Long-Term Safety of Azilsartan Medoxomil and Chlorthalidone Compared to Olmesartan Medoxomil and Hydrochlorothiazide in Participants With Hypertension and Kidney Disease
Information source: Takeda
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Safety
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): Medical Director, Clinical Science, Study Director, Affiliation: Takeda
Summary
The purpose of this study is to evaluate long term safety and tolerability of azilsartan
medoxomil and chlorthalidone, once daily (QD), compared with olmesartan medoxomil and
hydrochlorothiazide in hypertensive participants with moderate renal impairment.
Clinical Details
Official title: A Randomized, Open-Label, Phase 3 Study to Compare Long-Term Safety and Tolerability of the TAK-491 and Chlorthalidone Fixed-Dose Combination Versus Olmesartan Medoxomil and Hydrochlorothiazide Fixed-Dose Combination in Hypertensive Subjects With Moderate Renal Impairment
Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Number of Participants With at Least 1 Adverse Event (AE)
Secondary outcome: Percentage of Participants at Final Visit Who Achieve Target Systolic Blood Pressure <130 mm HgPercentage of Participants at Final Visit Who Achieved Target Diastolic Blood Pressure <80 mm Hg Percentage of Participants at Final Visit Who Achieved Both a Clinic Systolic and Diastolic Blood Pressure Response
Detailed description:
A major component of blood pressure regulation is the renin-angiotensin-aldosterone system
(RAAS). Drugs that modulate the RAAS are used commonly worldwide for the treatment of
hypertension. TAK-491 (azilsartan medoxomil) is a prodrug of TAK-536 (azilsartan), an
angiotensin II receptor blocker (ARB). Azilsartan medoxomil is being evaluated by Takeda to
treat participants with essential hypertension.
Chlorthalidone is an orally administered thiazide-like diuretic agent, and long-term
outcomes trials show blood pressure reductions associated with chlorthalidone treatment
reduce risk of cardiovascular morbidity and mortality.
Hypertensive patients with moderate renal impairment are a relatively more severe and
resistant hypertension population, and may benefit from effective fixed-dose combination
treatments such as an ARB plus a diuretic for blood pressure control.
Participants will be randomized to receive azilsartan medoxomil and chlorthalidone or
olmesartan medoxomil and hydrochlorothiazide for up to 52 weeks to evaluate long term safety
of azilsartan medoxomil and chlorthalidone. A titration-to-target blood pressure approach
will be used to guide the titration of study medication in this trial.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. Is treated with 2 or 3 antihypertensive medications and on stable therapy, defined as
≥6 weeks on medication, and has a mean sitting clinic systolic blood pressure ≥135
and ≤160 mm Hg at the Screening Visit and on Day 1.
2. Has an estimated glomerular filtration rate (eGFR) in the range of ≥30 to <60
mL/min/1. 73 m^2 (Stage 3 chronic kidney disease) at the Screening Visit.
3. Is a man or woman and aged 18 years or older.
4. A female participant of childbearing potential who is sexually active with a
nonsterilized male partner agrees to routinely use adequate contraception from
signing of the informed consent through 30 days after the last study drug dose.
5. In the opinion of the investigator, the participant is capable of understanding and
complying with protocol requirements.
6. The participant or, when applicable, the participant's legally acceptable
representative signs and dates a written, informed consent form and any required
privacy authorization prior to the initiation of any study procedures.
7. Has clinical laboratory test results (clinical chemistry, hematology, and complete
urinalysis) that the investigator does not consider to be clinically significant in
this moderate renal impaired population.
8. Is willing to discontinue the current antihypertensive medications 2 days prior to
randomization.
Exclusion Criteria:
1. Has received any investigational compound within 30 days prior to Screening or is
currently participating in another investigational study.
2. Has been randomized/enrolled in a previous TAK-491 or TAK-491CLD study. NOTE: This
criterion does not apply to participants who began participation in another TAK-491
or TAK-491CLD study but were not randomized/enrolled, nor does it apply to
participants who participated in observational studies that lacked an intervention or
invasive procedure.
3. Is receiving a combination of olmesartan and hydrochlorothiazide at the Screening
Visit.
4. Is an immediate family member, study site employee, or is in a dependent relationship
with a study site employee who is involved in conduct of this study (eg, spouse,
parent, child, sibling) or may consent under duress.
5. Has a mean clinic diastolic (sitting, trough) >110 mm Hg on Day 1.
6. Has secondary hypertension of any etiology (eg, renovascular disease,
pheochromocytoma, Cushing's syndrome).
7. 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.
8. Has clinically significant cardiac conduction defects (ie, third-degree
atrioventricular block, sick sinus syndrome).
9. Has hemodynamically significant left ventricular outflow obstruction due to aortic
valvular disease.
10. Has severe renal dysfunction or disease (based on eGFR <30 mL/min/1. 73m^2 at
Screening) prior renal transplantation or nephrotic syndrome (defined as a urinary
albumin/creatinine ratio >2000 mg/g at Screening).
11. Has known or suspected unilateral or bilateral renal artery stenosis.
12. Has a history of cancer that has not been in remission for at least 5 years prior to
the first dose of study drug. (This criterion does not apply to those participants
with basal cell or stage I squamous cell carcinoma of the skin.)
13. Has poorly-controlled type 1 or 2 diabetes mellitus (glycosylated hemoglobin A
[HbA1c] >8. 5%) at Screening.
14. Has hypokalemia or hyperkalemia (defined as serum potassium outside of the normal
reference range of the central laboratory).
15. Has an alanine aminotransferase or aspartate aminotransferase level of >2. 5 times the
upper limit of normal, active liver disease, or jaundice.
16. 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 the
participant according to the protocol.
17. has a history of hypersensitivity or allergies to ARBs or thiazide-type diuretics or
other sulfonamide-derived compounds.
18. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol
abuse within the past 2 years.
19. Is required to take excluded medications.
20. If female, is pregnant or lactating or intending to become pregnant before, during,
or within 30 days after participating in this study; or intending to donate ova
during such time period.
Locations and Contacts
Kazanlak, Bulgaria
Pleven, Bulgaria
Sevlievo, Bulgaria
Sofia, Bulgaria
Varna, Bulgaria
Berlin, Germany
Hamburg, Germany
Daugavpils, Latvia
Kuldiga, Latvia
Limbazi, Latvia
Riga, Latvia
Tukums, Latvia
Ventspils, Latvia
Alytus, Lithuania
Kaunas, Lithuania
Klaipeda, Lithuania
Siauliai, Lithuania
Vilnius, Lithuania
Amsterdam, Netherlands
Groningen, Netherlands
Maastricht, Netherlands
Venlo, Netherlands
Grodzisk Mazowiecki, Poland
Lodz, Poland
Torun, Poland
Warszawa, Poland
Warszaw, Poland
Zgierz, Poland
Banska Bystrica, Slovakia
Bardejov, Slovakia
Bratislava, Slovakia
Komarno, Slovakia
Kosice, Slovakia
Martin, Slovakia
Nitra, Slovakia
Ruzomberok, Slovakia
Svidnik, Slovakia
Donetsk, Ukraine
Ivano-Frankivsk, Ukraine
Kharkiv, Ukraine
Kiev, Ukraine
Kyiv, Ukraine
Lutsk, Ukraine
Lviv, Ukraine
Vinnitsya, Ukraine
Vinnytsya, Ukraine
Mannheim, Baden Wuerttemberg, Germany
Nurnberg, Bayern, Germany
Nürnberg, Bayern, Germany
Frankfurt, Hessen, Germany
Offenbach, Hessen, Germany
Rodgau Dudenhofen, Hessen, Germany
Essen, Nordrhein Westfalen, Germany
Goch, Nordrhein Westfalen, Germany
Wuppertal, Nordrhein Westfalen, Germany
Additional Information
EDARBYCLOR Package Insert FDA Safety Alerts and Recalls
Starting date: March 2011
Last updated: September 28, 2013
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