Evaluation of the Efficacy and Safety of TAK-491 Co-Administered With Chlorthalidone in Subjects With Essential Hypertension

Condition(s) targeted: Essential Hypertension

Intervention: TAK-491 (Drug); chlorthalidone (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:
Kelley Micklus, MS, Phone: 224-554-5903, Email: kmicklus@tgrd.com

The purpose of this study is to evaluate the efficacy and safety of TAK-491 co-administered with chlorthalidone in treating individuals with essential hypertension, compared to treatment with chlorthalidone alone.

Official title: A Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of TAK-491 When Co-Administered With Chlorthalidone in Subjects With Essential Hypertension

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

Primary outcome: Change in 24-hour mean ambulatory blood pressure monitoring (ABPM) systolic blood pressure (SBP).

Secondary outcome:

Change from baseline in 24-hour mean ABPM diastolic blood pressure (DBP)

Change from baseline in sitting trough clinic SBP and DBP

Change from baseline in SBP and DBP using additional ABPM parameters (daytime mean, nighttime mean, BP mean at 0-12 hours after dosing, and trough mean at 22 to 24 hours after dosing).

Safety endpoints (adverse events, laboratory values, ECG results, vital signs).

Detailed description: The purpose of the study is to evaluate the change in 24-hour mean systolic blood pressure (SBP) by ambulatory blood pressure monitoring (ABPM) in response to TAK-491 plus chlorthalidone compared to placebo plus chlorthalidone for 6 weeks in subjects with essential hypertension. Subjects who qualify for the study will discontinue their current antihypertensive medication. After a 2-week run-in period, subjects who meet entry criteria will receive TAK-491 plus chlorthalidone or placebo plus chlorthalidone once daily for 6 weeks. Blood pressure will be monitored during study visits, and ABPM will be used to evaluate blood pressure for 24-hour periods twice during the study. Subjects will receive physical examinations including measurement of vital signs, and blood and urine samples will be collected (for analyses related to safety monitoring) during study visits.

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

Criteria:

Inclusion Criteria:

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

- The subject has essential hypertension.

- A female subject of childbearing potential agrees to use adequate contraception from

screening throughout the duration of the study.

- The subject is willing to discontinue current antihypertensive medications at the

Screening Day - 21 visit. If the subject is taking amlodipine prior to screening, the

subject is willing to discontinue this medication at Screening Day - 28

Exclusion Criteria:

- The subject is hypersensitive to angiotensin II receptor blockers (ARBs).

- The subject has a history (within the past 6 months) of myocardial infarction (MI),

heart failure, unstable angina, coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), hypertensive encephalopathy, cerebrovascular accident, or transient ischemic attack (TIA).

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

atrioventricular [AV] block, left bundle branch block, sick sinus syndrome, atrial fibrillation or atrial flutter).

- The subject has hemodynamically significant left ventricular outflow obstruction due

to aortic valvular disease.

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

pheochromocytoma, Cushing's syndrome).

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

- The subject has type 1 or poorly controlled type 2 diabetes mellitus at Screening.

- The subject works night (3rd) shift (defined as 11 PM [2300] to 7 AM [0700]).

- If female, the subject is pregnant, intends to become pregnant during the course of

the study, or is lactating.

Kelley Micklus, MS, Phone: 224-554-5903, Email: kmicklus@tgrd.com

Huntsville, Alabama, United States; Recruiting

Montgomery, Alabama, United States; Not yet recruiting

Sacramento, California, United States; Recruiting

Mission Viejo, California, United States; Recruiting

Huntington Beach, California, United States; Recruiting

Long Beach, California, United States; Recruiting

Westlake Village, California, United States; Recruiting

Roseville, California, United States; Not yet recruiting

Buena Park, California, United States; Not yet recruiting

Coral Gables, Florida, United States; Recruiting

Hollywood, Florida, United States; Recruiting

Deland, Florida, United States; Recruiting

Miami, Florida, United States; Recruiting

Fort Lauderdale, Florida, United States; Not yet recruiting

Auburn, Maine, United States; Recruiting

Troy, Michigan, United States; Recruiting

Bingham Farms, Michigan, United States; Recruiting

Charlotte, North Carolina, United States; Recruiting

Huntersville, North Carolina, United States; Recruiting

Shelby, North Carolina, United States; Recruiting

Cincinnati, Ohio, United States; Recruiting

Centerville, Ohio, United States; Recruiting

Willoughby Hills, Ohio, United States; Recruiting

Akron, Ohio, United States; Recruiting

Zanesville, Ohio, United States; Active, not recruiting

Zanesville, Ohio, United States; Recruiting

Oklahoma City, Oklahoma, United States; Recruiting

Norman, Oklahoma, United States; Not yet recruiting

Tualatin, Oregon, United States; Recruiting

Portland, Oregon, United States; Recruiting

Eugene, Oregon, United States; Recruiting

Harleysville, Pennsylvania, United States; Not yet recruiting

Feasterville, Pennsylvania, United States; Recruiting

Bensalem, Pennsylvania, United States; Not yet recruiting

Cranston, Rhode Island, United States; Recruiting

Simpsonville, South Carolina, United States; Recruiting

Kingsport, Tennessee, United States; Recruiting

Pearland, Texas, United States; Recruiting

Houston, Texas, United States; Recruiting

San Antonio, Texas, United States; Recruiting

Corpus Christi, Texas, United States; Recruiting

Salt Lake City, Utah, United States; Recruiting

Burke, Virginia, United States; Recruiting

Arlington, Virginia, United States; Recruiting

Richmond, Virginia, United States; Not yet recruiting

Port Orchard, Washington, United States; Recruiting

Olympia, Washington, United States; Recruiting

Lakewood, Washington, United States; Recruiting

Starting date: September 2007
Ending date: September 2008
Last updated: October 26, 2008