Trial Outcomes & Findings for Efficacy and Safety of Azilsartan Medoxomil Plus Chlorthalidone in Participants With Moderate to Severe Hypertension (NCT NCT00846365)

NCT ID: NCT00846365

Last Updated: 2012-03-13

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1085 participants
• Primary outcome timeframe: Baseline and Week 8.
• Results posted on: 2012-03-13

Participant Flow

Participants enrolled at 93 investigative sites in Argentina, Chile, Mexico and the United States from 13 March 2009 to 25 June 2010.

Participants with moderate to severe essential hypertension were enrolled in one of 3, once-daily (QD) treatment groups.

Participant milestones

Measure	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD 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 40-80mg Plus Chlorthalidone 12.5-25 mg QD 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 20-40mg/Hydrochlorothiazide 12.5-25mg QD 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.
Overall Study STARTED	372	357	356
Overall Study COMPLETED	317	308	323
Overall Study NOT COMPLETED	55	49	33

Reasons for withdrawal

Measure	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD 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 40-80mg Plus Chlorthalidone 12.5-25 mg QD 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 20-40mg/Hydrochlorothiazide 12.5-25mg QD 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.
Overall Study Adverse Event	20	30	11
Overall Study Protocol Violation	5	4	0
Overall Study Lost to Follow-up	8	2	5
Overall Study Withdrawal by Subject	11	11	9
Overall Study Pregnancy	1	0	0
Overall Study Lack of Efficacy	1	1	2
Overall Study Other	9	1	6

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD n=372 Participants 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 40-80mg Plus Chlorthalidone 12.5-25 mg QD n=357 Participants 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 20-40mg/Hydrochlorothiazide 12.5-25mg QD n=356 Participants 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 n=1085 Participants Total of all reporting groups
Age Continuous	55.5 years STANDARD_DEVIATION 10.49 • n=5 Participants	56.7 years STANDARD_DEVIATION 10.83 • n=7 Participants	55.7 years STANDARD_DEVIATION 9.78 • n=5 Participants	56.0 years STANDARD_DEVIATION 10.38 • n=4 Participants
Age, Customized <45 years	47 participants n=5 Participants	38 participants n=7 Participants	41 participants n=5 Participants	126 participants n=4 Participants
Age, Customized 45 to 64 years	252 participants n=5 Participants	244 participants n=7 Participants	249 participants n=5 Participants	745 participants n=4 Participants
Age, Customized ≥65 years	73 participants n=5 Participants	75 participants n=7 Participants	66 participants n=5 Participants	214 participants n=4 Participants
Sex: Female, Male Female	175 Participants n=5 Participants	174 Participants n=7 Participants	173 Participants n=5 Participants	522 Participants n=4 Participants
Sex: Female, Male Male	197 Participants n=5 Participants	183 Participants n=7 Participants	183 Participants n=5 Participants	563 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	37 Participants n=5 Participants	41 Participants n=7 Participants	44 Participants n=5 Participants	122 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	265 Participants n=5 Participants	253 Participants n=7 Participants	251 Participants n=5 Participants	769 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	70 Participants n=5 Participants	63 Participants n=7 Participants	61 Participants n=5 Participants	194 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	37 participants n=5 Participants	34 participants n=7 Participants	35 participants n=5 Participants	106 participants n=4 Participants
Race (NIH/OMB) Asian	7 participants n=5 Participants	5 participants n=7 Participants	5 participants n=5 Participants	17 participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	3 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	3 participants n=4 Participants
Race (NIH/OMB) Black or African American	95 participants n=5 Participants	95 participants n=7 Participants	100 participants n=5 Participants	290 participants n=4 Participants
Race (NIH/OMB) White	235 participants n=5 Participants	225 participants n=7 Participants	220 participants n=5 Participants	680 participants n=4 Participants
Race (NIH/OMB) More than one race	5 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants	11 participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
Region of Enrollment United States	302 participants n=5 Participants	294 participants n=7 Participants	295 participants n=5 Participants	891 participants n=4 Participants
Region of Enrollment Mexico	45 participants n=5 Participants	44 participants n=7 Participants	43 participants n=5 Participants	132 participants n=4 Participants
Region of Enrollment Chile	12 participants n=5 Participants	10 participants n=7 Participants	9 participants n=5 Participants	31 participants n=4 Participants
Region of Enrollment Argentina	13 participants n=5 Participants	9 participants n=7 Participants	9 participants n=5 Participants	31 participants n=4 Participants
Weight	89.35 kg STANDARD_DEVIATION 20.995 • n=5 Participants	89.87 kg STANDARD_DEVIATION 21.281 • n=7 Participants	90.66 kg STANDARD_DEVIATION 20.700 • n=5 Participants	89.95 kg STANDARD_DEVIATION 20.981 • n=4 Participants
Height	167.5 cm STANDARD_DEVIATION 11.22 • n=5 Participants	167.8 cm STANDARD_DEVIATION 11.06 • n=7 Participants	168.2 cm STANDARD_DEVIATION 10.30 • n=5 Participants	167.8 cm STANDARD_DEVIATION 10.87 • n=4 Participants
Body Mass Index (BMI)	31.7 kg/m^2 STANDARD_DEVIATION 5.94 • n=5 Participants	31.8 kg/m^2 STANDARD_DEVIATION 6.40 • n=7 Participants	31.9 kg/m^2 STANDARD_DEVIATION 6.08 • n=5 Participants	31.8 kg/m^2 STANDARD_DEVIATION 6.14 • n=4 Participants
Estimated Glomerular Filtration Rate (eGFR) Category Moderate impairment	26 participants n=5 Participants	25 participants n=7 Participants	25 participants n=5 Participants	76 participants n=4 Participants
Estimated Glomerular Filtration Rate (eGFR) Category Mild impairment	220 participants n=5 Participants	207 participants n=7 Participants	205 participants n=5 Participants	632 participants n=4 Participants
Estimated Glomerular Filtration Rate (eGFR) Category Normal	126 participants n=5 Participants	125 participants n=7 Participants	126 participants n=5 Participants	377 participants n=4 Participants
Chronic Kidney Disease (CKD) Status Yes	25 participants n=5 Participants	41 participants n=7 Participants	28 participants n=5 Participants	94 participants n=4 Participants
Chronic Kidney Disease (CKD) Status No	347 participants n=5 Participants	315 participants n=7 Participants	328 participants n=5 Participants	990 participants n=4 Participants
Chronic Kidney Disease (CKD) Status Missing	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Diabetes Status Yes	58 participants n=5 Participants	59 participants n=7 Participants	71 participants n=5 Participants	188 participants n=4 Participants
Diabetes Status No	314 participants n=5 Participants	298 participants n=7 Participants	285 participants n=5 Participants	897 participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 8.

Population: 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.

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.

Outcome measures

Measure	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD n=363 Participants 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 40-80mg Plus Chlorthalidone 12.5-25 mg QD n=350 Participants 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 20-40mg/Hydrochlorothiazide 12.5-25mg QD n=353 Participants 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.
Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure.	-37.6 mmHg Standard Deviation 0.83	-38.2 mmHg Standard Deviation 0.85	-31.5 mmHg Standard Deviation 0.84

SECONDARY outcome

Timeframe: Baseline and Week 4.

Population: 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.

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.

Outcome measures

Measure	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD n=360 Participants 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 40-80mg Plus Chlorthalidone 12.5-25 mg QD n=347 Participants 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 20-40mg/Hydrochlorothiazide 12.5-25mg QD n=352 Participants 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.
Change From Baseline to Week 4 in Trough, Sitting, Clinic Systolic Blood Pressure.	-33.0 mmHg Standard Deviation 0.87	-34.1 mmHg Standard Deviation 0.88	-26.9 mmHg Standard Deviation 0.88

SECONDARY outcome

Timeframe: Baseline, Week 4 and Week 8.

Population: 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.

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.

Outcome measures

Measure	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD n=372 Participants 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 40-80mg Plus Chlorthalidone 12.5-25 mg QD n=357 Participants 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 20-40mg/Hydrochlorothiazide 12.5-25mg QD n=356 Participants 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.
Change From Baseline in Trough, Sitting, Clinic Diastolic Blood Pressure Week 4 (n=360; n=347; n=352)	-13.6 mmHg Standard Deviation 0.49	-14.2 mmHg Standard Deviation 0.50	-10.4 mmHg Standard Deviation 0.49
Change From Baseline in Trough, Sitting, Clinic Diastolic Blood Pressure Week 8 (n=363; n=350; n=353)	-16.1 mmHg Standard Deviation 0.47	-16.5 mmHg Standard Deviation 0.48	-12.8 mmHg Standard Deviation 0.48

SECONDARY outcome

Timeframe: Baseline, Week 4 and Week 8.

Population: 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.

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.

Outcome measures

Measure	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD n=372 Participants 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 40-80mg Plus Chlorthalidone 12.5-25 mg QD n=357 Participants 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 20-40mg/Hydrochlorothiazide 12.5-25mg QD n=356 Participants 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.
Change From Baseline in Trough Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. Week 4 (n=223; n=227; n=219)	-22.4 mmHg Standard Error 0.95	-23.6 mmHg Standard Error 0.94	-17.4 mmHg Standard Error 0.96
Change From Baseline in Trough Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. Week 8 (n=290; n=278; n=281)	-24.9 mmHg Standard Error 0.79	-26.8 mmHg Standard Error 0.81	-19.6 mmHg Standard Error 0.80

SECONDARY outcome

Timeframe: Baseline, Week 4 and Week 8.

Population: 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.

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.

Outcome measures

Measure	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD n=372 Participants 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 40-80mg Plus Chlorthalidone 12.5-25 mg QD n=357 Participants 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 20-40mg/Hydrochlorothiazide 12.5-25mg QD n=356 Participants 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.
Change From Baseline in Trough Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. Week 4 (n=223; n=227; n=219)	-13.4 mmHg Standard Error 0.66	-14.6 mmHg Standard Error 0.66	-10.9 mmHg Standard Error 0.67
Change From Baseline in Trough Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. Week 8 (n=290; n=278; n=281)	-14.6 mmHg Standard Error 0.56	-15.9 mmHg Standard Error 0.57	-12.0 mmHg Standard Error 0.57

SECONDARY outcome

Timeframe: Baseline, Week 4 and Week 8.

Population: 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.

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.

Outcome measures

Measure	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD n=372 Participants 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 40-80mg Plus Chlorthalidone 12.5-25 mg QD n=357 Participants 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 20-40mg/Hydrochlorothiazide 12.5-25mg QD n=356 Participants 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.
Change From Baseline in 24-hour Mean Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring. Week 4 (n=223; n=227; n=219)	-24.1 mmHg Standard Error 0.81	-24.4 mmHg Standard Error 0.80	-18.4 mmHg Standard Error 0.81
Change From Baseline in 24-hour Mean Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring. Week 8 (n=290; n=278; n=281)	-26.4 mmHg Standard Error 0.69	-27.9 mmHg Standard Error 0.70	-20.7 mmHg Standard Error 0.70

SECONDARY outcome

Timeframe: Baseline, Week 4 and Week 8.

Population: 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.

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.

Outcome measures

Measure	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD n=372 Participants 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 40-80mg Plus Chlorthalidone 12.5-25 mg QD n=357 Participants 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 20-40mg/Hydrochlorothiazide 12.5-25mg QD n=357 Participants 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.
Change From Baseline in 24-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. Week 4 (n=223; n=227; n=219)	-13.9 mmHg Standard Error 0.51	-14.4 mmHg Standard Error 0.51	-10.5 mmHg Standard Error 0.52
Change From Baseline in 24-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. Week 8 (n=290; n=278; n=281)	-15.1 mmHg Standard Error 0.45	-16.4 mmHg Standard Error 0.46	-12.0 mmHg Standard Error 0.46

SECONDARY outcome

Timeframe: Baseline, Week 4 and Week 8.

Population: 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.

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.

Outcome measures

Measure	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD n=372 Participants 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 40-80mg Plus Chlorthalidone 12.5-25 mg QD n=357 Participants 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 20-40mg/Hydrochlorothiazide 12.5-25mg QD n=356 Participants 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.
Change From Baseline in Daytime Mean (6am to 10pm) Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. Week 4 (n=223; n=227; n=219)	-24.5 mmHg Standard Error 0.84	-25.1 mmHg Standard Error 0.83	-18.9 mmHg Standard Error 0.85
Change From Baseline in Daytime Mean (6am to 10pm) Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. Week 8 (n=290; n=278; n=281)	-26.7 mmHg Standard Error 0.72	-28.4 mmHg Standard Error 0.74	-21.0 mmHg Standard Error 0.74

SECONDARY outcome

Timeframe: Baseline, Week 4 and Week 8.

Population: 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.

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.

Outcome measures

Measure	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD n=372 Participants 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 40-80mg Plus Chlorthalidone 12.5-25 mg QD n=357 Participants 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 20-40mg/Hydrochlorothiazide 12.5-25mg QD n=356 Participants 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.
Change From Baseline in Daytime Mean (6am to 10pm) Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. Week 4 (n=223; n=227; n=219)	-14.2 mmHg Standard Error 0.53	-14.7 mmHg Standard Error 0.53	-10.7 mmHg Standard Error 0.54
Change From Baseline in Daytime Mean (6am to 10pm) Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. Week 8 (n=290; n=278; n=281)	-15.3 mmHg Standard Error 0.47	-16.6 mmHg Standard Error 0.48	-12.1 mmHg Standard Error 0.48

SECONDARY outcome

Timeframe: Baseline, Week 4 and Week 8.

Population: 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.

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.

Outcome measures

Measure	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD n=372 Participants 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 40-80mg Plus Chlorthalidone 12.5-25 mg QD n=357 Participants 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 20-40mg/Hydrochlorothiazide 12.5-25mg QD n=356 Participants 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.
Change From Baseline in Nighttime Mean (12am to 6am) Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring Week 4 (n=223; n=227; n=219)	-22.3 mmHg Standard Error 0.87	-21.9 mmHg Standard Error 0.86	-16.6 mmHg Standard Error 0.88
Change From Baseline in Nighttime Mean (12am to 6am) Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring Week 8 (n=290; n=278; n=281)	-25.2 mmHg Standard Error 0.74	-26.3 mmHg Standard Error 0.75	-19.7 mmHg Standard Error 0.75

SECONDARY outcome

Timeframe: Baseline, Week 4 and Week 8.

Population: 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.

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.

Outcome measures

Measure	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD n=372 Participants 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 40-80mg Plus Chlorthalidone 12.5-25 mg QD n=357 Participants 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 20-40mg/Hydrochlorothiazide 12.5-25mg QD n=356 Participants 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.
Change From Baseline in Nighttime Mean (12am to 6am) Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. Week 4 (n=223; n=227; n=219)	-13.4 mmHg Standard Error 0.58	-13.3 mmHg Standard Error 0.58	-9.6 mmHg Standard Error 0.59
Change From Baseline in Nighttime Mean (12am to 6am) Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. Week 8 (n=290; n=278; n=281)	-14.9 mmHg Standard Error 0.51	-15.8 mmHg Standard Error 0.52	-11.8 mmHg Standard Error 0.52

SECONDARY outcome

Timeframe: Baseline, Week 4 and Week 8.

Population: 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.

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.

Outcome measures

Measure	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD n=372 Participants 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 40-80mg Plus Chlorthalidone 12.5-25 mg QD n=357 Participants 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 20-40mg/Hydrochlorothiazide 12.5-25mg QD n=356 Participants 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.
Change From Baseline in 12-hr Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. Week 4 (n=223; n=227; n=219)	-25.0 mmHg Standard Error 0.87	-25.5 mmHg Standard Error 0.86	-19.2 mmHg Standard Error 0.88
Change From Baseline in 12-hr Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. Week 8 (n=290; n=278; n=281)	-27.1 mmHg Standard Error 0.77	-28.8 mmHg Standard Error 0.78	-21.1 mmHg Standard Error 0.78

SECONDARY outcome

Timeframe: Baseline, Week 4 and Week 8.

Population: 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.

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.

Outcome measures

Measure	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD n=372 Participants 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 40-80mg Plus Chlorthalidone 12.5-25 mg QD n=357 Participants 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 20-40mg/Hydrochlorothiazide 12.5-25mg QD n=356 Participants 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.
Change From Baseline in 12-hr Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. Week 4 (n=223; n=227; n=219)	-14.4 mmHg Standard Error 0.56	-14.8 mmHg Standard Error 0.55	-10.8 mmHg Standard Error 0.56
Change From Baseline in 12-hr Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. Week 8 (n=290; n=278; n=281)	-15.4 mmHg Standard Error 0.50	-16.9 mmHg Standard Error 0.51	-12.1 mmHg Standard Error 0.51

SECONDARY outcome

Timeframe: Baseline, Week 2, Week 4, Week 6 and Week 8.

Population: 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.

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.

Outcome measures

Measure	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD n=372 Participants 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 40-80mg Plus Chlorthalidone 12.5-25 mg QD n=357 Participants 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 20-40mg/Hydrochlorothiazide 12.5-25mg QD n=356 Participants 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.
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 Week 2 (n=343; n=334; n=345)	60.3 percentage of participants	57.2 percentage of participants	44.9 percentage of participants
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 Week 4 (n=360; n=347; n=352)	66.1 percentage of participants	68.9 percentage of participants	52.3 percentage of participants
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 Week 6 (n=362; n=350; n=353)	76.8 percentage of participants	73.4 percentage of participants	64.9 percentage of participants
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 Week 8 (n=363; n=350; n=353)	76.0 percentage of participants	76.0 percentage of participants	64.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 2, Week 4, Week 6 and Week 8.

Population: 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.

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.

Outcome measures

Measure	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD n=372 Participants 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 40-80mg Plus Chlorthalidone 12.5-25 mg QD n=357 Participants 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 20-40mg/Hydrochlorothiazide 12.5-25mg QD n=356 Participants 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.
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 Week 4 (n=360; n=347; n=352)	71.4 percentage of participants	73.8 percentage of participants	58.2 percentage of participants
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 Week 2 (n=343; n=334; n=345)	63.6 percentage of participants	66.2 percentage of participants	47.8 percentage of participants
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 Week 6 (n=362; n=350; n=353)	77.9 percentage of participants	76.9 percentage of participants	66.9 percentage of participants
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 Week 8 (n=363; n=350; n=353)	79.9 percentage of participants	79.1 percentage of participants	66.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 2, Week 4, Week 6 and Week 8.

Population: 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.

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.

Outcome measures

Measure	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD n=372 Participants 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 40-80mg Plus Chlorthalidone 12.5-25 mg QD n=357 Participants 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 20-40mg/Hydrochlorothiazide 12.5-25mg QD n=356 Participants 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.
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 Week 2 (n=343; n=334; n=345)	51.3 percentage of participants	48.5 percentage of participants	35.9 percentage of participants
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 Week 4 (n=360; n=347; n=352)	58.1 percentage of participants	61.4 percentage of participants	44.6 percentage of participants
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 Week 6 (n=362; n=350; n=353)	68.8 percentage of participants	65.4 percentage of participants	55.5 percentage of participants
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 Week 8 (n=363; n=350; n=353)	69.4 percentage of participants	68.9 percentage of participants	54.7 percentage of participants

Adverse Events

Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD

Serious events: 4 serious events

Other events: 66 other events

Deaths: 0 deaths

Azilsartan Medoxomil 40-80mg Plus Chlorthalidone 12.5-25 mg QD

Serious events: 8 serious events

Other events: 72 other events

Deaths: 0 deaths

Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD

Serious events: 6 serious events

Other events: 56 other events

Deaths: 0 deaths

Serious adverse events

Measure	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD n=372 participants at risk 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 40-80mg Plus Chlorthalidone 12.5-25 mg QD n=357 participants at risk 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 20-40mg/Hydrochlorothiazide 12.5-25mg QD n=356 participants at risk 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.
Cardiac disorders Cardiac arrest	0.00% 0/372 • 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. 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.	0.28% 1/357 • 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. 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.	0.28% 1/356 • 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. 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.
Gastrointestinal disorders Nausea	0.27% 1/372 • 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. 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.	0.00% 0/357 • 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. 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.	0.00% 0/356 • 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. 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.
Cardiac disorders Coronary artery disease	0.00% 0/372 • 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. 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.	0.00% 0/357 • 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. 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.	0.28% 1/356 • 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. 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.
Cardiac disorders Diastolic dysfunction	0.00% 0/372 • 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. 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.	0.28% 1/357 • 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. 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.	0.00% 0/356 • 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. 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.
Gastrointestinal disorders Diarrhoea	0.27% 1/372 • 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. 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.	0.00% 0/357 • 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. 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.	0.00% 0/356 • 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. 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.
Gastrointestinal disorders Epigastric discomfort	0.27% 1/372 • 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. 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.	0.00% 0/357 • 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. 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.	0.00% 0/356 • 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. 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.
Gastrointestinal disorders Pancreatitis	0.00% 0/372 • 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. 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.	0.28% 1/357 • 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. 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.	0.00% 0/356 • 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. 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.
Gastrointestinal disorders Vomiting	0.27% 1/372 • 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. 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.	0.00% 0/357 • 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. 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.	0.00% 0/356 • 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. 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.
General disorders Chest pain	0.00% 0/372 • 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. 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.	0.00% 0/357 • 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. 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.	0.28% 1/356 • 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. 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.
General disorders Generalised oedema	0.00% 0/372 • 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. 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.	0.28% 1/357 • 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. 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.	0.00% 0/356 • 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. 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.
General disorders Systemic inflammatory response syndrome	0.00% 0/372 • 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. 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.	0.00% 0/357 • 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. 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.	0.28% 1/356 • 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. 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.
Infections and infestations Cellulitis	0.00% 0/372 • 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. 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.	0.28% 1/357 • 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. 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.	0.28% 1/356 • 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. 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.
Infections and infestations Gastroenteritis	0.00% 0/372 • 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. 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.	0.28% 1/357 • 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. 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.	0.00% 0/356 • 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. 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.
Infections and infestations Pneumonia	0.00% 0/372 • 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. 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.	0.28% 1/357 • 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. 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.	0.00% 0/356 • 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. 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.
Infections and infestations Viral infection	0.00% 0/372 • 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. 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.	0.28% 1/357 • 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. 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.	0.00% 0/356 • 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. 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.
Injury, poisoning and procedural complications Heat exhaustion	0.00% 0/372 • 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. 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.	0.00% 0/357 • 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. 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.	0.28% 1/356 • 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. 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.
Injury, poisoning and procedural complications Road traffic accident	0.27% 1/372 • 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. 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.	0.00% 0/357 • 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. 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.	0.00% 0/356 • 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. 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.
Investigations Blood creatinine increased	0.00% 0/372 • 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. 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.	0.28% 1/357 • 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. 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.	0.00% 0/356 • 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. 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.
Investigations Troponin increased	0.00% 0/372 • 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. 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.	0.00% 0/357 • 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. 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.	0.28% 1/356 • 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. 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.
Metabolism and nutrition disorders Dehydration	0.00% 0/372 • 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. 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.	0.00% 0/357 • 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. 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.	0.28% 1/356 • 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. 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.
Nervous system disorders Cerebral infarction	0.00% 0/372 • 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. 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.	0.28% 1/357 • 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. 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.	0.00% 0/356 • 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. 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.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.27% 1/372 • 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. 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.	0.00% 0/357 • 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. 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.	0.28% 1/356 • 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. 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.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/372 • 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. 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.	0.00% 0/357 • 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. 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.	0.28% 1/356 • 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. 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.
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.00% 0/372 • 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. 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.	0.28% 1/357 • 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. 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.	0.00% 0/356 • 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. 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.
Skin and subcutaneous tissue disorders Angioedema	0.00% 0/372 • 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. 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.	0.28% 1/357 • 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. 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.	0.00% 0/356 • 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. 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.
Vascular disorders Deep vein thrombosis	0.00% 0/372 • 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. 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.	0.00% 0/357 • 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. 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.	0.28% 1/356 • 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. 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.
Vascular disorders Shock	0.00% 0/372 • 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. 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.	0.00% 0/357 • 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. 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.	0.28% 1/356 • 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. 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.

Other adverse events

Measure	Azilsartan Medoxomil 20-40mg Plus Chlorthalidone 12.5-25 mg QD n=372 participants at risk 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 40-80mg Plus Chlorthalidone 12.5-25 mg QD n=357 participants at risk 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 20-40mg/Hydrochlorothiazide 12.5-25mg QD n=356 participants at risk 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.
Nervous system disorders Headache	3.8% 14/372 • 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. 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.	3.9% 14/357 • 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. 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.	5.1% 18/356 • 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. 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.
Investigations Blood creatinine increased	9.7% 36/372 • 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. 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.	12.3% 44/357 • 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. 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.	7.0% 25/356 • 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. 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.
Nervous system disorders Dizziness	6.7% 25/372 • 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. 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.	6.7% 24/357 • 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. 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.	5.6% 20/356 • 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. 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.

Additional Information

Sr. VP, Clinical Science

Takeda Global Research and Development Center, Inc.

Phone: 800-778-2860

Email: clinicaltrialregistry@tpna.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER