Efficacy and Safety of Azilsartan in Participants With Mild to Moderate Uncomplicated Essential Hypertension

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase 2, Double-Blind, Randomized, Placebo-Controlled Dose-Ranging Study of the Efficacy, Safety and Tolerability of TAK-536 in Subjects With Mild to Moderate Uncomplicated Essential Hypertension

Conditions
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Essential Hypertension

Intervention / Treatment
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* Drug: Placebo
* Drug: Azilsartan
* Drug: Azilsartan
* Drug: Azilsartan
* Drug: Azilsartan
* Drug: Azilsartan
* Drug: Candesartan cilexetil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has mild to moderate uncomplicated essential hypertension. 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: Has a cardiovascular disease or symptoms Has been treated with more than 3 different antihypertensives within 27 days prior to placebo run-in period. Has a significant hepatic disorder, hyperkalemia, malignant tumor or significant renal impairment.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo-matching tablets, orally, once daily for up to 12 weeks.<br>|
| Experimental: Azilsartan 5 mg QD<br> | Drug: Azilsartan<br>* Azilsartan 5 mg, tablets, orally, once daily for up to 12 weeks.<br>* Other names: TAK-536;|
| Experimental: Azilsartan 10 mg QD<br> | Drug: Azilsartan<br>* Azilsartan 10 mg, tablets, orally, once daily for up to 12 weeks.<br>* Other names: TAK-536;|
| Experimental: Azilsartan 20 mg QD<br> | Drug: Azilsartan<br>* Azilsartan 20 mg, tablets, orally, once daily for up to 12 weeks.<br>* Other names: TAK-536;|
| Experimental: Azilsartan 40 mg QD<br> | Drug: Azilsartan<br>* Azilsartan 40 mg, tablets, orally, once daily for up to 12 weeks.<br>* Other names: TAK-536;|
| Experimental: Azilsartan 80 mg QD<br> | Drug: Azilsartan<br>* Azilsartan 80 mg, tablets, orally, once daily for up to 12 weeks.<br>* Other names: TAK-536;|
| Active Comparator: Candesartan Cilexetil 8 mg titrated to12 mg QD<br> | Drug: Candesartan cilexetil<br>* Candesartan cilexetil 8 mg, tablets, orally, once daily for 4 weeks; titrated to 12 mg, tablets, orally, once daily for up to 8 weeks.<br>* Other names: TCV-116;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Sitting Trough Diastolic Blood Pressure (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. | Baseline and Week 12. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Sitting Trough Diastolic Blood Pressure (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. | Baseline and Week 2. | 
| Change from Baseline in Sitting Trough Diastolic Blood Pressure (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. | Baseline and Week 4. | 
| Change from Baseline in Sitting Trough Diastolic Blood Pressure (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. | Baseline and Week 6. | 
| Change from Baseline in Sitting Trough Diastolic Blood Pressure (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. | Baseline and Week 8. | 
| Change from Baseline in Sitting Trough Diastolic Blood Pressure (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. | Baseline and Week 10. | 
| Change from Baseline in Sitting Trough Systolic Blood Pressure (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. | Baseline and Week 2. | 
| Change from Baseline in Sitting Trough Systolic Blood Pressure (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. | Baseline and Week 4. | 
| Change from Baseline in Sitting Trough Systolic Blood Pressure (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. | Baseline and Week 6. | 
| Change from Baseline in Sitting Trough Systolic Blood Pressure (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. | Baseline and Week 8. | 
| Change from Baseline in Sitting Trough Systolic Blood Pressure (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. | Baseline and Week 10. | 
| Change from Baseline in Sitting Trough Systolic Blood Pressure (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. | Baseline and Week 12. | 
| 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. | 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. | Baseline and Week 12. | 
| Number of Participants with a Sitting Trough Systolic Blood Pressure of <130 mmHg and a Sitting Trough Diastolic Blood Pressure of <85 mmHg. | 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. | Baseline and Week 12. | 
| Incidence of Adverse Events. | 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. | On occurrence (up to Week 12). | 
| Change from Baseline in Supine Systolic Blood Pressure. | 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. | Baseline and Week 12. | 
| Change from Baseline in Supine Diastolic Blood Pressure. | 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. | Baseline and Week 12. | 
| Change from Baseline in Standing Systolic Blood Pressure. | 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. | Baseline and Week 12. | 
| Change from Baseline in Standing Diastolic Blood Pressure. | 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. | Baseline and Week 12. | 
| Change from Baseline in Sitting Pulse Rate. | 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. | Baseline and Week 12. | 
| Change from Baseline in Weight. | The change between weight recorded at week 12 or final visit from baseline. | Baseline and Week 12. | 
| Change from Baseline in Resting 12-lead Electrocardiogram. | 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. | Baseline and Week 12. | 
| Number of Participants with a Markedly Abnormal Blood Urea Nitrogen Clinical Laboratory Value. | The number of participants with a markedly abnormal blood urea value nitrogen collected at week 12 or final visit from baseline. | Baseline and Week 12. | 
| Number of Participants with a Markedly Abnormal Uric Acid Clinical Laboratory Value. | The number of participants with a markedly abnormal uric acid value collected at week 12 or final visit from baseline. | Baseline and Week 12. | 
| Number of Participants with a Markedly Abnormal Creatinine Clinical Laboratory Value. | The number of participants with a markedly abnormal creatinine value collected at week 12 or final visit from baseline. | Baseline and Week 12. | 
| Number of Participants with a Markedly Abnormal Creatine Kinase Clinical Laboratory Value. | The number of participants with a markedly abnormal creatine kinase value collected at week 12 or final visit from baseline. | Baseline and Week 12. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug Therapy