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

Condition(s) targeted: Grade I or II Essential Hypertension

Intervention: TAK-536CCB (Drug); TAK-536CCB + Hydrochlorothiazide (Drug); Hydrochlorothiazide (Drug); Hydrochlorothiazide (Drug); TAK-536CCB + Hydrochlorothiazide (Drug)

Phase: Phase 2/Phase 3

Status: Completed

Sponsored by: Takeda

Official(s) and/or principal investigator(s):
Senior Manager, Study Director, Affiliation: Takeda

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.

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 design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

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

Secondary outcome:

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

Proportion of patients achieving < 140/90 mmHg

Proportion of responders (140/90 mmHg criterion)

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

Time profile of office trough sitting diastolic blood pressure

Time profile of office trough sitting systolic blood pressure

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.

Minimum age: 20 Years. Maximum age: N/A. Gender(s): Both.

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.

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

Starting date: March 2013
Last updated: February 24, 2014