Long-Term Safety of Azilsartan Medoxomil and Chlorthalidone Compared to Olmesartan Medoxomil and Hydrochlorothiazide in Participants With Hypertension and Kidney Disease
Condition: Safety
MeSH terms: Kidney Diseases
Intervention: Azilsartan medoxomil and chlorthalidone; Olmesartan medoxomil and hydrochlorothiazide
Intervention description: Fixed-dose combination tablets.; Fixed-dose combination tablets.
Intervention MeSH terms: Hydrochlorothiazide; Olmesartan; Olmesartan Medoxomil; Chlorthalidone; Azilsartan medoxomil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 153.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Renal Insufficiency; Kidney Diseases; Hypertension; Drug Therapy

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.
    

Eligibility 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.