Efficacy and Safety Comparison of Azilsartan Medoxomil to Valsartan in Participants With Essential Hypertension

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00591578
• Collaborator: (none)
• Enrollment: 984
• Locations: 88
• Arms: 3
• Duration (Months): 27
• Patients Per Site: 11.2
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the efficacy and safety of TAK-491 (azilsartan medoxomil), once daily (QD), to valsartan in participants with essential hypertension.

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Drug: Azilsartan Medoxomil; Drug: Azilsartan Medoxomil; Drug: Valsartan	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 (WHO), 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.

This study is being conducted to determine whether administration of azilsartan medoxomil in subjects with essential hypertension is more efficacious in reducing systolic blood pressure than valsartan.

Study participation is anticipated to be approximately 7 months. Outside of the study center, participants will be required to wear an ambulatory blood pressure monitoring device at 24 hour intervals.

Following completion of the 6-month double-blind treatment period, all available subjects will be offered the option to continue in a 28-week extension study with open-label azilsartan medoxomil 40 mg.

For the extension study, participants will take azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 28 weeks. Hydrochlorothiazide 12.5 mg or 25 mg or any other antihypertensive (except angiotensin II receptor blockers) may be added in a step-wise fashion to maintain blood pressure within target <140/90 mmHg for non-diabetic subjects and <130/80 mmHg for diabetic subjects

Study Design

• Study Type: Interventional
• Actual Enrollment: 984 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 Valsartan in Subjects With Essential Hypertension
• Study Start Date: Dec 1, 2007
• Actual Primary Completion Date: Sep 1, 2009
• Actual Study Completion Date: Mar 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Azilsartan Medoxomil 40 mg QD	Drug: Azilsartan Medoxomil; Azilsartan Medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated 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 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks.; Other Names: TAK-491 Edarbi
Active Comparator: Valsartan 320 mg QD	Drug: Valsartan; Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.; Other Names: Diovan

Outcome Measures

Primary Outcome Measures

1. 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.

Secondary 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.

2. Change From Baseline in the 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.

3. 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 systolic 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 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.

5. 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 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.

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 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.

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 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.

8. 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.

9. 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 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.

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.

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 24.]

    Percentage of participants who achieve a clinic systolic blood pressure response measured at week 24, 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 24.]

    Percentage of participants who achieve a clinic diastolic blood pressure response measured at week 24, defined as less than 90 mm Hg and/or reduction from baseline of greater than or equal to 10 mm Hg. Diastolic blood pressure is the arithmetic mean of the 3 trough sitting diastolic blood pressure measurements.

14. Percentage of Participants Who Achieve Both a Clinic Diastolic and Systolic Blood Pressure Response. [Baseline and Week 24.]

    Percentage of participants who achieve both a clinic diastolic and systolic blood pressure response measured at week 24, 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. Essential hypertension (defined as sitting trough clinic systolic blood pressure between 150 and 180 mm Hg inclusive at Day minus 1 and 24-hour mean systolic blood pressure between 130 and 170 mm Hg inclusive at Day 1).

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

3. Clinical laboratory evaluations (including clinical chemistry, hematology, and complete urinalysis) 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. Willing to discontinue current antihypertensive medications at the Screening Day minus 21 visit. If the subject is on amlodipine prior to Screening, the subject is willing to discontinue this medication at Screening Day minus 28.

Exclusion Criteria

1. Sitting trough clinic diastolic blood pressure greater than 114 mm Hg at Day minus 1.

2. The subject has a baseline 24-hour ambulatory blood pressure monitor reading of insufficient quality.

3. 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.

4. Hypersensitive to angiotensin II receptor blockers.

5. 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.

6. Clinically significant cardiac conduction defects (eg, 3rd degree atrioventricular block, left bundle branch block, sick sinus syndrome, atrial fibrillation or flutter).

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

8. Secondary hypertension of any etiology.

9. Non-compliant (less than 70% or greater than 130%) with study medication during placebo run-in period.

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

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

12. History of drug or alcohol abuse within the past 2 years.

13. 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 subjects with basal cell or Stage 1 squamous cell carcinoma of the skin).

14. Type 1 or poorly controlled type 2 diabetes mellitus (glycosylated hemoglobin greater than 8.0%) at Screening.

15. Hyperkalemia as defined by the central laboratory normal reference range at Screening.

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

17. Works night (3rd) shift (defined as 11PM to 7AM).

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

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

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

21. Randomized in a previous azilsartan medoxomil study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Huntsville	Alabama	United States
2		Glendale	Arizona	United States
3		Phoenix	Arizona	United States
4		Scottsdale	Arizona	United States
5		Tuscon	Arizona	United States
6		Beverly Hills	California	United States
7		Burbank	California	United States
8		La Jolla	California	United States
9		Long Beach	California	United States
10		Los Angeles	California	United States
11		Paramount	California	United States
12		San Diego	California	United States
13		Santa Monica	California	United States
14		Spring Valley	California	United States
15		Tustin	California	United States
16		Vista	California	United States
17		Westlake Village	California	United States
18		Ridgefield	Connecticut	United States
19		Newark	Delaware	United States
20		Washington	District of Columbia	United States
21		DeLand	Florida	United States
22		Fort Lauderdale	Florida	United States
23		Hollywood	Florida	United States
24		Inverness	Florida	United States
25		Jacksonville	Florida	United States
26		Boise	Idaho	United States
27		Chicago	Illinois	United States
28		Gurnee	Illinois	United States
29		Morton	Illinois	United States
30		Park Ridge	Illinois	United States
31		Avon	Indiana	United States
32		Bloomington	Indiana	United States
33		Crestview Hills	Kentucky	United States
34		Baltimore	Maryland	United States
35		Columbia	Maryland	United States
36		Brockton	Massachusetts	United States
37		West Yarmouth	Massachusetts	United States
38		Ann Arbor	Michigan	United States
39		Florissant	Missouri	United States
40		Kansas City	Missouri	United States
41		St. Peters	Missouri	United States
42		Washington	Missouri	United States
43		Wentzville	Missouri	United States
44		Charlotte	North Carolina	United States
45		Salisbury	North Carolina	United States
46		Shelby	North Carolina	United States
47		Cincinnati	Ohio	United States
48		Delaware	Ohio	United States
49		Mogadore	Ohio	United States
50		Willoughby Hills	Ohio	United States
51		Zanesville	Ohio	United States
52		Oklahoma City	Oklahoma	United States
53		Eugene	Oregon	United States
54		Portland	Oregon	United States
55		Bridgeville	Pennsylvania	United States
56		Downingtown	Pennsylvania	United States
57		Jenkintown	Pennsylvania	United States
58		Lansdale	Pennsylvania	United States
59		Charleston	South Carolina	United States
60		Spartanburg	South Carolina	United States
61		Kingsport	Tennessee	United States
62		Austin	Texas	United States
63		Dallas	Texas	United States
64		Fort Worth	Texas	United States
65		Houston	Texas	United States
66		Pearland	Texas	United States
67		Rosenberg	Texas	United States
68		San Antonio	Texas	United States
69		Riverton	Utah	United States
70		Salt Lake City	Utah	United States
71		West Jordan	Utah	United States
72		Arlington	Virginia	United States
73		Burke	Virginia	United States
74		Norfolk	Virginia	United States
75		Lakewood	Washington	United States
76		Port Richard	Washington	United States
77		Menomonee Falls	Wisconsin	United States
78		Santiago		Chile
79		Temuco		Chile
80		Cabo San Lucas		Mexico
81		Colonia Escandon		Mexico
82		Culiacan		Mexico
83		Mexico City		Mexico
84		Monterrey Nuevo Leon		Mexico
85		Morelia		Mexico
86		Queretaro		Mexico
87		Chiclayo		Peru
88		Lima		Peru

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Executive Medical Director Clinical Science, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT00591578
• Other Study ID Numbers: TAK-491_301; U1111-1113-9238
• First Posted: Jan 11, 2008
• Last Update Posted: Feb 2, 2012
• Last Verified: Jan 1, 2012

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

Study Results

Participant Flow

Recruitment Details	Participants enrolled at 103 investigative sites from 09 November 2007 to 03 September 2009 (double-blind phase) and 04 March 2009 to 13 March 2010 (open-label extension phase). A total of 984 participants were randomized into the double-blind treatment phase, of which 170 participants entered into the open-label extension phase.
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	Valsartan 320 mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks. Open Label Extension: At Week 24/completion of the double-blind treatment phase, participants could elect to continue in 28 week, open-label extension (OLE) phase. All participants who elected to participate in the OLE phase initiated treatment with azilsartan medoxomil 40 mg, tablets, orally, independent of their double-blind treatment assignment. Investigators may have added, in a step-wise fashion, hydrochlorothiazide 12.5 mg, followed by hydrochlorothiazide 25 mg, followed by other antihypertensive medications (except angiotensin II receptor blockers) as needed to achieve target blood pressure (<140/90 mm Hg or <130/80 mm Hg for diabetics).	Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks. Open Label Extension: At Week 24/completion of the double-blind treatment phase, participants could elect to continue in 28 week, open-label extension (OLE) phase. All participants who elected to participate in the OLE phase initiated treatment with azilsartan medoxomil 40 mg, tablets, orally, independent of their double-blind treatment assignment. Investigators may have added, in a step-wise fashion, hydrochlorothiazide 12.5 mg, followed by hydrochlorothiazide 25 mg, followed by other antihypertensive medications (except angiotensin II receptor blockers) as needed to achieve target blood pressure (<140/90 mm Hg or <130/80 mm Hg for diabetics).	Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks. Open Label Extension: At Week 24/completion of the double-blind treatment phase, participants could elect to continue in 28 week, open-label extension (OLE) phase. All participants who elected to participate in the OLE phase initiated treatment with azilsartan medoxomil 40 mg, tablets, orally, independent of their double-blind treatment assignment. Investigators may have added, in a step-wise fashion, hydrochlorothiazide 12.5 mg, followed by hydrochlorothiazide 25 mg, followed by other antihypertensive medications (except angiotensin II receptor blockers) as needed to achieve target blood pressure (<140/90 mm Hg or <130/80 mm Hg for diabetics).
Period Title: Double-Blind Treatment Phase
STARTED	327	329	328
COMPLETED	249	249	244
NOT COMPLETED	78	80	84
Period Title: Double-Blind Treatment Phase
STARTED	55	115	0
COMPLETED	49	105	0
NOT COMPLETED	6	10	0

Baseline Characteristics

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Valsartan 320 mg QD	Total
Arm/Group Description	Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks. Open Label Extension: Azilsartan medoxomil 40 mg, tablets, orally, once daily for 28 weeks. Investigators may have added, in a step-wise fashion, hydrochlorothiazide 12.5 mg, followed by hydrochlorothiazide 25 mg, followed by other antihypertensive medications (except angiotensin II receptor blockers) as needed to achieve target blood pressure (<140/90 mm Hg or <130/80 mm Hg for diabetics). Open Label Extension: Azilsartan medoxomil 40 mg, tablets, orally, once daily for 28 weeks. Investigators may have added, in a step-wise fashion, hydrochlorothiazide 12.5 mg, followed by hydrochlorothiazide 25 mg, followed by other antihypertensive medications (except angiotensin II receptor blockers) as needed to achieve target blood pressure (<140/90 mm Hg or <130/80 mm Hg for diabetics).	Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks. Open Label Extension: Azilsartan medoxomil 40 mg, tablets, orally, once daily for 28 weeks. Investigators may have added, in a step-wise fashion, hydrochlorothiazide 12.5 mg, followed by hydrochlorothiazide 25 mg, followed by other antihypertensive medications (except angiotensin II receptor blockers) as needed to achieve target blood pressure (<140/90 mm Hg or <130/80 mm Hg for diabetics). Open Label Extension: Azilsartan medoxomil 40 mg, tablets, orally, once daily for 28 weeks. Investigators may have added, in a step-wise fashion, hydrochlorothiazide 12.5 mg, followed by hydrochlorothiazide 25 mg, followed by other antihypertensive medications (except angiotensin II receptor blockers) as needed to achieve target blood pressure (<140/90 mm Hg or <130/80 mm Hg for diabetics).	Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks. Open Label Extension: Azilsartan medoxomil 40 mg, tablets, orally, once daily for 28 weeks. Investigators may have added, in a step-wise fashion, hydrochlorothiazide 12.5 mg, followed by hydrochlorothiazide 25 mg, followed by other antihypertensive medications (except angiotensin II receptor blockers) as needed to achieve target blood pressure (<140/90 mm Hg or <130/80 mm Hg for diabetics).	Total of all reporting groups
Overall Participants	327	329	328	984
Age, Customized (participants) [Number]
<45 years (Double Blind Phase)	43 13.1%	39 11.9%	31 9.5%	113 11.5%
Between 45 and 64 years (Double Blind Phase)	181 55.4%	208 63.2%	199 60.7%	588 59.8%
≥65 years (Double Blind Phase)	103 31.5%	82 24.9%	98 29.9%	283 28.8%
<45 years (Open Label Phase)	10 3.1%	8 2.4%	0 0%	18 1.8%
Between 45 and 64 years (Open Label Phase)	25 7.6%	68 20.7%	0 0%	93 9.5%
≥65 years (Open Label Phase)	20 6.1%	39 11.9%	0 0%	59 6%
Sex/Gender, Customized (participants) [Number]
Female (Double Blind Phase)	163 49.8%	160 48.6%	152 46.3%	475 48.3%
Male (Double Blind Phase)	164 50.2%	169 51.4%	176 53.7%	509 51.7%
Female (Open Label Phase)	34 10.4%	57 17.3%	0 0%	91 9.2%
Male (Open Label Phase)	21 6.4%	58 17.6%	0 0%	79 8%

Outcome Measures

1. Primary 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 with last observation carried forward.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Valsartan 320 mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks.	Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks.	Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.
Measure Participants	284	271	277
Least Squares Mean (Standard Error) [mmHg]	-14.93 (0.698)	-15.32 (0.715)	-11.29 (0.707)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Valsartan 320 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. 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	-3.64
	Confidence Interval	(2-Sided) 95%; -5.59 to -1.69
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Valsartan 320 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	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	-4.03
	Confidence Interval	(2-Sided) 95%; -6.01 to -2.06
	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 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	Valsartan 320 mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks.	Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks.	Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.
Measure Participants	323	311	322
Least Squares Mean (Standard Error) [mmHg]	-14.86 (0.948)	-16.92 (0.966)	-11.59 (0.949)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Valsartan 320 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.015
	Comments	Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). The unadjusted p-value is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.27
	Confidence Interval	(2-Sided) 95%; -5.90 to -0.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Valsartan 320 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). The unadjusted p-value is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.34
	Confidence Interval	(2-Sided) 95%; -8.00 to -2.68
	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 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 with last observation carried forward.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Valsartan 320 mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks.	Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks.	Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.
Measure Participants	284	271	277
Least Squares Mean (Standard Error) [mmHg]	-9.23 (0.459)	-9.77 (0.470)	-7.07 (0.465)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Valsartan 320 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). The unadjusted p-value is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.16
	Confidence Interval	(2-Sided) 95%; -3.44 to -0.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Valsartan 320 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). The unadjusted p-value is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.69
	Confidence Interval	(2-Sided) 95%; -3.99 to -1.40
	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 24 relative to baseline. Diastolic 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	Valsartan 320 mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks.	Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks.	Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.
Measure Participants	323	311	322
Least Squares Mean (Standard Error) [mmHg]	-7.16 (0.554)	-7.41 (0.565)	-4.65 (0.555)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Valsartan 320 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). The unadjusted p-value is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.52
	Confidence Interval	(2-Sided) 95%; -4.06 to -0.98
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Valsartan 320 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). The unadjusted p-value is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.76
	Confidence Interval	(2-Sided) 95%; -4.32 to -1.21
	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 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 with last observation carried forward.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Valsartan 320 mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks.	Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks.	Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.
Measure Participants	284	271	277
Least Squares Mean (Standard Error) [mmHg]	-15.39 (0.732)	-15.80 (0.749)	-11.91 (0.741)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Valsartan 320 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). The unadjusted p-value is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.49
	Confidence Interval	(2-Sided) 95%; -5.53 to -1.44
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Valsartan 320 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). The unadjusted p-value is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.90
	Confidence Interval	(2-Sided) 95%; -5.96 to -1.83
	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 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 with last observation carried forward.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Valsartan 320 mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks.	Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks.	Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.
Measure Participants	284	271	277
Least Squares Mean (Standard Error) [mmHg]	-9.61 (0.493)	-10.11 (0.504)	-7.44 (0.499)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Valsartan 320 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). The unadjusted p-value is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.17
	Confidence Interval	(2-Sided) 95%; -3.54 to -0.79
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Valsartan 320 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). The unadjusted p-value is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.67
	Confidence Interval	(2-Sided) 95%; -4.06 to -1.28
	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 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 with last observation carried forward.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Valsartan 320 mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks.	Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks.	Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.
Measure Participants	284	271	277
Least Squares Mean (Standard Error) [mmHg]	-13.31 (0.777)	-13.95 (0.795)	-9.52 (0.786)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Valsartan 320 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). The unadjusted p-value is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.79
	Confidence Interval	(2-Sided) 95%; -5.96 to -1.62
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Valsartan 320 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). The unadjusted p-value is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.44
	Confidence Interval	(2-Sided) 95%; -6.63 to -2.24
	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 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 with last observation carried forward.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Valsartan 320 mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks.	Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks.	Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.
Measure Participants	284	271	277
Least Squares Mean (Standard Error) [mmHg]	-8.06 (0.526)	-8.90 (0.539)	-6.06 (0.533)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Valsartan 320 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). The unadjusted p-value is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.00
	Confidence Interval	(2-Sided) 95%; -3.48 to -0.53
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Valsartan 320 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). The unadjusted p-value is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.84
	Confidence Interval	(2-Sided) 95%; -4.33 to -1.35
	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 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 with last observation carried forward.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Valsartan 320 mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks.	Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks.	Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.
Measure Participants	284	271	277
Least Squares Mean (Standard Error) [mmHg]	-15.64 (0.764)	-16.20 (0.782)	-12.20 (0.774)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Valsartan 320 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). The unadjusted p-value is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.44
	Confidence Interval	(2-Sided) 95%; -5.57 to -1.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Valsartan 320 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). The unadjusted p-value is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.01
	Confidence Interval	(2-Sided) 95%; -6.16 to -1.85
	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 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 with last observation carried forward.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Valsartan 320 mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks.	Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks.	Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.
Measure Participants	284	271	277
Least Squares Mean (Standard Error) [mmHg]	-9.70 (0.522)	-10.26 (0.534)	-7.53 (0.528)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Valsartan 320 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). The unadjusted p-value is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.18
	Confidence Interval	(2-Sided) 95%; -3.63 to -0.72
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Valsartan 320 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). The unadjusted p-value is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.73
	Confidence Interval	(2-Sided) 95%; -4.20 to -1.25
	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 with last observation carried forward.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Valsartan 320 mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks.	Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks.	Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.
Measure Participants	284	271	277
Least Squares Mean (Standard Error) [mmHg]	-13.74 (0.851)	-13.83 (0.871)	-10.36 (0.861)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Valsartan 320 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments	Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). The unadjusted p-value is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.38
	Confidence Interval	(2-Sided) 95%; -5.76 to -1.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Valsartan 320 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments	Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). The unadjusted p-value is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.47
	Confidence Interval	(2-Sided) 95%; -5.87 to -1.06
	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 with last observation carried forward.

Arm/Group Title	Azilsartan Medoxomil 40 mg QD	Azilsartan Medoxomil 80 mg QD	Valsartan 320 mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks.	Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks.	Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.
Measure Participants	284	271	277
Least Squares Mean (Standard Error) [mmHg]	-9.37 (0.617)	-9.65 (0.632)	-7.06 (0.625)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Valsartan 320 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.009
	Comments	Postbaseline P-value was from ANCOVA with terms for treatment (as a factor) and baseline value (as a covariate). The unadjusted p-value is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.31
	Confidence Interval	(2-Sided) 95%; -4.04 to -0.59
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Valsartan 320 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). The unadjusted p-value is presented.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.59
	Confidence Interval	(2-Sided) 95%; -4.34 to -0.84
	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 24, 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 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	Valsartan 320 mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks.	Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks.	Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.
Measure Participants	323	311	322
Number [percentage of participants]	56.0 17.1%	59.2 18%	46.9 14.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Valsartan 320 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.016
	Comments	P-value for response criteria for systolic blood pressure was from a logistic regression with treatment as a factor and baseline clinic systolic blood pressure as a covariate. The unadjusted p-value is presented.
	Method	Regression, Logistic
	Comments	Includes only those participants with a baseline and at least one post-baseline value.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.46
	Confidence Interval	(2-Sided) 95%; 1.07 to 2.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Valsartan 320 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	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	Includes only those participants with a baseline and at least one post-baseline value.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.63
	Confidence Interval	(2-Sided) 95%; 1.19 to 2.23
	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 24, defined as less than 90 mm Hg and/or reduction from baseline of greater than or equal to 10 mm Hg. Diastolic blood pressure is the arithmetic mean of the 3 trough sitting diastolic blood pressure measurements.
Time Frame	Baseline and Week 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	Valsartan 320 mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks.	Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks.	Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.
Measure Participants	323	311	322
Number [percentage of participants]	72.4 22.1%	74.0 22.5%	65.8 20.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Valsartan 320 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.041
	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	Includes only those participants with a baseline and at least one post-baseline value.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.46
	Confidence Interval	(2-Sided) 95%; 1.02 to 2.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Valsartan 320 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.015
	Comments	P-value for response criteria for diastolic blood pressure was from a logistic regression with treatment as a factor and baseline clinic diastolic blood pressure as a covariate. The unadjusted p-value is presented.
	Method	Regression, Logistic
	Comments	Includes only those participants with a baseline and at least one post-baseline value.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.58
	Confidence Interval	(2-Sided) 95%; 1.09 to 2.28
	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 24, 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 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	Valsartan 320 mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks.	Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks.	Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.
Measure Participants	323	311	322
Number [percentage of participants]	50.2 15.4%	54.7 16.6%	41.3 12.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40 mg QD, Valsartan 320 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.018
	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	Includes only those participants with a baseline and at least one post-baseline value.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.46
	Confidence Interval	(2-Sided) 95%; 1.07 to 1.99
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 80 mg QD, Valsartan 320 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	Includes only those participants with a baseline and at least one post-baseline value.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.70
	Confidence Interval	(2-Sided) 95%; 1.24 to 2.33
	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		Valsartan 320 mg QD		Open Label Extension
Arm/Group Description	Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks. Open Label Extension: At Week 24/completion of the double-blind treatment phase, participants could elect to continue in 28 week, open-label extension (OLE) phase. All participants who elected to participate in the OLE phase initiated treatment with azilsartan medoxomil 40 mg, tablets, orally, independent of their double-blind treatment assignment. Investigators may have added, in a step-wise fashion, hydrochlorothiazide 12.5 mg, followed by hydrochlorothiazide 25 mg, followed by other antihypertensive medications (except angiotensin II receptor blockers) as needed to achieve target blood pressure (<140/90 mm Hg or <130/80 mm Hg for diabetics).		Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks. Open Label Extension: At Week 24/completion of the double-blind treatment phase, participants could elect to continue in 28 week, open-label extension (OLE) phase. All participants who elected to participate in the OLE phase initiated treatment with azilsartan medoxomil 40 mg, tablets, orally, independent of their double-blind treatment assignment. Investigators may have added, in a step-wise fashion, hydrochlorothiazide 12.5 mg, followed by hydrochlorothiazide 25 mg, followed by other antihypertensive medications (except angiotensin II receptor blockers) as needed to achieve target blood pressure (<140/90 mm Hg or <130/80 mm Hg for diabetics).		Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.		Azilsartan medoxomil 40 mg, tablets, orally, independent of participant's double-blind treatment assignment. Investigators may have added, in a step-wise fashion, hydrochlorothiazide 12.5 mg, followed by hydrochlorothiazide 25 mg, followed by other antihypertensive medications (except angiotensin II receptor blockers) as needed to achieve target blood pressure (<140/90 mm Hg or <130/80 mm Hg for diabetics).
All Cause Mortality
	Azilsartan Medoxomil 40 mg QD		Azilsartan Medoxomil 80 mg QD		Valsartan 320 mg QD		Open Label Extension
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Azilsartan Medoxomil 40 mg QD		Azilsartan Medoxomil 80 mg QD		Valsartan 320 mg QD		Open Label Extension
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/327 (2.4%)		5/329 (1.5%)		8/326 (2.5%)		4/170 (2.4%)
Cardiac disorders
Silent myocardial infarction	0/327 (0%)		1/329 (0.3%)		1/326 (0.3%)		0/170 (0%)
Cardiac failure acute	1/327 (0.3%)		0/329 (0%)		0/326 (0%)		0/170 (0%)
Coronary artery disease	0/327 (0%)		0/329 (0%)		1/326 (0.3%)		0/170 (0%)
Myocardial infarction	0/327 (0%)		1/329 (0.3%)		0/326 (0%)		1/170 (0.6%)
Gastrointestinal disorders
Abdominal pain	0/327 (0%)		0/329 (0%)		1/326 (0.3%)		0/170 (0%)
Pancreatitis	1/327 (0.3%)		0/329 (0%)		0/326 (0%)		0/170 (0%)
Inguinal hernia, obstructive	0/327 (0%)		0/329 (0%)		0/326 (0%)		1/170 (0.6%)
General disorders
Chest pain	0/327 (0%)		1/329 (0.3%)		0/326 (0%)		0/170 (0%)
Hepatobiliary disorders
Cholecystitis acute	1/327 (0.3%)		0/329 (0%)		0/326 (0%)		1/170 (0.6%)
Infections and infestations
Erysipelas	0/327 (0%)		0/329 (0%)		1/326 (0.3%)		0/170 (0%)
Hepatitis A	1/327 (0.3%)		0/329 (0%)		0/326 (0%)		0/170 (0%)
Scrotal abscess	0/327 (0%)		0/329 (0%)		1/326 (0.3%)		0/170 (0%)
Injury, poisoning and procedural complications
Cervical vertebral fracture	1/327 (0.3%)		0/329 (0%)		0/326 (0%)		0/170 (0%)
Fall	0/327 (0%)		0/329 (0%)		1/326 (0.3%)		0/170 (0%)
Hip fracture	0/327 (0%)		0/329 (0%)		0/326 (0%)		1/170 (0.6%)
Metabolism and nutrition disorders
Gout	0/327 (0%)		0/329 (0%)		1/326 (0.3%)		0/170 (0%)
Hypoglycaemia	1/327 (0.3%)		0/329 (0%)		0/326 (0%)		0/170 (0%)
Type 2 diabetes mellitus	1/327 (0.3%)		0/329 (0%)		0/326 (0%)		0/170 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Oesophageal adenocarcinoma	0/327 (0%)		1/329 (0.3%)		0/326 (0%)		0/170 (0%)
Psychiatric disorders
Bipolar I disorder	0/327 (0%)		1/329 (0.3%)		0/326 (0%)		0/170 (0%)
Renal and urinary disorders
Renal impairment	1/327 (0.3%)		0/329 (0%)		0/326 (0%)		0/170 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/327 (0.3%)		0/329 (0%)		0/326 (0%)		0/170 (0%)
Vascular disorders
Arteriosclerosis	1/327 (0.3%)		0/329 (0%)		1/326 (0.3%)		0/170 (0%)
Hypertension	1/327 (0.3%)		0/329 (0%)		0/326 (0%)		0/170 (0%)
Other (Not Including Serious) Adverse Events
	Azilsartan Medoxomil 40 mg QD		Azilsartan Medoxomil 80 mg QD		Valsartan 320 mg QD		Open Label Extension
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	77/327 (23.5%)		74/329 (22.5%)		53/326 (16.3%)		16/170 (9.4%)
Infections and infestations
Urinary tract infection	26/327 (8%)		25/329 (7.6%)		16/326 (4.9%)		10/170 (5.9%)
Nervous system disorders
Dizziness	27/327 (8.3%)		29/329 (8.8%)		15/326 (4.6%)		8/170 (4.7%)
Headache	33/327 (10.1%)		29/329 (8.8%)		28/326 (8.6%)		9/170 (5.3%)

Limitations/Caveats

For the Non-Serious Adverse Event Table, the total number of participants affected is based on the AEs with ≥5% in each phase, calculated separately.

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.