ClinicalTrials.gov
ClinicalTrials.gov Menu

Efficacy and Safety Comparison of Azilsartan Medoxomil to Valsartan in Participants With Essential Hypertension

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00591578
Recruitment Status : Completed
First Posted : January 11, 2008
Results First Posted : April 19, 2011
Last Update Posted : February 2, 2012
Sponsor:
Information provided by (Responsible Party):
Takeda

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Hypertension
Interventions Drug: Azilsartan Medoxomil
Drug: Valsartan
Enrollment 984
Recruitment Details Participants enrolled at 103 investigative sites from 09 November 2007 to 03 September 2009 (double-blind phase) and 04 March 2009 to 13 March 2010 (open-label extension phase). A total of 984 participants were randomized into the double-blind treatment phase, of which 170 participants entered into the open-label extension phase.
Pre-assignment Details Participants with essential hypertension were enrolled in one of three, once-daily (QD) treatment groups.
Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD
Hide Arm/Group Description

Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks.

Open Label Extension: At Week 24/completion of the double-blind treatment phase, participants could elect to continue in 28 week, open-label extension (OLE) phase. All participants who elected to participate in the OLE phase initiated treatment with azilsartan medoxomil 40 mg, tablets, orally, independent of their double-blind treatment assignment. Investigators may have added, in a step-wise fashion, hydrochlorothiazide 12.5 mg, followed by hydrochlorothiazide 25 mg, followed by other antihypertensive medications (except angiotensin II receptor blockers) as needed to achieve target blood pressure (<140/90 mm Hg or <130/80 mm Hg for diabetics).

Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks.

Open Label Extension: At Week 24/completion of the double-blind treatment phase, participants could elect to continue in 28 week, open-label extension (OLE) phase. All participants who elected to participate in the OLE phase initiated treatment with azilsartan medoxomil 40 mg, tablets, orally, independent of their double-blind treatment assignment. Investigators may have added, in a step-wise fashion, hydrochlorothiazide 12.5 mg, followed by hydrochlorothiazide 25 mg, followed by other antihypertensive medications (except angiotensin II receptor blockers) as needed to achieve target blood pressure (<140/90 mm Hg or <130/80 mm Hg for diabetics).

Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.

Open Label Extension: At Week 24/completion of the double-blind treatment phase, participants could elect to continue in 28 week, open-label extension (OLE) phase. All participants who elected to participate in the OLE phase initiated treatment with azilsartan medoxomil 40 mg, tablets, orally, independent of their double-blind treatment assignment. Investigators may have added, in a step-wise fashion, hydrochlorothiazide 12.5 mg, followed by hydrochlorothiazide 25 mg, followed by other antihypertensive medications (except angiotensin II receptor blockers) as needed to achieve target blood pressure (<140/90 mm Hg or <130/80 mm Hg for diabetics).

Period Title: Double-Blind Treatment Phase
Started 327 329 328 [1]
Completed 249 249 244
Not Completed 78 80 84
Reason Not Completed
Adverse Event             20             26             19
Protocol Violation             3             2             3
Lost to Follow-up             12             12             11
Withdrawal by Subject             22             22             22
Pregnancy             1             0             0
Lack of Efficacy             16             9             25
Other             4             9             4
[1]
Two participants randomized but not treated.
Period Title: Open-Label Extension Phase
Started 55 115 0
Completed 49 105 0
Not Completed 6 10 0
Reason Not Completed
Adverse Event             3             5             0
Lost to Follow-up             1             4             0
Withdrawal by Subject             1             1             0
Other             1             0             0
Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD Total
Hide Arm/Group Description

Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks.

Open Label Extension: Azilsartan medoxomil 40 mg, tablets, orally, once daily for 28 weeks. Investigators may have added, in a step-wise fashion, hydrochlorothiazide 12.5 mg, followed by hydrochlorothiazide 25 mg, followed by other antihypertensive medications (except angiotensin II receptor blockers) as needed to achieve target blood pressure (<140/90 mm Hg or <130/80 mm Hg for diabetics).

Open Label Extension: Azilsartan medoxomil 40 mg, tablets, orally, once daily for 28 weeks. Investigators may have added, in a step-wise fashion, hydrochlorothiazide 12.5 mg, followed by hydrochlorothiazide 25 mg, followed by other antihypertensive medications (except angiotensin II receptor blockers) as needed to achieve target blood pressure (<140/90 mm Hg or <130/80 mm Hg for diabetics).

Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks.

Open Label Extension: Azilsartan medoxomil 40 mg, tablets, orally, once daily for 28 weeks. Investigators may have added, in a step-wise fashion, hydrochlorothiazide 12.5 mg, followed by hydrochlorothiazide 25 mg, followed by other antihypertensive medications (except angiotensin II receptor blockers) as needed to achieve target blood pressure (<140/90 mm Hg or <130/80 mm Hg for diabetics).

Open Label Extension: Azilsartan medoxomil 40 mg, tablets, orally, once daily for 28 weeks. Investigators may have added, in a step-wise fashion, hydrochlorothiazide 12.5 mg, followed by hydrochlorothiazide 25 mg, followed by other antihypertensive medications (except angiotensin II receptor blockers) as needed to achieve target blood pressure (<140/90 mm Hg or <130/80 mm Hg for diabetics).

Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.

Open Label Extension: Azilsartan medoxomil 40 mg, tablets, orally, once daily for 28 weeks. Investigators may have added, in a step-wise fashion, hydrochlorothiazide 12.5 mg, followed by hydrochlorothiazide 25 mg, followed by other antihypertensive medications (except angiotensin II receptor blockers) as needed to achieve target blood pressure (<140/90 mm Hg or <130/80 mm Hg for diabetics).

Total of all reporting groups
Overall Number of Baseline Participants 327 329 328 984
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 327 participants 329 participants 328 participants 984 participants
<45 years (Double Blind Phase) 43 39 31 113
Between 45 and 64 years (Double Blind Phase) 181 208 199 588
≥65 years (Double Blind Phase) 103 82 98 283
<45 years (Open Label Phase) 10 8 0 18
Between 45 and 64 years (Open Label Phase) 25 68 0 93
≥65 years (Open Label Phase) 20 39 0 59
Sex/Gender, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 327 participants 329 participants 328 participants 984 participants
Female (Double Blind Phase) 163 160 152 475
Male (Double Blind Phase) 164 169 176 509
Female (Open Label Phase) 34 57 0 91
Male (Open Label Phase) 21 58 0 79
1.Primary Outcome
Title Change From Baseline in 24-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Hide Description The change in 24-hour mean systolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing.
Time Frame Baseline and Week 24.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set with last observation carried forward.
Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD
Hide Arm/Group Description:
Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks.
Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks.
Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.
Overall Number of Participants Analyzed 284 271 277
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
-14.93  (0.698) -15.32  (0.715) -11.29  (0.707)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Valsartan 320 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented. Overall 0.05 level of significance for multiple comparisons controlled using stepwise testing procedure.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.64
Confidence Interval (2-Sided) 95%
-5.59 to -1.69
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Valsartan 320 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Unadjusted p-value presented. Overall 0.05 level of significance for multiple comparisons controlled using stepwise testing procedure.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.03
Confidence Interval (2-Sided) 95%
-6.01 to -2.06
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Mean Trough Clinic Sitting Systolic Blood Pressure.
Hide Description The change in mean trough clinic sitting systolic blood pressure measured at final visit or week 24 relative to baseline. Systolic blood pressure is the arithmetic mean of the 3 trough sitting systolic blood pressure measurements.
Time Frame Baseline and Week 24.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set with last observation carried forward.
Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD
Hide Arm/Group Description:
Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks.
Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks.
Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.
Overall Number of Participants Analyzed 323 311 322
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
-14.86  (0.948) -16.92  (0.966) -11.59  (0.949)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Valsartan 320 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.015
Comments Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). The unadjusted p-value is presented.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.27
Confidence Interval (2-Sided) 95%
-5.90 to -0.63
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Valsartan 320 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). The unadjusted p-value is presented.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -5.34
Confidence Interval (2-Sided) 95%
-8.00 to -2.68
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in the 24-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Hide Description The change in 24-hour mean diastolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing.
Time Frame Baseline and Week 24.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set with last observation carried forward.
Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD
Hide Arm/Group Description:
Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks.
Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks.
Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.
Overall Number of Participants Analyzed 284 271 277
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
-9.23  (0.459) -9.77  (0.470) -7.07  (0.465)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Valsartan 320 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). The unadjusted p-value is presented.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.16
Confidence Interval (2-Sided) 95%
-3.44 to -0.88
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Valsartan 320 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). The unadjusted p-value is presented.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.69
Confidence Interval (2-Sided) 95%
-3.99 to -1.40
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in Mean Trough Clinic Sitting Diastolic Blood Pressure
Hide Description The change in mean trough clinic sitting diastolic blood pressure measured at final visit or week 24 relative to baseline. Diastolic blood pressure is the arithmetic mean of the 3 trough sitting systolic blood pressure measurements.
Time Frame Baseline and Week 24.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set with last observation carried forward.
Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD
Hide Arm/Group Description:
Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks.
Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks.
Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.
Overall Number of Participants Analyzed 323 311 322
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
-7.16  (0.554) -7.41  (0.565) -4.65  (0.555)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Valsartan 320 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). The unadjusted p-value is presented.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.52
Confidence Interval (2-Sided) 95%
-4.06 to -0.98
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Valsartan 320 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). The unadjusted p-value is presented.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.76
Confidence Interval (2-Sided) 95%
-4.32 to -1.21
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Daytime (6am to 10 pm) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Hide Description The change in daytime (6am to 10pm) mean systolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of all measurements recorded between the hours of 6 am and 10 pm.
Time Frame Baseline and Week 24.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set with last observation carried forward.
Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD
Hide Arm/Group Description:
Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks.
Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks.
Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.
Overall Number of Participants Analyzed 284 271 277
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
-15.39  (0.732) -15.80  (0.749) -11.91  (0.741)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Valsartan 320 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). The unadjusted p-value is presented.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.49
Confidence Interval (2-Sided) 95%
-5.53 to -1.44
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Valsartan 320 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). The unadjusted p-value is presented.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.90
Confidence Interval (2-Sided) 95%
-5.96 to -1.83
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in Daytime (6am to 10 pm) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Hide Description The change in daytime (6am to 10pm) mean systolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of all measurements recorded between the hours of 6 am and 10 pm.
Time Frame Baseline and Week 24.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set with last observation carried forward.
Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD
Hide Arm/Group Description:
Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks.
Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks.
Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.
Overall Number of Participants Analyzed 284 271 277
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
-9.61  (0.493) -10.11  (0.504) -7.44  (0.499)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Valsartan 320 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). The unadjusted p-value is presented.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.17
Confidence Interval (2-Sided) 95%
-3.54 to -0.79
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Valsartan 320 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). The unadjusted p-value is presented.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.67
Confidence Interval (2-Sided) 95%
-4.06 to -1.28
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in the Nighttime (12 am to 6 am) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Hide Description The change in nighttime (12am to 6am) mean systolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of all measurements recorded between the hours of 12 am and 6 am.
Time Frame Baseline and Week 24.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set with last observation carried forward.
Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD
Hide Arm/Group Description:
Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks.
Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks.
Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.
Overall Number of Participants Analyzed 284 271 277
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
-13.31  (0.777) -13.95  (0.795) -9.52  (0.786)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Valsartan 320 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). The unadjusted p-value is presented.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.79
Confidence Interval (2-Sided) 95%
-5.96 to -1.62
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Valsartan 320 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). The unadjusted p-value is presented.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.44
Confidence Interval (2-Sided) 95%
-6.63 to -2.24
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline in the Nighttime (12 am to 6 am) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Hide Description The change in nighttime (12am to 6am) mean diastolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of all measurements recorded between the hours of 12 am and 6 am.
Time Frame Baseline and Week 24.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set with last observation carried forward.
Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD
Hide Arm/Group Description:
Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks.
Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks.
Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.
Overall Number of Participants Analyzed 284 271 277
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
-8.06  (0.526) -8.90  (0.539) -6.06  (0.533)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Valsartan 320 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). The unadjusted p-value is presented.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.00
Confidence Interval (2-Sided) 95%
-3.48 to -0.53
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Valsartan 320 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). The unadjusted p-value is presented.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.84
Confidence Interval (2-Sided) 95%
-4.33 to -1.35
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline in the 12-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Hide Description The change in the 12-hour mean systolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 12-hour mean is the average of all measurements recorded in the first 12 hours after dosing.
Time Frame Baseline and Week 24.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set with last observation carried forward.
Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD
Hide Arm/Group Description:
Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks.
Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks.
Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.
Overall Number of Participants Analyzed 284 271 277
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
-15.64  (0.764) -16.20  (0.782) -12.20  (0.774)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Valsartan 320 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). The unadjusted p-value is presented.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.44
Confidence Interval (2-Sided) 95%
-5.57 to -1.30
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Valsartan 320 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). The unadjusted p-value is presented.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.01
Confidence Interval (2-Sided) 95%
-6.16 to -1.85
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change From Baseline in the 12-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Hide Description The change in the 12-hour mean diastolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 12-hour mean is the average of all measurements recorded in the first 12 hours after dosing.
Time Frame Baseline and Week 24.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set with last observation carried forward.
Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD
Hide Arm/Group Description:
Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks.
Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks.
Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.
Overall Number of Participants Analyzed 284 271 277
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
-9.70  (0.522) -10.26  (0.534) -7.53  (0.528)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Valsartan 320 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). The unadjusted p-value is presented.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.18
Confidence Interval (2-Sided) 95%
-3.63 to -0.72
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Valsartan 320 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). The unadjusted p-value is presented.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.73
Confidence Interval (2-Sided) 95%
-4.20 to -1.25
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Change From Baseline in the Trough (22-24-hr) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Hide Description The change in trough mean systolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough mean is the average of all measurements recorded from 22 to 24 hours after dosing.
Time Frame Baseline and Week 24.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set with last observation carried forward.
Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD
Hide Arm/Group Description:
Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks.
Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks.
Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.
Overall Number of Participants Analyzed 284 271 277
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
-13.74  (0.851) -13.83  (0.871) -10.36  (0.861)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Valsartan 320 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). The unadjusted p-value is presented.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.38
Confidence Interval (2-Sided) 95%
-5.76 to -1.00
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Valsartan 320 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). The unadjusted p-value is presented.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.47
Confidence Interval (2-Sided) 95%
-5.87 to -1.06
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Change From Baseline in the Trough (22-24-hr) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Hide Description The change in trough mean diastolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough mean is the average of all measurements recorded from 22 to 24 hours after dosing.
Time Frame Baseline and Week 24.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set with last observation carried forward.
Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD
Hide Arm/Group Description:
Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks.
Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks.
Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.
Overall Number of Participants Analyzed 284 271 277
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
-9.37  (0.617) -9.65  (0.632) -7.06  (0.625)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Valsartan 320 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.009
Comments Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). The unadjusted p-value is presented.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.31
Confidence Interval (2-Sided) 95%
-4.04 to -0.59
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Valsartan 320 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). The unadjusted p-value is presented.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.59
Confidence Interval (2-Sided) 95%
-4.34 to -0.84
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Percentage of Participants Who Achieve a Clinic Systolic Blood Pressure Response, Defined as < 140 mm Hg and/or Reduction From Baseline ≥ 20 mm Hg.
Hide Description Percentage of participants who achieve a clinic systolic blood pressure response measured at week 24, defined as less than 140 mm Hg and/or reduction from baseline of greater than or equal to 20 mm Hg. Systolic blood pressure is the arithmetic mean of the 3 trough sitting systolic blood pressure measurements.
Time Frame Baseline and Week 24.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set with last observation carried forward.
Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD
Hide Arm/Group Description:
Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks.
Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks.
Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.
Overall Number of Participants Analyzed 323 311 322
Measure Type: Number
Unit of Measure: percentage of participants
56.0 59.2 46.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Valsartan 320 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.016
Comments P-value for response criteria for systolic blood pressure was from a logistic regression with treatment as a factor and baseline clinic systolic blood pressure as a covariate. The unadjusted p-value is presented.
Method Regression, Logistic
Comments Includes only those participants with a baseline and at least one post-baseline value.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.46
Confidence Interval (2-Sided) 95%
1.07 to 2.00
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Valsartan 320 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments P-value for response criteria for systolic blood pressure was from a logistic regression with treatment as a factor and baseline clinic systolic blood pressure as a covariate. The unadjusted p-value is presented.
Method Regression, Logistic
Comments Includes only those participants with a baseline and at least one post-baseline value.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.63
Confidence Interval (2-Sided) 95%
1.19 to 2.23
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Percentage of Participants Who Achieve a Clinic Diastolic Blood Pressure Response, Defined as < 90 mm Hg and/or Reduction From Baseline ≥ 10 mm Hg.
Hide Description Percentage of participants who achieve a clinic diastolic blood pressure response measured at week 24, defined as less than 90 mm Hg and/or reduction from baseline of greater than or equal to 10 mm Hg. Diastolic blood pressure is the arithmetic mean of the 3 trough sitting diastolic blood pressure measurements.
Time Frame Baseline and Week 24.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set with last observation carried forward.
Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD
Hide Arm/Group Description:
Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks.
Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks.
Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.
Overall Number of Participants Analyzed 323 311 322
Measure Type: Number
Unit of Measure: percentage of participants
72.4 74.0 65.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Valsartan 320 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.041
Comments P-value for response criteria for diastolic blood pressure was from a logistic regression with treatment as a factor and baseline clinic diastolic blood pressure as a covariate. The unadjusted p-value is presented.
Method Regression, Logistic
Comments Includes only those participants with a baseline and at least one post-baseline value.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.46
Confidence Interval (2-Sided) 95%
1.02 to 2.10
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Valsartan 320 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.015
Comments P-value for response criteria for diastolic blood pressure was from a logistic regression with treatment as a factor and baseline clinic diastolic blood pressure as a covariate. The unadjusted p-value is presented.
Method Regression, Logistic
Comments Includes only those participants with a baseline and at least one post-baseline value.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.58
Confidence Interval (2-Sided) 95%
1.09 to 2.28
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Percentage of Participants Who Achieve Both a Clinic Diastolic and Systolic Blood Pressure Response.
Hide Description Percentage of participants who achieve both a clinic diastolic and systolic blood pressure response measured at week 24, defined as less than 90 mm Hg and/or reduction from baseline of greater than or equal to 10 mm Hg AND less than 140 mm Hg and/or reduction from baseline of greater than or equal to 20 mm Hg. Diastolic and systolic blood pressure is based on the arithmetic mean of the 3 sitting blood pressure measurements.
Time Frame Baseline and Week 24.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set with last observation carried forward.
Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD
Hide Arm/Group Description:
Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks.
Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks.
Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.
Overall Number of Participants Analyzed 323 311 322
Measure Type: Number
Unit of Measure: percentage of participants
50.2 54.7 41.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Valsartan 320 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.018
Comments P-value for joint response criteria for systolic blood pressure and diastolic blood pressure was from a logistic regression with treatment as a factor and baseline clinic systolic blood pressure as a covariate. The unadjusted p-value is presented.
Method Regression, Logistic
Comments Includes only those participants with a baseline and at least one post-baseline value.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.46
Confidence Interval (2-Sided) 95%
1.07 to 1.99
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Valsartan 320 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value for joint response criteria for systolic blood pressure and diastolic blood pressure was from a logistic regression with treatment as a factor and baseline clinic systolic blood pressure as a covariate. The unadjusted p-value is presented.
Method Regression, Logistic
Comments Includes only those participants with a baseline and at least one post-baseline value.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.70
Confidence Interval (2-Sided) 95%
1.24 to 2.33
Estimation Comments [Not Specified]
Time Frame Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug.
Adverse Event Reporting Description At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
 
Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD Open Label Extension
Hide Arm/Group Description

Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks.

Open Label Extension: At Week 24/completion of the double-blind treatment phase, participants could elect to continue in 28 week, open-label extension (OLE) phase. All participants who elected to participate in the OLE phase initiated treatment with azilsartan medoxomil 40 mg, tablets, orally, independent of their double-blind treatment assignment. Investigators may have added, in a step-wise fashion, hydrochlorothiazide 12.5 mg, followed by hydrochlorothiazide 25 mg, followed by other antihypertensive medications (except angiotensin II receptor blockers) as needed to achieve target blood pressure (<140/90 mm Hg or <130/80 mm Hg for diabetics).

Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks.

Open Label Extension: At Week 24/completion of the double-blind treatment phase, participants could elect to continue in 28 week, open-label extension (OLE) phase. All participants who elected to participate in the OLE phase initiated treatment with azilsartan medoxomil 40 mg, tablets, orally, independent of their double-blind treatment assignment. Investigators may have added, in a step-wise fashion, hydrochlorothiazide 12.5 mg, followed by hydrochlorothiazide 25 mg, followed by other antihypertensive medications (except angiotensin II receptor blockers) as needed to achieve target blood pressure (<140/90 mm Hg or <130/80 mm Hg for diabetics).

Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks. Azilsartan medoxomil 40 mg, tablets, orally, independent of participant’s double-blind treatment assignment. Investigators may have added, in a step-wise fashion, hydrochlorothiazide 12.5 mg, followed by hydrochlorothiazide 25 mg, followed by other antihypertensive medications (except angiotensin II receptor blockers) as needed to achieve target blood pressure (<140/90 mm Hg or <130/80 mm Hg for diabetics).
All-Cause Mortality
Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD Open Label Extension
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD Open Label Extension
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   8/327 (2.45%)   5/329 (1.52%)   8/326 (2.45%)   4/170 (2.35%) 
Cardiac disorders         
Silent myocardial infarction  1  0/327 (0.00%)  1/329 (0.30%)  1/326 (0.31%)  0/170 (0.00%) 
Cardiac failure acute  1  1/327 (0.31%)  0/329 (0.00%)  0/326 (0.00%)  0/170 (0.00%) 
Coronary artery disease  1  0/327 (0.00%)  0/329 (0.00%)  1/326 (0.31%)  0/170 (0.00%) 
Myocardial infarction  1  0/327 (0.00%)  1/329 (0.30%)  0/326 (0.00%)  1/170 (0.59%) 
Gastrointestinal disorders         
Abdominal pain  1  0/327 (0.00%)  0/329 (0.00%)  1/326 (0.31%)  0/170 (0.00%) 
Pancreatitis  1  1/327 (0.31%)  0/329 (0.00%)  0/326 (0.00%)  0/170 (0.00%) 
Inguinal hernia, obstructive  1  0/327 (0.00%)  0/329 (0.00%)  0/326 (0.00%)  1/170 (0.59%) 
General disorders         
Chest pain  1  0/327 (0.00%)  1/329 (0.30%)  0/326 (0.00%)  0/170 (0.00%) 
Hepatobiliary disorders         
Cholecystitis acute  1  1/327 (0.31%)  0/329 (0.00%)  0/326 (0.00%)  1/170 (0.59%) 
Infections and infestations         
Erysipelas  1  0/327 (0.00%)  0/329 (0.00%)  1/326 (0.31%)  0/170 (0.00%) 
Hepatitis A  1  1/327 (0.31%)  0/329 (0.00%)  0/326 (0.00%)  0/170 (0.00%) 
Scrotal abscess  1  0/327 (0.00%)  0/329 (0.00%)  1/326 (0.31%)  0/170 (0.00%) 
Injury, poisoning and procedural complications         
Cervical vertebral fracture  1  1/327 (0.31%)  0/329 (0.00%)  0/326 (0.00%)  0/170 (0.00%) 
Fall  1  0/327 (0.00%)  0/329 (0.00%)  1/326 (0.31%)  0/170 (0.00%) 
Hip fracture  1  0/327 (0.00%)  0/329 (0.00%)  0/326 (0.00%)  1/170 (0.59%) 
Metabolism and nutrition disorders         
Gout  1  0/327 (0.00%)  0/329 (0.00%)  1/326 (0.31%)  0/170 (0.00%) 
Hypoglycaemia  1  1/327 (0.31%)  0/329 (0.00%)  0/326 (0.00%)  0/170 (0.00%) 
Type 2 diabetes mellitus  1  1/327 (0.31%)  0/329 (0.00%)  0/326 (0.00%)  0/170 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Oesophageal adenocarcinoma  1  0/327 (0.00%)  1/329 (0.30%)  0/326 (0.00%)  0/170 (0.00%) 
Psychiatric disorders         
Bipolar I disorder  1  0/327 (0.00%)  1/329 (0.30%)  0/326 (0.00%)  0/170 (0.00%) 
Renal and urinary disorders         
Renal impairment  1  1/327 (0.31%)  0/329 (0.00%)  0/326 (0.00%)  0/170 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Asthma  1  1/327 (0.31%)  0/329 (0.00%)  0/326 (0.00%)  0/170 (0.00%) 
Vascular disorders         
Arteriosclerosis  1  1/327 (0.31%)  0/329 (0.00%)  1/326 (0.31%)  0/170 (0.00%) 
Hypertension  1  1/327 (0.31%)  0/329 (0.00%)  0/326 (0.00%)  0/170 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD Open Label Extension
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   77/327 (23.55%)   74/329 (22.49%)   53/326 (16.26%)   16/170 (9.41%) 
Infections and infestations         
Urinary tract infection  1  26/327 (7.95%)  25/329 (7.60%)  16/326 (4.91%)  10/170 (5.88%) 
Nervous system disorders         
Dizziness  1  27/327 (8.26%)  29/329 (8.81%)  15/326 (4.60%)  8/170 (4.71%) 
Headache  1  33/327 (10.09%)  29/329 (8.81%)  28/326 (8.59%)  9/170 (5.29%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.1
For the Non-Serious Adverse Event Table, the total number of participants affected is based on the AEs with ≥5% in each phase, calculated separately.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
No publication related to study results will be published prior to publication of a multi-center report submitted for publication within 18 months after conclusion or termination of a study at all study sites. Results publications will be submitted to sponsor for review 60 days in advance of publication. Sponsor can require removal of confidential information unrelated to study results. Sponsor can embargo a proposed publication for another 60 days to preserve intellectual property.
Results Point of Contact
Name/Title: Sr. VP, Clinical Science
Organization: Takeda Global Research and Development Center, Inc.
Phone: 800-778-2860
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT00591578     History of Changes
Other Study ID Numbers: TAK-491_301
U1111-1113-9238 ( Registry Identifier: WHO )
First Submitted: December 27, 2007
First Posted: January 11, 2008
Results First Submitted: March 24, 2011
Results First Posted: April 19, 2011
Last Update Posted: February 2, 2012