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 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.

Study Type: Interventional

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

Study Primary Completion Date: March 2009

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.

Intervention(s) in this Clinical Trial

• Drug: TAK-491
  • TAK-491 40 mg tablet, TAK-491 80 mg tablet and TAK-491 80 mg tablet + chlorthalidone 25 mg tablet orally, once daily, for up to 56 weeks* *The study investigator may add other antihypertensive agents to achieve the subjects target blood pressure along with chlorthanlidone throughout the study.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • TAK-491

Primary Measures

• To evaluate safety and tolerability of treatment with TAK-491 for up to 56 weeks in subjects with essential hypertension.
  • Time Frame: Up to 56 Weeks
    Safety Issue?: Yes

Secondary Measures

• To evaluate safety and tolerability of treatment with TAK-491 in combination with chlorthalidone for up to 48 weeks in subjects with essential hypertension.
  • Time Frame: Up to 48 Weeks
    Safety Issue?: Yes

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.

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

Information obtained from ClinicalTrials.gov on August 28, 2008

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