Study to Evaluate the Efficacy and Safety of Combined Administration of TAK-536CCB and Hydrochlorothiazide in Patients With Grade I or II Essential Hypertension.
- Conditions
- Grade I or II Essential Hypertension
- Interventions
- Registration Number
- NCT02072330
- Lead Sponsor
- Takeda
- Brief Summary
The objective of this study is to compare the efficacy and safety of combined administration of TAK-536CCB (Fix-dose combination of Azilsartan and Amlodipine) and Hydrochlorothiazide (HCTZ) with those of TAK-536CCB in patients with Grade I or II essential hypertension.
- Detailed Description
This study is a randomized, double-blind, multicenter, phase 2/3 study to evaluate the efficacy and safety of combined administration of TAK-536CCB and Hydrochlorothiazide (HCTZ) with those of TAK-536CCB or Hydrochlorothiazide in patients with grade I or II essential hypertension.
This study consists of a 4-week single-blind placebo run-in period and a 10-week double-blind treatment period.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 353
- Grade I or II essential hypertension.
- An office sitting systolic blood pressure of ≥ 150 and < 180 mmHg, and an office sitting diastolic blood pressure of ≥ 95 and < 110 mmHg during the placebo run-in period at Week -2 and Week 0.
- Male or female aged 20 years or older at the time of providing informed consent.
- Outpatient.
- Secondary hypertension, grade III hypertension or malignant hypertension.
- An office sitting systolic blood pressure of ≥160 mmHg or sitting diastolic blood pressure of ≥100 mmHg recorded while on combined therapy with 3 or more antihypertensives within 4 weeks prior to the initiation of the placebo run-in period and at Week -4.
3 Evident white coat hypertension or white coat phenomenon. 4. Day-night reversed lifestyle, such as night-time workers. 5. Sleep apnea syndrome requiring treatment. 6. Have any of the cardiovascular disease or symptoms listed below:
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Heart disease: myocardial infarction (within 24 weeks before the placebo run-in period), coronary arterial revascularization (within 24 weeks before the placebo run-in period), severe valvular disease, atrial fibrillation, or following diseases which require medication: angina pectoris, congested heart failure, or arrhythmia.
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Cerebrovascular disease: cerebral infarction, cerebral hemorrhage (within 24 weeks before the placebo run-in period), or transient ischemic attack (within 24 weeks before the placebo run-in period).
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Vascular diseases: peripheral arterial disease with intermittent claudication, artery dissection, aneurysm
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Advanced hypertensive retinopathy: bleeding, exudation, or papilledema (within 24 weeks before the placebo run-in period).
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Clinically significant hepatic disorder. 8. Clinically significant renal impairment. 9. Significantly low or high Potassium or Sodium levels. 10. Complicated by gout, or had a past history of gout within 24 weeks prior to the initiation of the placebo run-in period, or complicated by hyperuricemia requiring medication.
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Diabetic subject on insulin treatment or poorly controlled type 2 diabetes mellitus.
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Have a malignant tumor.
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Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description TAK-536CCB 20 mg/5 mg ＋HCTZ 6.25 mg (triple therapy) TAK-536CCB + Hydrochlorothiazide TAK-536CCB 20 mg/5 mg and Hydrochlorothiazide placebo (triple therapy) for the first 2 weeks of the treatment period and TAK-536CCB 20 mg/5 mg and HCTZ 6.25 mg for the remaining 8 weeks. Placebo ＋HCTZ 6.25 mg (HCTZ monotherapy) Hydrochlorothiazide TAK-536CCB placebo and Hydrochlorothiazide 6.25 mg (HCTZ monotherapy) for 10 weeks from the start of the treatment period. TAK-536CCB 20 mg/5 mg ＋HCTZ 12.5 mg (triple therapy) TAK-536CCB + Hydrochlorothiazide TAK-536CCB 20 mg/5 mg and Hydrochlorothiazide placebo for the first 2 weeks of the treatment period and TAK-536CCB 20 mg/5 mg and HCTZ 12.5 mg (triple therapy) for the remaining 8 weeks. TAK-536CCB 20 mg/5 mg ＋Placebo (dual therapy) TAK-536CCB TAK-536CCB 20 mg/5 mg and Hydrochlorothiazide (HCTZ) placebo for 10 weeks Placebo ＋Hydrochlorothiazide 12.5 mg (HCTZ monotherapy) Hydrochlorothiazide TAK-536CCB placebo and Hydrochlorothiazide 12.5 mg (HCTZ monotherapy) for 10 weeks from the start of the treatment period.
- Primary Outcome Measures
Name Time Method Change from Baseline in the office trough sitting diastolic blood pressure (DBP) Baseline and Week 10 Change in the office trough sitting DBP from the end of the placebo run-in period (baseline \[Week 0\]) to the end of the treatment period (Week 10, last observation carried forward \[LOCF\])
- Secondary Outcome Measures
Name Time Method Proportion of patients achieving < 140/90 mmHg 10 weeks Patients achieving \< 140/90 mmHg refer to those meeting both of the following criteria:
* A decrease to \< 90 mmHg in office trough sitting DBP
* A decrease to \< 140 mmHg in office trough sitting SBPFrequency of adverse events( including vital sign, body weight, ECG findings and laboratory tests) 10 weeks The frequency of adverse events by type, seriousness. Adverse events are defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug to the last dose of study drug
Time profile of office trough sitting diastolic blood pressure 10 weeks Time profile of office trough sitting systolic blood pressure 10 weeks Change from Baseline in the office trough sitting systolic blood pressure (SBP) Baseline and Week 10 Change in the office trough sitting SBP from the end of the placebo run-in period (baseline \[Week 0\]) to the end of the treatment period (Week 10, last observation carried forward \[LOCF\])
Proportion of responders (140/90 mmHg criterion) 10 weeks Patients who met either of the following conditions are regarded as responders (140/90 mmHg criterion).
* A ≥ 20 mmHg decrease in office trough sitting SBP and a ≥ 10 mmHg decrease in the office trough sitting DBP
* A decrease to \< 140 mmHg in office trough sitting SBP and a decrease to \< 90 mmHg in office trough sitting DBP