Efficacy and Safety of Azilsartan Medoxomil, Once Daily (QD), Co-Administered With Amlodipine in Participants With Essential Hypertension

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00591266
• Collaborator: (none)
• Enrollment: 566
• Locations: 50
• Arms: 3
• Duration (Months): 18
• Patients Per Site: 11.3
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of azilsartan medoxomil, once daily (QD), co-administered with amlodipine in treating individuals with essential hypertension, compared to treatment with amlodipine alone.

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Drug: Azilsartan Medoxomil and amlodipine; Drug: Azilsartan Medoxomil and amlodipine; Drug: Amlodipine	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.

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, azilsartan, which is a selective antagonist of the angiotensin II type 1 receptor subtype.

Amlodipine is a slow-channel blocker that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. It is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure.

This study is being conducted to determine whether administration of azilsartan medoxomil in combination with amlodipine in participants with uncontrolled hypertension is more efficacious in reducing systolic blood pressure than amlodipine alone. Participation in this study is anticipated to be approximately 10 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 566 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 When Co-administered With Amlodipine 5 mg in Subjects With Essential Hypertension
• Study Start Date: Oct 1, 2007
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Apr 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Azilsartan Medoxomil 40 mg QD and Amlodipine 5 mg QD	Drug: Azilsartan Medoxomil and amlodipine; Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.; Other Names: Norvasc TAK-491 Edarbi
Experimental: Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD	Drug: Azilsartan Medoxomil and amlodipine; Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.; Other Names: Norvasc TAK-491 Edarbi
Active Comparator: Amlodipine 5 mg QD	Drug: Amlodipine; Azilsartan medoxomil placebo-matching tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.; Other Names: Norvasc

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. Systolic blood pressure is the arithmetic mean of the 3 trough sitting systolic blood pressure measurements.

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. Diastolic blood pressure is the arithmetic mean of the 3 trough sitting diastolic blood pressure measurements.

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-hour 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-hour 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 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.

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 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.

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 relative to baseline, 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 relative to baseline, 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 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 relative to baseline, 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. Has essential hypertension and 24-hour mean systolic blood pressure greater than or equal to 140 mm Hg and less than or equal to 180 mm Hg.

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. Has clinical laboratory evaluations within the reference range for the testing laboratory or the results are deemed not clinically significant for inclusion into this study by the investigator.

4. Is willing to discontinue current antihypertensive medications.

Exclusion Criteria:

1. Has sitting trough clinic diastolic blood pressure greater than 119 mm Hg.

2. Has a baseline 24 hour ambulatory blood pressure monitoring reading of insufficient quality.

3. The subject is hypersensitive to angiotensin II receptor blockers or calcium channel blockers.

4. Has a recent history 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.

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

7. Has secondary hypertension of any etiology

8. Is non-compliant with study medication during placebo run-in period.

9. Has severe renal dysfunction or disease.

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

11. Has a history of drug abuse or a history of 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.

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

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

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

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

17. Works night (3rd) shift.

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

19. Has any other serious disease or condition that would compromise subject safety or make it difficult to successfully manage and follow the subject according to the protocol.

20. Has been randomized in a previous TAK-491 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		Mesa	Arizona	United States
2		Phoenix	Arizona	United States
3		Anaheim	California	United States
4		Beverly Hills	California	United States
5		Burbank	California	United States
6		Burlingame	California	United States
7		La Jolla	California	United States
8		Orange	California	United States
9		Roseville	California	United States
10		Tustin	California	United States
11		Wheat Ridge	Colorado	United States
12		Newark	Delaware	United States
13		Washington	District of Columbia	United States
14		Hialeah	Florida	United States
15		Longwood	Florida	United States
16		Tampa	Florida	United States
17		Honolulu	Hawaii	United States
18		Boise	Idaho	United States
19		Chicago	Illinois	United States
20		Gurnee	Illinois	United States
21		Peoria	Illinois	United States
22		Elkhart	Indiana	United States
23		Crestview Hills	Kentucky	United States
24		Lexington	Kentucky	United States
25		Riverdale	Maryland	United States
26		Brockton	Massachusetts	United States
27		Haverhill	Massachusetts	United States
28		North Dartmouth	Massachusetts	United States
29		Kansas City	Missouri	United States
30		Omaha	Nebraska	United States
31		Raleigh	North Carolina	United States
32		Akron	Ohio	United States
33		Canton	Ohio	United States
34		Cincinnati	Ohio	United States
35		Mogadore	Ohio	United States
36		Norman	Oklahoma	United States
37		Tulsa	Oklahoma	United States
38		Warminster	Pennsylvania	United States
39		Cumberland	Rhode Island	United States
40		Arlington	Texas	United States
41		Austin	Texas	United States
42		Carrollton	Texas	United States
43		Dallas	Texas	United States
44		Houston	Texas	United States
45		Irvine	Texas	United States
46		Lake Jackson	Texas	United States
47		North Richland Hills	Texas	United States
48		Manassas	Virginia	United States
49		Renton	Washington	United States
50		Menomonee Falls	Wisconsin	United States

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: NCT00591266
• Other Study ID Numbers: 01-05-TL-491-010; U1111-1113-9132
• First Posted: Jan 11, 2008
• Last Update Posted: Jul 22, 2011
• Last Verified: Jul 1, 2011

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

Study Results

Participant Flow

Recruitment Details	Participants enrolled at 65 investigative sites in Argentina, Chile, Mexico, Peru and the United States from 03 October 2007 to 03 April 2009.
Pre-assignment Detail	Participants with uncontrolled hypertension were enrolled in one of three, once-daily (QD) treatment groups.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD	Amlodipine 5 mg QD
Arm/Group Description	Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.
Period Title: Overall Study
STARTED	189	188	189
COMPLETED	180	177	175
NOT COMPLETED	9	11	14

Baseline Characteristics

Arm/Group Title	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD	Amlodipine 5 mg QD	Total
Arm/Group Description	Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Total of all reporting groups
Overall Participants	189	188	189	566
Age (participants) [Number]
<45 years	28 14.8%	23 12.2%	15 7.9%	66 11.7%
Between 45 and 64 years	97 51.3%	111 59%	115 60.8%	323 57.1%
≥65 years	64 33.9%	54 28.7%	59 31.2%	177 31.3%
Sex: Female, Male (Count of Participants)
Female	99 52.4%	85 45.2%	95 50.3%	279 49.3%
Male	90 47.6%	103 54.8%	94 49.7%	287 50.7%

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 Amlodipine 5 mg QD	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD	Amlodipine 5 mg QD
Arm/Group Description	Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.
Measure Participants	165	166	166
Least Squares Mean (Standard Error) [mmHg]	-24.79 (0.757)	-24.51 (0.754)	-13.60 (0.754)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD, Amlodipine 5 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 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	-11.19
	Confidence Interval	(2-Sided) 95%; -13.29 to -9.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD, Amlodipine 5 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 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	-10.91
	Confidence Interval	(2-Sided) 95%; -13.00 to -8.81
	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. 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 Amlodipine 5 mg QD	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD	Amlodipine 5 mg QD
Arm/Group Description	Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.
Measure Participants	187	183	179
Least Squares Mean (Standard Error) [mmHg]	-26.96 (1.037)	-25.50 (1.048)	-15.94 (1.060)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD, Amlodipine 5 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 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	-11.02
	Confidence Interval	(2-Sided) 95%; -13.93 to -8.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD, Amlodipine 5 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 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	-9.56
	Confidence Interval	(2-Sided) 95%; -12.48 to -6.63
	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 Amlodipine 5 mg QD	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD	Amlodipine 5 mg QD
Arm/Group Description	Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.
Measure Participants	165	166	166
Least Squares Mean (Standard Error) [mmHg]	-15.26 (0.492)	-15.43 (0.490)	-7.79 (0.490)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD, Amlodipine 5 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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-7.48
	Confidence Interval	(2-Sided) 95%; -8.84 to -6.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD, Amlodipine 5 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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-7.65
	Confidence Interval	(2-Sided) 95%; -9.01 to -6.28
	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. 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 Amlodipine 5 mg QD	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD	Amlodipine 5 mg QD
Arm/Group Description	Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.
Measure Participants	187	183	179
Least Squares Mean (Standard Error) [mmHg]	-12.00 (0.602)	-12.65 (0.609)	-7.07 (0.616)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD, Amlodipine 5 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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.93
	Confidence Interval	(2-Sided) 95%; -6.62 to -3.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD, Amlodipine 5 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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.58
	Confidence Interval	(2-Sided) 95%; -7.28 to -3.88
	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 Amlodipine 5 mg QD	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD	Amlodipine 5 mg QD
Arm/Group Description	Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.
Measure Participants	165	166	166
Least Squares Mean (Standard Error) [mmHg]	-25.42 (0.802)	-24.95 (0.800)	-13.79 (0.799)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD, Amlodipine 5 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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-11.64
	Confidence Interval	(2-Sided) 95%; -13.86 to -9.41
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD, Amlodipine 5 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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-11.17
	Confidence Interval	(2-Sided) 95%; -13.39 to -8.95
	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 Amlodipine 5 mg QD	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD	Amlodipine 5 mg QD
Arm/Group Description	Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.
Measure Participants	165	166	166
Least Squares Mean (Standard Error) [mmHg]	-15.81 (0.535)	-15.86 (0.533)	-7.82 (0.533)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD, Amlodipine 5 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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-7.99
	Confidence Interval	(2-Sided) 95%; -9.47 to -6.50
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD, Amlodipine 5 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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-8.04
	Confidence Interval	(2-Sided) 95%; -9.52 to -6.55
	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 Amlodipine 5 mg QD	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD	Amlodipine 5 mg QD
Arm/Group Description	Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.
Measure Participants	165	166	166
Least Squares Mean (Standard Error) [mmHg]	-22.75 (0.853)	-22.72 (0.849)	-13.05 (0.848)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD, Amlodipine 5 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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-9.70
	Confidence Interval	(2-Sided) 95%; -12.07 to -7.34
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD, Amlodipine 5 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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-9.67
	Confidence Interval	(2-Sided) 95%; -12.03 to -7.31
	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 Amlodipine 5 mg QD	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD	Amlodipine 5 mg QD
Arm/Group Description	Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.
Measure Participants	165	166	166
Least Squares Mean (Standard Error) [mmHg]	-13.76 (0.606)	-13.78 (0.604)	-7.50 (0.604)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD, Amlodipine 5 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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-6.26
	Confidence Interval	(2-Sided) 95%; -7.94 to -4.57
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD, Amlodipine 5 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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-6.28
	Confidence Interval	(2-Sided) 95%; -7.96 to -4.60
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. 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 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 Amlodipine 5 mg QD	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD	Amlodipine 5 mg QD
Arm/Group Description	Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.
Measure Participants	165	166	166
Least Squares Mean (Standard Error) [mmHg]	-26.10 (0.850)	-25.40 (0.847)	-13.82 (0.846)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD, Amlodipine 5 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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-12.27
	Confidence Interval	(2-Sided) 95%; -14.63 to -9.92
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD, Amlodipine 5 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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-11.58
	Confidence Interval	(2-Sided) 95%; -13.93 to -9.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. 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 6.

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD	Amlodipine 5 mg QD
Arm/Group Description	Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.
Measure Participants	165	166	166
Least Squares Mean (Standard Error) [mmHg]	-16.13 (0.575)	-15.97 (0.574)	-7.74 (0.574)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD, Amlodipine 5 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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-8.39
	Confidence Interval	(2-Sided) 95%; -9.98 to -6.79
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD, Amlodipine 5 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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-8.23
	Confidence Interval	(2-Sided) 95%; -9.82 to -6.64
	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 Amlodipine 5 mg QD	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD	Amlodipine 5 mg QD
Arm/Group Description	Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.
Measure Participants	165	166	166
Least Squares Mean (Standard Error) [mmHg]	-22.60 (0.942)	-22.67 (0.938)	-13.76 (0.938)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD, Amlodipine 5 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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-8.83
	Confidence Interval	(2-Sided) 95%; -11.45 to -6.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD, Amlodipine 5 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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-8.91
	Confidence Interval	(2-Sided) 95%; -11.51 to -6.30
	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 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 Amlodipine 5 mg QD	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD	Amlodipine 5 mg QD
Arm/Group Description	Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.
Measure Participants	165	166	166
Least Squares Mean (Standard Error) [mmHg]	-14.34 (0.698)	-14.93 (0.696)	-8.39 (0.696)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD, Amlodipine 5 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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.94
	Confidence Interval	(2-Sided) 95%; -7.88 to -4.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD, Amlodipine 5 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 is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-6.54
	Confidence Interval	(2-Sided) 95%; -8.47 to -4.61
	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 relative to baseline, 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 Amlodipine 5 mg QD	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD	Amlodipine 5 mg QD
Arm/Group Description	Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.
Measure Participants	187	183	179
Number [percentage of participants]	72.7 38.5%	71.6 38.1%	45.8 24.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD, Amlodipine 5 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	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	3.37
	Confidence Interval	(2-Sided) 95%; 2.15 to 5.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD, Amlodipine 5 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	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	3.21
	Confidence Interval	(2-Sided) 95%; 2.05 to 5.03
	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 relative to baseline, 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 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 Amlodipine 5 mg QD	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD	Amlodipine 5 mg QD
Arm/Group Description	Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.
Measure Participants	187	183	179
Number [percentage of participants]	86.1 45.6%	87.4 46.5%	65.9 34.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD, Amlodipine 5 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	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	3.54
	Confidence Interval	(2-Sided) 95%; 2.08 to 6.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD, Amlodipine 5 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	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	3.90
	Confidence Interval	(2-Sided) 95%; 2.25 to 6.75
	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 relative to baseline, 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 Amlodipine 5 mg QD	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD	Amlodipine 5 mg QD
Arm/Group Description	Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.	Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.
Measure Participants	187	183	179
Number [percentage of participants]	65.8 34.8%	69.4 36.9%	43.0 22.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD, Amlodipine 5 mg 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	2.62
	Confidence Interval	(2-Sided) 95%; 1.71 to 4.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD, Amlodipine 5 mg 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	3.12
	Confidence Interval	(2-Sided) 95%; 2.01 to 4.82
	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 Amlodipine 5 mg QD		Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD		Amlodipine 5 mg QD
Arm/Group Description	Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.		Azilsartan Medoxomil 80 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.		Amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks.
All Cause Mortality
	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD		Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD		Amlodipine 5 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 Amlodipine 5 mg QD		Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD		Amlodipine 5 mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/190 (0.5%)		2/188 (1.1%)		1/185 (0.5%)
General disorders
Chest pain	0/190 (0%)		0/188 (0%)		1/185 (0.5%)
Infections and infestations
Urinary tract infection	0/190 (0%)		1/188 (0.5%)		0/185 (0%)
Nervous system disorders
Syncope	1/190 (0.5%)		0/188 (0%)		0/185 (0%)
Reproductive system and breast disorders
Ovarian cyst torsion	0/190 (0%)		1/188 (0.5%)		0/185 (0%)
Other (Not Including Serious) Adverse Events
	Azilsartan Medoxomil 40 mg QD Amlodipine 5 mg QD		Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD		Amlodipine 5 mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/190 (5.8%)		10/188 (5.3%)		10/185 (5.4%)
Nervous system disorders
Headache	11/190 (5.8%)		10/188 (5.3%)		10/185 (5.4%)

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.