Efficacy and Safety of Azilsartan in Participants With Mild to Moderate Uncomplicated Essential Hypertension
Study Details
Study Description
Brief Summary
The purpose of this study was to evaluate the dose-response relationships of azilsartan, once daily (QD) in participants with mild to moderate uncomplicated essential hypertension.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 2 |
Detailed Description
Hypertension is known to cause multiple organ damage by being combined with not only blood pressure but also other hemodynamics, endocrinological/metabolic abnormalities and genetic factors. This becomes a medically and medical-economically significant problem in Japan The significance of early treatment of hypertension and of long-term control of blood pressure has been increasing year by year.
Takeda Pharmaceutical Company Limited invented TAK-536 (azilsartan), an angiotensin II receptor blocker for decreasing blood pressure. This study investigating the efficacy and safety of azilsartan using candesartan cilexetil, a widely used antihypertensive drug, as a reference control.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Placebo Comparator: Placebo
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Drug: Placebo
Placebo-matching tablets, orally, once daily for up to 12 weeks.
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Experimental: Azilsartan 5 mg QD
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Drug: Azilsartan
Azilsartan 5 mg, tablets, orally, once daily for up to 12 weeks.
Other Names:
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Experimental: Azilsartan 10 mg QD
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Drug: Azilsartan
Azilsartan 10 mg, tablets, orally, once daily for up to 12 weeks.
Other Names:
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Experimental: Azilsartan 20 mg QD
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Drug: Azilsartan
Azilsartan 20 mg, tablets, orally, once daily for up to 12 weeks.
Other Names:
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Experimental: Azilsartan 40 mg QD
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Drug: Azilsartan
Azilsartan 40 mg, tablets, orally, once daily for up to 12 weeks.
Other Names:
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Experimental: Azilsartan 80 mg QD
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Drug: Azilsartan
Azilsartan 80 mg, tablets, orally, once daily for up to 12 weeks.
Other Names:
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Active Comparator: Candesartan Cilexetil 8 mg titrated to12 mg QD
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Drug: Candesartan cilexetil
Candesartan cilexetil 8 mg, tablets, orally, once daily for 4 weeks; titrated to 12 mg, tablets, orally, once daily for up to 8 weeks.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Change from Baseline in Sitting Trough Diastolic Blood Pressure (Week 12). [Baseline and Week 12.]
The change between sitting trough clinic diastolic blood pressure measured at week 12 or final visit from diastolic blood pressure measured at baseline. Trough is a time point immediately before the next administration where drug blood concentration is lowest. Mean calculated by using the average (arithmetic mean) of 3 measurements performed at each visit.
Secondary Outcome Measures
- Change from Baseline in Sitting Trough Diastolic Blood Pressure (Week 2). [Baseline and Week 2.]
The change between sitting trough clinic diastolic blood pressure measured at week 2 from diastolic blood pressure measured at baseline. Trough is a time point immediately before the next administration where drug blood concentration is lowest. Mean calculated by using the average (arithmetic mean) of 3 measurements performed at each visit.
- Change from Baseline in Sitting Trough Diastolic Blood Pressure (Week 4). [Baseline and Week 4.]
The change between sitting trough clinic diastolic blood pressure measured at week 4 from diastolic blood pressure measured at baseline. Trough is a time point immediately before the next administration where drug blood concentration is lowest. Mean calculated by using the average (arithmetic mean) of 3 measurements performed at each visit.
- Change from Baseline in Sitting Trough Diastolic Blood Pressure (Week 6). [Baseline and Week 6.]
The change between sitting trough clinic diastolic blood pressure measured at week 6 from diastolic blood pressure measured at baseline. Trough is a time point immediately before the next administration where drug blood concentration is lowest. Mean calculated by using the average (arithmetic mean) of 3 measurements performed at each visit.
- Change from Baseline in Sitting Trough Diastolic Blood Pressure (Week 8). [Baseline and Week 8.]
The change between sitting trough clinic diastolic blood pressure measured at week 8 from diastolic blood pressure measured at baseline. Trough is a time point immediately before the next administration where drug blood concentration is lowest. Mean calculated by using the average (arithmetic mean) of 3 measurements performed at each visit.
- Change from Baseline in Sitting Trough Diastolic Blood Pressure (Week 10). [Baseline and Week 10.]
The change between sitting trough clinic diastolic blood pressure measured at week 10 from diastolic blood pressure measured at baseline. Trough is a time point immediately before the next administration where drug blood concentration is lowest. Mean calculated by using the average (arithmetic mean) of 3 measurements performed at each visit.
- Change from Baseline in Sitting Trough Systolic Blood Pressure (Week 2). [Baseline and Week 2.]
The change between sitting trough clinic systolic blood pressure measured at week 2 from systolic blood pressure measured at baseline. Trough is a time point immediately before the next administration where drug blood concentration is lowest. Mean calculated by using the average (arithmetic mean) of 3 measurements performed at each visit.
- Change from Baseline in Sitting Trough Systolic Blood Pressure (Week 4). [Baseline and Week 4.]
The change between sitting trough clinic systolic blood pressure measured at week 4 from systolic blood pressure measured at baseline. Trough is a time point immediately before the next administration where drug blood concentration is lowest. Mean calculated by using the average (arithmetic mean) of 3 measurements performed at each visit.
- Change from Baseline in Sitting Trough Systolic Blood Pressure (Week 6). [Baseline and Week 6.]
The change between sitting trough clinic systolic blood pressure measured at week 6 from systolic blood pressure measured at baseline. Trough is a time point immediately before the next administration where drug blood concentration is lowest. Mean calculated by using the average (arithmetic mean) of 3 measurements performed at each visit.
- Change from Baseline in Sitting Trough Systolic Blood Pressure (Week 8). [Baseline and Week 8.]
The change between sitting trough clinic systolic blood pressure measured at week 8 from systolic blood pressure measured at baseline. Trough is a time point immediately before the next administration where drug blood concentration is lowest. Mean calculated by using the average (arithmetic mean) of 3 measurements performed at each visit.
- Change from Baseline in Sitting Trough Systolic Blood Pressure (Week 10). [Baseline and Week 10.]
The change between sitting trough clinic systolic blood pressure measured at week 10 from systolic blood pressure measured at baseline. Trough is a time point immediately before the next administration where drug blood concentration is lowest. Mean calculated by using the average (arithmetic mean) of 3 measurements performed at each visit.
- Change from Baseline in Sitting Trough Systolic Blood Pressure (Week 12). [Baseline and Week 12.]
The change between sitting trough clinic systolic blood pressure measured at week 12 or final visit from systolic blood pressure measured at baseline. Trough is a time point immediately before the next administration where drug blood concentration is lowest. Mean calculated by using the average (arithmetic mean) of 3 measurements performed at each visit.
- Number of Participants with a ≥20 mmHg Decrease in Sitting Trough Systolic Blood Pressure and a ≥10 mmHg Decrease in Sitting Trough Diastolic Blood Pressure. [Baseline and Week 12.]
Number of participants designated as responders who have a ≥20 mmHg Decrease in sitting trough systolic blood pressure and a ≥10 mmHg Decrease in sitting trough diastolic blood pressure at week 12 or final visit from baseline.
- Number of Participants with a Sitting Trough Systolic Blood Pressure of <130 mmHg and a Sitting Trough Diastolic Blood Pressure of <85 mmHg. [Baseline and Week 12.]
Number of participants designated as responders with a sitting trough systolic blood pressure of <130 mmHg and a sitting trough diastolic blood pressure of <85 mmHg at week 12 or final visit from baseline.
- Incidence of Adverse Events. [On occurrence (up to Week 12).]
Treatment-emergent adverse events (TEAE) are adverse events with an onset that occurs after receiving study drug and within 30 days after receiving the last dose of study drug. A TEAE may also be a pretreatment adverse event or a concurrent medical condition diagnosed prior to the date of first dose of study drug that increases in severity after the start of dosing.
- Change from Baseline in Supine Systolic Blood Pressure. [Baseline and Week 12.]
The change between supine systolic blood pressure measured at week 12 or final visit from baseline. Supine systolic blood pressure is measured in participants laying on their back in a face-up position once after resting for 2 minutes.
- Change from Baseline in Supine Diastolic Blood Pressure. [Baseline and Week 12.]
The change between supine diastolic blood pressure measured at week 12 or final visit from baseline. Supine diastolic blood pressure is measured in participants laying on their back in a face-up position once after resting for 2 minutes.
- Change from Baseline in Standing Systolic Blood Pressure. [Baseline and Week 12.]
The change between standing systolic blood pressure measured at week 12 or final visit from baseline. Standing systolic blood pressure is measured once after participants keep a standing position for 1 minute.
- Change from Baseline in Standing Diastolic Blood Pressure. [Baseline and Week 12.]
The change between standing diastolic blood pressure measured at week 12 or final visit from baseline. Standing diastolic blood pressure is measured once after participants keep a standing position for 1 minute.
- Change from Baseline in Sitting Pulse Rate. [Baseline and Week 12.]
The change between sitting pulse rate measured at week 12 or final visit from baseline. Sitting pulse rate is measured at least 3 times in 1- to 2-minute intervals after sitting ≥5 minutes, repeated until 2 consecutive stable measurements are obtained.
- Change from Baseline in Weight. [Baseline and Week 12.]
The change between weight recorded at week 12 or final visit from baseline.
- Change from Baseline in Resting 12-lead Electrocardiogram. [Baseline and Week 12.]
The change between electrocardiogram recorded at week 12 or final visit from baseline. Electrocardiogram interpreted using one of the following categories: within normal limits, abnormal but not clinically significant, or abnormal and clinically significant.
- Number of Participants with a Markedly Abnormal Blood Urea Nitrogen Clinical Laboratory Value. [Baseline and Week 12.]
The number of participants with a markedly abnormal blood urea value nitrogen collected at week 12 or final visit from baseline.
- Number of Participants with a Markedly Abnormal Uric Acid Clinical Laboratory Value. [Baseline and Week 12.]
The number of participants with a markedly abnormal uric acid value collected at week 12 or final visit from baseline.
- Number of Participants with a Markedly Abnormal Creatinine Clinical Laboratory Value. [Baseline and Week 12.]
The number of participants with a markedly abnormal creatinine value collected at week 12 or final visit from baseline.
- Number of Participants with a Markedly Abnormal Creatine Kinase Clinical Laboratory Value. [Baseline and Week 12.]
The number of participants with a markedly abnormal creatine kinase value collected at week 12 or final visit from baseline.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Has mild to moderate uncomplicated essential hypertension.
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Has a sitting diastolic blood pressure between 95 and <110 mmHg and sitting systolic blood pressure between 150 and <180 mmHg at placebo run-in period (Week -2) or randomization visit.
Exclusion Criteria:
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Has a cardiovascular disease or symptoms
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Has been treated with more than 3 different antihypertensives within 27 days prior to placebo run-in period.
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Has a significant hepatic disorder, hyperkalemia, malignant tumor or significant renal impairment.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Takeda
Investigators
- Study Director: Professor Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TAK-536/CCT-001
- U1111-1118-3346