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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT00996281
First received: October 12, 2009
Last updated: October 15, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Essential Hypertension
Drug: Azilsartan medoxomil and chlorthalidone
Drug: Olmesartan medoxomil and hydrochlorothiazide
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 3, Open-Label, Randomized, Long-Term Comparison of the Safety and Tolerability of the TAK-491 Plus Chlorthalidone Fixed-Dose Combination vs. Olmesartan Medoxomil-Hydrochlorothiazide Fixed-Dose Combination in Subjects With Essential Hypertension

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Percentage of Participants With at Least 1 Adverse Event [ Time Frame: From Week 0 (Day 1) to Week 52. ] [ Designated as safety issue: Yes ]
    An adverse event is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product without regard to causality.


Secondary Outcome Measures:
  • Percentage of Participants With Serum Creatinine Elevations Greater Than 50% From Baseline and Greater Than the Upper Limit of Normal (ULN) [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: Yes ]
    Serum creatinine was measured at every visit and evaluated as a laboratory parameter of special interest. The percentage of participants with creatinine increase ≥50% from Baseline and greater than ULN was summarized: - At any visit (includes transient and persistent elevations). - At the Final Visit (includes persistent elevations and participants whose first elevation may have been at the Final Visit). - At least 2 consecutive visits (includes only persistent elevations).


Enrollment: 837
Study Start Date: October 2009
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.

Drug: Azilsartan medoxomil and chlorthalidone
Combination tablet.
Other Name: TAK-491CLD
Active Comparator: 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.

Drug: Olmesartan medoxomil and hydrochlorothiazide
Combination tablet.
Other Names:
  • Benicar HCT®
  • Olmetec Plus®

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00996281

Locations
Austria
Graz, Styria, Austria
Germany
Karlsruhe, Baden-Wurttemberg, Germany
Hannover, Lower Saxony, Germany
Kiel-Kronshagen, Schleswig-Holstein, Germany
Netherlands
Breda, North Brabant, Netherlands
Eindhoven, North Brabant, Netherlands
Amsterdam, North Holland, Netherlands
Velp, Rheden, Netherlands
Leiderdorp, South Holland, Netherlands
Zoetermeer, South Holland, Netherlands
Rotterdam, Zuid-Holland, Netherlands
Groningen, Netherlands
Poland
Bydgoszcz, Kuyavian-Pomeranian, Poland
Skierniewice, L0dz, Poland
Zgierz, L0dz, Poland
Gdansk, Pomeranian, Poland
Gdynia, Pomeranian, Poland
Sopot, Pomeranian, Poland
Mikolow, Silesian, Poland
United Kingdom
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
Sponsors and Collaborators
Takeda
Investigators
Study Director: Executive Medical Director, Clinical Science Takeda
  More Information

Additional Information:
No publications provided

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT00996281     History of Changes
Other Study ID Numbers: TAK-491CLD_308, 2008-008260-28, U1111-1111-7891
Study First Received: October 12, 2009
Results First Received: October 15, 2012
Last Updated: October 15, 2012
Health Authority: United States: Food and Drug Administration
United Kingdom: Department of Health
United Kingdom: Food Standards Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: National Health Service
United Kingdom: Research Ethics Committee
Netherlands: Independent Ethics Committee
Netherlands: Dutch Health Care Inspectorate
Netherlands: Medical Ethics Review Committee (METC)
Netherlands: Medicines Evaluation Board (MEB)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Poland: Ministry of Health
Poland: Ministry of Science and Higher Education
Austria: Agency for Health and Food Safety
Austria: Ethikkommission
Austria: Federal Ministry for Health and Women
Austria: Federal Office for Safety in Health Care
South Africa: Medicines Control Council

Keywords provided by Takeda:
Hypertensive
Blood Pressure, High
Cardiovascular disease
Vascular Disease
Drug Therapy

Additional relevant MeSH terms:
Hypertension
Cardiovascular Diseases
Vascular Diseases
Chlorthalidone
Hydrochlorothiazide
Olmesartan
Olmesartan medoxomil
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Antihypertensive Agents
Cardiovascular Agents
Diuretics
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Natriuretic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sodium Chloride Symporter Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014