Clinical trial NCT00760214
Conditions: Hypertension
Keywords: Essential Hypertension Hypertension Drug Therapy Blood Pressure, High Vascular Disease Cardiovascular Disease
Sponsor: Takeda
Start date: 2008-01-01; Completion date: 2009-04-01
Enrollment: 885 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine the efficacy and safety of azilsartan medoxomil, once daily (QD), compared to ramipril for treating Essential Hypertension.

Detailed description:
A major component of blood pressure regulation is the renin-angiotensin-aldosterone system, a system of hormone-mediated feedback interactions that results in the relaxation or constriction of blood vessels in response to various stimuli. Angiotensin II, a polypeptide hormone, is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme as part of the renin-angiotensin-aldosterone system. Angiotensin II is the principal pressor agent of the renin-angiotensin-aldosterone system with a myriad of effects on the cardiovascular system and on electrolyte homeostasis. Two receptors for angiotensin II have been identified. Angiotensin II type 1 receptors are located predominantly in vascular smooth muscle, where activation by angiotensin II results in vasoconstriction, hypertrophic proliferation, and inflammation. In contrast, stimulation of angiotensin II type 2 receptors by angiotensin II results in vasodilatation, antiproliferative effects that are opposite from those of angiotensin II type 1 receptor stimulation.

Drugs that modulate the renin-angiotensin-aldosterone system are used commonly worldwide for the treatment of hypertension. Of these, some block the synthesis of angiotensin II by inhibiting angiotensin-converting enzymes, while others inhibit the action of angiotensin II by binding directly to the angiotensin II type 1 receptor (called angiotensin II receptor blockers), thereby causing vasodilatation of blood vessels, resulting in a reduction in blood pressure. The effects of angiotensin II receptor blockers on other conditions in which the renin-angiotensin-aldosterone system plays a significant role, such as congestive heart failure, postmyocardial infarction management and diabetic nephropathy have also been investigated.

Although antihypertensive agents are effective at the appropriate dose, the majority have side effects that limit their use. Angiotensin-converting enzyme inhibitors are commonly associated with cough and more rarely with angioedema. Beta-blockers are associated with fatigue and erectile dysfunction, calcium antagonists with peripheral edema and diuretics with metabolic complications. As a class, angiotensin II receptor blockers generally are considered more tolerable than other classes of hypertensive agents, although there is still a need for compounds with improved tolerability and efficacy for the treatment of hypertension.

TAK-491 (azilsartan medoxomil) is an angiotensin II receptor blocker with high affinity for, and selective antagonistic activity at, the angiotensin II type 1 receptor, and is being developed for clinical use as an antihypertensive agent.

Ramipril is an angiotensin-converting enzyme inhibitor widely prescribed in Europe and Asia for the treatment of mild to moderate essential hypertension.

This study is designed to compare the efficacy and safety/tolerability of azilsartan medoxomil and ramipril for the treatment of hypertension.

Participants in this study will be seen twice during the first month, then once a month for five months. Participants will also be required to fast for 8 hours prior to each visit to the study center. Total duration of study participation is 24-weeks, plus a safety follow up phone call after the study has ended.

Arms: arm 1: None arm 2: None arm 3: None
Interventions: intervention 1: Azilsartan medoxomil intervention 2: Azilsartan medoxomil intervention 3: Ramipril
Intervention descriptions: intervention 1: Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 40 mg, tablets, orally, once daily for up to 22 weeks. intervention 2: Azilsartan medoxomil 20 mg, tablets, orally, once daily for two weeks; then increased to 80 mg, tablets, orally, once daily for up to 22 weeks. intervention 3: Ramipril 2.5 mg, tablets, orally, once daily for two weeks; then increased to 10 mg, tablets, orally, once daily for up to 22 weeks.

Protocol documents: