Efficacy and Safety of Azilsartan Medoxomil Combined With Chlorthalidone in Participants With Moderate to Severe Hypertension

NCT ID: NCT00847626

Last Updated: 2012-02-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1711 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-01-31
• Study Completion Date: 2010-07-31

Brief Summary

The purpose of this study is to determine the efficacy and safety of azilsartan medoxomil combined with chlorthalidone, once daily (QD), in participants with moderate to severe hypertension.

Detailed Description

According to the World Health Organization (WHO), hypertension is the most common attributable cause of preventable death in developed nations, as uncontrolled hypertension greatly increases the risk of cardiovascular disease, cerebrovascular disease, and renal failure. As the population ages, the prevalence of hypertension will continue to increase if broad and effective preventive measures are not implemented. Despite the availability of antihypertensive agents, hypertension remains inadequately controlled; only about one third of patients continue to maintain control successfully.

Although most antihypertensive agents are effective at the appropriate dose, the majority have side effects that limit their use. As a class, angiotensin II receptor blockers generally are considered more tolerable than other classes of antihypertensive agents. TAK-491 (azilsartan medoxomil) is an angiotensin II receptor blocker that is being evaluated by Takeda to treat essential hypertension.

Treatments for essential hypertension commonly include use of a thiazide-like diuretic, either alone or as part of combination treatment.

This study is designed to compare the antihypertensive effect and the safety and tolerability of the azilsartan medoxomil plus chlorthalidone fixed-dose combination product (TAK 491CLD FDC) with azilsartan monotherapy and chlorthalidone monotherapy during 8 weeks of treatment.

Participants in this study will be randomized to receive one of 11 possible dosing combinations of azilsartan medoxomil , chlorthalidone and placebo over an 8 week period. The total duration of the study will be approximately 13 weeks. Participants will make 12 visits to the clinic. Each participant will also be contacted by telephone 14 days after last dose of study drug for a follow-up assessment.

Conditions

Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Azilsartan medoxomil 20 mg/chlorthalidone 12.5 mg QD

Group Type: EXPERIMENTAL

Azilsartan medoxomil and chlorthalidone

Intervention Type: DRUG

Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for up to 8 weeks

Azilsartan medoxomil 20 mg/chlorthalidone 25 mg QD

Group Type: EXPERIMENTAL

Azilsartan medoxomil and chlorthalidone

Intervention Type: DRUG

Azilsartan medoxomil 20 mg and chlorthalidone 25 mg combination tablets, orally, once daily for up to 8 weeks

Azilsartan medoxomil 40 mg/chlorthalidone 12.5 mg QD

Group Type: EXPERIMENTAL

Azilsartan medoxomil and chlorthalidone

Intervention Type: DRUG

Azilsartan 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for up to 8 weeks

Azilsartan medoxomil 40 mg/chlorthalidone 25 mg QD

Group Type: EXPERIMENTAL

Azilsartan medoxomil and chlorthalidone

Intervention Type: DRUG

Azilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for up to 8 weeks

Azilsartan medoxomil 80 mg/chlorthalidone 12.5 mg QD

Group Type: EXPERIMENTAL

Azilsartan medoxomil and chlorthalidone

Intervention Type: DRUG

Azilsartan 80 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for up to 8 weeks

Azilsartan medoxomil 80 mg/chlorthalidone 25 mg QD

Group Type: EXPERIMENTAL

Azilsartan medoxomil and chlorthalidone

Intervention Type: DRUG

Azilsartan medoxomil 80 mg and chlorthalidone 25 mg combination tablets, orally, once daily for up to 8 weeks

Chlorthalidone 12.5 mg QD

Group Type: ACTIVE_COMPARATOR

Chlorthalidone

Intervention Type: DRUG

Azilsartan medoxomil placebo and chlorthalidone 12.5 mg combination tablets, orally, once daily for up to 8 weeks

Chlorthalidone 25 mg QD

Group Type: ACTIVE_COMPARATOR

Chlorthalidone

Intervention Type: DRUG

Azilsartan medoxomil placebo and chlorthalidone 25 mg combination tablets, orally, once daily for up to 8 weeks

Azilsartan medoxomil 20 mg QD

Group Type: EXPERIMENTAL

Azilsartan medoxomil

Intervention Type: DRUG

Azilsartan medoxomil 20 mg and chlorthalidone placebo combination tablets, orally, once daily for up to 8 weeks

Azilsartan medoxomil 40 mg QD

Group Type: EXPERIMENTAL

Azilsartan medoxomil

Intervention Type: DRUG

Azilsartan medoxomil 40 mg and chlorthalidone placebo combination tablets, orally, once daily for up to 8 weeks

Azilsartan medoxomil 80 mg QD

Group Type: EXPERIMENTAL

Azilsartan medoxomil

Intervention Type: DRUG

Azilsartan medoxomil 80 mg and chlorthalidone placebo combination tablets, orally, once daily for up to 8 weeks

Interventions

Azilsartan medoxomil and chlorthalidone

Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for up to 8 weeks

Intervention Type: DRUG

Azilsartan medoxomil and chlorthalidone

Azilsartan medoxomil 20 mg and chlorthalidone 25 mg combination tablets, orally, once daily for up to 8 weeks

Intervention Type: DRUG

Azilsartan medoxomil and chlorthalidone

Azilsartan 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for up to 8 weeks

Intervention Type: DRUG

Azilsartan medoxomil and chlorthalidone

Azilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for up to 8 weeks

Intervention Type: DRUG

Azilsartan medoxomil and chlorthalidone

Azilsartan 80 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for up to 8 weeks

Intervention Type: DRUG

Azilsartan medoxomil and chlorthalidone

Azilsartan medoxomil 80 mg and chlorthalidone 25 mg combination tablets, orally, once daily for up to 8 weeks

Intervention Type: DRUG

Chlorthalidone

Azilsartan medoxomil placebo and chlorthalidone 12.5 mg combination tablets, orally, once daily for up to 8 weeks

Intervention Type: DRUG

Chlorthalidone

Azilsartan medoxomil placebo and chlorthalidone 25 mg combination tablets, orally, once daily for up to 8 weeks

Intervention Type: DRUG

Azilsartan medoxomil

Azilsartan medoxomil 20 mg and chlorthalidone placebo combination tablets, orally, once daily for up to 8 weeks

Intervention Type: DRUG

Azilsartan medoxomil

Azilsartan medoxomil 40 mg and chlorthalidone placebo combination tablets, orally, once daily for up to 8 weeks

Intervention Type: DRUG

Azilsartan medoxomil

Azilsartan medoxomil 80 mg and chlorthalidone placebo combination tablets, orally, once daily for up to 8 weeks

Intervention Type: DRUG

Other Intervention Names

TAK-491CLD; TAK-491CLD; TAK-491CLD; TAK-491CLD; TAK-491CLD; TAK-491CLD; TAK-491CLD; TAK-491CLD; TAK-491CLD

Eligibility Criteria

Inclusion Criteria

1. 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 the day prior to randomization, or the participant has not received antihypertensive treatment within 28 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 the day prior to randomization.

2. Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.

3. 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.

4. Is willing to discontinue current antihypertensive medications on Day -21 or on Day -28 if on amlodipine or chlorthalidone.

Exclusion Criteria

1. Has a mean sitting clinic diastolic blood pressure greater than 119 mm Hg on the day prior to randomization.

2. Has a baseline 24-hour ambulatory blood pressure measurement reading of insufficient quality.

3. Has works a night (third) shift (defined as 11 PM [2300] to 7 AM [0700]).

4. Has an upper arm circumference less than 24 cm or greater than 42 cm.

5. Has is noncompliant with study medication during the placebo run-in period.

6. Has secondary hypertension of any etiology.

7. Has recent history of myocardial infarction, heart failure, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebrovascular accident, or transient ischemic attack.

8. Has clinically significant cardiac conduction defects.

9. Has hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease.

10. Has severe renal dysfunction or disease.

11. Has known or suspected unilateral or bilateral renal artery stenosis.

12. Has a history of cancer that has not been in remission for at least 5 years prior to the first dose of study drug.

13. Has poorly controlled type 1 or type 2 diabetes mellitus at Screening.

14. Has hypokalemia or hyperkalemia.

15. 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. 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 Has according to the protocol.

17. Has known hypersensitivity to angiotensin II receptor blockers, thiazide-type diuretics or other sulfonamide-derived compounds.

18. Has been randomized in a previous azilsartan medoxomil study.

19. Is currently participating in another investigational study or is receiving or has received any investigational compound within 30 days prior to Screening.

20. Has a history of drug abuse or a history of alcohol abuse within the past 2 years.

• 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

Role: STUDY_DIRECTOR

Takeda

Locations

Birmingham, Alabama, United States

Columbiana, Alabama, United States

Tuscaloosa, Alabama, United States

Chandler, Arizona, United States

Phoenix, Arizona, United States

Scottsdale, Arizona, United States

Tucson, Arizona, United States

Little Rock, Arkansas, United States

Buena Park, California, United States

Carmichael, California, United States

Costa Mesa, California, United States

Irvine, California, United States

Palm Springs, California, United States

Riverside, California, United States

Sacramento, California, United States

San Diego, California, United States

Vista, California, United States

Walnut Creek, California, United States

Middletown, Delaware, United States

Bradenton, Florida, United States

Deerfield Beach, Florida, United States

Fort Lauderdale, Florida, United States

Hallandale, Florida, United States

Hialeah, Florida, United States

Jacksonville, Florida, United States

Longwood, Florida, United States

Miami, Florida, United States

Ocala, Florida, United States

Ormond Beach, Florida, United States

St. Petersburg, Florida, United States

Atlanta, Georgia, United States

Buffalo Grove, Illinois, United States

Libertyville, Illinois, United States

Melrose Park, Illinois, United States

Fishers, Indiana, United States

Indianapolis, Indiana, United States

Erlanger, Kentucky, United States

Madisonville, Kentucky, United States

Paducah, Kentucky, United States

Rockville, Maryland, United States

Ann Arbor, Michigan, United States

Chesterfield, Michigan, United States

St Louis, Missouri, United States

Omaha, Nebraska, United States

Henderson, Nevada, United States

Brick, New Jersey, United States

Margate City, New Jersey, United States

Albuquerque, New Mexico, United States

Endwell, New York, United States

Cary, North Carolina, United States

Winston-Salem, North Carolina, United States

Cincinnati, Ohio, United States

Cleveland, Ohio, United States

Columbus, Ohio, United States

Dayton, Ohio, United States

Lyndhurst, Ohio, United States

Willoughby Hills, Ohio, United States

Oklahoma City, Oklahoma, United States

Ashland, Oregon, United States

Altoona, Pennsylvania, United States

Bensalem, Pennsylvania, United States

Feasterville, Pennsylvania, United States

Jenkintown, Pennsylvania, United States

Sellersville, Pennsylvania, United States

Warminster, Pennsylvania, United States

Charleston, South Carolina, United States

Florence, South Carolina, United States

Murrells Inlet, South Carolina, United States

Simpsonville, South Carolina, United States

Spartanburg, South Carolina, United States

Clarksville, Tennessee, United States

New Tazewell, Tennessee, United States

Austin, Texas, United States

Bellaire, Texas, United States

Dallas, Texas, United States

Houston, Texas, United States

McKinney, Texas, United States

Richardson, Texas, United States

San Antonio, Texas, United States

Magna, Utah, United States

West Jordan, Utah, United States

Arlington, Virginia, United States

Virginia Beach, Virginia, United States

Oregon, Wisconsin, United States

Santiago, , Chile

Temuco, , Chile

Aguascalientes, , Mexico

Mexico City, , Mexico

Mérida, , Mexico

Bellavista, , Peru

Chiclayo, , Peru

Jesus Maria, , Peru

Miraflores, , Peru

San Borja, , Peru

San Martín de Porres, , Peru

Trujillo, , Peru

Umacollo, , Peru

Moscow, , Russia

Saint Petersburg, , Russia

Countries

United States; Chile; Mexico; Peru; Russia

Other Identifiers

2008-004218-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1113-8735

Identifier Type: REGISTRY

Identifier Source: secondary_id

TAK-491CLD_302

Identifier Type: -

Identifier Source: org_study_id

NCT00892645

Identifier Type: -

Identifier Source: nct_alias