A One-Year Safety and Tolerability of TAK-491 in Subjects With Essential Hypertension

Condition(s) targeted: Essential Hypertension

Intervention: TAK-491 (Drug)

Phase: Phase 3

Status: Recruiting

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

Official(s) and/or principal investigator(s):
Stuart Kupfer, 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 TAK-491 at doses of 40 mg, 80 mg, 80 mg of TAK-491 plus 25 mg of chlorthalidone, and 80 mg of TAK-491 plus 25 mg of chlorthalidone plus other antihypertensive treatment if determined by the study investigator.

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

Study design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Primary outcome: To evaluate safety and tolerability of treatment with TAK-491 for up to 56 weeks in subjects with essential hypertension.

Secondary outcome: To evaluate safety and tolerability of treatment with TAK-491 in combination with chlorthalidone for up to 48 weeks in subjects with essential hypertension.

Detailed description: Subjects participating in this study will begin on Day 1 with a starting dose of TAK-491 40 mg once daily. At Week 4, if initial dose of 40 mg is tolerable, dose will be increased to 80 mg once daily. At Week 8, if the 80 mg dose is tolerable-and on an ongoing basis throughout the study-the study investigator may add chlorthalidone and other antihypertensive agents to achieve the subjects target blood pressure.

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

Criteria:

Inclusion Criteria:

- The subject is male or female and aged 18 years or older.

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

Hg at Screening Day - 7 and enrollment visit. For diabetic subjects and subjects with

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

- Females of childbearing potential agree to use appropriate birth control for the study

duration.

- The subject has clinical laboratory evaluations (including clinical chemistry,

hematology, and complete urinalysis) 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 angiotensin II receptor blockers other than the study

drug.

- The subject is taking more than two antihypertensive agents.

- The subject is hypersensitive to angiotensin II receptor blockers.

- The subject has a recent history (within the last 6 months) 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, 3rd 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 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 include those subjects with basal cell or Stage 1 squamous cell carcinoma of the skin).

- The subject has uncontrolled diabetes mellitus with poor glucose control at Screening

based on hemoglobin A1C >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 at Screening.

- 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 at Screening (or enrollment)

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

Ozark, Alabama, United States; Recruiting

Tallassee, Alabama, United States; Active, not recruiting

Tijuana, BC, Mexico; Recruiting

Long Beach, California, United States; Active, not recruiting

Santa Rosa, California, United States; Active, not recruiting

Spring Valley, California, United States; Active, not recruiting

Trumbull, Connecticut, United States; Active, not recruiting

Waterbury, Connecticut, United States; Active, not recruiting

Miami, Florida, United States; Active, not recruiting

Pinellas Park, Florida, United States; Active, not recruiting

Hollywood, Florida, United States; Active, not recruiting

Jacksonville, Florida, United States; Active, not recruiting

Atlanta, Georgia, United States; Active, not recruiting

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

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

Winston-Salem, North Carolina, United States; Active, not recruiting

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

Mogadore, Ohio, United States; Active, not recruiting

Cincinnati, Ohio, United States; Active, not recruiting

Philadelphia, Pennsylvania, United States; Recruiting

San Bernardo, Santiago, Chile; Recruiting

Simpsonville, South Carolina, United States; Active, not recruiting

Anderson, South Carolina, United States; Recruiting

Bristol, Tennessee, United States; Active, not recruiting

Nashville, Tennessee, United States; Active, not recruiting

Austin, Texas, United States; Recruiting

Arlington, Texas, United States; Active, not recruiting

North Richland Hi, Texas, United States; Active, not recruiting

Salt Lake City, Utah, United States; Active, not recruiting

Norfolk, Virginia, United States; Active, not recruiting

Starting date: June 2007
Ending date: March 2009
Last updated: October 6, 2008