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

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00846365
• Collaborator: (none)
• Enrollment: 1,085
• Locations: 80
• Arms: 3
• Duration (Months): 15
• Patients Per Site: 13.6
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the efficacy and safety of azilsartan medoxomil combined with chlorthalidone, once daily (QD), in participants with moderate to severe essential hypertension.

Condition or Disease	Intervention/Treatment	Phase
Essential Hypertension	Drug: Azilsartan medoxomil and chlorthalidone; Drug: Azilsartan medoxomil and chlorthalidone; Drug: Olmesartan medoxomil-hydrochlorothiazide	Phase 3

Detailed Description

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. As the population ages, the prevalence of hypertension will continue to increase if broad and effective preventive measures are not implemented. Despite the availability of antihypertensive agents, hypertension remains inadequately controlled; only about one-third of patients continue to maintain control successfully.

Although most antihypertensive agents are effective at the appropriate dose, the majority have side effects that limit their use. As a class, angiotensin II receptor blockers generally are considered more tolerable than other classes of antihypertensive agents. TAK-491 (azilsartan medoxomil) is an angiotensin II receptor blocker being evaluated by Takeda to treat essential hypertension.

Treatments for essential hypertension commonly include use of a thiazide-like diuretic, either alone or as part of combination treatment. Although chlorthalidone was commonly prescribed in the past, its use has widely been replaced with hydrochlorothiazide, presumably due to a lack of available combination products containing chlorthalidone, the assumption that hydrochlorothiazide and chlorthalidone have similar antihypertensive effects and cardiovascular benefits, and the perception that chlorthalidone use is associated with a greater frequency of hypokalemia. However, the frequency of hypokalemia with chlorthalidone use is relatively low in the dose range of 12.5 to 25 mg and these doses have been shown to be associated with potent blood pressure reduction. Several long-term outcomes trials have shown that blood pressure reductions associated with chlorthalidone treatment reduce risk of cardiovascular morbidity and mortality.

Most hypertensive patients require two or more agents to achieve target blood pressure and diuretics are commonly used in combination with other antihypertensive agents.

Participants in this study will be randomized to receive one of 3 possible dosing combinations of azilsartan medoxomil with either chlorthalidone or olmesartan medoxomil-hydrochlorothiazide over 8 weeks. The total duration of the study is approximately 13 weeks. Participants will make a total of 11 visits to the clinic, and will be required to participate in a follow-up telephone call 14 days after last dose of the study drug for adverse event assessment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1085 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Double-Blind, Randomized, Efficacy and Safety Study Comparing the TAK-491 Plus Chlorthalidone Fixed-Dose Combination vs Benicar HCT® (Olmesartan Medoxomil-Hydrochlorothiazide) in Subjects With Moderate to Severe Essential Hypertension
• Study Start Date: Mar 1, 2009
• Actual Primary Completion Date: Jun 1, 2010
• Actual Study Completion Date: Jun 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Azilsartan Medoxomil 20-40mg plus Chlorthalidone 12.5-25 mg QD (dependant on blood pressure)	Drug: Azilsartan medoxomil and chlorthalidone; Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.; Other Names: azilsartan medoxomil chlorthalidone TAK-491 TAK-491CLD
Experimental: Azilsartan Medoxomil 40-80mg plus Chlorthalidone 12.5-25 mg QD (dependant on blood pressure)	Drug: Azilsartan medoxomil and chlorthalidone; Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.; Other Names: azilsartan medoxomil chlorthalidone TAK-491 TAK-491CLD
Active Comparator: Olmesartan medoxomil 20-40mg/hydrochlorothiazide 12.5-25mg QD (dependant on blood pressure)	Drug: Olmesartan medoxomil-hydrochlorothiazide; Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.; Other Names: Benicar HCT®

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure. [Baseline and Week 8.]

   The change in trough systolic blood pressure measured at week 8 or final visit relative to baseline. Systolic blood pressure is the average of the 3 serial trough sitting systolic blood pressure measurements.

Secondary Outcome Measures

1. Change From Baseline to Week 4 in Trough, Sitting, Clinic Systolic Blood Pressure. [Baseline and Week 4.]

   The change in trough systolic blood pressure measured at week 4 relative to baseline. Systolic blood pressure is the average of the 3 serial trough sitting systolic blood pressure measurements.

2. Change From Baseline in Trough, Sitting, Clinic Diastolic Blood Pressure [Baseline, Week 4 and Week 8.]

   The change in trough diastolic blood pressure measured at week 4 and week 8 relative to baseline. Diastolic blood pressure is the average of the 3 serial trough sitting diastolic blood pressure measurements.

3. Change From Baseline in Trough Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [Baseline, Week 4 and Week 8.]

   The change in trough systolic blood pressure measured at week 4 and week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Trough is the average of all measurements recorded from 22 to 24 hours after dosing.

4. Change From Baseline in Trough Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [Baseline, Week 4 and Week 8.]

   The change in trough systolic blood pressure measured at week 4 and week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Trough is the average of all measurements recorded from 22 to 24 hours after dosing.

5. Change From Baseline in 24-hour Mean Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring. [Baseline, Week 4 and Week 8.]

   The change in the 24-hour mean systolic blood pressure at week4 and week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing.

6. Change From Baseline in 24-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [Baseline, Week 4 and Week 8.]

   The change in the 0 to 24-hours-after-dosing mean diastolic blood pressure measured at Week 4 and Week 8 relative to baseline. . Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The mean consists of the average of measurements collected over the subsequent 24 hours.

7. Change From Baseline in Daytime Mean (6am to 10pm) Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [Baseline, Week 4 and Week 8.]

   The change in the daytime, while awake (6am to 10pm) mean systolic blood pressure measured at Week 4 and Week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night Daytime mean is the average of measurements recorded between the hours of 6 AM (inclusive) and 10 PM (exclusive) included in the 24-hour mean calculations.

8. Change From Baseline in Daytime Mean (6am to 10pm) Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [Baseline, Week 4 and Week 8.]

   The change in the daytime, while awake (6am to 10pm) mean diastolic blood pressure measured at Week 4 and Week 8relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of measurements recorded between the hours of 6 AM (inclusive) and 10 PM (exclusive) included in the 24-hour mean calculations.

9. Change From Baseline in Nighttime Mean (12am to 6am) Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring [Baseline, Week 4 and Week 8.]

   The change in the nighttime, while asleep (12am to 6am) mean systolic blood pressure measured at Week 4 and Week 8 to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of measurements recorded between the hours of 12 AM (inclusive) and 6 AM (exclusive) included in the 24-hour mean calculations.

10. Change From Baseline in Nighttime Mean (12am to 6am) Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [Baseline, Week 4 and Week 8.]

    The change in the nighttime, while asleep (12am to 6am) mean diastolic blood pressure measured at Week 4 and Week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average (arithmetic mean) of measurements recorded between the hours of 12 AM (inclusive) and 6 AM (exclusive) included in the 24-hour mean calculations.

11. Change From Baseline in 12-hr Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [Baseline, Week 4 and Week 8.]

    The change in the 0 to 12 hours-after-dosing mean Systolic Blood Pressure measured at Week 4 and Week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night The mean consists of the average (arithmetic mean) of measurements collected at each time frame and includes all observations recorded over the subsequent 12 hours.

12. Change From Baseline in 12-hr Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [Baseline, Week 4 and Week 8.]

    The change in the 0 to 12 hours-after-dosing mean diastolic blood pressure measured at Week 4 and Week 8 to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The mean consists of the average (arithmetic mean) of measurements collected at each time frame and includes all observations recorded over the subsequent 12 hours.

13. Percentage of Participants Who Achieve a Clinic Systolic Blood Pressure Response, Defined as <140 mm Hg for Participants Without Diabetes or CKD or <130 mm Hg for Participants With Diabetes or CKD [Baseline, Week 2, Week 4, Week 6 and Week 8.]

    Percentage of participants who achieve a clinic systolic blood pressure response, defined as <140 mm Hg for participants without diabetes or CKD or <130 mm Hg for participants with diabetes or CKD at each time frame relative to baseline.

14. Percentage of Participants Who Achieve a Clinic Diastolic Blood Pressure Response, Defined as Defined as <90 mm Hg for Participants Without Diabetes or CKD or <80 mm Hg for Participants With Diabetes or CKD [Baseline, Week 2, Week 4, Week 6 and Week 8.]

    Percentage of participants who achieve a clinic diastolic blood pressure response, defined as defined as <90 mm Hg for participants without diabetes or CKD or <80 mm Hg for participants with diabetes or CKD at each time frame relative to baseline.

15. Percentage of Participants Who Achieve a Clinic Diastolic AND Systolic Blood Pressure Response, Defined as <140/90 mm Hg for Participants Without Diabetes or Chronic Kidney Disease (CKD) or <130/80 mm Hg for Participants With Diabetes or CKD [Baseline, Week 2, Week 4, Week 6 and Week 8.]

    Percentage of participants who achieve both a clinic diastolic blood pressure response, defined as <140/90 mm Hg for participants without diabetes or chronic kidney disease (CKD) or <130/80 mm Hg for participants with diabetes or CKD at each time frame relative to baseline.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. 190 mm Hg on Day -1 or if the participant has not received antihypertensive treatment within 28 days before screening and has a mean sitting clinic systolic blood pressure greater than or equal to 160 and less than or equal to 190 mm Hg at the Screening Visit and on 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. Has clinical laboratory test results within the reference range for the testing laboratory or the investigator does not consider the results to be clinically significant.

4. Is willing to discontinue current antihypertensive medications on Day -21 or on Day -28 if is on amlodipine or chlorthalidone.

Exclusion Criteria:

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

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

3. Works a night (third) shift (from 11 PM [2300] to 7 AM [0700]).

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

5. Is noncompliant with study medication during the placebo run-in period.

6. Has secondary hypertension of any etiology.

7. 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.

8. Has a clinically significant cardiac conduction.

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

10. Has severe renal dysfunction or disease.

11. Has a known or suspected unilateral or bilateral renal artery stenosis.

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

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

14. Has hypokalemia or hyperkalemia.

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

16. Has any other known serious disease or condition that would compromise safety, might affect life expectancy or make it difficult to successfully manage and follow the participant according to the protocol.

17. Has a known hypersensitivity to angiotensin II receptor blockers or thiazide-type diuretics or other sulfonamide-derived compounds.

18. Has been randomized in a previous Azilsartan Medoxomil study.

19. Is currently participating in another investigational study or has participated in an investigational study or is receiving or has received any investigational compound within 30 days prior to Randomization.

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Birmingham	Alabama	United States
2		Haleyville	Alabama	United States
3		Hueytown	Alabama	United States
4		Jasper	Alabama	United States
5		Tallassee	Alabama	United States
6		Green Valley	Arizona	United States
7		Phoenix	Arizona	United States
8		Long Beach	California	United States
9		National City	California	United States
10		Roseville	California	United States
11		San Francisco	California	United States
12		San Jose	California	United States
13		Newark	Delaware	United States
14		Clearwater	Florida	United States
15		Jacksonville	Florida	United States
16		Jupiter	Florida	United States
17		Miami	Florida	United States
18		Ocala	Florida	United States
19		Pembroke Pines	Florida	United States
20		Plant City	Florida	United States
21		Tallahassee	Florida	United States
22		Arlington Heights	Illinois	United States
23		Chicago	Illinois	United States
24		Gurnee	Illinois	United States
25		Avon	Indiana	United States
26		Wichita	Kansas	United States
27		Louisville	Kentucky	United States
28		Auburn	Maine	United States
29		Baltimore	Maryland	United States
30		Brockton	Massachusetts	United States
31		Haverhill	Massachusetts	United States
32		North Dartmouth	Massachusetts	United States
33		Bingham Farms	Michigan	United States
34		Stevensville	Michigan	United States
35		Olive Branch	Mississippi	United States
36		Kansas City	Missouri	United States
37		New York	New York	United States
38		Burlington	North Carolina	United States
39		Charlotte	North Carolina	United States
40		Hickory	North Carolina	United States
41		Shelby	North Carolina	United States
42		Akron	Ohio	United States
43		Cleveland	Ohio	United States
44		Columbus	Ohio	United States
45		Marion	Ohio	United States
46		Middleburg Heights	Ohio	United States
47		Willoughby Hills	Ohio	United States
48		Norman	Oklahoma	United States
49		Bensalem	Pennsylvania	United States
50		Erie	Pennsylvania	United States
51		Reading	Pennsylvania	United States
52		Cranston	Rhode Island	United States
53		Cumberland	Rhode Island	United States
54		North Charleston	South Carolina	United States
55		Jackson	Tennessee	United States
56		Kingsport	Tennessee	United States
57		Milan	Tennessee	United States
58		Austin	Texas	United States
59		Corpus Christi	Texas	United States
60		Dallas	Texas	United States
61		Houston	Texas	United States
62		San Antonio	Texas	United States
63		Salt Lake City	Utah	United States
64		Arlington	Virginia	United States
65		Burke	Virginia	United States
66		Charlottesville	Virginia	United States
67		Manassas	Virginia	United States
68		Lakewood	Washington	United States
69		Port Orchard	Washington	United States
70		Menomonee Falls	Wisconsin	United States
71		Temuco	Cautín	Chile
72		La Serena	Elqui	Chile
73		Vina del Mar	Valparaíso	Chile
74		Osorno		Chile
75		Santiago		Chile
76		Tijuana	Baja California	Mexico
77		Leon	Guanajuato	Mexico
78		Guadalajara	Jalisco	Mexico
79		Chihuahua		Mexico
80		San Luis Potosi		Mexico

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Executive Medical Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT00846365
• Other Study ID Numbers: TAK-491CLD_301; U1111-1112-4287
• First Posted: Feb 18, 2009
• Last Update Posted: Mar 13, 2012
• Last Verified: Feb 1, 2012

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

Study Results

Participant Flow

Recruitment Details	Participants enrolled at 93 investigative sites in Argentina, Chile, Mexico and the United States from 13 March 2009 to 25 June 2010.
Pre-assignment Detail	Participants with moderate to severe essential hypertension were enrolled in one of 3, once-daily (QD) treatment groups.

Arm/Group Title	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD	Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD	Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.
Period Title: Overall Study
STARTED	372	357	356
COMPLETED	317	308	323
NOT COMPLETED	55	49	33

Baseline Characteristics

Arm/Group Title	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD	Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD	Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD	Total
Arm/Group Description	Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Total of all reporting groups
Overall Participants	372	357	356	1085
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.5 (10.49)	56.7 (10.83)	55.7 (9.78)	56.0 (10.38)
Age, Customized (participants) [Number]
<45 years	47 12.6%	38 10.6%	41 11.5%	126 11.6%
45 to 64 years	252 67.7%	244 68.3%	249 69.9%	745 68.7%
≥65 years	73 19.6%	75 21%	66 18.5%	214 19.7%
Sex: Female, Male (Count of Participants)
Female	175 47%	174 48.7%	173 48.6%	522 48.1%
Male	197 53%	183 51.3%	183 51.4%	563 51.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	37 9.9%	41 11.5%	44 12.4%	122 11.2%
Not Hispanic or Latino	265 71.2%	253 70.9%	251 70.5%	769 70.9%
Unknown or Not Reported	70 18.8%	63 17.6%	61 17.1%	194 17.9%
Race (NIH/OMB) (participants) [Number]
American Indian or Alaska Native	37 9.9%	34 9.5%	35 9.8%	106 9.8%
Asian	7 1.9%	5 1.4%	5 1.4%	17 1.6%
Native Hawaiian or Other Pacific Islander	3 0.8%	0 0%	0 0%	3 0.3%
Black or African American	95 25.5%	95 26.6%	100 28.1%	290 26.7%
White	235 63.2%	225 63%	220 61.8%	680 62.7%
More than one race	5 1.3%	2 0.6%	4 1.1%	11 1%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	302 81.2%	294 82.4%	295 82.9%	891 82.1%
Mexico	45 12.1%	44 12.3%	43 12.1%	132 12.2%
Chile	12 3.2%	10 2.8%	9 2.5%	31 2.9%
Argentina	13 3.5%	9 2.5%	9 2.5%	31 2.9%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	89.35 (20.995)	89.87 (21.281)	90.66 (20.700)	89.95 (20.981)
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	167.5 (11.22)	167.8 (11.06)	168.2 (10.30)	167.8 (10.87)
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	31.7 (5.94)	31.8 (6.40)	31.9 (6.08)	31.8 (6.14)
Estimated Glomerular Filtration Rate (eGFR) Category (participants) [Number]
Moderate impairment	26 7%	25 7%	25 7%	76 7%
Mild impairment	220 59.1%	207 58%	205 57.6%	632 58.2%
Normal	126 33.9%	125 35%	126 35.4%	377 34.7%
Chronic Kidney Disease (CKD) Status (participants) [Number]
Yes	25 6.7%	41 11.5%	28 7.9%	94 8.7%
No	347 93.3%	315 88.2%	328 92.1%	990 91.2%
Missing	0 0%	1 0.3%	0 0%	1 0.1%
Diabetes Status (participants) [Number]
Yes	58 15.6%	59 16.5%	71 19.9%	188 17.3%
No	314 84.4%	298 83.5%	285 80.1%	897 82.7%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure.
Description	The change in trough systolic blood pressure measured at week 8 or final visit relative to baseline. Systolic blood pressure is the average of the 3 serial trough sitting systolic blood pressure measurements.
Time Frame	Baseline and Week 8.

Outcome Measure Data

Analysis Population Description

Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward.

Arm/Group Title	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD	Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD	Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.
Measure Participants	363	350	353
Least Squares Mean (Standard Deviation) [mmHg]	-37.6 (0.83)	-38.2 (0.85)	-31.5 (0.84)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD, Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
	Comments	Analysis of Covariance (ANCOVA) model with treatment as a fixed effect and Baseline as a covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Statistical significance was set at the 0.05 level per the predefined stepwise testing strategy used.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-6.1
	Confidence Interval	(2-Sided) 95%; -8.4 to -3.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD, Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
	Comments	ANCOVA model with treatment as a fixed effect and Baseline as a covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Statistical significance was set at the 0.05 level per the predefined stepwise testing strategy used.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-6.7
	Confidence Interval	(2-Sided) 95%; -9.1 to -4.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline to Week 4 in Trough, Sitting, Clinic Systolic Blood Pressure.
Description	The change in trough systolic blood pressure measured at week 4 relative to baseline. Systolic blood pressure is the average of the 3 serial trough sitting systolic blood pressure measurements.
Time Frame	Baseline and Week 4.

Outcome Measure Data

Analysis Population Description

Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. Participants who had not achieved target systolic blood pressure/diastolic blood pressure were titrated to the higher dose at week 4.

Arm/Group Title	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD	Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD	Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.
Measure Participants	360	347	352
Least Squares Mean (Standard Deviation) [mmHg]	-33.0 (0.87)	-34.1 (0.88)	-26.9 (0.88)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD, Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
	Comments	ANCOVA model with treatment as a fixed effect and Baseline as a covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Statistical significance was set at the 0.05 level per the predefined stepwise testing strategy used.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-6.1
	Confidence Interval	(2-Sided) 95%; -8.5 to -3.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD, Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
	Comments	ANCOVA model with treatment as a fixed effect and Baseline as a covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Statistical significance was set at the 0.05 level per the predefined stepwise testing strategy used.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-7.2
	Confidence Interval	(2-Sided) 95%; -9.6 to -4.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Trough, Sitting, Clinic Diastolic Blood Pressure
Description	The change in trough diastolic blood pressure measured at week 4 and week 8 relative to baseline. Diastolic blood pressure is the average of the 3 serial trough sitting diastolic blood pressure measurements.
Time Frame	Baseline, Week 4 and Week 8.

Outcome Measure Data

Analysis Population Description

Full analysis set , all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. Participants who had not achieved target systolic blood pressure/diastolic blood pressure were titrated to the higher dose at week 4.

Arm/Group Title	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD	Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD	Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.
Measure Participants	372	357	356
Week 4 (n=360; n=347; n=352)	-13.6 (0.49)	-14.2 (0.50)	-10.4 (0.49)
Week 8 (n=363; n=350; n=353)	-16.1 (0.47)	-16.5 (0.48)	-12.8 (0.48)

4. Secondary Outcome

Title	Change From Baseline in Trough Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Description	The change in trough systolic blood pressure measured at week 4 and week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Trough is the average of all measurements recorded from 22 to 24 hours after dosing.
Time Frame	Baseline, Week 4 and Week 8.

Outcome Measure Data

Analysis Population Description

Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. Participants who had not achieved target systolic blood pressure/diastolic blood pressure were titrated to the higher dose at week 4.

Arm/Group Title	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD	Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD	Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.
Measure Participants	372	357	356
Week 4 (n=223; n=227; n=219)	-22.4 (0.95)	-23.6 (0.94)	-17.4 (0.96)
Week 8 (n=290; n=278; n=281)	-24.9 (0.79)	-26.8 (0.81)	-19.6 (0.80)

5. Secondary Outcome

Title	Change From Baseline in Trough Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Description	The change in trough systolic blood pressure measured at week 4 and week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Trough is the average of all measurements recorded from 22 to 24 hours after dosing.
Time Frame	Baseline, Week 4 and Week 8.

Outcome Measure Data

Analysis Population Description

Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. Participants who had not achieved target systolic blood pressure/diastolic blood pressure were titrated to the higher dose at week 4.

Arm/Group Title	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD	Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD	Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.
Measure Participants	372	357	356
Week 4 (n=223; n=227; n=219)	-13.4 (0.66)	-14.6 (0.66)	-10.9 (0.67)
Week 8 (n=290; n=278; n=281)	-14.6 (0.56)	-15.9 (0.57)	-12.0 (0.57)

6. Secondary Outcome

Title	Change From Baseline in 24-hour Mean Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring.
Description	The change in the 24-hour mean systolic blood pressure at week4 and week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing.
Time Frame	Baseline, Week 4 and Week 8.

Outcome Measure Data

Analysis Population Description

Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. Participants who had not achieved target systolic blood pressure/diastolic blood pressure were titrated to the higher dose at week 4.

Arm/Group Title	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD	Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD	Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.
Measure Participants	372	357	356
Week 4 (n=223; n=227; n=219)	-24.1 (0.81)	-24.4 (0.80)	-18.4 (0.81)
Week 8 (n=290; n=278; n=281)	-26.4 (0.69)	-27.9 (0.70)	-20.7 (0.70)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD, Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
	Comments	Statistical analysis for Week 8. ANOVA model with treatment as a fixed effect. Post-baseline p-values are obtained from an ANCOVA model with treatment as a fixed effect and baseline as a covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Tested at the 0.05 significance level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.6
	Confidence Interval	(2-Sided) 95%; -7.5 to -3.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD, Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
	Comments	Statistical analysis for Week 8. ANOVA model with treatment as a fixed effect. Post-baseline p-values are obtained from an ANCOVA model with treatment as a fixed effect and baseline as a covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Tested at the 0.05 significance level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-7.2
	Confidence Interval	(2-Sided) 95%; -9.1 to -5.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline in 24-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Description	The change in the 0 to 24-hours-after-dosing mean diastolic blood pressure measured at Week 4 and Week 8 relative to baseline. . Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The mean consists of the average of measurements collected over the subsequent 24 hours.
Time Frame	Baseline, Week 4 and Week 8.

Outcome Measure Data

Analysis Population Description

Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. Participants who had not achieved target systolic blood pressure/diastolic blood pressure were titrated to the higher dose at week 4.

Arm/Group Title	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD	Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD	Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.
Measure Participants	372	357	357
Week 4 (n=223; n=227; n=219)	-13.9 (0.51)	-14.4 (0.51)	-10.5 (0.52)
Week 8 (n=290; n=278; n=281)	-15.1 (0.45)	-16.4 (0.46)	-12.0 (0.46)

8. Secondary Outcome

Title	Change From Baseline in Daytime Mean (6am to 10pm) Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Description	The change in the daytime, while awake (6am to 10pm) mean systolic blood pressure measured at Week 4 and Week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night Daytime mean is the average of measurements recorded between the hours of 6 AM (inclusive) and 10 PM (exclusive) included in the 24-hour mean calculations.
Time Frame	Baseline, Week 4 and Week 8.

Outcome Measure Data

Analysis Population Description

Full analysis set , all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. Participants who had not achieved target systolic blood pressure/diastolic blood pressure were titrated to the higher dose at week 4.

Arm/Group Title	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD	Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD	Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.
Measure Participants	372	357	356
Week 4 (n=223; n=227; n=219)	-24.5 (0.84)	-25.1 (0.83)	-18.9 (0.85)
Week 8 (n=290; n=278; n=281)	-26.7 (0.72)	-28.4 (0.74)	-21.0 (0.74)

9. Secondary Outcome

Title	Change From Baseline in Daytime Mean (6am to 10pm) Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Description	The change in the daytime, while awake (6am to 10pm) mean diastolic blood pressure measured at Week 4 and Week 8relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of measurements recorded between the hours of 6 AM (inclusive) and 10 PM (exclusive) included in the 24-hour mean calculations.
Time Frame	Baseline, Week 4 and Week 8.

Outcome Measure Data

Analysis Population Description

Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. Participants who had not achieved target systolic blood pressure/diastolic blood pressure were titrated to the higher dose at week 4.

Arm/Group Title	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD	Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD	Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.
Measure Participants	372	357	356
Week 4 (n=223; n=227; n=219)	-14.2 (0.53)	-14.7 (0.53)	-10.7 (0.54)
Week 8 (n=290; n=278; n=281)	-15.3 (0.47)	-16.6 (0.48)	-12.1 (0.48)

10. Secondary Outcome

Title	Change From Baseline in Nighttime Mean (12am to 6am) Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring
Description	The change in the nighttime, while asleep (12am to 6am) mean systolic blood pressure measured at Week 4 and Week 8 to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of measurements recorded between the hours of 12 AM (inclusive) and 6 AM (exclusive) included in the 24-hour mean calculations.
Time Frame	Baseline, Week 4 and Week 8.

Outcome Measure Data

Analysis Population Description

Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. Participants who had not achieved target systolic blood pressure/diastolic blood pressure were titrated to the higher dose at week 4.

Arm/Group Title	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD	Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD	Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.
Measure Participants	372	357	356
Week 4 (n=223; n=227; n=219)	-22.3 (0.87)	-21.9 (0.86)	-16.6 (0.88)
Week 8 (n=290; n=278; n=281)	-25.2 (0.74)	-26.3 (0.75)	-19.7 (0.75)

11. Secondary Outcome

Title	Change From Baseline in Nighttime Mean (12am to 6am) Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Description	The change in the nighttime, while asleep (12am to 6am) mean diastolic blood pressure measured at Week 4 and Week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average (arithmetic mean) of measurements recorded between the hours of 12 AM (inclusive) and 6 AM (exclusive) included in the 24-hour mean calculations.
Time Frame	Baseline, Week 4 and Week 8.

Outcome Measure Data

Analysis Population Description

Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. Participants who had not achieved target systolic blood pressure/diastolic blood pressure were titrated to the higher dose at week 4.

Arm/Group Title	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD	Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD	Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.
Measure Participants	372	357	356
Week 4 (n=223; n=227; n=219)	-13.4 (0.58)	-13.3 (0.58)	-9.6 (0.59)
Week 8 (n=290; n=278; n=281)	-14.9 (0.51)	-15.8 (0.52)	-11.8 (0.52)

12. Secondary Outcome

Title	Change From Baseline in 12-hr Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Description	The change in the 0 to 12 hours-after-dosing mean Systolic Blood Pressure measured at Week 4 and Week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night The mean consists of the average (arithmetic mean) of measurements collected at each time frame and includes all observations recorded over the subsequent 12 hours.
Time Frame	Baseline, Week 4 and Week 8.

Outcome Measure Data

Analysis Population Description

Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. Participants who had not achieved target systolic blood pressure/diastolic blood pressure were titrated to the higher dose at week 4.

Arm/Group Title	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD	Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD	Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.
Measure Participants	372	357	356
Week 4 (n=223; n=227; n=219)	-25.0 (0.87)	-25.5 (0.86)	-19.2 (0.88)
Week 8 (n=290; n=278; n=281)	-27.1 (0.77)	-28.8 (0.78)	-21.1 (0.78)

13. Secondary Outcome

Title	Change From Baseline in 12-hr Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
Description	The change in the 0 to 12 hours-after-dosing mean diastolic blood pressure measured at Week 4 and Week 8 to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The mean consists of the average (arithmetic mean) of measurements collected at each time frame and includes all observations recorded over the subsequent 12 hours.
Time Frame	Baseline, Week 4 and Week 8.

Outcome Measure Data

Analysis Population Description

Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. Participants who had not achieved target systolic blood pressure/diastolic blood pressure were titrated to the higher dose at week 4.

Arm/Group Title	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD	Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD	Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.
Measure Participants	372	357	356
Week 4 (n=223; n=227; n=219)	-14.4 (0.56)	-14.8 (0.55)	-10.8 (0.56)
Week 8 (n=290; n=278; n=281)	-15.4 (0.50)	-16.9 (0.51)	-12.1 (0.51)

14. Secondary Outcome

Title	Percentage of Participants Who Achieve a Clinic Systolic Blood Pressure Response, Defined as <140 mm Hg for Participants Without Diabetes or CKD or <130 mm Hg for Participants With Diabetes or CKD
Description	Percentage of participants who achieve a clinic systolic blood pressure response, defined as <140 mm Hg for participants without diabetes or CKD or <130 mm Hg for participants with diabetes or CKD at each time frame relative to baseline.
Time Frame	Baseline, Week 2, Week 4, Week 6 and Week 8.

Outcome Measure Data

Analysis Population Description

Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. Participants who had not achieved target systolic blood pressure/diastolic blood pressure were titrated to the higher dose at week 4.

Arm/Group Title	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD	Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD	Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.
Measure Participants	372	357	356
Week 2 (n=343; n=334; n=345)	60.3 16.2%	57.2 16%	44.9 12.6%
Week 4 (n=360; n=347; n=352)	66.1 17.8%	68.9 19.3%	52.3 14.7%
Week 6 (n=362; n=350; n=353)	76.8 20.6%	73.4 20.6%	64.9 18.2%
Week 8 (n=363; n=350; n=353)	76.0 20.4%	76.0 21.3%	64.6 18.1%

15. Secondary Outcome

Title	Percentage of Participants Who Achieve a Clinic Diastolic Blood Pressure Response, Defined as Defined as <90 mm Hg for Participants Without Diabetes or CKD or <80 mm Hg for Participants With Diabetes or CKD
Description	Percentage of participants who achieve a clinic diastolic blood pressure response, defined as defined as <90 mm Hg for participants without diabetes or CKD or <80 mm Hg for participants with diabetes or CKD at each time frame relative to baseline.
Time Frame	Baseline, Week 2, Week 4, Week 6 and Week 8.

Outcome Measure Data

Analysis Population Description

Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. Participants who had not achieved target systolic blood pressure/diastolic blood pressure were titrated to the higher dose at week 4.

Arm/Group Title	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD	Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD	Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.
Measure Participants	372	357	356
Week 2 (n=343; n=334; n=345)	63.6 17.1%	66.2 18.5%	47.8 13.4%
Week 4 (n=360; n=347; n=352)	71.4 19.2%	73.8 20.7%	58.2 16.3%
Week 6 (n=362; n=350; n=353)	77.9 20.9%	76.9 21.5%	66.9 18.8%
Week 8 (n=363; n=350; n=353)	79.9 21.5%	79.1 22.2%	66.0 18.5%

16. Secondary Outcome

Title	Percentage of Participants Who Achieve a Clinic Diastolic AND Systolic Blood Pressure Response, Defined as <140/90 mm Hg for Participants Without Diabetes or Chronic Kidney Disease (CKD) or <130/80 mm Hg for Participants With Diabetes or CKD
Description	Percentage of participants who achieve both a clinic diastolic blood pressure response, defined as <140/90 mm Hg for participants without diabetes or chronic kidney disease (CKD) or <130/80 mm Hg for participants with diabetes or CKD at each time frame relative to baseline.
Time Frame	Baseline, Week 2, Week 4, Week 6 and Week 8.

Outcome Measure Data

Analysis Population Description

Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. Participants who had not achieved target systolic blood pressure/diastolic blood pressure were titrated to the higher dose at week 4.

Arm/Group Title	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD	Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD	Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.	Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.
Measure Participants	372	357	356
Week 2 (n=343; n=334; n=345)	51.3 13.8%	48.5 13.6%	35.9 10.1%
Week 4 (n=360; n=347; n=352)	58.1 15.6%	61.4 17.2%	44.6 12.5%
Week 6 (n=362; n=350; n=353)	68.8 18.5%	65.4 18.3%	55.5 15.6%
Week 8 (n=363; n=350; n=353)	69.4 18.7%	68.9 19.3%	54.7 15.4%

Adverse Events

Time Frame	Treatment-emergent adverse events are adverse events that started on or after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug.
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Arm/Group Title	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD		Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD		Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
Arm/Group Description	Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.		Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.		Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.
All Cause Mortality
	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD		Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD		Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD		Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD		Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/372 (1.1%)		8/357 (2.2%)		6/356 (1.7%)
Cardiac disorders
Cardiac arrest	0/372 (0%)		1/357 (0.3%)		1/356 (0.3%)
Coronary artery disease	0/372 (0%)		0/357 (0%)		1/356 (0.3%)
Diastolic dysfunction	0/372 (0%)		1/357 (0.3%)		0/356 (0%)
Gastrointestinal disorders
Diarrhoea	1/372 (0.3%)		0/357 (0%)		0/356 (0%)
Epigastric discomfort	1/372 (0.3%)		0/357 (0%)		0/356 (0%)
Nausea	1/372 (0.3%)		0/357 (0%)		0/356 (0%)
Pancreatitis	0/372 (0%)		1/357 (0.3%)		0/356 (0%)
Vomiting	1/372 (0.3%)		0/357 (0%)		0/356 (0%)
General disorders
Chest pain	0/372 (0%)		0/357 (0%)		1/356 (0.3%)
Generalised oedema	0/372 (0%)		1/357 (0.3%)		0/356 (0%)
Systemic inflammatory response syndrome	0/372 (0%)		0/357 (0%)		1/356 (0.3%)
Infections and infestations
Cellulitis	0/372 (0%)		1/357 (0.3%)		1/356 (0.3%)
Gastroenteritis	0/372 (0%)		1/357 (0.3%)		0/356 (0%)
Pneumonia	0/372 (0%)		1/357 (0.3%)		0/356 (0%)
Viral infection	0/372 (0%)		1/357 (0.3%)		0/356 (0%)
Injury, poisoning and procedural complications
Heat exhaustion	0/372 (0%)		0/357 (0%)		1/356 (0.3%)
Road traffic accident	1/372 (0.3%)		0/357 (0%)		0/356 (0%)
Investigations
Blood creatinine increased	0/372 (0%)		1/357 (0.3%)		0/356 (0%)
Troponin increased	0/372 (0%)		0/357 (0%)		1/356 (0.3%)
Metabolism and nutrition disorders
Dehydration	0/372 (0%)		0/357 (0%)		1/356 (0.3%)
Nervous system disorders
Cerebral infarction	0/372 (0%)		1/357 (0.3%)		0/356 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/372 (0.3%)		0/357 (0%)		1/356 (0.3%)
Asthma	0/372 (0%)		0/357 (0%)		1/356 (0.3%)
Sleep apnoea syndrome	0/372 (0%)		1/357 (0.3%)		0/356 (0%)
Skin and subcutaneous tissue disorders
Angioedema	0/372 (0%)		1/357 (0.3%)		0/356 (0%)
Vascular disorders
Deep vein thrombosis	0/372 (0%)		0/357 (0%)		1/356 (0.3%)
Shock	0/372 (0%)		0/357 (0%)		1/356 (0.3%)
Other (Not Including Serious) Adverse Events
	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD		Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD		Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	66/372 (17.7%)		72/357 (20.2%)		56/356 (15.7%)
Investigations
Blood creatinine increased	36/372 (9.7%)		44/357 (12.3%)		25/356 (7%)
Nervous system disorders
Dizziness	25/372 (6.7%)		24/357 (6.7%)		20/356 (5.6%)
Headache	14/372 (3.8%)		14/357 (3.9%)		18/356 (5.1%)

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.