One-Year Safety and Tolerability Study of Azilsartan Medoxomil in Participants With Essential Hypertension

Official Title: “A One-Year Phase 3, Open-Label Study to Evaluate the Safety and Tolerability of TAK-491 in Subjects With Essential Hypertension”

This purpose of this study is to evaluate the long-term safety and tolerability of azilsartan medoxomil in individuals with essential hypertension.

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 continue to maintain control successfully.

Takeda Global Research and Development is developing TAK-491 (azilsartan medoxomil) for the treatment of essential hypertension. This study is being conducted to demonstrate the long-term safety and tolerability of azilsartan medoxomil in individuals with essential hypertension.

Study participation is anticipated to be approximately 1 year and 1.5 months, and participants will be required to return to the clinic for 10 study visits.

Intervention(s) in this Clinical Trial

• Drug: Azilsartan medoxomil with or without add-on chlorthalidone
  • Azilsartan medoxomil 40 mg, tablets, orally, once daily for four weeks; increased to azilsartan medoxomil 80 mg, tablets, orally, once daily for remainder of 56-week treatment period, if tolerated. Additional antihypertensive medications added, beginning with chlorthalidone 25 mg, once-daily, if target blood pressure not achieved.
• Drug: Azilsartan medoxomil with or without add-on hydrochlorothiazide
  • Azilsartan medoxomil 40 mg, tablets, orally, once daily for four weeks; increased to azilsartan medoxomil 80 mg, tablets, orally, once daily for remainder of 56-week treatment period, if tolerated. Additional antihypertensive medications added, beginning with hydrochlorothiazide 12.5 to 25 mg, once-daily, if target blood pressure not achieved.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Azilsartan Medoxomil

Primary Measures

• Number of Participants Reporting One or More Treatment-emergent Adverse Events From Day 1 Through End of the Study - Cohort 1.
  • Time Frame: 56 weeks.
    Safety Issue?: Yes
• Number of Participants Reporting One or More Treatment-emergent Adverse Events From Day 1 Through End of the Study - Cohort 2.
  • Time Frame: 56 weeks.
    Safety Issue?: Yes

Secondary Measures

• Change From Baseline in Sitting Clinic Systolic Blood Pressure - Cohort 1.
  • Time Frame: 52 weeks
    Safety Issue?: No
• Change From Baseline in Sitting Clinic Systolic Blood Pressure - Cohort 2
  • Time Frame: 52 weeks
    Safety Issue?: No
• Change From Baseline in Sitting Clinic Diastolic Blood Pressure - Cohort 1.
  • Time Frame: 52 weeks.
    Safety Issue?: No
• Change From Baseline in Sitting Clinic Diastolic Blood Pressure - Cohort 2.
  • Time Frame: 52 weeks.
    Safety Issue?: No

Inclusion Criteria

• 1. Diastolic blood pressure greater than or equal to 95 mm Hg and less than or equal to 119 mm Hg. For diabetic subjects and subjects with chronic kidney disease, diastolic blood pressure must be greater than or equal to 85 mm Hg and less than or equal to109 mm Hg).
• 2. Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating.
• 3. Clinical laboratory evaluations within the reference range for or deemed not clinically significant by the investigator.

Exclusion Criteria

• 1. Systolic blood pressure greater than 185 mm Hg.
• 2. Expected to take angiotensin II receptor blockers other than the study drug.
• 3. Taking more than 2 antihypertensive agents.
• 4. Hypersensitive to angiotensin II receptor blockers, thiazide-type diuretics or sulfonamide-derived compounds.
• 5. Recent history of major cardiovascular event.
• 6. History of moderate to severe heart failure or hypertensive encephalopathy.
• 7. Clinically significant cardiac conduction defects.
• 8. Secondary hypertension of any etiology.
• 9. Known or suspected unilateral or bilateral renal artery stenosis.
• 10. Severe renal dysfunction or disease.
• 11. History of drug abuse or a history of alcohol abuse within the past 2 years.
• 12. Previous history of cancer that has not been in remission for at least 5 years prior to the first dose of study drug..
• 13. Uncontrolled diabetes mellitus.
• 14. Alanine aminotransferase level of greater than 2.5 times the upper limit of normal, active liver disease, or jaundice.
• 15. Serum potassium level of greater than the upper limit of normal.
• 16. Currently is participating in another investigational study or has participated in an investigational study within 30 days prior to enrollment.
• 17. Any other serious disease or condition.
• 18. Randomized in a previous azilsartan medoxomil study.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Takeda Global Research & Development Center, Inc. Industry

Overall Clinical Trial Officials and Contacts

Executive Medical Director Clinical Science Study Director Takeda Global Research & Development Center, Inc.  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00695955

Study ID Number: 01-05-TL-491-006

ClinicalTrials.gov Identifier: NCT00695955

Health Authority: United States: Food and Drug Administration

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