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AzTrials

SafetyPhase 3NCT01309828

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

A Phase 3 study testing Azilsartan medoxomil and chlorthalidone and Olmesartan medoxomil and hydrochlorothiazide in people with Safety, run by Takeda at 53 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Safety
What is being tested?
Azilsartan medoxomil and chlorthalidone and Olmesartan medoxomil and hydrochlorothiazide
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
153 participants
Where
53 sitesin 8 countries
Study dates
Mar 2011to Oct 2012
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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).
Show all 20Show fewer
  • 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.
  • 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 the participant according to the protocol.
  • has a history of hypersensitivity or allergies to ARBs or thiazide-type diuretics or other sulfonamide-derived compounds.
  • Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within the past 2 years.
  • Is required to take excluded medications.
  • If female, is pregnant or lactating or intending to become pregnant before, during, or within 30 days after participating in this study; or intending to donate ova during such time period.

Trial locations and contacts

53 sites in 8 countries.

53 sites in 8 countries

Germany10 sites

  • Study site

    Berlin, State of Berlin

  • Study site

    Essen, North Rhine-Westphalia

  • Study site

    Frankfurt am Main, Hesse

  • Study site

    Goch, North Rhine-Westphalia

  • Study site

    Hamburg, Free and Hanseatic City of Hamburg

  • Study site

    Mannheim, Baden-Wurttemberg

  • Study site

    Nuremberg, Bavaria

  • Study site

    Offenbach, Hesse

  • Study site

    Rodgau Dudenhofen, Hesse

  • Study site

    Wuppertal, North Rhine-Westphalia

Other trials in Germany

Slovakia9 sites

  • Study site

    Banská Bystrica

  • Study site

    Bardejov

  • Study site

    Bratislava

  • Study site

    Komárno

  • Study site

    Košice

  • Study site

    Martin

  • Study site

    Nitra

  • Study site

    Ružomberok

  • Study site

    Svidník

Other trials in Slovakia

Ukraine9 sites

  • Study site

    Donetsk

  • Study site

    Ivano-Frankivsk

  • Study site

    Kharkiv

  • Study site

    Kiev

  • Study site

    Kyiv

  • Study site

    Lutsk

  • Study site

    Lviv

  • Study site

    Vinnitsya

  • Study site

    Vinnytsia

Other trials in Ukraine

Latvia6 sites

  • Study site

    Daugavpils

  • Study site

    Kuldīga

  • Study site

    Limbaži

  • Study site

    Riga

  • Study site

    Tukums

  • Study site

    Ventspils

Other trials in Latvia

Bulgaria5 sites

  • Study site

    Kazanlak

  • Study site

    Pleven

  • Study site

    Sevlievo

  • Study site

    Sofia

  • Study site

    Varna

Other trials in Bulgaria

Lithuania5 sites

  • Study site

    Alytus

  • Study site

    Kaunas

  • Study site

    Klaipėda

  • Study site

    Šiauliai

  • Study site

    Vilnius

Other trials in Lithuania

Poland5 sites

  • Study site

    Grodzisk Mazowiecki

  • Study site

    Lodz

  • Study site

    Torun

  • Study site

    Warsaw

  • Study site

    Zgierz

Other trials in Poland

Netherlands4 sites

  • Study site

    Amsterdam

  • Study site

    Groningen

  • Study site

    Maastricht

  • Study site

    Venlo

Other trials in Netherlands

About this study

Official title: A Randomized, Open-Label, Phase 3 Study to Compare Long-Term Safety and Tolerability of the TAK-491 and Chlorthalidone Fixed-Dose Combination Versus Olmesartan Medoxomil and Hydrochlorothiazide Fixed-Dose Combination in Hypertensive Subjects With Moderate Renal Impairment

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.

Read the detailed description

A major component of blood pressure regulation is the renin-angiotensin-aldosterone system (RAAS). Drugs that modulate the RAAS are used commonly worldwide for the treatment of hypertension. TAK-491 (azilsartan medoxomil) is a prodrug of TAK-536 (azilsartan), an angiotensin II receptor blocker (ARB). Azilsartan medoxomil is being evaluated by Takeda to treat participants with essential hypertension.

Chlorthalidone is an orally administered thiazide-like diuretic agent, and long-term outcomes trials show blood pressure reductions associated with chlorthalidone treatment reduce risk of cardiovascular morbidity and mortality.

Hypertensive patients with moderate renal impairment are a relatively more severe and resistant hypertension population, and may benefit from effective fixed-dose combination treatments such as an ARB plus a diuretic for blood pressure control.

Participants will be randomized to receive azilsartan medoxomil and chlorthalidone or olmesartan medoxomil and hydrochlorothiazide for up to 52 weeks to evaluate long term safety of azilsartan medoxomil and chlorthalidone. A titration-to-target blood pressure approach will be used to guide the titration of study medication in this trial.

Conditions
Safety
Being tested
Azilsartan medoxomil and chlorthalidone, Olmesartan medoxomil and hydrochlorothiazide
Keywords
Renal Insufficiency, Kidney Diseases, Hypertension, Drug Therapy
Medical subject headings
Renal Insufficiency, Kidney Diseases, Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Azilsartan medoxomil and chlorthalidoneDrug

    Also called TAK-491CLD

    Fixed-dose combination tablets.

  • Olmesartan medoxomil and hydrochlorothiazideDrug

    Also called Olmesartan medoxomil, Hydrochlorothiazide, Benicar hydrochlorothiazide, Olmetec Plus

    Fixed-dose combination tablets.

Study groups in NCT01309828
Study groupRoleWhat they receive
Azilsartan Medoxomil + ChlorthalidoneExperimentalUnited 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.
Receives: Drug: Azilsartan medoxomil and chlorthalidone
Olmesartan Medoxomil + HydrochlorothiazideActive comparatorUnited 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.
Receives: Drug: Olmesartan medoxomil and hydrochlorothiazide

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)

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

    Systolic blood pressure is the arithmetic mean of the 3 serial sitting systolic blood pressure measurements. Percentage of participants who achieve a sitting clinic systolic blood pressure response defined as less than 130 mm Hg at Week 52.

    Measured: Week 52

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

    Diastolic blood pressure is the arithmetic mean of the 3 serial sitting diastolic blood pressure measurements. Percentage of participants at Week 52 who achieved a sitting clinic diastolic blood pressure response, defined as less than 80 mm Hg.

    Measured: Week 52

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

    Systolic/diastolic blood pressure is the arithmetic mean of the 3 serial sitting systolic/diastolic blood pressure measurements. Percentage of participants who achieved both a sitting clinic systolic and diastolic blood pressure response, defined as systolic blood pressure less than 130 mm Hg and diastolic blood pressure less than 80 mm Hg at Week 52.

    Measured: Week 52

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Mar 2011 (estimated)
  2. Study startMar 2011
  3. Primary completionOct 2012
  4. Study completionOct 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
153 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01309828
Sponsor's protocol ID
TAK-491CLD_309
Other IDs
2010-023098-21, U1111-1119-5131, NL35552.072.11
Status last verified
Sep 2013
First submitted
4 Mar 2011
Last updated
13 Dec 2013
Data monitoring committee
No

Publications

  • 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.

    PubMed 29504252

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Azilsartan medoxomil and chlorthalidone and Olmesartan medoxomil and hydrochlorothiazide in people with Safety, run by Takeda at 53 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 53 sites in Germany, Slovakia, Ukraine, Latvia, Bulgaria and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Dec 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With at Least 1 Adverse Event (AE) (time frame: 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).). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01309828, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Dec 2013.

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