- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01033071
Efficacy and Safety of Azilsartan Medoxomil and Chlorthalidone Compared to Olmesartan Medoxomil and Hydrochlorothiazide in Participants With Moderate to Severe Hypertension.
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
Study Overview
Status
Conditions
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 Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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British Columbia
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Abbotsford, British Columbia, Canada
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Powell River, British Columbia, Canada
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Newfoundland and Labrador
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Mount Pearl, Newfoundland and Labrador, Canada
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Nova Scotia
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Halifax, Nova Scotia, Canada
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Ontario
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London, Ontario, Canada
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Ottawa, Ontario, Canada
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Sarnia, Ontario, Canada
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Vaughan, Ontario, Canada
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Whitby, Ontario, Canada
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Woodstock, Ontario, Canada
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Alabama
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Gulf Shores, Alabama, United States
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Arizona
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Litchfield Park, Arizona, United States
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Mesa, Arizona, United States
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Scottsdale, Arizona, United States
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Tucson, Arizona, United States
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California
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Buena Park, California, United States
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Carmichael, California, United States
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Greenbrae, California, United States
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Irvine, California, United States
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Paramount, California, United States
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Sacramento, California, United States
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San Diego, California, United States
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San Francisco, California, United States
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Spring Valley, California, United States
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Wildomar, California, United States
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Colorado
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Colorado Springs, Colorado, United States
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Connecticut
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Milford, Connecticut, United States
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Waterbury, Connecticut, United States
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Delaware
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Newark, Delaware, United States
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Florida
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Aventura, Florida, United States
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Clearwater, Florida, United States
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Deland, Florida, United States
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Fort Lauderdale, Florida, United States
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Miami, Florida, United States
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Ocala, Florida, United States
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Plant City, Florida, United States
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Tallahassee, Florida, United States
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Tampa, Florida, United States
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West Palm beach, Florida, United States
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Winter Haven, Florida, United States
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Georgia
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Dunwoody, Georgia, United States
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Roswell, Georgia, United States
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Suwanee, Georgia, United States
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Illinois
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Chicago, Illinois, United States
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Melrose Park, Illinois, United States
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Naperville, Illinois, United States
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Indiana
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Avon, Indiana, United States
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Indianapolis, Indiana, United States
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Valparaiso, Indiana, United States
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Kentucky
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Crestview Hills, Kentucky, United States
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Lexington, Kentucky, United States
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Maine
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Auburn, Maine, United States
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Massachusetts
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Brockton, Massachusetts, United States
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Hyannis, Massachusetts, United States
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West Yarmouth, Massachusetts, United States
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Michigan
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Ann Arbor, Michigan, United States
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Missouri
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St Louis, Missouri, United States
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St Peters, Missouri, United States
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Nevada
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Henderson, Nevada, United States
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New Jersey
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Margate, New Jersey, United States
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Wildwood Crest, New Jersey, United States
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New Mexico
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Albuquerque, New Mexico, United States
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New York
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Glens Falls, New York, United States
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North Carolina
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Boiling Springs, North Carolina, United States
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Raleigh, North Carolina, United States
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Salisbury, North Carolina, United States
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Ohio
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Cincinnati, Ohio, United States
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Columbus, Ohio, United States
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Willoughby Hills, Ohio, United States
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Oklahoma
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Oklahoma City, Oklahoma, United States
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Yukon, Oklahoma, United States
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Oregon
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Ashland, Oregon, United States
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Portland, Oregon, United States
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Pennsylvania
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Bensalem, Pennsylvania, United States
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Feasterville, Pennsylvania, United States
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Lansdale, Pennsylvania, United States
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Pittsburgh, Pennsylvania, United States
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Reading, Pennsylvania, United States
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Tipton, Pennsylvania, United States
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Rhode Island
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Cranston, Rhode Island, United States
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Cumberland, Rhode Island, United States
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South Carolina
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Mt Pleasant, South Carolina, United States
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Simpsonville, South Carolina, United States
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Texas
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Beaumont, Texas, United States
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Dallas, Texas, United States
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Houston, Texas, United States
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North Richland Hills, Texas, United States
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San Antonio, Texas, United States
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Utah
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Magna, Utah, United States
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Virginia
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Manassas, Virginia, United States
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Washington
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Lakewood, Washington, United States
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Port Orchard, Washington, United States
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Wisconsin
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Madison, Wisconsin, United States
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Menomonee Falls, Wisconsin, United States
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Azilsartan Medoxomil 20-40mg/Chlorthalidone 12.5-25mg QD
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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.
Other Names:
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.
Other Names:
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Experimental: Azilsartan Medoxomil 40-80mg/Chlorthalidone 12.5-25mg QD
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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.
Other Names:
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.
Other Names:
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Active Comparator: Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
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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.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Change From Baseline in Trough, Sitting, Clinic Systolic Blood Pressure.
Time Frame: Baseline and Week 12.
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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.
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Baseline and Week 12.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Change From Baseline in Trough, Sitting, Clinic Systolic Blood Pressure.
Time Frame: Baseline, Week 4 and Week 8.
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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.
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Baseline, Week 4 and Week 8.
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Change From Baseline in Trough, Sitting, Clinic Diastolic Blood Pressure.
Time Frame: Baseline, Week 4, Week 8 and Week 12.
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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.
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Baseline, Week 4, Week 8 and Week 12.
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Change From Baseline in Mean Trough Systolic Blood Pressure by Ambulatory Blood Pressure Monitoring.
Time Frame: Baseline and Week 12.
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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.
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Baseline and Week 12.
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Change From Baseline in Mean Trough Diastolic Blood Pressure by Ambulatory Blood Pressure Monitoring.
Time Frame: Baseline and Week 12.
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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.
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Baseline and Week 12.
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Change From Baseline in 24-hour Mean Systolic Blood Pressure by Ambulatory Blood Pressure Monitoring.
Time Frame: Baseline and Week 12.
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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.
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Baseline and Week 12.
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Change From Baseline in 24-hour Mean Diastolic Blood Pressure by Ambulatory Blood Pressure Monitoring.
Time Frame: Baseline and Week 12.
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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.
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Baseline and Week 12.
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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.
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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).
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Baseline and Week 12.
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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.
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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).
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Baseline and Week 12.
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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.
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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).
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Baseline and Week 12.
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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.
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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).
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Baseline and Week 12.
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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.
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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.
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Baseline and Week 12.
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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.
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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.
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Baseline and Week 12.
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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.
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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.
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Baseline and Week 12.
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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.
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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.
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Baseline and Week 12.
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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.
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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.
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Baseline, Week 4, Week 8 and Week 12.
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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.
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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.
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Baseline, Week 4, Week 8 and Week 12.
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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.
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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.
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Baseline, Week 4, Week 8 and Week 12.
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Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Hypertension
- Essential Hypertension
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antihypertensive Agents
- Natriuretic Agents
- Membrane Transport Modulators
- Diuretics
- Angiotensin II Type 1 Receptor Blockers
- Angiotensin Receptor Antagonists
- Sodium Chloride Symporter Inhibitors
- Olmesartan
- Olmesartan Medoxomil
- Hydrochlorothiazide
- Chlorthalidone
- Azilsartan medoxomil
Other Study ID Numbers
- TAK-491CLD_303
- U1111-1112-4298 (Registry Identifier: WHO)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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