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Trial record 92 of 134 for:    OLMESARTAN

Efficacy and Safety of Azilsartan Medoxomil Plus Chlorthalidone in Participants With Moderate to Severe Hypertension

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ClinicalTrials.gov Identifier: NCT00846365
Recruitment Status : Completed
First Posted : February 18, 2009
Results First Posted : March 13, 2012
Last Update Posted : March 13, 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 Essential Hypertension
Interventions Drug: Azilsartan medoxomil and chlorthalidone
Drug: Olmesartan medoxomil-hydrochlorothiazide
Enrollment 1085
Recruitment Details Participants enrolled at 93 investigative sites in Argentina, Chile, Mexico and the United States from 13 March 2009 to 25 June 2010.
Pre-assignment Details Participants with moderate to severe essential hypertension were enrolled in one of 3, once-daily (QD) treatment groups.
Arm/Group Title Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Hide Arm/Group Description

Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Period Title: Overall Study
Started 372 357 356
Completed 317 308 323
Not Completed 55 49 33
Reason Not Completed
Adverse Event             20             30             11
Protocol Violation             5             4             0
Lost to Follow-up             8             2             5
Withdrawal by Subject             11             11             9
Pregnancy             1             0             0
Lack of Efficacy             1             1             2
Other             9             1             6
Arm/Group Title Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD Total
Hide Arm/Group Description

Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Total of all reporting groups
Overall Number of Baseline Participants 372 357 356 1085
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 372 participants 357 participants 356 participants 1085 participants
55.5  (10.49) 56.7  (10.83) 55.7  (9.78) 56.0  (10.38)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 372 participants 357 participants 356 participants 1085 participants
<45 years 47 38 41 126
45 to 64 years 252 244 249 745
≥65 years 73 75 66 214
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 372 participants 357 participants 356 participants 1085 participants
Female
175
  47.0%
174
  48.7%
173
  48.6%
522
  48.1%
Male
197
  53.0%
183
  51.3%
183
  51.4%
563
  51.9%
Ethnicity (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 372 participants 357 participants 356 participants 1085 participants
Hispanic or Latino
37
   9.9%
41
  11.5%
44
  12.4%
122
  11.2%
Not Hispanic or Latino
265
  71.2%
253
  70.9%
251
  70.5%
769
  70.9%
Unknown or Not Reported
70
  18.8%
63
  17.6%
61
  17.1%
194
  17.9%
[1]
Measure Description: Ethnicity was not collected from Latin American sites.
Race (NIH/OMB)   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 372 participants 357 participants 356 participants 1085 participants
American Indian or Alaska Native 37 34 35 106
Asian 7 5 5 17
Native Hawaiian or Other Pacific Islander 3 0 0 3
Black or African American 95 95 100 290
White 235 225 220 680
More than one race 5 2 4 11
Unknown or Not Reported 0 0 0 0
[1]
Measure Description: Participants could choose more than one category for race. Participants who chose more than 1 race category are included in each category indicated and are also included in the multiracial category.
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 372 participants 357 participants 356 participants 1085 participants
United States 302 294 295 891
Mexico 45 44 43 132
Chile 12 10 9 31
Argentina 13 9 9 31
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 372 participants 357 participants 356 participants 1085 participants
89.35  (20.995) 89.87  (21.281) 90.66  (20.700) 89.95  (20.981)
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 372 participants 357 participants 356 participants 1085 participants
167.5  (11.22) 167.8  (11.06) 168.2  (10.30) 167.8  (10.87)
Body Mass Index (BMI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 372 participants 357 participants 356 participants 1085 participants
31.7  (5.94) 31.8  (6.40) 31.9  (6.08) 31.8  (6.14)
[1]
Measure Description: BMI was calculated using height at Screening and weight at Baseline.
Estimated Glomerular Filtration Rate (eGFR) Category   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 372 participants 357 participants 356 participants 1085 participants
Moderate impairment 26 25 25 76
Mild impairment 220 207 205 632
Normal 126 125 126 377
[1]
Measure Description:

eGFR = creatinine clearance, estimated using the Modification of Diet in Renal Disease equation with the following parameters:

  • Moderate impairment: ≥30 to <60 mL/min/1.73 m^2
  • Mild impairment: ≥60 to <90 mL/min/1.73 m^2
  • Normal: ≥90 mL/min/1.73 m^2
Chronic Kidney Disease (CKD) Status   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 372 participants 357 participants 356 participants 1085 participants
Yes 25 41 28 94
No 347 315 328 990
Missing 0 1 0 1
[1]
Measure Description: Participant was considered to have CKD if their eGFR was <60 ml/min/1.73 m^2 or urinary albumin:creatinine ratio was >200 mg albumin/g creatinine at Screening.
Diabetes Status  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 372 participants 357 participants 356 participants 1085 participants
Yes 58 59 71 188
No 314 298 285 897
1.Primary Outcome
Title Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure.
Hide Description The change in trough systolic blood pressure measured at week 8 or final visit relative to baseline. Systolic blood pressure is the average of the 3 serial trough sitting systolic blood pressure measurements.
Time Frame Baseline and Week 8.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward.
Arm/Group Title Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Hide Arm/Group Description:

Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Overall Number of Participants Analyzed 363 350 353
Least Squares Mean (Standard Deviation)
Unit of Measure: mmHg
-37.6  (0.83) -38.2  (0.85) -31.5  (0.84)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD, Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Comments Analysis of Covariance (ANCOVA) model with treatment as a fixed effect and Baseline as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Statistical significance was set at the 0.05 level per the predefined stepwise testing strategy used.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -6.1
Confidence Interval (2-Sided) 95%
-8.4 to -3.8
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD, Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Comments ANCOVA model with treatment as a fixed effect and Baseline as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Statistical significance was set at the 0.05 level per the predefined stepwise testing strategy used.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -6.7
Confidence Interval (2-Sided) 95%
-9.1 to -4.4
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline to Week 4 in Trough, Sitting, Clinic Systolic Blood Pressure.
Hide Description The change in trough systolic blood pressure measured at week 4 relative to baseline. Systolic blood pressure is the average of the 3 serial trough sitting systolic blood pressure measurements.
Time Frame Baseline and Week 4.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. Participants who had not achieved target systolic blood pressure/diastolic blood pressure were titrated to the higher dose at week 4.
Arm/Group Title Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Hide Arm/Group Description:

Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Overall Number of Participants Analyzed 360 347 352
Least Squares Mean (Standard Deviation)
Unit of Measure: mmHg
-33.0  (0.87) -34.1  (0.88) -26.9  (0.88)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD, Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Comments ANCOVA model with treatment as a fixed effect and Baseline as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Statistical significance was set at the 0.05 level per the predefined stepwise testing strategy used.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -6.1
Confidence Interval (2-Sided) 95%
-8.5 to -3.7
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD, Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Comments ANCOVA model with treatment as a fixed effect and Baseline as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Statistical significance was set at the 0.05 level per the predefined stepwise testing strategy used.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -7.2
Confidence Interval (2-Sided) 95%
-9.6 to -4.8
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Trough, Sitting, Clinic Diastolic Blood Pressure
Hide Description The change in trough diastolic blood pressure measured at week 4 and week 8 relative to baseline. Diastolic blood pressure is the average of the 3 serial trough sitting diastolic blood pressure measurements.
Time Frame Baseline, Week 4 and Week 8.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set , all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. Participants who had not achieved target systolic blood pressure/diastolic blood pressure were titrated to the higher dose at week 4.
Arm/Group Title Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Hide Arm/Group Description:

Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Overall Number of Participants Analyzed 372 357 356
Least Squares Mean (Standard Deviation)
Unit of Measure: mmHg
Week 4 (n=360; n=347; n=352) -13.6  (0.49) -14.2  (0.50) -10.4  (0.49)
Week 8 (n=363; n=350; n=353) -16.1  (0.47) -16.5  (0.48) -12.8  (0.48)
4.Secondary Outcome
Title Change From Baseline in Trough Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Hide Description The change in trough systolic blood pressure measured at week 4 and week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Trough is the average of all measurements recorded from 22 to 24 hours after dosing.
Time Frame Baseline, Week 4 and Week 8.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. Participants who had not achieved target systolic blood pressure/diastolic blood pressure were titrated to the higher dose at week 4.
Arm/Group Title Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Hide Arm/Group Description:

Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Overall Number of Participants Analyzed 372 357 356
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
Week 4 (n=223; n=227; n=219) -22.4  (0.95) -23.6  (0.94) -17.4  (0.96)
Week 8 (n=290; n=278; n=281) -24.9  (0.79) -26.8  (0.81) -19.6  (0.80)
5.Secondary Outcome
Title Change From Baseline in Trough Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Hide Description The change in trough systolic blood pressure measured at week 4 and week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Trough is the average of all measurements recorded from 22 to 24 hours after dosing.
Time Frame Baseline, Week 4 and Week 8.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. Participants who had not achieved target systolic blood pressure/diastolic blood pressure were titrated to the higher dose at week 4.
Arm/Group Title Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Hide Arm/Group Description:

Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Overall Number of Participants Analyzed 372 357 356
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
Week 4 (n=223; n=227; n=219) -13.4  (0.66) -14.6  (0.66) -10.9  (0.67)
Week 8 (n=290; n=278; n=281) -14.6  (0.56) -15.9  (0.57) -12.0  (0.57)
6.Secondary Outcome
Title Change From Baseline in 24-hour Mean Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring.
Hide Description The change in the 24-hour mean systolic blood pressure at week4 and week 8 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, Week 4 and Week 8.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. Participants who had not achieved target systolic blood pressure/diastolic blood pressure were titrated to the higher dose at week 4.
Arm/Group Title Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Hide Arm/Group Description:

Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Overall Number of Participants Analyzed 372 357 356
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
Week 4 (n=223; n=227; n=219) -24.1  (0.81) -24.4  (0.80) -18.4  (0.81)
Week 8 (n=290; n=278; n=281) -26.4  (0.69) -27.9  (0.70) -20.7  (0.70)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD, Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Comments Statistical analysis for Week 8. ANOVA model with treatment as a fixed effect. Post-baseline p-values are obtained from an ANCOVA model with treatment as a fixed effect and baseline as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Tested at the 0.05 significance level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -5.6
Confidence Interval (2-Sided) 95%
-7.5 to -3.7
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD, Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Comments Statistical analysis for Week 8. ANOVA model with treatment as a fixed effect. Post-baseline p-values are obtained from an ANCOVA model with treatment as a fixed effect and baseline as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Tested at the 0.05 significance level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -7.2
Confidence Interval (2-Sided) 95%
-9.1 to -5.2
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in 24-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Hide Description The change in the 0 to 24-hours-after-dosing mean diastolic blood pressure measured at Week 4 and Week 8 relative to baseline. . Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The mean consists of the average of measurements collected over the subsequent 24 hours.
Time Frame Baseline, Week 4 and Week 8.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. Participants who had not achieved target systolic blood pressure/diastolic blood pressure were titrated to the higher dose at week 4.
Arm/Group Title Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Hide Arm/Group Description:

Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Overall Number of Participants Analyzed 372 357 357
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
Week 4 (n=223; n=227; n=219) -13.9  (0.51) -14.4  (0.51) -10.5  (0.52)
Week 8 (n=290; n=278; n=281) -15.1  (0.45) -16.4  (0.46) -12.0  (0.46)
8.Secondary Outcome
Title Change From Baseline in Daytime Mean (6am to 10pm) Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Hide Description The change in the daytime, while awake (6am to 10pm) mean systolic blood pressure measured at Week 4 and 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 measurements recorded between the hours of 6 AM (inclusive) and 10 PM (exclusive) included in the 24-hour mean calculations.
Time Frame Baseline, Week 4 and Week 8.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set , all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. Participants who had not achieved target systolic blood pressure/diastolic blood pressure were titrated to the higher dose at week 4.
Arm/Group Title Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Hide Arm/Group Description:

Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Overall Number of Participants Analyzed 372 357 356
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
Week 4 (n=223; n=227; n=219) -24.5  (0.84) -25.1  (0.83) -18.9  (0.85)
Week 8 (n=290; n=278; n=281) -26.7  (0.72) -28.4  (0.74) -21.0  (0.74)
9.Secondary Outcome
Title Change From Baseline in Daytime Mean (6am to 10pm) Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Hide Description The change in the daytime, while awake (6am to 10pm) mean diastolic blood pressure measured at Week 4 and Week 8relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of measurements recorded between the hours of 6 AM (inclusive) and 10 PM (exclusive) included in the 24-hour mean calculations.
Time Frame Baseline, Week 4 and Week 8.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. Participants who had not achieved target systolic blood pressure/diastolic blood pressure were titrated to the higher dose at week 4.
Arm/Group Title Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Hide Arm/Group Description:

Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Overall Number of Participants Analyzed 372 357 356
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
Week 4 (n=223; n=227; n=219) -14.2  (0.53) -14.7  (0.53) -10.7  (0.54)
Week 8 (n=290; n=278; n=281) -15.3  (0.47) -16.6  (0.48) -12.1  (0.48)
10.Secondary Outcome
Title Change From Baseline in Nighttime Mean (12am to 6am) Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring
Hide Description The change in the nighttime, while asleep (12am to 6am) mean systolic blood pressure measured at Week 4 and Week 8 to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of measurements recorded between the hours of 12 AM (inclusive) and 6 AM (exclusive) included in the 24-hour mean calculations.
Time Frame Baseline, Week 4 and Week 8.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. Participants who had not achieved target systolic blood pressure/diastolic blood pressure were titrated to the higher dose at week 4.
Arm/Group Title Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Hide Arm/Group Description:

Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Overall Number of Participants Analyzed 372 357 356
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
Week 4 (n=223; n=227; n=219) -22.3  (0.87) -21.9  (0.86) -16.6  (0.88)
Week 8 (n=290; n=278; n=281) -25.2  (0.74) -26.3  (0.75) -19.7  (0.75)
11.Secondary Outcome
Title Change From Baseline in Nighttime Mean (12am to 6am) Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Hide Description The change in the nighttime, while asleep (12am to 6am) mean diastolic blood pressure measured at Week 4 and Week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average (arithmetic mean) of measurements recorded between the hours of 12 AM (inclusive) and 6 AM (exclusive) included in the 24-hour mean calculations.
Time Frame Baseline, Week 4 and Week 8.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. Participants who had not achieved target systolic blood pressure/diastolic blood pressure were titrated to the higher dose at week 4.
Arm/Group Title Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Hide Arm/Group Description:

Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Overall Number of Participants Analyzed 372 357 356
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
Week 4 (n=223; n=227; n=219) -13.4  (0.58) -13.3  (0.58) -9.6  (0.59)
Week 8 (n=290; n=278; n=281) -14.9  (0.51) -15.8  (0.52) -11.8  (0.52)
12.Secondary Outcome
Title Change From Baseline in 12-hr Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Hide Description The change in the 0 to 12 hours-after-dosing mean Systolic Blood Pressure measured at Week 4 and Week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night The mean consists of the average (arithmetic mean) of measurements collected at each time frame and includes all observations recorded over the subsequent 12 hours.
Time Frame Baseline, Week 4 and Week 8.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. Participants who had not achieved target systolic blood pressure/diastolic blood pressure were titrated to the higher dose at week 4.
Arm/Group Title Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Hide Arm/Group Description:

Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Overall Number of Participants Analyzed 372 357 356
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
Week 4 (n=223; n=227; n=219) -25.0  (0.87) -25.5  (0.86) -19.2  (0.88)
Week 8 (n=290; n=278; n=281) -27.1  (0.77) -28.8  (0.78) -21.1  (0.78)
13.Secondary Outcome
Title Change From Baseline in 12-hr Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Hide Description The change in the 0 to 12 hours-after-dosing mean diastolic blood pressure measured at Week 4 and Week 8 to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The mean consists of the average (arithmetic mean) of measurements collected at each time frame and includes all observations recorded over the subsequent 12 hours.
Time Frame Baseline, Week 4 and Week 8.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. Participants who had not achieved target systolic blood pressure/diastolic blood pressure were titrated to the higher dose at week 4.
Arm/Group Title Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Hide Arm/Group Description:

Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Overall Number of Participants Analyzed 372 357 356
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
Week 4 (n=223; n=227; n=219) -14.4  (0.56) -14.8  (0.55) -10.8  (0.56)
Week 8 (n=290; n=278; n=281) -15.4  (0.50) -16.9  (0.51) -12.1  (0.51)
14.Secondary Outcome
Title Percentage of Participants Who Achieve a Clinic Systolic Blood Pressure Response, Defined as <140 mm Hg for Participants Without Diabetes or CKD or <130 mm Hg for Participants With Diabetes or CKD
Hide Description Percentage of participants who achieve a clinic systolic blood pressure response, defined as <140 mm Hg for participants without diabetes or CKD or <130 mm Hg for participants with diabetes or CKD at each time frame relative to baseline.
Time Frame Baseline, Week 2, Week 4, Week 6 and Week 8.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. Participants who had not achieved target systolic blood pressure/diastolic blood pressure were titrated to the higher dose at week 4.
Arm/Group Title Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Hide Arm/Group Description:

Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Overall Number of Participants Analyzed 372 357 356
Measure Type: Number
Unit of Measure: percentage of participants
Week 2 (n=343; n=334; n=345) 60.3 57.2 44.9
Week 4 (n=360; n=347; n=352) 66.1 68.9 52.3
Week 6 (n=362; n=350; n=353) 76.8 73.4 64.9
Week 8 (n=363; n=350; n=353) 76.0 76.0 64.6
15.Secondary Outcome
Title Percentage of Participants Who Achieve a Clinic Diastolic Blood Pressure Response, Defined as Defined as <90 mm Hg for Participants Without Diabetes or CKD or <80 mm Hg for Participants With Diabetes or CKD
Hide Description Percentage of participants who achieve a clinic diastolic blood pressure response, defined as defined as <90 mm Hg for participants without diabetes or CKD or <80 mm Hg for participants with diabetes or CKD at each time frame relative to baseline.
Time Frame Baseline, Week 2, Week 4, Week 6 and Week 8.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. Participants who had not achieved target systolic blood pressure/diastolic blood pressure were titrated to the higher dose at week 4.
Arm/Group Title Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Hide Arm/Group Description:

Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Overall Number of Participants Analyzed 372 357 356
Measure Type: Number
Unit of Measure: percentage of participants
Week 2 (n=343; n=334; n=345) 63.6 66.2 47.8
Week 4 (n=360; n=347; n=352) 71.4 73.8 58.2
Week 6 (n=362; n=350; n=353) 77.9 76.9 66.9
Week 8 (n=363; n=350; n=353) 79.9 79.1 66.0
16.Secondary Outcome
Title Percentage of Participants Who Achieve a Clinic Diastolic AND Systolic Blood Pressure Response, Defined as <140/90 mm Hg for Participants Without Diabetes or Chronic Kidney Disease (CKD) or <130/80 mm Hg for Participants With Diabetes or CKD
Hide Description Percentage of participants who achieve both a clinic diastolic blood pressure response, defined as <140/90 mm Hg for participants without diabetes or chronic kidney disease (CKD) or <130/80 mm Hg for participants with diabetes or CKD at each time frame relative to baseline.
Time Frame Baseline, Week 2, Week 4, Week 6 and Week 8.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. Participants who had not achieved target systolic blood pressure/diastolic blood pressure were titrated to the higher dose at week 4.
Arm/Group Title Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Hide Arm/Group Description:

Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Overall Number of Participants Analyzed 372 357 356
Measure Type: Number
Unit of Measure: percentage of participants
Week 2 (n=343; n=334; n=345) 51.3 48.5 35.9
Week 4 (n=360; n=347; n=352) 58.1 61.4 44.6
Week 6 (n=362; n=350; n=353) 68.8 65.4 55.5
Week 8 (n=363; n=350; n=353) 69.4 68.9 54.7
Time Frame Treatment-emergent adverse events are adverse events that started on or 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 20-40mg Plus Chlorthalidone 12.5-25 mg QD Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Hide Arm/Group Description

Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.

Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks.

If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.

All-Cause Mortality
Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/372 (1.08%)   8/357 (2.24%)   6/356 (1.69%) 
Cardiac disorders       
Cardiac arrest  1  0/372 (0.00%)  1/357 (0.28%)  1/356 (0.28%) 
Coronary artery disease  1  0/372 (0.00%)  0/357 (0.00%)  1/356 (0.28%) 
Diastolic dysfunction  1  0/372 (0.00%)  1/357 (0.28%)  0/356 (0.00%) 
Gastrointestinal disorders       
Diarrhoea  1  1/372 (0.27%)  0/357 (0.00%)  0/356 (0.00%) 
Epigastric discomfort  1  1/372 (0.27%)  0/357 (0.00%)  0/356 (0.00%) 
Nausea  1  1/372 (0.27%)  0/357 (0.00%)  0/356 (0.00%) 
Pancreatitis  1  0/372 (0.00%)  1/357 (0.28%)  0/356 (0.00%) 
Vomiting  1  1/372 (0.27%)  0/357 (0.00%)  0/356 (0.00%) 
General disorders       
Chest pain  1  0/372 (0.00%)  0/357 (0.00%)  1/356 (0.28%) 
Generalised oedema  1  0/372 (0.00%)  1/357 (0.28%)  0/356 (0.00%) 
Systemic inflammatory response syndrome  1  0/372 (0.00%)  0/357 (0.00%)  1/356 (0.28%) 
Infections and infestations       
Cellulitis  1  0/372 (0.00%)  1/357 (0.28%)  1/356 (0.28%) 
Gastroenteritis  1  0/372 (0.00%)  1/357 (0.28%)  0/356 (0.00%) 
Pneumonia  1  0/372 (0.00%)  1/357 (0.28%)  0/356 (0.00%) 
Viral infection  1  0/372 (0.00%)  1/357 (0.28%)  0/356 (0.00%) 
Injury, poisoning and procedural complications       
Heat exhaustion  1  0/372 (0.00%)  0/357 (0.00%)  1/356 (0.28%) 
Road traffic accident  1  1/372 (0.27%)  0/357 (0.00%)  0/356 (0.00%) 
Investigations       
Blood creatinine increased  1  0/372 (0.00%)  1/357 (0.28%)  0/356 (0.00%) 
Troponin increased  1  0/372 (0.00%)  0/357 (0.00%)  1/356 (0.28%) 
Metabolism and nutrition disorders       
Dehydration  1  0/372 (0.00%)  0/357 (0.00%)  1/356 (0.28%) 
Nervous system disorders       
Cerebral infarction  1  0/372 (0.00%)  1/357 (0.28%)  0/356 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Pulmonary embolism  1  1/372 (0.27%)  0/357 (0.00%)  1/356 (0.28%) 
Asthma  1  0/372 (0.00%)  0/357 (0.00%)  1/356 (0.28%) 
Sleep apnoea syndrome  1  0/372 (0.00%)  1/357 (0.28%)  0/356 (0.00%) 
Skin and subcutaneous tissue disorders       
Angioedema  1  0/372 (0.00%)  1/357 (0.28%)  0/356 (0.00%) 
Vascular disorders       
Deep vein thrombosis  1  0/372 (0.00%)  0/357 (0.00%)  1/356 (0.28%) 
Shock  1  0/372 (0.00%)  0/357 (0.00%)  1/356 (0.28%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   66/372 (17.74%)   72/357 (20.17%)   56/356 (15.73%) 
Investigations       
Blood creatinine increased  1  36/372 (9.68%)  44/357 (12.32%)  25/356 (7.02%) 
Nervous system disorders       
Dizziness  1  25/372 (6.72%)  24/357 (6.72%)  20/356 (5.62%) 
Headache  1  14/372 (3.76%)  14/357 (3.92%)  18/356 (5.06%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.0
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
Layout table for Results Point of Contact information
Name/Title: Sr. VP, Clinical Science
Organization: Takeda Global Research and Development Center, Inc.
Phone: 800-778-2860
EMail: clinicaltrialregistry@tpna.com
Layout table for additonal information
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT00846365     History of Changes
Other Study ID Numbers: TAK-491CLD_301
U1111-1112-4287 ( Other Identifier: WHO )
First Submitted: February 13, 2009
First Posted: February 18, 2009
Results First Submitted: January 4, 2012
Results First Posted: March 13, 2012
Last Update Posted: March 13, 2012