Antihypertensive Efficacy and Tolerability and Determine the Adequate Antihypertensive Dosage of Fimasartan in Mild to Moderate Essential Hypertension Patients

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the antihypertensive efficacy and tolerability of 8 week treatment with Fimasartan (BR-A-657-K) 20, 60, 120, 240 mg and placebo in patients with mild to moderate essential hypertension and to determine the adequate antihypertensive dosage for later clinical study.

Detailed Description
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Fimasartan (BR-A-657-K), a selective blocker of AT1 receptor subtype, showed the rapid and potent antihypertensive effect in many hypertensive models. Phase I study, Fimasartan (BR-A-657-K) 20mg   480mg single dosing with healthy subjects, demonstrated that the Fimasartan (BR-A-657-K) was very safe and well tolerated. Another phase I study, Fimasartan (BR-A-657-K) 120mg and 360mg dosing for 7 days, also showed that Fimasartan (BR-A-657-K) was safe and tolerable though one temporal adverse event was observed in high dose. A randomized, double-blind, placebo-controlled, parallel grouped, clinical study will be conducted to evaluate the antihypertensive efficacy and tolerability and to determine adequate antihypertensive dosage of Fimasartan(BR-A-657-K) in patients with mild to moderate essential hypertension. Approximately 182 patients will be enrolled over 12 months in 8 centers nationwide. After 2 weeks of placebo run-in period, all subjects will be randomized into one of the following 5 groups. Subjects will take test/control drug for 8 weeks of treatment period. If subjects take any antihypertensive medications before screening, the subjects will have 1 week of wash-out period. Group I : Placebo, Group II : Fimasartan 20 mg, Group III: Fimasartan 60 mg, Group IV : Fimasartan 120 mg, Group V : Fimasartan 240 mg,

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Parallel Grouped, Clinical Study to Evaluate the Antihypertensive Efficacy and Tolerability and to Determine the Adequate Antihypertensive Dosage of Fimasartan(BR-A-657-K) in Patients With Mild to Moderate Essential Hypertension

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Fimasartan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Mild to moderate essential hypertension : sitting diastolic blood pressure measured at Screening and Baseline(Day1) are 95 114 mmHg inclusive and the difference between sitting diastolic blood pressures measured at Day -14 and Baseline(Day1) is under 7mmHg. Subjects who agree to participate in this sudy and give written informed consent Subjects considered to understand the study, be cooperative, and able to be followed-up until the end of the study Exclusion Criteria: The sitting DBP is less than 94mmHg or more than 115mmHg or severe hypertensive patient with sitting systolic blood pressure over 200mmHg Patients with secondary hypertension Patients with severe renal(Creatinine more 1.5 times than upper limit of normal), gastrointestinal, hematological or hepatic(AST, ALT more 2 twice more than upper limit of normal)disease etc. which might affect absorption, disposition, metabolism or excretion of the drug Patients with postural hypotension Patients with sever insulin dependent diabetes mellitus or uncontrolled diabetes mellitus(HbA1c>9%, regimen change of oral hypoglycemic agents within 3 months, treated insulin before screening) Patients with a history of myocardial infarction, severe coronary artery disease or clinically significant heart failure or valvular defect in last 6 months Patients with consumptive disease, autoimmune disease, connective tissue disease Patients with a history of type B or C hepatitis Patients with HIV or hepatitis Patients with clinically significant laboratory abnormality Patients receiving any drugs known to affect blood pressure or medical treatments that can influence the blood pressure Patients with allergy or contraindication to any angiotensin II receptor antagonists Female of childbearing potential who does not undergo hysterectomy or is not post-menopausal Patients judged to have a history of alcohol or drug abuse by the investigator Patients with average weight > +35% or <-15% in Modified Metropolitan Life Insurance table Patients participated other clinical trial 3 months before Screening Patients judged to be inappropriate for this study by the investigator with other reasons

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>3 tablets of placebo will be taken 30minutes after breakfast for 8 weeks | Drug: Fimasartan<br> <br> |
| Active Comparator: Fimasartan 20mg<br>2 tablets of placebo and 1 tablets of fimasartan 20mg will be taken 30minutes after breakfast for 8 weeks | Drug: Fimasartan<br> <br> |
| Active Comparator: Fimasartan 60mg<br>3 tablets of fimasartan 20mg will be taken 30minutes after breakfast for 8 weeks | Drug: Fimasartan<br> <br> |
| Active Comparator: Fimasartan 120mg<br>3 tablets of fimasartan 40mg will be taken 30minutes after breakfast | Drug: Fimasartan<br> <br> |
| Active Comparator: Fimasartan 240mg<br>3 tablets of fimasartan 80mg will be taken 30minutes after breakfast for 8 weeks | Drug: Fimasartan<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change from baseline to end of 8 week treatment in sitting diastolic blood pressure |  | 8 week from baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change from baseline to end of 2,4 week treatment in sitting diastolic blood pressure |  | 2, 4 week from baseline | 
| change from baseline to end of 2,4,8 week treatment in sitting systolic blood pressure |  | 2,4,8 week from baseline | 
| responders after end of 8 week treatment(portion of DBP<90mmHg or the difference from baseline and end of 8 week treatment>10mmHg |  | 8 week from baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension, Fimasartan