Efficacy and Safety of Azilsartan Medoxomil in African American Participants With Essential Hypertension

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00591253
• Collaborator: (none)
• Enrollment: 413
• Locations: 64
• Arms: 3
• Duration (Months): 18
• Patients Per Site: 6.5
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the effectiveness and safety of azilsartan medoxomil compared to placebo, once daily (QD), in African-American participants with essential hypertension.

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Drug: Azilsartan medoxomil; Drug: Azilsartan medoxomil; Drug: Placebo	Phase 3

Detailed Description

Hypertension affects approximately 50 million individuals in the United States. As the population ages, the prevalence of hypertension will continue to increase if broad and effective preventive measures are not implemented. According to the World Health Organization, hypertension is the most common attributable cause of preventable death in developed nations, as uncontrolled hypertension greatly increases the risk of cardiovascular disease, cerebrovascular disease, and renal failure. Despite the availability of antihypertensive treatments, hypertension remains inadequately controlled; only about one third of patients continue to maintain control successfully.

A major component of blood pressure regulation is the renin-angiotensin-aldosterone system, a system of hormone-mediated feedback interactions that results in the relaxation or constriction of blood vessels in response to various stimuli. Angiotensin II, a polypeptide hormone, is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme as part of the renin-angiotensin-aldosterone system. Angiotensin II is the principal pressor agent of the renin-angiotensin-aldosterone system with a myriad of effects on the cardiovascular system and on electrolyte homeostasis.

In the United States, a disproportionate number of African-Americans have hypertension compared to age-matched non-Hispanic Caucasians and Mexican Americans. Earlier onset and greater severity of hypertension in African-Americans contribute to greater target organ damage and may be a factor in shorter life expectancy in this population compared to Caucasian-Americans. Although genetic factors have been invoked to explain these racial differences, environmental factors probably play a more important role. Improved management of hypertension through both lifestyle intervention and pharmacotherapy, including combination therapy, are necessary to achieve target blood pressure in African Americans.

Takeda Global Research & Development Center, Inc. is developing TAK-491 (azilsartan medoxomil) to treat patients with essential hypertension. Azilsartan medoxomil is a prodrug that is hydrolyzed to the active moiety, TAK-536 (azilsartan), which is a selective antagonist of the angiotensin II type 1 receptor subtype.

This study is being conducted to evaluate the effectiveness and safety of oral azilsartan medoxomil compared with placebo in African-American participants with essential hypertension. Participation in this study is anticipated to be approximately 10 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 413 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of TAK-491 in Black Subjects With Essential Hypertension
• Study Start Date: Oct 1, 2007
• Actual Primary Completion Date: Apr 1, 2009
• Actual Study Completion Date: Apr 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Azilsartan Medoxomil 40 mg QD	Drug: Azilsartan medoxomil; Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 6 weeks.; Other Names: TAK-491 Edarbi
Experimental: Azilsartan Medoxomil 80 mg QD	Drug: Azilsartan medoxomil; Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 6 weeks.; Other Names: TAK-491 Edarbi
Placebo Comparator: Placebo QD	Drug: Placebo; Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 6 weeks.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the 24-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [Baseline and Week 6.]

   The change in 24-hour mean systolic blood pressure measured at week 6 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.

Secondary Outcome Measures

1. Change From Baseline in Mean Trough Clinic Sitting Systolic Blood Pressure [Baseline and Week 6.]

   The change in mean trough clinic sitting systolic blood pressure measured at final visit or week 6 relative to baseline.

2. Change From Baseline in the 24-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [Baseline and Week 6.]

   The change in 24-hour mean diastolic blood pressure measured at week 6 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.

3. Change From Baseline in Mean Trough Clinic Sitting Diastolic Blood Pressure [Baseline and Week 6.]

   The change in mean trough clinic sitting diastolic blood pressure measured at final visit or week 6 relative to baseline.

4. Change From Baseline in Daytime (6am to 10 pm) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [Baseline and Week 6.]

   The change in daytime (6am to 10pm) mean systolic blood pressure measured at week 6 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.

5. Change From Baseline in Daytime (6am to 10 pm) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [Baseline and Week 6.]

   The change in daytime (6am to 10pm) mean diastolic blood pressure measured at week 6 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.

6. Change From Baseline in the Nighttime (12 am to 6 am) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [Baseline and Week 6.]

   The change in nighttime (12am to 6am) mean systolic blood pressure measured at week 6 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.

7. Change From Baseline in the Nighttime (12 am to 6 am) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [Baseline and Week 6.]

   The change in nighttime (12am to 6am) mean diastolic blood pressure measured at week 6 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.

8. Change From Baseline in the 12-hr Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [Baseline and Week 6.]

   The change in the 12-hour mean systolic blood pressure measured at week 6 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.

9. Change From Baseline in the 12-hr Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [Baseline and Week 6.]

   The change in the 12-hour mean diastolic blood pressure measured at week 6 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.

10. Change From Baseline in the Trough (22-24-hr) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [Baseline and Week 6.]

    The change in trough mean systolic blood pressure measured at week 6 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.

11. Change From Baseline in the Trough (22-24-hr) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [Baseline and Week 6.]

    The change in trough mean diastolic blood pressure measured at week 6 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.

12. Percentage of Participants Who Achieve a Clinic Systolic Blood Pressure Response, Defined as < 140 mm Hg and/or Reduction From Baseline ≥ 20 mm Hg [Baseline and Week 6.]

    Percentage of participants who achieve a clinic systolic blood pressure response measured at week 6, defined as less than 140 mm Hg and/or reduction from baseline of greater than or equal to 20 mm Hg. Systolic blood pressure is the arithmetic mean of the 3 trough sitting systolic blood pressure measurements.

13. Percentage of Participants Who Achieve a Clinic Diastolic Blood Pressure Response, Defined as < 90 mm Hg and/or Reduction From Baseline ≥ 10 mm Hg [Baseline and Week 6.]

    Percentage of participants who achieve a clinic diastolic blood pressure response measured at week 6, defined as less than 90 mm Hg and/or reduction from baseline of greater than or equal to 10 mm Hg. Diastolic blood pressure is the arithmetic mean of the 3 trough sitting diastolic blood pressure measurements.

14. Percentage of Participants Who Achieve Both a Clinic Diastolic and Systolic Blood Pressure Response [Baseline and Week 6.]

    Percentage of participants who achieve both a clinic diastolic and systolic blood pressure response measured at week 6, defined as less than 90 mm Hg and/or reduction from baseline of greater than or equal to 10 mm Hg AND less than 140 mm Hg and/or reduction from baseline of greater than or equal to 20 mm Hg. Diastolic and systolic blood pressure is based on the arithmetic mean of the 3 sitting blood pressure measurements.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. The participant has essential hypertension (defined as sitting trough clinic systolic blood pressure between 150 and 180 mm Hg, inclusive at Day -1) and 24-hour mean systolic blood pressure 130-170 mm Hg, inclusive, at Day 1.

2. Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.

3. Clinical laboratory evaluations within the reference range for the testing laboratory unless the results are deemed not clinically significant for inclusion into this study by the investigator.

4. Willing to discontinue current antihypertensive medication.

Exclusion Criteria:

1. Has sitting trough clinic diastolic blood pressure greater than 114 mm Hg.

2. Baseline 24 hour ambulatory blood pressure monitor reading of insufficient quality.

3. Hypersensitive to angiotensin II receptor blockers.

4. History of myocardial infarction, heart failure, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebrovascular accident, or transient ischemic attack.

5. Clinically significant cardiac conduction defects.

6. Hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease.

7. Secondary hypertension of any etiology.

8. Non-compliant with study medication during run-in period.

9. Severe renal dysfunction or disease (based on calculated creatinine clearance less than 30 mL/min/1.73 m2) at Screening.

10. Known or suspected unilateral or bilateral renal artery stenosis.

11. History of drug abuse or a history of alcohol abuse within the past 2 years.

12. Previous history of cancer that has not been in remission for at least 5 years prior to the first dose of study drug.

13. Type 1 or poorly controlled type 2 diabetes mellitus.

14. Alanine aminotransferase level of greater than 2.5 times the upper limit of normal, active liver disease, or jaundice.

15. Hyperkalemia.

16. Upper arm circumference less than 24 cm or greater than 42 cm.

17. Works night (3rd) shift.

18. Currently is participating in another investigational study or has participated in an investigational study within 30 days prior to randomization.

19. Any other serious disease or condition at Screening (or Randomization) that would compromise participant safety, might affect life expectancy, or make it difficult to successfully manage and follow the participant according to the protocol.

20. Randomized in a previous azilsartan medoxomil study.

21. Is required to take or continues taking any disallowed medication, prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Alabaster	Alabama	United States
2		Huntsville	Alabama	United States
3		Tempe	Arizona	United States
4		Freemont	California	United States
5		Garden Grove	California	United States
6		Long Beach	California	United States
7		Riverside	California	United States
8		Sacramento	California	United States
9		San Diego	California	United States
10		Whittier	California	United States
11		Newark	Delaware	United States
12		Hialeah	Florida	United States
13		Hollywood	Florida	United States
14		Miami	Florida	United States
15		Pembroke Pines	Florida	United States
16		Atlanta	Georgia	United States
17		Waycross	Georgia	United States
18		Chicago	Illinois	United States
19		Avon	Indiana	United States
20		Elkhart	Indiana	United States
21		Indianapolis	Indiana	United States
22		Lexington	Kentucky	United States
23		Baltimore	Maryland	United States
24		Ann Arbor	Michigan	United States
25		Bingham Farms	Michigan	United States
26		Southfield	Michigan	United States
27		Florissant	Missouri	United States
28		Brooklyn	New York	United States
29		Hickory	North Carolina	United States
30		Raleigh	North Carolina	United States
31		Salisbury	North Carolina	United States
32		Shelby	North Carolina	United States
33		Akron	Ohio	United States
34		Centerville	Ohio	United States
35		Cincinnati	Ohio	United States
36		Columbus	Ohio	United States
37		Willoughby Hills	Ohio	United States
38		Zanesville	Ohio	United States
39		Oklahoma City	Oklahoma	United States
40		Downingtown	Pennsylvania	United States
41		Jenkintown	Pennsylvania	United States
42		Anderson	South Carolina	United States
43		Charleston	South Carolina	United States
44		Simpsonville	South Carolina	United States
45		Spartanburg	South Carolina	United States
46		Dallas	Texas	United States
47		Friendswood	Texas	United States
48		Houston	Texas	United States
49		Irving	Texas	United States
50		Katy	Texas	United States
51		Missouri City	Texas	United States
52		North Richland Hills	Texas	United States
53		Pearland	Texas	United States
54		Sugarland	Texas	United States
55		Riverton	Utah	United States
56		Salt Lake City	Utah	United States
57		Arlington	Virginia	United States
58		Burke	Virginia	United States
59		Manassas	Virginia	United States
60		Port Orchard	Washington	United States
61		Aguas Buenas		Puerto Rico
62		Aibonito		Puerto Rico
63		Loiza		Puerto Rico
64		San Juan		Puerto Rico

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Executive Medical Director Clinical Science, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00591253
• Other Study ID Numbers: 01-06-TL-491-011; U1111-1113-8925
• First Posted: Jan 11, 2008
• Last Update Posted: Apr 19, 2011
• Last Verified: Mar 1, 2011

• Keywords provided by , ,: Blood pressure; blood pressure monitoring ambulatory; Drug Therapy
• Additional relevant MeSH terms: Hypertension; Essential Hypertension; Azilsartan medoxomil

Study Results

Participant Flow

Recruitment Details	Participants enrolled at 74 investigative sites in Puerto Rico and the United States from 30 October 2007 to 30 April 2009.
Pre-assignment Detail	Black 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	Placebo QD
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 6 weeks.
Period Title: Overall Study
STARTED	140	137	138
COMPLETED	126	116	123
NOT COMPLETED	14	21	15

Baseline Characteristics

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Placebo QD	Total
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 6 weeks.	Total of all reporting groups
Overall Participants	138	137	138	413
Age (participants) [Number]
<45 years	29 21%	37 27%	36 26.1%	102 24.7%
Between 45 and 64 years	94 68.1%	86 62.8%	85 61.6%	265 64.2%
≥65 years	15 10.9%	14 10.2%	17 12.3%	46 11.1%
Sex: Female, Male (Count of Participants)
Female	78 56.5%	80 58.4%	78 56.5%	236 57.1%
Male	60 43.5%	57 41.6%	60 43.5%	177 42.9%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the 24-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Description	The change in 24-hour mean systolic blood pressure measured at week 6 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 6.

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Placebo QD
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 6 weeks.
Measure Participants	94	101	94
Least Squares Mean (Standard Error) [mmHg]	-7.70 (1.063)	-10.48 (1.026)	-2.70 (1.065)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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 is presented. Overall 0.05 level of significance for multiple comparisons controlled using closed testing procedure.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.00
	Confidence Interval	(2-Sided) 95%; -7.97 to -2.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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 is presented. Overall 0.05 level of significance for multiple comparisons controlled using closed testing procedure.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-7.78
	Confidence Interval	(2-Sided) 95%; -10.69 to -4.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Mean Trough Clinic Sitting Systolic Blood Pressure
Description	The change in mean trough clinic sitting systolic blood pressure measured at final visit or week 6 relative to baseline.
Time Frame	Baseline and Week 6.

Outcome Measure Data

Analysis Population Description

Full analysis set with last observation carried forward.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Placebo QD
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 6 weeks.
Measure Participants	134	130	133
Least Squares Mean (Standard Error) [mmHg]	-9.51 (1.330)	-9.58 (1.351)	-3.04 (1.333)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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 is presented. Overall 0.05 level of significance for multiple comparisons controlled using closed testing procedure.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-6.48
	Confidence Interval	(2-Sided) 95%; -10.18 to -2.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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 is presented. Overall 0.05 level of significance for multiple comparisons controlled using closed testing procedure.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-6.54
	Confidence Interval	(2-Sided) 95%; -10.27 to -2.81
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in the 24-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Description	The change in 24-hour mean diastolic blood pressure measured at week 6 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 6.

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Placebo QD
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 6 weeks.
Measure Participants	94	101	94
Least Squares Mean (Standard Error) [mmHg]	-4.93 (0.732)	-7.27 (0.706)	-1.49 (0.731)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.44
	Confidence Interval	(2-Sided) 95%; -5.47 to -1.40
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.77
	Confidence Interval	(2-Sided) 95%; -7.78 to -3.77
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in Mean Trough Clinic Sitting Diastolic Blood Pressure
Description	The change in mean trough clinic sitting diastolic blood pressure measured at final visit or week 6 relative to baseline.
Time Frame	Baseline and Week 6.

Outcome Measure Data

Analysis Population Description

Full analysis set with last observation carried forward.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Placebo QD
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 6 weeks.
Measure Participants	134	130	133
Least Squares Mean (Standard Error) [mmHg]	-5.48 (0.755)	-5.32 (0.766)	-2.36 (0.757)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.12
	Confidence Interval	(2-Sided) 95%; -5.22 to -1.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.96
	Confidence Interval	(2-Sided) 95%; -5.08 to -0.84
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in Daytime (6am to 10 pm) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Description	The change in daytime (6am to 10pm) mean systolic blood pressure measured at week 6 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 6.

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Placebo QD
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 6 weeks.
Measure Participants	94	101	94
Least Squares Mean (Standard Error) [mmHg]	-7.53 (1.094)	-10.40 (1.056)	-2.43 (1.096)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.09
	Confidence Interval	(2-Sided) 95%; -8.14 to -2.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-7.97
	Confidence Interval	(2-Sided) 95%; -10.96 to -4.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline in Daytime (6am to 10 pm) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Description	The change in daytime (6am to 10pm) mean diastolic blood pressure measured at week 6 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 6.

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Placebo QD
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 6 weeks.
Measure Participants	94	101	94
Least Squares Mean (Standard Error) [mmHg]	-5.08 (0.764)	-7.24 (0.738)	-1.34 (0.764)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.74
	Confidence Interval	(2-Sided) 95%; -5.86 to -1.61
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.90
	Confidence Interval	(2-Sided) 95%; -7.99 to -3.81
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline in the Nighttime (12 am to 6 am) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Description	The change in nighttime (12am to 6am) mean systolic blood pressure measured at week 6 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 6.

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Placebo QD
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 6 weeks.
Measure Participants	94	101	94
Least Squares Mean (Standard Error) [mmHg]	-7.97 (1.303)	-10.34 (1.259)	-3.06 (1.307)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.91
	Confidence Interval	(2-Sided) 95%; -8.54 to -1.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-7.27
	Confidence Interval	(2-Sided) 95%; -10.85 to -3.69
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Change From Baseline in the Nighttime (12 am to 6 am) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Description	The change in nighttime (12am to 6am) mean diastolic blood pressure measured at week 6 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 6.

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Placebo QD
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 6 weeks.
Measure Participants	94	101	94
Least Squares Mean (Standard Error) [mmHg]	-4.48 (0.950)	-7.23 (0.916)	-1.44 (0.950)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.024
	Comments	Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.05
	Confidence Interval	(2-Sided) 95%; -5.69 to -0.40
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.79
	Confidence Interval	(2-Sided) 95%; -8.39 to -3.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Change From Baseline in the 12-hr Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Description	The change in the 12-hour mean systolic blood pressure measured at week 6 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 6.

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Placebo QD
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 6 weeks.
Measure Participants	94	101	94
Least Squares Mean (Standard Error) [mmHg]	-7.70 (1.155)	-10.11 (1.114)	-2.40 (1.156)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.30
	Confidence Interval	(2-Sided) 95%; -8.52 to -2.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-7.71
	Confidence Interval	(2-Sided) 95%; -10.88 to -4.55
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Change From Baseline in the 12-hr Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Description	The change in the 12-hour mean diastolic blood pressure measured at week 6 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 6.

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Placebo QD
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 6 weeks.
Measure Participants	94	101	94
Least Squares Mean (Standard Error) [mmHg]	-5.15 (0.815)	-6.99 (0.788)	-1.34 (0.816)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.81
	Confidence Interval	(2-Sided) 95%; -6.08 to -1.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.65
	Confidence Interval	(2-Sided) 95%; -7.88 to -3.41
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Change From Baseline in the Trough (22-24-hr) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Description	The change in trough mean systolic blood pressure measured at week 6 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 6.

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Placebo QD
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 6 weeks.
Measure Participants	94	101	94
Least Squares Mean (Standard Error) [mmHg]	-7.14 (1.382)	-10.99 (1.334)	-2.28 (1.385)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.014
	Comments	Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.86
	Confidence Interval	(2-Sided) 95%; -8.72 to -1.01
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-8.71
	Confidence Interval	(2-Sided) 95%; -12.50 to -4.92
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Change From Baseline in the Trough (22-24-hr) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Description	The change in trough mean diastolic blood pressure measured at week 6 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 6.

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Placebo QD
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 6 weeks.
Measure Participants	94	101	94
Least Squares Mean (Standard Error) [mmHg]	-4.77 (1.126)	-8.28 (1.085)	-0.73 (1.125)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.012
	Comments	Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.04
	Confidence Interval	(2-Sided) 95%; -7.17 to -0.91
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-7.55
	Confidence Interval	(2-Sided) 95%; -10.63 to -4.48
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Percentage of Participants Who Achieve a Clinic Systolic Blood Pressure Response, Defined as < 140 mm Hg and/or Reduction From Baseline ≥ 20 mm Hg
Description	Percentage of participants who achieve a clinic systolic blood pressure response measured at week 6, defined as less than 140 mm Hg and/or reduction from baseline of greater than or equal to 20 mm Hg. Systolic blood pressure is the arithmetic mean of the 3 trough sitting systolic blood pressure measurements.
Time Frame	Baseline and Week 6.

Outcome Measure Data

Analysis Population Description

Full analysis set with last observation carried forward.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Placebo QD
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 6 weeks.
Measure Participants	134	130	133
Number [percentage of participants]	41.8 30.3%	37.7 27.5%	24.8 18%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments	P-value for response criteria for systolic blood pressure was from a logistic regression with treatment as a factor and baseline clinic systolic blood pressure as a covariate. The unadjusted p-value is presented.
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.15
	Confidence Interval	(2-Sided) 95%; 1.27 to 3.65
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.016
	Comments	P-value for response criteria for systolic blood pressure was from a logistic regression with treatment as a factor and baseline clinic systolic blood pressure as a covariate. The unadjusted p-value is presented.
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.93
	Confidence Interval	(2-Sided) 95%; 1.13 to 3.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Percentage of Participants Who Achieve a Clinic Diastolic Blood Pressure Response, Defined as < 90 mm Hg and/or Reduction From Baseline ≥ 10 mm Hg
Description	Percentage of participants who achieve a clinic diastolic blood pressure response measured at week 6, defined as less than 90 mm Hg and/or reduction from baseline of greater than or equal to 10 mm Hg. Diastolic blood pressure is the arithmetic mean of the 3 trough sitting diastolic blood pressure measurements.
Time Frame	Baseline and Week 6.

Outcome Measure Data

Analysis Population Description

Full analysis set with last observation carried forward.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Placebo QD
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 6 weeks.
Measure Participants	134	130	133
Number [percentage of participants]	53.0 38.4%	55.4 40.4%	39.8 28.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.018
	Comments	P-value for response criteria for diastolic blood pressure was from a logistic regression with treatment as a factor and baseline clinic diastolic blood pressure as a covariate. The unadjusted p-value is presented.
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.85
	Confidence Interval	(2-Sided) 95%; 1.11 to 3.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.015
	Comments	P-value for response criteria for diastolic blood pressure was from a logistic regression with treatment as a factor and baseline clinic diastolic blood pressure as a covariate. The unadjusted p-value is presented.
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.89
	Confidence Interval	(2-Sided) 95%; 1.13 to 3.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

Title	Percentage of Participants Who Achieve Both a Clinic Diastolic and Systolic Blood Pressure Response
Description	Percentage of participants who achieve both a clinic diastolic and systolic blood pressure response measured at week 6, defined as less than 90 mm Hg and/or reduction from baseline of greater than or equal to 10 mm Hg AND less than 140 mm Hg and/or reduction from baseline of greater than or equal to 20 mm Hg. Diastolic and systolic blood pressure is based on the arithmetic mean of the 3 sitting blood pressure measurements.
Time Frame	Baseline and Week 6.

Outcome Measure Data

Analysis Population Description

Full analysis set with last observation carried forward.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Placebo QD
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 6 weeks.
Measure Participants	134	130	133
Number [percentage of participants]	32.1 23.3%	34.6 25.3%	16.5 12%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments	P-value for joint response criteria for systolic blood pressure and diastolic blood pressure was from a logistic regression with treatment as a factor and baseline clinic systolic blood pressure as a covariate. The unadjusted p-value is presented.
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.35
	Confidence Interval	(2-Sided) 95%; 1.31 to 4.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value for joint response criteria for systolic blood pressure and diastolic blood pressure was from a logistic regression with treatment as a factor and baseline clinic systolic blood pressure as a covariate. The unadjusted p-value is presented.
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.84
	Confidence Interval	(2-Sided) 95%; 1.57 to 5.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

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		Placebo QD
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 6 weeks.		Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 6 weeks.		Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 6 weeks.
All Cause Mortality
	Azilsartan Medoxomil 40 mg QD		Azilsartan Medoxomil 80 mg QD		Placebo QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Azilsartan Medoxomil 40 mg QD		Azilsartan Medoxomil 80 mg QD		Placebo QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/137 (2.2%)		1/137 (0.7%)		0/138 (0%)
Gastrointestinal disorders
Vomiting	0/137 (0%)		1/137 (0.7%)		0/138 (0%)
Metabolism and nutrition disorders
Diabetic ketoacidosis	1/137 (0.7%)		0/137 (0%)		0/138 (0%)
Nervous system disorders
Cerebral haemorrhage	1/137 (0.7%)		0/137 (0%)		0/138 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/137 (0.7%)		0/137 (0%)		0/138 (0%)
Other (Not Including Serious) Adverse Events
	Azilsartan Medoxomil 40 mg QD		Azilsartan Medoxomil 80 mg QD		Placebo QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/137 (4.4%)		9/137 (6.6%)		3/138 (2.2%)
Nervous system disorders
Headache	6/137 (4.4%)		9/137 (6.6%)		3/138 (2.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.