A Randomized, Double-Blind, Multicenter, Phase 2/3 Study to Evaluate the Efficacy and Safety of Combined Administration of TAK-536CCB (Fix-dose Combination of Azilsartan and Amlodipine) and Hydrochlorothiazide in Comparison With TAK-536CCB or Hydrochlorothiazide Monotherapy in Patients With Grade I or II Essential Hypertension
Overview
- Phase
- Phase 2
- Intervention
- TAK-536CCB
- Conditions
- Grade I or II Essential Hypertension
- Sponsor
- Takeda
- Enrollment
- 353
- Primary Endpoint
- Change from Baseline in the office trough sitting diastolic blood pressure (DBP)
- Status
- Completed
- Last Updated
- 12 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
- •Male or female aged 20 years or older at the time of providing informed consent.
- •Outpatient.
Exclusion Criteria
- •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 -
- •3 Evident white coat hypertension or white coat phenomenon.
- •Day-night reversed lifestyle, such as night-time workers.
- •Sleep apnea syndrome requiring treatment.
- •Have any of the cardiovascular disease or symptoms listed below:
- •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.
- •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).
- •Vascular diseases: peripheral arterial disease with intermittent claudication, artery dissection, aneurysm
- •Advanced hypertensive retinopathy: bleeding, exudation, or papilledema (within 24 weeks before the placebo run-in period).
Arms & Interventions
TAK-536CCB 20 mg/5 mg ＋Placebo (dual therapy)
TAK-536CCB 20 mg/5 mg and Hydrochlorothiazide (HCTZ) placebo for 10 weeks
Intervention: TAK-536CCB
TAK-536CCB 20 mg/5 mg ＋HCTZ 6.25 mg (triple therapy)
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.
Intervention: TAK-536CCB + Hydrochlorothiazide
TAK-536CCB 20 mg/5 mg ＋HCTZ 12.5 mg (triple therapy)
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.
Intervention: TAK-536CCB + Hydrochlorothiazide
Placebo ＋HCTZ 6.25 mg (HCTZ monotherapy)
TAK-536CCB placebo and Hydrochlorothiazide 6.25 mg (HCTZ monotherapy) for 10 weeks from the start of the treatment period.
Intervention: Hydrochlorothiazide
Placebo ＋Hydrochlorothiazide 12.5 mg (HCTZ monotherapy)
TAK-536CCB placebo and Hydrochlorothiazide 12.5 mg (HCTZ monotherapy) for 10 weeks from the start of the treatment period.
Intervention: Hydrochlorothiazide
Outcomes
Primary Outcomes
Change from Baseline in the office trough sitting diastolic blood pressure (DBP)
Time Frame: 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 Outcomes
- Proportion of patients achieving < 140/90 mmHg(10 weeks)
- Frequency of adverse events( including vital sign, body weight, ECG findings and laboratory tests)(10 weeks)
- 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)
- Proportion of responders (140/90 mmHg criterion)(10 weeks)