A Study to Evaluate the Efficacy and Safety of Amlodipine Besylate and Candesartan Cilexetil in Essential Hypertension Patient Who Are Not Adequately Controlled With Amlodipine Besylate Monotherapy

Study Overview
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Brief Summary
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Compare the safety and efficacy of amlodipine besylate and candesartan cilexetil combination therapy on patients of essential hypertension who are not properly controlled by amlodipine besylate monotherapy.

Official Title
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A Randomized, Double-blind, Multi-center, Phase III Clinical Trial to Evaluate the Antihypertensive Efficacy and Safety of Amlodipine Besylate and Candesartan Cilexetil Combination in Patients With Essential Hypertension Who Are Not Adequately Controlled With Amlodipine Besylate Monotherapy

Conditions
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Essential Hypertension

Intervention / Treatment
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* Drug: Amlodipine 5mg
* Drug: Amlodipine 5mg, Candesartan cilexetil 16mg
* Drug: Amlodipine 10mg, Candesartan cilexetil 16mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged ≥ 19 and ≤ 75 years old Subject with essential hypertension Subject who have voluntarily agreed to participate in the trial and signed the written informed consent form, after having listened to the purpose, method, and effect of the clinical trial Exclusion Criteria: Subject who is siDBP ≥ 120 mmHg or siSBP ≥ 200 mmHg at Visit 1 (screening) Subject with difference in the mean blood pressure of over 10 mmHg for siDBP or 20 mmHg for siSBP between both arms at the screening visit Subject with known or suspected secondary hypertension [Including but not limited to any of the following: renovascular diseases, adrenal medullary and cortical hyperfunctions, coarctation of the aorta, primary hyperaldosteronism, unilateral or bilateral renal artery stenosis, Cushing's syndrome, pheochromo-cytoma, polycystic kidney disease, etc.] Subject with symptomatic orthostatic hypotension(a sudden fall in siDBP of at least 10 mmHg or siSBP of at least 20 mmHg after standing compared with blood pressure from the sitting or supin position) Subject with type 1 or type 2 diabetes mellitus with poor glucose control (defined as subject on inculin treatment, with HbA1c > 9.0% or with a modification in the oral anti-hyperglycemic medication regiment within the past 12 weeks prior to visit 1) Subject with severe heart disease(congestive heart failure(NYHA class 3 or 4), ischemic heart disease within the past 6 months(unstable angina, myocardial infarction), peripheral blood vascula disease, history of Percutaneous Transluminal Coronary Angioplasty or coronary artery bypass grafting) Subject with clinically significant ventricular tachycardia, atrial fibrillation, atrial flutter or other clinically significant arrhythmia Subject with hypertrophic obstructive cardiomyopathy, severe obstructive coronary artery disease, aortic stenosis, haemodynamically relevant stenosis of the aortic or mitral valve Subject with cardiogenic shock Subject with severe cerebrovascular disease (history of stroke, cerebral infraction, or cerebral hemorrhage within the past 6 months) Subject with a history of or ongoing wasting disease, autoimmune diseases(rheumatoid arthritis, systemic lupus erythematosus, etc.) or connective tissue disease Subject with known moderate or malignant retinopathy (history of retinal signs of hemorrhage, visual impairment, retinal microaneurysm etc. within the past 6 months) Subject with any surgical or medical condition of the gastrointestinal tract that might sugnificantly alter the absorption, distribution, metabolism or excretion of the drug Subject with a history of malignant tumors including leukemia and lymphoma within the past 5 yesrs(except for localized basal cell carcinoma of the skin) Subject with any chronic inflammatory condition needing chronic anti-inflammatory therapy Subject with chronic kidney disase on dialysis Subject with the following clinically significant laboratory abnormalities: AST or ALT > 3 x Upper Limit Normal(ULN) Serum Creatinine > 1.5 ULN Serum potassium < 3.5 mmol/L or > 5.5mmol/L Subject requiring concomitant use of other antihypertensive or contraindicated drugs during the entire study period Subject with known or suspected contraindications, including history of allergy or hypersensitivity to ARB or dihydropyridine derivatives Subject who have previously experienced symptoms characteristic of angioedema during treatment with ACE inhibitors or ARB Pregnant women or lactating mother, women suspected of being pregnant, women who wish to be pregnant during the study or women of child-bearing potential who are not using medically acceptable methods of contraception (oral contraceptinve, intra-uterine device, condom, etc.), except for women with surgical sterilization. Pre-menopausal women who are not surgically sterilized must have a negative pregnancy test result at Visit1 and maintain acceptable methods of contraception throughout the study. preiodic abstinence (eg. symptothermal, calendar, post-ovulation methods), or hormonal contraceptive are not acceptable methods of contraception History of drug or alcohol abuse within the past 1 year Use of other investigational products within the past 4 weeks Subject who are jdged unsuitable to participate in the study in the opinion of the investigator

Ages Eligible for Study
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Minimum Age: 19 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AML 5mg<br>- Amlodipine 5mg, once a day for 8 weeks | Drug: Amlodipine 5mg<br>* - Daily oral administration for 8 weeks<br>* Other names: Novarsc 5mg;|
| Experimental: AML 5mg / CC 16mg<br>- Amlodipine 5mg and Candesartan cilexetil 16mg, once a day for 8 weeks | Drug: Amlodipine 5mg, Candesartan cilexetil 16mg<br>* - Daily oral administration Amlodipine 5mg for 8 weeks<br>* Other names: Novarsc 5mg, Atacand 16mg;|
| Experimental: AML 10mg / CC 16mg<br>- After 8 weeks of treatment period, Amlodipine 10mg and Candesartan ceilexetil 16mg, once a day for 8 weeks | Drug: Amlodipine 10mg, Candesartan cilexetil 16mg<br>* - After 8 weeks of administration, Amlodipine 10mg and Candesartan cilexetil 16mg once a day for 8 weeks<br>* Other names: Novarsc 10mg, Atacand 16mg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in sitting Diastolic Blood Pressure (siDBP) at week 8 compared to baseline |  | Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in siDBP at week 4 |  | Week 4 | 
| Change in sitting Systolic Blood Pressure (siSBP) at week 4 and 8 |  | Week 4 and 8 | 
| Proportion of patients achieving ΔsiDBP ≥ 10 mmHg and ΔsiSBP ≥ 20 mmHg after 8 weeks |  | Week 8 | 
| Proportion of patients achieving siDBP < 90 mmHg and siSBP < 140 mmHg after 8 weeks |  | Week 8 |