Comparison of Efficacy and Safety of Combination Therapy and Monotherapy of Candesartan and Amlodipine for Dose-Finding in Patients With Essential Hypertension

Study Overview
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Brief Summary
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The purpose of this study is to explore the optimal dose of fixed-dose combination of candesartan cilexetil and amlodipine besylate by examining the safety and efficacy of the combination therapy compared to each of the monotherapy in patients with essential hypertension.

Official Title
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A Multi-center, Randomized, Double-blind, Phase II Clinical Trial to Evaluate the Efficacy and Safety of Combination Therapy vs. Monotherapy of Candesartan and Amlodipine for Dose-Finding in Patients With Essential Hypertension

Conditions
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Essential Hypertension

Intervention / Treatment
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* Drug: Candesartan Cilexetil 8mg
* Drug: Candesartan Cilexetil 16mg
* Drug: Amlodipine 5mg
* Drug: Amlodipine 10mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients greater than or equal to 19 years of age Subject who was diagnosed with essential hypertension or after administer the antihypertensive drug (Subject who may temporarily suspend antihypertensive treatment based on doctor's decision) Subject who have voluntarily agreed to participate in the trial and signed the written informed consent form Exclusion Criteria: Subject with severe hypertension (in a selected arm with msSBP ≥ 200 mmHg or msDBP ≥ 115 mmHg) during the Screening and Randomized Trial. Subject with difference of the blood pressure of over 20 mmHg for SBP or 10 mmHg for diastolic blood pressure (DSP) between three consecutive measurements in a selected arm during the screening visit Secondary hypertension (such as, coarctation of the aorta, primary hyperaldosteronism, renal artery stenosis, Cushing's disease, pheochromocytoma, polycystic kidney disease, etc.) Symptomatic orthostatic hypotension Severe heart failure( New York Heart Association(NYHA) Class III/IV) Subject with acute coronary syndrome(myocardial infarction or unstable angina), peripheral vascular disease within the past 6 months History of switching to another Antiarrhythmic drugs(not including electrolyte correction), or received Cardioversion or ICU treatment within the past 6 months Type 1 diabetes mellitus or Uncontrolled Type 2 diabetes mellitus (HbA1c > 9.0%) Subject with Haemodynamic disturbance, heart valve disease with structural defects Severe cerebrovascular disease (stroke, cerebral infarction, or cerebral hemorrhage, etc. within the past 6 months) Severe eye disease (retinal hemorrhage, visual impairment, retinal microaneurysm, etc. within the past 6 months) Autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, etc.) Chronic inflammatory disease requiring continuous anti-inflammatory treatment Clinically significant Renal or liver impairment, or laboratory abnormalities such as Ccr: below 30ml/min or Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) > 3 x Upper Limit Normal (ULN) Hypokalaemia(Serum potassium < 3.5 mmol/L) or hyperkalaemia(Serum potassium > 5.5 mmol/L) Subject with gastrointestinal disease(such as Crohn's disease, gastric ulcer, acute or chronic pancreatitis) or history of gastrointestinal surgery(not including appendectomy or hernia surgery) that might significantly alter the absorption of the drug history of allergy or hypersensitivity to Angiotensin II Receptor Blockers(Candesartan) or Calcium Channel Blocker(amlodipine) Subject with heredity defects such as galactose intolerance, Lapp lactose deficiency, or glucose-galactose malabsorption Subject requiring concomitant use of other antihypertensive or contraindicated drugs( Tizanidine, dolasetron, Itraconazole, potassium, potassium-sparing diuretics, etc.) during the clinical trial history of malignant tumors within the past 5 years history of alcohol or drug abuse Pregnant women and lactating mothers Women who is planning to be pregnant during or 2 months after the study, or women or men who are not using medically acceptable methods of contraception * * progestin oral or implant contraceptive, intra-uterine device, condom, partner with surgical sterilization, etc. Use of other investigational products within the past 1 month Subject who are judged by the investigator unsuitable to participate in the study

Ages Eligible for Study
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Minimum Age: 19 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: Candesartan Cilexetil (CC) 8mg<br>Candesartan Cilexetil 8mg, once a day for 8 weeks | Drug: Candesartan Cilexetil 8mg<br>* Candesartan Cilexetil 8mg Daily oral administration for 8 weeks<br>* Other names: Atacand 8mg;|
| Experimental: CC 16mg<br>Candesartan Cilexetil 16mg, once a day for 8 weeks | Drug: Candesartan Cilexetil 16mg<br>* Candesartan Cilexetil 16mg Daily oral administration for 8 weeks<br>* Other names: Atacand 16mg;|
| Experimental: Amlodipine(AML) 5mg<br>Amlodipine 5mg, once a day for 8 weeks | Drug: Amlodipine 5mg<br>* Amlodipine 5mg Daily oral administration for 8 weeks<br>* Other names: Norvasc 5mg;|
| Experimental: AML 10mg<br>Amlodipine 10mg, once a day for 8 weeks | Drug: Amlodipine 10mg<br>* Amlodipine 10mg Daily oral administration for 8 weeks<br>* Other names: Norvasc 10mg;|
| Experimental: CC 8mg / AML 5mg<br>Candesartan 8mg and Amlodipine 5mg, once a day for 8 weeks | Drug: Candesartan Cilexetil 8mg<br>* Candesartan Cilexetil 8mg Daily oral administration for 8 weeks<br>* Other names: Atacand 8mg;Drug: Amlodipine 5mg<br>* Amlodipine 5mg Daily oral administration for 8 weeks<br>* Other names: Norvasc 5mg;|
| Experimental: CC 8mg / AML 10mg<br>Candesartan 8mg and Amlodipine 10mg, once a day for 8 weeks | Drug: Candesartan Cilexetil 8mg<br>* Candesartan Cilexetil 8mg Daily oral administration for 8 weeks<br>* Other names: Atacand 8mg;Drug: Amlodipine 10mg<br>* Amlodipine 10mg Daily oral administration for 8 weeks<br>* Other names: Norvasc 10mg;|
| Experimental: CC 16mg / AML 5mg<br>Candesartan 16mg and Amlodipine 5mg, once a day for 8 weeks | Drug: Candesartan Cilexetil 16mg<br>* Candesartan Cilexetil 16mg Daily oral administration for 8 weeks<br>* Other names: Atacand 16mg;Drug: Amlodipine 5mg<br>* Amlodipine 5mg Daily oral administration for 8 weeks<br>* Other names: Norvasc 5mg;|
| Experimental: CC 16mg / AML 10mg<br>Candesartan 16mg and Amlodipine 10mg, once a day for 8 weeks | Drug: Candesartan Cilexetil 16mg<br>* Candesartan Cilexetil 16mg Daily oral administration for 8 weeks<br>* Other names: Atacand 16mg;Drug: Amlodipine 10mg<br>* Amlodipine 10mg Daily oral administration for 8 weeks<br>* Other names: Norvasc 10mg;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change mean sitting Diastolic Blood Pressure (msDBP) at week 4 compared to baseline |  | Week 4 | 
| Change mean sitting Systolic Blood Pressure (msSBP) at week 4 and 8 compared to baseline |  | Week 4 and 8 | 
| Proportion of patients achieving treatment goal at week 4 and 8: < 140/90 mmHg | Joint National Committee VII Guideline Treatment goal: < 140/90 mmHg (< 130/80 mmHg, diabetic or chronic renal failure patient) | Week 4 and 8 | 
| Blood Pressure Response rate at week 4 and 8: msSBP reduction ≥ 20 mmHg and msDBP reduction ≥ 10 mmHg |  | Week 4 and 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Candesartan, Amlodipine, Hypertension, Vascular Diseases, Cardiovascular Diseases, Antihypertensive Agents, Vasodilator Agents, Angiotensin II Type 1 Receptor Blockers, Angiotensin Receptor Antagonists, Calcium Channel Blockers