HypertensionPhase 2NCT00759551
Efficacy and Safety of Azilsartan in Subjects With Essential Hypertension
A Phase 2 study testing Azilsartan and Olmesartan in people with Hypertension, run by Takeda.
Trial summary
The purpose of this study is to determine the safety and efficacy of azilsartan, once daily (QD), in subjects with essential hypertension. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypertension
- What is being tested?
- Azilsartan and Olmesartan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 555 participants
- Where
- No sites listed yet
- Study dates
- Aug 2004to Jun 2005
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Has mild to moderate uncomplicated essential hypertension (diastolic blood pressure between 95 and 114 mm Hg at Screening Day -7 and randomization visit).
- Female patients of childbearing potential must be nonpregnant and nonlactating, and utilizing an acceptable method of contraception.
- Has clinical laboratory evaluations (including clinical chemistry, hematology, and complete urinalysis) within the reference range for the testing laboratory unless the results are deemed not clinically significant for inclusion into this study by the investigator or sponsor.
- Is willing to discontinue current antihypertensive medications.
Who cannot join
- Has a decrease of more than or equal to 8 mm Hg in clinic diastolic blood pressure between Screening Day -7 and randomization visit.
- Is hypersensitive to angiotensin II receptor blockers.
- The patient has Grade 3 or 4 hypertensive retinopathy (Keith-Wagener scale).
- Has significant cardiac disease (eg, primary, hemodynamically significant cardiac valvular disease) other than mild to moderate uncomplicated hypertensive cardiovascular disease.
- Has taken, within 7 days prior to placebo run-in, or is expected to take, medications known to affect blood pressure, including the following:
- Diuretics
Show all 30Show fewer
- Anti-hypertensives
- Vasodilators
- Tricyclic antidepressants
- Monoamine oxidase inhibitors
- Phenothiazines
- Diet medications
- Amphetamines or their derivatives
- Thiazolidinediones
- Lithium
- Chronic use of common cold medications or nonsteroidal anti-inflammatory drugs including aspirin >325 mg/day or cyclooxygenase-2 inhibitors).
- Has a history of myocardial infarction complicated by heart failure, post-myocardial infarction angina, hypertensive encephalopathy, or cerebrovascular accident.
- Has clinically significant cardiac conduction defects (eg, 2nd or 3rd degree atrioventricular block, left bundle branch block, sick sinus syndrome, atrial fibrillation or flutter).
- Has secondary hypertension of any etiology (eg, renal disease, pheochromocytoma, Cushing's syndrome).
- Has a history of collagen vascular disorder (eg systemic lupus erythematosus, scleroderma) within the last five years.
- Has an upper arm circumference less than 24 or greater than 42 cm.
- Works night (3rd) shift.
- Is non-compliant (less than 80%) with study medication during placebo run-in period.
- Has significant, moderate to severe renal dysfunction or disease (including renal artery stenosis).
- Has a history of drug abuse (defined as illicit drug use) or a history of alcohol abuse (defined as regular or daily consumption of more than 4 alcoholic drinks per day) within the past 2 years.
- Has a previous history of cancer, other than basal cell carcinoma, that has not been in remission for at least 5 years prior to the first dose of study drug.
- Has Type I or Type II diabetes mellitus.
- Has an alanine transaminase or aspartate transaminase level of greater than 3 times the upper limit of normal, active liver disease, or jaundice.
- Is participating in another investigational study or has participated in an investigational study within 30 days prior to randomization.
- Has -any other serious disease or condition at Screening (or randomization) that would compromise patient safety, might affect life expectancy, or make it difficult to successfully manage and follow the patient according to the protocol.
About this study
Official title: A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Dose-Ranging Study of the Efficacy, Safety, and Tolerability of TAK-536 in Patients With Mild to Moderate Uncomplicated Essential Hypertension
The purpose of this study is to determine the safety and efficacy of azilsartan, once daily (QD), in subjects with essential hypertension.
Read the detailed description
According to the National Health and Nutrition Examination Survey, approximately 60 million people in the United States are hypertensive. Although no single risk factor is responsible for the development of hypertension, some of the many risk factors can be controlled, and some cannot. Controllable risk factors include weight gain, smoking, a sedentary lifestyle, poor eating habits, emotional stress, physical tension, sodium sensitivity, alcohol abuse, and use of oral contraceptives. Uncontrollable risk factors include family history, gender, age and race.
Hypertension is termed the "silent killer" because many patients are asymptomatic. Chronic hypertension causes extensive arterial wall damage, which allows cholesterol to adhere to the damaged endothelial lining and produces increased cardiac stress. Hypertension dramatically increases the risk of myocardial infarction, stroke, renal damage, impaired vision, heart failure and overall mortality. Angiotensin II receptor blockers are a class of drugs used for the treatment of hypertension that not only decrease blood pressure, but also likely contribute to protecting hypertensive individuals from cardiac events, strokes and loss of renal function.
Angiotensin II has significant physiological effects on tissues and organs throughout the body including vascular smooth muscle, adrenal cortex, kidney, and brain. Angiotensin II receptors are located on the plasma membrane of target cells to facilitate the rapid onset of angiotensin II. Three distinct subtypes of angiotensin II receptors have been identified: angiotensin II type-1 receptor, angiotensin type 2, and angiotensin type 4; and the relative proportion of each vary from tissue to tissue. The angiotensin II type-1 receptor subtype is expressed predominantly in vascular smooth muscle cells where activation by angiotensin II results in vasoconstriction, cell proliferation, fibrosis, and cellular hypertrophy. In contrast, angiotensin II type-2 receptor stimulation produces pharmacologic activities that are opposite to those that occur after angiotensin II type-1 receptor stimulation. The angiotensin II type-4 receptor has been reported to be expressed in the adrenals, brain, and myocardium, but its exact function remains unknown. It is not considered to play an important role in human pathogenesis.
TAK-536 (azilsartan) is a synthetic angiotensin II type-1 receptor antagonist being developed as a treatment for mild to moderate uncomplicated essential hypertension
- Conditions
- Hypertension
- Being tested
- Azilsartan, Placebo, Olmesartan
- Keywords
- Blood Pressure, Drug Therapy, Systolic Pressure, Diastolic Pressure, Vascular Diseases
- Medical subject headings
- Hypertension, Vascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzilsartanDrug
Also called TAK-536
Azilsartan 2.5 mg, tablets, orally, once daily and olmesartan placebo-matching capsules and tablets, orally, once daily for up to 8 weeks.
AzilsartanDrug
Also called TAK-536
Azilsartan 5.0 mg, tablets, orally, once daily and olmesartan placebo-matching capsules and tablets, orally, once daily for up to 8 weeks.
AzilsartanDrug
Also called TAK-536
Azilsartan 10 mg, tablets, orally, once daily and olmesartan placebo-matching capsules and tablets, orally, once daily for up to 8 weeks.
AzilsartanDrug
Also called TAK-536
Azilsartan 20 mg, tablets, orally, once daily and olmesartan placebo-matching capsules and tablets, orally, once daily for up to 8 weeks.
AzilsartanDrug
Also called TAK-536
Azilsartan 40 mg, tablets, orally, once daily and olmesartan placebo-matching capsules and tablets, orally, once daily for up to 8 weeks.
PlaceboDrug
Azilsartan placebo-matching tablets, orally, once daily and olmesartan placebo-matching capsules, orally, once daily for up to 8 weeks.
OlmesartanDrug
Also called Benicar®, Olmetec®
Azilsartan placebo-matching tablets, orally, once daily and olmesartan 20 mg, capsules, orally, once daily for up to 8 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Azilsartan 2.5 mg QD | Experimental | Not described Receives: Drug: Azilsartan |
| Azilsartan 5 mg QD | Experimental | Not described Receives: Drug: Azilsartan |
| Azilsartan 10 mg QD | Experimental | Not described Receives: Drug: Azilsartan |
| Azilsartan 20 mg QD | Experimental | Not described Receives: Drug: Azilsartan |
| Azilsartan 40 mg QD | Experimental | Not described Receives: Drug: Azilsartan |
| Placebo QD | Placebo comparator | Not described Receives: Drug: Placebo |
| Olmesartan 20 mg QD | Active comparator | Not described Receives: Drug: Olmesartan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from Baseline in sitting clinic diastolic blood pressure.
Measured: Week 8 or Final Visit
Secondary outcomes (3)
Change from Baseline in sitting clinic systolic blood pressure.
Measured: Weeks 2, 4, 6, and 8 or Final Visit
The change from Baseline in standing clinic diastolic blood pressure and systolic blood pressure.
Measured: Weeks 2, 4, 6, and 8 or Final Visit
Change from Baseline in diastolic blood pressure and systolic blood pressure as measured by ambulatory blood pressure monitoring.
Measured: Week 8 or Final Visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2008 (estimated)
- Study startAug 2004
- Primary completionJun 2005
- Study completionJun 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 555 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- VP Clinical Science Strategy, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00759551
- Sponsor's protocol ID
- 01-03-TL-536-002
- Other IDs
- U1111-1113-8708
- Status last verified
- Jun 2010
- First submitted
- 24 Sep 2008
- Last updated
- 22 Jun 2010
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Dose-Ranging Study of the Efficacy, Safety, and Tolerability of TAK-536 in Patients With Mild to Moderate Uncomplicated Essential Hypertension
- ClinicalTrials.gov ID
- NCT00759551
- Acronym / sponsor ID
- 01-03-TL-536-002
- Conditions
- Hypertension
- Keywords
- Blood Pressure, Drug Therapy, Systolic Pressure, Diastolic Pressure, Vascular Diseases
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 555 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- Aug 2004
- Primary completion
- Jun 2005 (actual)
- Study completion
- Jun 2005 (actual)
- First posted
- 25 Sep 2008 (estimated)
- Results
- Not posted in the source record
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 determine the safety and efficacy of azilsartan, once daily (QD), in subjects with essential hypertension.
Detailed description
According to the National Health and Nutrition Examination Survey, approximately 60 million people in the United States are hypertensive. Although no single risk factor is responsible for the development of hypertension, some of the many risk factors can be controlled, and some cannot. Controllable risk factors include weight gain, smoking, a sedentary lifestyle, poor eating habits, emotional stress, physical tension, sodium sensitivity, alcohol abuse, and use of oral contraceptives. Uncontrollable risk factors include family history, gender, age and race.
Hypertension is termed the "silent killer" because many patients are asymptomatic. Chronic hypertension causes extensive arterial wall damage, which allows cholesterol to adhere to the damaged endothelial lining and produces increased cardiac stress. Hypertension dramatically increases the risk of myocardial infarction, stroke, renal damage, impaired vision, heart failure and overall mortality. Angiotensin II receptor blockers are a class of drugs used for the treatment of hypertension that not only decrease blood pressure, but also likely contribute to protecting hypertensive individuals from cardiac events, strokes and loss of renal function.
Angiotensin II has significant physiological effects on tissues and organs throughout the body including vascular smooth muscle, adrenal cortex, kidney, and brain. Angiotensin II receptors are located on the plasma membrane of target cells to facilitate the rapid onset of angiotensin II. Three distinct subtypes of angiotensin II receptors have been identified: angiotensin II type-1 receptor, angiotensin type 2, and angiotensin type 4; and the relative proportion of each vary from tissue to tissue. The angiotensin II type-1 receptor subtype is expressed predominantly in vascular smooth muscle cells where activation by angiotensin II results in vasoconstriction, cell proliferation, fibrosis, and cellular hypertrophy. In contrast, angiotensin II type-2 receptor stimulation produces pharmacologic activities that are opposite to those that occur after angiotensin II type-1 receptor stimulation. The angiotensin II type-4 receptor has been reported to be expressed in the adrenals, brain, and myocardium, but its exact function remains unknown. It is not considered to play an important role in human pathogenesis.
TAK-536 (azilsartan) is a synthetic angiotensin II type-1 receptor antagonist being developed as a treatment for mild to moderate uncomplicated essential hypertension
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Azilsartan 2.5 mg QD | Experimental | Drug: Azilsartan |
| Azilsartan 5 mg QD | Experimental | Drug: Azilsartan |
| Azilsartan 10 mg QD | Experimental | Drug: Azilsartan |
| Azilsartan 20 mg QD | Experimental | Drug: Azilsartan |
| Azilsartan 40 mg QD | Experimental | Drug: Azilsartan |
| Placebo QD | Placebo comparator | Drug: Placebo |
| Olmesartan 20 mg QD | Active comparator | Drug: Olmesartan |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Has mild to moderate uncomplicated essential hypertension (diastolic blood pressure between 95 and 114 mm Hg at Screening Day -7 and randomization visit).
- Female patients of childbearing potential must be nonpregnant and nonlactating, and utilizing an acceptable method of contraception.
- Has clinical laboratory evaluations (including clinical chemistry, hematology, and complete urinalysis) within the reference range for the testing laboratory unless the results are deemed not clinically significant for inclusion into this study by the investigator or sponsor.
- Is willing to discontinue current antihypertensive medications.
Key exclusion criteria (30 listed)
- Has a decrease of more than or equal to 8 mm Hg in clinic diastolic blood pressure between Screening Day -7 and randomization visit.
- Is hypersensitive to angiotensin II receptor blockers.
- The patient has Grade 3 or 4 hypertensive retinopathy (Keith-Wagener scale).
- Has significant cardiac disease (eg, primary, hemodynamically significant cardiac valvular disease) other than mild to moderate uncomplicated hypertensive cardiovascular disease.
- Has taken, within 7 days prior to placebo run-in, or is expected to take, medications known to affect blood pressure, including the following:
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 |
|---|---|---|
| AzilsartanAlso: TAK-536Azilsartan 2.5 mg, tablets, orally, once daily and olmesartan placebo-matching capsules and tablets, orally, once daily for up to 8 weeks. | Drug | Azilsartan 2.5 mg QD |
| AzilsartanAlso: TAK-536Azilsartan 5.0 mg, tablets, orally, once daily and olmesartan placebo-matching capsules and tablets, orally, once daily for up to 8 weeks. | Drug | Azilsartan 5 mg QD |
| AzilsartanAlso: TAK-536Azilsartan 10 mg, tablets, orally, once daily and olmesartan placebo-matching capsules and tablets, orally, once daily for up to 8 weeks. | Drug | Azilsartan 10 mg QD |
| AzilsartanAlso: TAK-536Azilsartan 20 mg, tablets, orally, once daily and olmesartan placebo-matching capsules and tablets, orally, once daily for up to 8 weeks. | Drug | Azilsartan 20 mg QD |
| AzilsartanAlso: TAK-536Azilsartan 40 mg, tablets, orally, once daily and olmesartan placebo-matching capsules and tablets, orally, once daily for up to 8 weeks. | Drug | Azilsartan 40 mg QD |
| PlaceboAzilsartan placebo-matching tablets, orally, once daily and olmesartan placebo-matching capsules, orally, once daily for up to 8 weeks. | Drug | Placebo QD |
| OlmesartanAlso: Benicar®, Olmetec®Azilsartan placebo-matching tablets, orally, once daily and olmesartan 20 mg, capsules, orally, once daily for up to 8 weeks. | Drug | Olmesartan 20 mg QD |
Primary outcome
Change from Baseline in sitting clinic diastolic blood pressure.
Time frame: Week 8 or Final Visit
3 secondary outcomes
Change from Baseline in sitting clinic systolic blood pressure.
Time frame: Weeks 2, 4, 6, and 8 or Final Visit
The change from Baseline in standing clinic diastolic blood pressure and systolic blood pressure.
Time frame: Weeks 2, 4, 6, and 8 or Final Visit
Change from Baseline in diastolic blood pressure and systolic blood pressure as measured by ambulatory blood pressure monitoring.
Time frame: Week 8 or Final Visit
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2010.
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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.
VP Clinical Science Strategy study director
Takeda
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Azilsartan and Olmesartan in people with Hypertension, run by Takeda.
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 30 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 22 Jun 2010. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 in sitting clinic diastolic blood pressure. (time frame: Week 8 or Final Visit). 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 22 Jun 2010.