Fimasartan/Amlodipine Combination Phase III

Study Overview
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Brief Summary
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The aim of this study is to ensure the superiority of Fimasartan/Amlodipine combination in hypotensive effect after 8 weeks of treatment over Fimasartan monotherapy in patients with hypertension who have no response to Fimasartan 60mg monotherapy.

Official Title
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A Randomized, Double-blind Multicenter, Phase III Study to Evaluate the Efficacy and Safety of Combination of Fimasartan/Amlodipine Versus Fimasartan Monotherapy in Patients With Essential Hypertension Who Fail to Respond Adequately to Fimasartan Monotherapy.

Conditions
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Essential Hypertension

Intervention / Treatment
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* Drug: Fimasartan and Amlodipine
* Drug: Fimasartan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who voluntarily signed informed consent for participating in this clinical trial Male and Female between 20 and 75 years old Patients with essential hypertension Patients who is unresponsive to Fimasartan 60mg monotherapy for 4 weeks (i.e. the mean SiDBP from 3 times of measurement is 140mmHg ≤ SiSBP <180 mmHg) Understand the trial procedures and be willing to cooperate and complete the trial. Exclusion Criteria: Severe Hypertension patients (SiDBP ≥ 110mmHg and/or SiSBP ≥ 180mmHg) Subjects with the difference between blood pressures from a selected arm, SiDBP ≥10 mmHg or SiSBP ≥20 mmHg, at screening assessment Secondary hypertension patients, but not limited to the following disease;(example: renovascular disease, adrenal medullary and cortical hyperfunctions, coarctation of the aorta, hyperaldosteronism, unilateral or bilateral renal artery stenosis, Cushing's syndrome, pheochromo-cytoma, polycystic kidney disease, etc.) Clinically significant renal function abnormality in the laboratory results at screening (i.e. serum creatine ≥ 1.5 times upper normal limit (UNL)), liver function abnormality (ALT, AST ≥ 2 times upper normal limit (UNL)), severe fatty liver disease that requires medication Clinically significant Hypokalemia(Less than 3.5mmol/L), Hyperkalemia(exceeded 5.5mmol/L) Subjects with following surgical and internal disease that may affect absorption, distribution, metabolism or excretion of drugs and have conditions which include the following (but are not limited to): history of major gastrointestinal surgeries including gastrectomy, gastro-enterostomy or bowel resection, gastrointestinal bypass graft and stapling; current active gastritis, ulcer, gastrointestinal and rectal bleeding, presence of active inflammatory bowel syndrome within the past 12 months; or clinically significant urinary obstruction at discretion of investigator Subjects with depletion of body fluid or sodium ion not able to correct Subjects with severe insulin-dependent Diabetes Mellitus (DM) or chronic DM (HbA1c>9%, dosage of an oral hypoglycemic agent was modified within the past 12 weeks, or use of active insulin treatment at screening) Subjects with severe heart disease (heart failure New York Heart Association(NYHA) Class III and IV), or history of any of the followings within the past 6 months; ischemic heart disease(e.g. angina pectoris, myocardial infarction), peripheral vascular disease, percutaneous transluminal coronary angioplasty, or coronary artery bypass graft. Subjects with clinically significant ventricular tachycardia, atrial fibrillation, atrial flutter or any other clinical significant arrhythmia conditions at discretion of investigator. Subjects with hypertrophic obstructive cardiomyopathy, severe obstructive coronary artery disease, aortic stenosis, hemodynamically significant aortic valve stenosis, or mitral valve stenosis. Subjects with severe cerebrovascular disorder (e.g. stroke, cerebral infarction or cerebral hemorrhage within the past 6 months). Subjects with chronic inflammatory disease requiring an chronic anti-inflammatory therapy, Past or current medical history with wasting disease, autoimmune diseases (e.g. rheumatoid arthritis, systemic lupus erythematosus ) or connective tissue disease. Subjects with known moderate or malignant retinosis (e.g. retinal hemorrhage, visual disturbance or retinal microaneurysm in the past 6 months). Subjects with hepatitis B (including positive test for HBsAg), hepatitis C-positive. Subjects with history or evidence of abusing drugs or alcohol within the past 2 years. Medical history with hypersensitivity to angiotensin II antagonist-based drugs or calcium-channel blockers Subjects with hereditary disorders of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption Pregnant women and lactating female Women of childbearing potential who are not using effective contraceptive methods. (Excluding subjects who had surgically sterilized. All women of childbearing potential who did not have surgical sterilization must prove negative in a pregnancy test, and continue to use accepted and effective contraceptive methods until the end of the study in order to participate. Not accepted contraceptive method: Periodic abstinence and celibacy (e.g. Basic body temperature method, menstrual cycle calculation), hormonal contraceptives. Subject who is participating in another trial or took other investigational product within12 weeks from the screening visit Medical history of all kinds of malignant tumor including leukemia and lymphoma in the past 5 years A subject with other reasons not specified above that, ineligible to participate in this clinical trial at discretion of study investigators.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fimasartan and Amlodipine<br>Combination of Fimasartan and Amlodipine | Drug: Fimasartan and Amlodipine<br> <br> |
| Active Comparator: Fimasartan<br>Fimasartan Monotherapy | Drug: Fimasartan<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Sitting Systolic Blood Pressure(SiSBP) at week 8 of Investigational Product(IP) Administration from the Baseline | To compare the difference of Mean Systolic Blood Pressure at 8 weeks from baseline visit | 8 weeks from Baseline Visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Sitting Systolic Blood Pressure(SiSBP) at week 4 of Investigational Product(IP) Administration from the Baseline |  | 4 weeks from Baseline Visit | 
| Changes of Sitting Diastolic Blood Pressure(SiDBP) at week 4 and 8 of Investigational Product(IP) Administration from the Baseline |  | 4 and 8 weeks from Baseline Visit | 
| Response rate of the Blood Pressure at week 8 of Investigational Product(IP) Administration |  | 8 weeks from Baseline Visit | 
| The Normalization ratio of Blood Pressure at week 8 of Investigational Product(IP) Administration |  | 8 weeks from Baseline Visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fimasartan, Fimasartan and Amlodipine, Antihypertension