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

Essential Hypertension Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01289132
• Other study ID #: TAK-536/CCT-001
• Secondary ID: U1111-1118-3346
• Status: Completed
• Phase: Phase 2
• First received: February 1, 2011
• Last updated: February 1, 2011
• Start date: July 2007
• Est. completion date: July 2008

Study information

• Verified date: February 2011
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 926
• Est. completion date: July 2008
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Essential Hypertension
• Hypertension

Intervention

Drug:
• Placebo
Placebo-matching tablets, orally, once daily for up to 12 weeks.
• Azilsartan
Azilsartan 5 mg, tablets, orally, once daily for up to 12 weeks.
• Azilsartan
Azilsartan 10 mg, tablets, orally, once daily for up to 12 weeks.
• Azilsartan
Azilsartan 20 mg, tablets, orally, once daily for up to 12 weeks.
• Azilsartan
Azilsartan 40 mg, tablets, orally, once daily for up to 12 weeks.
• Azilsartan
Azilsartan 80 mg, tablets, orally, once daily for up to 12 weeks.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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).	Yes
Secondary	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.	Yes
Secondary	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.	Yes
Secondary	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.	Yes
Secondary	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.	Yes
Secondary	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.	Yes
Secondary	Change from Baseline in Weight.	The change between weight recorded at week 12 or final visit from baseline.	Baseline and Week 12.	Yes
Secondary	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.	Yes
Secondary	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.	Yes
Secondary	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.	Yes
Secondary	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.	Yes
Secondary	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.	Yes