ClinicalTrials.gov
ClinicalTrials.gov Menu

Efficacy and Safety Study of Azilsartan Medoxomil Compared to Ramipril for Treating 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: NCT00760214
Recruitment Status : Completed
First Posted : September 26, 2008
Results First Posted : April 19, 2011
Last Update Posted : November 15, 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: Ramipril
Enrollment 885
Recruitment Details Participants enrolled at 122 investigative sites in Bulgaria, Estonia, Finland, Germany, the Netherlands, Poland, Russia, Serbia and Montenegro, Slovakia and Sweden from 24 January 2008 to 21 April 2009.
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 Ramipril 10 mg QD
Hide Arm/Group Description Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 40 mg, tablets, orally, once daily for up to 22 weeks. Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 80 mg, tablets, orally, once daily for up to 22 weeks. Ramipril 2.5 mg, tablets, orally, once daily for two weeks; then increased to 10 mg, tablets, orally, once daily for up to 22 weeks.
Period Title: Overall Study
Started 295 294 296
Completed 265 264 255
Not Completed 30 30 41
Reason Not Completed
Adverse Event             8             9             12
Protocol Violation             3             0             3
Lost to Follow-up             0             0             1
Withdrawal by Subject             12             14             13
Lack of Efficacy             3             2             4
Pregnancy             0             0             1
Physician Decision             1             1             1
Other             3             4             6
Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Ramipril 10 mg QD Total
Hide Arm/Group Description Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 40 mg, tablets, orally, once daily for up to 22 weeks. Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 80 mg, tablets, orally, once daily for up to 22 weeks. Ramipril 2.5 mg, tablets, orally, once daily for two weeks; then increased to 10 mg, tablets, orally, once daily for up to 22 weeks. Total of all reporting groups
Overall Number of Baseline Participants 295 294 295 884
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 295 participants 294 participants 295 participants 884 participants
<45 years 40 45 30 115
Between 45 and 64 years 166 168 195 529
≥65 years 89 81 70 240
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 295 participants 294 participants 295 participants 884 participants
Female
136
  46.1%
136
  46.3%
149
  50.5%
421
  47.6%
Male
159
  53.9%
158
  53.7%
146
  49.5%
463
  52.4%
1.Primary 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 Ramipril 10 mg QD
Hide Arm/Group Description:
Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 40 mg, tablets, orally, once daily for up to 22 weeks.
Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 80 mg, tablets, orally, once daily for up to 22 weeks.
Ramipril 2.5 mg, tablets, orally, once daily for two weeks; then increased to 10 mg, tablets, orally, once daily for up to 22 weeks.
Overall Number of Participants Analyzed 291 289 290
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
-20.63  (0.946) -21.24  (0.949) -12.22  (0.948)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Ramipril 10 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.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 -8.41
Confidence Interval (2-Sided) 95%
-11.04 to -5.78
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Ramipril 10 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.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 -9.03
Confidence Interval (2-Sided) 95%
-11.66 to -6.39
Estimation Comments [Not Specified]
2.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 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 Ramipril 10 mg QD
Hide Arm/Group Description:
Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 40 mg, tablets, orally, once daily for up to 22 weeks.
Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 80 mg, tablets, orally, once daily for up to 22 weeks.
Ramipril 2.5 mg, tablets, orally, once daily for two weeks; then increased to 10 mg, tablets, orally, once daily for up to 22 weeks.
Overall Number of Participants Analyzed 291 289 290
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
-10.18  (0.553) -10.54  (0.556) -4.87  (0.555)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Ramipril 10 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.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.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -5.31
Confidence Interval (2-Sided) 95%
-6.85 to -3.78
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Ramipril 10 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.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.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -5.66
Confidence Interval (2-Sided) 95%
-7.21 to -4.12
Estimation Comments [Not Specified]
3.Secondary 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.
Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Ramipril 10 mg QD
Hide Arm/Group Description:
Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 40 mg, tablets, orally, once daily for up to 22 weeks.
Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 80 mg, tablets, orally, once daily for up to 22 weeks.
Ramipril 2.5 mg, tablets, orally, once daily for two weeks; then increased to 10 mg, tablets, orally, once daily for up to 22 weeks.
Overall Number of Participants Analyzed 131 135 127
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
-12.65  (1.006) -12.29  (0.992) -7.83  (1.022)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Ramipril 10 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.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.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.82
Confidence Interval (2-Sided) 95%
-7.64 to -2.01
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Ramipril 10 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). Unadjusted p-value presented.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.47
Confidence Interval (2-Sided) 95%
-7.27 to -1.66
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in 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.
Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Ramipril 10 mg QD
Hide Arm/Group Description:
Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 40 mg, tablets, orally, once daily for up to 22 weeks.
Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 80 mg, tablets, orally, once daily for up to 22 weeks.
Ramipril 2.5 mg, tablets, orally, once daily for two weeks; then increased to 10 mg, tablets, orally, once daily for up to 22 weeks.
Overall Number of Participants Analyzed 131 135 127
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
-8.03  (0.655) -8.32  (0.646) -5.26  (0.666)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Ramipril 10 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). Unadjusted p-value presented.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.77
Confidence Interval (2-Sided) 95%
-4.61 to -0.94
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Ramipril 10 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.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.06
Confidence Interval (2-Sided) 95%
-4.89 to -1.24
Estimation Comments [Not Specified]
5.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.
Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Ramipril 10 mg QD
Hide Arm/Group Description:
Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 40 mg, tablets, orally, once daily for up to 22 weeks.
Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 80 mg, tablets, orally, once daily for up to 22 weeks.
Ramipril 2.5 mg, tablets, orally, once daily for two weeks; then increased to 10 mg, tablets, orally, once daily for up to 22 weeks.
Overall Number of Participants Analyzed 131 135 127
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
-12.06  (1.103) -11.71  (1.087) -8.28  (1.121)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Ramipril 10 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.017
Comments Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.77
Confidence Interval (2-Sided) 95%
-6.87 to -0.68
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Ramipril 10 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.029
Comments Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.43
Confidence Interval (2-Sided) 95%
-6.50 to -0.36
Estimation Comments [Not Specified]
6.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 8 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.
Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Ramipril 10 mg QD
Hide Arm/Group Description:
Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 40 mg, tablets, orally, once daily for up to 22 weeks.
Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 80 mg, tablets, orally, once daily for up to 22 weeks.
Ramipril 2.5 mg, tablets, orally, once daily for two weeks; then increased to 10 mg, tablets, orally, once daily for up to 22 weeks.
Overall Number of Participants Analyzed 131 135 127
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
-7.71  (0.743) -8.07  (0.732) -5.65  (0.755)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Ramipril 10 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.052
Comments Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.06
Confidence Interval (2-Sided) 95%
-4.15 to 0.02
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Ramipril 10 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.022
Comments Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.42
Confidence Interval (2-Sided) 95%
-4.49 to -0.35
Estimation Comments [Not Specified]
7.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.
Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Ramipril 10 mg QD
Hide Arm/Group Description:
Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 40 mg, tablets, orally, once daily for up to 22 weeks.
Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 80 mg, tablets, orally, once daily for up to 22 weeks.
Ramipril 2.5 mg, tablets, orally, once daily for two weeks; then increased to 10 mg, tablets, orally, once daily for up to 22 weeks.
Overall Number of Participants Analyzed 131 135 127
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
-12.61  (1.047) -12.35  (1.032) -8.08  (1.064)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Ramipril 10 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). Unadjusted p-value presented.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.53
Confidence Interval (2-Sided) 95%
-7.46 to -1.59
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Ramipril 10 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). Unadjusted p-value presented.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.26
Confidence Interval (2-Sided) 95%
-7.18 to -1.35
Estimation Comments [Not Specified]
8.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 diastolic blood pressure measured at week 8 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.
Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Ramipril 10 mg QD
Hide Arm/Group Description:
Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 40 mg, tablets, orally, once daily for up to 22 weeks.
Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 80 mg, tablets, orally, once daily for up to 22 weeks.
Ramipril 2.5 mg, tablets, orally, once daily for two weeks; then increased to 10 mg, tablets, orally, once daily for up to 22 weeks.
Overall Number of Participants Analyzed 131 135 127
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
-8.19  (0.700) -8.53  (0.689) -5.55  (0.711)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Ramipril 10 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). Unadjusted p-value presented.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.64
Confidence Interval (2-Sided) 95%
-4.60 to -0.68
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Ramipril 10 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). Unadjusted p-value presented.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.98
Confidence Interval (2-Sided) 95%
-4.93 to -1.04
Estimation Comments [Not Specified]
9.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.
Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Ramipril 10 mg QD
Hide Arm/Group Description:
Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 40 mg, tablets, orally, once daily for up to 22 weeks.
Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 80 mg, tablets, orally, once daily for up to 22 weeks.
Ramipril 2.5 mg, tablets, orally, once daily for two weeks; then increased to 10 mg, tablets, orally, once daily for up to 22 weeks.
Overall Number of Participants Analyzed 130 135 127
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
-12.82  (1.135) -12.69  (1.115) -6.87  (1.147)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Ramipril 10 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.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.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -5.95
Confidence Interval (2-Sided) 95%
-9.12 to -2.77
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Ramipril 10 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.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.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -5.82
Confidence Interval (2-Sided) 95%
-8.96 to -2.67
Estimation Comments [Not Specified]
10.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.
Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Ramipril 10 mg QD
Hide Arm/Group Description:
Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 40 mg, tablets, orally, once daily for up to 22 weeks.
Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 80 mg, tablets, orally, once daily for up to 22 weeks.
Ramipril 2.5 mg, tablets, orally, once daily for two weeks; then increased to 10 mg, tablets, orally, once daily for up to 22 weeks.
Overall Number of Participants Analyzed 130 135 127
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
-7.44  (0.764) -8.20  (0.750) -4.43  (0.773)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Ramipril 10 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.006
Comments Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.01
Confidence Interval (2-Sided) 95%
-5.15 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, Ramipril 10 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.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.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.77
Confidence Interval (2-Sided) 95%
-5.89 to -1.65
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.
Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Ramipril 10 mg QD
Hide Arm/Group Description:
Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 40 mg, tablets, orally, once daily for up to 22 weeks.
Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 80 mg, tablets, orally, once daily for up to 22 weeks.
Ramipril 2.5 mg, tablets, orally, once daily for two weeks; then increased to 10 mg, tablets, orally, once daily for up to 22 weeks.
Overall Number of Participants Analyzed 130 135 127
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
-15.60  (1.172) -14.93  (1.151) -6.73  (1.186)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Ramipril 10 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.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.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -8.87
Confidence Interval (2-Sided) 95%
-12.15 to -5.60
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Ramipril 10 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.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.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -8.20
Confidence Interval (2-Sided) 95%
-11.46 to -4.95
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.
Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Ramipril 10 mg QD
Hide Arm/Group Description:
Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 40 mg, tablets, orally, once daily for up to 22 weeks.
Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 80 mg, tablets, orally, once daily for up to 22 weeks.
Ramipril 2.5 mg, tablets, orally, once daily for two weeks; then increased to 10 mg, tablets, orally, once daily for up to 22 weeks.
Overall Number of Participants Analyzed 130 135 127
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
-10.21  (0.898) -9.85  (0.883) -4.53  (0.909)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Ramipril 10 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.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.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -5.68
Confidence Interval (2-Sided) 95%
-8.19 to -3.17
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Ramipril 10 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.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.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -5.32
Confidence Interval (2-Sided) 95%
-7.81 to -2.82
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 Ramipril 10 mg QD
Hide Arm/Group Description Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 40 mg, tablets, orally, once daily for up to 22 weeks. Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 80 mg, tablets, orally, once daily for up to 22 weeks. Ramipril 2.5 mg, tablets, orally, once daily for two weeks; then increased to 10 mg, tablets, orally, once daily for up to 22 weeks.
All-Cause Mortality
Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Ramipril 10 mg QD
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 Ramipril 10 mg QD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   8/294 (2.72%)   12/293 (4.10%)   6/293 (2.05%) 
Cardiac disorders       
Atrial fibrillation  1  1/294 (0.34%)  2/293 (0.68%)  1/293 (0.34%) 
Acute coronary syndrome  1  0/294 (0.00%)  0/293 (0.00%)  1/293 (0.34%) 
Angina pectoris  1  0/294 (0.00%)  1/293 (0.34%)  0/293 (0.00%) 
Congenital, familial and genetic disorders       
Hydrocele  1  0/294 (0.00%)  1/293 (0.34%)  0/293 (0.00%) 
Eye disorders       
Cataract  1  1/294 (0.34%)  0/293 (0.00%)  0/293 (0.00%) 
Retinal detachment  1  0/294 (0.00%)  1/293 (0.34%)  0/293 (0.00%) 
Gastrointestinal disorders       
Salivary gland calculus  1  0/294 (0.00%)  1/293 (0.34%)  0/293 (0.00%) 
Infections and infestations       
Appendicitis  1  1/294 (0.34%)  0/293 (0.00%)  1/293 (0.34%) 
Hepatitis C  1  1/294 (0.34%)  0/293 (0.00%)  1/293 (0.34%) 
Urosepsis  1  1/294 (0.34%)  0/293 (0.00%)  1/293 (0.34%) 
Upper respiratory tract infection  1  0/294 (0.00%)  1/293 (0.34%)  0/293 (0.00%) 
Injury, poisoning and procedural complications       
Ankle fracture  1  1/294 (0.34%)  0/293 (0.00%)  0/293 (0.00%) 
Fall  1  0/294 (0.00%)  0/293 (0.00%)  1/293 (0.34%) 
Road traffic accident  1  0/294 (0.00%)  1/293 (0.34%)  0/293 (0.00%) 
Metabolism and nutrition disorders       
Hyperkalaemia  1  0/294 (0.00%)  1/293 (0.34%)  0/293 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Lung neoplasm malignant  1  1/294 (0.34%)  0/293 (0.00%)  0/293 (0.00%) 
Renal cancer  1  0/294 (0.00%)  1/293 (0.34%)  0/293 (0.00%) 
Nervous system disorders       
Cerebral ischaemia  1  0/294 (0.00%)  1/293 (0.34%)  0/293 (0.00%) 
Epilepsy  1  0/294 (0.00%)  0/293 (0.00%)  1/293 (0.34%) 
Grand mal convulsion  1  1/294 (0.34%)  0/293 (0.00%)  0/293 (0.00%) 
Ischaemic stroke  1  0/294 (0.00%)  1/293 (0.34%)  0/293 (0.00%) 
Syncope  1  0/294 (0.00%)  1/293 (0.34%)  0/293 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Laryngeal oedema  1  0/294 (0.00%)  1/293 (0.34%)  0/293 (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 Ramipril 10 mg QD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   22/294 (7.48%)   16/293 (5.46%)   36/293 (12.29%) 
Infections and infestations       
Nasopharyngitis  1  19/294 (6.46%)  13/293 (4.44%)  17/293 (5.80%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  3/294 (1.02%)  4/293 (1.37%)  24/293 (8.19%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (11.1)
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: NCT00760214     History of Changes
Other Study ID Numbers: 01-06-TL-491-020
2007-002583-10 ( EudraCT Number )
U1111-1113-8982 ( Registry Identifier: WHO )
First Submitted: September 24, 2008
First Posted: September 26, 2008
Results First Submitted: March 24, 2011
Results First Posted: April 19, 2011
Last Update Posted: November 15, 2012