Efficacy and Safety of Azilsartan Medoxomil and Chlorthalidone Compared to Olmesartan Medoxomil and Hydrochlorothiazide in Participants With Moderate to Severe Hypertension.
Sponsor
Takeda (Industry)
Overall Status
Completed
CT.gov ID
NCT01033071
Collaborator
(none)
1,071
94
3
10
11.4
1.1
Study Details
Study Description
Brief Summary
The purpose of this study is to compare the antihypertensive effect of azilsartan medoxomil plus chlorthalidone, once daily (QD), to olmesartan medoxomil plus hydrochlorothiazide in participants with moderate to severe hypertension.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
According to the World Health Organization, hypertension is the most common attributable cause of preventable death in developed nations, as uncontrolled hypertension greatly increases the risk of cardiovascular disease, cerebrovascular disease, and renal failure. As the population ages, the prevalence of hypertension will continue to increase if broad and effective preventive measures are not implemented. Despite the availability of antihypertensive agents, hypertension remains inadequately controlled; only about one third of patients continue to maintain control successfully.
Treatment algorithms for essential hypertension commonly include thiazides or thiazide-like diuretics, either alone or as part of combination treatment. Chlorthalidone is a commercially available, orally administered thiazide-type diuretic agent.
TAK-491 (azilsartan medoxomil) is an angiotensin II receptor blocker developed by Takeda to treat participants with essential hypertension.
This study will compare the safety and tolerability of azilsartan medoxomil plus chlorthalidone (TAK-491CLD) fixed-dose combination to olmesartan medoxomil plus hydrochlorothiazide fixed-dose combination.
Study Design
Study Type:
Interventional
Actual Enrollment
:
1071 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 3b, Double-Blind, Randomized, 12-Week Efficacy and Safety Study Comparing the TAK-491 Plus Chlorthalidone Fixed-Dose Combination vs Olmesartan Medoxomil-Hydrochlorothiazide in Subjects With Moderate to Severe Hypertension
Study Start Date
:
Jan 1, 2010
Actual Primary Completion Date
:
Oct 1, 2010
Actual Study Completion Date
:
Nov 1, 2010
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Azilsartan Medoxomil 20-40mg/Chlorthalidone 12.5-25mg QD
|
Drug: Azilsartan medoxomil and chlorthalidone
Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks.
Participants will be force titrated at Week 4 to azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks.
Participants will then be force titrated at Week 8 to azilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks.
Other Names:
|
| Experimental: Azilsartan Medoxomil 40-80mg/Chlorthalidone 12.5-25mg QD
|
Drug: Azilsartan medoxomil and chlorthalidone
Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks.
Participants will be force titrated at Week 4 to azilsartan medoxomil 80 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks.
Participants will then be force titrated at Week 8 to azilsartan medoxomil 80 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks.
Other Names:
|
| Active Comparator: Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD
|
Drug: Olmesartan medoxomil and hydrochlorothiazide
Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily and azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for up to 4 weeks.
Participants will be force titrated at Week 4 to olmesartan medoxomil 40 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily for the next 4 weeks.
Participants will then be force titrated at Week 8 to olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg combination tablets, orally, once daily for the next 4 weeks.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in Trough, Sitting, Clinic Systolic Blood Pressure. [Baseline and Week 12.]
The change in sitting trough clinic systolic blood pressure measured at week 12 or final visit relative to baseline. Trough blood pressure is the average of the non-missing values of the 3 serial trough sitting systolic blood pressure measurements.
Secondary Outcome Measures
- Change From Baseline in Trough, Sitting, Clinic Systolic Blood Pressure. [Baseline, Week 4 and Week 8.]
The change in sitting trough clinic systolic blood pressure measured at each week indicated relative to baseline. Trough blood pressure is the average of the non-missing values of the 3 serial trough sitting systolic blood pressure measurements.
- Change From Baseline in Trough, Sitting, Clinic Diastolic Blood Pressure. [Baseline, Week 4, Week 8 and Week 12.]
The change in sitting trough clinic diastolic blood pressure measured at each week indicated relative to baseline. Trough blood pressure is the average (arithmetic mean) of the non-missing values of the 3 serial trough sitting systolic blood pressure measurements.
- Change From Baseline in Mean Trough Systolic Blood Pressure by Ambulatory Blood Pressure Monitoring. [Baseline and Week 12.]
The change in trough systolic blood pressure measured at week 12 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.
- Change From Baseline in Mean Trough Diastolic Blood Pressure by Ambulatory Blood Pressure Monitoring. [Baseline and Week 12.]
The change in trough diastolic blood pressure measured at week 12 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.
- Change From Baseline in 24-hour Mean Systolic Blood Pressure by Ambulatory Blood Pressure Monitoring. [Baseline and Week 12.]
The change in 24-hour mean systolic blood pressure measured at week 12 or final visit 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.
- Change From Baseline in 24-hour Mean Diastolic Blood Pressure by Ambulatory Blood Pressure Monitoring. [Baseline and Week 12.]
The change in 24-hour mean diastolic blood pressure measured at week 12 or final visit 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.
- Change From Baseline in Mean Daytime (6 AM to 10 PM) Systolic Blood Pressure by Ambulatory Blood Pressure Monitoring. [Baseline and Week 12.]
The change in daytime (6am to 10pm) mean systolic blood pressure measured at week 12 or final visit relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of all measurements recorded between the hours of 6 AM (inclusive) and 10 PM (exclusive).
- Change From Baseline in Mean Daytime (6 AM to 10 PM) Diastolic Blood Pressure by Ambulatory Blood Pressure Monitoring. [Baseline and Week 12.]
The change in daytime (6am to 10pm) mean diastolic blood pressure measured at week 12 or final visit relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of all measurements recorded between the hours of 6 AM (inclusive) and 10 PM (exclusive).
- Change From Baseline in Mean Nighttime (12 AM to 6 AM) Systolic Blood Pressure by Ambulatory Blood Pressure Monitoring. [Baseline and Week 12.]
The change in the mean nighttime (12am to 6am) systolic blood pressure measured at week 12 or final visit relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Mean nighttime is the average (arithmetic mean) of measurements recorded between the hours of 12 AM (inclusive) and 6 AM (exclusive).
- Change From Baseline in Mean Nighttime (12 AM to 6 AM) Diastolic Blood Pressure by Ambulatory Blood Pressure Monitoring. [Baseline and Week 12.]
The change in the mean nighttime (12am to 6am) diastolic blood pressure measured at week 12 or final visit relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Mean nighttime is the average (arithmetic mean) of measurements recorded between the hours of 12 AM (inclusive) and 6 AM (exclusive).
- Change From Baseline in the Mean Systolic Blood Pressure at 0 to 12 Hours After Dosing by Ambulatory Blood Pressure Monitoring. [Baseline and Week 12.]
The change in the mean 12 hour systolic blood pressure measured at week 12 or final visit 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.
- Change From Baseline in the Mean Diastolic Blood Pressure at 0 to 12 Hours After Dosing by Ambulatory Blood Pressure Monitoring. [Baseline and Week 12.]
The change in the mean 12 hour diastolic blood pressure measured at week 12 or final visit 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.
- Change From Baseline in the Mean Systolic Blood Pressure During Each Hour of the 24-hour Ambulatory Blood Pressure Monitoring. [Baseline and Week 12.]
The change from baseline for each hour interval of the 24-hour ambulatory blood pressure monitoring measured at week 12 or final visit. 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 hour.
- Change From Baseline in the Mean Diastolic Blood Pressure During Each Hour of the 24-hour Ambulatory Blood Pressure Monitoring. [Baseline and Week 12.]
The change from baseline for each hour interval of the 24-hour ambulatory blood pressure monitoring measured at week 12 or final visit. 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 hour.
- Percentage of Participants Who Reached Target Clinic Systolic Blood Pressure of <140 mm Hg and/or Reduction of ≥20 mm Hg From Baseline. [Baseline, Week 4, Week 8 and Week 12.]
Percentage of participants who achieve a clinic systolic blood pressure response measured at each week indicated, defined as less than 140 mm Hg and/or reduction from baseline of greater than or equal to 20 mm Hg. Systolic blood pressure is the arithmetic mean of the non-missing values of the 3serial trough sitting systolic blood pressure measurements.
- Percentage of Participants Who Reached Target Clinic Diastolic Blood Pressure of <90 mm Hg and/or Reduction of ≥10 mm Hg From Baseline. [Baseline, Week 4, Week 8 and Week 12.]
Percentage of participants who achieve a clinic diastolic blood pressure response measured at each week indicated, defined as less than 90 mm Hg and/or reduction from baseline of greater than or equal to 10 mm Hg. Diastolic blood pressure is the arithmetic mean of the non-missing values of the 3 serial trough sitting diastolic blood pressure measurements.
- Percent of Participants Who Reached Target Clinic Systolic Blood Pressure of <140 mm Hg and/or Reduction of ≥20 mm Hg From Baseline and Target Clinic Diastolic Blood Pressure of <90 mm Hg and/or Reduction of ≥10 mm Hg From Baseline. [Baseline, Week 4, Week 8 and Week 12.]
Percentage of participants who achieve both a clinic diastolic and systolic blood pressure response measured at each week indicated, defined as less than 90 mm Hg and/or reduction from baseline of greater than or equal to 10 mm Hg AND less than 140 mm Hg and/or reduction from baseline of greater than or equal to 20 mm Hg. Diastolic and systolic blood pressure is based on the arithmetic mean of the non-missing values of the 3 serial trough sitting blood pressure measurements.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Has a mean sitting clinic systolic blood pressure greater than or equal to 160 and less than or equal to 190 mm Hg.
-
Females of childbearing potential who are sexually active agree to routinely use adequate contraception from Screening through 30 days after the last administered study drug dose.
-
Has clinical laboratory test results within the reference range for the testing laboratory or the investigator does not consider the results to be clinically significant.
-
Is willing to discontinue current antihypertensive medications on Day -21 or Day -28 if the participant is on amlodipine or chlorthalidone.
Exclusion Criteria:
-
Has a mean sitting clinic diastolic blood pressure greater than 119 mm Hg on Day -1.
-
Has a baseline 24-hour ambulatory blood pressure monitoring reading of insufficient quality.
-
Works a night (third) shift.
-
Has an upper arm circumference less than 24 cm or greater than 42 cm.
-
Has secondary hypertension of any etiology.
-
Has a recent history of myocardial infarction, heart failure, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebrovascular accident, or transient ischemic attack.
-
Has clinically significant cardiac conduction defects.
-
Has hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease.
-
Has severe renal dysfunction or disease.
-
Has known or suspected unilateral or bilateral renal artery stenosis.
-
Has a history of cancer that has not been in remission for at least 5 years prior to the first dose of study drug.
-
Has poorly-controlled diabetes mellitus at Screening.
-
Has hypokalemia or hyperkalemia.
-
Has an alanine aminotransferase or aspartate aminotransferase level of greater than 2.5 times the upper limit of normal, active liver disease, or jaundice.
-
Has any other known serious disease or condition that would compromise safety, might affect life expectancy, or make it difficult to successfully manage and follow the participant according to the protocol.
-
Has known hypersensitivity to angiotensin II receptor blockers or thiazide-type diuretics or other sulfonamide-derived compounds.
-
Has a history of drug abuse or a history of alcohol abuse within the past 2 years.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Gulf Shores | Alabama | United States | ||
| 2 | Litchfield Park | Arizona | United States | ||
| 3 | Mesa | Arizona | United States | ||
| 4 | Scottsdale | Arizona | United States | ||
| 5 | Tucson | Arizona | United States | ||
| 6 | Buena Park | California | United States | ||
| 7 | Carmichael | California | United States | ||
| 8 | Greenbrae | California | United States | ||
| 9 | Irvine | California | United States | ||
| 10 | Paramount | California | United States | ||
| 11 | Sacramento | California | United States | ||
| 12 | San Diego | California | United States | ||
| 13 | San Francisco | California | United States | ||
| 14 | Spring Valley | California | United States | ||
| 15 | Wildomar | California | United States | ||
| 16 | Colorado Springs | Colorado | United States | ||
| 17 | Milford | Connecticut | United States | ||
| 18 | Waterbury | Connecticut | United States | ||
| 19 | Newark | Delaware | United States | ||
| 20 | Aventura | Florida | United States | ||
| 21 | Clearwater | Florida | United States | ||
| 22 | Deland | Florida | United States | ||
| 23 | Fort Lauderdale | Florida | United States | ||
| 24 | Miami | Florida | United States | ||
| 25 | Ocala | Florida | United States | ||
| 26 | Plant City | Florida | United States | ||
| 27 | Tallahassee | Florida | United States | ||
| 28 | Tampa | Florida | United States | ||
| 29 | West Palm beach | Florida | United States | ||
| 30 | Winter Haven | Florida | United States | ||
| 31 | Dunwoody | Georgia | United States | ||
| 32 | Roswell | Georgia | United States | ||
| 33 | Suwanee | Georgia | United States | ||
| 34 | Chicago | Illinois | United States | ||
| 35 | Melrose Park | Illinois | United States | ||
| 36 | Naperville | Illinois | United States | ||
| 37 | Avon | Indiana | United States | ||
| 38 | Indianapolis | Indiana | United States | ||
| 39 | Valparaiso | Indiana | United States | ||
| 40 | Crestview Hills | Kentucky | United States | ||
| 41 | Lexington | Kentucky | United States | ||
| 42 | Auburn | Maine | United States | ||
| 43 | Brockton | Massachusetts | United States | ||
| 44 | Hyannis | Massachusetts | United States | ||
| 45 | West Yarmouth | Massachusetts | United States | ||
| 46 | Ann Arbor | Michigan | United States | ||
| 47 | St Louis | Missouri | United States | ||
| 48 | St Peters | Missouri | United States | ||
| 49 | Henderson | Nevada | United States | ||
| 50 | Margate | New Jersey | United States | ||
| 51 | Wildwood Crest | New Jersey | United States | ||
| 52 | Albuquerque | New Mexico | United States | ||
| 53 | Glens Falls | New York | United States | ||
| 54 | Boiling Springs | North Carolina | United States | ||
| 55 | Raleigh | North Carolina | United States | ||
| 56 | Salisbury | North Carolina | United States | ||
| 57 | Cincinnati | Ohio | United States | ||
| 58 | Columbus | Ohio | United States | ||
| 59 | Willoughby Hills | Ohio | United States | ||
| 60 | Oklahoma City | Oklahoma | United States | ||
| 61 | Yukon | Oklahoma | United States | ||
| 62 | Ashland | Oregon | United States | ||
| 63 | Portland | Oregon | United States | ||
| 64 | Bensalem | Pennsylvania | United States | ||
| 65 | Feasterville | Pennsylvania | United States | ||
| 66 | Lansdale | Pennsylvania | United States | ||
| 67 | Pittsburgh | Pennsylvania | United States | ||
| 68 | Reading | Pennsylvania | United States | ||
| 69 | Tipton | Pennsylvania | United States | ||
| 70 | Cranston | Rhode Island | United States | ||
| 71 | Cumberland | Rhode Island | United States | ||
| 72 | Mt Pleasant | South Carolina | United States | ||
| 73 | Simpsonville | South Carolina | United States | ||
| 74 | Beaumont | Texas | United States | ||
| 75 | Dallas | Texas | United States | ||
| 76 | Houston | Texas | United States | ||
| 77 | North Richland Hills | Texas | United States | ||
| 78 | San Antonio | Texas | United States | ||
| 79 | Magna | Utah | United States | ||
| 80 | Manassas | Virginia | United States | ||
| 81 | Lakewood | Washington | United States | ||
| 82 | Port Orchard | Washington | United States | ||
| 83 | Madison | Wisconsin | United States | ||
| 84 | Menomonee Falls | Wisconsin | United States | ||
| 85 | Abbotsford | British Columbia | Canada | ||
| 86 | Powell River | British Columbia | Canada | ||
| 87 | Mount Pearl | Newfoundland and Labrador | Canada | ||
| 88 | Halifax | Nova Scotia | Canada | ||
| 89 | London | Ontario | Canada | ||
| 90 | Ottawa | Ontario | Canada | ||
| 91 | Sarnia | Ontario | Canada | ||
| 92 | Vaughan | Ontario | Canada | ||
| 93 | Whitby | Ontario | Canada | ||
| 94 | Woodstock | Ontario | Canada |
Sponsors and Collaborators
- Takeda
Investigators
- Study Director: Sr VP Clinical Science, Takeda
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Takeda
ClinicalTrials.gov Identifier:
NCT01033071
Other Study ID Numbers:
- TAK-491CLD_303
- U1111-1112-4298
First Posted:
Dec 16, 2009
Last Update Posted:
Feb 7, 2012
Last Verified:
Jan 1, 2012
Keywords provided by Takeda
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants enrolled at 130 investigative sites in Canada and the United States from 08 December 2009 to 04 November 2010. |
|---|---|
| Pre-assignment Detail | Participants with essential hypertension were enrolled in one of three, once-daily (QD) treatment groups. |
| Arm/Group Title | Azilsartan Medoxomil 20-40mg/Chlorthalidone 12.5-25mg QD | Azilsartan Medoxomil 40-80mg/Chlorthalidone 12.5-25mg QD | Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD |
|---|---|---|---|
| Arm/Group Description | Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 80 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 80 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily and azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to olmesartan medoxomil 40 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg combination tablets, orally, once daily for the next 4 weeks. |
| Period Title: Overall Study | |||
| STARTED | 355 | 352 | 364 |
| COMPLETED | 300 | 275 | 317 |
| NOT COMPLETED | 55 | 77 | 47 |
Baseline Characteristics
| Arm/Group Title | Azilsartan Medoxomil 20-40mg/Chlorthalidone 12.5-25mg QD | Azilsartan Medoxomil 40-80mg/Chlorthalidone 12.5-25mg QD | Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD | Total |
|---|---|---|---|---|
| Arm/Group Description | Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 80 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 80 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily and azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to olmesartan medoxomil 40 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg combination tablets, orally, once daily for the next 4 weeks. | Total of all reporting groups |
| Overall Participants | 355 | 352 | 364 | 1071 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
56.4
(10.49)
|
56.7
(10.07)
|
56.7
(10.86)
|
56.6
(10.47)
|
| Age, Customized (participants) [Number] | ||||
| <45 years |
46
13%
|
33
9.4%
|
46
12.6%
|
125
11.7%
|
| Between 45 to 64 years |
235
66.2%
|
241
68.5%
|
234
64.3%
|
710
66.3%
|
| ≥65 years |
74
20.8%
|
78
22.2%
|
84
23.1%
|
236
22%
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
132
37.2%
|
151
42.9%
|
159
43.7%
|
442
41.3%
|
| Male |
223
62.8%
|
201
57.1%
|
205
56.3%
|
629
58.7%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
28
7.9%
|
36
10.2%
|
34
9.3%
|
98
9.2%
|
| Not Hispanic or Latino |
248
69.9%
|
241
68.5%
|
251
69%
|
740
69.1%
|
| Unknown or Not Reported |
79
22.3%
|
75
21.3%
|
79
21.7%
|
233
21.8%
|
| Race (NIH/OMB) (participants) [Number] | ||||
| American Indian or Alaska Native |
2
0.6%
|
5
1.4%
|
5
1.4%
|
12
1.1%
|
| Asian |
13
3.7%
|
11
3.1%
|
11
3%
|
35
3.3%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
1
0.3%
|
2
0.5%
|
3
0.3%
|
| Black or African American |
80
22.5%
|
80
22.7%
|
80
22%
|
240
22.4%
|
| White |
261
73.5%
|
258
73.3%
|
267
73.4%
|
786
73.4%
|
| More than one race |
1
0.3%
|
2
0.6%
|
1
0.3%
|
4
0.4%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | ||||
| United States |
276
77.7%
|
277
78.7%
|
285
78.3%
|
838
78.2%
|
| Canada |
79
22.3%
|
75
21.3%
|
79
21.7%
|
233
21.8%
|
| Weight (kg) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [kg] |
92.34
(20.296)
|
91.47
(20.987)
|
90.83
(18.590)
|
91.54
(19.960)
|
| Height (cm) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [cm] |
171.2
(10.15)
|
169.3
(10.88)
|
169.4
(10.15)
|
170.0
(10.42)
|
| Body Mass Index (BMI) (kg/m2) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [kg/m2] |
31.4
(5.94)
|
31.9
(6.59)
|
31.6
(5.92)
|
31.6
(6.15)
|
| Estimated glomerular filtration rate (eGFR) (participants) [Number] | ||||
| ≥0 to <30 |
0
0%
|
0
0%
|
1
0.3%
|
1
0.1%
|
| ≥30 to <60 |
26
7.3%
|
29
8.2%
|
25
6.9%
|
80
7.5%
|
| ≥60 to <90 |
224
63.1%
|
220
62.5%
|
246
67.6%
|
690
64.4%
|
| ≥90 |
105
29.6%
|
103
29.3%
|
91
25%
|
299
27.9%
|
| Missing |
0
0%
|
0
0%
|
1
0.3%
|
1
0.1%
|
Outcome Measures
| Title | Change From Baseline in Trough, Sitting, Clinic Systolic Blood Pressure. |
|---|---|
| Description | The change in sitting trough clinic systolic blood pressure measured at week 12 or final visit relative to baseline. Trough blood pressure is the average of the non-missing values of the 3 serial trough sitting systolic blood pressure measurements. |
| Time Frame | Baseline and Week 12. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. |
| Arm/Group Title | Azilsartan Medoxomil 20-40mg/Chlorthalidone 12.5-25mg QD | Azilsartan Medoxomil 40-80mg/Chlorthalidone 12.5-25mg QD | Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD |
|---|---|---|---|
| Arm/Group Description | Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 80 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 80 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily and azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to olmesartan medoxomil 40 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg combination tablets, orally, once daily for the next 4 weeks. |
| Measure Participants | 344 | 330 | 354 |
| Least Squares Mean (Standard Error) [mmHg] |
-42.5
(0.81)
|
-44.0
(0.83)
|
-37.1
(0.80)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Azilsartan Medoxomil 20-40mg/Chlorthalidone 12.5-25mg QD, Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD |
|---|---|---|
| Comments | Analysis of covariance (ANCOVA) model with treatment group as a fixed effect and baseline value as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | Overall Type 1 error rate of 0.05 controlled using 'Closed Testing' principle (hypothesis of "all treatment groups equal" first tested at 0.05 significance level; upon rejection of this hypothesis, pairwise comparison was tested at the 0.05 level. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -5.3 | |
| Confidence Interval |
() 95% -7.6 to -3.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Azilsartan Medoxomil 40-80mg/Chlorthalidone 12.5-25mg QD, Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD |
|---|---|---|
| Comments | ANCOVA model with treatment group as a fixed effect and baseline value as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | Overall Type 1 error rate of 0.05 controlled using 'Closed Testing' principle (hypothesis of "all treatment groups equal" first tested at 0.05 significance level; upon rejection of this hypothesis, pairwise comparison was tested at the 0.05 level. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -6.9 | |
| Confidence Interval |
(2-Sided) 95% -9.2 to -4.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in Trough, Sitting, Clinic Systolic Blood Pressure. |
|---|---|
| Description | The change in sitting trough clinic systolic blood pressure measured at each week indicated relative to baseline. Trough blood pressure is the average of the non-missing values of the 3 serial trough sitting systolic blood pressure measurements. |
| Time Frame | Baseline, Week 4 and Week 8. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. |
| Arm/Group Title | Azilsartan Medoxomil 20-40mg/Chlorthalidone 12.5-25mg QD | Azilsartan Medoxomil 40-80mg/Chlorthalidone 12.5-25mg QD | Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD |
|---|---|---|---|
| Arm/Group Description | Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 80 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 80 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily and azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to olmesartan medoxomil 40 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg combination tablets, orally, once daily for the next 4 weeks. |
| Measure Participants | 355 | 352 | 364 |
| Week 4 (n=343; n=330; n=352) |
-34.7
(0.77)
|
-36.7
(0.79)
|
-29.7
(0.76)
|
| Week 8 (n=344; n=330; n=353) |
-39.1
(0.78)
|
-39.4
(0.80)
|
-33.5
(0.77)
|
| Title | Change From Baseline in Trough, Sitting, Clinic Diastolic Blood Pressure. |
|---|---|
| Description | The change in sitting trough clinic diastolic blood pressure measured at each week indicated relative to baseline. Trough blood pressure is the average (arithmetic mean) of the non-missing values of the 3 serial trough sitting systolic blood pressure measurements. |
| Time Frame | Baseline, Week 4, Week 8 and Week 12. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. |
| Arm/Group Title | Azilsartan Medoxomil 20-40mg/Chlorthalidone 12.5-25mg QD | Azilsartan Medoxomil 40-80mg/Chlorthalidone 12.5-25mg QD | Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD |
|---|---|---|---|
| Arm/Group Description | Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 80 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 80 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily and azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to olmesartan medoxomil 40 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg combination tablets, orally, once daily for the next 4 weeks. |
| Measure Participants | 355 | 352 | 364 |
| Week 4 (n=343; n=330; n=352) |
-14.9
(0.46)
|
-15.8
(0.47)
|
-11.7
(0.45)
|
| Week 8 (n=344; n=330; n=353) |
-17.0
(0.48)
|
-17.7
(0.49)
|
-13.9
(0.48)
|
| Week 12 (n=344; n=330; n=354) |
-18.8
(0.47)
|
-20.5
(0.48)
|
-16.4
(0.46)
|
| Title | Change From Baseline in Mean Trough Systolic Blood Pressure by Ambulatory Blood Pressure Monitoring. |
|---|---|
| Description | The change in trough systolic blood pressure measured at week 12 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Trough is the average of all measurements recorded from 22 to 24 hours after dosing. |
| Time Frame | Baseline and Week 12. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. |
| Arm/Group Title | Azilsartan Medoxomil 20-40mg/Chlorthalidone 12.5-25mg QD | Azilsartan Medoxomil 40-80mg/Chlorthalidone 12.5-25mg QD | Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD |
|---|---|---|---|
| Arm/Group Description | Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 80 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 80 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily and azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to olmesartan medoxomil 40 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg combination tablets, orally, once daily for the next 4 weeks. |
| Measure Participants | 232 | 214 | 238 |
| Least Squares Mean (Standard Error) [mmHg] |
-32.9
(0.86)
|
-34.9
(0.90)
|
-25.9
(0.85)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Azilsartan Medoxomil 20-40mg/Chlorthalidone 12.5-25mg QD, Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD |
|---|---|---|
| Comments | ANCOVA model with treatment group as a fixed effect and baseline value as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | Tested at the 0.05 significance level. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -7.0 | |
| Confidence Interval |
(2-Sided) 95% -9.4 to -4.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Azilsartan Medoxomil 40-80mg/Chlorthalidone 12.5-25mg QD, Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD |
|---|---|---|
| Comments | ANCOVA model with treatment group as a fixed effect and baseline value as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | Tested at the 0.05 significance level. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -9.0 | |
| Confidence Interval |
(2-Sided) 95% -11.5 to -6.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in Mean Trough Diastolic Blood Pressure by Ambulatory Blood Pressure Monitoring. |
|---|---|
| Description | The change in trough diastolic blood pressure measured at week 12 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Trough is the average of all measurements recorded from 22 to 24 hours after dosing. |
| Time Frame | Baseline and Week 12. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. |
| Arm/Group Title | Azilsartan Medoxomil 20-40mg/Chlorthalidone 12.5-25mg QD | Azilsartan Medoxomil 40-80mg/Chlorthalidone 12.5-25mg QD | Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD |
|---|---|---|---|
| Arm/Group Description | Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 80 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 80 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily and azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to olmesartan medoxomil 40 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg combination tablets, orally, once daily for the next 4 weeks. |
| Measure Participants | 232 | 214 | 238 |
| Least Squares Mean (Standard Error) [mmHg] |
-19.8
(0.55)
|
-20.2
(0.57)
|
-16.0
(0.54)
|
| Title | Change From Baseline in 24-hour Mean Systolic Blood Pressure by Ambulatory Blood Pressure Monitoring. |
|---|---|
| Description | The change in 24-hour mean systolic blood pressure measured at week 12 or final visit relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing. |
| Time Frame | Baseline and Week 12. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. |
| Arm/Group Title | Azilsartan Medoxomil 20-40mg/Chlorthalidone 12.5-25mg QD | Azilsartan Medoxomil 40-80mg/Chlorthalidone 12.5-25mg QD | Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD |
|---|---|---|---|
| Arm/Group Description | Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 80 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 80 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily and azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to olmesartan medoxomil 40 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg combination tablets, orally, once daily for the next 4 weeks. |
| Measure Participants | 232 | 214 | 238 |
| Least Squares Mean (Standard Error) [mmHg] |
-33.9
(0.76)
|
-36.3
(0.79)
|
-27.5
(0.75)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Azilsartan Medoxomil 20-40mg/Chlorthalidone 12.5-25mg QD, Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD |
|---|---|---|
| Comments | ANCOVA model with treatment group as a fixed effect and baseline value as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | Tested at the 0.05 significance level. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -6.4 | |
| Confidence Interval |
(2-Sided) 95% -8.5 to -4.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Azilsartan Medoxomil 40-80mg/Chlorthalidone 12.5-25mg QD, Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD |
|---|---|---|
| Comments | ANCOVA model with treatment group as a fixed effect and baseline value as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | Tested at the 0.05 significance level. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -8.8 | |
| Confidence Interval |
(2-Sided) 95% -11.0 to -6.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in 24-hour Mean Diastolic Blood Pressure by Ambulatory Blood Pressure Monitoring. |
|---|---|
| Description | The change in 24-hour mean diastolic blood pressure measured at week 12 or final visit relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing. |
| Time Frame | Baseline and Week 12. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. |
| Arm/Group Title | Azilsartan Medoxomil 20-40mg/Chlorthalidone 12.5-25mg QD | Azilsartan Medoxomil 40-80mg/Chlorthalidone 12.5-25mg QD | Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD |
|---|---|---|---|
| Arm/Group Description | Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 80 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 80 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily and azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to olmesartan medoxomil 40 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg combination tablets, orally, once daily for the next 4 weeks. |
| Measure Participants | 232 | 214 | 238 |
| Least Squares Mean (Standard Error) [mmHg] |
-19.4
(0.45)
|
-20.7
(0.46)
|
-16.2
(0.44)
|
| Title | Change From Baseline in Mean Daytime (6 AM to 10 PM) Systolic Blood Pressure by Ambulatory Blood Pressure Monitoring. |
|---|---|
| Description | The change in daytime (6am to 10pm) mean systolic blood pressure measured at week 12 or final visit relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of all measurements recorded between the hours of 6 AM (inclusive) and 10 PM (exclusive). |
| Time Frame | Baseline and Week 12. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. |
| Arm/Group Title | Azilsartan Medoxomil 20-40mg/Chlorthalidone 12.5-25mg QD | Azilsartan Medoxomil 40-80mg/Chlorthalidone 12.5-25mg QD | Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD |
|---|---|---|---|
| Arm/Group Description | Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 80 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 80 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily and azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to olmesartan medoxomil 40 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg combination tablets, orally, once daily for the next 4 weeks. |
| Measure Participants | 232 | 214 | 238 |
| Least Squares Mean (Standard Error) [mmHg] |
-35.3
(0.80)
|
-37.9
(0.84)
|
-28.8
(0.79)
|
| Title | Change From Baseline in Mean Daytime (6 AM to 10 PM) Diastolic Blood Pressure by Ambulatory Blood Pressure Monitoring. |
|---|---|
| Description | The change in daytime (6am to 10pm) mean diastolic blood pressure measured at week 12 or final visit relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of all measurements recorded between the hours of 6 AM (inclusive) and 10 PM (exclusive). |
| Time Frame | Baseline and Week 12. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. |
| Arm/Group Title | Azilsartan Medoxomil 20-40mg/Chlorthalidone 12.5-25mg QD | Azilsartan Medoxomil 40-80mg/Chlorthalidone 12.5-25mg QD | Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD |
|---|---|---|---|
| Arm/Group Description | Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 80 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 80 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily and azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to olmesartan medoxomil 40 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg combination tablets, orally, once daily for the next 4 weeks. |
| Measure Participants | 232 | 214 | 238 |
| Least Squares Mean (Standard Error) [mmHg] |
-20.1
(0.48)
|
-21.8
(0.50)
|
-17.0
(0.47)
|
| Title | Change From Baseline in Mean Nighttime (12 AM to 6 AM) Systolic Blood Pressure by Ambulatory Blood Pressure Monitoring. |
|---|---|
| Description | The change in the mean nighttime (12am to 6am) systolic blood pressure measured at week 12 or final visit relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Mean nighttime is the average (arithmetic mean) of measurements recorded between the hours of 12 AM (inclusive) and 6 AM (exclusive). |
| Time Frame | Baseline and Week 12. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. |
| Arm/Group Title | Azilsartan Medoxomil 20-40mg/Chlorthalidone 12.5-25mg QD | Azilsartan Medoxomil 40-80mg/Chlorthalidone 12.5-25mg QD | Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD |
|---|---|---|---|
| Arm/Group Description | Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 80 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 80 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily and azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to olmesartan medoxomil 40 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg combination tablets, orally, once daily for the next 4 weeks. |
| Measure Participants | 232 | 214 | 238 |
| Least Squares Mean (Standard Error) [mmHg] |
-29.6
(0.78)
|
-31.8
(0.81)
|
-23.9
(0.77)
|
| Title | Change From Baseline in Mean Nighttime (12 AM to 6 AM) Diastolic Blood Pressure by Ambulatory Blood Pressure Monitoring. |
|---|---|
| Description | The change in the mean nighttime (12am to 6am) diastolic blood pressure measured at week 12 or final visit relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Mean nighttime is the average (arithmetic mean) of measurements recorded between the hours of 12 AM (inclusive) and 6 AM (exclusive). |
| Time Frame | Baseline and Week 12. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. |
| Arm/Group Title | Azilsartan Medoxomil 20-40mg/Chlorthalidone 12.5-25mg QD | Azilsartan Medoxomil 40-80mg/Chlorthalidone 12.5-25mg QD | Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD |
|---|---|---|---|
| Arm/Group Description | Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 80 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 80 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily and azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to olmesartan medoxomil 40 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg combination tablets, orally, once daily for the next 4 weeks. |
| Measure Participants | 232 | 214 | 238 |
| Least Squares Mean (Standard Error) [mmHg] |
-17.5
(0.48)
|
-18.0
(0.50)
|
-14.0
(0.48)
|
| Title | Change From Baseline in the Mean Systolic Blood Pressure at 0 to 12 Hours After Dosing by Ambulatory Blood Pressure Monitoring. |
|---|---|
| Description | The change in the mean 12 hour systolic blood pressure measured at week 12 or final visit 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. |
| Time Frame | Baseline and Week 12. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. |
| Arm/Group Title | Azilsartan Medoxomil 20-40mg/Chlorthalidone 12.5-25mg QD | Azilsartan Medoxomil 40-80mg/Chlorthalidone 12.5-25mg QD | Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD |
|---|---|---|---|
| Arm/Group Description | Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 80 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 80 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily and azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to olmesartan medoxomil 40 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg combination tablets, orally, once daily for the next 4 weeks. |
| Measure Participants | 232 | 214 | 238 |
| Least Squares Mean (Standard Error) [mmHg] |
-36.2
(0.86)
|
-38.8
(0.89)
|
-29.7
(0.85)
|
| Title | Change From Baseline in the Mean Diastolic Blood Pressure at 0 to 12 Hours After Dosing by Ambulatory Blood Pressure Monitoring. |
|---|---|
| Description | The change in the mean 12 hour diastolic blood pressure measured at week 12 or final visit 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. |
| Time Frame | Baseline and Week 12. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. |
| Arm/Group Title | Azilsartan Medoxomil 20-40mg/Chlorthalidone 12.5-25mg QD | Azilsartan Medoxomil 40-80mg/Chlorthalidone 12.5-25mg QD | Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD |
|---|---|---|---|
| Arm/Group Description | Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 80 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 80 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily and azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to olmesartan medoxomil 40 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg combination tablets, orally, once daily for the next 4 weeks. |
| Measure Participants | 232 | 214 | 238 |
| Least Squares Mean (Standard Error) [mmHg] |
-20.4
(0.51)
|
-22.2
(0.53)
|
-17.5
(0.50)
|
| Title | Change From Baseline in the Mean Systolic Blood Pressure During Each Hour of the 24-hour Ambulatory Blood Pressure Monitoring. |
|---|---|
| Description | The change from baseline for each hour interval of the 24-hour ambulatory blood pressure monitoring measured at week 12 or final visit. 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 hour. |
| Time Frame | Baseline and Week 12. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. |
| Arm/Group Title | Azilsartan Medoxomil 20-40mg/Chlorthalidone 12.5-25mg QD | Azilsartan Medoxomil 40-80mg/Chlorthalidone 12.5-25mg QD | Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD |
|---|---|---|---|
| Arm/Group Description | Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 80 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 80 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily and azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to olmesartan medoxomil 40 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg combination tablets, orally, once daily for the next 4 weeks. |
| Measure Participants | 355 | 352 | 364 |
| 0 to 1 Hour (n=232; n=212; n=237) |
-33.6
(0.96)
|
-36.2
(1.00)
|
-26.8
(0.95)
|
| 1 to 2 Hour (n=232; n=214; n=238) |
-33.4
(0.98)
|
-36.4
(1.02)
|
-27.5
(0.97)
|
| 2 to 3 Hour (n=232; n=214; n=238) |
-36.7
(1.02)
|
-39.3
(1.06)
|
-30.0
(1.00)
|
| 3 to 4 Hour (n=232; n=214; n=238) |
-36.6
(1.07)
|
-40.3
(1.12)
|
-29.6
(1.06)
|
| 4 to 5 Hour (n=232; n=214; n=238) |
-36.8
(1.07)
|
-40.8
(1.11)
|
-30.1
(1.06)
|
| 5 to 6 Hour (n=232; n=214; n=238) |
-37.2
(1.02)
|
-41.2
(1.06)
|
-31.5
(1.00)
|
| 6 to 7 Hour (n=232; n=214; n=238) |
-36.3
(1.04)
|
-38.6
(1.08)
|
-29.8
(1.02)
|
| 7 to 8 Hour (n=232; n=214; n=238) |
-37.2
(1.02)
|
-38.5
(1.06)
|
-29.7
(1.00)
|
| 8 to 9 Hour (n=232; n=214; n=238) |
-37.3
(1.02)
|
-38.1
(1.06)
|
-30.5
(1.01)
|
| 9 to 10 Hour (n=232; n=214; n=238) |
-36.9
(0.99)
|
-38.0
(1.04)
|
-30.8
(0.98)
|
| 10 to 11 Hour (n=232; n=214; n=238) |
-36.1
(1.02)
|
-37.6
(1.06)
|
-29.4
(1.01)
|
| 11 to 12 Hour (n=232; n=214; n=238) |
-35.2
(1.01)
|
-38.2
(1.05)
|
-29.3
(1.00)
|
| 12 to 13 Hour (n=232; n=214; n=238) |
-34.8
(1.05)
|
-36.2
(1.09)
|
-27.7
(1.04)
|
| 13 to 14 Hour (n=232; n=214; n=238) |
-34.1
(1.06)
|
-35.3
(1.11)
|
-26.4
(1.05)
|
| 14 to 15 Hour (n=232; n=214; n=238) |
-33.4
(1.06)
|
-35.0
(1.10)
|
-26.2
(1.04)
|
| 15 to 16 Hour (n=232; n=214; n=238) |
-30.9
(0.99)
|
-32.9
(1.03)
|
-25.3
(0.97)
|
| 16 to 17 Hour (n=232; n=214; n=238) |
-29.6
(0.94)
|
-31.1
(0.98)
|
-24.5
(0.93)
|
| 17 to 18 Hour (n=231; n=214; n=238) |
-28.5
(0.93)
|
-30.8
(0.97)
|
-23.1
(0.92)
|
| 18 to 19 Hour (n=232; n=214; n=238) |
-29.5
(0.90)
|
-31.9
(0.94)
|
-24.3
(0.89)
|
| 19 to 20 Hour (n=232; n=214; n=238) |
-29.7
(0.89)
|
-32.5
(0.93)
|
-23.5
(0.88)
|
| 20 to 21 Hour (n=232; n=214; n=238) |
-28.2
(0.94)
|
-31.2
(0.98)
|
-23.0
(0.92)
|
| 21 to 22 Hour (n=232; n=214; n=238) |
-30.6
(0.95)
|
-32.8
(0.99)
|
-24.6
(0.93)
|
| 22 to 23 Hour (n=232; n=214; n=238) |
-32.9
(0.94)
|
-34.0
(0.98)
|
-25.9
(0.92)
|
| 23 to 24 Hour (n=232; n=214; n=238) |
-33.1
(0.92)
|
-35.8
(0.96)
|
-26.1
(0.91)
|
| Title | Change From Baseline in the Mean Diastolic Blood Pressure During Each Hour of the 24-hour Ambulatory Blood Pressure Monitoring. |
|---|---|
| Description | The change from baseline for each hour interval of the 24-hour ambulatory blood pressure monitoring measured at week 12 or final visit. 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 hour. |
| Time Frame | Baseline and Week 12. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. |
| Arm/Group Title | Azilsartan Medoxomil 20-40mg/Chlorthalidone 12.5-25mg QD | Azilsartan Medoxomil 40-80mg/Chlorthalidone 12.5-25mg QD | Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD |
|---|---|---|---|
| Arm/Group Description | Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 80 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 80 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily and azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to olmesartan medoxomil 40 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg combination tablets, orally, once daily for the next 4 weeks. |
| Measure Participants | 355 | 352 | 364 |
| 0 to 1 Hour (n=232; n=212; n=237) |
-18.2
(0.59)
|
-20.4
(0.62)
|
-15.2
(0.59)
|
| 1 to 2 Hour (n=232; n=214; n=238) |
-18.8
(0.65)
|
-20.9
(0.67)
|
-15.9
(0.64)
|
| 2 to 3 Hour (n=232; n=214; n=238) |
-21.2
(0.66)
|
-23.4
(0.69)
|
-17.7
(0.65)
|
| 3 to 4 Hour (n=232; n=214; n=238) |
-20.8
(0.69)
|
-23.7
(0.72)
|
-18.2
(0.68)
|
| 4 to 5 Hour (n=232; n=214; n=238) |
-21.7
(0.67)
|
-23.7
(0.70)
|
-17.9
(0.66)
|
| 5 to 6 Hour (n=232; n=214; n=238) |
-20.9
(0.67)
|
-23.6
(0.70)
|
-19.0
(0.66)
|
| 6 to 7 Hour (n=232; n=214; n=238) |
-20.8
(0.65)
|
-22.0
(0.67)
|
-18.0
(0.64)
|
| 7 to 8 Hour (n=232; n=214; n=238) |
-20.5
(0.66)
|
-21.9
(0.69)
|
-17.7
(0.65)
|
| 8 to 9 Hour (n=232; n=214; n=238) |
-20.7
(0.67)
|
-21.5
(0.69)
|
-17.9
(0.66)
|
| 9 to 10 Hour (n=232; n=214; n=238) |
-21.0
(0.66)
|
-21.9
(0.68)
|
-18.3
(0.65)
|
| 10 to 11 Hour (n=232; n=214; n=238) |
-19.7
(0.67)
|
-20.7
(0.70)
|
-16.7
(0.66)
|
| 11 to 12 Hour (n=232; n=214; n=238) |
-19.3
(0.69)
|
-21.2
(0.72)
|
-17.0
(0.68)
|
| 12 to 13 Hour (n=232; n=214; n=238) |
-19.2
(0.73)
|
-20.3
(0.76)
|
-16.0
(0.72)
|
| 13 to 14 Hour (n=232; n=214; n=238) |
-19.6
(0.72)
|
-19.5
(0.75)
|
-15.3
(0.71)
|
| 14 to 15 Hour (n=232; n=214; n=238) |
-18.9
(0.72)
|
-19.7
(0.75)
|
-15.4
(0.71)
|
| 15 to 16 Hour (n=232; n=214; n=238) |
-17.8
(0.65)
|
-18.6
(0.68)
|
-14.5
(0.65)
|
| 16 to 17 Hour (n=232; n=214; n=238) |
-17.2
(0.65)
|
-16.9
(0.68)
|
-13.9
(0.64)
|
| 17 to 18 Hour (n=231; n=214; n=238) |
-16.6
(0.64)
|
-17.1
(0.66)
|
-13.2
(0.63)
|
| 18 to 19 Hour (n=232; n=214; n=238) |
-17.4
(0.65)
|
-18.1
(0.67)
|
-14.3
(0.64)
|
| 19 to 20 Hour (n=232; n=214; n=238) |
-17.8
(0.60)
|
-18.5
(0.63)
|
-13.8
(0.60)
|
| 20 to 21 Hour (n=232; n=214; n=238) |
-16.7
(0.64)
|
-18.4
(0.67)
|
-13.9
(0.63)
|
| 21 to 22 Hour (n=232; n=214; n=238) |
-17.8
(0.66)
|
-18.5
(0.69)
|
-14.7
(0.65)
|
| 22 to 23 Hour (n=232; n=214; n=238) |
-19.5
(0.62)
|
-19.6
(0.65)
|
-15.6
(0.62)
|
| 23 to 24 Hour (n=232; n=214; n=238) |
-20.2
(0.60)
|
-21.0
(0.62)
|
-16.4
(0.59)
|
| Title | Percentage of Participants Who Reached Target Clinic Systolic Blood Pressure of <140 mm Hg and/or Reduction of ≥20 mm Hg From Baseline. |
|---|---|
| Description | Percentage of participants who achieve a clinic systolic blood pressure response measured at each week indicated, defined as less than 140 mm Hg and/or reduction from baseline of greater than or equal to 20 mm Hg. Systolic blood pressure is the arithmetic mean of the non-missing values of the 3serial trough sitting systolic blood pressure measurements. |
| Time Frame | Baseline, Week 4, Week 8 and Week 12. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. |
| Arm/Group Title | Azilsartan Medoxomil 20-40mg/Chlorthalidone 12.5-25mg QD | Azilsartan Medoxomil 40-80mg/Chlorthalidone 12.5-25mg QD | Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD |
|---|---|---|---|
| Arm/Group Description | Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 80 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 80 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily and azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to olmesartan medoxomil 40 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg combination tablets, orally, once daily for the next 4 weeks. |
| Measure Participants | 355 | 352 | 364 |
| Week 4 (n=343; n=330; n=352) |
87.8
24.7%
|
90.0
25.6%
|
79.8
21.9%
|
| Week 8 (n=344; n=330; n=353) |
93.3
26.3%
|
92.4
26.3%
|
85.6
23.5%
|
| Week 12 (n=344; n=330; n=354) |
93.0
26.2%
|
94.2
26.8%
|
89.3
24.5%
|
| Title | Percentage of Participants Who Reached Target Clinic Diastolic Blood Pressure of <90 mm Hg and/or Reduction of ≥10 mm Hg From Baseline. |
|---|---|
| Description | Percentage of participants who achieve a clinic diastolic blood pressure response measured at each week indicated, defined as less than 90 mm Hg and/or reduction from baseline of greater than or equal to 10 mm Hg. Diastolic blood pressure is the arithmetic mean of the non-missing values of the 3 serial trough sitting diastolic blood pressure measurements. |
| Time Frame | Baseline, Week 4, Week 8 and Week 12. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. |
| Arm/Group Title | Azilsartan Medoxomil 20-40mg/Chlorthalidone 12.5-25mg QD | Azilsartan Medoxomil 40-80mg/Chlorthalidone 12.5-25mg QD | Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD |
|---|---|---|---|
| Arm/Group Description | Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 80 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 80 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily and azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to olmesartan medoxomil 40 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg combination tablets, orally, once daily for the next 4 weeks. |
| Measure Participants | 355 | 352 | 364 |
| Week 4 (n=343; n=330; n=352) |
89.2
25.1%
|
89.7
25.5%
|
85.2
23.4%
|
| Week 8 (n=344; n=330; n=353) |
90.7
25.5%
|
90.9
25.8%
|
87.8
24.1%
|
| Week 12 (n=344; n=330; n=354) |
94.5
26.6%
|
95.8
27.2%
|
91.5
25.1%
|
| Title | Percent of Participants Who Reached Target Clinic Systolic Blood Pressure of <140 mm Hg and/or Reduction of ≥20 mm Hg From Baseline and Target Clinic Diastolic Blood Pressure of <90 mm Hg and/or Reduction of ≥10 mm Hg From Baseline. |
|---|---|
| Description | Percentage of participants who achieve both a clinic diastolic and systolic blood pressure response measured at each week indicated, defined as less than 90 mm Hg and/or reduction from baseline of greater than or equal to 10 mm Hg AND less than 140 mm Hg and/or reduction from baseline of greater than or equal to 20 mm Hg. Diastolic and systolic blood pressure is based on the arithmetic mean of the non-missing values of the 3 serial trough sitting blood pressure measurements. |
| Time Frame | Baseline, Week 4, Week 8 and Week 12. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set, all participants that took at least 1 dose of double-blind study drug and have a baseline and post-baseline value, with last observation carried forward. |
| Arm/Group Title | Azilsartan Medoxomil 20-40mg/Chlorthalidone 12.5-25mg QD | Azilsartan Medoxomil 40-80mg/Chlorthalidone 12.5-25mg QD | Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD |
|---|---|---|---|
| Arm/Group Description | Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 80 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 80 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily and azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to olmesartan medoxomil 40 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg combination tablets, orally, once daily for the next 4 weeks. |
| Measure Participants | 355 | 352 | 364 |
| Week 4 (n=343; n=330; n=352) |
81.3
22.9%
|
84.8
24.1%
|
74.4
20.4%
|
| Week 8 (n=344; n=330; n=353) |
88.1
24.8%
|
87.3
24.8%
|
81.0
22.3%
|
| Week 12 (n=344; n=330; n=354) |
91.3
25.7%
|
92.4
26.3%
|
84.7
23.3%
|
Adverse Events
| Time Frame | Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. | |||||
| Arm/Group Title | Azilsartan Medoxomil 20-40mg/Chlorthalidone 12.5-25mg QD | Azilsartan Medoxomil 40-80mg/Chlorthalidone 12.5-25mg QD | Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD | |||
| Arm/Group Description | Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily and olmesartan and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to azilsartan medoxomil 80 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to azilsartan medoxomil 80 mg and chlorthalidone 25 mg combination tablets, orally, once daily for the next 4 weeks. | Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily and azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for up to 4 weeks. Participants will be force titrated at Week 4 to olmesartan medoxomil 40 mg and hydrochlorothiazide 12.5 mg combination tablets, orally, once daily for the next 4 weeks. Participants will then be force titrated at Week 8 to olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg combination tablets, orally, once daily for the next 4 weeks. | |||
All Cause Mortality |
||||||
| Azilsartan Medoxomil 20-40mg/Chlorthalidone 12.5-25mg QD | Azilsartan Medoxomil 40-80mg/Chlorthalidone 12.5-25mg QD | Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Azilsartan Medoxomil 20-40mg/Chlorthalidone 12.5-25mg QD | Azilsartan Medoxomil 40-80mg/Chlorthalidone 12.5-25mg QD | Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/355 (0.3%) | 10/352 (2.8%) | 8/364 (2.2%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 0/355 (0%) | 1/352 (0.3%) | 0/364 (0%) | |||
| Cardiac disorders | ||||||
| Arrhythmia | 0/355 (0%) | 1/352 (0.3%) | 0/364 (0%) | |||
| Atrial fibrillation | 0/355 (0%) | 0/352 (0%) | 1/364 (0.3%) | |||
| Cardiac failure congestive | 0/355 (0%) | 1/352 (0.3%) | 0/364 (0%) | |||
| Myocardial infarction | 0/355 (0%) | 0/352 (0%) | 1/364 (0.3%) | |||
| Ear and labyrinth disorders | ||||||
| Vertigo | 0/355 (0%) | 1/352 (0.3%) | 0/364 (0%) | |||
| Gastrointestinal disorders | ||||||
| Inguinal hernia | 0/355 (0%) | 0/352 (0%) | 1/364 (0.3%) | |||
| Pancreatitis acute | 0/355 (0%) | 0/352 (0%) | 1/364 (0.3%) | |||
| Vomiting | 0/355 (0%) | 1/352 (0.3%) | 0/364 (0%) | |||
| General disorders | ||||||
| Non-cardiac chest pain | 1/355 (0.3%) | 1/352 (0.3%) | 0/364 (0%) | |||
| Infections and infestations | ||||||
| Clostridial infection | 0/355 (0%) | 0/352 (0%) | 1/364 (0.3%) | |||
| Lobar pneumonia | 0/355 (0%) | 1/352 (0.3%) | 0/364 (0%) | |||
| Pneumonia | 0/355 (0%) | 1/352 (0.3%) | 0/364 (0%) | |||
| Sinusitis | 0/355 (0%) | 0/352 (0%) | 1/364 (0.3%) | |||
| Investigations | ||||||
| Blood creatine phosphokinase increased | 0/355 (0%) | 0/352 (0%) | 1/364 (0.3%) | |||
| Metabolism and nutrition disorders | ||||||
| Dehydration | 0/355 (0%) | 2/352 (0.6%) | 0/364 (0%) | |||
| Diabetes mellitus | 0/355 (0%) | 1/352 (0.3%) | 0/364 (0%) | |||
| Electrolyte imbalance | 0/355 (0%) | 0/352 (0%) | 1/364 (0.3%) | |||
| Hyperkalaemia | 0/355 (0%) | 1/352 (0.3%) | 0/364 (0%) | |||
| Hypomagnesaemia | 0/355 (0%) | 0/352 (0%) | 1/364 (0.3%) | |||
| Hyponatraemia | 0/355 (0%) | 0/352 (0%) | 1/364 (0.3%) | |||
| Nervous system disorders | ||||||
| Syncope | 0/355 (0%) | 2/352 (0.6%) | 0/364 (0%) | |||
| Ischaemic stroke | 0/355 (0%) | 1/352 (0.3%) | 0/364 (0%) | |||
| Renal and urinary disorders | ||||||
| Renal failure acute | 0/355 (0%) | 1/352 (0.3%) | 0/364 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Respiratory failure | 0/355 (0%) | 1/352 (0.3%) | 0/364 (0%) | |||
| Vascular disorders | ||||||
| Hypotension | 0/355 (0%) | 3/352 (0.9%) | 0/364 (0%) | |||
| Accelerated hypertension | 0/355 (0%) | 0/352 (0%) | 1/364 (0.3%) | |||
| Hypertension | 0/355 (0%) | 0/352 (0%) | 1/364 (0.3%) | |||
| Hypertensive emergency | 0/355 (0%) | 1/352 (0.3%) | 0/364 (0%) | |||
| Intermittent claudication | 0/355 (0%) | 1/352 (0.3%) | 0/364 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Azilsartan Medoxomil 20-40mg/Chlorthalidone 12.5-25mg QD | Azilsartan Medoxomil 40-80mg/Chlorthalidone 12.5-25mg QD | Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 141/355 (39.7%) | 144/352 (40.9%) | 94/364 (25.8%) | |||
| General disorders | ||||||
| Fatigue | 33/355 (9.3%) | 14/352 (4%) | 16/364 (4.4%) | |||
| Investigations | ||||||
| Blood creatinine increased | 66/355 (18.6%) | 78/352 (22.2%) | 34/364 (9.3%) | |||
| Blood uric acid increased | 19/355 (5.4%) | 17/352 (4.8%) | 12/364 (3.3%) | |||
| Nervous system disorders | ||||||
| Dizziness | 41/355 (11.5%) | 58/352 (16.5%) | 29/364 (8%) | |||
| Headache | 19/355 (5.4%) | 13/352 (3.7%) | 26/364 (7.1%) | |||
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.
Results Point of Contact
| Name/Title | Sr. VP, Clinical Science |
|---|---|
| Organization | Takeda Global Research and Development Center, Inc. |
| Phone | 800-778-2860 |
| clinicaltrialregistry@tpna.com |
Responsible Party:
Takeda
ClinicalTrials.gov Identifier:
NCT01033071
Other Study ID Numbers:
- TAK-491CLD_303
- U1111-1112-4298
First Posted:
Dec 16, 2009
Last Update Posted:
Feb 7, 2012
Last Verified:
Jan 1, 2012