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An Efficacy and Safety Study of Azilsartan Medoxomil Compared to Valsartan and Olmesartan in Participants With Essential Hypertension.

Sponsor
Takeda (Industry)
Overall Status
Completed
CT.gov ID
NCT00696436
Collaborator
(none)
1,291
Enrollment
131
Locations
5
Arms
16
Duration (Months)
9.9
Patients Per Site
0.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of azilsartan medoxomil, once daily (QD), compared to placebo, valsartan and olmesartan in participants with essential hypertension.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

Hypertension affects approximately 50 million individuals in the United States. As the population ages, the prevalence of hypertension will continue to increase if broad and effective preventive measures are not implemented. According to the World Health Organization, hypertension is the most common attributable cause of preventable death in developed nations, as uncontrolled hypertension greatly increases the risk of cardiovascular disease, cerebrovascular disease, and renal failure. Despite the availability of antihypertensive treatments, hypertension remains inadequately controlled: only about one-third of patients successfully maintain control.

A major component of blood pressure regulation is the renin-angiotensin-aldosterone system. This is a system of hormone-mediated feedback interactions that result in the relaxation or constriction of blood vessels in response to various stimuli. Angiotensin II, a polypeptide hormone, is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme as part of the renin-angiotensin-aldosterone system. Angiotensin II is the principal pressor agent of the renin-angiotensin-aldosterone system and has multiple effects on the cardiovascular system and on electrolyte homeostasis.

TAK-491 (azilsartan medoxomil) is an angiotensin II type 1 receptor antagonist currently being tested as a treatment for essential hypertension.

Study participation is anticipated to be about 10 weeks. Multiple procedures will occur at each visit which may include fasting, blood collection, urine collection, physical examinations, electrocardiograms and ambulatory blood pressure monitoring. Outside of the study center, participants will be required wear an ambulatory blood pressure monitoring device at 24 hour intervals.

Study Design

Study Type:
Interventional
Actual Enrollment :
1291 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Double-Blind, Randomized, Placebo-Controlled, 5-Arm Titration Study to Evaluate the Efficacy and Safety of TAK-491 When Compared With Valsartan and Olmesartan in Subjects With Essential Hypertension
Study Start Date :
Apr 1, 2008
Actual Primary Completion Date :
Aug 1, 2009
Actual Study Completion Date :
Aug 1, 2009

Arms and Interventions

Arm Intervention/Treatment
Experimental: Azilsartan Medoxomil 40 mg QD

Drug: Azilsartan medoxomil
Azilsartan medoxomil 20 mg, tablets and matching placebo comparator orally once daily for two weeks. Increased to azilsartan medoxomil 40 mg tablets and matching placebo comparator orally, once daily for up to four weeks.
Other Names:
  • TAK-491
  • Edarbi

    		•
    Experimental: Azilsartan Medoxomil 80 mg QD

    Drug: Azilsartan medoxomil
    Azilsartan medoxomil 40 mg, tablets and matching placebo comparator orally, once daily for two weeks. Increased to Azilsartan medoxomil 80 mg, tablets and matching placebo comparator orally, once daily for up to four weeks.
    Other Names:
  • TAK-491
  • Edarbi

    		•
    Active Comparator: Valsartan 320 mg QD

    Drug: Valsartan
    Valsartan 160 mg, tablets, and matching placebo comparator orally, once daily for two weeks. Increased to Valsartan 320 mg, tablets, and matching placebo comparator, orally, once daily for up to four weeks.
    Other Names:
  • Diovan®

    		•
    Active Comparator: Olmesartan 40 mg QD

    Drug: Olmesartan
    Olmesartan 20 mg, tablets and matching placebo comparator, orally, once daily for two weeks. Increased to Olmesartan 40 mg, tablets and matching placebo comparator, orally, once daily for up to four weeks.
    Other Names:
  • Benicar®

    		•
    Placebo Comparator: Placebo QD

    Drug: Placebo
    Matching placebo, orally, once daily for up to six weeks.

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline in the 24-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [Baseline and Week 6.]

      The change in 24-hour mean systolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing.

    Secondary Outcome Measures

    1. Change From Baseline in Mean Trough Clinic Sitting Systolic Blood Pressure. [Baseline and Week 6.]

      The change in mean trough clinic sitting systolic blood pressure measured at final visit or week 6 relative to baseline.

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

      The change in 24-hour mean diastolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing.

    3. Change From Baseline in Mean Trough Clinic Sitting Diastolic Blood Pressure [Baseline and Week 6.]

      The change in mean trough clinic sitting systolic blood pressure measured at final visit or week 6 relative to baseline.

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

      The change in daytime (6am to 10pm) mean systolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of all measurements recorded between the hours of 6 am and 10 pm.

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

      The change in daytime (6am to 10pm) mean diastolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of all measurements recorded between the hours of 6 am and 10 pm.

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

      The change in nighttime (12am to 6am) mean systolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of all measurements recorded between the hours of 12 am and 6 am.

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

      The change in nighttime (12am to 6am) mean diastolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of all measurements recorded between the hours of 12 am and 6 am.

    8. Change From Baseline in the 12-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [Baseline and Week 6.]

      The change in the 12-hour mean systolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 12-hour mean is the average of all measurements recorded in the first 12 hours after dosing.

    9. Change From Baseline in the 12-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [Baseline and Week 6.]

      The change in the 12-hour mean diastolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 12-hour mean is the average of all measurements recorded in the first 12 hours after dosing.

    10. Change From Baseline in the Trough (22-24-hr) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [Baseline and Week 6.]

      The change in trough mean systolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough mean is the average of all measurements recorded from 22 to 24 hours after dosing.

    11. Change From Baseline in the Trough (22-24-hr) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. [Baseline and Week 6.]

      The change in trough mean diastolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough mean is the average of all measurements recorded from 22 to 24 hours after dosing.

    12. Percentage of Participants Who Achieve a Clinic Systolic Blood Pressure Response, Defined as < 140 mm Hg and/or Reduction From Baseline ≥ 20 mm Hg [Baseline and Week 6.]

      Percentage of participants who achieve a clinic systolic blood pressure response measured at week 6, defined as less than 140 mm Hg and/or reduction from baseline of greater than or equal to 20 mm Hg. Systolic blood pressure is the arithmetic mean of the 3 trough sitting systolic blood pressure measurements.

    13. Percentage of Participants Who Achieve a Clinic Diastolic Blood Pressure Response, Defined as < 90 mm Hg and/or Reduction From Baseline ≥ 10 mm Hg [Baseline and Week 6.]

      Percentage of participants who achieve a clinic diastolic blood pressure response measured at week 6, defined as less than 90 mm Hg and/or reduction from baseline of greater than or equal to 10 mm Hg. Diastolic blood pressure is the arithmetic mean of the 3 trough sitting diastolic blood pressure measurements.

    14. Percentage of Participants Who Achieve Both a Clinic Diastolic and Systolic Blood Pressure Response [Baseline and Week 6.]

      Percentage of participants who achieve both a clinic diastolic and systolic blood pressure response measured at week 6, defined as less than 90 mm Hg and/or reduction from baseline of greater than or equal to 10 mm Hg AND less than 140 mm Hg and/or reduction from baseline of greater than or equal to 20 mm Hg. Diastolic and systolic blood pressure is based on the arithmetic mean of the 3 sitting blood pressure measurements.

    Eligibility Criteria

    Criteria

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

    1. Essential hypertension (sitting systolic blood pressure between 150 and 180 mm Hg, inclusive, at Day -1 and 24-hour mean systolic blood pressure between 130 and 170 mm Hg, inclusive, at Day 1).

    2. Capable of understanding and complying with protocol requirements.

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

    4. Clinical laboratory evaluations within the reference range for the testing laboratory or the results are deemed not clinically significant for inclusion into this study by the investigator.

    5. Willing to discontinue current antihypertensive medications at Screening Day 21 visit. If the participant is on amlodipine prior to Screening, the participant is willing to discontinue this medication at Screening Day -28.

    Exclusion Criteria:

    1. Sitting diastolic blood pressure greater than 114 mm Hg at Day -1 (day prior to Randomization).

    2. Baseline 24-hour ambulatory blood pressure monitor reading of insufficient quality.

    3. Taking or expected to take an excluded medication as described in the Excluded Medications.

    4. Hypersensitive to angiotensin II receptor blockers.

    5. History of myocardial infarction, heart failure, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebrovascular accident, or transient ischemic attack.

    6. Clinically significant cardiac conduction defects.

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

    8. Secondary hypertension of any etiology.

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

    10. Moderate to severe renal dysfunction or disease.

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

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

    13. Previous history of cancer that has not been in remission for at least 5 years prior to the first dose of study drug. (This criterion does not apply to those participants with basal cell or stage I squamous cell carcinoma of the skin).

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

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

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

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

    18. Works night (3rd) shift (defined as 11 PM [2300] to 7 AM [0700]).

    19. Unwilling or unable to comply with the protocol or scheduled appointments.

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

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

    22. Has been randomized in a previous azilsartan medoxomil study.

    23. Is required to take or continues taking any disallowed medication, prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Alabaster Alabama United States
    2 Ozark Alabama United States
    3 Green Valley Arizona United States
    4 Litchfield Park Arizona United States
    5 Mesa Arizona United States
    6 Tempe Arizona United States
    7 Carmichael California United States
    8 Chula Vista California United States
    9 Lincoln California United States
    10 Mission Viejo California United States
    11 National City California United States
    12 Pasadena California United States
    13 Riverside California United States
    14 Sacramento California United States
    15 San Diego California United States
    16 San Dimas California United States
    17 San Fransisco California United States
    18 San Ramon California United States
    19 Santa Ana California United States
    20 Vista California United States
    21 Colorado Springs Colorado United States
    22 Denver Colorado United States
    23 Littleton Colorado United States
    24 Longmont Colorado United States
    25 Cape Coral Florida United States
    26 Clearwater Florida United States
    27 Largo Florida United States
    28 Miami Florida United States
    29 New Port Richey Florida United States
    30 New Smyrna Beach Florida United States
    31 Palm Harbor Florida United States
    32 Tallahassee Florida United States
    33 Dunwoody Georgia United States
    34 Roswell Georgia United States
    35 Arlington Heights Illinois United States
    36 Belleville Illinois United States
    37 Champaign Illinois United States
    38 Chicago Illinois United States
    39 Peoria Illinois United States
    40 Vernon Hills Illinois United States
    41 Evansville Indiana United States
    42 Indianapolis Indiana United States
    43 Terre Haute Indiana United States
    44 Kansas City Kansas United States
    45 Overland Park Kansas United States
    46 Shawnee Kansas United States
    47 Biddeford Maine United States
    48 Norwood Maine United States
    49 Baltimore Maryland United States
    50 Towson Maryland United States
    51 Brooklyn Center Minnesota United States
    52 Chesterfield Missouri United States
    53 Jefferson City Missouri United States
    54 Kansas City Missouri United States
    55 St Louis Missouri United States
    56 Billings Montana United States
    57 Las Vegas Nevada United States
    58 Margate New Jersey United States
    59 Glens Falls New York United States
    60 Great Neck New York United States
    61 New Hyde Park New York United States
    62 New Windsor New York United States
    63 New York New York United States
    64 Charlotte North Carolina United States
    65 Raleigh North Carolina United States
    66 Columbus Ohio United States
    67 Norman Oklahoma United States
    68 Tulsa Oklahoma United States
    69 Yukon Oklahoma United States
    70 Ashland Oregon United States
    71 Eugene Oregon United States
    72 Medford Oregon United States
    73 Portland Oregon United States
    74 Pittsburgh Pennsylvania United States
    75 Tipton Pennsylvania United States
    76 Charleston South Carolina United States
    77 Murrells Inlet South Carolina United States
    78 North Charleston South Carolina United States
    79 Cleveland Tennessee United States
    80 Bedford Texas United States
    81 Dallas Texas United States
    82 Houston Texas United States
    83 Missouri City Texas United States
    84 San Antonio Texas United States
    85 Sugarland Texas United States
    86 Tacoma Washington United States
    87 Carlos Paz Córdoba Argentina
    88 Guaymayen Mendoza Argentina
    89 Bahía Blanca Argentina
    90 Berazategui Argentina
    91 Buenos Aires Argentina
    92 Corrientes Argentina
    93 Córdoba Argentina
    94 Haedo Pcia. de Buenos Aires Argentina
    95 Jujuy Argentina
    96 La Plata Argentina
    97 Ramos Mejía Pcia. de Buenos Aires Argentina
    98 Rosario Argentina
    99 Salta Argentina
    100 San Miguel de Tucumán Argentina
    101 Belo Horizonte Brazil
    102 Campinas Brazil
    103 Fortaleza Brazil
    104 Goiaenia Brazil
    105 Joildille Brazil
    106 Porto Alegre Brazil
    107 Rio Janeiro Brazil
    108 Sao Paulo Brazil
    109 Sorocava Brazil
    110 Tijuana Baja California Mexico
    111 León Guanajuato Mexico
    112 Guadalajara Jalapa Mexico
    113 Monterrey Nuevo Leon Mexico
    114 Xalapa Veracruz Mexico
    115 Aguascalientes Mexico
    116 Chihuahua Mexico
    117 Mexico City Mexico
    118 Querètaro Mexico
    119 San Luis Potosí Mexico
    120 Arequipa Peru
    121 Cusco Peru
    122 Huaura Peru
    123 Ica Peru
    124 Lima Peru
    125 Trujillo Peru
    126 Aguas Buenas Puerto Rico
    127 Carolina Puerto Rico
    128 Jardines de Loiza Puerto Rico
    129 Orocovis Puerto Rico
    130 Ponce Puerto Rico
    131 San Juan Puerto Rico

    Sponsors and Collaborators

    • Takeda

    Investigators

    • Study Director: Executive Medical Director Clinical Science, Takeda

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00696436
    Other Study ID Numbers:
    • 01-06-TL-491-019
    • U1111-1113-9161
    First Posted:
    Jun 12, 2008
    Last Update Posted:
    Apr 19, 2011
    Last Verified:
    Mar 1, 2011
    Keywords provided by , ,
    Essential Hypertension
    Cardiovascular Disease
    High Blood Pressure
    Drug Therapy
    Additional relevant MeSH terms:
    Hypertension
    Essential Hypertension
    Valsartan
    Olmesartan
    Azilsartan medoxomil

    Study Results

    Participant Flow

    Recruitment Details Participants enrolled at 141 investigative sites in Guatemala, Mexico, Peru, Puerto Rico and the United States from 02 April 2008 to 19 August 2009.
    Pre-assignment Detail Participants with essential hypertension were enrolled in one of five, once-daily (QD) treatment groups.
    Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD Olmesartan 40 mg QD Placebo QD
    Arm/Group Description Azilsartan medoxomil 20 mg, tablets and matching placebo comparator orally once daily for two weeks. Increased to azilsartan medoxomil 40 mg tablets and matching placebo comparator orally, once daily for up to four weeks. Azilsartan medoxomil 40 mg, tablets and matching placebo comparator orally, once daily for two weeks. Increased to Azilsartan medoxomil 80 mg, tablets and matching placebo comparator orally, once daily for up to four weeks. Valsartan 160 mg, tablets, and matching placebo comparator orally, once daily for two weeks. Increased to Valsartan 320 mg, tablets, and matching placebo comparator, orally, once daily for up to four weeks. Olmesartan 20 mg, tablets and matching placebo comparator, orally, once daily for two weeks. Increased to Olmesartan 40 mg, tablets and matching placebo comparator, orally, once daily for up to four weeks. Matching placebo, orally, once daily for up to six weeks.
    Period Title: Overall Study
    STARTED 280 285 282 290 154
    COMPLETED 257 255 254 268 141
    NOT COMPLETED 23 30 28 22 13

    Baseline Characteristics

    Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD Olmesartan 40 mg QD Placebo QD Total
    Arm/Group Description Azilsartan medoxomil 20 mg, tablets and matching placebo comparator orally once daily for two weeks. Increased to azilsartan medoxomil 40 mg tablets and matching placebo comparator orally, once daily for up to four weeks. Azilsartan medoxomil 40 mg, tablets and matching placebo comparator orally, once daily for two weeks. Increased to Azilsartan medoxomil 80 mg, tablets and matching placebo comparator orally, once daily for up to four weeks. Valsartan 160 mg, tablets, and matching placebo comparator orally, once daily for two weeks. Increased to Valsartan 320 mg, tablets, and matching placebo comparator, orally, once daily for up to four weeks. Olmesartan 20 mg, tablets and matching placebo comparator, orally, once daily for two weeks. Increased to Olmesartan 40 mg, tablets and matching placebo comparator, orally, once daily for up to four weeks. Matching placebo, orally, once daily for up to six weeks. Total of all reporting groups
    Overall Participants 280 285 282 290 154 1291
    Age (participants) [Number]
    <45 years
    41
    14.6%
    38
    13.3%
    56
    19.9%
    39
    13.4%
    20
    13%
    194
    15%
    Between 45 and 64 years
    170
    60.7%
    184
    64.6%
    178
    63.1%
    185
    63.8%
    98
    63.6%
    815
    63.1%
    ≥65 years
    69
    24.6%
    63
    22.1%
    48
    17%
    66
    22.8%
    36
    23.4%
    282
    21.8%
    Sex: Female, Male (Count of Participants)
    Female
    133
    47.5%
    134
    47%
    130
    46.1%
    131
    45.2%
    64
    41.6%
    592
    45.9%
    Male
    147
    52.5%
    151
    53%
    152
    53.9%
    159
    54.8%
    90
    58.4%
    699
    54.1%

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline in the 24-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
    Description The change in 24-hour mean systolic blood pressure measured at week 6 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 6.

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set.
    Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD Olmesartan 40 mg QD Placebo QD
    Arm/Group Description Azilsartan medoxomil 20 mg, tablets and matching placebo comparator orally once daily for two weeks. Increased to azilsartan medoxomil 40 mg tablets and matching placebo comparator orally, once daily for up to four weeks. Azilsartan medoxomil 40 mg, tablets and matching placebo comparator orally, once daily for two weeks. Increased to Azilsartan medoxomil 80 mg, tablets and matching placebo comparator orally, once daily for up to four weeks. Valsartan 160 mg, tablets, and matching placebo comparator orally, once daily for two weeks. Increased to Valsartan 320 mg, tablets, and matching placebo comparator, orally, once daily for up to four weeks. Olmesartan 20 mg, tablets and matching placebo comparator, orally, once daily for two weeks. Increased to Olmesartan 40 mg, tablets and matching placebo comparator, orally, once daily for up to four weeks. Matching placebo, orally, once daily for up to six weeks.
    Measure Participants 237 229 234 254 134
    Least Squares Mean (Standard Error) [mmHg]
    -13.42
    (0.690)
    -14.53
    (0.702)
    -10.22
    (0.696)
    -11.99
    (0.666)
    -0.25
    (0.917)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Placebo QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented. Overall 0.05 level of significance for multiple comparisons was controlled using stepwise testing procedure.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -14.27
    Confidence Interval (2-Sided) 95%
    -16.54 to -12.01
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Placebo QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented. Overall 0.05 level of significance for multiple comparisons was controlled using stepwise testing procedure.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -13.16
    Confidence Interval (2-Sided) 95%
    -15.41 to -10.91
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Olmesartan 40 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.009
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented. Overall 0.05 level of significance for multiple comparisons was controlled using stepwise testing procedure.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.54
    Confidence Interval (2-Sided) 95%
    -4.44 to -0.64
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Valsartan 320 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented. Overall 0.05 level of significance for multiple comparisons was controlled using stepwise testing procedure.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -4.31
    Confidence Interval (2-Sided) 95%
    -6.25 to -2.37
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Olmesartan 40 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.136
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented. Overall 0.05 level of significance for multiple comparisons was controlled using stepwise testing procedure.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.43
    Confidence Interval (2-Sided) 95%
    -3.31 to 0.45
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Valsartan 320 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented. Overall 0.05 level of significance for multiple comparisons was controlled using stepwise testing procedure.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -3.20
    Confidence Interval (2-Sided) 95%
    -5.12 to -1.27
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Change From Baseline in Mean Trough Clinic Sitting Systolic Blood Pressure.
    Description The change in mean trough clinic sitting systolic blood pressure measured at final visit or week 6 relative to baseline.
    Time Frame Baseline and Week 6.

    Outcome Measure Data

    Analysis Population Description
    Full analysis set with last observation carried forward.
    Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD Olmesartan 40 mg QD Placebo QD
    Arm/Group Description Azilsartan medoxomil 20 mg, tablets and matching placebo comparator orally once daily for two weeks. Increased to azilsartan medoxomil 40 mg tablets and matching placebo comparator orally, once daily for up to four weeks. Azilsartan medoxomil 40 mg, tablets and matching placebo comparator orally, once daily for two weeks. Increased to Azilsartan medoxomil 80 mg, tablets and matching placebo comparator orally, once daily for up to four weeks. Valsartan 160 mg, tablets, and matching placebo comparator orally, once daily for two weeks. Increased to Valsartan 320 mg, tablets, and matching placebo comparator, orally, once daily for up to four weeks. Olmesartan 20 mg, tablets and matching placebo comparator, orally, once daily for two weeks. Increased to Olmesartan 40 mg, tablets and matching placebo comparator, orally, once daily for up to four weeks. Matching placebo, orally, once daily for up to six weeks.
    Measure Participants 269 270 271 283 148
    Least Squares Mean (Standard Error) [mmHg]
    -16.38
    (0.959)
    -16.74
    (0.957)
    -11.31
    (0.955)
    -13.20
    (0.935)
    -1.83
    (1.293)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Placebo QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented. Overall 0.05 level of significance for multiple comparisons was controlled using stepwise testing procedure.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -14.92
    Confidence Interval (2-Sided) 95%
    -18.07 to -11.76
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Placebo QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented. Overall 0.05 level of significance for multiple comparisons was controlled using stepwise testing procedure.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -14.55
    Confidence Interval (2-Sided) 95%
    -17.71 to -11.40
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Olmesartan 40 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.008
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented. Overall 0.05 level of significance for multiple comparisons was controlled using stepwise testing procedure.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -3.54
    Confidence Interval (2-Sided) 95%
    -6.17 to -0.92
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Valsartan 320 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented. Overall 0.05 level of significance for multiple comparisons was controlled using stepwise testing procedure.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -5.43
    Confidence Interval (2-Sided) 95%
    -8.09 to -2.78
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Olmesartan 40 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.018
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented. Overall 0.05 level of significance for multiple comparisons was controlled using stepwise testing procedure.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -3.18
    Confidence Interval (2-Sided) 95%
    -5.81 to -0.55
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Valsartan 320 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented. Overall 0.05 level of significance for multiple comparisons was controlled using stepwise testing procedure.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -5.07
    Confidence Interval (2-Sided) 95%
    -7.73 to -2.42
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Change From Baseline in the 24-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
    Description The change in 24-hour mean diastolic blood pressure measured at week 6 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 6.

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set.
    Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD Olmesartan 40 mg QD Placebo QD
    Arm/Group Description Azilsartan medoxomil 20 mg, tablets and matching placebo comparator orally once daily for two weeks. Increased to azilsartan medoxomil 40 mg tablets and matching placebo comparator orally, once daily for up to four weeks. Azilsartan medoxomil 40 mg, tablets and matching placebo comparator orally, once daily for two weeks. Increased to Azilsartan medoxomil 80 mg, tablets and matching placebo comparator orally, once daily for up to four weeks. Valsartan 160 mg, tablets, and matching placebo comparator orally, once daily for two weeks. Increased to Valsartan 320 mg, tablets, and matching placebo comparator, orally, once daily for up to four weeks. Olmesartan 20 mg, tablets and matching placebo comparator, orally, once daily for two weeks. Increased to Olmesartan 40 mg, tablets and matching placebo comparator, orally, once daily for up to four weeks. Matching placebo, orally, once daily for up to six weeks.
    Measure Participants 237 229 234 254 134
    Least Squares Mean (Standard Error) [mmHg]
    -8.65
    (0.472)
    -9.43
    (0.480)
    -7.09
    (0.476)
    -7.74
    (0.456)
    -0.07
    (0.627)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Placebo QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -9.36
    Confidence Interval (2-Sided) 95%
    -10.91 to -7.81
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Placebo QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -8.58
    Confidence Interval (2-Sided) 95%
    -10.12 to -7.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Olmesartan 40 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.011
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.70
    Confidence Interval (2-Sided) 95%
    -2.99 to -0.40
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Valsartan 320 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.35
    Confidence Interval (2-Sided) 95%
    -3.67 to -1.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Olmesartan 40 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.166
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.91
    Confidence Interval (2-Sided) 95%
    -2.19 to 0.38
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Valsartan 320 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.020
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.56
    Confidence Interval (2-Sided) 95%
    -2.88 to -0.24
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Change From Baseline in Mean Trough Clinic Sitting Diastolic Blood Pressure
    Description The change in mean trough clinic sitting systolic blood pressure measured at final visit or week 6 relative to baseline.
    Time Frame Baseline and Week 6.

    Outcome Measure Data

    Analysis Population Description
    Full analysis set with last observation carried forward.
    Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD Olmesartan 40 mg QD Placebo QD
    Arm/Group Description Azilsartan medoxomil 20 mg, tablets and matching placebo comparator orally once daily for two weeks. Increased to azilsartan medoxomil 40 mg tablets and matching placebo comparator orally, once daily for up to four weeks. Azilsartan medoxomil 40 mg, tablets and matching placebo comparator orally, once daily for two weeks. Increased to Azilsartan medoxomil 80 mg, tablets and matching placebo comparator orally, once daily for up to four weeks. Valsartan 160 mg, tablets, and matching placebo comparator orally, once daily for two weeks. Increased to Valsartan 320 mg, tablets, and matching placebo comparator, orally, once daily for up to four weeks. Olmesartan 20 mg, tablets and matching placebo comparator, orally, once daily for two weeks. Increased to Olmesartan 40 mg, tablets and matching placebo comparator, orally, once daily for up to four weeks. Matching placebo, orally, once daily for up to six weeks.
    Measure Participants 269 270 271 283 148
    Least Squares Mean (Standard Error) [mmHg]
    -6.97
    (0.552)
    -8.27
    (0.551)
    -5.11
    (0.550)
    -6.10
    (0.538)
    -0.76
    (0.744)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Placebo QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -7.51
    Confidence Interval (2-Sided) 95%
    -9.33 to -5.69
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Placebo QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -6.21
    Confidence Interval (2-Sided) 95%
    -8.03 to -4.39
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Olmesartan 40 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.005
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.18
    Confidence Interval (2-Sided) 95%
    -3.69 to -0.67
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Valsartan 320 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -3.17
    Confidence Interval (2-Sided) 95%
    -4.69 to -1.64
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Olmesartan 40 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.257
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.87
    Confidence Interval (2-Sided) 95%
    -2.39 to 0.64
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Valsartan 320 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.017
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.86
    Confidence Interval (2-Sided) 95%
    -3.39 to -0.33
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title Change From Baseline in Daytime (6am to 10 pm) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
    Description The change in daytime (6am to 10pm) mean systolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of all measurements recorded between the hours of 6 am and 10 pm.
    Time Frame Baseline and Week 6.

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set.
    Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD Olmesartan 40 mg QD Placebo QD
    Arm/Group Description Azilsartan medoxomil 20 mg, tablets and matching placebo comparator orally once daily for two weeks. Increased to azilsartan medoxomil 40 mg tablets and matching placebo comparator orally, once daily for up to four weeks. Azilsartan medoxomil 40 mg, tablets and matching placebo comparator orally, once daily for two weeks. Increased to Azilsartan medoxomil 80 mg, tablets and matching placebo comparator orally, once daily for up to four weeks. Valsartan 160 mg, tablets, and matching placebo comparator orally, once daily for two weeks. Increased to Valsartan 320 mg, tablets, and matching placebo comparator, orally, once daily for up to four weeks. Olmesartan 20 mg, tablets and matching placebo comparator, orally, once daily for two weeks. Increased to Olmesartan 40 mg, tablets and matching placebo comparator, orally, once daily for up to four weeks. Matching placebo, orally, once daily for up to six weeks.
    Measure Participants 237 229 234 254 134
    Least Squares Mean (Standard Error) [mmHg]
    -13.73
    (0.724)
    -15.02
    (0.736)
    -10.26
    (0.730)
    -12.16
    (0.699)
    -0.11
    (0.963)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Placebo QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -14.92
    Confidence Interval (2-Sided) 95%
    -17.30 to -12.54
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Placebo QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -13.63
    Confidence Interval (2-Sided) 95%
    -15.99 to -11.27
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Olmesartan 40 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.005
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.86
    Confidence Interval (2-Sided) 95%
    -4.85 to -0.87
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Valsartan 320 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -4.76
    Confidence Interval (2-Sided) 95%
    -6.80 to -2.73
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Olmesartan 40 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.119
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.57
    Confidence Interval (2-Sided) 95%
    -3.55 to 0.40
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Valsartan 320 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -3.47
    Confidence Interval (2-Sided) 95%
    -5.49 to -1.45
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Change From Baseline in Daytime (6am to 10 pm) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
    Description The change in daytime (6am to 10pm) mean diastolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of all measurements recorded between the hours of 6 am and 10 pm.
    Time Frame Baseline and Week 6.

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set.
    Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD Olmesartan 40 mg QD Placebo QD
    Arm/Group Description Azilsartan medoxomil 20 mg, tablets and matching placebo comparator orally once daily for two weeks. Increased to azilsartan medoxomil 40 mg tablets and matching placebo comparator orally, once daily for up to four weeks. Azilsartan medoxomil 40 mg, tablets and matching placebo comparator orally, once daily for two weeks. Increased to Azilsartan medoxomil 80 mg, tablets and matching placebo comparator orally, once daily for up to four weeks. Valsartan 160 mg, tablets, and matching placebo comparator orally, once daily for two weeks. Increased to Valsartan 320 mg, tablets, and matching placebo comparator, orally, once daily for up to four weeks. Olmesartan 20 mg, tablets and matching placebo comparator, orally, once daily for two weeks. Increased to Olmesartan 40 mg, tablets and matching placebo comparator, orally, once daily for up to four weeks. Matching placebo, orally, once daily for up to six weeks.
    Measure Participants 237 229 234 254 134
    Least Squares Mean (Standard Error) [mmHg]
    -8.96
    (0.510)
    -9.80
    (0.518)
    -7.23
    (0.514)
    -7.82
    (0.492)
    0.01
    (0.677)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Placebo QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -9.81
    Confidence Interval (2-Sided) 95%
    -11.48 to -8.13
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Placebo QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -8.96
    Confidence Interval (2-Sided) 95%
    -10.63 to -7.30
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Olmesartan 40 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.006
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.99
    Confidence Interval (2-Sided) 95%
    -3.39 to -0.58
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Valsartan 320 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.57
    Confidence Interval (2-Sided) 95%
    -4.00 to -1.14
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Olmesartan 40 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.107
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.14
    Confidence Interval (2-Sided) 95%
    -2.53 to 0.25
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Valsartan 320 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.017
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.73
    Confidence Interval (2-Sided) 95%
    -3.15 to -0.30
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title Change From Baseline in the Nighttime (12 am to 6 am) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
    Description The change in nighttime (12am to 6am) mean systolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of all measurements recorded between the hours of 12 am and 6 am.
    Time Frame Baseline and Week 6.

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set.
    Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD Olmesartan 40 mg QD Placebo QD
    Arm/Group Description Azilsartan medoxomil 20 mg, tablets and matching placebo comparator orally once daily for two weeks. Increased to azilsartan medoxomil 40 mg tablets and matching placebo comparator orally, once daily for up to four weeks. Azilsartan medoxomil 40 mg, tablets and matching placebo comparator orally, once daily for two weeks. Increased to Azilsartan medoxomil 80 mg, tablets and matching placebo comparator orally, once daily for up to four weeks. Valsartan 160 mg, tablets, and matching placebo comparator orally, once daily for two weeks. Increased to Valsartan 320 mg, tablets, and matching placebo comparator, orally, once daily for up to four weeks. Olmesartan 20 mg, tablets and matching placebo comparator, orally, once daily for two weeks. Increased to Olmesartan 40 mg, tablets and matching placebo comparator, orally, once daily for up to four weeks. Matching placebo, orally, once daily for up to six weeks.
    Measure Participants 237 229 234 254 134
    Least Squares Mean (Standard Error) [mmHg]
    -12.28
    (0.778)
    -13.32
    (0.792)
    -9.66
    (0.784)
    -11.90
    (0.752)
    -0.31
    (1.035)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Placebo QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -13.00
    Confidence Interval (2-Sided) 95%
    -15.56 to -10.45
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Placebo QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -11.97
    Confidence Interval (2-Sided) 95%
    -14.51 to -9.43
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Olmesartan 40 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.194
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.42
    Confidence Interval (2-Sided) 95%
    -3.56 to 0.72
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Valsartan 320 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -3.65
    Confidence Interval (2-Sided) 95%
    -5.84 to -1.46
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Olmesartan 40 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.720
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.39
    Confidence Interval (2-Sided) 95%
    -2.51 to 1.73
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Valsartan 320 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.018
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.62
    Confidence Interval (2-Sided) 95%
    -4.79 to -0.45
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. Secondary Outcome
    Title Change From Baseline in the Nighttime (12 am to 6 am) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
    Description The change in nighttime (12am to 6am) mean diastolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of all measurements recorded between the hours of 12 am and 6 am.
    Time Frame Baseline and Week 6.

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set.
    Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD Olmesartan 40 mg QD Placebo QD
    Arm/Group Description Azilsartan medoxomil 20 mg, tablets and matching placebo comparator orally once daily for two weeks. Increased to azilsartan medoxomil 40 mg tablets and matching placebo comparator orally, once daily for up to four weeks. Azilsartan medoxomil 40 mg, tablets and matching placebo comparator orally, once daily for two weeks. Increased to Azilsartan medoxomil 80 mg, tablets and matching placebo comparator orally, once daily for up to four weeks. Valsartan 160 mg, tablets, and matching placebo comparator orally, once daily for two weeks. Increased to Valsartan 320 mg, tablets, and matching placebo comparator, orally, once daily for up to four weeks. Olmesartan 20 mg, tablets and matching placebo comparator, orally, once daily for two weeks. Increased to Olmesartan 40 mg, tablets and matching placebo comparator, orally, once daily for up to four weeks. Matching placebo, orally, once daily for up to six weeks.
    Measure Participants 237 229 234 254 134
    Least Squares Mean (Standard Error) [mmHg]
    -7.65
    (0.540)
    -8.54
    (0.550)
    -6.26
    (0.544)
    -7.82
    (0.522)
    0.10
    (0.718)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Placebo QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -8.64
    Confidence Interval (2-Sided) 95%
    -10.42 to -6.87
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Placebo QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -7.75
    Confidence Interval (2-Sided) 95%
    -9.52 to -5.99
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Olmesartan 40 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.341
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.72
    Confidence Interval (2-Sided) 95%
    -2.21 to 0.77
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Valsartan 320 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.28
    Confidence Interval (2-Sided) 95%
    -3.80 to -0.76
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Olmesartan 40 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.821
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.17
    Confidence Interval (2-Sided) 95%
    -1.30 to 1.64
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Valsartan 320 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.071
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.39
    Confidence Interval (2-Sided) 95%
    -2.89 to 0.12
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    9. Secondary Outcome
    Title Change From Baseline in the 12-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
    Description The change in the 12-hour mean systolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 12-hour mean is the average of all measurements recorded in the first 12 hours after dosing.
    Time Frame Baseline and Week 6.

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set.
    Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD Olmesartan 40 mg QD Placebo QD
    Arm/Group Description Azilsartan medoxomil 20 mg, tablets and matching placebo comparator orally once daily for two weeks. Increased to azilsartan medoxomil 40 mg tablets and matching placebo comparator orally, once daily for up to four weeks. Azilsartan medoxomil 40 mg, tablets and matching placebo comparator orally, once daily for two weeks. Increased to Azilsartan medoxomil 80 mg, tablets and matching placebo comparator orally, once daily for up to four weeks. Valsartan 160 mg, tablets, and matching placebo comparator orally, once daily for two weeks. Increased to Valsartan 320 mg, tablets, and matching placebo comparator, orally, once daily for up to four weeks. Olmesartan 20 mg, tablets and matching placebo comparator, orally, once daily for two weeks. Increased to Olmesartan 40 mg, tablets and matching placebo comparator, orally, once daily for up to four weeks. Matching placebo, orally, once daily for up to six weeks.
    Measure Participants 237 229 234 254 134
    Least Squares Mean (Standard Error) [mmHg]
    -14.03
    (0.764)
    -15.55
    (0.777)
    -10.44
    (0.770)
    -12.23
    (0.738)
    -0.10
    (1.016)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Placebo QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -15.45
    Confidence Interval (2-Sided) 95%
    -17.96 to -12.94
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Placebo QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -13.93
    Confidence Interval (2-Sided) 95%
    -16.42 to -11.43
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Olmesartan 40 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -3.32
    Confidence Interval (2-Sided) 95%
    -5.42 to -1.22
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Valsartan 320 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -5.11
    Confidence Interval (2-Sided) 95%
    -7.26 to -2.97
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Olmesartan 40 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.091
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.80
    Confidence Interval (2-Sided) 95%
    -3.88 to 0.29
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Valsartan 320 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -3.59
    Confidence Interval (2-Sided) 95%
    -5.72 to -1.46
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    10. Secondary Outcome
    Title Change From Baseline in the 12-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
    Description The change in the 12-hour mean diastolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 12-hour mean is the average of all measurements recorded in the first 12 hours after dosing.
    Time Frame Baseline and Week 6.

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set.
    Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD Olmesartan 40 mg QD Placebo QD
    Arm/Group Description Azilsartan medoxomil 20 mg, tablets and matching placebo comparator orally once daily for two weeks. Increased to azilsartan medoxomil 40 mg tablets and matching placebo comparator orally, once daily for up to four weeks. Azilsartan medoxomil 40 mg, tablets and matching placebo comparator orally, once daily for two weeks. Increased to Azilsartan medoxomil 80 mg, tablets and matching placebo comparator orally, once daily for up to four weeks. Valsartan 160 mg, tablets, and matching placebo comparator orally, once daily for two weeks. Increased to Valsartan 320 mg, tablets, and matching placebo comparator, orally, once daily for up to four weeks. Olmesartan 20 mg, tablets and matching placebo comparator, orally, once daily for two weeks. Increased to Olmesartan 40 mg, tablets and matching placebo comparator, orally, once daily for up to four weeks. Matching placebo, orally, once daily for up to six weeks.
    Measure Participants 237 229 234 254 134
    Least Squares Mean (Standard Error) [mmHg]
    -9.16
    (0.542)
    -10.13
    (0.551)
    -7.42
    (0.547)
    -7.82
    (0.524)
    0.01
    (0.721)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Placebo QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -10.14
    Confidence Interval (2-Sided) 95%
    -11.92 to -8.36
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Placebo QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -9.17
    Confidence Interval (2-Sided) 95%
    -10.94 to -7.40
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Olmesartan 40 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.31
    Confidence Interval (2-Sided) 95%
    -3.81 to -0.82
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Valsartan 320 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.71
    Confidence Interval (2-Sided) 95%
    -4.24 to -1.19
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Olmesartan 40 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.076
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.34
    Confidence Interval (2-Sided) 95%
    -2.82 to 0.14
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Valsartan 320 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.024
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.74
    Confidence Interval (2-Sided) 95%
    -3.25 to -0.22
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    11. Secondary Outcome
    Title Change From Baseline in the Trough (22-24-hr) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
    Description The change in trough mean systolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough mean is the average of all measurements recorded from 22 to 24 hours after dosing.
    Time Frame Baseline and Week 6.

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set.
    Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD Olmesartan 40 mg QD Placebo QD
    Arm/Group Description Azilsartan medoxomil 20 mg, tablets and matching placebo comparator orally once daily for two weeks. Increased to azilsartan medoxomil 40 mg tablets and matching placebo comparator orally, once daily for up to four weeks. Azilsartan medoxomil 40 mg, tablets and matching placebo comparator orally, once daily for two weeks. Increased to Azilsartan medoxomil 80 mg, tablets and matching placebo comparator orally, once daily for up to four weeks. Valsartan 160 mg, tablets, and matching placebo comparator orally, once daily for two weeks. Increased to Valsartan 320 mg, tablets, and matching placebo comparator, orally, once daily for up to four weeks. Olmesartan 20 mg, tablets and matching placebo comparator, orally, once daily for two weeks. Increased to Olmesartan 40 mg, tablets and matching placebo comparator, orally, once daily for up to four weeks. Matching placebo, orally, once daily for up to six weeks.
    Measure Participants 236 229 234 254 134
    Least Squares Mean (Standard Error) [mmHg]
    -12.46
    (0.860)
    -13.38
    (0.873)
    -9.14
    (0.865)
    -11.65
    (0.829)
    -0.55
    (1.142)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Placebo QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -12.84
    Confidence Interval (2-Sided) 95%
    -15.66 to -10.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Placebo QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -11.91
    Confidence Interval (2-Sided) 95%
    -14.72 to -9.11
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Olmesartan 40 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.149
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.74
    Confidence Interval (2-Sided) 95%
    -4.10 to 0.62
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Valsartan 320 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -4.24
    Confidence Interval (2-Sided) 95%
    -6.65 to -1.83
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Olmesartan 40 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.494
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.82
    Confidence Interval (2-Sided) 95%
    -3.16 to 1.53
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Valsartan 320 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.007
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -3.32
    Confidence Interval (2-Sided) 95%
    -5.72 to -0.93
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    12. Secondary Outcome
    Title Change From Baseline in the Trough (22-24-hr) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
    Description The change in trough mean diastolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough mean is the average of all measurements recorded from 22 to 24 hours after dosing.
    Time Frame Baseline and Week 6.

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set.
    Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD Olmesartan 40 mg QD Placebo QD
    Arm/Group Description Azilsartan medoxomil 20 mg, tablets and matching placebo comparator orally once daily for two weeks. Increased to azilsartan medoxomil 40 mg tablets and matching placebo comparator orally, once daily for up to four weeks. Azilsartan medoxomil 40 mg, tablets and matching placebo comparator orally, once daily for two weeks. Increased to Azilsartan medoxomil 80 mg, tablets and matching placebo comparator orally, once daily for up to four weeks. Valsartan 160 mg, tablets, and matching placebo comparator orally, once daily for two weeks. Increased to Valsartan 320 mg, tablets, and matching placebo comparator, orally, once daily for up to four weeks. Olmesartan 20 mg, tablets and matching placebo comparator, orally, once daily for two weeks. Increased to Olmesartan 40 mg, tablets and matching placebo comparator, orally, once daily for up to four weeks. Matching placebo, orally, once daily for up to six weeks.
    Measure Participants 236 229 234 254 134
    Least Squares Mean (Standard Error) [mmHg]
    -8.69
    (0.648)
    -8.61
    (0.657)
    -6.22
    (0.651)
    -8.25
    (0.624)
    -0.69
    (0.859)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Placebo QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -7.91
    Confidence Interval (2-Sided) 95%
    -10.03 to -5.79
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Placebo QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -7.99
    Confidence Interval (2-Sided) 95%
    -10.10 to -5.88
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Olmesartan 40 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.691
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.36
    Confidence Interval (2-Sided) 95%
    -2.14 to 1.42
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Valsartan 320 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.010
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.39
    Confidence Interval (2-Sided) 95%
    -4.20 to -0.57
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Olmesartan 40 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.625
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.44
    Confidence Interval (2-Sided) 95%
    -2.20 to 1.32
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Valsartan 320 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.008
    Comments Postbaseline P-value was from ANCOVA with treatment as a factor and baseline value as a covariate. Unadjusted p-value was presented.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.46
    Confidence Interval (2-Sided) 95%
    -4.27 to -0.66
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    13. Secondary Outcome
    Title Percentage of Participants Who Achieve a Clinic Systolic Blood Pressure Response, Defined as < 140 mm Hg and/or Reduction From Baseline ≥ 20 mm Hg
    Description Percentage of participants who achieve a clinic systolic blood pressure response measured at week 6, defined as less than 140 mm Hg and/or reduction from baseline of greater than or equal to 20 mm Hg. Systolic blood pressure is the arithmetic mean of the 3 trough sitting systolic blood pressure measurements.
    Time Frame Baseline and Week 6.

    Outcome Measure Data

    Analysis Population Description
    Full analysis set with last observation carried forward.
    Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD Olmesartan 40 mg QD Placebo QD
    Arm/Group Description Azilsartan medoxomil 20 mg, tablets and matching placebo comparator orally once daily for two weeks. Increased to azilsartan medoxomil 40 mg tablets and matching placebo comparator orally, once daily for up to four weeks. Azilsartan medoxomil 40 mg, tablets and matching placebo comparator orally, once daily for two weeks. Increased to Azilsartan medoxomil 80 mg, tablets and matching placebo comparator orally, once daily for up to four weeks. Valsartan 160 mg, tablets, and matching placebo comparator orally, once daily for two weeks. Increased to Valsartan 320 mg, tablets, and matching placebo comparator, orally, once daily for up to four weeks. Olmesartan 20 mg, tablets and matching placebo comparator, orally, once daily for two weeks. Increased to Olmesartan 40 mg, tablets and matching placebo comparator, orally, once daily for up to four weeks. Matching placebo, orally, once daily for up to six weeks.
    Measure Participants 269 270 271 283 148
    Number [percentage of participants]
    56.5
    20.2%
    57.8
    20.3%
    48.7
    17.3%
    48.8
    16.8%
    22.3
    14.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Placebo QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value for response criteria for systolic blood pressure was from a logistic regression with treatment as a factor and baseline clinic systolic blood pressure as a covariate. The unadjusted p-value was presented.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.98
    Confidence Interval (2-Sided) 95%
    3.15 to 7.88
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Placebo QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value for response criteria for systolic blood pressure was from a logistic regression with treatment as a factor and baseline clinic systolic blood pressure as a covariate. The unadjusted p-value was presented.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.66
    Confidence Interval (2-Sided) 95%
    2.94 to 7.37
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Olmesartan 40 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.032
    Comments P-value for response criteria for systolic blood pressure was from a logistic regression with treatment as a factor and baseline clinic systolic blood pressure as a covariate. The unadjusted p-value was presented.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.45
    Confidence Interval (2-Sided) 95%
    1.03 to 2.03
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Valsartan 320 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.029
    Comments P-value for response criteria for systolic blood pressure was from a logistic regression with treatment as a factor and baseline clinic systolic blood pressure as a covariate. The unadjusted p-value was presented.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.46
    Confidence Interval (2-Sided) 95%
    1.04 to 2.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Olmesartan 40 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.080
    Comments P-value for response criteria for systolic blood pressure was from a logistic regression with treatment as a factor and baseline clinic systolic blood pressure as a covariate. The unadjusted p-value was presented.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.35
    Confidence Interval (2-Sided) 95%
    0.96 to 1.89
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Valsartan 320 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.071
    Comments P-value for response criteria for systolic blood pressure was from a logistic regression with treatment as a factor and baseline clinic systolic blood pressure as a covariate. The unadjusted p-value was presented.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.37
    Confidence Interval (2-Sided) 95%
    0.97 to 1.92
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    14. Secondary Outcome
    Title Percentage of Participants Who Achieve a Clinic Diastolic Blood Pressure Response, Defined as < 90 mm Hg and/or Reduction From Baseline ≥ 10 mm Hg
    Description Percentage of participants who achieve a clinic diastolic blood pressure response measured at week 6, defined as less than 90 mm Hg and/or reduction from baseline of greater than or equal to 10 mm Hg. Diastolic blood pressure is the arithmetic mean of the 3 trough sitting diastolic blood pressure measurements.
    Time Frame Baseline and Week 6.

    Outcome Measure Data

    Analysis Population Description
    Full analysis set with last observation carried forward.
    Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD Olmesartan 40 mg QD Placebo QD
    Arm/Group Description Azilsartan medoxomil 20 mg, tablets and matching placebo comparator orally once daily for two weeks. Increased to azilsartan medoxomil 40 mg tablets and matching placebo comparator orally, once daily for up to four weeks. Azilsartan medoxomil 40 mg, tablets and matching placebo comparator orally, once daily for two weeks. Increased to Azilsartan medoxomil 80 mg, tablets and matching placebo comparator orally, once daily for up to four weeks. Valsartan 160 mg, tablets, and matching placebo comparator orally, once daily for two weeks. Increased to Valsartan 320 mg, tablets, and matching placebo comparator, orally, once daily for up to four weeks. Olmesartan 20 mg, tablets and matching placebo comparator, orally, once daily for two weeks. Increased to Olmesartan 40 mg, tablets and matching placebo comparator, orally, once daily for up to four weeks. Matching placebo, orally, once daily for up to six weeks.
    Measure Participants 269 270 271 283 148
    Number [percentage of participants]
    68.8
    24.6%
    71.1
    24.9%
    63.8
    22.6%
    68.2
    23.5%
    43.9
    28.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Placebo QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value for response criteria for diastolic blood pressure was from a logistic regression with treatment as a factor and baseline clinic diastolic blood pressure as a covariate. The unadjusted p-value was presented.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.29
    Confidence Interval (2-Sided) 95%
    2.10 to 5.15
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Placebo QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value for response criteria for diastolic blood pressure was from a logistic regression with treatment as a factor and baseline clinic diastolic blood pressure as a covariate. The unadjusted p-value was presented.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.91
    Confidence Interval (2-Sided) 95%
    1.86 to 4.54
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Olmesartan 40 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.306
    Comments P-value for response criteria for diastolic blood pressure was from a logistic regression with treatment as a factor and baseline clinic diastolic blood pressure as a covariate. The unadjusted p-value was presented.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.22
    Confidence Interval (2-Sided) 95%
    0.83 to 1.80
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Valsartan 320 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.132
    Comments P-value for response criteria for diastolic blood pressure was from a logistic regression with treatment as a factor and baseline clinic diastolic blood pressure as a covariate. The unadjusted p-value was presented.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.34
    Confidence Interval (2-Sided) 95%
    0.92 to 1.97
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Olmesartan 40 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.695
    Comments P-value for response criteria for diastolic blood pressure was from a logistic regression with treatment as a factor and baseline clinic diastolic blood pressure as a covariate. The unadjusted p-value was presented.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.08
    Confidence Interval (2-Sided) 95%
    0.74 to 1.58
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Valsartan 320 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.381
    Comments P-value for response criteria for diastolic blood pressure was from a logistic regression with treatment as a factor and baseline clinic diastolic blood pressure as a covariate. The unadjusted p-value was presented.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.19
    Confidence Interval (2-Sided) 95%
    0.81 to 1.74
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    15. Secondary Outcome
    Title Percentage of Participants Who Achieve Both a Clinic Diastolic and Systolic Blood Pressure Response
    Description Percentage of participants who achieve both a clinic diastolic and systolic blood pressure response measured at week 6, defined as less than 90 mm Hg and/or reduction from baseline of greater than or equal to 10 mm Hg AND less than 140 mm Hg and/or reduction from baseline of greater than or equal to 20 mm Hg. Diastolic and systolic blood pressure is based on the arithmetic mean of the 3 sitting blood pressure measurements.
    Time Frame Baseline and Week 6.

    Outcome Measure Data

    Analysis Population Description
    Full analysis set with last observation carried forward.
    Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD Olmesartan 40 mg QD Placebo QD
    Arm/Group Description Azilsartan medoxomil 20 mg, tablets and matching placebo comparator orally once daily for two weeks. Increased to azilsartan medoxomil 40 mg tablets and matching placebo comparator orally, once daily for up to four weeks. Azilsartan medoxomil 40 mg, tablets and matching placebo comparator orally, once daily for two weeks. Increased to Azilsartan medoxomil 80 mg, tablets and matching placebo comparator orally, once daily for up to four weeks. Valsartan 160 mg, tablets, and matching placebo comparator orally, once daily for two weeks. Increased to Valsartan 320 mg, tablets, and matching placebo comparator, orally, once daily for up to four weeks. Olmesartan 20 mg, tablets and matching placebo comparator, orally, once daily for two weeks. Increased to Olmesartan 40 mg, tablets and matching placebo comparator, orally, once daily for up to four weeks. Matching placebo, orally, once daily for up to six weeks.
    Measure Participants 269 270 271 283 148
    Number [percentage of participants]
    49.1
    17.5%
    52.6
    18.5%
    43.9
    15.6%
    44.5
    15.3%
    18.2
    11.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Placebo QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value for joint response criteria for systolic blood pressure and diastolic blood pressure was from a logistic regression with treatment as a factor and baseline clinic systolic blood pressure as a covariate. The unadjusted p-value was presented.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 5.18
    Confidence Interval (2-Sided) 95%
    3.20 to 8.41
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Placebo QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value for joint response criteria for systolic blood pressure and diastolic blood pressure was from a logistic regression with treatment as a factor and baseline clinic systolic blood pressure as a covariate. The unadjusted p-value was presented.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.43
    Confidence Interval (2-Sided) 95%
    2.73 to 7.19
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Olmesartan 40 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.056
    Comments P-value for joint response criteria for systolic blood pressure and diastolic blood pressure was from a logistic regression with treatment as a factor and baseline clinic systolic blood pressure as a covariate. The unadjusted p-value was presented.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.39
    Confidence Interval (2-Sided) 95%
    0.99 to 1.94
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 80 mg QD, Valsartan 320 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.036
    Comments P-value for joint response criteria for systolic blood pressure and diastolic blood pressure was from a logistic regression with treatment as a factor and baseline clinic systolic blood pressure as a covariate. The unadjusted p-value was presented.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.44
    Confidence Interval (2-Sided) 95%
    1.02 to 2.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Olmesartan 40 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.317
    Comments P-value for joint response criteria for systolic blood pressure and diastolic blood pressure was from a logistic regression with treatment as a factor and baseline clinic systolic blood pressure as a covariate. The unadjusted p-value was presented.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.19
    Confidence Interval (2-Sided) 95%
    0.85 to 1.66
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Azilsartan Medoxomil 40 mg QD, Valsartan 320 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.234
    Comments P-value for joint response criteria for systolic blood pressure and diastolic blood pressure was from a logistic regression with treatment as a factor and baseline clinic systolic blood pressure as a covariate. The unadjusted p-value was presented.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.23
    Confidence Interval (2-Sided) 95%
    0.87 to 1.73
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    Time Frame Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug.
    Adverse Event Reporting Description At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
    Arm/Group Title Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD Olmesartan 40 mg QD Placebo QD
    Arm/Group Description Azilsartan medoxomil 20 mg, tablets and matching placebo comparator orally once daily for two weeks. Increased to azilsartan medoxomil 40 mg tablets and matching placebo comparator orally, once daily for up to four weeks. Azilsartan medoxomil 40 mg, tablets and matching placebo comparator orally, once daily for two weeks. Increased to Azilsartan medoxomil 80 mg, tablets and matching placebo comparator orally, once daily for up to four weeks. Valsartan 160 mg, tablets, and matching placebo comparator orally, once daily for two weeks. Increased to Valsartan 320 mg, tablets, and matching placebo comparator, orally, once daily for up to four weeks. Olmesartan 20 mg, tablets and matching placebo comparator, orally, once daily for two weeks. Increased to Olmesartan 40 mg, tablets and matching placebo comparator, orally, once daily for up to four weeks. Matching placebo, orally, once daily for up to six weeks.
    All Cause Mortality
    Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD Olmesartan 40 mg QD Placebo QD
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD Olmesartan 40 mg QD Placebo QD
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/280 (0.7%) 3/284 (1.1%) 3/277 (1.1%) 4/290 (1.4%) 2/155 (1.3%)
    Eye disorders
    Eye irritation 0/280 (0%) 1/284 (0.4%) 0/277 (0%) 0/290 (0%) 0/155 (0%)
    Gastrointestinal disorders
    Abdominal adhesions 0/280 (0%) 0/284 (0%) 0/277 (0%) 0/290 (0%) 1/155 (0.6%)
    Gastrointestinal haemorrhage 0/280 (0%) 1/284 (0.4%) 0/277 (0%) 0/290 (0%) 0/155 (0%)
    Hepatobiliary disorders
    Cholecystitis 1/280 (0.4%) 0/284 (0%) 0/277 (0%) 0/290 (0%) 0/155 (0%)
    Cholelithiasis 1/280 (0.4%) 0/284 (0%) 0/277 (0%) 0/290 (0%) 0/155 (0%)
    Infections and infestations
    Cellulitis 0/280 (0%) 0/284 (0%) 0/277 (0%) 1/290 (0.3%) 0/155 (0%)
    Diverticulitis 0/280 (0%) 1/284 (0.4%) 0/277 (0%) 0/290 (0%) 0/155 (0%)
    Infected bites 0/280 (0%) 0/284 (0%) 0/277 (0%) 1/290 (0.3%) 0/155 (0%)
    Injury, poisoning and procedural complications
    Fall 0/280 (0%) 0/284 (0%) 1/277 (0.4%) 0/290 (0%) 1/155 (0.6%)
    Intentional overdose 0/280 (0%) 0/284 (0%) 1/277 (0.4%) 0/290 (0%) 0/155 (0%)
    Subdural haematoma 0/280 (0%) 0/284 (0%) 0/277 (0%) 1/290 (0.3%) 0/155 (0%)
    Investigations
    Blood pressure increased 0/280 (0%) 1/284 (0.4%) 0/277 (0%) 0/290 (0%) 0/155 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer 0/280 (0%) 0/284 (0%) 0/277 (0%) 1/290 (0.3%) 0/155 (0%)
    Nervous system disorders
    Partial seizures 0/280 (0%) 0/284 (0%) 0/277 (0%) 1/290 (0.3%) 0/155 (0%)
    Reproductive system and breast disorders
    Dysfunctional uterine bleeding 1/280 (0.4%) 0/284 (0%) 0/277 (0%) 0/290 (0%) 0/155 (0%)
    Vascular disorders
    Deep vein thrombosis 0/280 (0%) 0/284 (0%) 1/277 (0.4%) 0/290 (0%) 0/155 (0%)
    Other (Not Including Serious) Adverse Events
    Azilsartan Medoxomil 40 mg QD Azilsartan Medoxomil 80 mg QD Valsartan 320 mg QD Olmesartan 40 mg QD Placebo QD
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 18/280 (6.4%) 12/284 (4.2%) 21/277 (7.6%) 23/290 (7.9%) 14/155 (9%)
    Nervous system disorders
    Headache 18/280 (6.4%) 12/284 (4.2%) 21/277 (7.6%) 23/290 (7.9%) 14/155 (9%)

    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
    Email clinicaltrialregistry@tpna.com
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00696436
    Other Study ID Numbers:
    • 01-06-TL-491-019
    • U1111-1113-9161
    First Posted:
    Jun 12, 2008
    Last Update Posted:
    Apr 19, 2011
    Last Verified:
    Mar 1, 2011