Efficacy and Safety of Carvedilol SR Versus Carvedilol IR in Patients With Essential Hypertension

Study Overview
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Brief Summary
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The aim of present study is to evaluate the efficacy and safety of Carvedilol SR versus Carvedilol IR in Patients With Essential Hypertension

Detailed Description
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In patients with Essential hypertension to evaluate the efficacy and safety of Carvedilol SR (32mg, 64mg) or Carvedilol IR (25mg QD, 25mg BID) during 8 weeks. This study is consist of placebo run-in period(2 4 weeks_single blind) and treatment period(8 weeks_double blind).

Official Title
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A Randomized, Double-blind, Multi-center, Phase 3 Trial to Evaluate the Efficacy and Safety of Carvedilol SR Versus Carvedilol IR in Patients With Essential Hypertension

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Carvedilol SR 32mg, QD
* Drug: Carvedilol SR 64mg, QD
* Drug: Carvedilol IR 25mg, QD
* Drug: Carvedilol IR 25mg, BID


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 18 years or older at the screening visit(visit 1) antihypertensive drugs not taking: 90mmHg ≤ mean sitDBP ≤ 109mmHg and mean sitSBP < 180mmHg antihypertensive drugs taking: mean sitDBP ≤ 104mmHg and mean sitSBP < 180mmHg at the randomization visit(visit 2): 90mmHg ≤ mean sitDBP ≤ 109mmHg and mean sitSBP < 180mmHg willing and able to provide written informed consent Exclusion Criteria: At Screening, difference in measured blood pressure of the selected arm(sitDBP ≥ 10mmHg or sitSBP ≥ 20mmHg) known or suspected secondary hypertension(ex. aortic coarctation, Primary hyperaldosteronism, renal artery stenosis, pheochromocytoma) Type I Diabetes Mellitus, Type II Diabetes Mellitus with poor glucose control as defined by fasting glucosylated hemoglobin(HbA1c > 9%) Corresponding to the following has severe heart disease(Heart failure NYHA functional class 3, 4) ischaemic heart diseases within 6 months (unstable angina or myocardial infarction) myocardiopathy Cor pulmonale aortic stenosis , aortic valvular stenosis , mitral stenosis abnormality of the conduction system as 2nd degree AV block, Complete AV block, Sick Sinus Syndrome, Sinus Block(In particular, pulse <50beats / min) has heart attack with complication. has cerebrovascular disease as cerebral infarction, cerebral hemorrhage within 6 months has edema glottitis, allergic rhinitis, Respiratory diseases as Asthma, Chronic Obstructive Pulmonary Disease. Peripheral circulatory disturbance( ex. Raynaud syndrome, intermittent claudication) Fluid retention or overload to required intravenous inotropes. known severe or malignant retinopathy(retinal hemorrhage, visual disturbance, Retinal microaneurysms and so on within 6 months) defined by the following laboratory parameters: hepatic dysfunction(AST/ALT ≥ UNL X 3) renal dysfunction(serum creatinine ≥ UNL X 2) any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of investigational products(ex. gastrointestinal tract surgery such as gastrectomy, gastroenterostomy or bypass, active inflammatory bowel syndrome within 12 months prior to screening, gastric ulcers need to treatment, gastrointestinal/rectal bleeding, impaired pancreatic function such as pancreatitis, obstructions of the urinary tract or difficulty in voiding) history of drug or alcohol dependency within 6 months premenopausal women(last menstruation < 12 months) not using adequate contraception, pregnant or breast-feeding chronic inflammatory status need to treatment known hypersensitivity related to carvedilol history of malignancy including leukemia and lymphoma within the past 5 years administration of other study drugs within 28 days prior to the first IP administration in investigator's judgment

Ages Eligible for Study
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Minimum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Carvedilol SR 32mg, 64mg<br>•Carvedilol SR 32mg QD for first 4 weeks and Carvedilol SR 64mg QD for following 4 weeks. | Drug: Carvedilol SR 32mg, QD<br>* Carvedilol SR 32mg QD for 4 weeks With the others investigation product placebo 1 capsule QD and 1 tablet BID for 4 weeks.<br>* Other names: Dilatrend SR;Drug: Carvedilol SR 64mg, QD<br>* Carvedilol SR 64mg QD for 4 weeks With the others investigation product placebo 1 capsule QD and 1 tablet BID for 4 weeks.<br>* Other names: Dilatrend SR;|
| Active Comparator: Carvedilol IR 25mg<br>•Carvedilol IR 25mg QD for first 4 weeks and Carvedilol IR 25mg BID for following 4 weeks. | Drug: Carvedilol IR 25mg, QD<br>* Carvedilol IR 25mg QD for 4 weeks With the others investigation product placebo 2 capsules and 1 tablet QD for 4 weeks.<br>* Other names: Dilatrend IR;Drug: Carvedilol IR 25mg, BID<br>* Carvedilol IR 25mg BID for 4 weeks With the others investigation product placebo 2 capsules QD for 4 weeks.<br>* Other names: Dilatrend IR;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Sitting Diastolic Blood Pressure (MSDBP) |  | After 4 and 8 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Sitting systolic Blood Pressure (MSSBP) |  | After 4 weeks and 8 weeks of treatment | 
| Control Rate | Sitting DBP<90mmHg, Sitting SBP<140mmHg | After 8 weeks of treatment | 
| Response Rate | Reduction of Sitting DBP≥10mmHg, Sitting SBP ≥20mmHg | After 8 weeks of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Carvedilol SR, Carvedilol IR, Hypertension, Essential Hypertension