relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Mean nighttime is the average (arithmetic mean) of measurements recorded between the hours of 12 AM (inclusive) and 6 AM (exclusive).
Measured: Baseline and Week 12.
Change From Baseline in Mean Nighttime (12 AM to 6 AM) Diastolic Blood Pressure by Ambulatory Blood Pressure Monitoring.
The change in the mean nighttime (12am to 6am) diastolic blood pressure measured at week 12 or final visit relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Mean nighttime is the average (arithmetic mean) of measurements recorded between the hours of 12 AM (inclusive) and 6 AM (exclusive).
Measured: Baseline and Week 12.
Change From Baseline in the Mean Systolic Blood Pressure at 0 to 12 Hours After Dosing by Ambulatory Blood Pressure Monitoring.
The change in the mean 12 hour systolic blood pressure measured at week 12 or final visit 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.
Measured: Baseline and Week 12.
Change From Baseline in the Mean Diastolic Blood Pressure at 0 to 12 Hours After Dosing by Ambulatory Blood Pressure Monitoring.
The change in the mean 12 hour diastolic blood pressure measured at week 12 or final visit 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.
Measured: Baseline and Week 12.
Change From Baseline in the Mean Systolic Blood Pressure During Each Hour of the 24-hour Ambulatory Blood Pressure Monitoring.
The change from baseline for each hour interval of the 24-hour ambulatory blood pressure monitoring measured at week 12 or final visit. 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 hour.
Measured: Baseline and Week 12.
Change From Baseline in the Mean Diastolic Blood Pressure During Each Hour of the 24-hour Ambulatory Blood Pressure Monitoring.
The change from baseline for each hour interval of the 24-hour ambulatory blood pressure monitoring measured at week 12 or final visit. 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 hour.
Measured: Baseline and Week 12.
Percentage of Participants Who Reached Target Clinic Systolic Blood Pressure of <140 mm Hg and/or Reduction of ≥20 mm Hg From Baseline.
Percentage of participants who achieve a clinic systolic blood pressure response measured at each week indicated, 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 non-missing values of the 3serial trough sitting systolic blood pressure measurements.
Measured: Baseline, Week 4, Week 8 and Week 12.
Percentage of Participants Who Reached Target Clinic Diastolic Blood Pressure of <90 mm Hg and/or Reduction of ≥10 mm Hg From Baseline.
Percentage of participants who achieve a clinic diastolic blood pressure response measured at each week indicated, 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 non-missing values of the 3 serial trough sitting diastolic blood pressure measurements.
Measured: Baseline, Week 4, Week 8 and Week 12.
Percent of Participants Who Reached Target Clinic Systolic Blood Pressure of <140 mm Hg and/or Reduction of ≥20 mm Hg From Baseline and Target Clinic Diastolic Blood Pressure of <90 mm Hg and/or Reduction of ≥10 mm Hg From Baseline.
Percentage of participants who achieve both a clinic diastolic and systolic blood pressure response measured at each week indicated, 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 non-missing values of the 3 serial trough sitting blood pressure measurements.
Measured: Baseline, Week 4, Week 8 and Week 12.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2009 (estimated)
- Study startJan 2010
- Primary completionOct 2010
- Study completionNov 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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Essential 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
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,071 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Sr VP Clinical Science, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01033071
- Sponsor's protocol ID
- TAK-491CLD_303
- Other IDs
- U1111-1112-4298
- Status last verified
- Jan 2012
- First submitted
- 14 Dec 2009
- Last updated
- 7 Feb 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Cushman WC, Bakris GL, White WB, Weber MA, Sica D, Roberts A, Lloyd E, Kupfer S. Azilsartan medoxomil plus chlorthalidone reduces blood pressure more effectively than olmesartan plus hydrochlorothiazide in stage 2 systolic hypertension. Hypertension. 2012 Aug;60(2):310-8. doi: 10.1161/HYPERTENSIONAHA.111.188284. Epub 2012 Jun 18.
PubMed 22710649
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 3b, Double-Blind, Randomized, 12-Week Efficacy and Safety Study Comparing the TAK-491 Plus Chlorthalidone Fixed-Dose Combination vs Olmesartan Medoxomil-Hydrochlorothiazide in Subjects With Moderate to Severe Hypertension
- ClinicalTrials.gov ID
- NCT01033071
- Acronym / sponsor ID
- TAK-491CLD_303
- Conditions
- Essential Hypertension
- Keywords
- Hypertensive, Blood Pressure, High, Cardiovascular disease, Vascular Disease, Drug Therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,071 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- Jan 2010
- Primary completion
- Oct 2010 (actual)
- Study completion
- Nov 2010 (actual)
- First posted
- 16 Dec 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 compare the antihypertensive effect of azilsartan medoxomil plus chlorthalidone, once daily (QD), to olmesartan medoxomil plus hydrochlorothiazide in participants with moderate to severe hypertension.
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.
Treatment algorithms for essential hypertension commonly include thiazides or thiazide-like diuretics, either alone or as part of combination treatment. Chlorthalidone is a commercially available, orally administered thiazide-type diuretic agent.
TAK-491 (azilsartan medoxomil) is an angiotensin II receptor blocker developed by Takeda to treat participants with essential hypertension.
This study will compare the safety and tolerability of azilsartan medoxomil plus chlorthalidone (TAK-491CLD) fixed-dose combination to olmesartan medoxomil plus hydrochlorothiazide fixed-dose combination.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Azilsartan Medoxomil 20-40mg/Chlorthalidone 12.5-25mg QD | Experimental | Drug: Azilsartan medoxomil and chlorthalidone |
| Azilsartan Medoxomil 40-80mg/Chlorthalidone 12.5-25mg QD | Experimental | Drug: Azilsartan medoxomil and chlorthalidone |
| Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD | Active comparator | Drug: Olmesartan medoxomil and hydrochlorothiazide |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Has a mean sitting clinic systolic blood pressure greater than or equal to 160 and less than or equal to 190 mm Hg.
- Females of childbearing potential who are sexually active agree to routinely use adequate contraception from Screening through 30 days after the last administered study drug dose.
- 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 Day -28 if the participant is on amlodipine or chlorthalidone.
Key exclusion criteria (17 listed)
- Has a mean sitting clinic diastolic blood pressure greater than 119 mm Hg on Day -1.
- Has a baseline 24-hour ambulatory blood pressure monitoring reading of insufficient quality.
- Works a night (third) shift.
- Has an upper arm circumference less than 24 cm or greater than 42 cm.
- Has secondary hypertension of any etiology.
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: azilsartan medoxomil plus chlorthalidone, TAK-491CLDAzilsartan medoxomil 20 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Drug | Azilsartan Medoxomil 20-40mg/Chlorthalidone 12.5-25mg QD |
| Azilsartan medoxomil and chlorthalidoneAlso: azilsartan medoxomil plus chlorthalidone, TAK-491CLDAzilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 80 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 80 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Drug | Azilsartan Medoxomil 40-80mg/Chlorthalidone 12.5-25mg QD |
| Olmesartan medoxomil and hydrochlorothiazideAlso: Benicar HCT®Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily and azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to olmesartan medoxomil 40 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg combination tablets, orally, once daily for the next 4 weeks. | Drug | Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD |
Primary outcome
Change From Baseline in Trough, Sitting, Clinic Systolic Blood Pressure.
Time frame: Baseline and Week 12.
The change in sitting trough clinic systolic blood pressure measured at week 12 or final visit relative to baseline. Trough blood pressure is the average of the non-missing values of the 3 serial trough sitting systolic blood pressure measurements.
17 secondary outcomes
Change From Baseline in Trough, Sitting, Clinic Systolic Blood Pressure.
Time frame: Baseline, Week 4 and Week 8.
Change From Baseline in Trough, Sitting, Clinic Diastolic Blood Pressure.
Time frame: Baseline, Week 4, Week 8 and Week 12.
Change From Baseline in Mean Trough Systolic Blood Pressure by Ambulatory Blood Pressure Monitoring.
Time frame: Baseline and Week 12.
Change From Baseline in Mean Trough Diastolic Blood Pressure by Ambulatory Blood Pressure Monitoring.
Time frame: Baseline and Week 12.
Change From Baseline in 24-hour Mean Systolic Blood Pressure by Ambulatory Blood Pressure Monitoring.
Time frame: Baseline and Week 12.
Change From Baseline in 24-hour Mean Diastolic Blood Pressure by Ambulatory Blood Pressure Monitoring.
Time frame: Baseline and Week 12.
Change From Baseline in Mean Daytime (6 AM to 10 PM) Systolic Blood Pressure by Ambulatory Blood Pressure Monitoring.
Time frame: Baseline and Week 12.
Change From Baseline in Mean Daytime (6 AM to 10 PM) Diastolic Blood Pressure by Ambulatory Blood Pressure Monitoring.
Time frame: Baseline and Week 12.
Change From Baseline in Mean Nighttime (12 AM to 6 AM) Systolic Blood Pressure by Ambulatory Blood Pressure Monitoring.
Time frame: Baseline and Week 12.
Change From Baseline in Mean Nighttime (12 AM to 6 AM) Diastolic Blood Pressure by Ambulatory Blood Pressure Monitoring.
Time frame: Baseline and Week 12.
Change From Baseline in the Mean Systolic Blood Pressure at 0 to 12 Hours After Dosing by Ambulatory Blood Pressure Monitoring.
Time frame: Baseline and Week 12.
Change From Baseline in the Mean Diastolic Blood Pressure at 0 to 12 Hours After Dosing by Ambulatory Blood Pressure Monitoring.
Time frame: Baseline and Week 12.
Change From Baseline in the Mean Systolic Blood Pressure During Each Hour of the 24-hour Ambulatory Blood Pressure Monitoring.
Time frame: Baseline and Week 12.
Change From Baseline in the Mean Diastolic Blood Pressure During Each Hour of the 24-hour Ambulatory Blood Pressure Monitoring.
Time frame: Baseline and Week 12.
Percentage of Participants Who Reached Target Clinic Systolic Blood Pressure of <140 mm Hg and/or Reduction of ≥20 mm Hg From Baseline.
Time frame: Baseline, Week 4, Week 8 and Week 12.
Percentage of Participants Who Reached Target Clinic Diastolic Blood Pressure of <90 mm Hg and/or Reduction of ≥10 mm Hg From Baseline.
Time frame: Baseline, Week 4, Week 8 and Week 12.
Percent of Participants Who Reached Target Clinic Systolic Blood Pressure of <140 mm Hg and/or Reduction of ≥20 mm Hg From Baseline and Target Clinic Diastolic Blood Pressure of <90 mm Hg and/or Reduction of ≥10 mm Hg From Baseline.
Time frame: Baseline, Week 4, Week 8 and Week 12.
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.
- Derived from this study: PubMed 22710649Cushman WC, Bakris GL, White WB, Weber MA, Sica D, Roberts A, Lloyd E, Kupfer S. Azilsartan medoxomil plus chlorthalidone reduces blood pressure more effectively than olmesartan plus hydrochlorothiazide in stage 2 systolic hypertension. Hypertension. 2012 Aug;60(2):310-8. doi: 10.1161/HYPERTENSIONAHA.111.188284. Epub 2012 Jun 18.
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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.
Sr VP Clinical Science study director
Takeda
94 sites in 2 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 and Olmesartan medoxomil and hydrochlorothiazide in people with Essential Hypertension, run by Takeda at 94 sites in 2 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 17 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 94 sites in United States, Canada. 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 in Trough, Sitting, Clinic Systolic Blood Pressure. (time frame: Baseline and Week 12.). 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 NCT01033071, 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 7 Feb 2012.