Efficacy and Safety of Azilsartan Medoxomil Plus Chlorthalidone in Participants With Moderate to Severe Hypertension
A Phase 3, Double-Blind, Randomized, Efficacy and Safety Study Comparing the TAK-491 Plus Chlorthalidone Fixed-Dose Combination vs Benicar HCT® (Olmesartan Medoxomil-Hydrochlorothiazide) in Subjects With Moderate to Severe Essential Hypertension
2 other identifiers
interventional
1,085
3 countries
80
Brief Summary
The purpose of this study is to determine the efficacy and safety of azilsartan medoxomil combined with chlorthalidone, once daily (QD), in participants with moderate to severe 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 Mar 2009
Shorter than P25 for phase_3
80 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
February 13, 2009
CompletedFirst Posted
Study publicly available on registry
February 18, 2009
CompletedStudy Start
First participant enrolled
March 1, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2010
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2010
CompletedResults Posted
Study results publicly available
March 13, 2012
CompletedMarch 13, 2012
February 1, 2012
1.3 years
February 13, 2009
January 4, 2012
February 9, 2012
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure.
The change in trough systolic blood pressure measured at week 8 or final visit relative to baseline. Systolic blood pressure is the average of the 3 serial trough sitting systolic blood pressure measurements.
Baseline and Week 8.
Secondary Outcomes (15)
Change From Baseline to Week 4 in Trough, Sitting, Clinic Systolic Blood Pressure.
Baseline and Week 4.
Change From Baseline in Trough, Sitting, Clinic Diastolic Blood Pressure
Baseline, Week 4 and Week 8.
Change From Baseline in Trough Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Baseline, Week 4 and Week 8.
Change From Baseline in Trough Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Baseline, Week 4 and Week 8.
Change From Baseline in 24-hour Mean Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring.
Baseline, Week 4 and Week 8.
- +10 more secondary outcomes
Study Arms (3)
Azilsartan Medoxomil 20-40mg plus Chlorthalidone 12.5-25 mg QD
EXPERIMENTAL(dependant on blood pressure)
Azilsartan Medoxomil 40-80mg plus Chlorthalidone 12.5-25 mg QD
EXPERIMENTAL(dependant on blood pressure)
Olmesartan medoxomil 20-40mg/hydrochlorothiazide 12.5-25mg QD
ACTIVE COMPARATOR(dependant on blood pressure)
Interventions
Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.
Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.
Eligibility Criteria
You may qualify if:
- mm Hg on Day -1 or if the participant has not received antihypertensive treatment within 28 days before screening and has a mean sitting clinic systolic blood pressure greater than or equal to 160 and less than or equal to 190 mm Hg at the Screening Visit and on Day -1.
- Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.
- Has clinical laboratory test results within the reference range for the testing laboratory or the investigator does not consider the results to be clinically significant.
- Is willing to discontinue current antihypertensive medications on Day -21 or on Day -28 if is on amlodipine or chlorthalidone.
You may not qualify if:
- Has a mean sitting clinic diastolic blood pressure greater than 119 mm Hg.
- Has a baseline 24-hour ambulatory blood pressure monitoring reading of insufficient quality.
- Works a night (third) shift (from 11 PM \[2300\] to 7 AM \[0700\]).
- Has an upper arm circumference less than 24 cm or greater than 42 cm.
- Is noncompliant with study medication during the placebo run-in period.
- 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 a clinically significant cardiac conduction.
- Has hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease.
- Has severe renal dysfunction or disease.
- Has a known or suspected unilateral or bilateral renal artery stenosis.
- Has a history of cancer that has not been in remission for at least 5 years prior to the first dose of study drug.
- Has poorly controlled type 1 or type 2 diabetes mellitus.
- 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.
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Takedalead
Study Sites (80)
Unknown Facility
Birmingham, Alabama, United States
Unknown Facility
Haleyville, Alabama, United States
Unknown Facility
Hueytown, Alabama, United States
Unknown Facility
Jasper, Alabama, United States
Unknown Facility
Tallassee, Alabama, United States
Unknown Facility
Green Valley, Arizona, United States
Unknown Facility
Phoenix, Arizona, United States
Unknown Facility
Long Beach, California, United States
Unknown Facility
National City, California, United States
Unknown Facility
Roseville, California, United States
Unknown Facility
San Francisco, California, United States
Unknown Facility
San Jose, California, United States
Unknown Facility
Newark, Delaware, United States
Unknown Facility
Clearwater, Florida, United States
Unknown Facility
Jacksonville, Florida, United States
Unknown Facility
Jupiter, Florida, United States
Unknown Facility
Miami, Florida, United States
Unknown Facility
Ocala, Florida, United States
Unknown Facility
Pembroke Pines, Florida, United States
Unknown Facility
Plant City, Florida, United States
Unknown Facility
Tallahassee, Florida, United States
Unknown Facility
Arlington Heights, Illinois, United States
Unknown Facility
Chicago, Illinois, United States
Unknown Facility
Gurnee, Illinois, United States
Unknown Facility
Avon, Indiana, United States
Unknown Facility
Wichita, Kansas, United States
Unknown Facility
Louisville, Kentucky, United States
Unknown Facility
Auburn, Maine, United States
Unknown Facility
Baltimore, Maryland, United States
Unknown Facility
Brockton, Massachusetts, United States
Unknown Facility
Haverhill, Massachusetts, United States
Unknown Facility
North Dartmouth, Massachusetts, United States
Unknown Facility
Bingham Farms, Michigan, United States
Unknown Facility
Stevensville, Michigan, United States
Unknown Facility
Olive Branch, Mississippi, United States
Unknown Facility
Kansas City, Missouri, United States
Unknown Facility
New York, New York, United States
Unknown Facility
Burlington, North Carolina, United States
Unknown Facility
Charlotte, North Carolina, United States
Unknown Facility
Hickory, North Carolina, United States
Unknown Facility
Shelby, North Carolina, United States
Unknown Facility
Akron, Ohio, United States
Unknown Facility
Cleveland, Ohio, United States
Unknown Facility
Columbus, Ohio, United States
Unknown Facility
Marion, Ohio, United States
Unknown Facility
Middleburg Heights, Ohio, United States
Unknown Facility
Willoughby Hills, Ohio, United States
Unknown Facility
Norman, Oklahoma, United States
Unknown Facility
Bensalem, Pennsylvania, United States
Unknown Facility
Erie, Pennsylvania, United States
Unknown Facility
Reading, Pennsylvania, United States
Unknown Facility
Cranston, Rhode Island, United States
Unknown Facility
Cumberland, Rhode Island, United States
Unknown Facility
North Charleston, South Carolina, United States
Unknown Facility
Jackson, Tennessee, United States
Unknown Facility
Kingsport, Tennessee, United States
Unknown Facility
Milan, Tennessee, United States
Unknown Facility
Austin, Texas, United States
Unknown Facility
Corpus Christi, Texas, United States
Unknown Facility
Dallas, Texas, United States
Unknown Facility
Houston, Texas, United States
Unknown Facility
San Antonio, Texas, United States
Unknown Facility
Salt Lake City, Utah, United States
Unknown Facility
Arlington, Virginia, United States
Unknown Facility
Burke, Virginia, United States
Unknown Facility
Charlottesville, Virginia, United States
Unknown Facility
Manassas, Virginia, United States
Unknown Facility
Lakewood, Washington, United States
Unknown Facility
Port Orchard, Washington, United States
Unknown Facility
Menomonee Falls, Wisconsin, United States
Unknown Facility
Temuco, Cautín, Chile
Unknown Facility
La Serena, Elqui, Chile
Unknown Facility
Osorno, Osorno, Chile
Unknown Facility
Viña del Mar, Región de Valparaíso, Chile
Unknown Facility
Santiago, Santiago Metropolitan, Chile
Unknown Facility
Chihuahua City, Chihuahua, Mexico
Unknown Facility
Tijuana, Estado de Baja California, Mexico
Unknown Facility
León, Guanajuato, Mexico
Unknown Facility
Guadalajara, Jalisco, Mexico
Unknown Facility
San Luis Potosí City, San Luis Potosí, Mexico
Related Publications (1)
Cushman WC, Bakris GL, White WB, Weber MA, Sica D, Roberts A, Lloyd E, Kupfer S. A randomized titrate-to-target study comparing fixed-dose combinations of azilsartan medoxomil and chlorthalidone with olmesartan and hydrochlorothiazide in stage-2 systolic hypertension. J Hypertens. 2018 Apr;36(4):947-956. doi: 10.1097/HJH.0000000000001647.
PMID: 29334491DERIVED
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
February 13, 2009
First Posted
February 18, 2009
Study Start
March 1, 2009
Primary Completion
June 1, 2010
Study Completion
June 1, 2010
Last Updated
March 13, 2012
Results First Posted
March 13, 2012
Record last verified: 2012-02