A Phase III Long-term Study of TAK-536TCH in Participants With Essential Hypertension
Condition: Essential Hypertension
MeSH terms: Hypertension; Essential Hypertension
Intervention: TAK-536TCH tablet; TAK-536CCB tablet; HCTZ 12.5 mg tablet
Intervention description: TAK-536TCH tablets; TAK-536CCB tablets; HCTZ tablets
Intervention MeSH terms: Azilsartan medoxomil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 341.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No
Keywords: Pharmacological therapy; Drug Therapy

Summary:

      The purpose of this study is to evaluate the safety of long-term administration of TAK-536,
      amlodipine (AML), and hydrochlorothiazide (HCTZ) in participants with essential hypertension.
    

Eligibility criteria:

        Inclusion Criteria:

          1. In the opinion of the investigator or subinvestigator, the participant is capable of
             understanding and complying with protocol requirements.

          2. The participant signs and dates a written informed consent form prior to the
             initiation of any study procedures.

          3. The participant has essential hypertension.

          4. The participant has an office sitting systolic blood pressure (SBP) of <180 mmHg and
             office sitting diastolic blood pressure (DBP) of < 110 mmHg at the start of the run-in
             period (Week -4). Participants receiving combined therapy with a 3-drug
             antihypertensive within 4 weeks prior to the start of the run-in period is required to
             have an office sitting SBP of < 160 mmHg and an office sitting DBP of < 100 mmHg.

          5. The participant's office sitting blood pressure at Week -2 and at the end of the
             run-in period (Week 0) need to be either:

               -  Participants without concurrent diabetes mellitus or chronic kidney disease
                  (CKD)*: Sitting SBP of ≥ 140 mmHg or sitting DBP of ≥ 90 mmHg

               -  Participants with concurrent diabetes mellitus or CKD*: Sitting SBP of ≥ 130 mmHg
                  or sitting DBP of ≥ 80 mmHg.

                    -  Estimate glomerular filtration rate according to creatinine (eGFRcreat) of
                       <60 mL/min/1.73 m^2, or urinary albumin (spot urine) of ≥30 μg/mL in
                       laboratory tests performed at Week -2 of the run-in period, and diagnosed
                       with CKD by the investigator or subinvestigator.

          6. The participant has an office sitting SBP of < 160 mmHg and office sitting DBP of <
             100 mmHg at the end of the run-in period (Week 0).

          7. The participant is male or female, aged 20 years or older at the time of providing
             informed consent.

          8. The participant is an outpatient.

          9. A female participant of childbearing potential who is sexually active with a
             nonsterilized male partner agree to use routinely adequate contraception from signing
             of informed consent through 1 month following the end of the study.

        Exclusion Criteria:

          1. The participant has received any study drugs within 12 weeks prior to the start of the
             run-in period.

          2. The participant has participated in another clinical study or a post-marketing study
             within 30 days prior to the start of the run-in period.

          3. The participant 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 (e.g. spouse, parent, child, sibling), or may consent under duress.

          4. The participant requires taking prohibited concomitant drugs during the study.

          5. The participant has a history of hypersensitivity or allergies to TAK-536, AML, HCTZ,
             any thiazide diuretic or analog, any dihydropyridine drug, or any analog of
             TAK-536TCH.

          6. The participant is judged by the investigator or subinvestigator to be in danger of
             experiencing an excessive increase in blood pressure when changing or discontinuing
             premedication.

          7. The participant received combination therapy with antihypertensive drugs of the 3
             ingredients contained in TAK-536TCH.

          8. The participant received combined therapy with antihypertensive drugs, including 4 or
             more components, within 4 weeks prior to the start of the run-in period.

          9. The participant has secondary or malignant hypertension.

         10. The participant has a difference of ≥ 20 mmHg between left and right arms in office
             sitting SBP at the start of the run-in period (Week -4).

         11. The participant has apparent white coat hypertension or exhibits a white coat effect.

         12. . The participant has a day-night reversed lifestyle, such as those working during the
             night.

         13. The participant has sleep apnea syndrome requiring treatment.

         14. The participant has any of the following cardiovascular diseases:

               -  Cardiac disease: Myocardial infarction*, coronary arterial revascularization*,
                  severe valvular disorder, atrial fibrillation, any of the following conditions
                  requiring treatment: angina pectoris, congestive heart failure, arrhythmia

               -  Cerebrovascular disorders: Cerebral infarction/cerebral hemorrhage*, transient
                  ischemic attack*

               -  Vascular disease: Peripheral artery disease with intermittent claudication,
                  artery dissection, aneurysm

               -  Advanced hypertensive retinopathy: With bleeding or exudate/papilledema** *
                  Occurring or performed within 24 weeks of the start of the run-in period **
                  Observed within 24 weeks of the start of the run-in period

         15. The participant has a clinically apparent hepatic disorder (e.g., aspartate
             aminotransferase (AST) or alanine aminotransferase (ALT) at Week -2 of the run-in
             period ≥ 2.5 times the upper limit of normal (ULN).

         16. The participant has a clinically severe renal disorder (e.g., eGFRcreat in laboratory
             tests performed at Week -2 of run-in period < 30 mL/minute/1.73 m^2).

         17. The participant's body fluid sodium or potassium level is markedly low* or high*.

             *Based on normal ranges

         18. The participant has gout or a history of gout within 24 weeks of the start of the
             run-in period or has hyperuricemia requiring drug treatment.

         19. The participant has uncontrolled diabetes (e.g., HbA1c ≥ 7.4% in laboratory tests
             performed at Week -2 of the run-in period).

         20. The participant has a malignant tumor.

         21. If female, the participant is pregnant or lactating or before giving informed consent,
             intending to become pregnant or donate ova during or within 1 month after
             participating in the study.

         22. The participant has a history of drug abuse (defined as any illicit drug use) or a
             history of alcohol abuse within 2 years prior to the run-in period.

         23. The participant who, in the opinion of the investigator or subinvestigator, is
             unsuitable for any other reason.