Hypertension
Conditions
Keywords
Hypertensive, Blood Pressure, High, Vascular Disease, Cardiovascular Disease, Drug Therapy
Brief summary
The purpose of this study is to determine the efficacy and safety of azilsartan medoxomil combined with chlorthalidone, once daily (QD), in participants with moderate to severe hypertension.
Detailed description
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. As the population ages, the prevalence of hypertension will continue to increase if broad and effective preventive measures are not implemented. Despite the availability of antihypertensive agents, hypertension remains inadequately controlled; only about one third of patients continue to maintain control successfully. Although most antihypertensive agents are effective at the appropriate dose, the majority have side effects that limit their use. As a class, angiotensin II receptor blockers generally are considered more tolerable than other classes of antihypertensive agents. TAK-491 (azilsartan medoxomil) is an angiotensin II receptor blocker that is being evaluated by Takeda to treat essential hypertension. Treatments for essential hypertension commonly include use of a thiazide-like diuretic, either alone or as part of combination treatment. This study is designed to compare the antihypertensive effect and the safety and tolerability of the azilsartan medoxomil plus chlorthalidone fixed-dose combination product (TAK 491CLD FDC) with azilsartan monotherapy and chlorthalidone monotherapy during 8 weeks of treatment. Participants in this study will be randomized to receive one of 11 possible dosing combinations of azilsartan medoxomil , chlorthalidone and placebo over an 8 week period. The total duration of the study will be approximately 13 weeks. Participants will make 12 visits to the clinic. Each participant will also be contacted by telephone 14 days after last dose of study drug for a follow-up assessment.
Interventions
Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for up to 8 weeks
DRUGChlorthalidone
Azilsartan medoxomil placebo and chlorthalidone 12.5 mg combination tablets, orally, once daily for up to 8 weeks
Azilsartan medoxomil 20 mg and chlorthalidone placebo combination tablets, orally, once daily for up to 8 weeks
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
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. Is treated with antihypertensive therapy and has a post-washout mean sitting clinic systolic blood pressure greater than or equal to 160 and less than or equal to 190 mm Hg on the day prior to randomization, or the participant has not received antihypertensive treatment within 28 days prior to Screening and has a mean sitting clinic systolic blood pressure greater than or equal to 160 and less than or equal to 190 mm Hg at the Screening Visit and on the day prior to randomization. 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. Has clinical laboratory test results within the reference range for the testing laboratory or the investigator does not consider the results to be clinically significant. 4. Is willing to discontinue current antihypertensive medications on Day -21 or on Day -28 if on amlodipine or chlorthalidone.
Exclusion criteria
1. Has a mean sitting clinic diastolic blood pressure greater than 119 mm Hg on the day prior to randomization. 2. Has a baseline 24-hour ambulatory blood pressure measurement reading of insufficient quality. 3. Has works a night (third) shift (defined as 11 PM \[2300\] to 7 AM \[0700\]). 4. Has an upper arm circumference less than 24 cm or greater than 42 cm. 5. Has is noncompliant with study medication during the placebo run-in period. 6. Has secondary hypertension of any etiology. 7. Has recent history of myocardial infarction, heart failure, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebrovascular accident, or transient ischemic attack. 8. Has clinically significant cardiac conduction defects. 9. Has hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease. 10. Has severe renal dysfunction or disease. 11. Has known or suspected unilateral or bilateral renal artery stenosis. 12. Has a history of cancer that has not been in remission for at least 5 years prior to the first dose of study drug. 13. Has poorly controlled type 1 or type 2 diabetes mellitus at Screening. 14. Has hypokalemia or hyperkalemia. 15. Has an alanine aminotransferase or aspartate aminotransferase level of greater than 2.5 times the upper limit of normal, active liver disease, or jaundice. 16. 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 Has according to the protocol. 17. Has known hypersensitivity to angiotensin II receptor blockers, thiazide-type diuretics or other sulfonamide-derived compounds. 18. Has been randomized in a previous azilsartan medoxomil study. 19. Is currently participating in another investigational study or is receiving or has received any investigational compound within 30 days prior to Screening. 20. Has a history of drug abuse or a history of alcohol abuse within the past 2 years.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 8 in Trough, Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring (Pooled Analysis) | Baseline and Week 8. | 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, Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring (Pairwise Analysis) | Baseline and Week 8. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 8 in Trough Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring in Black Participants (Pairwise Analysis) | Baseline and Week 8. | The change in trough systolic blood pressure in black participants as 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, Sitting, Clinic Diastolic Blood Pressure | Baseline and Week 8. | The change in trough diastolic blood pressure measured at final visit or week 8 relative to baseline. Diastolic blood pressure is the average of the 3 serial trough clinic sitting diastolic blood pressure measurements. |
| Change From Baseline to Week 8 in the Mean Trough Diastolic Blood Pressure (22 to 24 Hours After Dosing), as Measured by Ambulatory Blood Pressure Monitoring. | Baseline and Week 8. | 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 (6 AM to 10 PM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | Baseline and Week 8. | The change in daytime (6am to 10pm) 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 (6 AM to 10 PM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | Baseline and Week 8. | The change in daytime (6am to 10pm) 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 Systolic Blood Pressure | Baseline and Week 8 | The change in trough systolic blood pressure measured at final visit or week 8 relative to baseline. Systolic blood pressure is the arithmetic mean of the 3 serial trough sitting systolic blood pressure measurements. |
| Change From Baseline to Week 8 in the Mean Nighttime (12 AM to 6 AM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | Baseline and Week 8. | The change in nighttime (12am to 6am) 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 at 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 at 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 Clinic Systolic Blood Pressure Response at Week 8, as Defined by Clinic Systolic Blood Pressure <140 mm Hg and/or a Reduction of ≥20 mm Hg From Baseline. | Baseline and Week 8 | Percentage of participants who achieve a clinic systolic blood pressure response measured at week 8, 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 average of the 3 serial trough sitting clinic systolic blood pressure measurements. |
| Percentage of Participants Who Achieve a Clinic Diastolic Blood Pressure Response at Week 8, Defined as Clinic Diastolic Blood Pressure <90 mm Hg and/or a Reduction of ≥10 mm Hg From Baseline. | Baseline and Week 8. | Percentage of participants who achieve a clinic diastolic blood pressure response measured at week 8, 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 average of the 3 serial trough sitting clinic diastolic blood pressure measurements. |
| Percentage of Participants Who Achieve Both a Clinic Systolic and Diastolic Blood Pressure Response at Week 8. | Baseline and Week 8. | Percentage of participants who achieve both a clinic systolic and diastolic blood pressure response measured at week 8, defined as systolic blood pressure less than 140 mm Hg and/or reduction from baseline of greater than or equal to 20 mm Hg AND diastolic blood pressure less than 90 mm Hg and/or reduction from baseline of greater than or equal to 10 mm Hg . Systolic/diastolic blood pressure is based on the average of the 3 serial trough clinic sitting systolic/diastolic blood pressure measurements. |
| Change From Baseline to Week 8 in the Mean Nighttime (12 AM to 6 AM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | Baseline and Week 8. | The change in nighttime (12am to 6am) 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. |
| Change From Baseline to Week 8 in Trough Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring in Black Participants (Pooled Analysis) | Baseline and Week 8. | The change in trough systolic blood pressure in black subjects 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. |
Countries
Chile, Mexico, Peru, Russia, United States
Participant flow
Recruitment details
Participants enrolled at 175 investigative sites in Austria, Chile, Germany, Guatemala, Mexico, Netherlands, Peru, Poland, Russian Federation and the United States from 29 January 2009 to 10 July 2010.
Pre-assignment details
Participants with moderate to severe essential hypertension were enrolled in one of 11, once-daily (QD) treatment groups.
Participants by arm
| Arm | Count |
|---|---|
| Azilsartan Medoxomil 20 mg/Chlorthalidone 12.5 mg QD Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for up to 8 weeks. | 156 |
| Azilsartan Medoxomil 20 mg/Chlorthalidone 25 mg QD Azilsartan medoxomil 20 mg and chlorthalidone 25 mg combination tablets, orally, once daily for up to 8 weeks. | 154 |
| Azilsartan Medoxomil 40 mg/Chlorthalidone 12.5 mg QD Azilsartan 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for up to 8 weeks. | 147 |
| Azilsartan Medoxomil 40 mg/Chlorthalidone 25 mg QD Azilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for up to 8 weeks. | 156 |
| Azilsartan Medoxomil 80 mg/Chlorthalidone 12.5 mg QD Azilsartan 80 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for up to 8 weeks. | 153 |
| Azilsartan Medoxomil 80 mg/Chlorthalidone 25 mg QD Azilsartan medoxomil 80 mg and chlorthalidone 25 mg combination tablets, orally, once daily for up to 8 weeks. | 162 |
| Chlorthalidone 12.5 mg QD Azilsartan medoxomil placebo and chlorthalidone 12.5 mg combination tablets, orally, once daily for up to 8 weeks. | 157 |
| Chlorthalidone 25 mg QD Azilsartan medoxomil placebo and chlorthalidone 25 mg combination tablets, orally, once daily for up to 8 weeks. | 159 |
| Azilsartan Medoxomil 20 mg QD Azilsartan medoxomil 20 mg and chlorthalidone placebo combination tablets, orally, once daily for up to 8 weeks. | 155 |
| Azilsartan Medoxomil 40 mg QD Azilsartan medoxomil 40 mg and chlorthalidone placebo combination tablets, orally, once daily for up to 8 weeks. | 153 |
| Azilsartan Medoxomil 80 mg QD Azilsartan medoxomil 80 mg and chlorthalidone placebo combination tablets, orally, once daily for up to 8 weeks. | 162 |
| Total | 1,714 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 10 | 10 | 6 | 19 | 11 | 22 | 4 | 6 | 3 | 6 | 6 |
| Overall Study | Lack of Efficacy | 3 | 1 | 0 | 1 | 2 | 0 | 6 | 2 | 5 | 1 | 7 |
| Overall Study | Lost to Follow-up | 0 | 1 | 1 | 1 | 0 | 3 | 1 | 3 | 1 | 0 | 1 |
| Overall Study | Other | 1 | 5 | 4 | 1 | 2 | 2 | 2 | 3 | 1 | 1 | 3 |
| Overall Study | Protocol Violation | 2 | 1 | 2 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 5 | 5 | 3 | 8 | 12 | 9 | 8 | 4 | 4 | 5 | 2 |
Baseline characteristics
| Characteristic | Azilsartan Medoxomil 40 mg/Chlorthalidone 12.5 mg QD | Azilsartan Medoxomil 20 mg/Chlorthalidone 12.5 mg QD | Azilsartan Medoxomil 20 mg/Chlorthalidone 25 mg QD | Azilsartan Medoxomil 40 mg/Chlorthalidone 25 mg QD | Azilsartan Medoxomil 80 mg/Chlorthalidone 12.5 mg QD | Azilsartan Medoxomil 80 mg/Chlorthalidone 25 mg QD | Chlorthalidone 12.5 mg QD | Chlorthalidone 25 mg QD | Azilsartan Medoxomil 20 mg QD | Azilsartan Medoxomil 40 mg QD | Azilsartan Medoxomil 80 mg QD | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | 56.2 years STANDARD_DEVIATION 10.5 | 58.2 years STANDARD_DEVIATION 10.57 | 57.4 years STANDARD_DEVIATION 11.13 | 57.4 years STANDARD_DEVIATION 11.07 | 55.8 years STANDARD_DEVIATION 11.22 | 57.6 years STANDARD_DEVIATION 11.04 | 57.3 years STANDARD_DEVIATION 11.3 | 56.2 years STANDARD_DEVIATION 10.04 | 57.3 years STANDARD_DEVIATION 11.04 | 57.8 years STANDARD_DEVIATION 10.28 | 57.3 years STANDARD_DEVIATION 10.87 | 57.2 years STANDARD_DEVIATION 10.82 |
| Age, Customized <45 years | 17 participants | 15 participants | 16 participants | 21 participants | 25 participants | 19 participants | 21 participants | 18 participants | 18 participants | 17 participants | 16 participants | 203 participants |
| Age, Customized ≥65 years | 30 participants | 43 participants | 41 participants | 42 participants | 38 participants | 39 participants | 39 participants | 33 participants | 40 participants | 38 participants | 39 participants | 422 participants |
| Age, Customized Between 45 to 64 years | 100 participants | 98 participants | 97 participants | 93 participants | 90 participants | 104 participants | 97 participants | 108 participants | 97 participants | 98 participants | 107 participants | 1089 participants |
| Body Mass Index (BMI) | 31.8 kg/m^2 STANDARD_DEVIATION 6.57 | 32.2 kg/m^2 STANDARD_DEVIATION 5.73 | 31.0 kg/m^2 STANDARD_DEVIATION 5.65 | 32.2 kg/m^2 STANDARD_DEVIATION 6.01 | 31.4 kg/m^2 STANDARD_DEVIATION 5.84 | 31.5 kg/m^2 STANDARD_DEVIATION 6.28 | 31.2 kg/m^2 STANDARD_DEVIATION 5.85 | 31.2 kg/m^2 STANDARD_DEVIATION 5.78 | 31.3 kg/m^2 STANDARD_DEVIATION 5.23 | 31.0 kg/m^2 STANDARD_DEVIATION 5.85 | 30.8 kg/m^2 STANDARD_DEVIATION 6.28 | 31.4 kg/m^2 STANDARD_DEVIATION 5.92 |
| Estimated glomerular filtration rate (eGFR) ≥0 and <30 | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 1 participants |
| Estimated glomerular filtration rate (eGFR) ≥30 and <60 | 6 participants | 13 participants | 14 participants | 8 participants | 6 participants | 10 participants | 12 participants | 9 participants | 11 participants | 11 participants | 8 participants | 108 participants |
| Estimated glomerular filtration rate (eGFR) ≥60 and <90 | 93 participants | 95 participants | 90 participants | 97 participants | 109 participants | 110 participants | 101 participants | 100 participants | 94 participants | 95 participants | 99 participants | 1083 participants |
| Estimated glomerular filtration rate (eGFR) ≥90 | 48 participants | 48 participants | 50 participants | 51 participants | 38 participants | 42 participants | 44 participants | 50 participants | 49 participants | 46 participants | 55 participants | 521 participants |
| Estimated glomerular filtration rate (eGFR) Missing | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 10 Participants | 19 Participants | 15 Participants | 19 Participants | 15 Participants | 17 Participants | 19 Participants | 20 Participants | 17 Participants | 15 Participants | 177 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 76 Participants | 90 Participants | 75 Participants | 85 Participants | 71 Participants | 87 Participants | 84 Participants | 86 Participants | 77 Participants | 80 Participants | 86 Participants | 897 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 60 Participants | 56 Participants | 60 Participants | 56 Participants | 63 Participants | 60 Participants | 56 Participants | 54 Participants | 58 Participants | 56 Participants | 61 Participants | 640 Participants |
| Height | 167.1 cm STANDARD_DEVIATION 11.44 | 166.3 cm STANDARD_DEVIATION 11.71 | 166.6 cm STANDARD_DEVIATION 10.85 | 166.8 cm STANDARD_DEVIATION 11.64 | 166.6 cm STANDARD_DEVIATION 10.81 | 165.4 cm STANDARD_DEVIATION 10.79 | 168.3 cm STANDARD_DEVIATION 11.07 | 166.1 cm STANDARD_DEVIATION 11.36 | 166.4 cm STANDARD_DEVIATION 10.65 | 167.7 cm STANDARD_DEVIATION 12.27 | 167.1 cm STANDARD_DEVIATION 11.85 | 166.8 cm STANDARD_DEVIATION 11.32 |
| Race (NIH/OMB) American Indian or Alaska Native | 13 participants | 9 participants | 13 participants | 13 participants | 12 participants | 16 participants | 14 participants | 14 participants | 11 participants | 13 participants | 14 participants | 142 participants |
| Race (NIH/OMB) Asian | 4 participants | 4 participants | 3 participants | 4 participants | 2 participants | 3 participants | 1 participants | 7 participants | 1 participants | 1 participants | 4 participants | 34 participants |
| Race (NIH/OMB) Black or African American | 29 participants | 34 participants | 28 participants | 30 participants | 26 participants | 34 participants | 31 participants | 29 participants | 31 participants | 35 participants | 35 participants | 342 participants |
| Race (NIH/OMB) More than one race | 1 participants | 2 participants | 2 participants | 2 participants | 1 participants | 0 participants | 1 participants | 2 participants | 1 participants | 1 participants | 2 participants | 15 participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 2 participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race (NIH/OMB) White | 102 participants | 111 participants | 112 participants | 111 participants | 114 participants | 109 participants | 111 participants | 111 participants | 113 participants | 105 participants | 111 participants | 1210 participants |
| Region of Enrollment Austria | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 2 participants |
| Region of Enrollment Chile | 3 participants | 3 participants | 3 participants | 2 participants | 2 participants | 3 participants | 2 participants | 1 participants | 2 participants | 3 participants | 2 participants | 26 participants |
| Region of Enrollment Germany | 6 participants | 4 participants | 6 participants | 5 participants | 6 participants | 5 participants | 4 participants | 5 participants | 3 participants | 4 participants | 5 participants | 53 participants |
| Region of Enrollment Guatemala | 9 participants | 8 participants | 8 participants | 10 participants | 10 participants | 8 participants | 8 participants | 9 participants | 8 participants | 9 participants | 9 participants | 96 participants |
| Region of Enrollment Mexico | 11 participants | 10 participants | 11 participants | 9 participants | 12 participants | 11 participants | 11 participants | 8 participants | 13 participants | 11 participants | 12 participants | 119 participants |
| Region of Enrollment Netherlands | 6 participants | 6 participants | 7 participants | 5 participants | 7 participants | 5 participants | 6 participants | 6 participants | 6 participants | 6 participants | 7 participants | 67 participants |
| Region of Enrollment Peru | 13 participants | 11 participants | 12 participants | 12 participants | 12 participants | 14 participants | 12 participants | 11 participants | 13 participants | 12 participants | 12 participants | 134 participants |
| Region of Enrollment Poland | 7 participants | 8 participants | 8 participants | 8 participants | 8 participants | 8 participants | 7 participants | 8 participants | 8 participants | 7 participants | 8 participants | 85 participants |
| Region of Enrollment Russian Federation | 5 participants | 5 participants | 5 participants | 5 participants | 5 participants | 6 participants | 6 participants | 6 participants | 5 participants | 4 participants | 6 participants | 58 participants |
| Region of Enrollment United States | 87 participants | 100 participants | 94 participants | 100 participants | 90 participants | 102 participants | 101 participants | 105 participants | 97 participants | 97 participants | 101 participants | 1074 participants |
| Sex: Female, Male Female | 76 Participants | 86 Participants | 77 Participants | 85 Participants | 82 Participants | 100 Participants | 74 Participants | 90 Participants | 87 Participants | 68 Participants | 84 Participants | 909 Participants |
| Sex: Female, Male Male | 71 Participants | 70 Participants | 77 Participants | 71 Participants | 71 Participants | 62 Participants | 83 Participants | 69 Participants | 68 Participants | 85 Participants | 78 Participants | 805 Participants |
| Smoking Status Current smoker | 25 participants | 22 participants | 28 participants | 35 participants | 26 participants | 28 participants | 25 participants | 29 participants | 25 participants | 31 participants | 29 participants | 303 participants |
| Smoking Status Ex-smoker | 41 participants | 40 participants | 42 participants | 42 participants | 36 participants | 40 participants | 39 participants | 39 participants | 38 participants | 32 participants | 39 participants | 428 participants |
| Smoking Status Never smoked | 81 participants | 94 participants | 84 participants | 79 participants | 91 participants | 94 participants | 93 participants | 91 participants | 92 participants | 90 participants | 94 participants | 983 participants |
| Weight | 89.28 kg STANDARD_DEVIATION 21.484 | 89.85 kg STANDARD_DEVIATION 22.076 | 86.06 kg STANDARD_DEVIATION 18.056 | 90.16 kg STANDARD_DEVIATION 21.949 | 87.31 kg STANDARD_DEVIATION 19.209 | 86.44 kg STANDARD_DEVIATION 20.412 | 89.12 kg STANDARD_DEVIATION 21.049 | 86.70 kg STANDARD_DEVIATION 20.27 | 87.27 kg STANDARD_DEVIATION 18.934 | 87.54 kg STANDARD_DEVIATION 19.019 | 86.27 kg STANDARD_DEVIATION 20.354 | 87.80 kg STANDARD_DEVIATION 20.289 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 52 / 156 | 55 / 154 | 40 / 146 | 74 / 156 | 52 / 153 | 67 / 161 | 51 / 156 | 53 / 160 | 25 / 155 | 36 / 153 | 32 / 162 |
| serious Total, serious adverse events | 3 / 156 | 0 / 154 | 1 / 146 | 2 / 156 | 2 / 153 | 2 / 161 | 0 / 156 | 2 / 160 | 2 / 155 | 2 / 153 | 3 / 162 |
Outcome results
Primary
Change From Baseline to Week 8 in Trough, Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring (Pairwise Analysis)
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.
Population: Full analysis set, defined as all randomized participants who received at least 1 dose of double-blind study medication, with both a baseline value and at least 1 post-baseline value, with last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan Medoxomil 40 mg or 80 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in Trough, Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring (Pairwise Analysis) | -22.9 mmHg | Standard Error 1.19 |
| Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in Trough, Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring (Pairwise Analysis) | -26.3 mmHg | Standard Error 1.24 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 8 in Trough, Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring (Pairwise Analysis) | -24.4 mmHg | Standard Error 1.24 |
| Azilsartan Medoxomil 40 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in Trough, Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring (Pairwise Analysis) | -29.8 mmHg | Standard Error 1.26 |
| Azilsartan Medoxomil 80 mg/Chlorthalidone 12.5 mg QD | Change From Baseline to Week 8 in Trough, Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring (Pairwise Analysis) | -26.3 mmHg | Standard Error 1.28 |
| Azilsartan Medoxomil 80 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in Trough, Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring (Pairwise Analysis) | -28.0 mmHg | Standard Error 1.26 |
| Chlorthalidone 12.5 mg QD | Change From Baseline to Week 8 in Trough, Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring (Pairwise Analysis) | -12.7 mmHg | Standard Error 1.18 |
| Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in Trough, Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring (Pairwise Analysis) | -15.9 mmHg | Standard Error 1.16 |
| Azilsartan Medoxomil 20 mg QD | Change From Baseline to Week 8 in Trough, Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring (Pairwise Analysis) | -12.1 mmHg | Standard Error 1.19 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline to Week 8 in Trough, Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring (Pairwise Analysis) | -12.8 mmHg | Standard Error 1.17 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 8 in Trough, Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring (Pairwise Analysis) | -15.1 mmHg | Standard Error 1.19 |
Comparison: ANCOVA using treatment as a fixed effect and baseline as a covariate was performed.p-value: <0.00195% CI: [-13.6, -7]ANCOVA
Comparison: ANCOVA using treatment as a fixed effect and baseline as a covariate was performed.p-value: <0.00195% CI: [-13.7, -7]ANCOVA
Comparison: ANCOVA using treatment as a fixed effect and baseline as a covariate was performed.p-value: <0.00195% CI: [-15.1, -8.4]ANCOVA
Comparison: ANCOVA using treatment as a fixed effect and baseline as a covariate was performed.p-value: <0.00195% CI: [-17.3, -10.6]ANCOVA
Comparison: ANCOVA using treatment as a fixed effect and baseline as a covariate was performed.p-value: <0.00195% CI: [-17.1, -10.3]ANCOVA
Comparison: ANCOVA using treatment as a fixed effect and baseline as a covariate was performed.p-value: <0.00195% CI: [-15.4, -8.7]ANCOVA
Comparison: ANCOVA using treatment as a fixed effect and baseline as a covariate was performed.p-value: <0.00195% CI: [-14.2, -7.6]ANCOVA
Comparison: ANCOVA using treatment as a fixed effect and baseline as a covariate was performed.p-value: <0.00195% CI: [-17.6, -10.9]ANCOVA
Comparison: ANCOVA using treatment as a fixed effect and baseline as a covariate was performed.p-value: <0.00195% CI: [-15, -8.3]ANCOVA
Comparison: ANCOVA using treatment as a fixed effect and baseline as a covariate was performed.p-value: <0.00195% CI: [-20.4, -13.6]ANCOVA
Comparison: ANCOVA using treatment as a fixed effect and baseline as a covariate was performed.p-value: <0.00195% CI: [-14.7, -7.8]ANCOVA
Comparison: ANCOVA using treatment as a fixed effect and baseline as a covariate was performed.p-value: <0.00195% CI: [-16.2, -9.4]ANCOVA
Primary
Change From Baseline to Week 8 in Trough, Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring (Pooled Analysis)
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.
Population: Full analysis set, defined as all randomized participants who received at least 1 dose of double-blind study medication, with both a baseline value and at least 1 post-baseline value, with last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan Medoxomil 40 mg or 80 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in Trough, Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring (Pooled Analysis) | -28.9 mmHg | Standard Error 0.89 |
| Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in Trough, Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring (Pooled Analysis) | -15.9 mmHg | Standard Error 1.16 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 8 in Trough, Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring (Pooled Analysis) | -15.1 mmHg | Standard Error 1.19 |
Comparison: Analysis of covariance model (ANCOVA) using treatment as a fixed effect and baseline as a covariate was performed. Results for Azilsartan Medoxomil 40 mg/Chlorthalidone 25 mg QD and Azilsartan Medoxomil 80 mg/Chlorthalidone 25 mg QD pool were obtained using contrast with coefficients of 0.5 for Azilsartan Medoxomil 40 mg/Chlorthalidone 25 mg QD and 0.5 for Azilsartan Medoxomil 80 mg/Chlorthalidone 25 mg QD from the ANCOVA model.p-value: <0.00195% CI: [-15.8, -9.5]ANCOVA
Comparison: ANCOVA using treatment as a fixed effect and baseline as a covariate was performed. Results for Azilsartan Medoxomil 40 mg/Chlorthalidone 25 mg QD and Azilsartan Medoxomil 80 mg/Chlorthalidone 25 mg QD pool were obtained using contrast with coefficients of 0.5 for Azilsartan Medoxomil 40 mg/Chlorthalidone 25 mg QD and 0.5 for Azilsartan Medoxomil 80 mg/Chlorthalidone 25 mg QD from the ANCOVA model.p-value: <0.00195% CI: [-16.7, -10.9]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, defined as all randomized participants who received at least 1 dose of double-blind study medication, with both a baseline value and at least 1 post-baseline value, with last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan Medoxomil 40 mg or 80 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the 24-hour Mean Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -13.5 mmHg | Standard Error 0.6 |
| Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the 24-hour Mean Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -15.0 mmHg | Standard Error 0.62 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 8 in the 24-hour Mean Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -14.9 mmHg | Standard Error 0.63 |
| Azilsartan Medoxomil 40 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the 24-hour Mean Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -17.3 mmHg | Standard Error 0.64 |
| Azilsartan Medoxomil 80 mg/Chlorthalidone 12.5 mg QD | Change From Baseline to Week 8 in the 24-hour Mean Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -16.5 mmHg | Standard Error 0.65 |
| Azilsartan Medoxomil 80 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the 24-hour Mean Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -15.9 mmHg | Standard Error 0.64 |
| Chlorthalidone 12.5 mg QD | Change From Baseline to Week 8 in the 24-hour Mean Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -5.6 mmHg | Standard Error 0.59 |
| Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the 24-hour Mean Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -6.7 mmHg | Standard Error 0.59 |
| Azilsartan Medoxomil 20 mg QD | Change From Baseline to Week 8 in the 24-hour Mean Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -6.8 mmHg | Standard Error 0.6 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline to Week 8 in the 24-hour Mean Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -7.6 mmHg | Standard Error 0.59 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 8 in the 24-hour Mean Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -8.8 mmHg | Standard Error 0.6 |
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, defined as all randomized participants who received at least 1 dose of double-blind study medication, with both a baseline value and at least 1 post-baseline value, with last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan Medoxomil 40 mg or 80 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the 24-hour Mean Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -24.0 mmHg | Standard Error 0.97 |
| Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the 24-hour Mean Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -26.7 mmHg | Standard Error 1.01 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 8 in the 24-hour Mean Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -26.1 mmHg | Standard Error 1.01 |
| Azilsartan Medoxomil 40 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the 24-hour Mean Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -30.4 mmHg | Standard Error 1.03 |
| Azilsartan Medoxomil 80 mg/Chlorthalidone 12.5 mg QD | Change From Baseline to Week 8 in the 24-hour Mean Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -27.9 mmHg | Standard Error 1.04 |
| Azilsartan Medoxomil 80 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the 24-hour Mean Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -28.1 mmHg | Standard Error 1.03 |
| Chlorthalidone 12.5 mg QD | Change From Baseline to Week 8 in the 24-hour Mean Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -10.9 mmHg | Standard Error 0.96 |
| Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the 24-hour Mean Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -14.7 mmHg | Standard Error 0.95 |
| Azilsartan Medoxomil 20 mg QD | Change From Baseline to Week 8 in the 24-hour Mean Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -11.7 mmHg | Standard Error 0.97 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline to Week 8 in the 24-hour Mean Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -12.6 mmHg | Standard Error 0.96 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 8 in the 24-hour Mean Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring | -15.3 mmHg | Standard Error 0.97 |
Secondary
Change From Baseline to Week 8 in the Mean Daytime (6 AM to 10 PM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring.
The change in daytime (6am to 10pm) 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, defined as all randomized participants who received at least 1 dose of double-blind study medication, with both a baseline value and at least 1 post-baseline value, with last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan Medoxomil 40 mg or 80 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the Mean Daytime (6 AM to 10 PM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -13.7 mmHg | Standard Error 0.64 |
| Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the Mean Daytime (6 AM to 10 PM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -15.6 mmHg | Standard Error 0.66 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 8 in the Mean Daytime (6 AM to 10 PM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -15.1 mmHg | Standard Error 0.66 |
| Azilsartan Medoxomil 40 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the Mean Daytime (6 AM to 10 PM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -17.6 mmHg | Standard Error 0.67 |
| Azilsartan Medoxomil 80 mg/Chlorthalidone 12.5 mg QD | Change From Baseline to Week 8 in the Mean Daytime (6 AM to 10 PM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -16.8 mmHg | Standard Error 0.69 |
| Azilsartan Medoxomil 80 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the Mean Daytime (6 AM to 10 PM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -16.2 mmHg | Standard Error 0.67 |
| Chlorthalidone 12.5 mg QD | Change From Baseline to Week 8 in the Mean Daytime (6 AM to 10 PM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -5.6 mmHg | Standard Error 0.63 |
| Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the Mean Daytime (6 AM to 10 PM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -6.5 mmHg | Standard Error 0.62 |
| Azilsartan Medoxomil 20 mg QD | Change From Baseline to Week 8 in the Mean Daytime (6 AM to 10 PM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -6.8 mmHg | Standard Error 0.64 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline to Week 8 in the Mean Daytime (6 AM to 10 PM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -7.7 mmHg | Standard Error 0.63 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 8 in the Mean Daytime (6 AM to 10 PM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -9.1 mmHg | Standard Error 0.64 |
Secondary
Change From Baseline to Week 8 in the Mean Daytime (6 AM to 10 PM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring.
The change in daytime (6am to 10pm) 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, defined as all randomized participants who received at least 1 dose of double-blind study medication, with both a baseline value and at least 1 post-baseline value, with last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan Medoxomil 40 mg or 80 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the Mean Daytime (6 AM to 10 PM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -24.4 mmHg | Standard Error 1.01 |
| Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the Mean Daytime (6 AM to 10 PM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -27.7 mmHg | Standard Error 1.05 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 8 in the Mean Daytime (6 AM to 10 PM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -26.7 mmHg | Standard Error 1.06 |
| Azilsartan Medoxomil 40 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the Mean Daytime (6 AM to 10 PM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -31.2 mmHg | Standard Error 1.07 |
| Azilsartan Medoxomil 80 mg/Chlorthalidone 12.5 mg QD | Change From Baseline to Week 8 in the Mean Daytime (6 AM to 10 PM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -28.4 mmHg | Standard Error 1.09 |
| Azilsartan Medoxomil 80 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the Mean Daytime (6 AM to 10 PM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -28.5 mmHg | Standard Error 1.07 |
| Chlorthalidone 12.5 mg QD | Change From Baseline to Week 8 in the Mean Daytime (6 AM to 10 PM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -10.8 mmHg | Standard Error 1 |
| Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the Mean Daytime (6 AM to 10 PM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -14.7 mmHg | Standard Error 0.99 |
| Azilsartan Medoxomil 20 mg QD | Change From Baseline to Week 8 in the Mean Daytime (6 AM to 10 PM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -11.7 mmHg | Standard Error 1.01 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline to Week 8 in the Mean Daytime (6 AM to 10 PM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -12.8 mmHg | Standard Error 1 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 8 in the Mean Daytime (6 AM to 10 PM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -15.7 mmHg | Standard Error 1.01 |
Secondary
Change From Baseline to Week 8 in the Mean Diastolic Blood Pressure at 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, defined as all randomized participants who received at least 1 dose of double-blind study medication, with both a baseline value and at least 1 post-baseline value, with last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan Medoxomil 40 mg or 80 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the Mean Diastolic Blood Pressure at 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring. | -13.6 mmHg | Standard Error 0.68 |
| Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the Mean Diastolic Blood Pressure at 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring. | -15.6 mmHg | Standard Error 0.71 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 8 in the Mean Diastolic Blood Pressure at 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring. | -15.4 mmHg | Standard Error 0.71 |
| Azilsartan Medoxomil 40 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the Mean Diastolic Blood Pressure at 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring. | -17.8 mmHg | Standard Error 0.72 |
| Azilsartan Medoxomil 80 mg/Chlorthalidone 12.5 mg QD | Change From Baseline to Week 8 in the Mean Diastolic Blood Pressure at 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring. | -16.8 mmHg | Standard Error 0.73 |
| Azilsartan Medoxomil 80 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the Mean Diastolic Blood Pressure at 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring. | -16.2 mmHg | Standard Error 0.72 |
| Chlorthalidone 12.5 mg QD | Change From Baseline to Week 8 in the Mean Diastolic Blood Pressure at 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring. | -5.3 mmHg | Standard Error 0.67 |
| Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the Mean Diastolic Blood Pressure at 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring. | -6.3 mmHg | Standard Error 0.66 |
| Azilsartan Medoxomil 20 mg QD | Change From Baseline to Week 8 in the Mean Diastolic Blood Pressure at 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring. | -6.8 mmHg | Standard Error 0.68 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline to Week 8 in the Mean Diastolic Blood Pressure at 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring. | -7.6 mmHg | Standard Error 0.67 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 8 in the Mean Diastolic Blood Pressure at 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring. | -9.2 mmHg | Standard Error 0.68 |
Secondary
Change From Baseline to Week 8 in the Mean Nighttime (12 AM to 6 AM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring.
The change in nighttime (12am to 6am) 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, defined as all randomized participants who received at least 1 dose of double-blind study medication, with both a baseline value and at least 1 post-baseline value, with last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan Medoxomil 40 mg or 80 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the Mean Nighttime (12 AM to 6 AM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -12.8 mmHg | Standard Error 0.71 |
| Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the Mean Nighttime (12 AM to 6 AM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -13.5 mmHg | Standard Error 0.73 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 8 in the Mean Nighttime (12 AM to 6 AM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -14.4 mmHg | Standard Error 0.74 |
| Azilsartan Medoxomil 40 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the Mean Nighttime (12 AM to 6 AM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -16.2 mmHg | Standard Error 0.75 |
| Azilsartan Medoxomil 80 mg/Chlorthalidone 12.5 mg QD | Change From Baseline to Week 8 in the Mean Nighttime (12 AM to 6 AM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -15.8 mmHg | Standard Error 0.76 |
| Azilsartan Medoxomil 80 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the Mean Nighttime (12 AM to 6 AM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -14.9 mmHg | Standard Error 0.75 |
| Chlorthalidone 12.5 mg QD | Change From Baseline to Week 8 in the Mean Nighttime (12 AM to 6 AM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -6.0 mmHg | Standard Error 0.7 |
| Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the Mean Nighttime (12 AM to 6 AM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -7.1 mmHg | Standard Error 0.69 |
| Azilsartan Medoxomil 20 mg QD | Change From Baseline to Week 8 in the Mean Nighttime (12 AM to 6 AM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -6.9 mmHg | Standard Error 0.7 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline to Week 8 in the Mean Nighttime (12 AM to 6 AM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -7.5 mmHg | Standard Error 0.69 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 8 in the Mean Nighttime (12 AM to 6 AM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -8.0 mmHg | Standard Error 0.71 |
Secondary
Change From Baseline to Week 8 in the Mean Nighttime (12 AM to 6 AM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring.
The change in nighttime (12am to 6am) 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, defined as all randomized participants who received at least 1 dose of double-blind study medication, with both a baseline value and at least 1 post-baseline value, with last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan Medoxomil 40 mg or 80 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the Mean Nighttime (12 AM to 6 AM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -22.5 mmHg | Standard Error 1.09 |
| Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the Mean Nighttime (12 AM to 6 AM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -24.0 mmHg | Standard Error 1.13 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 8 in the Mean Nighttime (12 AM to 6 AM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -24.3 mmHg | Standard Error 1.14 |
| Azilsartan Medoxomil 40 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the Mean Nighttime (12 AM to 6 AM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -28.1 mmHg | Standard Error 1.15 |
| Azilsartan Medoxomil 80 mg/Chlorthalidone 12.5 mg QD | Change From Baseline to Week 8 in the Mean Nighttime (12 AM to 6 AM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -26.5 mmHg | Standard Error 1.17 |
| Azilsartan Medoxomil 80 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the Mean Nighttime (12 AM to 6 AM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -26.3 mmHg | Standard Error 1.15 |
| Chlorthalidone 12.5 mg QD | Change From Baseline to Week 8 in the Mean Nighttime (12 AM to 6 AM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -11.3 mmHg | Standard Error 1.08 |
| Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the Mean Nighttime (12 AM to 6 AM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -14.4 mmHg | Standard Error 1.06 |
| Azilsartan Medoxomil 20 mg QD | Change From Baseline to Week 8 in the Mean Nighttime (12 AM to 6 AM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -11.8 mmHg | Standard Error 1.09 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline to Week 8 in the Mean Nighttime (12 AM to 6 AM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -11.8 mmHg | Standard Error 1.08 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 8 in the Mean Nighttime (12 AM to 6 AM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring. | -14.2 mmHg | Standard Error 1.09 |
Secondary
Change From Baseline to Week 8 in the Mean Systolic Blood Pressure at 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, defined as all randomized participants who received at least 1 dose of double-blind study medication, with both a baseline value and at least 1 post-baseline value, with last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan Medoxomil 40 mg or 80 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the Mean Systolic Blood Pressure at 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring. | -24.6 mmHg | Standard Error 1.07 |
| Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the Mean Systolic Blood Pressure at 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring. | -28.0 mmHg | Standard Error 1.11 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 8 in the Mean Systolic Blood Pressure at 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring. | -27.1 mmHg | Standard Error 1.12 |
| Azilsartan Medoxomil 40 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the Mean Systolic Blood Pressure at 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring. | -31.7 mmHg | Standard Error 1.13 |
| Azilsartan Medoxomil 80 mg/Chlorthalidone 12.5 mg QD | Change From Baseline to Week 8 in the Mean Systolic Blood Pressure at 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring. | -28.5 mmHg | Standard Error 1.15 |
| Azilsartan Medoxomil 80 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the Mean Systolic Blood Pressure at 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring. | -28.7 mmHg | Standard Error 1.13 |
| Chlorthalidone 12.5 mg QD | Change From Baseline to Week 8 in the Mean Systolic Blood Pressure at 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring. | -10.4 mmHg | Standard Error 1.06 |
| Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the Mean Systolic Blood Pressure at 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring. | -14.5 mmHg | Standard Error 1.04 |
| Azilsartan Medoxomil 20 mg QD | Change From Baseline to Week 8 in the Mean Systolic Blood Pressure at 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring. | -11.8 mmHg | Standard Error 1.07 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline to Week 8 in the Mean Systolic Blood Pressure at 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring. | -12.7 mmHg | Standard Error 1.05 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 8 in the Mean Systolic Blood Pressure at 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring. | -15.8 mmHg | Standard Error 1.07 |
Secondary
Change From Baseline to Week 8 in the Mean Trough Diastolic Blood Pressure (22 to 24 Hours After Dosing), 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.
Population: Full analysis set, defined as all randomized participants who received at least 1 dose of double-blind study medication, with both a baseline value and at least 1 post-baseline value, with last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan Medoxomil 40 mg or 80 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the Mean Trough Diastolic Blood Pressure (22 to 24 Hours After Dosing), as Measured by Ambulatory Blood Pressure Monitoring. | -13.3 mmHg | Standard Error 0.8 |
| Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the Mean Trough Diastolic Blood Pressure (22 to 24 Hours After Dosing), as Measured by Ambulatory Blood Pressure Monitoring. | -15.0 mmHg | Standard Error 0.83 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 8 in the Mean Trough Diastolic Blood Pressure (22 to 24 Hours After Dosing), as Measured by Ambulatory Blood Pressure Monitoring. | -13.5 mmHg | Standard Error 0.83 |
| Azilsartan Medoxomil 40 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the Mean Trough Diastolic Blood Pressure (22 to 24 Hours After Dosing), as Measured by Ambulatory Blood Pressure Monitoring. | -17.3 mmHg | Standard Error 0.85 |
| Azilsartan Medoxomil 80 mg/Chlorthalidone 12.5 mg QD | Change From Baseline to Week 8 in the Mean Trough Diastolic Blood Pressure (22 to 24 Hours After Dosing), as Measured by Ambulatory Blood Pressure Monitoring. | -16.5 mmHg | Standard Error 0.86 |
| Azilsartan Medoxomil 80 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the Mean Trough Diastolic Blood Pressure (22 to 24 Hours After Dosing), as Measured by Ambulatory Blood Pressure Monitoring. | -16.1 mmHg | Standard Error 0.85 |
| Chlorthalidone 12.5 mg QD | Change From Baseline to Week 8 in the Mean Trough Diastolic Blood Pressure (22 to 24 Hours After Dosing), as Measured by Ambulatory Blood Pressure Monitoring. | -6.5 mmHg | Standard Error 0.79 |
| Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in the Mean Trough Diastolic Blood Pressure (22 to 24 Hours After Dosing), as Measured by Ambulatory Blood Pressure Monitoring. | -7.5 mmHg | Standard Error 0.78 |
| Azilsartan Medoxomil 20 mg QD | Change From Baseline to Week 8 in the Mean Trough Diastolic Blood Pressure (22 to 24 Hours After Dosing), as Measured by Ambulatory Blood Pressure Monitoring. | -7.9 mmHg | Standard Error 0.8 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline to Week 8 in the Mean Trough Diastolic Blood Pressure (22 to 24 Hours After Dosing), as Measured by Ambulatory Blood Pressure Monitoring. | -7.3 mmHg | Standard Error 0.79 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 8 in the Mean Trough Diastolic Blood Pressure (22 to 24 Hours After Dosing), as Measured by Ambulatory Blood Pressure Monitoring. | -8.9 mmHg | Standard Error 0.8 |
Secondary
Change From Baseline to Week 8 in Trough, Sitting, Clinic Diastolic Blood Pressure
The change in trough diastolic blood pressure measured at final visit or week 8 relative to baseline. Diastolic blood pressure is the average of the 3 serial trough clinic sitting diastolic blood pressure measurements.
Time frame: Baseline and Week 8.
Population: Full analysis set, defined as all randomized participants who received at least 1 dose of double-blind study medication, with both a baseline value and at least 1 post-baseline value, with last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan Medoxomil 40 mg or 80 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in Trough, Sitting, Clinic Diastolic Blood Pressure | -14.4 mmHg | Standard Error 0.72 |
| Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in Trough, Sitting, Clinic Diastolic Blood Pressure | -15.5 mmHg | Standard Error 0.72 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 8 in Trough, Sitting, Clinic Diastolic Blood Pressure | -15.6 mmHg | Standard Error 0.74 |
| Azilsartan Medoxomil 40 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in Trough, Sitting, Clinic Diastolic Blood Pressure | -17.0 mmHg | Standard Error 0.72 |
| Azilsartan Medoxomil 80 mg/Chlorthalidone 12.5 mg QD | Change From Baseline to Week 8 in Trough, Sitting, Clinic Diastolic Blood Pressure | -16.9 mmHg | Standard Error 0.73 |
| Azilsartan Medoxomil 80 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in Trough, Sitting, Clinic Diastolic Blood Pressure | -18.5 mmHg | Standard Error 0.71 |
| Chlorthalidone 12.5 mg QD | Change From Baseline to Week 8 in Trough, Sitting, Clinic Diastolic Blood Pressure | -7.4 mmHg | Standard Error 0.72 |
| Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in Trough, Sitting, Clinic Diastolic Blood Pressure | -9.2 mmHg | Standard Error 0.72 |
| Azilsartan Medoxomil 20 mg QD | Change From Baseline to Week 8 in Trough, Sitting, Clinic Diastolic Blood Pressure | -6.7 mmHg | Standard Error 0.72 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline to Week 8 in Trough, Sitting, Clinic Diastolic Blood Pressure | -9.2 mmHg | Standard Error 0.73 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 8 in Trough, Sitting, Clinic Diastolic Blood Pressure | -9.9 mmHg | Standard Error 0.7 |
Secondary
Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure
The change in trough systolic blood pressure measured at final visit or week 8 relative to baseline. Systolic blood pressure is the arithmetic mean of the 3 serial trough sitting systolic blood pressure measurements.
Time frame: Baseline and Week 8
Population: Full analysis set, defined as all randomized participants who received at least 1 dose of double-blind study medication, with both a baseline value and at least 1 post-baseline value, with last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan Medoxomil 40 mg or 80 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure | -33.8 mmHg | Standard Error 1.26 |
| Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure | -37.0 mmHg | Standard Error 1.26 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure | -36.8 mmHg | Standard Error 1.3 |
| Azilsartan Medoxomil 40 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure | -39.5 mmHg | Standard Error 1.25 |
| Azilsartan Medoxomil 80 mg/Chlorthalidone 12.5 mg QD | Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure | -36.9 mmHg | Standard Error 1.27 |
| Azilsartan Medoxomil 80 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure | -40.1 mmHg | Standard Error 1.24 |
| Chlorthalidone 12.5 mg QD | Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure | -21.1 mmHg | Standard Error 1.25 |
| Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure | -27.1 mmHg | Standard Error 1.25 |
| Azilsartan Medoxomil 20 mg QD | Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure | -19.8 mmHg | Standard Error 1.26 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure | -23.3 mmHg | Standard Error 1.27 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure | -24.2 mmHg | Standard Error 1.23 |
Comparison: ANCOVA using treatment as a fixed effect and baseline as a covariate was performed.p-value: <0.00195% CI: [-16.2, -9.2]ANCOVA
Comparison: ANCOVA using treatment as a fixed effect and baseline as a covariate was performed.p-value: <0.00195% CI: [-13.4, -6.4]ANCOVA
Comparison: ANCOVA using treatment as a fixed effect and baseline as a covariate was performed.p-value: <0.00195% CI: [-19.2, -12.1]ANCOVA
Comparison: ANCOVA using treatment as a fixed effect and baseline as a covariate was performed.p-value: <0.00195% CI: [-15.8, -8.9]ANCOVA
Comparison: ANCOVA using treatment as a fixed effect and baseline as a covariate was performed.p-value: <0.00195% CI: [-19.3, -12.3]ANCOVA
Comparison: ANCOVA using treatment as a fixed effect and baseline as a covariate was performed.p-value: <0.00195% CI: [-16.5, -9.5]ANCOVA
Comparison: ANCOVA using treatment as a fixed effect and baseline as a covariate was performed.p-value: <0.00195% CI: [-17.5, -10.5]ANCOVA
Comparison: ANCOVA using treatment as a fixed effect and baseline as a covariate was performed.p-value: <0.00195% CI: [-20.6, -13.7]ANCOVA
Comparison: ANCOVA using treatment as a fixed effect and baseline as a covariate was performed.p-value: <0.00195% CI: [-17, -9.9]ANCOVA
Comparison: ANCOVA using treatment as a fixed effect and baseline as a covariate was performed.p-value: <0.00195% CI: [-19.7, -12.7]ANCOVA
Comparison: ANCOVA using treatment as a fixed effect and baseline as a covariate was performed.p-value: <0.00195% CI: [-16.3, -9.3]ANCOVA
Comparison: ANCOVA using treatment as a fixed effect and baseline as a covariate was performed.p-value: <0.00195% CI: [-19.4, -12.6]ANCOVA
Secondary
Change From Baseline to Week 8 in Trough Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring in Black Participants (Pairwise Analysis)
The change in trough systolic blood pressure in black participants as 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.
Population: Full analysis set, defined as all randomized participants who received at least 1 dose of double-blind study medication, with both a baseline value and at least 1 post-baseline value, with last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan Medoxomil 40 mg or 80 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in Trough Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring in Black Participants (Pairwise Analysis) | -27.2 mmHg | Standard Error 3.21 |
| Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in Trough Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring in Black Participants (Pairwise Analysis) | -25.4 mmHg | Standard Error 3.36 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 8 in Trough Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring in Black Participants (Pairwise Analysis) | -21.5 mmHg | Standard Error 3.21 |
| Azilsartan Medoxomil 40 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in Trough Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring in Black Participants (Pairwise Analysis) | -31.9 mmHg | Standard Error 3.61 |
| Azilsartan Medoxomil 80 mg/Chlorthalidone 12.5 mg QD | Change From Baseline to Week 8 in Trough Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring in Black Participants (Pairwise Analysis) | -24.8 mmHg | Standard Error 3.71 |
| Azilsartan Medoxomil 80 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in Trough Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring in Black Participants (Pairwise Analysis) | -24.4 mmHg | Standard Error 3.43 |
| Chlorthalidone 12.5 mg QD | Change From Baseline to Week 8 in Trough Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring in Black Participants (Pairwise Analysis) | -12.2 mmHg | Standard Error 3.22 |
| Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in Trough Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring in Black Participants (Pairwise Analysis) | -23.4 mmHg | Standard Error 3.36 |
| Azilsartan Medoxomil 20 mg QD | Change From Baseline to Week 8 in Trough Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring in Black Participants (Pairwise Analysis) | -10.7 mmHg | Standard Error 3.1 |
| Azilsartan Medoxomil 40 mg QD | Change From Baseline to Week 8 in Trough Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring in Black Participants (Pairwise Analysis) | -11.0 mmHg | Standard Error 3.04 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 8 in Trough Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring in Black Participants (Pairwise Analysis) | -9.9 mmHg | Standard Error 2.97 |
Secondary
Change From Baseline to Week 8 in Trough Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring in Black Participants (Pooled Analysis)
The change in trough systolic blood pressure in black subjects 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.
Population: Full analysis set, defined as all randomized participants who received at least 1 dose of double-blind study medication, with both a baseline value and at least 1 post-baseline value, with last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan Medoxomil 40 mg or 80 mg/Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in Trough Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring in Black Participants (Pooled Analysis) | -28.2 mmHg | Standard Error 2.49 |
| Chlorthalidone 25 mg QD | Change From Baseline to Week 8 in Trough Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring in Black Participants (Pooled Analysis) | -23.4 mmHg | Standard Error 3.36 |
| Azilsartan Medoxomil 80 mg QD | Change From Baseline to Week 8 in Trough Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring in Black Participants (Pooled Analysis) | -9.9 mmHg | Standard Error 2.97 |
Comparison: ANCOVA using treatment as a fixed effect and baseline as a covariate was performed. Results for Azilsartan Medoxomil 40 mg/Chlorthalidone 25 mg QD and Azilsartan Medoxomil 80mg/Chlorthalidone 25 mg QD pool were obtained using contrast with coefficients of 0.5 for Azilsartan Medoxomil 40 mg/Chlorthalidone 25 mg QD and 0.5 for Azilsartan Medoxomil 80 mg/Chlorthalidone 25 mg QD from the ANCOVA model.p-value: 0.25595% CI: [-13, 3.5]ANCOVA
Comparison: ANCOVA using treatment as a fixed effect and baseline as a covariate was performed. Results for Azilsartan Medoxomil 40 mg/Chlorthalidone 25 mg QD and Azilsartan Medoxomil 80mg/Chlorthalidone 25 mg QD pool were obtained using contrast with coefficients of 0.5 for Azilsartan Medoxomil 40 mg/Chlorthalidone 25 mg QD and 0.5 for Azilsartan Medoxomil 80 mg/Chlorthalidone 25 mg QD from the ANCOVA model.p-value: <0.00195% CI: [-25.9, -10.6]ANCOVA
Secondary
Percentage of Participants Who Achieve a Clinic Diastolic Blood Pressure Response at Week 8, Defined as Clinic Diastolic Blood Pressure <90 mm Hg and/or a Reduction of ≥10 mm Hg From Baseline.
Percentage of participants who achieve a clinic diastolic blood pressure response measured at week 8, 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 average of the 3 serial trough sitting clinic diastolic blood pressure measurements.
Time frame: Baseline and Week 8.
Population: Full analysis set, defined as all randomized participants who received at least 1 dose of double-blind study medication, with both a baseline value and at least 1 post-baseline value, with last observation carried forward.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Azilsartan Medoxomil 40 mg or 80 mg/Chlorthalidone 25 mg QD | Percentage of Participants Who Achieve a Clinic Diastolic Blood Pressure Response at Week 8, Defined as Clinic Diastolic Blood Pressure <90 mm Hg and/or a Reduction of ≥10 mm Hg From Baseline. | 89.6 percentage of participants |
| Chlorthalidone 25 mg QD | Percentage of Participants Who Achieve a Clinic Diastolic Blood Pressure Response at Week 8, Defined as Clinic Diastolic Blood Pressure <90 mm Hg and/or a Reduction of ≥10 mm Hg From Baseline. | 89.5 percentage of participants |
| Azilsartan Medoxomil 80 mg QD | Percentage of Participants Who Achieve a Clinic Diastolic Blood Pressure Response at Week 8, Defined as Clinic Diastolic Blood Pressure <90 mm Hg and/or a Reduction of ≥10 mm Hg From Baseline. | 87.6 percentage of participants |
| Azilsartan Medoxomil 40 mg/Chlorthalidone 25 mg QD | Percentage of Participants Who Achieve a Clinic Diastolic Blood Pressure Response at Week 8, Defined as Clinic Diastolic Blood Pressure <90 mm Hg and/or a Reduction of ≥10 mm Hg From Baseline. | 94.8 percentage of participants |
| Azilsartan Medoxomil 80 mg/Chlorthalidone 12.5 mg QD | Percentage of Participants Who Achieve a Clinic Diastolic Blood Pressure Response at Week 8, Defined as Clinic Diastolic Blood Pressure <90 mm Hg and/or a Reduction of ≥10 mm Hg From Baseline. | 90.1 percentage of participants |
| Azilsartan Medoxomil 80 mg/Chlorthalidone 25 mg QD | Percentage of Participants Who Achieve a Clinic Diastolic Blood Pressure Response at Week 8, Defined as Clinic Diastolic Blood Pressure <90 mm Hg and/or a Reduction of ≥10 mm Hg From Baseline. | 96.8 percentage of participants |
| Chlorthalidone 12.5 mg QD | Percentage of Participants Who Achieve a Clinic Diastolic Blood Pressure Response at Week 8, Defined as Clinic Diastolic Blood Pressure <90 mm Hg and/or a Reduction of ≥10 mm Hg From Baseline. | 63.9 percentage of participants |
| Chlorthalidone 25 mg QD | Percentage of Participants Who Achieve a Clinic Diastolic Blood Pressure Response at Week 8, Defined as Clinic Diastolic Blood Pressure <90 mm Hg and/or a Reduction of ≥10 mm Hg From Baseline. | 78.8 percentage of participants |
| Azilsartan Medoxomil 20 mg QD | Percentage of Participants Who Achieve a Clinic Diastolic Blood Pressure Response at Week 8, Defined as Clinic Diastolic Blood Pressure <90 mm Hg and/or a Reduction of ≥10 mm Hg From Baseline. | 60.6 percentage of participants |
| Azilsartan Medoxomil 40 mg QD | Percentage of Participants Who Achieve a Clinic Diastolic Blood Pressure Response at Week 8, Defined as Clinic Diastolic Blood Pressure <90 mm Hg and/or a Reduction of ≥10 mm Hg From Baseline. | 71.1 percentage of participants |
| Azilsartan Medoxomil 80 mg QD | Percentage of Participants Who Achieve a Clinic Diastolic Blood Pressure Response at Week 8, Defined as Clinic Diastolic Blood Pressure <90 mm Hg and/or a Reduction of ≥10 mm Hg From Baseline. | 74.7 percentage of participants |
Secondary
Percentage of Participants Who Achieve a Clinic Systolic Blood Pressure Response at Week 8, as Defined by Clinic Systolic Blood Pressure <140 mm Hg and/or a Reduction of ≥20 mm Hg From Baseline.
Percentage of participants who achieve a clinic systolic blood pressure response measured at week 8, 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 average of the 3 serial trough sitting clinic systolic blood pressure measurements.
Time frame: Baseline and Week 8
Population: Full analysis set, defined as all randomized participants who received at least 1 dose of double-blind study medication, with both a baseline value and at least 1 post-baseline value, with last observation carried forward.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Azilsartan Medoxomil 40 mg or 80 mg/Chlorthalidone 25 mg QD | Percentage of Participants Who Achieve a Clinic Systolic Blood Pressure Response at Week 8, as Defined by Clinic Systolic Blood Pressure <140 mm Hg and/or a Reduction of ≥20 mm Hg From Baseline. | 86.4 percentage of participants |
| Chlorthalidone 25 mg QD | Percentage of Participants Who Achieve a Clinic Systolic Blood Pressure Response at Week 8, as Defined by Clinic Systolic Blood Pressure <140 mm Hg and/or a Reduction of ≥20 mm Hg From Baseline. | 88.9 percentage of participants |
| Azilsartan Medoxomil 80 mg QD | Percentage of Participants Who Achieve a Clinic Systolic Blood Pressure Response at Week 8, as Defined by Clinic Systolic Blood Pressure <140 mm Hg and/or a Reduction of ≥20 mm Hg From Baseline. | 90.3 percentage of participants |
| Azilsartan Medoxomil 40 mg/Chlorthalidone 25 mg QD | Percentage of Participants Who Achieve a Clinic Systolic Blood Pressure Response at Week 8, as Defined by Clinic Systolic Blood Pressure <140 mm Hg and/or a Reduction of ≥20 mm Hg From Baseline. | 93.5 percentage of participants |
| Azilsartan Medoxomil 80 mg/Chlorthalidone 12.5 mg QD | Percentage of Participants Who Achieve a Clinic Systolic Blood Pressure Response at Week 8, as Defined by Clinic Systolic Blood Pressure <140 mm Hg and/or a Reduction of ≥20 mm Hg From Baseline. | 86.8 percentage of participants |
| Azilsartan Medoxomil 80 mg/Chlorthalidone 25 mg QD | Percentage of Participants Who Achieve a Clinic Systolic Blood Pressure Response at Week 8, as Defined by Clinic Systolic Blood Pressure <140 mm Hg and/or a Reduction of ≥20 mm Hg From Baseline. | 94.9 percentage of participants |
| Chlorthalidone 12.5 mg QD | Percentage of Participants Who Achieve a Clinic Systolic Blood Pressure Response at Week 8, as Defined by Clinic Systolic Blood Pressure <140 mm Hg and/or a Reduction of ≥20 mm Hg From Baseline. | 56.1 percentage of participants |
| Chlorthalidone 25 mg QD | Percentage of Participants Who Achieve a Clinic Systolic Blood Pressure Response at Week 8, as Defined by Clinic Systolic Blood Pressure <140 mm Hg and/or a Reduction of ≥20 mm Hg From Baseline. | 76.9 percentage of participants |
| Azilsartan Medoxomil 20 mg QD | Percentage of Participants Who Achieve a Clinic Systolic Blood Pressure Response at Week 8, as Defined by Clinic Systolic Blood Pressure <140 mm Hg and/or a Reduction of ≥20 mm Hg From Baseline. | 53.5 percentage of participants |
| Azilsartan Medoxomil 40 mg QD | Percentage of Participants Who Achieve a Clinic Systolic Blood Pressure Response at Week 8, as Defined by Clinic Systolic Blood Pressure <140 mm Hg and/or a Reduction of ≥20 mm Hg From Baseline. | 64.5 percentage of participants |
| Azilsartan Medoxomil 80 mg QD | Percentage of Participants Who Achieve a Clinic Systolic Blood Pressure Response at Week 8, as Defined by Clinic Systolic Blood Pressure <140 mm Hg and/or a Reduction of ≥20 mm Hg From Baseline. | 66.7 percentage of participants |
Secondary
Percentage of Participants Who Achieve Both a Clinic Systolic and Diastolic Blood Pressure Response at Week 8.
Percentage of participants who achieve both a clinic systolic and diastolic blood pressure response measured at week 8, defined as systolic blood pressure less than 140 mm Hg and/or reduction from baseline of greater than or equal to 20 mm Hg AND diastolic blood pressure less than 90 mm Hg and/or reduction from baseline of greater than or equal to 10 mm Hg . Systolic/diastolic blood pressure is based on the average of the 3 serial trough clinic sitting systolic/diastolic blood pressure measurements.
Time frame: Baseline and Week 8.
Population: Full analysis set, defined as all randomized participants who received at least 1 dose of double-blind study medication, with both a baseline value and at least 1 post-baseline value, with last observation carried forward.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Azilsartan Medoxomil 40 mg or 80 mg/Chlorthalidone 25 mg QD | Percentage of Participants Who Achieve Both a Clinic Systolic and Diastolic Blood Pressure Response at Week 8. | 83.1 percentage of participants |
| Chlorthalidone 25 mg QD | Percentage of Participants Who Achieve Both a Clinic Systolic and Diastolic Blood Pressure Response at Week 8. | 84.3 percentage of participants |
| Azilsartan Medoxomil 80 mg QD | Percentage of Participants Who Achieve Both a Clinic Systolic and Diastolic Blood Pressure Response at Week 8. | 84.8 percentage of participants |
| Azilsartan Medoxomil 40 mg/Chlorthalidone 25 mg QD | Percentage of Participants Who Achieve Both a Clinic Systolic and Diastolic Blood Pressure Response at Week 8. | 91.0 percentage of participants |
| Azilsartan Medoxomil 80 mg/Chlorthalidone 12.5 mg QD | Percentage of Participants Who Achieve Both a Clinic Systolic and Diastolic Blood Pressure Response at Week 8. | 82.8 percentage of participants |
| Azilsartan Medoxomil 80 mg/Chlorthalidone 25 mg QD | Percentage of Participants Who Achieve Both a Clinic Systolic and Diastolic Blood Pressure Response at Week 8. | 93.0 percentage of participants |
| Chlorthalidone 12.5 mg QD | Percentage of Participants Who Achieve Both a Clinic Systolic and Diastolic Blood Pressure Response at Week 8. | 45.8 percentage of participants |
| Chlorthalidone 25 mg QD | Percentage of Participants Who Achieve Both a Clinic Systolic and Diastolic Blood Pressure Response at Week 8. | 67.9 percentage of participants |
| Azilsartan Medoxomil 20 mg QD | Percentage of Participants Who Achieve Both a Clinic Systolic and Diastolic Blood Pressure Response at Week 8. | 39.4 percentage of participants |
| Azilsartan Medoxomil 40 mg QD | Percentage of Participants Who Achieve Both a Clinic Systolic and Diastolic Blood Pressure Response at Week 8. | 55.3 percentage of participants |
| Azilsartan Medoxomil 80 mg QD | Percentage of Participants Who Achieve Both a Clinic Systolic and Diastolic Blood Pressure Response at Week 8. | 62.3 percentage of participants |