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

• ClinicalTrials.gov Identifier: NCT02072330
• Recruitment Status: Completed
• First Posted: February 26, 2014
• Last Update Posted: February 26, 2014
• Sponsor: Takeda
• Information provided by (Responsible Party): Takeda

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.

Condition or disease	Intervention/treatment	Phase
Grade I or II Essential Hypertension	Drug: TAK-536CCB; Drug: TAK-536CCB + Hydrochlorothiazide; Drug: Hydrochlorothiazide	Phase 2; Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 353 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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 Start Date: March 2013
• Actual Primary Completion Date: December 2013
• Actual Study Completion Date: December 2013

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: TAK-536CCB 20 mg/5 mg ＋Placebo (dual therapy); TAK-536CCB 20 mg/5 mg and Hydrochlorothiazide (HCTZ) placebo for 10 weeks	Drug: TAK-536CCB; TAK-536CCB 20 mg/5 mg ＋Hydrochlorothiazide placebo tablets; Other Name: Fix-dose combination of Azilsartan and Amlodipine
Experimental: 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.	Drug: TAK-536CCB + Hydrochlorothiazide; TAK-536CCB 20 mg/5 mg and Hydrochlorothiazide 6.25 mg tablets; Other Name: Hydrochlorothiazide and fix-dose combination of Azilsartan and Amlodipine
Experimental: 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.	Drug: TAK-536CCB + Hydrochlorothiazide; TAK-536CCB 20 mg/5 mg and Hydrochlorothiazide 6.25 mg tablets x2; Other Name: Hydrochlorothiazide and fix-dose combination of Azilsartan and Amlodipine
Active Comparator: 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.	Drug: Hydrochlorothiazide; TAK-536CCB placebo and Hydrochlorothiazide 6.25 mg tablets
Active Comparator: 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.	Drug: Hydrochlorothiazide; TAK-536CCB placebo and Hydrochlorothiazide 6.25 mg tablets x2

Outcome Measures

Primary Outcome Measures :

1. 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 Outcome Measures :

1. Change from Baseline in the office trough sitting systolic blood pressure (SBP) [ Time Frame: 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])
2. Proportion of patients achieving < 140/90 mmHg [ Time Frame: 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 SBP
3. Proportion of responders (140/90 mmHg criterion) [ Time Frame: 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
4. Frequency of adverse events( including vital sign, body weight, ECG findings and laboratory tests) [ Time Frame: 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
5. Time profile of office trough sitting diastolic blood pressure [ Time Frame: 10 weeks ]
6. Time profile of office trough sitting systolic blood pressure [ Time Frame: 10 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 20 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

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

  12. Have a malignant tumor.

Contacts and Locations

Locations

Japan

Touon-shi, Ehime, Japan

Fukuoka-shi, Fukuoka, Japan

Hiroshima-shi, Hiroshima, Japan

Sapporo-shi, Hokkaido, Japan

Hanamaki-shi, Iwate, Japan

Morioka-shi, Iwate, Japan

Kumamoto-shi, Kumamoto, Japan

Kyoto-shi, Kyoto, Japan

Sendai-shi, Miyagi, Japan

Osaka-shi, Osaka, Japan

Suita-shi, Osaka, Japan

Shinjuku-ku, Tokyo, Japan

Toyama-shi, Toyama, Japan

Sponsors and Collaborators

Takeda

Investigators

• Study Director: Senior Manager; Takeda

More Information

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT02072330
• Other Study ID Numbers: TAK-536TCH/CCT-001; JapicCTI-121962 ( Registry Identifier: Japic CTI )
• First Posted: February 26, 2014
• Last Update Posted: February 26, 2014
• Last Verified: February 2014

Keywords provided by Takeda:

Hypertension, Drug therapy

Additional relevant MeSH terms:

Hypertension; Essential Hypertension; Vascular Diseases; Cardiovascular Diseases; Amlodipine; Hydrochlorothiazide; Azilsartan medoxomil; Antihypertensive Agents; Calcium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Vasodilator Agents; Diuretics; Natriuretic Agents; Sodium Chloride Symporter Inhibitors; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists