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 essential hypertension.
According to the World Health Organization, hypertension is the most common attributable cause of preventable death in developed nations, as uncontrolled hypertension greatly increases the risk of cardiovascular disease, cerebrovascular disease and renal failure. As the population ages, the prevalence of hypertension will continue to increase if broad and effective preventive measures are not implemented. Despite the availability of antihypertensive agents, hypertension remains inadequately controlled; only about one-third of patients continue to maintain control successfully. 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 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. Although chlorthalidone was commonly prescribed in the past, its use has widely been replaced with hydrochlorothiazide, presumably due to a lack of available combination products containing chlorthalidone, the assumption that hydrochlorothiazide and chlorthalidone have similar antihypertensive effects and cardiovascular benefits, and the perception that chlorthalidone use is associated with a greater frequency of hypokalemia. However, the frequency of hypokalemia with chlorthalidone use is relatively low in the dose range of 12.5 to 25 mg and these doses have been shown to be associated with potent blood pressure reduction. Several long-term outcomes trials have shown that blood pressure reductions associated with chlorthalidone treatment reduce risk of cardiovascular morbidity and mortality. Most hypertensive patients require two or more agents to achieve target blood pressure and diuretics are commonly used in combination with other antihypertensive agents. Participants in this study will be randomized to receive one of 3 possible dosing combinations of azilsartan medoxomil with either chlorthalidone or olmesartan medoxomil-hydrochlorothiazide over 8 weeks. The total duration of the study is approximately 13 weeks. Participants will make a total of 11 visits to the clinic, and will be required to participate in a follow-up telephone call 14 days after last dose of the study drug for adverse event assessment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
1,085
Azilsartan medoxomil 20 mg and chlorthalidone 12.5 mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 40 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.
Azilsartan medoxomil 40 mg and chlorthalidone 12.5, mg, tablets, orally, and olmesartan medoxomil-hydrochlorothiazide placebo tablets once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to azilsartan medoxomil 80 mg and chlorthalidone 25 mg, tablets, orally, once daily for the remaining 4 weeks.
Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure.
The change in trough systolic blood pressure measured at week 8 or final visit relative to baseline. Systolic blood pressure is the average of the 3 serial trough sitting systolic blood pressure measurements.
Time frame: Baseline and Week 8.
Change From Baseline to Week 4 in Trough, Sitting, Clinic Systolic Blood Pressure.
The change in trough systolic blood pressure measured at week 4 relative to baseline. Systolic blood pressure is the average of the 3 serial trough sitting systolic blood pressure measurements.
Time frame: Baseline and Week 4.
Change From Baseline in Trough, Sitting, Clinic Diastolic Blood Pressure
The change in trough diastolic blood pressure measured at week 4 and week 8 relative to baseline. Diastolic blood pressure is the average of the 3 serial trough sitting diastolic blood pressure measurements.
Time frame: Baseline, Week 4 and Week 8.
Change From Baseline in Trough Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
The change in trough systolic blood pressure measured at week 4 and week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Trough is the average of all measurements recorded from 22 to 24 hours after dosing.
Time frame: Baseline, Week 4 and Week 8.
Change From Baseline in Trough Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
The change in trough systolic blood pressure measured at week 4 and week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Trough is the average of all measurements recorded from 22 to 24 hours after dosing.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks.
Unnamed facility
Birmingham, Alabama, United States
Unnamed facility
Haleyville, Alabama, United States
Unnamed facility
Hueytown, Alabama, United States
Unnamed facility
Jasper, Alabama, United States
Unnamed facility
Tallassee, Alabama, United States
Unnamed facility
Green Valley, Arizona, United States
Unnamed facility
Phoenix, Arizona, United States
Unnamed facility
Long Beach, California, United States
Unnamed facility
National City, California, United States
Unnamed facility
Roseville, California, United States
...and 70 more locations
Time frame: Baseline, Week 4 and Week 8.
Change From Baseline in 24-hour Mean Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring.
The change in the 24-hour mean systolic blood pressure at week4 and 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, Week 4 and Week 8.
Change From Baseline in 24-hour Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
The change in the 0 to 24-hours-after-dosing mean diastolic blood pressure measured at Week 4 and Week 8 relative to baseline. . Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The mean consists of the average of measurements collected over the subsequent 24 hours.
Time frame: Baseline, Week 4 and Week 8.
Change From Baseline in Daytime Mean (6am to 10pm) Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
The change in the daytime, while awake (6am to 10pm) mean systolic blood pressure measured at Week 4 and 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 measurements recorded between the hours of 6 AM (inclusive) and 10 PM (exclusive) included in the 24-hour mean calculations.
Time frame: Baseline, Week 4 and Week 8.
Change From Baseline in Daytime Mean (6am to 10pm) Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
The change in the daytime, while awake (6am to 10pm) mean diastolic blood pressure measured at Week 4 and Week 8relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of measurements recorded between the hours of 6 AM (inclusive) and 10 PM (exclusive) included in the 24-hour mean calculations.
Time frame: Baseline, Week 4 and Week 8.
Change From Baseline in Nighttime Mean (12am to 6am) Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring
The change in the nighttime, while asleep (12am to 6am) mean systolic blood pressure measured at Week 4 and Week 8 to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of measurements recorded between the hours of 12 AM (inclusive) and 6 AM (exclusive) included in the 24-hour mean calculations.
Time frame: Baseline, Week 4 and Week 8.
Change From Baseline in Nighttime Mean (12am to 6am) Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
The change in the nighttime, while asleep (12am to 6am) mean diastolic blood pressure measured at Week 4 and 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 (arithmetic mean) of measurements recorded between the hours of 12 AM (inclusive) and 6 AM (exclusive) included in the 24-hour mean calculations.
Time frame: Baseline, Week 4 and Week 8.
Change From Baseline in 12-hr Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
The change in the 0 to 12 hours-after-dosing mean Systolic Blood Pressure measured at Week 4 and Week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night The mean consists of the average (arithmetic mean) of measurements collected at each time frame and includes all observations recorded over the subsequent 12 hours.
Time frame: Baseline, Week 4 and Week 8.
Change From Baseline in 12-hr Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring.
The change in the 0 to 12 hours-after-dosing mean diastolic blood pressure measured at Week 4 and Week 8 to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The mean consists of the average (arithmetic mean) of measurements collected at each time frame and includes all observations recorded over the subsequent 12 hours.
Time frame: Baseline, Week 4 and Week 8.
Percentage of Participants Who Achieve a Clinic Systolic Blood Pressure Response, Defined as <140 mm Hg for Participants Without Diabetes or CKD or <130 mm Hg for Participants With Diabetes or CKD
Percentage of participants who achieve a clinic systolic blood pressure response, defined as \<140 mm Hg for participants without diabetes or CKD or \<130 mm Hg for participants with diabetes or CKD at each time frame relative to baseline.
Time frame: Baseline, Week 2, Week 4, Week 6 and Week 8.
Percentage of Participants Who Achieve a Clinic Diastolic Blood Pressure Response, Defined as Defined as <90 mm Hg for Participants Without Diabetes or CKD or <80 mm Hg for Participants With Diabetes or CKD
Percentage of participants who achieve a clinic diastolic blood pressure response, defined as defined as \<90 mm Hg for participants without diabetes or CKD or \<80 mm Hg for participants with diabetes or CKD at each time frame relative to baseline.
Time frame: Baseline, Week 2, Week 4, Week 6 and Week 8.
Percentage of Participants Who Achieve a Clinic Diastolic AND Systolic Blood Pressure Response, Defined as <140/90 mm Hg for Participants Without Diabetes or Chronic Kidney Disease (CKD) or <130/80 mm Hg for Participants With Diabetes or CKD
Percentage of participants who achieve both a clinic diastolic blood pressure response, defined as \<140/90 mm Hg for participants without diabetes or chronic kidney disease (CKD) or \<130/80 mm Hg for participants with diabetes or CKD at each time frame relative to baseline.
Time frame: Baseline, Week 2, Week 4, Week 6 and Week 8.