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

This study has been completed.
Sponsor:
Information provided by:
Takeda
ClinicalTrials.gov Identifier:
NCT01289132
First received: February 1, 2011
Last updated: NA
Last verified: February 2011
History: No changes posted
  Purpose

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 Intervention Phase
Essential Hypertension
Drug: Placebo
Drug: Azilsartan
Drug: Candesartan cilexetil
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Change from Baseline in Sitting Trough Diastolic Blood Pressure (Week 12). [ Time Frame: Baseline and Week 12. ] [ Designated as safety issue: No ]
    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). [ Time Frame: Baseline and Week 2. ] [ Designated as safety issue: No ]
    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). [ Time Frame: Baseline and Week 4. ] [ Designated as safety issue: No ]
    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). [ Time Frame: Baseline and Week 6. ] [ Designated as safety issue: No ]
    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). [ Time Frame: Baseline and Week 8. ] [ Designated as safety issue: No ]
    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). [ Time Frame: Baseline and Week 10. ] [ Designated as safety issue: No ]
    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). [ Time Frame: Baseline and Week 2. ] [ Designated as safety issue: No ]
    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). [ Time Frame: Baseline and Week 4. ] [ Designated as safety issue: No ]
    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). [ Time Frame: Baseline and Week 6. ] [ Designated as safety issue: No ]
    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). [ Time Frame: Baseline and Week 8. ] [ Designated as safety issue: No ]
    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). [ Time Frame: Baseline and Week 10. ] [ Designated as safety issue: No ]
    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). [ Time Frame: Baseline and Week 12. ] [ Designated as safety issue: No ]
    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. [ Time Frame: Baseline and Week 12. ] [ Designated as safety issue: No ]
    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. [ Time Frame: Baseline and Week 12. ] [ Designated as safety issue: No ]
    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. [ Time Frame: On occurrence (up to Week 12). ] [ Designated as safety issue: Yes ]
    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. [ Time Frame: Baseline and Week 12. ] [ Designated as safety issue: Yes ]
    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. [ Time Frame: Baseline and Week 12. ] [ Designated as safety issue: Yes ]
    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. [ Time Frame: Baseline and Week 12. ] [ Designated as safety issue: Yes ]
    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. [ Time Frame: Baseline and Week 12. ] [ Designated as safety issue: Yes ]
    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. [ Time Frame: Baseline and Week 12. ] [ Designated as safety issue: Yes ]
    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. [ Time Frame: Baseline and Week 12. ] [ Designated as safety issue: Yes ]
    The change between weight recorded at week 12 or final visit from baseline.

  • Change from Baseline in Resting 12-lead Electrocardiogram. [ Time Frame: Baseline and Week 12. ] [ Designated as safety issue: Yes ]
    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. [ Time Frame: Baseline and Week 12. ] [ Designated as safety issue: Yes ]
    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. [ Time Frame: Baseline and Week 12. ] [ Designated as safety issue: Yes ]
    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. [ Time Frame: Baseline and Week 12. ] [ Designated as safety issue: Yes ]
    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. [ Time Frame: Baseline and Week 12. ] [ Designated as safety issue: Yes ]
    The number of participants with a markedly abnormal creatine kinase value collected at week 12 or final visit from baseline.


Enrollment: 926
Study Start Date: July 2007
Study Completion Date: July 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Drug: Placebo
Placebo-matching tablets, orally, once daily for up to 12 weeks.
Experimental: Azilsartan 5 mg QD Drug: Azilsartan
Azilsartan 5 mg, tablets, orally, once daily for up to 12 weeks.
Other Name: TAK-536
Experimental: Azilsartan 10 mg QD Drug: Azilsartan
Azilsartan 10 mg, tablets, orally, once daily for up to 12 weeks.
Other Name: TAK-536
Experimental: Azilsartan 20 mg QD Drug: Azilsartan
Azilsartan 20 mg, tablets, orally, once daily for up to 12 weeks.
Other Name: TAK-536
Experimental: Azilsartan 40 mg QD Drug: Azilsartan
Azilsartan 40 mg, tablets, orally, once daily for up to 12 weeks.
Other Name: TAK-536
Experimental: Azilsartan 80 mg QD Drug: Azilsartan
Azilsartan 80 mg, tablets, orally, once daily for up to 12 weeks.
Other Name: TAK-536
Active Comparator: Candesartan Cilexetil 8 mg titrated to12 mg QD 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:
  • Blopress®
  • TCV-116

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.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01289132

Sponsors and Collaborators
Takeda
Investigators
Study Director: Professor Geriatric Medicine and Nephrology Osaka University Graduate School of Medicine
  More Information

No publications provided

Responsible Party: Sr. Manager, Clinical Planning, Takeda Pharmaceutical Company Limited (Japan)
ClinicalTrials.gov Identifier: NCT01289132     History of Changes
Other Study ID Numbers: TAK-536/CCT-001, U1111-1118-3346
Study First Received: February 1, 2011
Last Updated: February 1, 2011
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Takeda:
Drug Therapy

Additional relevant MeSH terms:
Hypertension
Cardiovascular Diseases
Vascular Diseases
Candesartan
Candesartan cilexetil
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Antihypertensive Agents
Cardiovascular Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014