A Study to Evaluate the Effectiveness and Safety of a Fixed Dose Combination of Azilsartan Medoxomil and Chlorthalidone in Patients With High Blood Pressure Who do Not Achieve Target Blood Pressure Following Treatment With Azilsartan Medoxomil Alone

NCT01456169 | Completed Phase 3 Results

• 5 other identifiers: TAK-491CLD_3072011-000220-16U1111-1119-474311-028NL36272.072.11
• Study Type: interventional
• Target: 507
• Locations: 12 countries
• Sites: 99

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of the fixed dose combinations of azilsartan medoxomil plus chlorthalidone (40/12.5 and 40/25 mg), once daily, in participants with grades 2 or 3 essential hypertension who do not reach target blood pressure following treatment with 40 mg azilsartan medoxomil monotherapy after 4 weeks.

Conditions

Essential Hypertension

Keywords

High Blood Pressure; Drug Therapy

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure

  The change between trough systolic blood pressure measured at final visit or Week 8 relative to baseline. Systolic blood pressure is the arithmetic mean of the 3 trough sitting systolic blood pressure measurements.

  Baseline (of the double-blind treatment period) and Week 8

Secondary Outcomes (14)

• Change From Baseline to Week 8 in Trough, Sitting, Clinic Diastolic Blood Pressure

  Baseline and Week 8

• Change From Baseline to Week 8 in Trough Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring

  Baseline and Week 8, 22-24 hours after dosing

• Change From Baseline to Week 8 in Trough Diastolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring

  Baseline and Week 8, 22-24 hours after dosing

• Change From Baseline to Week 8 in the 24-hour Mean Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring

  Baseline and Week 8

• Change From Baseline to Week 8 in the 24-hour Mean Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring

  Baseline and Week 8

Study Arms (3)

Azilsartan medoxomil 40 mg

ACTIVE COMPARATOR

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

Drug: Azilsartan medoxomil/placebo

Azilsartan medoxomil + chlorthalidone 40/12.5 mg

EXPERIMENTAL

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

Drug: Azilsartan medoxomil - chlorthalidone

Azilsartan medoxomil + chlorthalidone 40/25 mg

EXPERIMENTAL

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

Drug: Azilsartan medoxomil - chlorthalidone

Interventions

Azilsartan medoxomil/placebo DRUG

Azilsartan medoxomil and placebo to chlorthalidone combination tablets

Also known as: TAK-491, EDARBI

Azilsartan medoxomil 40 mg

Azilsartan medoxomil - chlorthalidone DRUG

Azilsartan medoxomil and chlorthalidone fixed dose combination tablets

Also known as: TAK-491CLD, Edarbyclor

Azilsartan medoxomil + chlorthalidone 40/12.5 mg; Azilsartan medoxomil + chlorthalidone 40/25 mg

Eligibility Criteria

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

You may qualify if:

• At Screening
• The participant has grade 2-3 essential hypertension which is not adequately controlled, as defined by mean, trough, sitting, clinic systolic blood pressure (SBP):
• ≥160 to ≤180 mm Hg in participants who have not received any antihypertensive medication in the 14 days prior to Visit 1.
• ≥150 to ≤170 mm Hg in participants taking 1 antihypertensive medication at Visit 1.
• ≥140 to ≤160 mm Hg in participants taking 2 antihypertensive medications at Visit 1.
• The participant has clinical laboratory test results (clinical chemistry, hematology, and complete urinalysis) within the reference range for the testing laboratory or the investigator does not consider the results to be clinically relevant for precluding entry in to the study in this hypertensive population.
• The participant is willing to discontinue current antihypertensive medications.
• 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.
• Male or female adult, at least 18 years of age.
• A female 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. NOTE: Women NOT of childbearing potential are defined as those who have been surgically sterilized (hysterectomy, bilateral oophorectomy, tubal ligation \[performed more than one 1 year prior to Screening\]) or who are postmenopausal (defined as at least 1 year since last regular menses).
• Post-placebo run-in:
• The participant must have a post-placebo run-in, 24-hour mean SBP by ambulatory blood pressure monitoring (ABPM) of 140-175 mm Hg inclusive, and a clinic SBP measurement of 160 to 190 mm Hg inclusive (determined by the mean of 3 sitting, trough, measurements on Day -29) to qualify for entry in to the 4 week single-blind TAK-491 40 mg monotherapy treatment period.
• Post-4 week, single-blind TAK-491 40 mg monotherapy treatment:
• The participant does not achieve target blood pressure (defined as clinic SBP ≥140 mm Hg as determined by the mean of 3 sitting, trough, measurements) following 4 weeks single-blind treatment with TAK-491 40 mg monotherapy at Day -1, prior to randomization to double-blind treatment.

You may not qualify if:

• At Screening
• The participant has clinic diastolic blood pressure (DBP) \>110 mm Hg.
• The participant's 3 SBP measurements differ by more than 15 mm Hg (confirmed by a second set of three measurements).
• The participant has received any investigational compound within 30 days prior to Screening or is currently participating in another investigational study. NOTE: Participants participating in observational studies (per local definition) may enter Screening provided that the last intervention or invasive procedure was \>30 days prior to Visit 1.
• The participant has been randomized/enrolled in a previous TAK-491 or TAK-491CLD study. NOTE: This criterion does not apply to participants who entered screening or placebo run-in in another TAK-491 or TAK-491CLD study but were not randomized/enrolled.
• The participant is a study site employee or is in a dependent relationship with a study site employee who is involved in conduct of this study (e.g., spouse, parent, child, sibling) or may consent under duress.
• The participant is currently treated with more than 2 antihypertensive medications.
• The participant works a night (third) shift (defined as 11 PM \[2300\] to 7 AM \[0700\]).
• The participant has an upper arm circumference \<24 cm or \>42 cm.
• The participant has secondary hypertension of any etiology (e.g., renovascular disease, pheochromocytoma, Cushing's syndrome).
• The participant has any history of myocardial infarction, heart failure, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebrovascular accident, persistent or permanent atrial fibrillation or transient ischemic attack.
• The participant has clinically significant cardiac conduction defects (e.g., third-degree atrioventricular block, sick sinus syndrome).
• The participant has hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease or hypertrophic cardiomyopathy.
• The participant has severe renal dysfunction or disease \[based on estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73m\^2 at screening\], prior renal transplantation or nephrotic syndrome (defined as a urinary albumin/creatinine ratio \>2000 mg/g at Screening).
• Participant has known hemodynamically significant bilateral renal artery stenosis or unilateral disease in a single kidney.

Sponsors & Collaborators

• Takeda: lead

Study Sites (108)

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Haskovo, Bulgaria

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Pazardzhik, Bulgaria

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Pleven, Bulgaria

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Plovdiv, Bulgaria

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Sofia, Bulgaria

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Varna, Bulgaria

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Veliko Tarnovo, Bulgaria

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Paide, Estonia

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Saku, Estonia

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Tallinn, Estonia

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Tartu, Estonia

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Võru, Estonia

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Labarthe-sur-Lèze, Haute Garonne, France

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Bourg-des-Comptes, Ille et Vilaine, France

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Tours, Indre et Loire, France

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Vourey, Isere, France

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Saint-Étienne-de-Montluc, Pays de la Loire Region, France

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Orthez, Pyrenees Atlantiques, France

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Karlsruhe, Baden-Wurttemberg, Germany

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Bad Wörishofen, Bavaria, 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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Stuhr, Lower Saxony, Germany

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Essen, North Rhine-Westphalia, Germany

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Kamp-Lintfort, North Rhine-Westphalia, Germany

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Mainz, Rhineland-Palatinate, Germany

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Dresden, Saxony, Germany

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Budapest, Hungary

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Debrecen, Hungary

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Gyöngyös, Hungary

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Gyula, Hungary

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Mosonmagyaróvár, Hungary

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Nyíregyháza, Hungary

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Pécs, Hungary

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Szikszó, Hungary

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Torrette Di Ancona, Ancona, Italy

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Acquaviva delle Fonti, Bari, Italy

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Brescia, Brescia, Italy

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Ferrara, Ferrara, Italy

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L’Aquila, L'Aquila, Italy

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Milan, Milano, Italy

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Palermo, Palermo, Italy

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Pavia, Pavia, Italy

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Pisa, Pisa, Italy

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Roma, Roma, Italy

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Sassari, Sassari, Italy

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Legnago, Verona, Italy

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Bologna, Italy

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Alytus, Lithuania

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Kaunas, Lithuania

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Beek, Netherlands

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Breda, Netherlands

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Eindhoven, Netherlands

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Groningen, Netherlands

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Leiderdorp, Netherlands

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Maastricht, Netherlands

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Rotterdam, Netherlands

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Velp, Netherlands

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Zoetermeer, Netherlands

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Zwijndrecht, Netherlands

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Bydgoszcz, Poland

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Gdansk, Poland

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Gdynia, Poland

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Krakow, Poland

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Lodz, Poland

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Lublin, Poland

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Oświęcim, Poland

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Parczew, Poland

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Poznan, Poland

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Pulway, Poland

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Rzeszów, Poland

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Sopot, Poland

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Torun, Poland

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Zgierz, Poland

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Belgrade, Serbia

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Kamenitz, Serbia

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Kragujevac, Serbia

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Kruševac, Serbia

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Niš, Serbia

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Zemun, Serbia

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Bardejov, Slovakia

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Bratislava, Slovakia

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Galanta, Slovakia

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Komárno, Slovakia

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Košice, Slovakia

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Lučenec, Slovakia

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Martin, Slovakia

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Nitra, Slovakia

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Nové Zámky, Slovakia

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Prešov, Slovakia

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Svidník, Slovakia

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Žilina, Slovakia

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Barcelona, Barcelona, Spain

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Centelles, Barcelona, Spain

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Madrid, Madrid, Spain

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Málaga, Malaga, Spain

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Gothenburg, Sweden

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Lund, Sweden

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Malmo, Sweden

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Vällingby, Sweden

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London, Greater London, United Kingdom

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Glasgow, Lanarkshire, United Kingdom

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Blackpool, Lancashire, United Kingdom

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Northwood, Middlesex, United Kingdom

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Bath, Somerset, United Kingdom

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Royal Leamington Spa, Warwickshire, United Kingdom

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Westbury, Wiltshire, United Kingdom

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MeSH Terms

Conditions

Essential Hypertension; Hypertension

Interventions

azilsartan medoxomil; azilsartan

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

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

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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2011
• First Posted: October 20, 2011
• Study Start: October 1, 2011
• Primary Completion: December 1, 2012
• Study Completion: January 1, 2013
• Last Updated: April 23, 2014
• Results First Posted: April 23, 2014

Record last verified: 2014-03

Locations

IT (13); HU (8); SE (6); ES (4); DE (10); BU (7); PL (14); SL (12); LI (2); NL (10); FR (6); GB (7)