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”

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.

Study Type: Interventional

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

Study Primary Completion Date: April 2009

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.

Intervention(s) in this Clinical Trial

• Drug: TAK-491
  • Current dose of TAK-491 achieved through 26 week open-label phase, tablet form, orally, once daily for 6 weeks* *may also include 25 mg of chlorthalidone and/or other current antihypertensive medication.
• Drug: Placebo
  • Placebo tablet, orally, once daily for 6 weeks* *may also include 25 mg of chlorthalidone and/or other current antihypertensive medication.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • TAK-491
• Placebo Comparator: 2
  • Placebo

Primary Measures

• To evaluate safety and tolerability of treatment with TAK-491 in subjects with essential hypertension.
  • Time Frame: 26 Weeks
    Safety Issue?: Yes

Secondary Measures

• 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.
  • Time Frame: 6 Weeks
    Safety Issue?: No
• To evaluate safety and tolerability of treatment with TAK-491 in combination with chlorthalidone in subjects with essential hypertension.
  • Time Frame: 26 Weeks
    Safety Issue?: Yes

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.

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

Alfonso Perez, 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 27, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00696384

Study ID Number: 01-06-TL-491-016

ClinicalTrials.gov Identifier: NCT00696384

Health Authority: United States: Food and Drug Administration