The purpose of this study is to determine the safety and efficacy of azilsartan, once daily (QD), in subjects with essential hypertension.
According to the National Health and Nutrition Examination Survey, approximately 60 million people in the United States are hypertensive. Although no single risk factor is responsible for the development of hypertension, some of the many risk factors can be controlled, and some cannot. Controllable risk factors include weight gain, smoking, a sedentary lifestyle, poor eating habits, emotional stress, physical tension, sodium sensitivity, alcohol abuse, and use of oral contraceptives. Uncontrollable risk factors include family history, gender, age and race. Hypertension is termed the "silent killer" because many patients are asymptomatic. Chronic hypertension causes extensive arterial wall damage, which allows cholesterol to adhere to the damaged endothelial lining and produces increased cardiac stress. Hypertension dramatically increases the risk of myocardial infarction, stroke, renal damage, impaired vision, heart failure and overall mortality. Angiotensin II receptor blockers are a class of drugs used for the treatment of hypertension that not only decrease blood pressure, but also likely contribute to protecting hypertensive individuals from cardiac events, strokes and loss of renal function. Angiotensin II has significant physiological effects on tissues and organs throughout the body including vascular smooth muscle, adrenal cortex, kidney, and brain. Angiotensin II receptors are located on the plasma membrane of target cells to facilitate the rapid onset of angiotensin II. Three distinct subtypes of angiotensin II receptors have been identified: angiotensin II type-1 receptor, angiotensin type 2, and angiotensin type 4; and the relative proportion of each vary from tissue to tissue. The angiotensin II type-1 receptor subtype is expressed predominantly in vascular smooth muscle cells where activation by angiotensin II results in vasoconstriction, cell proliferation, fibrosis, and cellular hypertrophy. In contrast, angiotensin II type-2 receptor stimulation produces pharmacologic activities that are opposite to those that occur after angiotensin II type-1 receptor stimulation. The angiotensin II type-4 receptor has been reported to be expressed in the adrenals, brain, and myocardium, but its exact function remains unknown. It is not considered to play an important role in human pathogenesis. TAK-536 (azilsartan) is a synthetic angiotensin II type-1 receptor antagonist being developed as a treatment for mild to moderate uncomplicated essential hypertension
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
555
Azilsartan 2.5 mg, tablets, orally, once daily and olmesartan placebo-matching capsules and tablets, orally, once daily for up to 8 weeks.
Azilsartan 5.0 mg, tablets, orally, once daily and olmesartan placebo-matching capsules and tablets, orally, once daily for up to 8 weeks.
Azilsartan 10 mg, tablets, orally, once daily and olmesartan placebo-matching capsules and tablets, orally, once daily for up to 8 weeks.
Change from Baseline in sitting clinic diastolic blood pressure.
Time frame: Week 8 or Final Visit
Change from Baseline in sitting clinic systolic blood pressure.
Time frame: Weeks 2, 4, 6, and 8 or Final Visit
The change from Baseline in standing clinic diastolic blood pressure and systolic blood pressure.
Time frame: Weeks 2, 4, 6, and 8 or Final Visit
Change from Baseline in diastolic blood pressure and systolic blood pressure as measured by ambulatory blood pressure monitoring.
Time frame: Week 8 or Final Visit
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Azilsartan 20 mg, tablets, orally, once daily and olmesartan placebo-matching capsules and tablets, orally, once daily for up to 8 weeks.
Azilsartan 40 mg, tablets, orally, once daily and olmesartan placebo-matching capsules and tablets, orally, once daily for up to 8 weeks.
Azilsartan placebo-matching tablets, orally, once daily and olmesartan placebo-matching capsules, orally, once daily for up to 8 weeks.
Azilsartan placebo-matching tablets, orally, once daily and olmesartan 20 mg, capsules, orally, once daily for up to 8 weeks.