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
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
Vascular Diseases
Cardiovascular Diseases
Candesartan cilexetil
Candesartan
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 15, 2014