Essential HypertensionPhase 3NCT00996281
Safety and Tolerability of Azilsartan Medoxomil Plus Chlorthalidone Compared to Olmesartan Medoxomil Plus Hydrochlorothiazide in Participants With Essential Hypertension
A Phase 3 study testing Azilsartan medoxomil and chlorthalidone and Olmesartan medoxomil and hydrochlorothiazide in people with Essential Hypertension, run by Takeda at 26 sites in 5 countries.
Trial 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. 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 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
- 837 participants
- Where
- 26 sitesin 5 countries
- Study dates
- Oct 2009to Nov 2011
- 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 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.
Who cannot join
- 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.
Show all 20Show fewer
- 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.
- Has a history of drug abuse or a history of alcohol abuse within the past 2 years.
- Is taking or expected to take any excluded medication, including:
- Antihypertensive medications must be discontinued completely by Day -14, except antihypertensive medications used in the open-label treatment period in accordance with the titration-to-target blood pressure titration.
- Angiotensin II receptor blockers or thiazide-type diuretics other than study medication.
- Over-the-counter products not permitted by investigator.
Trial locations and contacts
26 sites in 5 countries.
26 sites in 5 countries
Netherlands8 sites
Study site
Amsterdam, North Holland
Study site
Breda, North Brabant
Study site
Eindhoven, North Brabant
Study site
Groningen, Provincie Groningen
Study site
Leiderdorp, South Holland
Study site
Rotterdam, South Holland
Study site
Velp, Rheden
Study site
Zoetermeer, South Holland
Poland7 sites
Study site
Bydgoszcz, Kuyavian-Pomeranian Voivodeship
Study site
Gdansk, Pomeranian
Study site
Gdynia, Pomeranian
Study site
Mikołów, Silesian
Study site
Skierniewice, L0dz
Study site
Sopot, Pomeranian
Study site
Zgierz, L0dz
United Kingdom7 sites
Study site
Avon, England
Study site
Bolton, England
Study site
Chorley, England
Study site
Inverness, England
Study site
Liverpool, England
Study site
Surrey, England
Study site
Warwickshire, England
Germany3 sites
Study site
Hanover, Lower Saxony
Study site
Karlsruhe, Baden-Wurttemberg
Study site
Kiel-Kronshagen, Schleswig-Holstein
About this study
Official title: A Phase 3, Open-Label, Randomized, Long-Term Comparison of the Safety and Tolerability of the TAK-491 Plus Chlorthalidone Fixed-Dose Combination vs. Olmesartan Medoxomil-Hydrochlorothiazide Fixed-Dose Combination in Subjects With Essential Hypertension
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.
Read the detailed description
High Blood Pressure (Hypertension) is the most common cause of preventable death in developed nations. Uncontrolled hypertension greatly increases the risk of heart disease, brain disease, and kidney failure. As the population ages, the incidence of hypertension will continue to increase if effective preventive measures are not implemented. Despite the availability of antihypertensive agents, hypertension is not adequately controlled; only about one in three patients successfully keep blood pressure normal.
Treatment for high blood pressure includes thiazides or thiazide-like diuretics, either alone or as part of combination treatment. Chlorthalidone is a commercially available, orally administered thiazide-type diuretic agent.
TAK-491 (azilsartan) is an angiotensin II receptor blocker being evaluated by Takeda to treat patients with high blood pressure (essential hypertension).
This study will compare the safety and tolerability of azilsartan medoxomil plus chlorthalidone (TAK-491CLD) fixed-dose combination to olmesartan medoxomil-hydrochlorothiazide fixed-dose combination.
Initially patients will undergo a Screening Visit to confirm that they are eligible to participate in the study. All participants will receive the study drug for up to 52 weeks. The dose of the study drug may be gradually increased throughout the study so that a target blood pressure value can be reached for each participant.
Throughout the treatment period of the study, participants will be required to visit the research site for 11 visits. At these study visits participants will be required to undergo certain study procedures including physical examinations, vital sign measurements (blood pressure, heart rate, weight and height), electrocardiograms (monitoring of the heart), and blood and urine samples taken for clinical laboratory tests.
- Conditions
- Essential Hypertension
- Being tested
- Azilsartan medoxomil and chlorthalidone, Olmesartan medoxomil and hydrochlorothiazide
- Keywords
- Hypertensive, Blood Pressure, High, Cardiovascular disease, Vascular Disease, Drug Therapy
- Medical subject headings
- Essential Hypertension, Hypertension, Cardiovascular Diseases, Vascular Diseases
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
Combination tablet.
Olmesartan medoxomil and hydrochlorothiazideDrug
Also called Benicar HCT®, Olmetec Plus®
Combination tablet.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Olmesartan medoxomil and hydrochlorothiazide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
Serum creatinine was measured at every visit and evaluated as a laboratory parameter of special interest. The percentage of participants with creatinine increase ≥50% from Baseline and greater than ULN was summarized: - At any visit (includes transient and persistent elevations). - At the Final Visit (includes persistent elevations and participants whose first elevation may have been at the Final Visit). - At least 2 consecutive visits (includes only persistent elevations).
Measured: Baseline and Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2009 (estimated)
- Study startOct 2009
- Primary completionNov 2011
- Study completionNov 2011
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
- None (open label)
- Enrolment
- 837 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Executive Medical Director, Clinical Science, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00996281
- Sponsor's protocol ID
- TAK-491CLD_308
- Other IDs
- 2008-008260-28, U1111-1111-7891, 2008
- Status last verified
- Oct 2012
- First submitted
- 12 Oct 2009
- Last updated
- 12 Nov 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Open-Label, Randomized, Long-Term Comparison of the Safety and Tolerability of the TAK-491 Plus Chlorthalidone Fixed-Dose Combination vs. Olmesartan Medoxomil-Hydrochlorothiazide Fixed-Dose Combination in Subjects With Essential Hypertension
- ClinicalTrials.gov ID
- NCT00996281
- Acronym / sponsor ID
- TAK-491CLD_308
- Conditions
- Essential Hypertension
- Keywords
- Hypertensive, Blood Pressure, High, Cardiovascular disease, Vascular Disease, Drug Therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 837 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- Oct 2009
- Primary completion
- Nov 2011 (actual)
- Study completion
- Nov 2011 (actual)
- First posted
- 16 Oct 2009 (estimated)
- Results
- Posted 12 Nov 2012
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 compare the safety and tolerability of azilsartan medoxomil plus chlorthalidone, once daily (QD), versus olmesartan medoxomil-hydrochlorothiazide in adults with essential hypertension.
Detailed description
High Blood Pressure (Hypertension) is the most common cause of preventable death in developed nations. Uncontrolled hypertension greatly increases the risk of heart disease, brain disease, and kidney failure. As the population ages, the incidence of hypertension will continue to increase if effective preventive measures are not implemented. Despite the availability of antihypertensive agents, hypertension is not adequately controlled; only about one in three patients successfully keep blood pressure normal.
Treatment for high blood pressure includes thiazides or thiazide-like diuretics, either alone or as part of combination treatment. Chlorthalidone is a commercially available, orally administered thiazide-type diuretic agent.
TAK-491 (azilsartan) is an angiotensin II receptor blocker being evaluated by Takeda to treat patients with high blood pressure (essential hypertension).
This study will compare the safety and tolerability of azilsartan medoxomil plus chlorthalidone (TAK-491CLD) fixed-dose combination to olmesartan medoxomil-hydrochlorothiazide fixed-dose combination.
Initially patients will undergo a Screening Visit to confirm that they are eligible to participate in the study. All participants will receive the study drug for up to 52 weeks. The dose of the study drug may be gradually increased throughout the study so that a target blood pressure value can be reached for each participant.
Throughout the treatment period of the study, participants will be required to visit the research site for 11 visits. At these study visits participants will be required to undergo certain study procedures including physical examinations, vital sign measurements (blood pressure, heart rate, weight and height), electrocardiograms (monitoring of the heart), and blood and urine samples taken for clinical laboratory tests.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Azilsartan Medoxomil and Chlorthalidone | Experimental | Drug: Azilsartan medoxomil and chlorthalidoneAzilsartan 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. |
| Olmesartan Medoxomil and Hydrochlorothiazide QD | Active comparator | Drug: Olmesartan medoxomil and hydrochlorothiazideParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (20 listed)
- 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.
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 and chlorthalidoneAlso: TAK-491CLDCombination tablet. | Drug | Azilsartan Medoxomil and Chlorthalidone |
| Olmesartan medoxomil and hydrochlorothiazideAlso: Benicar HCT®, Olmetec Plus®Combination tablet. | Drug | Olmesartan Medoxomil and Hydrochlorothiazide QD |
Primary outcome
Percentage of Participants With at Least 1 Adverse Event
Time frame: From Week 0 (Day 1) to Week 52.
An adverse event is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product without regard to causality.
1 secondary outcome
Percentage of Participants With Serum Creatinine Elevations Greater Than 50% From Baseline and Greater Than the Upper Limit of Normal (ULN)
Time frame: Baseline and Week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Executive Medical Director, Clinical Science study director
Takeda
26 sites in 5 countries: see every site and its status.
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 Essential Hypertension, run by Takeda at 26 sites in 5 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 4 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 12 Nov 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in Netherlands, Poland, United Kingdom, Germany, Austria. 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 12 Nov 2012). 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?
Percentage of Participants With at Least 1 Adverse Event (time frame: From Week 0 (Day 1) to Week 52.). 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 12 Nov 2012.