Safety and Tolerability of Azilsartan Medoxomil Plus Chlorthalidone Compared to Olmesartan Medoxomil Plus Hydrochlorothiazide in Participants With Essential Hypertension
Information source: Takeda
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Essential Hypertension
Intervention: Azilsartan medoxomil and chlorthalidone (Drug); Olmesartan medoxomil and hydrochlorothiazide (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: Takeda Official(s) and/or principal investigator(s): Executive Medical Director, Clinical Science, Study Director, Affiliation: Takeda
Summary
The purpose of this study is to compare the safety and tolerability of azilsartan medoxomil
plus chlorthalidone, once daily (QD), versus olmesartan medoxomil-hydrochlorothiazide in
adults with essential hypertension.
Clinical Details
Official title: A Phase 3, Open-Label, Randomized, Long-Term Comparison of the Safety and Tolerability of the TAK-491 Plus Chlorthalidone Fixed-Dose Combination vs. Olmesartan Medoxomil-Hydrochlorothiazide Fixed-Dose Combination in Subjects With Essential Hypertension
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Percentage of Participants With at Least 1 Adverse Event
Secondary outcome: Percentage of Participants With Serum Creatinine Elevations Greater Than 50% From Baseline and Greater Than the Upper Limit of Normal (ULN)
Detailed description:
High Blood Pressure (Hypertension) is the most common cause of preventable death in
developed nations. Uncontrolled hypertension greatly increases the risk of heart disease,
brain disease, and kidney failure. As the population ages, the incidence of hypertension
will continue to increase if effective preventive measures are not implemented. Despite the
availability of antihypertensive agents, hypertension is not adequately controlled; only
about one in three patients successfully keep blood pressure normal.
Treatment for high blood pressure includes thiazides or thiazide-like diuretics, either
alone or as part of combination treatment. Chlorthalidone is a commercially available,
orally administered thiazide-type diuretic agent.
TAK-491 (azilsartan) is an angiotensin II receptor blocker being evaluated by Takeda to
treat patients with high blood pressure (essential hypertension).
This study will compare the safety and tolerability of azilsartan medoxomil plus
chlorthalidone (TAK-491CLD) fixed-dose combination to olmesartan
medoxomil-hydrochlorothiazide fixed-dose combination.
Initially patients will undergo a Screening Visit to confirm that they are eligible to
participate in the study. All participants will receive the study drug for up to 52 weeks.
The dose of the study drug may be gradually increased throughout the study so that a target
blood pressure value can be reached for each participant.
Throughout the treatment period of the study, participants will be required to visit the
research site for 11 visits. At these study visits participants will be required to undergo
certain study procedures including physical examinations, vital sign measurements (blood
pressure, heart rate, weight and height), electrocardiograms (monitoring of the heart), and
blood and urine samples taken for clinical laboratory tests.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- 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 Day, or has not received antihypertensive treatment within 14 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 Day 1.
- Females of childbearing potential who are sexually active agree to routinely use
adequate contraception, and can neither be pregnant nor lactating from before study
participation to Screening to 30 days after the last study drug dose.
- 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.
- Is willing to discontinue current antihypertensive medications up to 3 weeks before
enrollment.
Exclusion Criteria:
- Has a mean clinic diastolic blood pressure (sitting, trough) greater than 119 mm Hg
on Day 1.
- Has secondary hypertension of any etiology (eg, renovascular disease,
pheochromocytoma, Cushing's syndrome).
- Has a recent history (within the last 6 months) of myocardial infarction, heart
failure, unstable angina, coronary artery bypass graft, percutaneous coronary
intervention, hypertensive encephalopathy, cerebrovascular accident or transient
ischemic attack.
- Has clinically significant cardiac conduction defects (ie, third-degree
atrioventricular block, sick sinus syndrome).
- Has hemodynamically significant left ventricular outflow obstruction due to aortic
valvular disease.
- Has severe renal dysfunction or disease.
- Has known or suspected unilateral or bilateral renal artery stenosis.
- Has a history of cancer that has not been in remission for at least 5 years prior to
the first dose of study drug.
- Has poorly-controlled type 1 or 2 diabetes mellitus at Screening.
- Has hypokalemia or hyperkalemia at Screening.
- Has an alanine aminotransferase or aspartate aminotransferase level of greater than
2. 5 times the upper limit of normal, active liver disease, or jaundice at Screening.
- 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
according to the protocol.
- Has known hypersensitivity to angiotensin II receptor blockers or thiazide-type
diuretics or other sulfonamide-derived compounds.
- Has been randomized/enrolled in a previous azilsartan or azilsartan medoxomil plus
chlorthalidone study.
- Currently is participating in another investigational study or has received any
investigational compound within 30 days prior to Screening.
- Has a history of drug abuse or a history of alcohol abuse within the past 2 years.
- Is taking or expected to take any excluded medication, including:
- Antihypertensive medications must be discontinued completely by Day -14, except
antihypertensive medications used in the open-label treatment period in
accordance with the titration-to-target blood pressure titration.
- Angiotensin II receptor blockers or thiazide-type diuretics other than study
medication.
- Over-the-counter products not permitted by investigator.
Locations and Contacts
Groningen, Netherlands
Karlsruhe, Baden-Wurttemberg, Germany
Avon, England, United Kingdom
Bolton, England, United Kingdom
Chorley, England, United Kingdom
Inverness, England, United Kingdom
Liverpool, England, United Kingdom
Surrey, England, United Kingdom
Warwickshire, England, United Kingdom
Bydgoszcz, Kuyavian-Pomeranian, Poland
Skierniewice, L0dz, Poland
Zgierz, L0dz, Poland
Hannover, Lower Saxony, Germany
Breda, North Brabant, Netherlands
Eindhoven, North Brabant, Netherlands
Amsterdam, North Holland, Netherlands
Gdansk, Pomeranian, Poland
Gdynia, Pomeranian, Poland
Sopot, Pomeranian, Poland
Velp, Rheden, Netherlands
Kiel-Kronshagen, Schleswig-Holstein, Germany
Mikolow, Silesian, Poland
Leiderdorp, South Holland, Netherlands
Zoetermeer, South Holland, Netherlands
Graz, Styria, Austria
Rotterdam, Zuid-Holland, Netherlands
Additional Information
EDARBYCLOR Package Insert FDA Safety Alerts and Recalls
Starting date: October 2009
Last updated: October 15, 2012
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