Efficacy and Safety of Azilsartan Medoxomil and Chlorthalidone in Participants With Moderate to Severe Hypertension
A Phase 3, Double-Blind, Randomized, Efficacy and Safety Study of the TAK 491 Plus Chlorthalidone Fixed-Dose Combination Compared With TAK-491 and Hydrochlorothiazide Coadministration Therapy in Subjects With Moderate to Severe Essential Hypertension
2 other identifiers
interventional
609
2 countries
53
Brief Summary
The purpose of this study is to compare the antihypertensive effect of chlorthalidone vs hydrochlorothiazide when each is used with azilsartan medoxomil, once daily (QD), in participants with moderate to severe essential 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 Feb 2009
Shorter than P25 for phase_3
53 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
January 7, 2009
CompletedFirst Posted
Study publicly available on registry
January 8, 2009
CompletedStudy Start
First participant enrolled
February 1, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2009
CompletedStudy Completion
Last participant's last visit for all outcomes
November 1, 2009
CompletedResults Posted
Study results publicly available
February 7, 2012
CompletedFebruary 7, 2012
January 1, 2012
9 months
January 7, 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 each week indicated including final visit relative to baseline. Systolic blood pressure is the average of the 3 serial trough sitting systolic blood pressure measurements.
Baseline, Week 6 and Week 10.
Secondary Outcomes (14)
Change From Baseline in Trough, Sitting, Clinic Diastolic Blood Pressure
Baseline, Week 6 and Week 10.
Change From Baseline in Mean Trough Systolic Blood Pressure (22 to 24 Hours After Dosing) as Measured by Ambulatory Blood Pressure Monitoring.
Baseline, Week 6 and Week 10.
Change From Baseline in Mean Trough Diastolic Blood Pressure (22 to 24 Hours After Dosing) as Measured by Ambulatory Blood Pressure Monitoring.
Baseline, Week 6 and Week 10.
Change From Baseline in 24-hour Mean Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring.
Baseline, Week 6 and Week 10.
Change From Baseline in 24-hour Mean Diastolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring.
Baseline, Week 6 and Week 10.
- +9 more secondary outcomes
Study Arms (2)
Azilsartan Medoxomil 40 mg/Chlorthalidone 12.5 mg QD
EXPERIMENTALAzilsartan Medoxomil 40 mg + Hydrochlorothiazide 12.5 mg QD
EXPERIMENTALInterventions
Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablet, orally, once daily and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 10 weeks. For participants who do not achieve target blood pressure by Week 6, the dose of chlorthalidone will be increased for the remaining 4 weeks of treatment.
Azilsartan medoxomil 40 mg, tablets, orally, once daily and hydrochlorothiazide 12.5 mg, tablets, orally, once daily for up to 10 weeks. For participants who do not achieve target blood pressure by Week 6, the dose of hydrochlorothiazide will be increased for the remaining 4 weeks of treatment.
Eligibility Criteria
You may qualify if:
- Is treated with antihypertensive therapy and has a post-washout mean sitting clinic SBP greater than or equal to 160 and less than or equal to 190 mm Hg on Day -1; or the participant has not received antihypertensive treatment within 28 days prior to Screening and has a mean sitting clinic SBP greater than or equal to 160 and less than or equal to 190 mm Hg at the Screening Visit and on Day -1.
- 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 (clinical chemistry, hematology, and complete urinalysis) 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 (defined as 11 PM \[2300\] to 7 AM \[0700\]).
- Has an upper arm circumference less than 24 cm or greater than 42 cm.
- Is noncompliant (less than 70% or greater than 130%) with study medication during the placebo run-in period.
- Has secondary hypertension of any etiology (eg, renovascular disease, pheochromocytoma, Cushing's syndrome).
- Has a recent history (within the last 6 months) of myocardial infarction, heart failure, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebrovascular accident, or transient ischemic attack.
- Has clinically significant cardiac conduction defects (ie, third-degree atrioventricular block, sick sinus syndrome, atrial fibrillation, or atrial flutter).
- Has hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease.
- Has severe renal dysfunction or disease \[based on estimated glomerular filtration rate less than 30 mL/min/1.73m2 at Screening\].
- 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. (This criterion does not apply to those participants with basal cell or stage I squamous cell carcinoma of the skin).
- Has poorly-controlled type 1 or type 2 diabetes mellitus at Screening.
- Has hypokalemia or hyperkalemia (defined as serum potassium outside of the normal reference range of the central laboratory).
- Has an alanine aminotransferase or aspartate aminotransferase level of greater than 2.5 times the upper limit of normal, active liver disease, or jaundice.
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Takedalead
Study Sites (53)
Unknown Facility
Birmingham, Alabama, United States
Unknown Facility
Gulf Shores, Alabama, United States
Unknown Facility
Scottsboro, Alabama, United States
Unknown Facility
Gilbert, Arizona, United States
Unknown Facility
Sierra Vista, Arizona, United States
Unknown Facility
Paramount, California, United States
Unknown Facility
Sacramento, California, United States
Unknown Facility
San Diego, California, United States
Unknown Facility
Colorado Springs, Colorado, United States
Unknown Facility
Wheat Ridge, Colorado, United States
Unknown Facility
Milford, Connecticut, United States
Unknown Facility
Adventura, Florida, United States
Unknown Facility
Aventura, Florida, United States
Unknown Facility
Brooksville, Florida, United States
Unknown Facility
Crystal River, Florida, United States
Unknown Facility
DeLand, Florida, United States
Unknown Facility
Doral, Florida, United States
Unknown Facility
Miami, Florida, United States
Unknown Facility
Naranja, Florida, United States
Unknown Facility
Sarasota, Florida, United States
Unknown Facility
Tampa, Florida, United States
Unknown Facility
West Palm Beach, Florida, United States
Unknown Facility
Winter Haven, Florida, United States
Unknown Facility
Atlanta, Georgia, United States
Unknown Facility
Stockbridge, Georgia, United States
Unknown Facility
Suwanee, Georgia, United States
Unknown Facility
Huntsville, Illinois, United States
Unknown Facility
Bloomington, Indiana, United States
Unknown Facility
Valparaiso, Indiana, United States
Unknown Facility
Crestview Hills, Kentucky, United States
Unknown Facility
Lexington, Kentucky, United States
Unknown Facility
West Yarmouth, Massachusetts, United States
Unknown Facility
Ann Arbor, Michigan, United States
Unknown Facility
City of Saint Peters, Missouri, United States
Unknown Facility
St Louis, Missouri, United States
Unknown Facility
New Windsor, New York, United States
Unknown Facility
Asheboro, North Carolina, United States
Unknown Facility
Cincinnati, Ohio, United States
Unknown Facility
Kettering, Ohio, United States
Unknown Facility
Downingtown, Pennsylvania, United States
Unknown Facility
Lancaster, Pennsylvania, United States
Unknown Facility
Lansdale, Pennsylvania, United States
Unknown Facility
Pittsburgh, Pennsylvania, United States
Unknown Facility
Goose Creek, South Carolina, United States
Unknown Facility
Taylors, South Carolina, United States
Unknown Facility
Bryan, Texas, United States
Unknown Facility
San Antonio, Texas, United States
Unknown Facility
Ettrick, Virginia, United States
Unknown Facility
Seattle, Washington, United States
Unknown Facility
Madison, Wisconsin, United States
Unknown Facility
Moscow, Russia
Unknown Facility
Perm, Russia
Unknown Facility
Saint Petersburg, Russia
Related Publications (1)
Bakris GL, Sica D, White WB, Cushman WC, Weber MA, Handley A, Song E, Kupfer S. Antihypertensive efficacy of hydrochlorothiazide vs chlorthalidone combined with azilsartan medoxomil. Am J Med. 2012 Dec;125(12):1229.e1-1229.e10. doi: 10.1016/j.amjmed.2012.05.023. Epub 2012 Aug 30.
PMID: 22939358DERIVED
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
Executive Medical Director
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
January 7, 2009
First Posted
January 8, 2009
Study Start
February 1, 2009
Primary Completion
November 1, 2009
Study Completion
November 1, 2009
Last Updated
February 7, 2012
Results First Posted
February 7, 2012
Record last verified: 2012-01