Essential HypertensionPhase 3NCT01456169
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
A Phase 3 study testing Azilsartan medoxomil - chlorthalidone in people with Essential Hypertension, run by Takeda at 108 sites in 14 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Essential Hypertension
- What is being tested?
- Azilsartan medoxomil - chlorthalidone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 507 participants
- Where
- 108 sitesin 14 countries
- Study dates
- Oct 2011to Jan 2013
- 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
- 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.
Show all 15Show fewer
- 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.
Who cannot join
- 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.
Show all 31Show fewer
- 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.
- The participant has a history of cancer that has not been in remission for at least 5 years prior to the first dose of single-blind TAK-491 monotherapy study drug. (This criterion does not apply to those participants with basal cell or Stage 1 squamous cell carcinoma of the skin).
- The participant has poorly-controlled type 1 or 2 diabetes mellitus (hemoglobin A1c [HbA1c] >8.5%) at Screening.
- The participant has hypokalemia or hyperkalemia (defined as serum potassium outside of the normal reference range of the central laboratory) at Screening.
- The participant has an alanine aminotransferase or aspartate aminotransferase level >2.5 times the upper limit of normal, active liver disease, or jaundice at Screening.
- The participant 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.
- The participant has a history of hypersensitivity or allergies to angiotensin II receptor blockers (ARB) or thiazide-type diuretics or other sulfonamide-derived compounds.
- The participant has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse per local guidelines within the past 2 years.
- The participant is required to take excluded medications at any point during the study.
- If female, the participant is pregnant or lactating or intending to become pregnant before, during, or within 1 month after participating in this study; or intending to donate ova during such time period.
- Post-placebo run-in period
- The participant has a clinic SBP >190 mm Hg and DBP >115 mm Hg.
- The participant is noncompliant (<70% or >130%) with study medication during the placebo run-in period.
- The participant has a 24-hour mean eligibility ABPM reading of insufficient quality.
- Post-single-blind TAK-491 40 mg treatment period
- The participant has a clinic SBP >180 mm Hg and DBP >110 mm Hg.
- The participant is noncompliant (<70% or >130%) with study medication during the TAK-491 40 mg single-blind treatment period.
Trial locations and contacts
108 sites in 14 countries.
108 sites in 14 countries
Poland14 sites
Study site
Bydgoszcz
Study site
Gdansk
Study site
Gdynia
Study site
Krakow
Study site
Lodz
Study site
Lublin
Study site
Oświęcim
Study site
Parczew
Study site
Poznan
Study site
Pulway
Study site
Rzeszów
Study site
Sopot
Study site
Torun
Study site
Zgierz
Italy13 sites
Study site
Acquaviva delle Fonti, Bari
Study site
Bologna
Study site
Brescia, Brescia
Study site
Ferrara, Ferrara
Study site
L’Aquila, L'Aquila
Study site
Legnago, Verona
Study site
Milan, Milano
Study site
Palermo, Palermo
Study site
Pavia, Pavia
Study site
Pisa, Pisa
Study site
Roma, Roma
Study site
Sassari, Sassari
Study site
Torrette Di Ancona, Ancona
Slovakia12 sites
Study site
Bardejov
Study site
Bratislava
Study site
Galanta
Study site
Komárno
Study site
Košice
Study site
Lučenec
Study site
Martin
Study site
Nitra
Study site
Nové Zámky
Study site
Prešov
Study site
Svidník
Study site
Žilina
Germany10 sites
Study site
Bad Wörishofen, Bavaria
Study site
Dresden, Saxony
Study site
Essen, North Rhine-Westphalia
Study site
Frankfurt am Main, Hesse
Study site
Hamburg, Free and Hanseatic City of Hamburg
Study site
Kamp-Lintfort, North Rhine-Westphalia
Study site
Karlsruhe, Baden-Wurttemberg
Study site
Mainz, Rhineland-Palatinate
Study site
Nuremberg, Bavaria
Study site
Stuhr, Lower Saxony
Netherlands10 sites
Study site
Beek
Study site
Breda
Study site
Eindhoven
Study site
Groningen
Study site
Leiderdorp
Study site
Maastricht
Study site
Rotterdam
Study site
Velp
Study site
Zoetermeer
Study site
Zwijndrecht
Hungary8 sites
Study site
Budapest
Study site
Debrecen
Study site
Gyöngyös
Study site
Gyula
Study site
Mosonmagyaróvár
Study site
Nyíregyháza
Study site
Pécs
Study site
Szikszó
Bulgaria7 sites
Study site
Haskovo
Study site
Pazardzhik
Study site
Pleven
Study site
Plovdiv
Study site
Sofia
Study site
Varna
Study site
Veliko Tarnovo
United Kingdom7 sites
Study site
Bath, Somerset
Study site
Blackpool, Lancashire
Study site
Glasgow, Lanarkshire
Study site
London, Greater London
Study site
Northwood, Middlesex
Study site
Royal Leamington Spa, Warwickshire
Study site
Westbury, Wiltshire
France6 sites
Study site
Bourg-des-Comptes, Ille et Vilaine
Study site
Labarthe-sur-Lèze, Haute Garonne
Study site
Orthez, Pyrenees Atlantiques
Study site
Saint-Étienne-de-Montluc, Pays de la Loire Region
Study site
Tours, Indre et Loire
Study site
Vourey, Isere
Serbia6 sites
Study site
Belgrade
Study site
Kamenitz
Study site
Kragujevac
Study site
Kruševac
Study site
Niš
Study site
Zemun
Estonia5 sites
Study site
Paide
Study site
Saku
Study site
Tallinn
Study site
Tartu
Study site
Võru
Spain4 sites
Study site
Barcelona, Barcelona
Study site
Centelles, Barcelona
Study site
Madrid, Madrid
Study site
Málaga, Malaga
Sweden4 sites
Study site
Gothenburg
Study site
Lund
Study site
Malmö
Study site
Vällingby
About this study
Official title: A Phase-3 Randomized, Double-Blind, Efficacy and Safety Study Evaluating the Fixed Dose Combinations of TAK-491 Plus Chlorthalidone (40/12.5 mg and 40/25 mg) in Subjects With Grades 2 or 3 Essential Hypertension, Who Do Not Achieve Target Blood Pressure Following Treatment With TAK-491 40 mg Monotherapy
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.
Read the detailed description
Eligible participants completed a 2-week single-blind run-in period (Days -42 to -29) prior to a Single-Blind Monotherapy Treatment Period (Day -28 to Day -1) where they received azilsartan medoxomil 40 mg. After the Single-Blind Monotherapy Treatment Period, those participants who achieved target blood pressure discontinued treatment and resumed standard of care management at the discretion of their treating physician, while those participants who did not achieve target blood pressure (defined as clinic systolic blood pressure ≥140 mmHg) were randomly assigned to 1 of 3 active treatment arms: azilsartan medoxomil 40 mg plus placebo, azilsartan medoxomil plus chlorthalidone 40/12.5 mg, or azilsartan medoxomil plus chlorthalidone 40/25 mg.
- Conditions
- Essential Hypertension
- Being tested
- Azilsartan medoxomil/placebo, Azilsartan medoxomil - chlorthalidone
- Keywords
- High Blood Pressure, Drug Therapy
- Medical subject headings
- Essential Hypertension, Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Azilsartan medoxomil/placeboDrug
Also called TAK-491, EDARBI
Azilsartan medoxomil and placebo to chlorthalidone combination tablets
Azilsartan medoxomil - chlorthalidoneDrug
Also called TAK-491CLD, Edarbyclor
Azilsartan medoxomil and chlorthalidone fixed dose combination tablets
| Study group | Role | What they receive |
|---|---|---|
| Azilsartan medoxomil 40 mg | Active comparator | Azilsartan medoxomil 40 mg and placebo to chlorthalidone combination tablets, orally, once daily for up to 8 weeks. Receives: 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. Receives: 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. Receives: Drug: Azilsartan medoxomil - chlorthalidone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
The change between trough diastolic blood pressure measured at final visit or week 8 relative to baseline Diastolic blood pressure is the arithmetic mean of the 3 trough sitting diastolic blood pressure measurements.
Measured: Baseline and Week 8
Change From Baseline to Week 8 in Trough Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring
The change in trough systolic blood pressure measured at final visit or week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough is the average of all measurements recorded from 22 to 24 hours after dosing.
Measured: 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
The change in trough diastolic blood pressure measured at final visit or week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough is the average of all measurements recorded from 22 to 24 hours after dosing.
Measured: 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
The change in 24-hour mean systolic blood pressure measured at final visit or week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing.
Measured: 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
The change in 24-hour mean diastolic blood pressure measured at final visit or week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing.
Measured: Baseline and Week 8
Change From Baseline to Week 8 in the Mean Daytime Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring
The change in daytime (6 am to 10 pm) mean systolic blood pressure measured at final visit or week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of all measurements recorded between the hours of 6 am and 10 pm.
Measured: Baseline and Week 8
Change From Baseline to Week 8 in the Mean Daytime Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring
The change in daytime (6 am to 10 pm) mean diastolic blood pressure measured at final visit or week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of all measurements recorded between the hours of 6 am and 10 pm.
Measured: Baseline and Week 8
Change From Baseline to Week 8 in the Mean Nighttime Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring
The change in nighttime (12 am to 6 am) mean systolic blood pressure measured at final visit or week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of all measurements recorded between the hours of 12 am and 6 am.
Measured: Baseline and Week 8
Change From Baseline to Week 8 in the Mean Nighttime Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring
The change in nighttime (12 am to 6 am) mean diastolic blood pressure measured at final visit or week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of all measurements recorded between the hours of 12 am and 6 am.
Measured: Baseline and Week 8.
Change From Baseline to Week 8 in the Mean Systolic Blood Pressure 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring
The change in the 12-hour mean systolic blood pressure measured at final visit or week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 12-hour mean is the average of all measurements recorded in the first 12 hours after dosing.
Measured: Baseline and Week 8
Change From Baseline to Week 8 in the Mean Diastolic Blood Pressure 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring
The change in the 12-hour mean diastolic blood pressure measured at final visit or Week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 12-hour mean is the average of all measurements recorded in the first 12 hours after dosing.
Measured: Baseline and Week 8
Percentage of Participants Who Achieve a Target Clinic Systolic Blood Pressure at Week 8
Percentage of participants who achieve a target clinic systolic blood pressure measured at final visit or week 8, defined as less than 140 mm Hg (or less than 130 mm Hg for participants with diabetes or chronic kidney disease). Systolic blood pressure is the arithmetic mean of the 3 trough sitting Systolic blood pressure measurements.
Measured: Week 8
Percentage of Participants Who Achieve a Target Clinic Diastolic Blood Pressure at Week 8
Percentage of participants who achieve a target clinic diastolic blood pressure measured at final visit or week 8, defined as less than 90 mm Hg (or less than 80 mm Hg for participants with diabetes or chronic kidney disease). Diastolic blood pressure is based on the arithmetic mean of the 3 trough sitting diastolic blood pressure measurements.
Measured: Week 8
Percentage of Participants Who Achieve Both Clinic Systolic and Diastolic Blood Pressure Targets at Week 8
Percentage of participants who achieve both clinic systolic and diastolic blood pressure targets at Week 8, defined as less than 140 mm Hg (or less than 130 mm Hg for participants with diabetes or chronic kidney disease) for systolic AND less than 90 mm Hg (or less than 80 mm Hg for participants with diabetes or chronic kidney disease) for diastolic blood pressure.
Measured: Week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2011 (estimated)
- Study startOct 2011
- Primary completionDec 2012
- Study completionJan 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Essential HypertensionStudies of the same condition, open and under way.
- More trials run by TakedaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 507 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Clinical Science, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01456169
- Sponsor's protocol ID
- TAK-491CLD_307
- Other IDs
- 2011-000220-16, U1111-1119-4743, 11-028, NL36272.072.11
- Status last verified
- Mar 2014
- First submitted
- 18 Oct 2011
- Last updated
- 23 Apr 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase-3 Randomized, Double-Blind, Efficacy and Safety Study Evaluating the Fixed Dose Combinations of TAK-491 Plus Chlorthalidone (40/12.5 mg and 40/25 mg) in Subjects With Grades 2 or 3 Essential Hypertension, Who Do Not Achieve Target Blood Pressure Following Treatment With TAK-491 40 mg Monotherapy
- ClinicalTrials.gov ID
- NCT01456169
- Acronym / sponsor ID
- TAK-491CLD_307
- Conditions
- Essential Hypertension
- Keywords
- High Blood Pressure, Drug Therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 507 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- Oct 2011
- Primary completion
- Dec 2012 (actual)
- Study completion
- Jan 2013 (actual)
- First posted
- 20 Oct 2011 (estimated)
- Results
- Posted 23 Apr 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Eligible participants completed a 2-week single-blind run-in period (Days -42 to -29) prior to a Single-Blind Monotherapy Treatment Period (Day -28 to Day -1) where they received azilsartan medoxomil 40 mg. After the Single-Blind Monotherapy Treatment Period, those participants who achieved target blood pressure discontinued treatment and resumed standard of care management at the discretion of their treating physician, while those participants who did not achieve target blood pressure (defined as clinic systolic blood pressure ≥140 mmHg) were randomly assigned to 1 of 3 active treatment arms: azilsartan medoxomil 40 mg plus placebo, azilsartan medoxomil plus chlorthalidone 40/12.5 mg, or azilsartan medoxomil plus chlorthalidone 40/25 mg.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Azilsartan medoxomil 40 mg | Active comparator | Drug: Azilsartan medoxomil/placeboAzilsartan medoxomil 40 mg and placebo to chlorthalidone combination tablets, orally, once daily for up to 8 weeks. |
| Azilsartan medoxomil + chlorthalidone 40/12.5 mg | Experimental | Drug: Azilsartan medoxomil - chlorthalidoneAzilsartan 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for up to 8 weeks. |
| Azilsartan medoxomil + chlorthalidone 40/25 mg | Experimental | Drug: Azilsartan medoxomil - chlorthalidoneAzilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for up to 8 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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):
- 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.
Key exclusion criteria (31 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Azilsartan medoxomil/placeboAlso: TAK-491, EDARBIAzilsartan medoxomil and placebo to chlorthalidone combination tablets | Drug | Azilsartan medoxomil 40 mg |
| Azilsartan medoxomil - chlorthalidoneAlso: TAK-491CLD, EdarbyclorAzilsartan medoxomil and chlorthalidone fixed dose combination tablets | Drug | Azilsartan medoxomil + chlorthalidone 40/12.5 mg, Azilsartan medoxomil + chlorthalidone 40/25 mg |
Primary outcome
Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure
Time frame: Baseline (of the double-blind treatment period) and Week 8
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.
14 secondary outcomes
Change From Baseline to Week 8 in Trough, Sitting, Clinic Diastolic Blood Pressure
Time frame: Baseline and Week 8
Change From Baseline to Week 8 in Trough Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Baseline and Week 8
Change From Baseline to Week 8 in the Mean Daytime Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring
Time frame: Baseline and Week 8
Change From Baseline to Week 8 in the Mean Daytime Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring
Time frame: Baseline and Week 8
Change From Baseline to Week 8 in the Mean Nighttime Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring
Time frame: Baseline and Week 8
Change From Baseline to Week 8 in the Mean Nighttime Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring
Time frame: Baseline and Week 8.
Change From Baseline to Week 8 in the Mean Systolic Blood Pressure 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring
Time frame: Baseline and Week 8
Change From Baseline to Week 8 in the Mean Diastolic Blood Pressure 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring
Time frame: Baseline and Week 8
Percentage of Participants Who Achieve a Target Clinic Systolic Blood Pressure at Week 8
Time frame: Week 8
Percentage of Participants Who Achieve a Target Clinic Diastolic Blood Pressure at Week 8
Time frame: Week 8
Percentage of Participants Who Achieve Both Clinic Systolic and Diastolic Blood Pressure Targets at Week 8
Time frame: Week 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Essential Hypertension
Recruiting
The Effect of Self-Acupressure on Blood Pressure, Stress, and Well-Being Levels in Individuals With Hypertension
PRIMARY HYPERTENSION
Active, not recruiting
Smartphone-Guided Paced Breathing and Aerobic Exercise for Essential Hypertension
Essential (Primary) Hypertension
Recruiting
Isometric Resistance Exercise on Accelerated Atherosclerosis in Hypertension
Atherosclerosis Cardiovascular Disease
Not yet recruitingObservational study
A Study to Evaluate the Effectiveness and Safety of S-amlodipine-based Monotherapy and Combination Therapy
Hypertension (HTN), Hypertension
Recruiting
Community Health Worker Support to Lower Blood Pressure After a Pregnancy With High Blood Pressure
Pregnancy-Associated Hypertension, Gestational Hypertension
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director, Clinical Science study director
Takeda
108 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Azilsartan medoxomil - chlorthalidone in people with Essential Hypertension, run by Takeda at 108 sites in 14 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 15 inclusion and 31 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 23 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 108 sites in Poland, Italy, Slovakia, Germany, Netherlands and 9 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 23 Apr 2014). 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?
Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure (time frame: Baseline (of the double-blind treatment period) and Week 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Apr 2014.