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

Primary Purpose

Grade I or II Essential Hypertension

Status

Completed

Phase

Phase 2

Locations

Japan

Study Type

Interventional

Intervention

TAK-536CCB

TAK-536CCB + Hydrochlorothiazide

Hydrochlorothiazide

TAK-536CCB + Hydrochlorothiazide

About this trial

This is an interventional treatment trial for Grade I or II Essential Hypertension focused on measuring Hypertension, Drug therapy

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 0.
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 -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.
11. Diabetic subject on insulin treatment or poorly controlled type 2 diabetes mellitus.
12. Have a malignant tumor.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Active Comparator

Experimental

Active Comparator

Arm Label

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

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

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

Placebo ＋HCTZ 6.25 mg (HCTZ monotherapy)

Placebo ＋Hydrochlorothiazide 12.5 mg (HCTZ monotherapy)

Arm Description

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

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.

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

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

Outcomes

Primary Outcome Measures

Change from Baseline in the office trough sitting diastolic blood pressure (DBP)

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

Change from Baseline in the office trough sitting systolic blood pressure (SBP)

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 patients achieving < 140/90 mmHg

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 SBP

Proportion of responders (140/90 mmHg criterion)

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

Frequency of adverse events( including vital sign, body weight, ECG findings and laboratory tests)

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

Time profile of office trough sitting systolic blood pressure

Full Information

NCT ID

NCT02072330

First Posted

February 24, 2014

Last Updated

February 24, 2014

Sponsor

Takeda

1. Study Identification

Unique Protocol Identification Number

NCT02072330

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2014

Overall Recruitment Status

Completed

Study Start Date

March 2013 (undefined)

Primary Completion Date

December 2013 (Actual)

Study Completion Date

December 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Takeda

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Grade I or II Essential Hypertension

Keywords

Hypertension, Drug therapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

353 (Actual)

8. Arms, Groups, and Interventions

Arm Title

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

Arm Type

Active Comparator

Arm Description

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

Arm Title

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

Arm Type

Experimental

Arm 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.

Arm Title

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

Arm Type

Experimental

Arm 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.

Arm Title

Placebo ＋HCTZ 6.25 mg (HCTZ monotherapy)

Arm Type

Active Comparator

Arm Description

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

Arm Title

Placebo ＋Hydrochlorothiazide 12.5 mg (HCTZ monotherapy)

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

TAK-536CCB

Other Intervention Name(s)

Fix-dose combination of Azilsartan and Amlodipine

Intervention Description

TAK-536CCB 20 mg/5 mg ＋Hydrochlorothiazide placebo tablets

Intervention Type

Drug

Intervention Name(s)

TAK-536CCB + Hydrochlorothiazide

Other Intervention Name(s)

Hydrochlorothiazide and fix-dose combination of Azilsartan and Amlodipine

Intervention Description

TAK-536CCB 20 mg/5 mg and Hydrochlorothiazide 6.25 mg tablets

Intervention Type

Drug

Intervention Name(s)

Hydrochlorothiazide

Intervention Description

TAK-536CCB placebo and Hydrochlorothiazide 6.25 mg tablets

Intervention Type

Drug

Intervention Name(s)

Hydrochlorothiazide

Intervention Description

TAK-536CCB placebo and Hydrochlorothiazide 6.25 mg tablets x2

Intervention Type

Drug

Intervention Name(s)

TAK-536CCB + Hydrochlorothiazide

Other Intervention Name(s)

Hydrochlorothiazide and fix-dose combination of Azilsartan and Amlodipine

Intervention Description

TAK-536CCB 20 mg/5 mg and Hydrochlorothiazide 6.25 mg tablets x2

Primary Outcome Measure Information:

Title

Change from Baseline in the office trough sitting diastolic blood pressure (DBP)

Description

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])

Time Frame

Baseline and Week 10

Secondary Outcome Measure Information:

Title

Change from Baseline in the office trough sitting systolic blood pressure (SBP)

Description

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])

Time Frame

Baseline and Week 10

Title

Proportion of patients achieving < 140/90 mmHg

Description

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 SBP

Time Frame

10 weeks

Title

Proportion of responders (140/90 mmHg criterion)

Description

Time Frame

10 weeks

Title

Frequency of adverse events( including vital sign, body weight, ECG findings and laboratory tests)

Description

Time Frame

10 weeks

Title

Time profile of office trough sitting diastolic blood pressure

Time Frame

10 weeks

Title

Time profile of office trough sitting systolic blood pressure

Time Frame

10 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Accepts Healthy Volunteers

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 0. 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 -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. 11. Diabetic subject on insulin treatment or poorly controlled type 2 diabetes mellitus. 12. Have a malignant tumor.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Senior Manager

Organizational Affiliation

Takeda

Official's Role

Study Director

Facility Information:

City

Touon-shi

State/Province

Ehime

Country

Japan

City

Fukuoka-shi

State/Province

Fukuoka

Country

Japan

City

Hiroshima-shi

State/Province

Hiroshima

Country

Japan

City

Sapporo-shi

State/Province

Hokkaido

Country

Japan

City

Hanamaki-shi

State/Province

Iwate

Country

Japan

City

Morioka-shi

State/Province

Iwate

Country

Japan

City

Kumamoto-shi

State/Province

Kumamoto

Country

Japan

City

Kyoto-shi

State/Province

Kyoto

Country

Japan

City

Sendai-shi

State/Province

Miyagi

Country

Japan

City

Osaka-shi

State/Province

Osaka

Country

Japan

City

Suita-shi

State/Province

Osaka

Country

Japan

City

Shinjuku-ku

State/Province

Tokyo

Country

Japan

City

Toyama-shi

State/Province

Toyama

Country

Japan

12. IPD Sharing Statement

Learn more about this trial

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

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