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”

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.

Study Type: Interventional

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

Study Primary Completion Date: September 2008

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.

Intervention(s) in this Clinical Trial

• Drug: TAK-491
  • oral TAK-491 40 mg or 80 mg QD for 6 weeks
• Drug: chlorthalidone
  • oral chlorthalidone 25 mg QD, active comparator

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: chlorthalidone 25 mg
  • oral chlorthalidone 25 mg QD
• Experimental: TAK-491 40 mg
  • oral TAK-491 40 mg QD plus oral chlorthalidone 25 mg QD
• Experimental: TAK-491 80 mg
  • oral TAK-491 80 mg QD plus oral chlorthalidone 25 mg QD

Primary Measures

• Change in 24-hour mean ambulatory blood pressure monitoring (ABPM) systolic blood pressure (SBP).
  • Time Frame: 6 weeks
    Safety Issue?: No

Secondary Measures

• Change from baseline in 24-hour mean ABPM diastolic blood pressure (DBP)
  • Time Frame: 6 weeks
    Safety Issue?: No
• Change from baseline in sitting trough clinic SBP and DBP
  • Time Frame: 6 weeks
    Safety Issue?: No
• 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).
  • Time Frame: 6 weeks
    Safety Issue?: No
• Safety endpoints (adverse events, laboratory values, ECG results, vital signs).
  • Time Frame: 6 weeks
    Safety Issue?: No

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.

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 Sponsor: Takeda Global Research & Development Center, Inc.

Overall Clinical Trial Officials and Contacts

Stuart Kupfer, MD Study Director Takeda Global Research & Development Center, Inc.  

Overall Contact: Kelley Micklus, MS 224-554-5903 kmicklus@tgrd.com

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00591773

Study ID Number: 01-05-TL-491-009

ClinicalTrials.gov Identifier: NCT00591773

Health Authority: United States: Food and Drug Administration