Study to Evaluate the Efficacy and Safety of Combined Administration of TAK-536CCB and Hydrochlorothiazide in Patients With Grade I or II Essential Hypertension.

Takeda

Status and phase: Completed; Phase 3; Phase 2

Conditions: Grade I or II Essential Hypertension

Treatments: Drug: TAK-536CCB + Hydrochlorothiazide; Drug: Hydrochlorothiazide; Drug: TAK-536CCB

Study type: Interventional

Funder types: Industry

Identifiers

NCT02072330

TAK-536TCH/CCT-001

JapicCTI-121962 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 353 patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Grade I or II essential hypertension.
2. 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.
3. Male or female aged 20 years or older at the time of providing informed consent.
4. Outpatient.

Exclusion criteria

1. Secondary hypertension, grade III hypertension or malignant hypertension.
2. 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:

• 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).

  7. 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.

  8. Diabetic subject on insulin treatment or poorly controlled type 2 diabetes mellitus.

  9. Have a malignant tumor.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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353 participants in 5 patient groups

TAK-536CCB 20 mg/5 mg ＋Placebo (dual therapy)

Active Comparator group

Description:

TAK-536CCB 20 mg/5 mg and Hydrochlorothiazide (HCTZ) placebo for 10 weeks

Treatment:

Drug: TAK-536CCB

TAK-536CCB 20 mg/5 mg ＋HCTZ 6.25 mg (triple therapy)

Experimental group

Description:

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.

Treatment:

Drug: TAK-536CCB + Hydrochlorothiazide

Drug: TAK-536CCB + Hydrochlorothiazide

TAK-536CCB 20 mg/5 mg ＋HCTZ 12.5 mg (triple therapy)

Experimental group

Description:

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.

Treatment:

Drug: TAK-536CCB + Hydrochlorothiazide

Drug: TAK-536CCB + Hydrochlorothiazide

Placebo ＋HCTZ 6.25 mg (HCTZ monotherapy)

Active Comparator group

Description:

TAK-536CCB placebo and Hydrochlorothiazide 6.25 mg (HCTZ monotherapy) for 10 weeks from the start of the treatment period.

Treatment:

Drug: Hydrochlorothiazide

Drug: Hydrochlorothiazide

Placebo ＋Hydrochlorothiazide 12.5 mg (HCTZ monotherapy)

Active Comparator group

Description:

TAK-536CCB placebo and Hydrochlorothiazide 12.5 mg (HCTZ monotherapy) for 10 weeks from the start of the treatment period.

Treatment:

Drug: Hydrochlorothiazide

Drug: Hydrochlorothiazide