Essential Hypertension
Conditions
Keywords
High Blood Pressure, Drug Therapy
Brief summary
The purpose of this study is to evaluate the efficacy and safety of the fixed dose combinations of azilsartan medoxomil plus chlorthalidone (40/12.5 and 40/25 mg), once daily, in participants with grades 2 or 3 essential hypertension who do not reach target blood pressure following treatment with 40 mg azilsartan medoxomil monotherapy after 4 weeks.
Detailed description
Eligible participants completed a 2-week single-blind run-in period (Days -42 to -29) prior to a Single-Blind Monotherapy Treatment Period (Day -28 to Day -1) where they received azilsartan medoxomil 40 mg. After the Single-Blind Monotherapy Treatment Period, those participants who achieved target blood pressure discontinued treatment and resumed standard of care management at the discretion of their treating physician, while those participants who did not achieve target blood pressure (defined as clinic systolic blood pressure ≥140 mmHg) were randomly assigned to 1 of 3 active treatment arms: azilsartan medoxomil 40 mg plus placebo, azilsartan medoxomil plus chlorthalidone 40/12.5 mg, or azilsartan medoxomil plus chlorthalidone 40/25 mg.
Interventions
DRUGAzilsartan medoxomil/placebo
Azilsartan medoxomil and placebo to chlorthalidone combination tablets
DRUGAzilsartan medoxomil - chlorthalidone
Azilsartan medoxomil and chlorthalidone fixed dose combination tablets
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
At Screening 1. The participant has grade 2-3 essential hypertension which is not adequately controlled, as defined by mean, trough, sitting, clinic systolic blood pressure (SBP): * ≥160 to ≤180 mm Hg in participants who have not received any antihypertensive medication in the 14 days prior to Visit 1. * ≥150 to ≤170 mm Hg in participants taking 1 antihypertensive medication at Visit 1. * ≥140 to ≤160 mm Hg in participants taking 2 antihypertensive medications at Visit 1. 2. The participant has clinical laboratory test results (clinical chemistry, hematology, and complete urinalysis) within the reference range for the testing laboratory or the investigator does not consider the results to be clinically relevant for precluding entry in to the study in this hypertensive population. 3. The participant is willing to discontinue current antihypertensive medications. 4. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements. 5. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures. 6. Male or female adult, at least 18 years of age. 7. A female of childbearing potential who is sexually active with a nonsterilized male partner agrees to routinely use adequate contraception from signing of the informed consent through 30 days after the last study drug dose. NOTE: Women NOT of childbearing potential are defined as those who have been surgically sterilized (hysterectomy, bilateral oophorectomy, tubal ligation \[performed more than one 1 year prior to Screening\]) or who are postmenopausal (defined as at least 1 year since last regular menses). Post-placebo run-in: 8. The participant must have a post-placebo run-in, 24-hour mean SBP by ambulatory blood pressure monitoring (ABPM) of 140-175 mm Hg inclusive, and a clinic SBP measurement of 160 to 190 mm Hg inclusive (determined by the mean of 3 sitting, trough, measurements on Day -29) to qualify for entry in to the 4 week single-blind TAK-491 40 mg monotherapy treatment period. Post-4 week, single-blind TAK-491 40 mg monotherapy treatment: 9. The participant does not achieve target blood pressure (defined as clinic SBP ≥140 mm Hg as determined by the mean of 3 sitting, trough, measurements) following 4 weeks single-blind treatment with TAK-491 40 mg monotherapy at Day -1, prior to randomization to double-blind treatment.
Exclusion criteria
At Screening 1. The participant has clinic diastolic blood pressure (DBP) \>110 mm Hg. 2. The participant's 3 SBP measurements differ by more than 15 mm Hg (confirmed by a second set of three measurements). 3. The participant has received any investigational compound within 30 days prior to Screening or is currently participating in another investigational study. NOTE: Participants participating in observational studies (per local definition) may enter Screening provided that the last intervention or invasive procedure was \>30 days prior to Visit 1. 4. The participant has been randomized/enrolled in a previous TAK-491 or TAK-491CLD study. NOTE: This criterion does not apply to participants who entered screening or placebo run-in in another TAK-491 or TAK-491CLD study but were not randomized/enrolled. 5. The participant is a study site employee or is in a dependent relationship with a study site employee who is involved in conduct of this study (e.g., spouse, parent, child, sibling) or may consent under duress. 6. The participant is currently treated with more than 2 antihypertensive medications. 7. The participant works a night (third) shift (defined as 11 PM \[2300\] to 7 AM \[0700\]). 8. The participant has an upper arm circumference \<24 cm or \>42 cm. 9. The participant has secondary hypertension of any etiology (e.g., renovascular disease, pheochromocytoma, Cushing's syndrome). 10. The participant has any history of myocardial infarction, heart failure, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebrovascular accident, persistent or permanent atrial fibrillation or transient ischemic attack. 11. The participant has clinically significant cardiac conduction defects (e.g., third-degree atrioventricular block, sick sinus syndrome). 12. The participant has hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease or hypertrophic cardiomyopathy. 13. The participant has severe renal dysfunction or disease \[based on estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73m\^2 at screening\], prior renal transplantation or nephrotic syndrome (defined as a urinary albumin/creatinine ratio \>2000 mg/g at Screening). 14. Participant has known hemodynamically significant bilateral renal artery stenosis or unilateral disease in a single kidney. 15. The participant has a history of cancer that has not been in remission for at least 5 years prior to the first dose of single-blind TAK-491 monotherapy study drug. (This criterion does not apply to those participants with basal cell or Stage 1 squamous cell carcinoma of the skin). 16. The participant has poorly-controlled type 1 or 2 diabetes mellitus (hemoglobin A1c \[HbA1c\] \>8.5%) at Screening. 17. The participant has hypokalemia or hyperkalemia (defined as serum potassium outside of the normal reference range of the central laboratory) at Screening. 18. The participant has an alanine aminotransferase or aspartate aminotransferase level \>2.5 times the upper limit of normal, active liver disease, or jaundice at Screening. 19. The participant has any other known serious disease or condition that would compromise safety, might affect life expectancy, or make it difficult to successfully manage and follow the participant according to the protocol. 20. The participant has a history of hypersensitivity or allergies to angiotensin II receptor blockers (ARB) or thiazide-type diuretics or other sulfonamide-derived compounds. 21. The participant has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse per local guidelines within the past 2 years. 22. The participant is required to take excluded medications at any point during the study. 23. If female, the participant is pregnant or lactating or intending to become pregnant before, during, or within 1 month after participating in this study; or intending to donate ova during such time period. Post-placebo run-in period 24. The participant has a clinic SBP \>190 mm Hg and DBP \>115 mm Hg. 25. The participant is noncompliant (\<70% or \>130%) with study medication during the placebo run-in period. 26. The participant has a 24-hour mean eligibility ABPM reading of insufficient quality. Post-single-blind TAK-491 40 mg treatment period 27. The participant has a clinic SBP \>180 mm Hg and DBP \>110 mm Hg. 28. The participant is noncompliant (\<70% or \>130%) with study medication during the TAK-491 40 mg single-blind treatment period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure | Baseline (of the double-blind treatment period) and Week 8 | The change between trough systolic blood pressure measured at final visit or Week 8 relative to baseline. Systolic blood pressure is the arithmetic mean of the 3 trough sitting systolic blood pressure measurements. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 8 in Trough Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring | Baseline and Week 8, 22-24 hours after dosing | The change in trough systolic blood pressure measured at final visit or week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough is the average of all measurements recorded from 22 to 24 hours after dosing. |
| Change From Baseline to Week 8 in Trough Diastolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring | Baseline and Week 8, 22-24 hours after dosing | The change in trough diastolic blood pressure measured at final visit or week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough is the average of all measurements recorded from 22 to 24 hours after dosing. |
| Change From Baseline to Week 8 in the 24-hour Mean Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Baseline and Week 8 | The change in 24-hour mean systolic blood pressure measured at final visit or week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing. |
| Change From Baseline to Week 8 in the 24-hour Mean Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Baseline and Week 8 | The change in 24-hour mean diastolic blood pressure measured at final visit or week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing. |
| Change From Baseline to Week 8 in the Mean Daytime Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Baseline and Week 8 | The change in daytime (6 am to 10 pm) mean systolic blood pressure measured at final visit or week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of all measurements recorded between the hours of 6 am and 10 pm. |
| Change From Baseline to Week 8 in the Mean Daytime Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Baseline and Week 8 | The change in daytime (6 am to 10 pm) mean diastolic blood pressure measured at final visit or week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of all measurements recorded between the hours of 6 am and 10 pm. |
| Change From Baseline to Week 8 in Trough, Sitting, Clinic Diastolic Blood Pressure | Baseline and Week 8 | The change between trough diastolic blood pressure measured at final visit or week 8 relative to baseline Diastolic blood pressure is the arithmetic mean of the 3 trough sitting diastolic blood pressure measurements. |
| Change From Baseline to Week 8 in the Mean Nighttime Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Baseline and Week 8. | The change in nighttime (12 am to 6 am) mean diastolic blood pressure measured at final visit or week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of all measurements recorded between the hours of 12 am and 6 am. |
| Change From Baseline to Week 8 in the Mean Systolic Blood Pressure 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring | Baseline and Week 8 | The change in the 12-hour mean systolic blood pressure measured at final visit or week 8 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 to Week 8 in the Mean Diastolic Blood Pressure 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring | Baseline and Week 8 | The change in the 12-hour mean diastolic blood pressure measured at final visit or Week 8 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. |
| Percentage of Participants Who Achieve a Target Clinic Systolic Blood Pressure at Week 8 | Week 8 | Percentage of participants who achieve a target clinic systolic blood pressure measured at final visit or week 8, defined as less than 140 mm Hg (or less than 130 mm Hg for participants with diabetes or chronic kidney disease). Systolic blood pressure is the arithmetic mean of the 3 trough sitting Systolic blood pressure measurements. |
| Percentage of Participants Who Achieve a Target Clinic Diastolic Blood Pressure at Week 8 | Week 8 | Percentage of participants who achieve a target clinic diastolic blood pressure measured at final visit or week 8, defined as less than 90 mm Hg (or less than 80 mm Hg for participants with diabetes or chronic kidney disease). Diastolic blood pressure is based on the arithmetic mean of the 3 trough sitting diastolic blood pressure measurements. |
| Percentage of Participants Who Achieve Both Clinic Systolic and Diastolic Blood Pressure Targets at Week 8 | Week 8 | Percentage of participants who achieve both clinic systolic and diastolic blood pressure targets at Week 8, defined as less than 140 mm Hg (or less than 130 mm Hg for participants with diabetes or chronic kidney disease) for systolic AND less than 90 mm Hg (or less than 80 mm Hg for participants with diabetes or chronic kidney disease) for diastolic blood pressure. |
| Change From Baseline to Week 8 in the Mean Nighttime Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Baseline and Week 8 | The change in nighttime (12 am to 6 am) mean systolic blood pressure measured at final visit or week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of all measurements recorded between the hours of 12 am and 6 am. |
Countries
Bulgaria, Estonia, France, Germany, Hungary, Italy, Lithuania, Netherlands, Poland, Serbia, Slovakia, Spain, Sweden, United Kingdom
Participant flow
Recruitment details
A total of 1754 patients were screened at 125 investigative sites in Bulgaria, Estonia, France, Germany, Hungary, Italy, Lithuania, the Netherlands, Poland, Serbia, Slovakia, Spain, Sweden, and the United Kingdom from 31 October 2011 to 24 January 2013.
Pre-assignment details
507 participants entered the azilsartan medoxomil 40 mg Single-Blind Monotherapy Treatment Period and 395 participants were eligible to enter the Double-Blind Treatment Period and were randomly assigned to 1 of 3 active treatment arms.
Participants by arm
| Arm | Count |
|---|---|
| Azilsartan Medoxomil 40 mg Azilsartan medoxomil 40 mg and chlorthalidone placebo combination tablets, orally, once daily for up to 8 weeks. | 133 |
| Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg Azilsartan 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for up to 8 weeks. | 127 |
| Azilsartan Medoxomil + Chlorthalidone 40/25 mg Azilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for up to 8 weeks. | 135 |
| Total | 395 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 7 |
| Overall Study | Lack of Efficacy | 2 | 0 | 0 |
| Overall Study | Major Protocol Deviation | 3 | 2 | 3 |
| Overall Study | Other | 1 | 1 | 0 |
| Overall Study | Voluntary Withdrawal | 3 | 0 | 2 |
Baseline characteristics
| Characteristic | Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg | Total | Azilsartan Medoxomil + Chlorthalidone 40/25 mg | Azilsartan Medoxomil 40 mg |
|---|---|---|---|---|
| Age, Continuous | 59.2 years STANDARD_DEVIATION 10.72 | 58.2 years STANDARD_DEVIATION 10.45 | 57.7 years STANDARD_DEVIATION 10.46 | 57.9 years STANDARD_DEVIATION 10.18 |
| Age, Customized 45 to < 65 years | 79 participants | 254 participants | 88 participants | 87 participants |
| Age, Customized < 45 years | 10 participants | 35 participants | 12 participants | 13 participants |
| Age, Customized ≥ 65 years | 38 participants | 106 participants | 35 participants | 33 participants |
| Baseline eGFR Categories (mL/min/1.73 m^2) 30 to < 60 ml/min/1.73 m^2 | 10 participants | 32 participants | 11 participants | 11 participants |
| Baseline eGFR Categories (mL/min/1.73 m^2) 60 to < 90 ml/min/1.73 m^2 | 85 participants | 243 participants | 80 participants | 78 participants |
| Baseline eGFR Categories (mL/min/1.73 m^2) ≥ 90 ml/min/1.73 m^2 | 32 participants | 120 participants | 44 participants | 44 participants |
| Body Mass Index (BMI) | 29.78 kg/m^2 STANDARD_DEVIATION 5.206 | 29.64 kg/m^2 STANDARD_DEVIATION 4.937 | 29.52 kg/m^2 STANDARD_DEVIATION 4.572 | 29.63 kg/m^2 STANDARD_DEVIATION 5.066 |
| Diabetes Status No | 100 participants | 328 participants | 115 participants | 113 participants |
| Diabetes Status Yes | 27 participants | 67 participants | 20 participants | 20 participants |
| Estimated Glomerular Filtration Rate (eGFR) | 81.5 mL/min/1.73 m^2 STANDARD_DEVIATION 16.25 | 82.9 mL/min/1.73 m^2 STANDARD_DEVIATION 16.41 | 82.4 mL/min/1.73 m^2 STANDARD_DEVIATION 16.51 | 84.8 mL/min/1.73 m^2 STANDARD_DEVIATION 16.41 |
| Height | 170.6 cm STANDARD_DEVIATION 9.96 | 171.5 cm STANDARD_DEVIATION 9.53 | 172.1 cm STANDARD_DEVIATION 9.74 | 171.8 cm STANDARD_DEVIATION 8.87 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 participants | 2 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Asian | 1 participants | 1 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Black or African American | 0 participants | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Multiracial | 0 participants | 2 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 participants | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized White | 126 participants | 392 participants | 134 participants | 132 participants |
| Region of Enrollment Bulgaria | 10 participants | 32 participants | 11 participants | 11 participants |
| Region of Enrollment Estonia | 16 participants | 52 participants | 18 participants | 18 participants |
| Region of Enrollment France | 1 participants | 5 participants | 2 participants | 2 participants |
| Region of Enrollment Germany | 29 participants | 86 participants | 28 participants | 29 participants |
| Region of Enrollment Hungary | 9 participants | 29 participants | 10 participants | 10 participants |
| Region of Enrollment Italy | 4 participants | 15 participants | 5 participants | 6 participants |
| Region of Enrollment Lithuania | 4 participants | 15 participants | 6 participants | 5 participants |
| Region of Enrollment Netherlands | 6 participants | 15 participants | 5 participants | 4 participants |
| Region of Enrollment Poland | 18 participants | 52 participants | 17 participants | 17 participants |
| Region of Enrollment Serbia | 3 participants | 11 participants | 4 participants | 4 participants |
| Region of Enrollment Slovakia | 24 participants | 74 participants | 26 participants | 24 participants |
| Region of Enrollment Spain | 1 participants | 3 participants | 1 participants | 1 participants |
| Region of Enrollment Sweden | 2 participants | 4 participants | 1 participants | 1 participants |
| Region of Enrollment United Kingdom | 0 participants | 2 participants | 1 participants | 1 participants |
| Sex: Female, Male Female | 54 Participants | 144 Participants | 44 Participants | 46 Participants |
| Sex: Female, Male Male | 73 Participants | 251 Participants | 91 Participants | 87 Participants |
| Smoking Classification Current smoker | 25 participants | 86 participants | 30 participants | 31 participants |
| Smoking Classification Ex-smoker | 19 participants | 72 participants | 28 participants | 25 participants |
| Smoking Classification Never smoked | 83 participants | 237 participants | 77 participants | 77 participants |
| Trough Clinic DBP Categories (mmHg) <90 mmHg | 72 participants | 210 participants | 70 participants | 68 participants |
| Trough Clinic DBP Categories (mmHg) ≥90 mmHg | 55 participants | 185 participants | 65 participants | 65 participants |
| Trough Clinic Diastolic Blood Pressure (DBP) | 87.6 mmHg STANDARD_DEVIATION 9.31 | 88.7 mmHg STANDARD_DEVIATION 8.39 | 88.8 mmHg STANDARD_DEVIATION 7.99 | 89.8 mmHg STANDARD_DEVIATION 7.76 |
| Trough Clinic SBP Category (mmHg) ≥140 - <160 mmHg | 87 participants | 266 participants | 93 participants | 86 participants |
| Trough Clinic SBP Category (mmHg) <140 mmHg | 17 participants | 50 participants | 17 participants | 16 participants |
| Trough Clinic SBP Category (mmHg) ≥160 - <180 mmHg | 23 participants | 79 participants | 25 participants | 31 participants |
| Trough Clinic SBP Category (mmHg) ≥180 mmHg | 0 participants | 0 participants | 0 participants | 0 participants |
| Trough Clinic Systolic Blood Pressure (SBP) | 149.6 mmHg STANDARD_DEVIATION 11.54 | 150.0 mmHg STANDARD_DEVIATION 11.04 | 149.8 mmHg STANDARD_DEVIATION 10.95 | 150.7 mmHg STANDARD_DEVIATION 10.69 |
| Weight | 86.71 kg STANDARD_DEVIATION 17.037 | 87.24 kg STANDARD_DEVIATION 15.868 | 87.39 kg STANDARD_DEVIATION 14.876 | 87.59 kg STANDARD_DEVIATION 15.794 |
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 | 15 / 507 | 15 / 133 | 13 / 127 | 26 / 135 |
| serious Total, serious adverse events | 3 / 507 | 2 / 133 | 0 / 127 | 0 / 135 |
Outcome results
Primary
Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure
The change between trough systolic blood pressure measured at final visit or Week 8 relative to baseline. Systolic blood pressure is the arithmetic mean of the 3 trough sitting systolic blood pressure measurements.
Time frame: Baseline (of the double-blind treatment period) and Week 8
Population: Full analysis set, consisting of all randomized participants who received at least 1 dose of double-blind study drug. A participant was included in the analyses only when there was both a baseline value and at least 1 value during the double-blind treatment period. Last observation carried forward (LOCF) was used.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Azilsartan Medoxomil 40 mg | Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure | Baseline | 150.7 mm Hg | Standard Error 0.96 |
| Azilsartan Medoxomil 40 mg | Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure | Change from Baseline to Week 8 | -6.4 mm Hg | Standard Error 1.05 |
| Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg | Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure | Baseline | 149.8 mm Hg | Standard Error 0.98 |
| Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg | Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure | Change from Baseline to Week 8 | -15.8 mm Hg | Standard Error 1.08 |
| Azilsartan Medoxomil + Chlorthalidone 40/25 mg | Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure | Baseline | 149.8 mm Hg | Standard Error 0.95 |
| Azilsartan Medoxomil + Chlorthalidone 40/25 mg | Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure | Change from Baseline to Week 8 | -21.1 mm Hg | Standard Error 1.04 |
Comparison: The type I error was controlled using a 2-step hierarchical testing procedure. In the first step, the high dose (40/25 mg) of Azilsartan medoxomil + chlorthalidone was compared to Azilsartan medoxomil alone. If the comparison in step 1 was statistically significant at a significance level of 5%, then step 2 was performed by comparing the low dose (40/12.5 mg) and monotherapy at the 5% significance level.p-value: <0.00195% CI: [-17.6, -11.8]ANCOVA
p-value: <0.00195% CI: [-12.4, -6.5]ANCOVA
Secondary
Change From Baseline to Week 8 in the 24-hour Mean Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring
The change in 24-hour mean diastolic blood pressure measured at final visit or week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing.
Time frame: Baseline and Week 8
Population: Full analysis set. Only participants with a Baseline and at least 1 post-baseline value of acceptable quality were included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Azilsartan Medoxomil 40 mg | Change From Baseline to Week 8 in the 24-hour Mean Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Baseline | 81.9 mm Hg | Standard Error 0.89 |
| Azilsartan Medoxomil 40 mg | Change From Baseline to Week 8 in the 24-hour Mean Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Change from Baseline to Week 8 | -1.6 mm Hg | Standard Error 0.66 |
| Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg | Change From Baseline to Week 8 in the 24-hour Mean Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Baseline | 80.3 mm Hg | Standard Error 0.93 |
| Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg | Change From Baseline to Week 8 in the 24-hour Mean Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Change from Baseline to Week 8 | -8.5 mm Hg | Standard Error 0.69 |
| Azilsartan Medoxomil + Chlorthalidone 40/25 mg | Change From Baseline to Week 8 in the 24-hour Mean Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Baseline | 82.5 mm Hg | Standard Error 0.91 |
| Azilsartan Medoxomil + Chlorthalidone 40/25 mg | Change From Baseline to Week 8 in the 24-hour Mean Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Change from Baseline to Week 8 | -10.1 mm Hg | Standard Error 0.67 |
Secondary
Change From Baseline to Week 8 in the 24-hour Mean Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring
The change in 24-hour mean systolic blood pressure measured at final visit or week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing.
Time frame: Baseline and Week 8
Population: Full analysis set. Only participants with a Baseline and at least 1 post-baseline value of acceptable quality were included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Azilsartan Medoxomil 40 mg | Change From Baseline to Week 8 in the 24-hour Mean Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Baseline | 138.0 mm Hg | Standard Error 1.21 |
| Azilsartan Medoxomil 40 mg | Change From Baseline to Week 8 in the 24-hour Mean Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Change from Baseline to Week 8 | -2.3 mm Hg | Standard Error 1.02 |
| Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg | Change From Baseline to Week 8 in the 24-hour Mean Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Baseline | 137.0 mm Hg | Standard Error 1.26 |
| Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg | Change From Baseline to Week 8 in the 24-hour Mean Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Change from Baseline to Week 8 | -14.7 mm Hg | Standard Error 1.07 |
| Azilsartan Medoxomil + Chlorthalidone 40/25 mg | Change From Baseline to Week 8 in the 24-hour Mean Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Baseline | 138.2 mm Hg | Standard Error 1.22 |
| Azilsartan Medoxomil + Chlorthalidone 40/25 mg | Change From Baseline to Week 8 in the 24-hour Mean Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Change from Baseline to Week 8 | -18.1 mm Hg | Standard Error 1.03 |
Secondary
Change From Baseline to Week 8 in the Mean Daytime Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring
The change in daytime (6 am to 10 pm) mean diastolic blood pressure measured at final visit or week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of all measurements recorded between the hours of 6 am and 10 pm.
Time frame: Baseline and Week 8
Population: Full analysis set. Only participants with a Baseline and at least 1 post-baseline value of acceptable quality were included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Azilsartan Medoxomil 40 mg | Change From Baseline to Week 8 in the Mean Daytime Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Baseline | 84.9 mm Hg | Standard Error 0.96 |
| Azilsartan Medoxomil 40 mg | Change From Baseline to Week 8 in the Mean Daytime Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Change from Baseline to Week 8 | -1.7 mm Hg | Standard Error 0.72 |
| Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg | Change From Baseline to Week 8 in the Mean Daytime Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Baseline | 83.6 mm Hg | Standard Error 1.01 |
| Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg | Change From Baseline to Week 8 in the Mean Daytime Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Change from Baseline to Week 8 | -8.9 mm Hg | Standard Error 0.75 |
| Azilsartan Medoxomil + Chlorthalidone 40/25 mg | Change From Baseline to Week 8 in the Mean Daytime Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Baseline | 85.7 mm Hg | Standard Error 0.98 |
| Azilsartan Medoxomil + Chlorthalidone 40/25 mg | Change From Baseline to Week 8 in the Mean Daytime Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Change from Baseline to Week 8 | -10.1 mm Hg | Standard Error 0.73 |
Secondary
Change From Baseline to Week 8 in the Mean Daytime Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring
The change in daytime (6 am to 10 pm) mean systolic blood pressure measured at final visit or week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of all measurements recorded between the hours of 6 am and 10 pm.
Time frame: Baseline and Week 8
Population: Full analysis set. Only participants with a Baseline and at least 1 post-baseline value of acceptable quality were included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Azilsartan Medoxomil 40 mg | Change From Baseline to Week 8 in the Mean Daytime Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Baseline | 141.5 mm Hg | Standard Error 1.24 |
| Azilsartan Medoxomil 40 mg | Change From Baseline to Week 8 in the Mean Daytime Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Change from Baseline to Week 8 | -2.4 mm Hg | Standard Error 1.09 |
| Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg | Change From Baseline to Week 8 in the Mean Daytime Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Baseline | 141.1 mm Hg | Standard Error 1.3 |
| Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg | Change From Baseline to Week 8 in the Mean Daytime Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Change from Baseline to Week 8 | -15.3 mm Hg | Standard Error 1.14 |
| Azilsartan Medoxomil + Chlorthalidone 40/25 mg | Change From Baseline to Week 8 in the Mean Daytime Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Baseline | 141.9 mm Hg | Standard Error 1.26 |
| Azilsartan Medoxomil + Chlorthalidone 40/25 mg | Change From Baseline to Week 8 in the Mean Daytime Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Change from Baseline to Week 8 | -18.2 mm Hg | Standard Error 1.11 |
Secondary
Change From Baseline to Week 8 in the Mean Diastolic Blood Pressure 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring
The change in the 12-hour mean diastolic blood pressure measured at final visit or Week 8 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 8
Population: Full analysis set. Only participants with a Baseline and at least 1 post-baseline value of acceptable quality were included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Azilsartan Medoxomil 40 mg | Change From Baseline to Week 8 in the Mean Diastolic Blood Pressure 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring | Baseline | 85.2 mm Hg | Standard Error 1.01 |
| Azilsartan Medoxomil 40 mg | Change From Baseline to Week 8 in the Mean Diastolic Blood Pressure 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring | Week 8 | -1.6 mm Hg | Standard Error 0.75 |
| Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg | Change From Baseline to Week 8 in the Mean Diastolic Blood Pressure 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring | Baseline | 84.2 mm Hg | Standard Error 1.05 |
| Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg | Change From Baseline to Week 8 in the Mean Diastolic Blood Pressure 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring | Week 8 | -8.9 mm Hg | Standard Error 0.78 |
| Azilsartan Medoxomil + Chlorthalidone 40/25 mg | Change From Baseline to Week 8 in the Mean Diastolic Blood Pressure 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring | Baseline | 86.0 mm Hg | Standard Error 1.02 |
| Azilsartan Medoxomil + Chlorthalidone 40/25 mg | Change From Baseline to Week 8 in the Mean Diastolic Blood Pressure 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring | Week 8 | -10.1 mm Hg | Standard Error 0.76 |
Secondary
Change From Baseline to Week 8 in the Mean Nighttime Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring
The change in nighttime (12 am to 6 am) mean diastolic blood pressure measured at final visit or week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of all measurements recorded between the hours of 12 am and 6 am.
Time frame: Baseline and Week 8.
Population: Full analysis set. Only participants with a Baseline and at least 1 post-baseline value of acceptable quality were included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Azilsartan Medoxomil 40 mg | Change From Baseline to Week 8 in the Mean Nighttime Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Baseline | 73.2 mm Hg | Standard Error 0.95 |
| Azilsartan Medoxomil 40 mg | Change From Baseline to Week 8 in the Mean Nighttime Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Change from Baseline to Week 8 | -1.6 mm Hg | Standard Error 0.78 |
| Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg | Change From Baseline to Week 8 in the Mean Nighttime Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Baseline | 70.6 mm Hg | Standard Error 0.99 |
| Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg | Change From Baseline to Week 8 in the Mean Nighttime Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Change from Baseline to Week 8 | -7.2 mm Hg | Standard Error 0.82 |
| Azilsartan Medoxomil + Chlorthalidone 40/25 mg | Change From Baseline to Week 8 in the Mean Nighttime Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Baseline | 72.9 mm Hg | Standard Error 0.97 |
| Azilsartan Medoxomil + Chlorthalidone 40/25 mg | Change From Baseline to Week 8 in the Mean Nighttime Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Change from Baseline to Week 8 | -9.8 mm Hg | Standard Error 0.79 |
Secondary
Change From Baseline to Week 8 in the Mean Nighttime Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring
The change in nighttime (12 am to 6 am) mean systolic blood pressure measured at final visit or week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of all measurements recorded between the hours of 12 am and 6 am.
Time frame: Baseline and Week 8
Population: Full analysis set. Only participants with a Baseline and at least 1 post-baseline value of acceptable quality were included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Azilsartan Medoxomil 40 mg | Change From Baseline to Week 8 in the Mean Nighttime Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Baseline | 127.3 mm Hg | Standard Error 1.5 |
| Azilsartan Medoxomil 40 mg | Change From Baseline to Week 8 in the Mean Nighttime Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Change from Baseline to Week 8 | -2.2 mm Hg | Standard Error 1.18 |
| Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg | Change From Baseline to Week 8 in the Mean Nighttime Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Baseline | 124.2 mm Hg | Standard Error 1.57 |
| Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg | Change From Baseline to Week 8 in the Mean Nighttime Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Change from Baseline to Week 8 | -12.7 mm Hg | Standard Error 1.24 |
| Azilsartan Medoxomil + Chlorthalidone 40/25 mg | Change From Baseline to Week 8 in the Mean Nighttime Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Baseline | 126.3 mm Hg | Standard Error 1.52 |
| Azilsartan Medoxomil + Chlorthalidone 40/25 mg | Change From Baseline to Week 8 in the Mean Nighttime Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | Change from Baseline to Week 8 | -17.3 mm Hg | Standard Error 1.2 |
Secondary
Change From Baseline to Week 8 in the Mean Systolic Blood Pressure 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring
The change in the 12-hour mean systolic blood pressure measured at final visit or week 8 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 8
Population: Full analysis set. Only participants with a Baseline and at least 1 post-baseline value of acceptable quality were included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Azilsartan Medoxomil 40 mg | Change From Baseline to Week 8 in the Mean Systolic Blood Pressure 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring | Change from Baseline to Week 8 | -2.3 mm Hg | Standard Error 1.14 |
| Azilsartan Medoxomil 40 mg | Change From Baseline to Week 8 in the Mean Systolic Blood Pressure 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring | Baseline | 141.6 mm Hg | Standard Error 1.3 |
| Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg | Change From Baseline to Week 8 in the Mean Systolic Blood Pressure 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring | Baseline | 141.8 mm Hg | Standard Error 1.36 |
| Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg | Change From Baseline to Week 8 in the Mean Systolic Blood Pressure 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring | Change from Baseline to Week 8 | -15.4 mm Hg | Standard Error 1.19 |
| Azilsartan Medoxomil + Chlorthalidone 40/25 mg | Change From Baseline to Week 8 in the Mean Systolic Blood Pressure 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring | Baseline | 142.3 mm Hg | Standard Error 1.32 |
| Azilsartan Medoxomil + Chlorthalidone 40/25 mg | Change From Baseline to Week 8 in the Mean Systolic Blood Pressure 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring | Change from Baseline to Week 8 | -18.2 mm Hg | Standard Error 1.16 |
Secondary
Change From Baseline to Week 8 in Trough Diastolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring
The change in trough diastolic blood pressure measured at final visit or week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough is the average of all measurements recorded from 22 to 24 hours after dosing.
Time frame: Baseline and Week 8, 22-24 hours after dosing
Population: Full analysis set. Only participants with a Baseline and at least 1 post-baseline value of acceptable quality were included
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Azilsartan Medoxomil 40 mg | Change From Baseline to Week 8 in Trough Diastolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring | Baseline | 86.4 mm Hg | Standard Error 1.11 |
| Azilsartan Medoxomil 40 mg | Change From Baseline to Week 8 in Trough Diastolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring | Change from Baseline to Week 8 | -2.2 mm Hg | Standard Error 0.88 |
| Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg | Change From Baseline to Week 8 in Trough Diastolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring | Baseline | 83.6 mm Hg | Standard Error 1.16 |
| Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg | Change From Baseline to Week 8 in Trough Diastolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring | Change from Baseline to Week 8 | -8.8 mm Hg | Standard Error 0.92 |
| Azilsartan Medoxomil + Chlorthalidone 40/25 mg | Change From Baseline to Week 8 in Trough Diastolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring | Baseline | 86.0 mm Hg | Standard Error 1.12 |
| Azilsartan Medoxomil + Chlorthalidone 40/25 mg | Change From Baseline to Week 8 in Trough Diastolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring | Change from Baseline to Week 8 | -9.4 mm Hg | Standard Error 0.89 |
Secondary
Change From Baseline to Week 8 in Trough, Sitting, Clinic Diastolic Blood Pressure
The change between trough diastolic blood pressure measured at final visit or week 8 relative to baseline Diastolic blood pressure is the arithmetic mean of the 3 trough sitting diastolic blood pressure measurements.
Time frame: Baseline and Week 8
Population: Full analysis set; LOCF was used.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Azilsartan Medoxomil 40 mg | Change From Baseline to Week 8 in Trough, Sitting, Clinic Diastolic Blood Pressure | Baseline | 89.8 mm Hg | Standard Error 0.73 |
| Azilsartan Medoxomil 40 mg | Change From Baseline to Week 8 in Trough, Sitting, Clinic Diastolic Blood Pressure | Change from Baseline to Week 8 | -3.2 mm Hg | Standard Error 0.65 |
| Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg | Change From Baseline to Week 8 in Trough, Sitting, Clinic Diastolic Blood Pressure | Baseline | 87.7 mm Hg | Standard Error 0.75 |
| Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg | Change From Baseline to Week 8 in Trough, Sitting, Clinic Diastolic Blood Pressure | Change from Baseline to Week 8 | -7.7 mm Hg | Standard Error 0.67 |
| Azilsartan Medoxomil + Chlorthalidone 40/25 mg | Change From Baseline to Week 8 in Trough, Sitting, Clinic Diastolic Blood Pressure | Baseline | 88.8 mm Hg | Standard Error 0.72 |
| Azilsartan Medoxomil + Chlorthalidone 40/25 mg | Change From Baseline to Week 8 in Trough, Sitting, Clinic Diastolic Blood Pressure | Change from Baseline to Week 8 | -10.3 mm Hg | Standard Error 0.65 |
Secondary
Change From Baseline to Week 8 in Trough Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring
The change in trough systolic blood pressure measured at final visit or week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough is the average of all measurements recorded from 22 to 24 hours after dosing.
Time frame: Baseline and Week 8, 22-24 hours after dosing
Population: Full analysis set. Only participants with a baseline and at least 1 post-baseline value of acceptable quality were included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Azilsartan Medoxomil 40 mg | Change From Baseline to Week 8 in Trough Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring | Baseline | 143.1 mm Hg | Standard Error 1.55 |
| Azilsartan Medoxomil 40 mg | Change From Baseline to Week 8 in Trough Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring | Change from Baseline to Week 8 | -2.5 mm Hg | Standard Error 1.31 |
| Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg | Change From Baseline to Week 8 in Trough Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring | Baseline | 140.2 mm Hg | Standard Error 1.62 |
| Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg | Change From Baseline to Week 8 in Trough Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring | Change from Baseline to Week 8 | -14.0 mm Hg | Standard Error 1.36 |
| Azilsartan Medoxomil + Chlorthalidone 40/25 mg | Change From Baseline to Week 8 in Trough Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring | Baseline | 142.0 mm Hg | Standard Error 1.58 |
| Azilsartan Medoxomil + Chlorthalidone 40/25 mg | Change From Baseline to Week 8 in Trough Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring | Change from Baseline to Week 8 | -16.6 mm Hg | Standard Error 1.32 |
Secondary
Percentage of Participants Who Achieve a Target Clinic Diastolic Blood Pressure at Week 8
Percentage of participants who achieve a target clinic diastolic blood pressure measured at final visit or week 8, defined as less than 90 mm Hg (or less than 80 mm Hg for participants with diabetes or chronic kidney disease). Diastolic blood pressure is based on the arithmetic mean of the 3 trough sitting diastolic blood pressure measurements.
Time frame: Week 8
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Azilsartan Medoxomil 40 mg | Percentage of Participants Who Achieve a Target Clinic Diastolic Blood Pressure at Week 8 | 60.2 percentage of participants |
| Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg | Percentage of Participants Who Achieve a Target Clinic Diastolic Blood Pressure at Week 8 | 81.0 percentage of participants |
| Azilsartan Medoxomil + Chlorthalidone 40/25 mg | Percentage of Participants Who Achieve a Target Clinic Diastolic Blood Pressure at Week 8 | 85.9 percentage of participants |
Secondary
Percentage of Participants Who Achieve a Target Clinic Systolic Blood Pressure at Week 8
Percentage of participants who achieve a target clinic systolic blood pressure measured at final visit or week 8, defined as less than 140 mm Hg (or less than 130 mm Hg for participants with diabetes or chronic kidney disease). Systolic blood pressure is the arithmetic mean of the 3 trough sitting Systolic blood pressure measurements.
Time frame: Week 8
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Azilsartan Medoxomil 40 mg | Percentage of Participants Who Achieve a Target Clinic Systolic Blood Pressure at Week 8 | 35.3 percentage of participants |
| Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg | Percentage of Participants Who Achieve a Target Clinic Systolic Blood Pressure at Week 8 | 62.7 percentage of participants |
| Azilsartan Medoxomil + Chlorthalidone 40/25 mg | Percentage of Participants Who Achieve a Target Clinic Systolic Blood Pressure at Week 8 | 77.8 percentage of participants |
Secondary
Percentage of Participants Who Achieve Both Clinic Systolic and Diastolic Blood Pressure Targets at Week 8
Percentage of participants who achieve both clinic systolic and diastolic blood pressure targets at Week 8, defined as less than 140 mm Hg (or less than 130 mm Hg for participants with diabetes or chronic kidney disease) for systolic AND less than 90 mm Hg (or less than 80 mm Hg for participants with diabetes or chronic kidney disease) for diastolic blood pressure.
Time frame: Week 8
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Azilsartan Medoxomil 40 mg | Percentage of Participants Who Achieve Both Clinic Systolic and Diastolic Blood Pressure Targets at Week 8 | 30.8 percentage of participants |
| Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg | Percentage of Participants Who Achieve Both Clinic Systolic and Diastolic Blood Pressure Targets at Week 8 | 59.5 percentage of participants |
| Azilsartan Medoxomil + Chlorthalidone 40/25 mg | Percentage of Participants Who Achieve Both Clinic Systolic and Diastolic Blood Pressure Targets at Week 8 | 74.1 percentage of participants |