Hypertension
Conditions
Keywords
Blood pressure, blood pressure monitoring, ambulatory
Brief summary
The purpose of this study is to compare the efficacy and safety of TAK-491 (azilsartan medoxomil), once daily (QD), to valsartan in participants with essential hypertension.
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 (WHO), 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 continue to maintain control successfully. This study is being conducted to determine whether administration of azilsartan medoxomil in subjects with essential hypertension is more efficacious in reducing systolic blood pressure than valsartan. Study participation is anticipated to be approximately 7 months. Outside of the study center, participants will be required to wear an ambulatory blood pressure monitoring device at 24 hour intervals. Following completion of the 6-month double-blind treatment period, all available subjects will be offered the option to continue in a 28-week extension study with open-label azilsartan medoxomil 40 mg. For the extension study, participants will take azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 28 weeks. Hydrochlorothiazide 12.5 mg or 25 mg or any other antihypertensive (except angiotensin II receptor blockers) may be added in a step-wise fashion to maintain blood pressure within target \<140/90 mmHg for non-diabetic subjects and \<130/80 mmHg for diabetic subjects
Interventions
Azilsartan Medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks.
DRUGValsartan
Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Essential hypertension (defined as sitting trough clinic systolic blood pressure between 150 and 180 mm Hg inclusive at Day minus 1 and 24-hour mean systolic blood pressure between 130 and 170 mm Hg inclusive at Day 1). 2. Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study. 3. Clinical laboratory evaluations (including clinical chemistry, hematology, and complete urinalysis) within the reference range for the testing laboratory or the results are deemed not clinically significant for inclusion into this study by the investigator. 4. Willing to discontinue current antihypertensive medications at the Screening Day minus 21 visit. If the subject is on amlodipine prior to Screening, the subject is willing to discontinue this medication at Screening Day minus 28.
Exclusion criteria
1. Sitting trough clinic diastolic blood pressure greater than 114 mm Hg at Day minus 1. 2. The subject has a baseline 24-hour ambulatory blood pressure monitor reading of insufficient quality. 3. 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. 4. Hypersensitive to angiotensin II receptor blockers. 5. Recent history (within the last 6 months) 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 (eg, 3rd degree atrioventricular block, left bundle branch block, sick sinus syndrome, atrial fibrillation or flutter). 7. Hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease. 8. Secondary hypertension of any etiology. 9. Non-compliant (less than 70% or greater than 130%) with study medication during placebo run-in period. 10. Severe renal dysfunction or disease (based on calculated creatinine clearance less than 30 mL per min/1.73m2) at Screening. 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 subjects with basal cell or Stage 1 squamous cell carcinoma of the skin). 14. Type 1 or poorly controlled type 2 diabetes mellitus (glycosylated hemoglobin greater than 8.0%) at Screening. 15. Hyperkalemia as defined by the central laboratory normal reference range at Screening. 16. Upper arm circumference less than 24 cm or greater than 42 cm. 17. Works night (3rd) shift (defined as 11PM to 7AM). 18. Alanine aminotransferase level of greater than 2.5 times the upper limit of normal, active liver disease, or jaundice at Screening. 19. Currently is participating in another investigational study or has participated in an investigational study within 30 days prior to randomization. 20. Any other serious disease or condition at Screening (or Randomization) that would compromise subject safety, might affect life expectancy, or make it difficult to successfully manage and follow the subject according to the protocol. 21. Randomized in a previous azilsartan medoxomil study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in 24-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | Baseline and Week 24. | The change in 24-hour mean systolic blood pressure measured at week 24 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
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the 24-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | Baseline and Week 24. | The change in 24-hour mean diastolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing. |
| Change From Baseline in Mean Trough Clinic Sitting Diastolic Blood Pressure | Baseline and Week 24. | The change in mean trough clinic sitting diastolic blood pressure measured at final visit or week 24 relative to baseline. Diastolic blood pressure is the arithmetic mean of the 3 trough sitting systolic blood pressure measurements. |
| Change From Baseline in Daytime (6am to 10 pm) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | Baseline and Week 24. | The change in daytime (6am to 10pm) mean systolic blood pressure measured at week 24 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. |
| Change From Baseline in Daytime (6am to 10 pm) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | Baseline and Week 24. | The change in daytime (6am to 10pm) mean systolic blood pressure measured at week 24 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. |
| Change From Baseline in the Nighttime (12 am to 6 am) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | Baseline and Week 24. | The change in nighttime (12am to 6am) mean systolic blood pressure measured at week 24 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. |
| Change From Baseline in the Nighttime (12 am to 6 am) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | Baseline and Week 24. | The change in nighttime (12am to 6am) mean diastolic blood pressure measured at week 24 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. |
| Change From Baseline in Mean Trough Clinic Sitting Systolic Blood Pressure. | Baseline and Week 24. | The change in mean trough clinic sitting systolic blood pressure measured at final visit or week 24 relative to baseline. Systolic blood pressure is the arithmetic mean of the 3 trough sitting systolic blood pressure measurements. |
| Change From Baseline in the 12-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | Baseline and Week 24. | The change in the 12-hour mean diastolic blood pressure measured at week 24 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. |
| Change From Baseline in the Trough (22-24-hr) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | Baseline and Week 24. | The change in trough mean systolic blood pressure measured at week 24 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. |
| Change From Baseline in the Trough (22-24-hr) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | Baseline and Week 24. | The change in trough mean diastolic blood pressure measured at week 24 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. |
| 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 24. | Percentage of participants who achieve a clinic systolic blood pressure response measured at week 24, 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. |
| 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 24. | Percentage of participants who achieve a clinic diastolic blood pressure response measured at week 24, 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. |
| Percentage of Participants Who Achieve Both a Clinic Diastolic and Systolic Blood Pressure Response. | Baseline and Week 24. | Percentage of participants who achieve both a clinic diastolic and systolic blood pressure response measured at week 24, 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. |
| Change From Baseline in the 12-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | Baseline and Week 24. | The change in the 12-hour mean systolic blood pressure measured at week 24 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. |
Countries
Chile, Mexico, Peru, United States
Participant flow
Recruitment details
Participants enrolled at 103 investigative sites from 09 November 2007 to 03 September 2009 (double-blind phase) and 04 March 2009 to 13 March 2010 (open-label extension phase). A total of 984 participants were randomized into the double-blind treatment phase, of which 170 participants entered into the open-label extension phase.
Pre-assignment details
Participants with essential hypertension were enrolled in one of three, once-daily (QD) treatment groups.
Participants by arm
| Arm | Count |
|---|---|
| Azilsartan Medoxomil 40 mg QD Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 40 mg, tablets, orally, once daily for up to 22 weeks.
Open Label Extension: Azilsartan medoxomil 40 mg, tablets, orally, once daily for 28 weeks. Investigators may have added, in a step-wise fashion, hydrochlorothiazide 12.5 mg, followed by hydrochlorothiazide 25 mg, followed by other antihypertensive medications (except angiotensin II receptor blockers) as needed to achieve target blood pressure (\<140/90 mm Hg or \<130/80 mm Hg for diabetics).
Open Label Extension: Azilsartan medoxomil 40 mg, tablets, orally, once daily for 28 weeks. Investigators may have added, in a step-wise fashion, hydrochlorothiazide 12.5 mg, followed by hydrochlorothiazide 25 mg, followed by other antihypertensive medications (except angiotensin II receptor blockers) as needed to achieve target blood pressure (\<140/90 mm Hg or \<130/80 mm Hg for diabetics). | 327 |
| Azilsartan Medoxomil 80 mg QD Azilsartan medoxomil 20 mg, tablets, orally, once daily for 2 weeks; titrated to 80 mg, tablets, orally, once daily for up to 22 weeks.
Open Label Extension: Azilsartan medoxomil 40 mg, tablets, orally, once daily for 28 weeks. Investigators may have added, in a step-wise fashion, hydrochlorothiazide 12.5 mg, followed by hydrochlorothiazide 25 mg, followed by other antihypertensive medications (except angiotensin II receptor blockers) as needed to achieve target blood pressure (\<140/90 mm Hg or \<130/80 mm Hg for diabetics).
Open Label Extension: Azilsartan medoxomil 40 mg, tablets, orally, once daily for 28 weeks. Investigators may have added, in a step-wise fashion, hydrochlorothiazide 12.5 mg, followed by hydrochlorothiazide 25 mg, followed by other antihypertensive medications (except angiotensin II receptor blockers) as needed to achieve target blood pressure (\<140/90 mm Hg or \<130/80 mm Hg for diabetics). | 329 |
| Valsartan 320 mg QD Valsartan 80 mg, tablets, orally, once daily for 2 weeks; titrated to 320 mg, tablets, orally, once daily for up to 22 weeks.
Open Label Extension: Azilsartan medoxomil 40 mg, tablets, orally, once daily for 28 weeks. Investigators may have added, in a step-wise fashion, hydrochlorothiazide 12.5 mg, followed by hydrochlorothiazide 25 mg, followed by other antihypertensive medications (except angiotensin II receptor blockers) as needed to achieve target blood pressure (\<140/90 mm Hg or \<130/80 mm Hg for diabetics). | 328 |
| Total | 984 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-Blind Treatment Phase | Adverse Event | 20 | 26 | 19 |
| Double-Blind Treatment Phase | Lack of Efficacy | 16 | 9 | 25 |
| Double-Blind Treatment Phase | Lost to Follow-up | 12 | 12 | 11 |
| Double-Blind Treatment Phase | Other | 4 | 9 | 4 |
| Double-Blind Treatment Phase | Pregnancy | 1 | 0 | 0 |
| Double-Blind Treatment Phase | Protocol Violation | 3 | 2 | 3 |
| Double-Blind Treatment Phase | Withdrawal by Subject | 22 | 22 | 22 |
| Open-Label Extension Phase | Adverse Event | 3 | 5 | 0 |
| Open-Label Extension Phase | Lost to Follow-up | 1 | 4 | 0 |
| Open-Label Extension Phase | Other | 1 | 0 | 0 |
| Open-Label Extension Phase | Withdrawal by Subject | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Azilsartan Medoxomil 40 mg QD | Azilsartan Medoxomil 80 mg QD | Valsartan 320 mg QD | Total |
|---|---|---|---|---|
| Age, Customized <45 years (Double Blind Phase) | 43 participants | 39 participants | 31 participants | 113 participants |
| Age, Customized <45 years (Open Label Phase) | 10 participants | 8 participants | 0 participants | 18 participants |
| Age, Customized ≥65 years (Double Blind Phase) | 103 participants | 82 participants | 98 participants | 283 participants |
| Age, Customized ≥65 years (Open Label Phase) | 20 participants | 39 participants | 0 participants | 59 participants |
| Age, Customized Between 45 and 64 years (Double Blind Phase) | 181 participants | 208 participants | 199 participants | 588 participants |
| Age, Customized Between 45 and 64 years (Open Label Phase) | 25 participants | 68 participants | 0 participants | 93 participants |
| Sex/Gender, Customized Female (Double Blind Phase) | 163 participants | 160 participants | 152 participants | 475 participants |
| Sex/Gender, Customized Female (Open Label Phase) | 34 participants | 57 participants | 0 participants | 91 participants |
| Sex/Gender, Customized Male (Double Blind Phase) | 164 participants | 169 participants | 176 participants | 509 participants |
| Sex/Gender, Customized Male (Open Label Phase) | 21 participants | 58 participants | 0 participants | 79 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 77 / 327 | 74 / 329 | 53 / 326 | 16 / 170 |
| serious Total, serious adverse events | 8 / 327 | 5 / 329 | 8 / 326 | 4 / 170 |
Outcome results
Primary
Change From Baseline in 24-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
The change in 24-hour mean systolic blood pressure measured at week 24 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 24.
Population: Full analysis set with last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in 24-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | -14.93 mmHg | Standard Error 0.698 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in 24-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | -15.32 mmHg | Standard Error 0.715 |
| Valsartan 320 mg QD | Change From Baseline in 24-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | -11.29 mmHg | Standard Error 0.707 |
p-value: <0.00195% CI: [-5.59, -1.69]ANCOVA
p-value: <0.00195% CI: [-6.01, -2.06]ANCOVA
Secondary
Change From Baseline in Daytime (6am to 10 pm) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
The change in daytime (6am to 10pm) mean systolic blood pressure measured at week 24 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 24.
Population: Full analysis set with last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in Daytime (6am to 10 pm) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | -9.61 mmHg | Standard Error 0.493 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in Daytime (6am to 10 pm) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | -10.11 mmHg | Standard Error 0.504 |
| Valsartan 320 mg QD | Change From Baseline in Daytime (6am to 10 pm) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | -7.44 mmHg | Standard Error 0.499 |
p-value: 0.00295% CI: [-3.54, -0.79]ANCOVA
p-value: <0.00195% CI: [-4.06, -1.28]ANCOVA
Secondary
Change From Baseline in Daytime (6am to 10 pm) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
The change in daytime (6am to 10pm) mean systolic blood pressure measured at week 24 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 24.
Population: Full analysis set with last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in Daytime (6am to 10 pm) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | -15.39 mmHg | Standard Error 0.732 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in Daytime (6am to 10 pm) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | -15.80 mmHg | Standard Error 0.749 |
| Valsartan 320 mg QD | Change From Baseline in Daytime (6am to 10 pm) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | -11.91 mmHg | Standard Error 0.741 |
p-value: <0.00195% CI: [-5.53, -1.44]ANCOVA
p-value: <0.00195% CI: [-5.96, -1.83]ANCOVA
Secondary
Change From Baseline in Mean Trough Clinic Sitting Diastolic Blood Pressure
The change in mean trough clinic sitting diastolic blood pressure measured at final visit or week 24 relative to baseline. Diastolic blood pressure is the arithmetic mean of the 3 trough sitting systolic blood pressure measurements.
Time frame: Baseline and Week 24.
Population: Full analysis set with last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in Mean Trough Clinic Sitting Diastolic Blood Pressure | -7.16 mmHg | Standard Error 0.554 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in Mean Trough Clinic Sitting Diastolic Blood Pressure | -7.41 mmHg | Standard Error 0.565 |
| Valsartan 320 mg QD | Change From Baseline in Mean Trough Clinic Sitting Diastolic Blood Pressure | -4.65 mmHg | Standard Error 0.555 |
p-value: 0.00195% CI: [-4.06, -0.98]ANCOVA
p-value: <0.00195% CI: [-4.32, -1.21]ANCOVA
Secondary
Change From Baseline in Mean Trough Clinic Sitting Systolic Blood Pressure.
The change in mean trough clinic sitting systolic blood pressure measured at final visit or week 24 relative to baseline. Systolic blood pressure is the arithmetic mean of the 3 trough sitting systolic blood pressure measurements.
Time frame: Baseline and Week 24.
Population: Full analysis set with last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in Mean Trough Clinic Sitting Systolic Blood Pressure. | -14.86 mmHg | Standard Error 0.948 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in Mean Trough Clinic Sitting Systolic Blood Pressure. | -16.92 mmHg | Standard Error 0.966 |
| Valsartan 320 mg QD | Change From Baseline in Mean Trough Clinic Sitting Systolic Blood Pressure. | -11.59 mmHg | Standard Error 0.949 |
p-value: 0.01595% CI: [-5.9, -0.63]ANCOVA
p-value: <0.00195% CI: [-8, -2.68]ANCOVA
Secondary
Change From Baseline in the 12-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
The change in the 12-hour mean diastolic blood pressure measured at week 24 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 24.
Population: Full analysis set with last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in the 12-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | -9.70 mmHg | Standard Error 0.522 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in the 12-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | -10.26 mmHg | Standard Error 0.534 |
| Valsartan 320 mg QD | Change From Baseline in the 12-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | -7.53 mmHg | Standard Error 0.528 |
p-value: 0.00395% CI: [-3.63, -0.72]ANCOVA
p-value: <0.00195% CI: [-4.2, -1.25]ANCOVA
Secondary
Change From Baseline in the 12-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
The change in the 12-hour mean systolic blood pressure measured at week 24 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 24.
Population: Full analysis set with last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in the 12-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | -15.64 mmHg | Standard Error 0.764 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in the 12-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | -16.20 mmHg | Standard Error 0.782 |
| Valsartan 320 mg QD | Change From Baseline in the 12-hour Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | -12.20 mmHg | Standard Error 0.774 |
p-value: 0.00295% CI: [-5.57, -1.3]ANCOVA
p-value: <0.00195% CI: [-6.16, -1.85]ANCOVA
Secondary
Change From Baseline in the 24-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
The change in 24-hour mean diastolic blood pressure measured at week 24 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 24.
Population: Full analysis set with last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in the 24-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | -9.23 mmHg | Standard Error 0.459 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in the 24-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | -9.77 mmHg | Standard Error 0.47 |
| Valsartan 320 mg QD | Change From Baseline in the 24-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | -7.07 mmHg | Standard Error 0.465 |
p-value: <0.00195% CI: [-3.44, -0.88]ANCOVA
p-value: <0.00195% CI: [-3.99, -1.4]ANCOVA
Secondary
Change From Baseline in the Nighttime (12 am to 6 am) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
The change in nighttime (12am to 6am) mean diastolic blood pressure measured at week 24 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 24.
Population: Full analysis set with last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in the Nighttime (12 am to 6 am) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | -8.06 mmHg | Standard Error 0.526 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in the Nighttime (12 am to 6 am) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | -8.90 mmHg | Standard Error 0.539 |
| Valsartan 320 mg QD | Change From Baseline in the Nighttime (12 am to 6 am) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | -6.06 mmHg | Standard Error 0.533 |
p-value: 0.00895% CI: [-3.48, -0.53]ANCOVA
p-value: <0.00195% CI: [-4.33, -1.35]ANCOVA
Secondary
Change From Baseline in the Nighttime (12 am to 6 am) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
The change in nighttime (12am to 6am) mean systolic blood pressure measured at week 24 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 24.
Population: Full analysis set with last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in the Nighttime (12 am to 6 am) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | -13.31 mmHg | Standard Error 0.777 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in the Nighttime (12 am to 6 am) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | -13.95 mmHg | Standard Error 0.795 |
| Valsartan 320 mg QD | Change From Baseline in the Nighttime (12 am to 6 am) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | -9.52 mmHg | Standard Error 0.786 |
p-value: <0.00195% CI: [-5.96, -1.62]ANCOVA
p-value: <0.00195% CI: [-6.63, -2.24]ANCOVA
Secondary
Change From Baseline in the Trough (22-24-hr) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
The change in trough mean diastolic blood pressure measured at week 24 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 24.
Population: Full analysis set with last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in the Trough (22-24-hr) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | -9.37 mmHg | Standard Error 0.617 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in the Trough (22-24-hr) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | -9.65 mmHg | Standard Error 0.632 |
| Valsartan 320 mg QD | Change From Baseline in the Trough (22-24-hr) Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | -7.06 mmHg | Standard Error 0.625 |
p-value: 0.00995% CI: [-4.04, -0.59]ANCOVA
p-value: 0.00495% CI: [-4.34, -0.84]ANCOVA
Secondary
Change From Baseline in the Trough (22-24-hr) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
The change in trough mean systolic blood pressure measured at week 24 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 24.
Population: Full analysis set with last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan Medoxomil 40 mg QD | Change From Baseline in the Trough (22-24-hr) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | -13.74 mmHg | Standard Error 0.851 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline in the Trough (22-24-hr) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | -13.83 mmHg | Standard Error 0.871 |
| Valsartan 320 mg QD | Change From Baseline in the Trough (22-24-hr) Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring. | -10.36 mmHg | Standard Error 0.861 |
p-value: 0.00595% CI: [-5.76, -1]ANCOVA
p-value: 0.00595% CI: [-5.87, -1.06]ANCOVA
Secondary
Percentage of Participants Who Achieve a Clinic Diastolic Blood Pressure Response, Defined as < 90 mm Hg and/or Reduction From Baseline ≥ 10 mm Hg.
Percentage of participants who achieve a clinic diastolic blood pressure response measured at week 24, 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 24.
Population: Full analysis set with last observation carried forward.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Azilsartan Medoxomil 40 mg QD | Percentage of Participants Who Achieve a Clinic Diastolic Blood Pressure Response, Defined as < 90 mm Hg and/or Reduction From Baseline ≥ 10 mm Hg. | 72.4 percentage of participants |
| Azilsartan Medoxomil 80 mg QD | Percentage of Participants Who Achieve a Clinic Diastolic Blood Pressure Response, Defined as < 90 mm Hg and/or Reduction From Baseline ≥ 10 mm Hg. | 74.0 percentage of participants |
| Valsartan 320 mg QD | Percentage of Participants Who Achieve a Clinic Diastolic Blood Pressure Response, Defined as < 90 mm Hg and/or Reduction From Baseline ≥ 10 mm Hg. | 65.8 percentage of participants |
p-value: 0.04195% CI: [1.02, 2.1]Regression, Logistic
p-value: 0.01595% CI: [1.09, 2.28]Regression, Logistic
Secondary
Percentage of Participants Who Achieve a Clinic Systolic Blood Pressure Response, Defined as < 140 mm Hg and/or Reduction From Baseline ≥ 20 mm Hg.
Percentage of participants who achieve a clinic systolic blood pressure response measured at week 24, 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 24.
Population: Full analysis set with last observation carried forward.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Azilsartan Medoxomil 40 mg QD | Percentage of Participants Who Achieve a Clinic Systolic Blood Pressure Response, Defined as < 140 mm Hg and/or Reduction From Baseline ≥ 20 mm Hg. | 56.0 percentage of participants |
| Azilsartan Medoxomil 80 mg QD | Percentage of Participants Who Achieve a Clinic Systolic Blood Pressure Response, Defined as < 140 mm Hg and/or Reduction From Baseline ≥ 20 mm Hg. | 59.2 percentage of participants |
| Valsartan 320 mg QD | Percentage of Participants Who Achieve a Clinic Systolic Blood Pressure Response, Defined as < 140 mm Hg and/or Reduction From Baseline ≥ 20 mm Hg. | 46.9 percentage of participants |
p-value: 0.01695% CI: [1.07, 2]Regression, Logistic
p-value: 0.00295% CI: [1.19, 2.23]Regression, Logistic
Secondary
Percentage of Participants Who Achieve Both a Clinic Diastolic and Systolic Blood Pressure Response.
Percentage of participants who achieve both a clinic diastolic and systolic blood pressure response measured at week 24, 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 24.
Population: Full analysis set with last observation carried forward.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Azilsartan Medoxomil 40 mg QD | Percentage of Participants Who Achieve Both a Clinic Diastolic and Systolic Blood Pressure Response. | 50.2 percentage of participants |
| Azilsartan Medoxomil 80 mg QD | Percentage of Participants Who Achieve Both a Clinic Diastolic and Systolic Blood Pressure Response. | 54.7 percentage of participants |
| Valsartan 320 mg QD | Percentage of Participants Who Achieve Both a Clinic Diastolic and Systolic Blood Pressure Response. | 41.3 percentage of participants |
p-value: 0.01895% CI: [1.07, 1.99]Regression, Logistic
p-value: <0.00195% CI: [1.24, 2.33]Regression, Logistic