An Efficacy and Safety Study of Azilsartan Medoxomil Compared to Valsartan and Olmesartan in Participants With Essential Hypertension.

This study has been completed.
Sponsor:
Information provided by:
Takeda
ClinicalTrials.gov Identifier:
NCT00696436
First received: June 10, 2008
Last updated: March 24, 2011
Last verified: March 2011
  Purpose

The purpose of this study is to evaluate the efficacy and safety of azilsartan medoxomil, once daily (QD), compared to placebo, valsartan and olmesartan in participants with essential hypertension.


Condition Intervention Phase
Hypertension
Drug: Azilsartan medoxomil
Drug: Valsartan
Drug: Olmesartan
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-Blind, Randomized, Placebo-Controlled, 5-Arm Titration Study to Evaluate the Efficacy and Safety of TAK-491 When Compared With Valsartan and Olmesartan in Subjects With Essential Hypertension

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Change From Baseline in the 24-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [ Time Frame: Baseline and Week 6. ] [ Designated as safety issue: No ]
    The change in 24-hour mean systolic blood pressure measured at week 6 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.


Secondary Outcome Measures:
  • Change From Baseline in Mean Trough Clinic Sitting Systolic Blood Pressure. [ Time Frame: Baseline and Week 6. ] [ Designated as safety issue: No ]
    The change in mean trough clinic sitting systolic blood pressure measured at final visit or week 6 relative to baseline.

  • Change From Baseline in the 24-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [ Time Frame: Baseline and Week 6. ] [ Designated as safety issue: No ]
    The change in 24-hour mean diastolic blood pressure measured at week 6 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.

  • Change From Baseline in Mean Trough Clinic Sitting Diastolic Blood Pressure [ Time Frame: Baseline and Week 6. ] [ Designated as safety issue: No ]
    The change in mean trough clinic sitting systolic blood pressure measured at final visit or week 6 relative to baseline.

  • Change From Baseline in Daytime (6am to 10 pm) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [ Time Frame: Baseline and Week 6. ] [ Designated as safety issue: No ]
    The change in daytime (6am to 10pm) mean systolic blood pressure measured at week 6 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 and 10 pm.

  • Change From Baseline in Daytime (6am to 10 pm) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [ Time Frame: Baseline and Week 6. ] [ Designated as safety issue: No ]
    The change in daytime (6am to 10pm) mean diastolic blood pressure measured at week 6 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 and 10 pm.

  • Change From Baseline in the Nighttime (12 am to 6 am) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [ Time Frame: Baseline and Week 6. ] [ Designated as safety issue: No ]
    The change in nighttime (12am to 6am) mean systolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of all measurements recorded between the hours of 12 am and 6 am.

  • Change From Baseline in the Nighttime (12 am to 6 am) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [ Time Frame: Baseline and Week 6. ] [ Designated as safety issue: No ]
    The change in nighttime (12am to 6am) mean diastolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of all measurements recorded between the hours of 12 am and 6 am.

  • Change From Baseline in the 12-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [ Time Frame: Baseline and Week 6. ] [ Designated as safety issue: No ]
    The change in the 12-hour mean systolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 12-hour mean is the average of all measurements recorded in the first 12 hours after dosing.

  • Change From Baseline in the 12-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [ Time Frame: Baseline and Week 6. ] [ Designated as safety issue: No ]
    The change in the 12-hour mean diastolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 12-hour mean is the average of all measurements recorded in the first 12 hours after dosing.

  • Change From Baseline in the Trough (22-24-hr) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [ Time Frame: Baseline and Week 6. ] [ Designated as safety issue: No ]
    The change in trough mean systolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough mean is the average of all measurements recorded from 22 to 24 hours after dosing.

  • Change From Baseline in the Trough (22-24-hr) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [ Time Frame: Baseline and Week 6. ] [ Designated as safety issue: No ]
    The change in trough mean diastolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough mean is the average of all measurements recorded from 22 to 24 hours after dosing.

  • Percentage of Participants Who Achieve a Clinic Systolic Blood Pressure Response, Defined as < 140 mm Hg and/or Reduction From Baseline ≥ 20 mm Hg [ Time Frame: Baseline and Week 6. ] [ Designated as safety issue: No ]
    Percentage of participants who achieve a clinic systolic blood pressure response measured at week 6, 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 3 trough sitting systolic blood pressure measurements.

  • Percentage of Participants Who Achieve a Clinic Diastolic Blood Pressure Response, Defined as < 90 mm Hg and/or Reduction From Baseline ≥ 10 mm Hg [ Time Frame: Baseline and Week 6. ] [ Designated as safety issue: No ]
    Percentage of participants who achieve a clinic diastolic blood pressure response measured at week 6, 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 3 trough sitting diastolic blood pressure measurements.

  • Percentage of Participants Who Achieve Both a Clinic Diastolic and Systolic Blood Pressure Response [ Time Frame: Baseline and Week 6. ] [ Designated as safety issue: No ]
    Percentage of participants who achieve both a clinic diastolic and systolic blood pressure response measured at week 6, 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 3 sitting blood pressure measurements.


Enrollment: 1291
Study Start Date: April 2008
Study Completion Date: August 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Azilsartan Medoxomil 40 mg QD Drug: Azilsartan medoxomil

Azilsartan medoxomil 20 mg, tablets and matching placebo comparator orally once daily for two weeks.

Increased to azilsartan medoxomil 40 mg tablets and matching placebo comparator orally, once daily for up to four weeks.

Other Names:
  • TAK-491
  • Edarbi
Experimental: Azilsartan Medoxomil 80 mg QD Drug: Azilsartan medoxomil

Azilsartan medoxomil 40 mg, tablets and matching placebo comparator orally, once daily for two weeks.

Increased to Azilsartan medoxomil 80 mg, tablets and matching placebo comparator orally, once daily for up to four weeks.

Other Names:
  • TAK-491
  • Edarbi
Active Comparator: Valsartan 320 mg QD Drug: Valsartan

Valsartan 160 mg, tablets, and matching placebo comparator orally, once daily for two weeks.

Increased to Valsartan 320 mg, tablets, and matching placebo comparator, orally, once daily for up to four weeks.

Other Name: Diovan®
Active Comparator: Olmesartan 40 mg QD Drug: Olmesartan

Olmesartan 20 mg, tablets and matching placebo comparator, orally, once daily for two weeks.

Increased to Olmesartan 40 mg, tablets and matching placebo comparator, orally, once daily for up to four weeks.

Other Name: Benicar®
Placebo Comparator: Placebo QD Drug: Placebo
Matching placebo, orally, once daily for up to six weeks.

Detailed Description:

Hypertension affects approximately 50 million individuals in the United States. As the population ages, the prevalence of hypertension will continue to increase if broad and effective preventive measures are not implemented. 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. Despite the availability of antihypertensive treatments, hypertension remains inadequately controlled: only about one-third of patients successfully maintain control.

A major component of blood pressure regulation is the renin-angiotensin-aldosterone system. This is a system of hormone-mediated feedback interactions that result in the relaxation or constriction of blood vessels in response to various stimuli. Angiotensin II, a polypeptide hormone, is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme as part of the renin-angiotensin-aldosterone system. Angiotensin II is the principal pressor agent of the renin-angiotensin-aldosterone system and has multiple effects on the cardiovascular system and on electrolyte homeostasis.

TAK-491 (azilsartan medoxomil) is an angiotensin II type 1 receptor antagonist currently being tested as a treatment for essential hypertension.

Study participation is anticipated to be about 10 weeks. Multiple procedures will occur at each visit which may include fasting, blood collection, urine collection, physical examinations, electrocardiograms and ambulatory blood pressure monitoring. Outside of the study center, participants will be required wear an ambulatory blood pressure monitoring device at 24 hour intervals.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Essential hypertension (sitting systolic blood pressure between 150 and 180 mm Hg, inclusive, at Day -1 and 24-hour mean systolic blood pressure between 130 and 170 mm Hg, inclusive, at Day 1).
  2. Capable of understanding and complying with protocol requirements.
  3. 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
  4. Clinical laboratory evaluations within the reference range for the testing laboratory or the results are deemed not clinically significant for inclusion into this study by the investigator.
  5. Willing to discontinue current antihypertensive medications at Screening Day 21 visit. If the participant is on amlodipine prior to Screening, the participant is willing to discontinue this medication at Screening Day -28.

Exclusion Criteria:

  1. Sitting diastolic blood pressure greater than 114 mm Hg at Day -1 (day prior to Randomization).
  2. Baseline 24-hour ambulatory blood pressure monitor reading of insufficient quality.
  3. Taking or expected to take an excluded medication as described in the Excluded Medications.
  4. Hypersensitive to angiotensin II receptor blockers.
  5. History of myocardial infarction, heart failure, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebrovascular accident, or transient ischemic attack.
  6. Clinically significant cardiac conduction defects.
  7. Hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease.
  8. Secondary hypertension of any etiology.
  9. Noncompliant (less than 70% or greater than 130%) with study medication during run-in period.
  10. Moderate to severe renal dysfunction or disease.
  11. Known or suspected unilateral or bilateral renal artery stenosis.
  12. History of drug or alcohol abuse within the past 2 years.
  13. Previous 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).
  14. Type 1 or poorly-controlled type 2 diabetes mellitus (glycosylate hemoglobin greater than 8.0%) at Screening.
  15. Hyperkalemia as defined by the central laboratory normal reference range at Screening.
  16. Alanine aminotransferase level of greater than 2.5 times the upper limit of normal, active liver disease, or jaundice at Screening.
  17. Upper arm circumference less than 24 cm or greater than 42 cm.
  18. Works night (3rd) shift (defined as 11 PM [2300] to 7 AM [0700]).
  19. Unwilling or unable to comply with the protocol or scheduled appointments.
  20. Currently is participating in another investigational study or has participated in an investigational study within 30 days prior to Randomization.
  21. Any other serious disease or condition at Screening or Randomization that would compromise participant's safety, might affect life expectancy, or make it difficult to successfully manage and follow the subject according to the protocol.
  22. Has been randomized in a previous azilsartan medoxomil study.
  23. Is required to take or continues taking any disallowed medication, prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00696436

  Hide Study Locations
Locations
United States, Alabama
Alabaster, Alabama, United States
Ozark, Alabama, United States
United States, Arizona
Green Valley, Arizona, United States
Litchfield Park, Arizona, United States
Mesa, Arizona, United States
Tempe, Arizona, United States
United States, California
Carmichael, California, United States
Chula Vista, California, United States
Lincoln, California, United States
Mission Viejo, California, United States
National City, California, United States
Pasadena, California, United States
Riverside, California, United States
Sacramento, California, United States
San Diego, California, United States
San Dimas, California, United States
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Dunwoody, Georgia, United States
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Las Vegas, Nevada, United States
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Columbus, Ohio, United States
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Norman, Oklahoma, United States
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Pittsburgh, Pennsylvania, United States
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Charleston, South Carolina, United States
Murrells Inlet, South Carolina, United States
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Cleveland, Tennessee, United States
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Bedford, Texas, United States
Dallas, Texas, United States
Houston, Texas, United States
Missouri City, Texas, United States
San Antonio, Texas, United States
Sugarland, Texas, United States
United States, Washington
Tacoma, Washington, United States
Argentina
Carlos Paz, Córdoba, Argentina
Guaymayen, Mendoza, Argentina
Bahía Blanca, Argentina
Berazategui, Argentina
Buenos Aires, Argentina
Corrientes, Argentina
Córdoba, Argentina
Haedo Pcia. de Buenos Aires, Argentina
Jujuy, Argentina
La Plata, Argentina
Ramos Mejía Pcia. de Buenos Aires, Argentina
Rosario, Argentina
Salta, Argentina
San Miguel de Tucumán, Argentina
Brazil
Belo Horizonte, Brazil
Campinas, Brazil
Fortaleza, Brazil
Goiaenia, Brazil
Joildille, Brazil
Porto Alegre, Brazil
Rio Janeiro, Brazil
Sao Paulo, Brazil
Sorocava, Brazil
Mexico
Tijuana, Baja California, Mexico
León, Guanajuato, Mexico
Guadalajara, Jalapa, Mexico
Monterrey, Nuevo Leon, Mexico
Xalapa, Veracruz, Mexico
Aguascalientes, Mexico
Chihuahua, Mexico
Mexico City, Mexico
Querètaro, Mexico
San Luis Potosí, Mexico
Peru
Arequipa, Peru
Cusco, Peru
Huaura, Peru
Ica, Peru
Lima, Peru
Trujillo, Peru
Puerto Rico
Aguas Buenas, Puerto Rico
Carolina, Puerto Rico
Jardines de Loiza, Puerto Rico
Orocovis, Puerto Rico
Ponce, Puerto Rico
San Juan, Puerto Rico
Sponsors and Collaborators
Takeda
Investigators
Study Director: Executive Medical Director Clinical Science Takeda
  More Information

Additional Information:
Publications:
Responsible Party: Sr. VP, Clinical Science, Takeda Global Research & Development Center, Inc.
ClinicalTrials.gov Identifier: NCT00696436     History of Changes
Other Study ID Numbers: 01-06-TL-491-019, U1111-1113-9161
Study First Received: June 10, 2008
Results First Received: March 24, 2011
Last Updated: March 24, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Takeda:
Essential Hypertension
Cardiovascular Disease
High Blood Pressure
Drug Therapy

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases
Valsartan
Olmesartan
Olmesartan medoxomil
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 19, 2014