Azilsartan Medoxomil in the Treatment of Essential Hypertension and Type 2 Diabetes in Asia

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02517866
• Collaborator: (none)
• Enrollment: 380
• Locations: 12
• Arm: 1
• Actual Duration (Months): 16.5
• Patients Per Site: 31.7
• Patients Per Site Per Month: 1.9

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of azilsartan medoxomil (AZM) in Asian adult participants with both essential hypertension and type 2 diabetes.

Condition or Disease	Intervention/Treatment	Phase
Essential Hypertension; Type 2 Diabetes Mellitus	Drug: Azilsartan Medoxomil	Phase 4

Detailed Description

The drug being tested in this study is called azilsartan medoxomil. Azilsartan medoxomil is being tested to treat people who have essential hypertension and type 2 diabetes mellitus (T2DM). This study will look at the blood pressure of people who take azilsartan medoxomil in addition to standard care for T2DM.

The study will enroll approximately 380 patients. All participants will receive azilsartan medoxomil 40 mg tablets to be administered orally, once a day, for 12 weeks. If a participant's blood pressure (BP) has not reached BP goal of <140/85 mmHg at week 6, azilsartan medoxomil dose will be up-titrated to 80 mg daily.

All participants will be asked to take one tablet at the same time each day throughout the study.

This multi-center trial will be conducted in Asia. The overall time to participate in this study is 14 weeks. Participants will make multiple visits to the clinic, and will be contacted by 14 days after last dose of study drug for a follow-up assessment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 380 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective Study of Azilsartan Medoxomil in the Treatment of Patients With Essential Hypertension and Type 2 Diabetes in Asia
• Actual Study Start Date: Jul 13, 2015
• Actual Primary Completion Date: Nov 15, 2016
• Actual Study Completion Date: Nov 25, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Azilsartan medoxomil Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6.	Drug: Azilsartan Medoxomil; Azilsartan medoxomil tablets; Other Names: Edarbi®

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Blood Pressure (BP) <140/85 mmHg (Systolic BP <140 mmHg and Diastolic BP <85 mmHg) by Clinic-Measured Sitting BP at Week 12 [Week 12]

   Three serial BP measurements were determined while the participant was seated, with a sphygmomanometer.

Secondary Outcome Measures

1. Percentage of "Treatment-Naïve" Participants Reaching BP <140/85 mmHg [Up to Week 12]

   Treatment-naïve participants are defined as participants who have not received anti-hypertensive treatment for at least four weeks prior to screening. At each visit 3 serial BP measurements were determined while the participant was seated, with a sphygmomanometer.

2. Percentage of Participants Treated With Calcium Channel Blocker (CCB) Before Baseline Reaching BP<140/85 mmHg [Weeks 6 and 12]

   At each visit three serial BP measurements were determined while the participant was seated, with a sphygmomanometer.

3. Percentage of Participants Treated With Angiotensin Converting Enzyme (ACE) Inhibitors or Other Angiotensin Receptor Blockers (ARBs) Before Baseline Reaching BP <140/85 mmHg [Weeks 6 and 12]

   At each visit 3 serial BP measurements were determined while the participant was seated, with a sphygmomanometer.

4. Percentage of Participants Treated With Thiazides Before Baseline Reaching BP <140/85 mmHg [Weeks 6 and 12]

   At each visit three serial BP measurements were determined while the participant was seated, with a sphygmomanometer.

5. Percentage of "Treatment-Naïve" Participants Reaching BP <130/80 mmHg [Up to Week 12]

   Treatment-naïve participants are defined as participants who have not received anti-hypertensive treatment for at least four weeks prior to screening. At each visit 3 serial BP measurements were determined while the participant was seated, with a sphygmomanometer.

6. Percentage of Participants Treated With CCB Before Baseline Reaching BP <130/80 mmHg [Weeks 6 and 12]

   At each visit 3 serial BP measurements were determined while the participant was seated, with a sphygmomanometer.

7. Percentage of Participants Treated With ACE Inhibitors or Other ARBs Before Baseline Reaching BP <130/80 mmHg [Weeks 6 and 12]

   At each visit 3 serial BP measurements were determined while the participant was seated, with a sphygmomanometer.

8. Percentage of Participants Treated With Thiazides Before Baseline Reaching BP <130/80 mmHg [Weeks 6 and 12]

   At each visit 3 serial BP measurements were determined while the participant was seated, with a sphygmomanometer.

9. Percentage of Participants With Systolic Blood Pressure (SBP) <140 mmHg at Week 12 [Week 12]

   Three serial BP measurements were determined while the participant was seated, with a sphygmomanometer.

10. Percentage of Participants With Diastolic Blood Pressure (DBP) <85 mmHg at Week 12 [Week 12]

    Three serial BP measurements were determined while the participant was seated, with a sphygmomanometer.

11. Percentage of Participants With DBP <90 mmHg at Week 12 [Week 12]

    Three serial BP measurements were determined while the participant was seated, with a sphygmomanometer.

12. Percentage of Participants With BP <130/80 mmHg at Week 12 [Week 12]

    Three serial BP measurements were determined while the participant was seated, with a sphygmomanometer.

13. Percentage of Participants With SBP <130 mmHg at Week 12 [Week 12]

    Three serial BP measurements were determined while the participant was seated, with a sphygmomanometer.

14. Percentage of Participants With DBP <80 mmHg at Week 12 [Week 12]

    Three serial BP measurements were determined while the participant was seated, with a sphygmomanometer.

15. Percentage of Participants With BP <140/90 mmHg at Week 12 [Week 12]

    Three serial BP measurements were determined while the participant was seated, with a sphygmomanometer.

16. Change From Baseline in Trough Sitting SBP at Week 12 [Baseline and Week 12]

    At each visit 3 serial BP measurements were determined while the participant was seated, with a sphygmomanometer. Change from Baseline was estimated using an ANCOVA model with fixed effects, country, baseline hypertension therapy (BHT) and baseline SBP (or DBP) included as a covariate. A negative change from baseline indicates improvement.

17. Change From Baseline in Trough Sitting SBP at Week 12 in "Treatment-Naïve" Participants [Baseline and Week 12]

    At each visit 3 serial BP measurements were determined while the participant was seated, with a sphygmomanometer. Change from Baseline was estimated using an ANCOVA model with fixed effects, country, baseline hypertension therapy (BHT) and baseline SBP (or DBP) included as a covariate. A negative change from baseline indicates improvement.

18. Change From Baseline in DBP at Week 12 [Baseline and Week 12]

    At each visit 3 serial BP measurements were determined while the participant was seated, with a sphygmomanometer. Change from Baseline was estimated using an ANCOVA model with fixed effects, country, BHT and baseline SBP (or DBP) included as a covariate. A negative change from baseline indicates improvement.

19. Change From Baseline in DBP at Week 12 in "Treatment-Naïve" Participants [Baseline and Week 12]

    At each visit 3 serial BP measurements were determined while the participant was seated, with a sphygmomanometer. Change from Baseline was estimated using an ANCOVA model with fixed effects, country, BHT and baseline SBP (or DBP) included as a covariate. A negative change from baseline indicates improvement.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.

2. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.

3. Has type 2 diabetes mellitus (T2DM) with essential hypertension.

4. T2DM participants are either treated by stable life style intervention or by oral antidiabetic drugs (OADs) that are stable, including no dose adjustment within 12 weeks before baseline.

5. Is male or female and aged 18 to 75 years, inclusive.

6. Uncontrolled hypertension (systolic blood pressure ≥140 mmHg to <180 mmHg, or diastolic blood pressure ≥85 mmHg and <110 mmHg at screening and baseline.

7. Has screening glycosylated hemoglobin (HbA1C) <9.5%.

8. Female participants must be either of non-childbearing potential, ie, surgically sterilized (defined as having undergone hysterectomy and/or bilateral oophorectomy and/or bilateral salpingectomy; tubal ligation alone is not considered sufficient) or one year after the last menstrual period; or, if of childbearing potential and participant is sexually active with a nonsterilized male partner, must agree to use routinely adequate contraception from signing of informed consent throughout the duration of study.

Exclusion Criteria:

1. Has systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg despite concurrent treatment with three antihypertensive medications from different classes at adequate doses including a diuretic.

2. Has type 1 or poorly controlled type 2 diabetes mellitus, defined as HbA1c ≥9.5% at screening.

3. Is treated with OADs has not been on stable treatment including no dose change of their OADs for at least 12 weeks prior to baseline.

4. Has been previously treated with azilsartan medoxomil (AZM) or azilsartan.

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

6. Has congestive heart failure (New York Heart Association class III or IV), clinically relevant cardiac arrhythmias (as determined by the investigator's clinical judgment on a participant-by-participant basis), severe obstructive coronary artery disease.

7. Has participated in a clinical trial including interventional and observational studies, or received any investigational compound currently or 30 days prior to screening.

8. Has severe renal impairment (based on estimated glomerular filtration rate [GFR] <30 mL/min/1.73m^2) at Screening.

9. Has hyperkalemia defined as serum potassium >5.0 mEq/L.

10. Has an alanine aminotransferase (ALT) level of greater than 2.5 times the upper limit of normal, active liver disease, or jaundice at screening.

11. Has any clinically relevant disease (eg malignancy, neurological, hepatic abnormalities) and/or significant abnormal laboratory findings (past or present), which, in the opinion of the investigator, may put the participant at risk because of participation in the study.

12. Is taking prohibited medications including lithium and aliskiren (refer to Edarbi® product insert).

13. Has known hypersensitivity to any excipients or angiotensin converting enzyme inhibitor (ACEIs)/ angiotensin receptor blockers (ARBs).

14. Has prior angioedema due to an ACE inhibitor or ARB.

15. Breast feeding or pregnant women or women who are intending to become pregnant before, during or within 1 month after participating in the study; or intending to donate ova during such time period, or refusal to submit to a urine test to rule out pregnancy prior to enrolment and at end of study.

16. Have a history of alcohol abuse, drug abuse or illegal drug addiction within the 6 months prior to signing the informed consent.

17. Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Hong Kong	Hong Kong	China
2		Changhua County		Taiwan
3		Kaohsiung City		Taiwan
4		Kaohsiung		Taiwan
5		Taichung		Taiwan
6		Tainan City		Taiwan
7		Taipei		Taiwan
8		Taoyuan County		Taiwan
9		Bangkok		Thailand
10		Chiang Mai		Thailand
11		Khon Kaen		Thailand
12		Pathumthani		Thailand

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Medical Director Clinical Science, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT02517866
• Other Study ID Numbers: AZI-P4-002; U1111-1156-8501
• First Posted: Aug 7, 2015
• Last Update Posted: Mar 1, 2019
• Last Verified: Oct 1, 2018

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Takeda: Drug therapy
• Additional relevant MeSH terms: Hypertension; Essential Hypertension; Diabetes Mellitus; Diabetes Mellitus, Type 2; Azilsartan medoxomil

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 34 investigative sites in Hong Kong, Taiwan and Thailand from 13 July 2015 to 25 November 2016.
Pre-assignment Detail	Participants with a diagnosis of essential hypertension and type 2 diabetes mellitus (T2DM) were enrolled to receive azilsartan medoxomil at a starting dose of 40 mg increased to 80 mg if blood pressure of <140/85 mmHg was not achieved at Week 6.

Arm/Group Title	Azilsartan Medoxomil (Switched)	Azilsartan Medoxomil (Add-On)	Azilsartan Medoxomil (Treatment-Naïve)
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6. Switched includes participants who switched from their baseline hypertension therapy to azilsartan medoxomil.	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6. Add-On includes participants who added azilsartan medoxomil to their baseline hypertension therapy.	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6. Treatment-naïve includes participants never treated with antihypertensive therapy or participants who did not receive hypertension therapy for at least 4 weeks prior to screening.
Period Title: Overall Study
STARTED	289	90	1
COMPLETED	269	84	1
NOT COMPLETED	20	6	0

Baseline Characteristics

Arm/Group Title	Azilsartan Medoxomil
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6.
Overall Participants	380
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.6 (9.77)
Age, Customized (Count of Participants)
< 65 years old	221 58.2%
>=65 to <75 years old	159 41.8%
Sex: Female, Male (Count of Participants)
Female	197 51.8%
Male	183 48.2%
Race/Ethnicity, Customized (Count of Participants)
Asian	380 100%
Region of Enrollment (Count of Participants)
Taiwan, Province Of China	139 36.6%
Thailand	219 57.6%
Hong Kong	22 5.8%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	161.1 (9.57)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	72.04 (15.072)
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	27.64 (4.354)
Smoking history (Count of Participants)
The participant has never smoked	279 73.4%
The participant is an ex-smoker	75 19.7%
The participant is a current smoker	26 6.8%
Baseline Antihypertensive Treatment Status (participants) [Number]
Treated with ACE inhibitor or ARB before Baseline	202 53.2%
Treated with CCB before Baseline	112 29.5%
Treated with Thiazide before Baseline	30 7.9%
Other	121 31.8%
Glycosylated Hemoglobin (HbA1c) (mmoL/moL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmoL/moL]	7.00 (0.875)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Blood Pressure (BP) <140/85 mmHg (Systolic BP <140 mmHg and Diastolic BP <85 mmHg) by Clinic-Measured Sitting BP at Week 12
Description	Three serial BP measurements were determined while the participant was seated, with a sphygmomanometer.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all participants who took at least 1 dose of azilsartan medoxomil. Missing data was computed using last observation carried forward (LOCF) method. Here, number of participants analyzed is the total number of participants who were evaluable for this outcome measure.

Arm/Group Title	Azilsartan Medoxomil (Switched)	Azilsartan Medoxomil (Add-On)
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6. Switched includes participants who switched from their baseline hypertension therapy to azilsartan medoxomil.	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6. Add-On includes participants who added azilsartan medoxomil to their baseline hypertension therapy.
Measure Participants	276	85
Number (99% Confidence Interval) [percentage of participants]	59.8 15.7%	65.9 NaN

2. Secondary Outcome

Title	Percentage of "Treatment-Naïve" Participants Reaching BP <140/85 mmHg
Description	Treatment-naïve participants are defined as participants who have not received anti-hypertensive treatment for at least four weeks prior to screening. At each visit 3 serial BP measurements were determined while the participant was seated, with a sphygmomanometer.
Time Frame	Up to Week 12

Outcome Measure Data

Analysis Population Description

FAS included all participants who took at least 1 dose of azilsartan medoxomil.

Arm/Group Title	Azilsartan Medoxomil (Treatment-Naïve)
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6. Treatment-naïve includes participants never treated with antihypertensive therapy or participants who did not receive hypertension therapy for at least 4 weeks prior to screening.
Measure Participants	1
Number (99% Confidence Interval) [percentage of participants]	0.0 0%

3. Secondary Outcome

Title	Percentage of Participants Treated With Calcium Channel Blocker (CCB) Before Baseline Reaching BP<140/85 mmHg
Description	At each visit three serial BP measurements were determined while the participant was seated, with a sphygmomanometer.
Time Frame	Weeks 6 and 12

Outcome Measure Data

Analysis Population Description

FAS included all participants who took at least 1 dose of azilsartan medoxomil. Missing data was computed using LOCF method. Here, number of participants analyzed is the participants who received CCB before baseline and are evaluable for this outcome measure.

Arm/Group Title	Azilsartan Medoxomil
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6.
Measure Participants	109
Week 6	57.8 15.2%
Week 12	52.3 13.8%

4. Secondary Outcome

Title	Percentage of Participants Treated With Angiotensin Converting Enzyme (ACE) Inhibitors or Other Angiotensin Receptor Blockers (ARBs) Before Baseline Reaching BP <140/85 mmHg
Description	At each visit 3 serial BP measurements were determined while the participant was seated, with a sphygmomanometer.
Time Frame	Weeks 6 and 12

Outcome Measure Data

Analysis Population Description

FAS included all participants who took at least 1 dose of azilsartan medoxomil. Missing data was computed using LOCF method. Here, number of participants analyzed is the participants who received ACE inhibitors or other ARBs before baseline and are evaluable for this outcome measure.

Arm/Group Title	Azilsartan Medoxomil
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6.
Measure Participants	193
Week 6	63.7 16.8%
Week 12	63.7 16.8%

5. Secondary Outcome

Title	Percentage of Participants Treated With Thiazides Before Baseline Reaching BP <140/85 mmHg
Description	At each visit three serial BP measurements were determined while the participant was seated, with a sphygmomanometer.
Time Frame	Weeks 6 and 12

Outcome Measure Data

Analysis Population Description

FAS included all participants who took at least 1 dose of azilsartan medoxomil. Missing data was computed using LOCF method. Here, number of participants analyzed is the participants who received thiazides before baseline and are evaluable for this outcome measure.

Arm/Group Title	Azilsartan Medoxomil
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6.
Measure Participants	29
Week 6	79.3 20.9%
Week 12	86.2 22.7%

6. Secondary Outcome

Title	Percentage of "Treatment-Naïve" Participants Reaching BP <130/80 mmHg
Description	Treatment-naïve participants are defined as participants who have not received anti-hypertensive treatment for at least four weeks prior to screening. At each visit 3 serial BP measurements were determined while the participant was seated, with a sphygmomanometer.
Time Frame	Up to Week 12

Outcome Measure Data

Analysis Population Description

FAS included all participants who took at least 1 dose of azilsartan medoxomil.

Arm/Group Title	Azilsartan Medoxomil (Treatment-Naïve)
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6. Treatment-naïve includes participants never treated with antihypertensive therapy or participants who did not receive hypertension therapy for at least 4 weeks prior to screening.
Measure Participants	1
Number (99% Confidence Interval) [percentage of participants]	0.0 0%

7. Secondary Outcome

Title	Percentage of Participants Treated With CCB Before Baseline Reaching BP <130/80 mmHg
Description	At each visit 3 serial BP measurements were determined while the participant was seated, with a sphygmomanometer.
Time Frame	Weeks 6 and 12

Outcome Measure Data

Analysis Population Description

FAS included all participants who took at least 1 dose of azilsartan medoxomil. Missing data was computed using LOCF method. Here, number of participants analyzed is the participants who received CCB before baseline and are evaluable for this outcome measure.

Arm/Group Title	Azilsartan Medoxomil
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6.
Measure Participants	109
Week 6	26.6 7%
Week 12	27.5 7.2%

8. Secondary Outcome

Title	Percentage of Participants Treated With ACE Inhibitors or Other ARBs Before Baseline Reaching BP <130/80 mmHg
Description	At each visit 3 serial BP measurements were determined while the participant was seated, with a sphygmomanometer.
Time Frame	Weeks 6 and 12

Outcome Measure Data

Analysis Population Description

FAS included all participants who took at least 1 dose of azilsartan medoxomil. Missing data was computed using LOCF method. Here, number of participants analyzed is the participants who received ACE inhibitors or other ARBs before baseline and are evaluable for this outcome measure.

Arm/Group Title	Azilsartan Medoxomil
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6.
Measure Participants	193
Week 6	31.1 8.2%
Week 12	35.2 9.3%

9. Secondary Outcome

Title	Percentage of Participants Treated With Thiazides Before Baseline Reaching BP <130/80 mmHg
Description	At each visit 3 serial BP measurements were determined while the participant was seated, with a sphygmomanometer.
Time Frame	Weeks 6 and 12

Outcome Measure Data

Analysis Population Description

FAS included all participants who took at least 1 dose of azilsartan medoxomil. Missing data was computed using LOCF method. Here, number of participants analyzed is the participants who received thiazides before baseline and are evaluable for this outcome measure.

Arm/Group Title	Azilsartan Medoxomil
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6.
Measure Participants	29
Week 6	41.4 10.9%
Week 12	51.7 13.6%

10. Secondary Outcome

Title	Percentage of Participants With Systolic Blood Pressure (SBP) <140 mmHg at Week 12
Description	Three serial BP measurements were determined while the participant was seated, with a sphygmomanometer.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

FAS included all participants who took at least 1 dose of azilsartan medoxomil. Missing data was computed using LOCF method. Here, number of participants analyzed is the total number of participants who were evaluable for this outcome measure.

Arm/Group Title	Azilsartan Medoxomil (Switched)	Azilsartan Medoxomil (Add-On)	Azilsartan Medoxomil (Treatment-Naïve)
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6. Switched includes participants who switched from their baseline hypertension therapy to azilsartan medoxomil.	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6. Add-On includes participants who added azilsartan medoxomil to their baseline hypertension therapy.	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6. Treatment-naïve includes participants never treated with antihypertensive therapy or participants who did not receive hypertension therapy for at least 4 weeks prior to screening.
Measure Participants	276	85	1
Number (99% Confidence Interval) [percentage of participants]	68.8 18.1%	70.6 NaN	0.0 NaN

11. Secondary Outcome

Title	Percentage of Participants With Diastolic Blood Pressure (DBP) <85 mmHg at Week 12
Description	Three serial BP measurements were determined while the participant was seated, with a sphygmomanometer.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

FAS included all participants who took at least 1 dose of azilsartan medoxomil. Missing data was computed using LOCF method. Here, number of participants analyzed is the total number of participants who were evaluable for this outcome measure.

Arm/Group Title	Azilsartan Medoxomil (Switched)	Azilsartan Medoxomil (Add-On)	Azilsartan Medoxomil (Treatment-Naïve)
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6. Switched includes participants who switched from their baseline hypertension therapy to azilsartan medoxomil.	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6. Add-On includes participants who added azilsartan medoxomil to their baseline hypertension therapy.	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6. Treatment-naïve includes participants never treated with antihypertensive therapy or participants who did not receive hypertension therapy for at least 4 weeks prior to screening.
Measure Participants	276	85	1
Number (99% Confidence Interval) [percentage of participants]	74.6 19.6%	81.2 NaN	0.0 NaN

12. Secondary Outcome

Title	Percentage of Participants With DBP <90 mmHg at Week 12
Description	Three serial BP measurements were determined while the participant was seated, with a sphygmomanometer.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

FAS included all participants who took at least 1 dose of azilsartan medoxomil. Missing data was computed using LOCF method. Here, number of participants analyzed is the total number of participants who were evaluable for this outcome measure.

Arm/Group Title	Azilsartan Medoxomil (Switched)	Azilsartan Medoxomil (Add-On)	Azilsartan Medoxomil (Treatment-Naïve)
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6. Switched includes participants who switched from their baseline hypertension therapy to azilsartan medoxomil.	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6. Add-On includes participants who added azilsartan medoxomil to their baseline hypertension therapy.	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6. Treatment-naïve includes participants never treated with antihypertensive therapy or participants who did not receive hypertension therapy for at least 4 weeks prior to screening.
Measure Participants	276	85	1
Number (99% Confidence Interval) [percentage of participants]	87.3 23%	87.1 NaN	0.0 NaN

13. Secondary Outcome

Title	Percentage of Participants With BP <130/80 mmHg at Week 12
Description	Three serial BP measurements were determined while the participant was seated, with a sphygmomanometer.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

FAS included all participants who took at least 1 dose of azilsartan medoxomil. Missing data was computed using LOCF method. Here, number of participants analyzed is the total number of participants who were evaluable for this outcome measure.

Arm/Group Title	Azilsartan Medoxomil (Switched)	Azilsartan Medoxomil (Add-On)	Azilsartan Medoxomil (Treatment-Naïve)
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6. Switched includes participants who switched from their baseline hypertension therapy to azilsartan medoxomil.	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6. Add-On includes participants who added azilsartan medoxomil to their baseline hypertension therapy.	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6. Treatment-naïve includes participants never treated with antihypertensive therapy or participants who did not receive hypertension therapy for at least 4 weeks prior to screening.
Measure Participants	276	85	1
Number (99% Confidence Interval) [percentage of participants]	33.7 8.9%	40.0 NaN	0.0 NaN

14. Secondary Outcome

Title	Percentage of Participants With SBP <130 mmHg at Week 12
Description	Three serial BP measurements were determined while the participant was seated, with a sphygmomanometer.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

FAS included all participants who took at least 1 dose of azilsartan medoxomil. Missing data was computed using LOCF method. Here, number of participants analyzed is the total number of participants who were evaluable for this outcome measure.

Arm/Group Title	Azilsartan Medoxomil (Switched)	Azilsartan Medoxomil (Add-On)	Azilsartan Medoxomil (Treatment-Naïve)
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6. Switched includes participants who switched from their baseline hypertension therapy to azilsartan medoxomil.	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6. Add-On includes participants who added azilsartan medoxomil to their baseline hypertension therapy.	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6. Treatment-naïve includes participants never treated with antihypertensive therapy or participants who did not receive hypertension therapy for at least 4 weeks prior to screening.
Measure Participants	276	85	1
Number (99% Confidence Interval) [percentage of participants]	41.3 10.9%	43.5 NaN	0.0 NaN

15. Secondary Outcome

Title	Percentage of Participants With DBP <80 mmHg at Week 12
Description	Three serial BP measurements were determined while the participant was seated, with a sphygmomanometer.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

FAS included all participants who took at least 1 dose of azilsartan medoxomil. Missing data was computed using LOCF method. Here, number of participants analyzed is the total number of participants who were evaluable for this outcome measure.

Arm/Group Title	Azilsartan Medoxomil (Switched)	Azilsartan Medoxomil (Add-On)	Azilsartan Medoxomil (Treatment-Naïve)
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6. Switched includes participants who switched from their baseline hypertension therapy to azilsartan medoxomil.	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6. Add-On includes participants who added azilsartan medoxomil to their baseline hypertension therapy.	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6. Treatment-naïve includes participants never treated with antihypertensive therapy or participants who did not receive hypertension therapy for at least 4 weeks prior to screening.
Measure Participants	276	85	1
Number (99% Confidence Interval) [percentage of participants]	57.6 15.2%	65.9 NaN	0.0 NaN

16. Secondary Outcome

Title	Percentage of Participants With BP <140/90 mmHg at Week 12
Description	Three serial BP measurements were determined while the participant was seated, with a sphygmomanometer.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

FAS included all participants who took at least 1 dose of azilsartan medoxomil. Missing data was computed using LOCF method. Here, number of participants analyzed is the total number of participants who were evaluable for this outcome measure.

Arm/Group Title	Azilsartan Medoxomil (Switched)	Azilsartan Medoxomil (Add-On)	Azilsartan Medoxomil (Treatment-Naïve)
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6. Switched includes participants who switched from their baseline hypertension therapy to azilsartan medoxomil.	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6. Add-On includes participants who added azilsartan medoxomil to their baseline hypertension therapy.	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6. Treatment-naïve includes participants never treated with antihypertensive therapy or participants who did not receive hypertension therapy for at least 4 weeks prior to screening.
Measure Participants	276	85	1
Number (99% Confidence Interval) [percentage of participants]	65.9 17.3%	68.2 NaN	0.0 NaN

17. Secondary Outcome

Title	Change From Baseline in Trough Sitting SBP at Week 12
Description	At each visit 3 serial BP measurements were determined while the participant was seated, with a sphygmomanometer. Change from Baseline was estimated using an ANCOVA model with fixed effects, country, baseline hypertension therapy (BHT) and baseline SBP (or DBP) included as a covariate. A negative change from baseline indicates improvement.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

FAS included all participants who took at least 1 dose of azilsartan medoxomil. Missing data was computed using LOCF method. Here, number of participants analyzed is the total number of participants who were evaluable for this outcome measure.

Arm/Group Title	Azilsartan Medoxomil (Switched)	Azilsartan Medoxomil (Add-On)
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6. Switched includes participants who switched from their baseline hypertension therapy to azilsartan medoxomil.	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6. Add-On includes participants who added azilsartan medoxomil to their baseline hypertension therapy.
Measure Participants	276	90
Least Squares Mean (Standard Error) [mmHg]	-14.1 (1.39)	-13.3 (2.12)

18. Secondary Outcome

Title	Change From Baseline in Trough Sitting SBP at Week 12 in "Treatment-Naïve" Participants
Description	At each visit 3 serial BP measurements were determined while the participant was seated, with a sphygmomanometer. Change from Baseline was estimated using an ANCOVA model with fixed effects, country, baseline hypertension therapy (BHT) and baseline SBP (or DBP) included as a covariate. A negative change from baseline indicates improvement.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

FAS included all participants who took at least 1 dose of azilsartan medoxomil. Missing data was computed using LOCF method. Here, number of participants analyzed is the total number of participants who were evaluable for this outcome measure.

Arm/Group Title	Azilsartan Medoxomil (Treatment-Naïve)
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6. Treatment-naïve includes participants never treated with antihypertensive therapy or participants who did not receive hypertension therapy for at least 4 weeks prior to screening.
Measure Participants	1
Mean (Standard Deviation) [mmHg]	-7 (NA)

19. Secondary Outcome

Title	Change From Baseline in DBP at Week 12
Description	At each visit 3 serial BP measurements were determined while the participant was seated, with a sphygmomanometer. Change from Baseline was estimated using an ANCOVA model with fixed effects, country, BHT and baseline SBP (or DBP) included as a covariate. A negative change from baseline indicates improvement.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

FAS included all participants who took at least 1 dose of azilsartan medoxomil. Missing data was computed using LOCF method. Here, number of participants analyzed is the total number of participants who were analysed for this outcome measure.

Arm/Group Title	Azilsartan Medoxomil (Switched)	Azilsartan Medoxomil (Add-On)
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6. Switched includes participants who switched from their baseline hypertension therapy to azilsartan medoxomil.	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6. Add-On includes participants who added azilsartan medoxomil to their baseline hypertension therapy.
Measure Participants	276	85
Least Squares Mean (Standard Error) [mmHg]	-4.9 (0.76)	-5.7 (1.16)

20. Secondary Outcome

Title	Change From Baseline in DBP at Week 12 in "Treatment-Naïve" Participants
Description	At each visit 3 serial BP measurements were determined while the participant was seated, with a sphygmomanometer. Change from Baseline was estimated using an ANCOVA model with fixed effects, country, BHT and baseline SBP (or DBP) included as a covariate. A negative change from baseline indicates improvement.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

FAS included all participants who took at least 1 dose of azilsartan medoxomil. Missing data was computed using LOCF method. Here, number of participants analyzed is the total number of participants who were analysed for this outcome measure.

Arm/Group Title	Azilsartan Medoxomil (Treatment-Naïve)
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of <140/85 mmHg at Week 6. Treatment-naïve includes participants never treated with antihypertensive therapy or participants who did not receive hypertension therapy for at least 4 weeks prior to screening.
Measure Participants	1
Mean (Standard Deviation) [mmHg]	20 (NA)

Adverse Events

Time Frame	From first dose of study drug up to 14 days after the date of the last dose of study drug (up to 14 weeks)
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Adverse Events are reported as per dose received.
Arm/Group Title	Before Week 6 Azilsartan Medoxomil 40 mg		After Week 6 Azilsartan Medoxomil 40 mg		After Week 6 Azilsartan Medoxomil 80 mg
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 6 weeks.		Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for Week 6 up to Week 12.		Azilsartan medoxomil 80 mg, tablets, orally, once, daily, for Week 6 up to Week 12.
All Cause Mortality
	Before Week 6 Azilsartan Medoxomil 40 mg		After Week 6 Azilsartan Medoxomil 40 mg		After Week 6 Azilsartan Medoxomil 80 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Before Week 6 Azilsartan Medoxomil 40 mg		After Week 6 Azilsartan Medoxomil 40 mg		After Week 6 Azilsartan Medoxomil 80 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/380 (1.1%)		3/258 (1.2%)		1/97 (1%)
Cardiac disorders
Acute myocardial infarction	0/380 (0%)		1/258 (0.4%)		0/97 (0%)
Cardiac failure	1/380 (0.3%)		0/258 (0%)		0/97 (0%)
Infections and infestations
Pneumonia	0/380 (0%)		0/258 (0%)		1/97 (1%)
Sepsis	0/380 (0%)		0/258 (0%)		1/97 (1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	0/380 (0%)		1/258 (0.4%)		0/97 (0%)
Renal and urinary disorders
Acute kidney injury	1/380 (0.3%)		1/258 (0.4%)		1/97 (1%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure	1/380 (0.3%)		0/258 (0%)		0/97 (0%)
Vascular disorders
Hypotension	1/380 (0.3%)		0/258 (0%)		0/97 (0%)
Other (Not Including Serious) Adverse Events
	Before Week 6 Azilsartan Medoxomil 40 mg		After Week 6 Azilsartan Medoxomil 40 mg		After Week 6 Azilsartan Medoxomil 80 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/380 (0%)		0/258 (0%)		0/97 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.