A Study to Evaluate the Safety and Tolerability of TAK-491 in Subjects With Essential Hypertension

Condition(s) targeted: Essential Hypertension

Intervention: TAK-491 (Drug); Placebo (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Takeda Global Research & Development Center, Inc.

Official(s) and/or principal investigator(s):
Alfonso Perez, MD, Study Director, Affiliation: Takeda Global Research & Development Center, Inc.

Overall contact:
Dawn Bradford, Phone: 224-554-5266, Email: dbradford@tgrd.com

This is a safety and tolerability study of individualized TAK-491 doses compared to a placebo in subjects with Essential Hypertension over an eight month period.

Official title: An 8-Month Phase 3, Open-Label Study With a Blinded Reversal Phase to Evaluate the Safety and Tolerability of TAK-491 in Subjects With Essential Hypertension

Study design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: To evaluate safety and tolerability of treatment with TAK-491 in subjects with essential hypertension.

Secondary outcome:

To evaluate long-term efficacy of TAK-491 in a placebo-controlled, double-blind reversal phase after 26 weeks of open-label TAK-491 treatment in subjects with essential hypertension.

To evaluate safety and tolerability of treatment with TAK-491 in combination with chlorthalidone in subjects with essential hypertension.

Detailed description: Subjects participating in this study will begin at a starting dose of 40 mg TAK-491 once daily. Over the next 26 weeks, dosage of TAK-491 may increase to achieve the subject's target blood pressure. Chlorthalidone and other antihypertensive agents may be added to help achieve subject's target blood pressure.

At the double-blind phase, subjects will discontinue TAK-491 and be randomized to receive either TAK-491 at their current dose, or placebo for six weeks.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- The subject has essential hypertension (diastolic blood pressure ≥95mm Hg and ≤119 mm

Hg at Screening Day - 7 and enrollment visit. For subjects with diabetes or chronic

kidney disease diastolic blood pressure must be ≥85 mm Hg and ≤109 mm Hg).

- The female subject is not of childbearing potential, and agrees to use adequate

contraception if sexually active throughout the duration of the study.

- The subject has clinical laboratory evaluations within the reference range for the

testing laboratory unless the results are deemed not clinically significant for inclusion into this study by the investigator.

Exclusion Criteria:

- The subject has a systolic blood pressure greater than 185 mm Hg.

- The subject is expected to take, or anticipates taking, angiotensin II receptor

blockers other than the study drug.

- The subject is taking more than 2 antihypertensive agents.

- The subject is hypersensitive to angiotensin II receptor blockers.

- The subject has a recent history of myocardial infarction, unstable angina, coronary

artery bypass graft, percutaneous coronary intervention, cerebrovascular accident, or transient ischemic attack.

- The subject has a history of moderate to severe heart failure or hypertensive

encephalopathy.

- The subject has clinically significant cardiac conduction defects (eg, third-degree

atrioventricular block, sick sinus syndrome).

- The subject has secondary hypertension of any etiology (eg, renal disease,

pheochromocytoma, Cushing's syndrome).

- The subject has known or suspected unilateral or bilateral renal artery stenosis.

- The subject has severe renal dysfunction or disease (based on calculated creatinine

clearance <30 mL/min/1. 73 m2) at Screening.

- The subject 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 include those subjects with basal cell or stage 1 squamous cell carcinoma of the skin).

- Subject has uncontrolled diabetes mellitus with poor glucose control at screening

based on glycosylated hemoglobin >8. 5%.

- The subject has an alanine aminotransferase level of greater than 2. 5 times the upper

limit of normal, active liver disease, or jaundice.

- The subject has a serum potassium level of greater than the upper limit of normal, per

the central laboratory reference ranges.

- The subject currently is participating in another investigational study or has

participated in an investigational study within 30 days prior to enrollment.

- The subject has any other serious disease or condition that would compromise subject

safety, might affect life expectancy, or make it difficult to successfully manage and follow the subject according to the protocol.

- The subject has been randomized in a previous TAK-491 study.

Dawn Bradford, Phone: 224-554-5266, Email: dbradford@tgrd.com

Mexico DF, Mexico; Recruiting

Huntsville, Alabama, United States; Active, not recruiting

Tempe, Arizona, United States; Active, not recruiting

Chandler, Arizona, United States; Active, not recruiting

Mesa, Arizona, United States; Active, not recruiting

Los Gatos, California, United States; Active, not recruiting

Tustin, California, United States; Active, not recruiting

Westlake Village, California, United States; Active, not recruiting

Sacramento, California, United States; Active, not recruiting

Wheat Ridge, Colorado, United States; Active, not recruiting

Colorado Springs, Colorado, United States; Active, not recruiting

Pembroke Pines, Florida, United States; Active, not recruiting

Melbourne, Florida, United States; Active, not recruiting

Augusta, Georgia, United States; Active, not recruiting

South Bend, Indiana, United States; Active, not recruiting

Auburn, Maine, United States; Active, not recruiting

Chelsea, Michigan, United States; Active, not recruiting

St. Louis, Missouri, United States; Active, not recruiting

Trenton, New Jersey, United States; Active, not recruiting

Rochester, New York, United States; Active, not recruiting

Wilmington, North Carolina, United States; Active, not recruiting

Burlington, North Carolina, United States; Active, not recruiting

Cleveland, Ohio, United States; Active, not recruiting

Columbus, Ohio, United States; Active, not recruiting

Oklahoma City, Oklahoma, United States; Active, not recruiting

Philadelphia, Pennsylvania, United States; Active, not recruiting

Carlisle, Pennsylvania, United States; Active, not recruiting

Mt. Pleasant, South Carolina, United States; Active, not recruiting

North Richland Hills, Texas, United States; Recruiting

San Antonio, Texas, United States; Active, not recruiting

Norfolk, Virginia, United States; Active, not recruiting

Lakewood, Washington, United States; Active, not recruiting

Renton, Washington, United States; Active, not recruiting

Madison, Wisconsin, United States; Active, not recruiting

Starting date: July 2007
Ending date: April 2009
Last updated: October 8, 2008