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

NCT00996281 | Completed Phase 3 Results

• 3 other identifiers: TAK-491CLD_3082008-008260-28U1111-1111-7891
• Study Type: interventional
• Target: 837
• Locations: 5 countries
• Sites: 26

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.

Conditions

Essential Hypertension

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With at Least 1 Adverse Event

  An adverse event is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product without regard to causality.

  From Week 0 (Day 1) to Week 52.

Secondary Outcomes (1)

• Percentage of Participants With Serum Creatinine Elevations Greater Than 50% From Baseline and Greater Than the Upper Limit of Normal (ULN)

  Baseline and Week 52

Study Arms (2)

Azilsartan Medoxomil and Chlorthalidone

EXPERIMENTAL

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

Olmesartan Medoxomil and Hydrochlorothiazide QD

ACTIVE COMPARATOR

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

Interventions

Azilsartan medoxomil and chlorthalidone DRUG

Combination tablet.

Also known as: TAK-491CLD

Azilsartan Medoxomil and Chlorthalidone

Olmesartan medoxomil and hydrochlorothiazide DRUG

Combination tablet.

Also known as: Benicar HCT®, Olmetec Plus®

Olmesartan Medoxomil and Hydrochlorothiazide QD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Takeda: lead

Study Sites (26)

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Graz, Styria, Austria

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Karlsruhe, Baden-Wurttemberg, Germany

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Hanover, Lower Saxony, Germany

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Kiel-Kronshagen, Schleswig-Holstein, Germany

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Breda, North Brabant, Netherlands

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Eindhoven, North Brabant, Netherlands

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Amsterdam, North Holland, Netherlands

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Groningen, Provincie Groningen, Netherlands

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Velp, Rheden, Netherlands

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Leiderdorp, South Holland, Netherlands

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Rotterdam, South Holland, Netherlands

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Zoetermeer, South Holland, Netherlands

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Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland

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Skierniewice, L0dz, Poland

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Zgierz, L0dz, Poland

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Gdansk, Pomeranian, Poland

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Gdynia, Pomeranian, Poland

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Sopot, Pomeranian, Poland

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Mikołów, Silesian, Poland

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Avon, England, United Kingdom

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Bolton, England, United Kingdom

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Chorley, England, United Kingdom

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Inverness, England, United Kingdom

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Liverpool, England, United Kingdom

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Surrey, England, United Kingdom

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Warwickshire, England, United Kingdom

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MeSH Terms

Conditions

Essential Hypertension; Hypertension; Cardiovascular Diseases; Vascular Diseases

Interventions

azilsartan medoxomil; Chlorthalidone; Olmesartan Medoxomil; Hydrochlorothiazide

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Benzophenones; Phthalimides; Imides; Ketones; Sulfones; Sulfur Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Tetrazoles; Chlorothiazide; Benzothiadiazines; Thiazides

Results Point of Contact

• Title: Sr. VP, Clinical Science
• Organization: Takeda Global Research and Development Center, Inc.

clinicaltrialregistry@tpna.com

800-778-2860

Study Officials

• Executive Medical Director, Clinical Science

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2009
• First Posted: October 16, 2009
• Study Start: October 1, 2009
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2011
• Last Updated: November 12, 2012
• Results First Posted: November 12, 2012

Record last verified: 2012-10

Locations

GB (7); AU (1); NL (8); PL (7); DE (3)