A Phase 3 Long-term Study of TAK-536 in Pediatric Patients 6 to Less Than 16 Years With Hypertension
Condition: Pediatric Hypertension
MeSH terms: Hypertension
Intervention: Azilsartan; Placebo
Intervention description: Azilsartan granules and tablets; Placebo-matching azilsartan granules and tablets
Intervention MeSH terms: Azilsartan medoxomil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 27.0
Sex: All
Minimum age: 6 Years
Maximum age: 15 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate the safety of administration of azilsartan in
      pediatric patients aged 6 to less than 16 years with hypertension.
    

Eligibility criteria:

        Inclusion Criteria:

          1. In the opinion of the investigator or subinvestigator, the participant's parent or the
             participant's legal guardian is capable of understanding and complying with protocol
             requirements.

          2. The participant's parent or the participant's legal guardian is capable of signing and
             dating a written, informed consent form on behalf of the participant prior to the
             initiation of any study procedures. Written informed assent is also obtained from the
             participant as much as possible.

          3. The Japanese participant who has a diagnosis of hypertension. A participant is
             eligible if he/she is deemed hypertensive according to the Reference Blood Pressure
             Values of Children by Gender and Age; office sitting diastolic or systolic blood
             pressure ≥ 95 percentile for essential hypertension without concomitant hypertensive
             organ damage, and ≥ 90 percentile for secondary hypertension with concomitant chronic
             kidney disease (CKD), diabetes mellitus, heart failure or any hypertensive organ
             damage.

             In addition, participants need to meet the following criteria:

             - If currently treated with any antihypertensive drugs at the start of the Run-in
             Period: Participant has a documented historical diagnosis of hypertension and an
             office sitting diastolic or systolic blood pressure meeting the above criteria at the
             end of the Run-in Period (Week 0).

             - If currently untreated with any antihypertensive drugs at the start of the Run-in
             Period: Participant who meets the above criteria on 3 separate time points including
             screening and the end of the Run-in Period (Week 0). In addition, participant with
             essential hypertension without concomitant hypertensive organ damage still maintains
             hypertension with non-pharmacotherapy including foods or exercises for at least 3
             months within 1 year prior to the start of screening.

          4. The participant is male or female and aged 6 to less than 16 years at the time of
             informed consent.

          5. The participant weighs at least 20 kg at screening.

          6. The participant is capable of taking the tablets or granules supplied as the study
             drug.

          7. A participant who has undergone kidney transplantation is eligible if he/she underwent
             the transplantation at least 6 months earlier at screening, and the graft has been
             functionally stable (estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m^2)
             for at least 6 months with evidence (eg, Doppler echography, computed tomography (CT)
             scan or magnetic resonance imaging (MRI) excluding grafted kidney arterial stenosis. A
             participant on immunosuppressive therapy with a stable dose at least 30 days prior to
             screening is eligible.

          8. A female participant of childbearing potential who is sexually active with a
             nonsterilized male partner agrees to use routinely adequate contraception from signing
             of informed consent through 1 month after the completion of the study, and proves
             negative in the pregnancy test at screening.

          9. The participants judged by the investigator or subinvestigator that he/she can
             discontinue the therapy with renin-angiotensin-system (RAS) inhibitors for 2 weeks
             (acceptable range, 1 to 4 weeks) in safe prior to the Treatment Period.

        Exclusion Criteria:

          1. The participant has received any investigational compound within 30 days prior to
             screening or is participating in another clinical study or a post-marketing clinical
             study.

             Note: This does not apply to participants participating in observational studies
             without interventional or invasive therapy.

          2. The participant previously received therapy with azilsartan. Note: This does not apply
             to participants participating in single dose pharmacokinetic studies of TAK-536.

          3. The participant has poorly controlled hypertension indicated by an office sitting
             systolic blood pressure higher by at least 15 mmHg and/or an office sitting diastolic
             blood pressure higher by at least 10 mmHg than the 99 percentiles of the Reference
             Blood Pressure Values of Children by Gender and Age.

          4. The participant has a diagnosis of malignant or accelerated hypertension.

          5. The participant was noncompliant (< 70% or > 130%) with the study drug during the
             Run-in Period.

          6. The participant has severe renal dysfunction (eGFR < 30 mL/min/1.73 m^2), is receiving
             dialysis, has a renovascular disease affecting one or both kidneys, severe nephrotic
             syndrome not in remission, or a serum albumin level < 2.5 g/dL.

          7. The participant has a history of, or the signs/symptoms of serious cardiovascular,
             hepatobiliary, gastrointestinal, endocrine (eg, hyperthyroidism, Cushing's syndrome),
             hematological, immunological, urinogenital, psychiatric disease, cancer, or any other
             disease that adversely affects participant's health, or, in the opinion of the
             investigator or subinvestigator, potentially confounds the study results.

          8. The participant has hemodynamically significant left ventricular outflow obstruction
             due to aortic stenosis or aortic valvular disease, or is scheduled to undergo a
             medical procedure affecting blood pressure during the study (eg, correction of
             arterial anomaly).

          9. The participant has a history of or concurrent clinically significant abnormality of
             12-lead electrocardiogram (ECG) that, in the opinion of the investigator or
             subinvestigator, disqualifies the participant for participation in the study.

         10. The participant has poorly controlled diabetes mellitus indicated by hemoglobin A1c
             (HbA1c) > 9.0% at screening.

         11. The participant has an alanine aminotransferase (ALT) or aspartate aminotransferase
             (AST) level ≥ 2.5 × the upper limit of normal (ULN), or a total bilirubin level ≥ 1.5
             × ULN at screening, severely impaired hepatic function, any active liver disease
             (regardless of the cause), or jaundice.

         12. The participant has hyperkalemia exceeding ULN at screening.

         13. The participant has a history of hepatitis B, hepatitis C, or human immunodeficiency
             virus (HIV) infection at screening.

         14. The participant has a known hypersensitivity or allergy to any angiotensin II receptor
             blocker (ARBs).

         15. The participant needs treatment with any of the excluded medication.

         16. If female, the participant is pregnant or lactating or intending to become pregnant
             before, during, or within 1 month after the completion of this study.