Safety and Tolerability of Azilsartan Medoxomil Plus Chlorthalidone Compared to Olmesartan Medoxomil Plus Hydrochlorothiazide in Participants With Essential Hypertension

NCT ID: NCT00996281

Last Updated: 2012-11-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 837 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-31
• Study Completion Date: 2011-11-30

Brief Summary

The purpose of this study is to compare the safety and tolerability of azilsartan medoxomil plus chlorthalidone, once daily (QD), versus olmesartan medoxomil-hydrochlorothiazide in adults with essential hypertension.

Detailed Description

High Blood Pressure (Hypertension) is the most common cause of preventable death in developed nations. Uncontrolled hypertension greatly increases the risk of heart disease, brain disease, and kidney failure. As the population ages, the incidence of hypertension will continue to increase if effective preventive measures are not implemented. Despite the availability of antihypertensive agents, hypertension is not adequately controlled; only about one in three patients successfully keep blood pressure normal.

Treatment for high blood pressure includes thiazides or thiazide-like diuretics, either alone or as part of combination treatment. Chlorthalidone is a commercially available, orally administered thiazide-type diuretic agent.

TAK-491 (azilsartan) is an angiotensin II receptor blocker being evaluated by Takeda to treat patients with high blood pressure (essential hypertension).

This study will compare the safety and tolerability of azilsartan medoxomil plus chlorthalidone (TAK-491CLD) fixed-dose combination to olmesartan medoxomil-hydrochlorothiazide fixed-dose combination.

Initially patients will undergo a Screening Visit to confirm that they are eligible to participate in the study. All participants will receive the study drug for up to 52 weeks. The dose of the study drug may be gradually increased throughout the study so that a target blood pressure value can be reached for each participant.

Throughout the treatment period of the study, participants will be required to visit the research site for 11 visits. At these study visits participants will be required to undergo certain study procedures including physical examinations, vital sign measurements (blood pressure, heart rate, weight and height), electrocardiograms (monitoring of the heart), and blood and urine samples taken for clinical laboratory tests.

Conditions

Essential Hypertension

Keywords

Hypertensive; Blood Pressure, High; Cardiovascular disease; Vascular Disease; Drug Therapy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Azilsartan Medoxomil and Chlorthalidone

Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablet, orally, once daily for up to 52 weeks.

For participants who did not achieve target blood pressure by Week 4, titration to a maximum dose of azilsartan medoxomil 80 mg and chlorthalidone 25 mg.

Group Type: EXPERIMENTAL

Azilsartan medoxomil and chlorthalidone

Intervention Type: DRUG

Combination tablet.

Olmesartan Medoxomil and Hydrochlorothiazide QD

Participants in the United States:

Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablet, orally, once daily for up to 52 weeks. For participants who did not achieve target blood pressure by Week 4, titration to a maximum dose of Olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg.

Participants in Europe:

Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablet, orally, once daily for up to 52 weeks. For participants who did not achieve target blood pressure by Week 4, titration to a maximum dose of Olmesartan medoxomil 20 mg and hydrochlorothiazide 25 mg.

Group Type: ACTIVE_COMPARATOR

Olmesartan medoxomil and hydrochlorothiazide

Intervention Type: DRUG

Combination tablet.

Interventions

Azilsartan medoxomil and chlorthalidone

Combination tablet.

Intervention Type: DRUG

Olmesartan medoxomil and hydrochlorothiazide

Combination tablet.

Intervention Type: DRUG

Other Intervention Names

TAK-491CLD; Benicar HCT®; Olmetec Plus®

Eligibility Criteria

Inclusion Criteria

• Is treated with antihypertensive therapy and has a post-washout mean sitting clinic systolic blood pressure greater than or equal to 160 and less than or equal to 190 mm Hg on Day, or has not received antihypertensive treatment within 14 days prior to Screening and has a mean sitting clinic systolic blood pressure greater than or equal to 160 and less than or equal to 190 mm Hg at the Screening Visit and on Day 1.
• Females of childbearing potential who are sexually active agree to routinely use adequate contraception, and can neither be pregnant nor lactating from before study participation to Screening to 30 days after the last study drug dose.
• Has clinical laboratory test results within the reference range for the testing laboratory or the investigator does not consider the results to be clinically significant.
• Is willing to discontinue current antihypertensive medications up to 3 weeks before enrollment.

Exclusion Criteria

• Has a mean clinic diastolic blood pressure (sitting, trough) greater than 119 mm Hg on Day 1.
• Has secondary hypertension of any etiology (eg, renovascular disease, pheochromocytoma, Cushing's syndrome).
• Has a 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.
• Has clinically significant cardiac conduction defects (ie, third-degree atrioventricular block, sick sinus syndrome).
• Has hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease.
• Has severe renal dysfunction or disease.
• Has known or suspected unilateral or bilateral renal artery stenosis.
• Has a history of cancer that has not been in remission for at least 5 years prior to the first dose of study drug.
• Has poorly-controlled type 1 or 2 diabetes mellitus at Screening.
• Has hypokalemia or hyperkalemia at Screening.
• Has an alanine aminotransferase or aspartate aminotransferase level of greater than 2.5 times the upper limit of normal, active liver disease, or jaundice at Screening.
• 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 according to the protocol.
• Has known hypersensitivity to angiotensin II receptor blockers or thiazide-type diuretics or other sulfonamide-derived compounds.
• Has been randomized/enrolled in a previous azilsartan or azilsartan medoxomil plus chlorthalidone study.
• Currently is participating in another investigational study or has received any investigational compound within 30 days prior to Screening.
• Has a history of drug abuse or a history of alcohol abuse within the past 2 years.
• Is taking or expected to take any excluded medication, including:

• Antihypertensive medications must be discontinued completely by Day -14, except antihypertensive medications used in the open-label treatment period in accordance with the titration-to-target blood pressure titration.
• Angiotensin II receptor blockers or thiazide-type diuretics other than study medication.
• Over-the-counter products not permitted by investigator.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Executive Medical Director, Clinical Science

Role: STUDY_DIRECTOR

Takeda

Locations

Graz, Styria, Austria

Karlsruhe, Baden-Wurttemberg, Germany

Hanover, Lower Saxony, Germany

Kiel-Kronshagen, Schleswig-Holstein, Germany

Breda, North Brabant, Netherlands

Eindhoven, North Brabant, Netherlands

Amsterdam, North Holland, Netherlands

Groningen, Provincie Groningen, Netherlands

Velp, Rheden, Netherlands

Leiderdorp, South Holland, Netherlands

Rotterdam, South Holland, Netherlands

Zoetermeer, South Holland, Netherlands

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland

Skierniewice, L0dz, Poland

Zgierz, L0dz, Poland

Gdansk, Pomeranian, Poland

Gdynia, Pomeranian, Poland

Sopot, Pomeranian, Poland

Mikołów, Silesian, Poland

Avon, England, United Kingdom

Bolton, England, United Kingdom

Chorley, England, United Kingdom

Inverness, England, United Kingdom

Liverpool, England, United Kingdom

Surrey, England, United Kingdom

Warwickshire, England, United Kingdom

Countries

South Africa; United States; Austria; Germany; Netherlands; Poland; United Kingdom

Other Identifiers

2008-008260-28

Identifier Type: REGISTRY

Identifier Source: secondary_id

U1111-1111-7891

Identifier Type: OTHER

Identifier Source: secondary_id

TAK-491CLD_308

Identifier Type: -

Identifier Source: org_study_id