Skip to main content
OpenTrials
Completed

NCT Number: NCT00696384

A Safety and Tolerability Study of Azilsartan Medoxomil in Participants With Essential Hypertension

The purpose of this study is to determine the long term safety and tolerability of azilsartan medoxomil, once daily (QD), in participants with Essential Hypertension.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Hypertension Cardiovascular Diseases Essential Hypertension Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Berazategui, Buenos Aires, Argentina

Loading trial locations.

About this study

Hypertension affects approximately 50 million individuals in the United States. As the population ages, the prevalence of hypertension will continue to increase if broad and effective preventive measures are not implemented. 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.

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. AII 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 (AT1) 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 (AT2) receptors by angiotensin II results in vasodilation, antiproliferative effects, and other effects that are opposite from those of AT1 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 enzyme inhibitors, while others inhibit the action of angiotensin II by binding directly to the AT1 receptor (angiotensin II receptor blockers), thereby allowing blood vessels to dilate, 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, post-myocardial infarction management, and diabetic nephropathy, also are being investigated.

Takeda Global Research & Development Center, Inc. is developing TAK-491 (azilsartan medoxomil) to treat mild to moderate essential hypertension. Nonclinical studies have indicated that azilsartan medoxomil is an antagonist of the AT1 receptor subtype.

This study consists of 2 phases. The first phase will be a 26-week, open-label, multicenter phase to evaluate the safety and tolerability of TAK-491 in participants with essential hypertension. Investigators were instructed to manage participants according to a protocol-specified treatment algorithm to achieve target blood pressure. All participants who completed the open-label phase then were randomized into a 6-week double-blind, placebo-controlled (azilsartan medoxomil [maintained at the final dose from the open-label phase] or placebo, in addition to their current other antihypertensive medications including chlorthalidone, as applicable) reversal phase to evaluate maintenance/durability of azilsartan medoxomil -mediated blood pressure reduction, as well as potential rebound following the cessation of azilsartan medoxomil.

Study participation is anticipated to be about 8.5 Months. Multiple procedures will occur at each visit which may include fasting, blood collection, urine collection, vital signs including sitting and standing blood pressure and pulse, body height and weight, physical examinations and electrocardiograms.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Has essential hypertension (diastolic blood pressure ≥ 95mm Hg and ≤ 119 mm Hg. For participants with diabetes or chronic kidney disease diastolic blood pressure must be ≥ 85 mm Hg and ≤ to 109 mm Hg.
  • Female participant is not of childbearing potential (eg, sterilized, postmenopausal).
  • Female participants 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.
  • Clinical laboratory evaluations (including clinical chemistry, hematology, and complete urinalysis) are within the reference range for the testing laboratory unless the results are deemed not clinically significant for inclusion into this study by the investigator.

Exclusion criteria

  • Systolic blood pressure greater than 185 mm Hg.
  • Is required to take or intends to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:
  • Is hypersensitive to AII receptor blockers.
  • Recent history (within the last 6 months) of myocardial infarction, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, cerebrovascular accident, or transient ischemic attack.
  • History of moderate to severe heart failure or hypertensive encephalopathy.
  • Has clinically significant cardiac conduction defects (eg, third-degree atrioventricular block, sick sinus syndrome).
  • Has secondary hypertension of any etiology.
  • Known or suspected unilateral or bilateral renal artery stenosis.
  • Has severe renal dysfunction or disease (based on calculated creatinine clearance < 30 mL/min/1.73 m2) at Screening.

Treatment and study plan

Azilsartan medoxomil

Drug

All subjects initiated azilsartan medoxomil 40 mg, tablets, orally, once daily for four weeks, force-titrated to 80 mg, tablets, orally, once daily. After Week 8, chlorthalidone, 25 mg, tablets, orally, once daily as needed and other antihypertensive medications as needed to achieve target blood pressure (defined as <140/90 mm Hg for participants without diabetes or chronic kidney disease (CKD) and <130/80 mm Hg for participants with diabetes or CKD) for up to 26 weeks.

Study medication could have been up-titrated only after the subject had been at the previous dose level for a minimum of 2 weeks. Study medication could only have been up- or down-titrated by 1 dose level per scheduled or unscheduled visit.

Other names: TAK-491, Edarbi

Azilsartan medoxomil, with or without chlorthalidone and other non-angiotensin II receptor blocker antihypertensive medications.

Drug

Azilsartan medoxomil at the final dose received during the open-label phase: (20 mg, 40 mg or 80 mg), tablets, orally, once daily with or without chlorthalidone 25 mg, tablets, orally once daily and other non-ARB antihypertensive medications (if currently taking), for 6 weeks/Week 32.

Other names: TAK-491, Edarbi

Placebo

Drug

Azilsartan medoxomil placebo-matching tablets, orally, once daily with or without chlorthalidone 25 mg or other non-ARB antihypertensive (if currently taking), tablets, orally, once daily for 6 weeks/Week 32.

Primary outcomes

  1. Change From Double-blind Baseline (Week 26) in Sitting Clinic Diastolic Blood Pressure to Week 32

    Time frame: Double-blind Baseline (Week 26) and Week 32.

    The change in sitting clinic diastolic blood pressure measured at final visit or week 32 from Double-blind Baseline/Week 26. Diastolic blood pressure is the arithmetic mean of the 3 trough sitting diastolic blood pressure measurements. Each participant's blood pressure at the Final Visit/Week 26 of the open-label phase represented their Baseline blood pressure for the double-blind reversal phase.

Secondary outcomes

  1. Change From Double-blind Baseline (Week 26) in Sitting Clinic Systolic Blood Pressure to Week 32

    Time frame: Double-blind Baseline (Week 26) and Week 32.

    The change in sitting clinic systolic blood pressure measured at final visit or week 32 from Double-blind Baseline/Week 26.. Systolic blood pressure is the arithmetic mean of the 3 trough sitting systolic blood pressure measurements. Each participant's blood pressure at the Final Visit/Week 26 of the open-label phase represented their Baseline blood pressure for the double-blind reversal phase.

  2. Change From Open Label Baseline (Week 0) in Sitting Clinic Diastolic Blood Pressure to Week 26

    Time frame: Baseline and Week 26.

    The change from baseline in sitting clinic diastolic blood pressure measured at final visit or week 26.

  3. Change From Open Label Baseline (Week 0) in Sitting Clinic Systolic Blood Pressure to Week 26

    Time frame: Baseline and Week 26.

    The change from baseline in sitting clinic systolic blood pressure measured at final visit or week 26.

  4. Number of Participants With Adverse Events During the Open-Label Phase

    Time frame: Baseline to Week 26

    Treatment-emergent adverse events defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through 14 days after last dose of study drug, or within 30 days after the last dose of study drug for serious adverse event (SAE). A SAE is defined as any untoward medical occurrence that either results in death; is life-threatening; requires hospitalization; results in persistent or significant disability/incapacity; leads to a congenital anomaly/birth defect; or is an important medical event.

  5. Number of Participants With Adverse Events in the Double-Blind Baseline Phase

    Time frame: Double-blind Baseline/Week 26 to Week 32

    Treatment-emergent adverse events defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through 14 days after last dose of study drug, or within 30 days after the last dose of study drug for SAE. A SAE is defined as any untoward medical occurrence that either results in death; is life-threatening; requires hospitalization; results in persistent or significant disability/incapacity; leads to a congenital anomaly/birth defect; or is an important medical event.

Sponsors and collaborators

Lead sponsor

Takeda

Industry

Registry information

Official study title

An 8-Month Phase 3, Open-Label Study With a Blinded Reversal Phase to Evaluate the Safety and Tolerability of TAK-491 in Subjects With Essential Hypertension

Important dates

Study start
2007
Primary completion
2009
Study completion
2009
First posted
Jun 12, 2008
Registry last updated
Jan 4, 2012

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.