Efficacy and Safety Study of Azilsartan Medoxomil Compared to Ramipril for Treating Essential Hypertension

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00760214
• Collaborator: (none)
• Enrollment: 885
• Locations: 72
• Arms: 3
• Duration (Months): 15
• Patients Per Site: 12.3
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the efficacy and safety of azilsartan medoxomil, once daily (QD), compared to ramipril for treating Essential Hypertension.

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

Detailed Description

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. Two receptors for angiotensin II have been identified. Angiotensin II type 1 receptors are located predominantly in vascular smooth muscle, where activation by angiotensin II results in vasoconstriction, hypertrophic proliferation, and inflammation. In contrast, stimulation of angiotensin II type 2 receptors by angiotensin II results in vasodilatation, antiproliferative effects that are opposite from those of angiotensin II type 1 receptor stimulation.

Drugs that modulate the renin-angiotensin-aldosterone system are used commonly worldwide for the treatment of hypertension. Of these, some block the synthesis of angiotensin II by inhibiting angiotensin-converting enzymes, while others inhibit the action of angiotensin II by binding directly to the angiotensin II type 1 receptor (called angiotensin II receptor blockers), thereby causing vasodilatation of blood vessels, resulting in a reduction in blood pressure. The effects of angiotensin II receptor blockers on other conditions in which the renin-angiotensin-aldosterone system plays a significant role, such as congestive heart failure, postmyocardial infarction management and diabetic nephropathy have also been investigated.

Although antihypertensive agents are effective at the appropriate dose, the majority have side effects that limit their use. Angiotensin-converting enzyme inhibitors are commonly associated with cough and more rarely with angioedema. Beta-blockers are associated with fatigue and erectile dysfunction, calcium antagonists with peripheral edema and diuretics with metabolic complications. As a class, angiotensin II receptor blockers generally are considered more tolerable than other classes of hypertensive agents, although there is still a need for compounds with improved tolerability and efficacy for the treatment of hypertension.

TAK-491 (azilsartan medoxomil) is an angiotensin II receptor blocker with high affinity for, and selective antagonistic activity at, the angiotensin II type 1 receptor, and is being developed for clinical use as an antihypertensive agent.

Ramipril is an angiotensin-converting enzyme inhibitor widely prescribed in Europe and Asia for the treatment of mild to moderate essential hypertension.

This study is designed to compare the efficacy and safety/tolerability of azilsartan medoxomil and ramipril for the treatment of hypertension.

Participants in this study will be seen twice during the first month, then once a month for five months. Participants will also be required to fast for 8 hours prior to each visit to the study center. Total duration of study participation is 24-weeks, plus a safety follow up phone call after the study has ended.

Study Design

• Study Type: Interventional
• Actual Enrollment: 885 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double-Blind, Randomized, Parallel-Group Study to Compare the Efficacy and Safety of TAK-491 With Ramipril in Subjects With Essential Hypertension
• Study Start Date: Jan 1, 2008
• 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 20 mg, tablets, orally, once daily for two weeks; then increased to 40 mg, tablets, orally, once daily for up to 22 weeks.; Other Names: TAK-491 Edarbi
Experimental: Azilsartan Medoxomil 80 mg QD	Drug: Azilsartan medoxomil; Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 80 mg, tablets, orally, once daily for up to 22 weeks.; Other Names: TAK-491 Edarbi
Active Comparator: Ramipril 10 mg QD	Drug: Ramipril; Ramipril 2.5 mg, tablets, orally, once daily for two weeks; then increased to 10 mg, tablets, orally, once daily for up to 22 weeks.; Other Names: Tritace Ramace Altace

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Mean Trough Clinic Sitting Systolic Blood Pressure. [Baseline and Week 24.]

   The change in mean trough clinic sitting systolic blood pressure measured at final visit or week 24 relative to baseline. Systolic blood pressure is the arithmetic mean of the 3 trough sitting systolic blood pressure measurements.

Secondary Outcome Measures

1. Change From Baseline in Mean Trough Clinic Sitting Diastolic Blood Pressure [Baseline and Week 24.]

   The change in mean trough clinic sitting diastolic blood pressure measured at final visit or week 24 relative to baseline. Diastolic blood pressure is the arithmetic mean of the 3 trough sitting diastolic blood pressure measurements.

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

   The change in 24-hour mean systolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing.

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

   The change in 24-hour mean diastolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing.

4. Change From Baseline in the 12-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring [Baseline and Week 24.]

   The change in the 12-hour mean systolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 12-hour mean is the average of all measurements recorded in the first 12 hours after dosing.

5. Change From Baseline in the 12-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring [Baseline and Week 24.]

   The change in the 12-hour mean diastolic blood pressure measured at week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 12-hour mean is the average of all measurements recorded in the first 12 hours after dosing.

6. Change From Baseline in Daytime (6am to 10 pm) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [Baseline and Week 24.]

   The change in daytime (6am to 10pm) mean systolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of all measurements recorded between the hours of 6 am and 10 pm.

7. Change From Baseline in Daytime (6am to 10 pm) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [Baseline and Week 24.]

   The change in daytime (6am to 10pm) mean diastolic blood pressure measured at week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of all measurements recorded between the hours of 6 am and 10 pm.

8. Change From Baseline in the Nighttime (12 am to 6 am) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [Baseline and Week 24.]

   The change in nighttime (12am to 6am) mean systolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of all measurements recorded between the hours of 12 am and 6 am.

9. Change From Baseline in the Nighttime (12 am to 6 am) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [Baseline and Week 24.]

   The change in nighttime (12am to 6am) mean diastolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of all measurements recorded between the hours of 12 am and 6 am.

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

    The change in trough mean systolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough mean is the average of all measurements recorded from 22 to 24 hours after dosing.

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

    The change in trough mean diastolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough mean is the average of all measurements recorded from 22 to 24 hours after dosing.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Essential hypertension (sitting systolic blood pressure between 150 and 180 mm Hg, inclusive).

2. A female participant of childbearing potential who is sexually active agrees to use adequate contraception from screening throughout the duration of the study, and cannot be pregnant.

3. Has clinical laboratory evaluations (including clinical chemistry, hematology, and complete urinalysis) within the reference range for the testing laboratory at Screening or the results are deemed not clinically significant for inclusion into this study by the investigator.

4. Is willing to discontinue current antihypertensive medications at Screening Day -21. If the participant is on amlodipine prior to screening, the participant is willing to discontinue this medication at Screening Day -28.

Exclusion Criteria:

1. Has an systolic blood pressure greater than 180 mmHg or diastolic blood pressure greater than 114 mmHg at Randomization.

2. Is taking or expected to take an excluded medication including antihypertensive agents, insulin or other agents that alter blood pressure.

3. Is hypersensitive to angiotensin II receptor blockers and/or angiotensin-converting enzyme inhibitors.

4. Has a recent history within the last 6 months of myocardial infarction, heart failure, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebrovascular accident, or transient ischemic attack.

5. Has clinically significant cardiac conduction defects (eg, third-degree atrioventricular block, left bundle branch block, sick sinus syndrome, atrial fibrillation or flutter).

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

7. Has secondary hypertension of any etiology (eg, renovascular disease, pheochromocytoma, Cushing's syndrome).

8. Is noncompliant (less than 70% or greater than 130%) with study medication during placebo run-in period.

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

10. Has known or suspected unilateral or bilateral renal artery stenosis.

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

12. Has a previous history of cancer that has not been in remission for at least 5 years prior to the first dose of study drug. (This criterion does not apply to those participants with basal cell or stage I squamous cell carcinoma of the skin).

13. Has type 1 or poorly controlled type 2 diabetes mellitus (hemoglobin A1c greater than 8.0%) or is taking insulin.

14. Has hyperkalemia as defined by the central laboratory normal reference range at Screening.

15. Has an upper arm circumference less than 24 cm or greater than 42 cm.

16. Works night (third) shift (defined as 11 PM to 7 AM).

17. Has an alanine aminotransferase level at Screening of greater than 2.5 times the upper limit of normal, active liver disease, or jaundice.

18. Is currently participating in another investigational study or has participated in an investigational study within 30 days prior to Screening.

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

20. Has been randomized in a previous azilsartan medoxomil study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Pleven		Bulgaria
2		Plovdiv		Bulgaria
3		Rouse		Bulgaria
4		Sofia		Bulgaria
5		Varna		Bulgaria
6		Paide		Estonia
7		Tallinn		Estonia
8		Tartu		Estonia
9		Viljandi		Estonia
10		Joensuu		Finland
11		Mikkeli		Finland
12		Tampere		Finland
13		Turku		Finland
14		Augsburg		Germany
15		Bad Krozingen		Germany
16		Bad Segeberg		Germany
17		Berlin		Germany
18		Dortmund		Germany
19		Dresden		Germany
20		Essen		Germany
21		Frankfurt		Germany
22		Goch		Germany
23		Grossheirath		Germany
24		Hamburg		Germany
25		Karlsruhe		Germany
26		Koeln		Germany
27		Kuenzing		Germany
28		Leipzig		Germany
29		Luebeck		Germany
30		Mannheim		Germany
31		Muenchen		Germany
32		Nuernberg		Germany
33		Siegen		Germany
34		Deurne		Netherlands
35		Ewijk		Netherlands
36		Geleen		Netherlands
37		Lichtenvoorde		Netherlands
38		Oude Pekela		Netherlands
39		Rijswijk		Netherlands
40		Roelofarendsveen		Netherlands
41		Rotterdam		Netherlands
42		Wildervank		Netherlands
43		Gdansk		Poland
44		Gniewkowo		Poland
45		Kamieniec Zabkowicki		Poland
46		Katowice		Poland
47		Libiaz		Poland
48		Lodz		Poland
49		Olawa		Poland
50		Plock		Poland
51		Poznan		Poland
52		Skierniewice		Poland
53		Tarnow		Poland
54		Moscow		Russian Federation
55		Perm		Russian Federation
56		St Petersburg		Russian Federation
57		Belgrade		Serbia
58		Niska Banja		Serbia
59		Nis		Serbia
60		Zemun		Serbia
61		Bratislava		Slovakia
62		Galanta		Slovakia
63		Levice		Slovakia
64		Lucenec		Slovakia
65		Rimavska Sobota		Slovakia
66		Boden		Sweden
67		Göteborg		Sweden
68		Luleå		Sweden
69		Lund		Sweden
70		Malmö		Sweden
71		Skene		Sweden
72		Örebro		Sweden

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Medical Director, Takeda Global Research & Development Center (Europe), Ltd.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT00760214
• Other Study ID Numbers: 01-06-TL-491-020; 2007-002583-10; U1111-1113-8982
• First Posted: Sep 26, 2008
• Last Update Posted: Nov 15, 2012
• Last Verified: Nov 1, 2012

• Keywords provided by Takeda: Essential Hypertension; Hypertension; Drug Therapy; Blood Pressure, High; Vascular Disease; Cardiovascular Disease
• Additional relevant MeSH terms: Hypertension; Essential Hypertension; Ramipril; Azilsartan medoxomil

Study Results

Participant Flow

Recruitment Details	Participants enrolled at 122 investigative sites in Bulgaria, Estonia, Finland, Germany, the Netherlands, Poland, Russia, Serbia and Montenegro, Slovakia and Sweden from 24 January 2008 to 21 April 2009.
Pre-assignment Detail	Participants with essential hypertension were enrolled in one of three, once-daily (QD) treatment groups.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Ramipril 10 mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 40 mg, tablets, orally, once daily for up to 22 weeks.	Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 80 mg, tablets, orally, once daily for up to 22 weeks.	Ramipril 2.5 mg, tablets, orally, once daily for two weeks; then increased to 10 mg, tablets, orally, once daily for up to 22 weeks.
Period Title: Overall Study
STARTED	295	294	296
COMPLETED	265	264	255
NOT COMPLETED	30	30	41

Baseline Characteristics

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Ramipril 10 mg QD	Total
Arm/Group Description	Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 40 mg, tablets, orally, once daily for up to 22 weeks.	Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 80 mg, tablets, orally, once daily for up to 22 weeks.	Ramipril 2.5 mg, tablets, orally, once daily for two weeks; then increased to 10 mg, tablets, orally, once daily for up to 22 weeks.	Total of all reporting groups
Overall Participants	295	294	295	884
Age, Customized (Number) [Number]
<45 years	40 13.6%	45 15.3%	30 10.2%	115 13%
Between 45 and 64 years	166 56.3%	168 57.1%	195 66.1%	529 59.8%
≥65 years	89 30.2%	81 27.6%	70 23.7%	240 27.1%
Sex: Female, Male (Count of Participants)
Female	136 46.1%	136 46.3%	149 50.5%	421 47.6%
Male	159 53.9%	158 53.7%	146 49.5%	463 52.4%

Outcome Measures

1. Primary 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 24 relative to baseline. Systolic blood pressure is the arithmetic mean of the 3 trough sitting systolic blood pressure measurements.
Time Frame	Baseline and Week 24.

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	Ramipril 10 mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 40 mg, tablets, orally, once daily for up to 22 weeks.	Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 80 mg, tablets, orally, once daily for up to 22 weeks.	Ramipril 2.5 mg, tablets, orally, once daily for two weeks; then increased to 10 mg, tablets, orally, once daily for up to 22 weeks.
Measure Participants	291	289	290
Least Squares Mean (Standard Error) [mmHg]	-20.63 (0.946)	-21.24 (0.949)	-12.22 (0.948)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Ramipril 10 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments	Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented. Overall 0.05 level of significance for multiple comparisons controlled using stepwise testing procedure.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-8.41
	Confidence Interval	(2-Sided) 95%; -11.04 to -5.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Ramipril 10 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments	Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented. Overall 0.05 level of significance for multiple comparisons controlled using stepwise testing procedure.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-9.03
	Confidence Interval	(2-Sided) 95%; -11.66 to -6.39
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. 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 24 relative to baseline. Diastolic blood pressure is the arithmetic mean of the 3 trough sitting diastolic blood pressure measurements.
Time Frame	Baseline and Week 24.

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	Ramipril 10 mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 40 mg, tablets, orally, once daily for up to 22 weeks.	Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 80 mg, tablets, orally, once daily for up to 22 weeks.	Ramipril 2.5 mg, tablets, orally, once daily for two weeks; then increased to 10 mg, tablets, orally, once daily for up to 22 weeks.
Measure Participants	291	289	290
Least Squares Mean (Standard Error) [mmHg]	-10.18 (0.553)	-10.54 (0.556)	-4.87 (0.555)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Ramipril 10 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments	Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.31
	Confidence Interval	(2-Sided) 95%; -6.85 to -3.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Ramipril 10 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments	Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.66
	Confidence Interval	(2-Sided) 95%; -7.21 to -4.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in 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 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing.
Time Frame	Baseline and Week 24.

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Ramipril 10 mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 40 mg, tablets, orally, once daily for up to 22 weeks.	Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 80 mg, tablets, orally, once daily for up to 22 weeks.	Ramipril 2.5 mg, tablets, orally, once daily for two weeks; then increased to 10 mg, tablets, orally, once daily for up to 22 weeks.
Measure Participants	131	135	127
Least Squares Mean (Standard Error) [mmHg]	-12.65 (1.006)	-12.29 (0.992)	-7.83 (1.022)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Ramipril 10 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments	Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.82
	Confidence Interval	(2-Sided) 95%; -7.64 to -2.01
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Ramipril 10 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments	Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.47
	Confidence Interval	(2-Sided) 95%; -7.27 to -1.66
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in 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 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing.
Time Frame	Baseline and Week 24.

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Ramipril 10 mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 40 mg, tablets, orally, once daily for up to 22 weeks.	Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 80 mg, tablets, orally, once daily for up to 22 weeks.	Ramipril 2.5 mg, tablets, orally, once daily for two weeks; then increased to 10 mg, tablets, orally, once daily for up to 22 weeks.
Measure Participants	131	135	127
Least Squares Mean (Standard Error) [mmHg]	-8.03 (0.655)	-8.32 (0.646)	-5.26 (0.666)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Ramipril 10 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments	Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.77
	Confidence Interval	(2-Sided) 95%; -4.61 to -0.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Ramipril 10 mg 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 presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.06
	Confidence Interval	(2-Sided) 95%; -4.89 to -1.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in the 12-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring
Description	The change in the 12-hour mean systolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 12-hour mean is the average of all measurements recorded in the first 12 hours after dosing.
Time Frame	Baseline and Week 24.

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Ramipril 10 mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 40 mg, tablets, orally, once daily for up to 22 weeks.	Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 80 mg, tablets, orally, once daily for up to 22 weeks.	Ramipril 2.5 mg, tablets, orally, once daily for two weeks; then increased to 10 mg, tablets, orally, once daily for up to 22 weeks.
Measure Participants	131	135	127
Least Squares Mean (Standard Error) [mmHg]	-12.06 (1.103)	-11.71 (1.087)	-8.28 (1.121)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Ramipril 10 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.017
	Comments	Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.77
	Confidence Interval	(2-Sided) 95%; -6.87 to -0.68
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Ramipril 10 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.029
	Comments	Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.43
	Confidence Interval	(2-Sided) 95%; -6.50 to -0.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline in the 12-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring
Description	The change in the 12-hour mean diastolic blood pressure measured at week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 12-hour mean is the average of all measurements recorded in the first 12 hours after dosing.
Time Frame	Baseline and Week 24.

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Ramipril 10 mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 40 mg, tablets, orally, once daily for up to 22 weeks.	Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 80 mg, tablets, orally, once daily for up to 22 weeks.	Ramipril 2.5 mg, tablets, orally, once daily for two weeks; then increased to 10 mg, tablets, orally, once daily for up to 22 weeks.
Measure Participants	131	135	127
Least Squares Mean (Standard Error) [mmHg]	-7.71 (0.743)	-8.07 (0.732)	-5.65 (0.755)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Ramipril 10 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.052
	Comments	Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.06
	Confidence Interval	(2-Sided) 95%; -4.15 to 0.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Ramipril 10 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.022
	Comments	Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.42
	Confidence Interval	(2-Sided) 95%; -4.49 to -0.35
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. 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 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of all measurements recorded between the hours of 6 am and 10 pm.
Time Frame	Baseline and Week 24.

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Ramipril 10 mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 40 mg, tablets, orally, once daily for up to 22 weeks.	Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 80 mg, tablets, orally, once daily for up to 22 weeks.	Ramipril 2.5 mg, tablets, orally, once daily for two weeks; then increased to 10 mg, tablets, orally, once daily for up to 22 weeks.
Measure Participants	131	135	127
Least Squares Mean (Standard Error) [mmHg]	-12.61 (1.047)	-12.35 (1.032)	-8.08 (1.064)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Ramipril 10 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments	Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.53
	Confidence Interval	(2-Sided) 95%; -7.46 to -1.59
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Ramipril 10 mg 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 presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.26
	Confidence Interval	(2-Sided) 95%; -7.18 to -1.35
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. 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 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of all measurements recorded between the hours of 6 am and 10 pm.
Time Frame	Baseline and Week 24.

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Ramipril 10 mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 40 mg, tablets, orally, once daily for up to 22 weeks.	Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 80 mg, tablets, orally, once daily for up to 22 weeks.	Ramipril 2.5 mg, tablets, orally, once daily for two weeks; then increased to 10 mg, tablets, orally, once daily for up to 22 weeks.
Measure Participants	131	135	127
Least Squares Mean (Standard Error) [mmHg]	-8.19 (0.700)	-8.53 (0.689)	-5.55 (0.711)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Ramipril 10 mg 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 presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.64
	Confidence Interval	(2-Sided) 95%; -4.60 to -0.68
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Ramipril 10 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments	Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.98
	Confidence Interval	(2-Sided) 95%; -4.93 to -1.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Change From Baseline in the Nighttime (12 am to 6 am) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Description	The change in nighttime (12am to 6am) mean systolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of all measurements recorded between the hours of 12 am and 6 am.
Time Frame	Baseline and Week 24.

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Ramipril 10 mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 40 mg, tablets, orally, once daily for up to 22 weeks.	Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 80 mg, tablets, orally, once daily for up to 22 weeks.	Ramipril 2.5 mg, tablets, orally, once daily for two weeks; then increased to 10 mg, tablets, orally, once daily for up to 22 weeks.
Measure Participants	130	135	127
Least Squares Mean (Standard Error) [mmHg]	-12.82 (1.135)	-12.69 (1.115)	-6.87 (1.147)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Ramipril 10 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments	Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.95
	Confidence Interval	(2-Sided) 95%; -9.12 to -2.77
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Ramipril 10 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments	Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.82
	Confidence Interval	(2-Sided) 95%; -8.96 to -2.67
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Change From Baseline in the Nighttime (12 am to 6 am) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Description	The change in nighttime (12am to 6am) mean diastolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of all measurements recorded between the hours of 12 am and 6 am.
Time Frame	Baseline and Week 24.

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Ramipril 10 mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 40 mg, tablets, orally, once daily for up to 22 weeks.	Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 80 mg, tablets, orally, once daily for up to 22 weeks.	Ramipril 2.5 mg, tablets, orally, once daily for two weeks; then increased to 10 mg, tablets, orally, once daily for up to 22 weeks.
Measure Participants	130	135	127
Least Squares Mean (Standard Error) [mmHg]	-7.44 (0.764)	-8.20 (0.750)	-4.43 (0.773)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Ramipril 10 mg 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 presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.01
	Confidence Interval	(2-Sided) 95%; -5.15 to -0.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Ramipril 10 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments	Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.77
	Confidence Interval	(2-Sided) 95%; -5.89 to -1.65
	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 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough mean is the average of all measurements recorded from 22 to 24 hours after dosing.
Time Frame	Baseline and Week 24.

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Ramipril 10 mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 40 mg, tablets, orally, once daily for up to 22 weeks.	Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 80 mg, tablets, orally, once daily for up to 22 weeks.	Ramipril 2.5 mg, tablets, orally, once daily for two weeks; then increased to 10 mg, tablets, orally, once daily for up to 22 weeks.
Measure Participants	130	135	127
Least Squares Mean (Standard Error) [mmHg]	-15.60 (1.172)	-14.93 (1.151)	-6.73 (1.186)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Ramipril 10 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments	Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-8.87
	Confidence Interval	(2-Sided) 95%; -12.15 to -5.60
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Ramipril 10 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments	Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-8.20
	Confidence Interval	(2-Sided) 95%; -11.46 to -4.95
	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 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough mean is the average of all measurements recorded from 22 to 24 hours after dosing.
Time Frame	Baseline and Week 24.

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Ramipril 10 mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 40 mg, tablets, orally, once daily for up to 22 weeks.	Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 80 mg, tablets, orally, once daily for up to 22 weeks.	Ramipril 2.5 mg, tablets, orally, once daily for two weeks; then increased to 10 mg, tablets, orally, once daily for up to 22 weeks.
Measure Participants	130	135	127
Least Squares Mean (Standard Error) [mmHg]	-10.21 (0.898)	-9.85 (0.883)	-4.53 (0.909)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Ramipril 10 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments	Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.68
	Confidence Interval	(2-Sided) 95%; -8.19 to -3.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Ramipril 10 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments	Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). Unadjusted p-value presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.32
	Confidence Interval	(2-Sided) 95%; -7.81 to -2.82
	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		Ramipril 10 mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 40 mg, tablets, orally, once daily for up to 22 weeks.		Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 80 mg, tablets, orally, once daily for up to 22 weeks.		Ramipril 2.5 mg, tablets, orally, once daily for two weeks; then increased to 10 mg, tablets, orally, once daily for up to 22 weeks.
All Cause Mortality
	Azilsartan Medoxomil 40 mg QD		Azilsartan Medoxomil 80 mg QD		Ramipril 10 mg QD
	Affected / at Risk (%)	# 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		Ramipril 10 mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/294 (2.7%)		12/293 (4.1%)		6/293 (2%)
Cardiac disorders
Atrial fibrillation	1/294 (0.3%)		2/293 (0.7%)		1/293 (0.3%)
Acute coronary syndrome	0/294 (0%)		0/293 (0%)		1/293 (0.3%)
Angina pectoris	0/294 (0%)		1/293 (0.3%)		0/293 (0%)
Congenital, familial and genetic disorders
Hydrocele	0/294 (0%)		1/293 (0.3%)		0/293 (0%)
Eye disorders
Cataract	1/294 (0.3%)		0/293 (0%)		0/293 (0%)
Retinal detachment	0/294 (0%)		1/293 (0.3%)		0/293 (0%)
Gastrointestinal disorders
Salivary gland calculus	0/294 (0%)		1/293 (0.3%)		0/293 (0%)
Infections and infestations
Appendicitis	1/294 (0.3%)		0/293 (0%)		1/293 (0.3%)
Hepatitis C	1/294 (0.3%)		0/293 (0%)		1/293 (0.3%)
Urosepsis	1/294 (0.3%)		0/293 (0%)		1/293 (0.3%)
Upper respiratory tract infection	0/294 (0%)		1/293 (0.3%)		0/293 (0%)
Injury, poisoning and procedural complications
Ankle fracture	1/294 (0.3%)		0/293 (0%)		0/293 (0%)
Fall	0/294 (0%)		0/293 (0%)		1/293 (0.3%)
Road traffic accident	0/294 (0%)		1/293 (0.3%)		0/293 (0%)
Metabolism and nutrition disorders
Hyperkalaemia	0/294 (0%)		1/293 (0.3%)		0/293 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant	1/294 (0.3%)		0/293 (0%)		0/293 (0%)
Renal cancer	0/294 (0%)		1/293 (0.3%)		0/293 (0%)
Nervous system disorders
Cerebral ischaemia	0/294 (0%)		1/293 (0.3%)		0/293 (0%)
Epilepsy	0/294 (0%)		0/293 (0%)		1/293 (0.3%)
Grand mal convulsion	1/294 (0.3%)		0/293 (0%)		0/293 (0%)
Ischaemic stroke	0/294 (0%)		1/293 (0.3%)		0/293 (0%)
Syncope	0/294 (0%)		1/293 (0.3%)		0/293 (0%)
Respiratory, thoracic and mediastinal disorders
Laryngeal oedema	0/294 (0%)		1/293 (0.3%)		0/293 (0%)
Other (Not Including Serious) Adverse Events
	Azilsartan Medoxomil 40 mg QD		Azilsartan Medoxomil 80 mg QD		Ramipril 10 mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/294 (7.5%)		16/293 (5.5%)		36/293 (12.3%)
Infections and infestations
Nasopharyngitis	19/294 (6.5%)		13/293 (4.4%)		17/293 (5.8%)
Respiratory, thoracic and mediastinal disorders
Cough	3/294 (1%)		4/293 (1.4%)		24/293 (8.2%)

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.