A Phase 3, Double-Blind, Randomized, Factorial, Efficacy and Safety Study of TAK 491 Plus Chlorthalidone Fixed-Dose Combination in Subjects with Moderate to Severe Hypertensio

Active, not recruiting

• Conditions: TAK-491CLD is being evaluated to treat moderate to severe essential hypertension; MedDRA version: 9.1Level: LLTClassification code 10015488Term: Essential hypertension

• Registration Number: EUCTR2008-004218-28-NL
• Lead Sponsor: Takeda Global Research & Development Centre (Europe) Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-02-26
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 1815

Inclusion Criteria

Each subject must satisfy the following criteria to qualify for study entry:

1.The subject is treated with antihypertensive therapy and has a post-washout mean sitting clinic SBP =160 and =190 mm Hg on Day -1 (day prior to randomization); or the subject has not received antihypertensive treatment within 28 days prior to Screening and has a mean sitting clinic SBP =160 and =190 mm Hg at the Screening Visit and on Day -1.
2.The subject is a man or woman aged 18 years or older.
3.A female subject of childbearing potential who is sexually active agrees to routinely use adequate contraception from Screening through 30 days after last administered study drug dose.

NOTE: Women NOT of childbearing potential are defined as those who have been surgically sterilized (hysterectomy, bilateral oophorectomy, tubal ligation [performed more than one year prior to Screening]) or who are postmenopausal (defined as at least 1 year since last regular menses). Acceptable methods of contraception are defined in Section 9.1.9 Contraception and Pregnancy Avoidance Procedure.
4.The subject is capable of understanding and willing to comply with the protocol requirements.
5.The subject or the subject’s legally acceptable representative signs an informed consent form prior to the initiation of any study procedures.
6.The subject has clinical laboratory test results (clinical chemistry, hematology, and complete urinalysis) within the reference range for the testing laboratory or the investigator does not consider the results to be clinically significant.
7.The subject is willing to discontinue current antihypertensive medications on Day -21 or on Day -28 if the subject is on amlodipine or chlorthalidone.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

A subject who meets any of the following criteria will not qualify for study entry:

1.The subject has a mean sitting clinic DBP (sitting, trough) >119 mm Hg on Day -1 (day prior to randomization).
2.The subject has a baseline 24-hour ABPM reading of insufficient quality (as described in Appendix E).
3.The subject works a night (third) shift (defined as 11 PM [2300] to 7 AM [0700]).
4.The subject has an upper arm circumference <24 cm or >42 cm.
5.The subject is noncompliant (<70% or >130%) with study medication during the placebo run-in period.
6.The subject has secondary hypertension of any etiology (eg, renovascular disease, pheochromocytoma, Cushing’s syndrome).
7.The subject has recent history (within the last 6 months) of myocardial infarction, heart failure, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebrovascular accident, or transient ischemic attack.
8.The subject has clinically significant cardiac conduction defects (ie, third-degree atrioventricular block, sick sinus syndrome, atrial fibrillation, or atrial flutter).
9.The subject has hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease.
10.The subject has severe renal dysfunction or disease (based on estimated glomerular filtration rate [GFR] <30 mL/min/1.73 m2 at Screening).
11.The subject has known or suspected unilateral or bilateral renal artery stenosis.
12.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 apply to those subjects with basal cell or stage I squamous cell carcinoma of the skin.)
13.The subject has poorly controlled type 1 or type 2 diabetes mellitus (hemoglobin A1c [HbA1c] >8.0%) at Screening.
14.The subject has hypokalemia or hyperkalemia (defined as serum potassium outside of the normal reference range of the central laboratory).
15.The subject has an alanine aminotransferase or aspartate aminotransferase level of greater than 2.5 times the upper limit of normal, active liver disease, or jaundice.
16.The subject has any other known serious disease or condition that would compromise safety, might affect life expectancy, or make it difficult to successfully manage and follow the subject according to the protocol.
17.The subject has known hypersensitivity to ARBs or thiazide-type diuretics or other sulfonamide-derived compounds.
18.The subject has been randomized in a previous TAK-491 study.
19.If female, the subject is pregnant or lactating or intending to become pregnant before or during study participation, or within 30 days after last study drug dose.
20.The subject currently is participating in another investigational study or is receiving or has received any investigational compound within 30 days prior to Screening. NOTE: This criterion does not apply to subjects who began participation in another TAK-491 study but were not randomized, nor does it apply to subjects who participated in observational studies that lacked an intervention or invasive procedure.
21.The subject is a study site employee or is an immediate family member (ie, spouse, parent, child, sibling) of a study site employee who is involved in conduct of this study.
22.The subject has a history of drug abuse (defined as illicit drug use) or a history of alcohol abuse within the past 2 years.
23.The subject is taking or expected to take an excluded me

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified