Long-Term Safety of Azilsartan Medoxomil and Chlorthalidone Compared to Olmesartan Medoxomil and Hydrochlorothiazide in Participants With Hypertension and Kidney Disease

NCT01309828 | Completed Phase 3 Results

• 4 other identifiers: TAK-491CLD_3092010-023098-21U1111-1119-5131NL35552.072.11
• Study Type: interventional
• Target: 153
• Locations: 8 countries
• Sites: 53

Brief Summary

The purpose of this study is to evaluate long term safety and tolerability of azilsartan medoxomil and chlorthalidone, once daily (QD), compared with olmesartan medoxomil and hydrochlorothiazide in hypertensive participants with moderate renal impairment.

Conditions

Safety

Keywords

Renal Insufficiency; Kidney Diseases; Hypertension; Drug Therapy

Outcome Measures

Primary Outcomes (1)

• Number of Participants With at Least 1 Adverse Event (AE)

  An AE is any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have a causal relationship with this treatment. A serious AE is defined as any untoward medical occurrence that resulted in death, was life threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability or incapacity, led to a congenital anomaly/birth defect or was an important medical event that may have required intervention to prevent any of items above.

  From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open- label study drug (up to 56 weeks).

Secondary Outcomes (3)

• Percentage of Participants at Final Visit Who Achieve Target Systolic Blood Pressure <130 mm Hg

  Week 52

• Percentage of Participants at Final Visit Who Achieved Target Diastolic Blood Pressure <80 mm Hg

  Week 52

• Percentage of Participants at Final Visit Who Achieved Both a Clinic Systolic and Diastolic Blood Pressure Response

  Week 52

Study Arms (2)

Azilsartan Medoxomil + Chlorthalidone

EXPERIMENTAL

United States and Europe: Azilsartan medoxomil 20 mg plus chlorthalidone 12.5 mg fixed dose combination tablets, titrated up to azilsartan medoxomil 40 mg plus chlorthalidone 25 mg orally, once daily for up to 52 weeks.

Drug: Azilsartan medoxomil and chlorthalidone

Olmesartan Medoxomil + Hydrochlorothiazide

ACTIVE COMPARATOR

United States: Olmesartan medoxomil 20 mg plus hydrochlorothiazide 12.5 mg fixed dose combination tablets, titrated up to olmesartan medoxomil 40 mg plus hydrochlorothiazide 25 mg orally, once daily for up to 52 weeks. Europe: Olmesartan medoxomil 20 mg plus hydrochlorothiazide 12.5 mg fixed dose combination tablets, titrated up to olmesartan medoxomil 20 mg plus hydrochlorothiazide 25 mg orally, once daily for up to 52 weeks.

Drug: Olmesartan medoxomil and hydrochlorothiazide

Interventions

Azilsartan medoxomil and chlorthalidone DRUG

Fixed-dose combination tablets.

Also known as: TAK-491CLD

Azilsartan Medoxomil + Chlorthalidone

Olmesartan medoxomil and hydrochlorothiazide DRUG

Fixed-dose combination tablets.

Also known as: Olmesartan medoxomil, Hydrochlorothiazide, Benicar hydrochlorothiazide, Olmetec Plus

Olmesartan Medoxomil + Hydrochlorothiazide

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 2 or 3 antihypertensive medications and on stable therapy, defined as ≥6 weeks on medication, and has a mean sitting clinic systolic blood pressure ≥135 and ≤160 mm Hg at the Screening Visit and on Day 1.
• Has an estimated glomerular filtration rate (eGFR) in the range of ≥30 to \<60 mL/min/1.73 m\^2 (Stage 3 chronic kidney disease) at the Screening Visit.
• Is a man or woman and aged 18 years or older.
• A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to routinely use adequate contraception from signing of the informed consent through 30 days after the last study drug dose.
• In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
• The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
• Has clinical laboratory test results (clinical chemistry, hematology, and complete urinalysis) that the investigator does not consider to be clinically significant in this moderate renal impaired population.
• Is willing to discontinue the current antihypertensive medications 2 days prior to randomization.

You may not qualify if:

• Has received any investigational compound within 30 days prior to Screening or is currently participating in another investigational study.
• Has been randomized/enrolled in a previous TAK-491 or TAK-491CLD study. NOTE: This criterion does not apply to participants who began participation in another TAK-491 or TAK-491CLD study but were not randomized/enrolled, nor does it apply to participants who participated in observational studies that lacked an intervention or invasive procedure.
• Is receiving a combination of olmesartan and hydrochlorothiazide at the Screening Visit.
• Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.
• Has a mean clinic diastolic (sitting, trough) \>110 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 (based on eGFR \<30 mL/min/1.73m\^2 at Screening) prior renal transplantation or nephrotic syndrome (defined as a urinary albumin/creatinine ratio \>2000 mg/g at Screening).
• 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. (This criterion does not apply to those participants with basal cell or stage I squamous cell carcinoma of the skin.)
• Has poorly-controlled type 1 or 2 diabetes mellitus (glycosylated hemoglobin A \[HbA1c\] \>8.5%) at Screening.
• Has hypokalemia or hyperkalemia (defined as serum potassium outside of the normal reference range of the central laboratory).
• Has an alanine aminotransferase or aspartate aminotransferase level of \>2.5 times the upper limit of normal, active liver disease, or jaundice.

Sponsors & Collaborators

• Takeda: lead

Study Sites (53)

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Kazanlak, Bulgaria

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Pleven, Bulgaria

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Sevlievo, Bulgaria

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Sofia, Bulgaria

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Varna, Bulgaria

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Mannheim, Baden-Wurttemberg, Germany

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Nuremberg, Bavaria, Germany

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Hamburg, Hamburg, Germany

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Frankfurt am Main, Hesse, Germany

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Offenbach, Hesse, Germany

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Rodgau Dudenhofen, Hesse, Germany

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Essen, North Rhine-Westphalia, Germany

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Goch, North Rhine-Westphalia, Germany

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Wuppertal, North Rhine-Westphalia, Germany

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Berlin, State of Berlin, Germany

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Daugavpils, Latvia

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Kuldīga, Latvia

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Limbaži, Latvia

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Riga, Latvia

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Tukums, Latvia

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Ventspils, Latvia

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Alytus, Lithuania

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Kaunas, Lithuania

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Klaipėda, Lithuania

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Šiauliai, Lithuania

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Vilnius, Lithuania

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Amsterdam, Netherlands

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Groningen, Netherlands

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Maastricht, Netherlands

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Venlo, Netherlands

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Grodzisk Mazowiecki, Poland

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Lodz, Poland

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Torun, Poland

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Warsaw, Poland

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Zgierz, Poland

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Banská Bystrica, Slovakia

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Bardejov, Slovakia

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Bratislava, Slovakia

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Komárno, Slovakia

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Košice, Slovakia

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Martin, Slovakia

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Nitra, Slovakia

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Ružomberok, Slovakia

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Svidník, Slovakia

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Donetsk, Ukraine

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Ivano-Frankivsk, Ukraine

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Kharkiv, Ukraine

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Kiev, Ukraine

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Kyiv, Ukraine

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Lutsk, Ukraine

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Lviv, Ukraine

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Vinnitsya, Ukraine

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Vinnytsia, Ukraine

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Related Publications (1)

• Bakris GL, Zhao L, Kupfer S, Juhasz A, Hisada M, Lloyd E, Oparil S. Long-term efficacy and tolerability of azilsartan medoxomil/chlorthalidone vs olmesartan medoxomil/hydrochlorothiazide in chronic kidney disease. J Clin Hypertens (Greenwich). 2018 Apr;20(4):694-702. doi: 10.1111/jch.13230. Epub 2018 Mar 4.

  PMID: 29504252 DERIVED

MeSH Terms

Conditions

Renal Insufficiency; Kidney Diseases; Hypertension

Interventions

azilsartan medoxomil; Chlorthalidone; Olmesartan Medoxomil; Hydrochlorothiazide

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases

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: Medical Director, Clinical Science
• Organization: Takeda

clinicaltrialregistry@tpna.com

800-778-2860

Study Officials

• 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: March 4, 2011
• First Posted: March 7, 2011
• Study Start: March 1, 2011
• Primary Completion: October 1, 2012
• Study Completion: October 1, 2012
• Last Updated: December 13, 2013
• Results First Posted: December 13, 2013

Record last verified: 2013-09

Locations

SL (9); PL (5); DE (10); UA (9); NL (4); BU (5); LI (5); LA (6)