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
2 other identifiers
interventional
1,071
2 countries
94
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jan 2010
Shorter than P25 for phase_3
94 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 14, 2009
CompletedFirst Posted
Study publicly available on registry
December 16, 2009
CompletedStudy Start
First participant enrolled
January 1, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2010
CompletedStudy Completion
Last participant's last visit for all outcomes
November 1, 2010
CompletedResults Posted
Study results publicly available
February 7, 2012
CompletedFebruary 7, 2012
January 1, 2012
9 months
December 14, 2009
January 4, 2012
January 4, 2012
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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.
Baseline and Week 12.
Secondary Outcomes (17)
Change From Baseline in Trough, Sitting, Clinic Systolic Blood Pressure.
Baseline, Week 4 and Week 8.
Change From Baseline in Trough, Sitting, Clinic Diastolic Blood Pressure.
Baseline, Week 4, Week 8 and Week 12.
Change From Baseline in Mean Trough Systolic Blood Pressure by Ambulatory Blood Pressure Monitoring.
Baseline and Week 12.
Change From Baseline in Mean Trough Diastolic Blood Pressure by Ambulatory Blood Pressure Monitoring.
Baseline and Week 12.
Change From Baseline in 24-hour Mean Systolic Blood Pressure by Ambulatory Blood Pressure Monitoring.
Baseline and Week 12.
- +12 more secondary outcomes
Study Arms (3)
Azilsartan Medoxomil 20-40mg/Chlorthalidone 12.5-25mg QD
EXPERIMENTALAzilsartan Medoxomil 40-80mg/Chlorthalidone 12.5-25mg QD
EXPERIMENTALOlmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
ACTIVE COMPARATORInterventions
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.
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.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Takedalead
Study Sites (94)
Unknown Facility
Gulf Shores, Alabama, United States
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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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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 Springs, Colorado, United States
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Milford, Connecticut, United States
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Waterbury, Connecticut, United States
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Newark, Delaware, United States
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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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Dunwoody, Georgia, United States
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Roswell, Georgia, United States
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Suwanee, Georgia, United States
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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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Avon, Indiana, United States
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Indianapolis, Indiana, United States
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Valparaiso, Indiana, United States
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Crestview Hills, Kentucky, United States
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Lexington, Kentucky, United States
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Auburn, Maine, United States
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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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Ann Arbor, Michigan, United States
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City of Saint Peters, Missouri, United States
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St Louis, Missouri, United States
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Henderson, Nevada, United States
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Margate City, New Jersey, United States
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Wildwood Crest, New Jersey, United States
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Albuquerque, New Mexico, United States
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Glens Falls, New York, United States
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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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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 City, Oklahoma, United States
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Yukon, Oklahoma, United States
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Ashland, Oregon, United States
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Portland, Oregon, United States
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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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Cranston, Rhode Island, United States
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Cumberland, Rhode Island, United States
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Mt. Pleasant, South Carolina, United States
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Simpsonville, South Carolina, United States
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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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Magna, Utah, United States
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Manassas, Virginia, United States
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Lakewood, Washington, United States
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Port Orchard, Washington, United States
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Madison, Wisconsin, United States
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Menomonee Falls, Wisconsin, United States
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Abbotsford, British Columbia, Canada
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Powell River, British Columbia, Canada
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Mount Pearl, Newfoundland and Labrador, Canada
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Halifax, Nova Scotia, Canada
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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
Unknown Facility
Woodstock, Ontario, Canada
Related Publications (1)
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.
PMID: 22710649DERIVED
MeSH Terms
Conditions
Interventions
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Sr. VP, Clinical Science
- Organization
- Takeda Global Research and Development Center, Inc.
Study Officials
- STUDY DIRECTOR
Sr VP Clinical Science
Takeda
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 14, 2009
First Posted
December 16, 2009
Study Start
January 1, 2010
Primary Completion
October 1, 2010
Study Completion
November 1, 2010
Last Updated
February 7, 2012
Results First Posted
February 7, 2012
Record last verified: 2012-01