Study to Compare the Pharmacokinetic Characteristics and Safety of Dilatrend SR Capsule 32mg and Dilatrend Tablet 25mg

Study Overview
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Brief Summary
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The purpose of this study is to compare the pharmacokinetic characteristics and safety of dilatrend SR capsule 32mg and Dilatrend tablet 25mg in healthy male subjects.

Detailed Description
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Healthy male subjects are administrated multiple-dose over the period I and II (Crossover) of dilatrend SR capsule 32mg and dilatrend tablet 25mg.

Official Title
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A Randomized, Open-label, Multiple-dose, Crossover Phase I Study to Compare the Pharmacokinetic Characteristics and Safety of Dilatrend SR Capsule 32 mg and Dilatrend Tablet 25 mg in Healthy Male Subjects

Conditions
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Essential Hypertension, Chronic Stable Angina, Congestive Heart Failure

Intervention / Treatment
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* Drug: Dilatrend SR capsule 32mg
* Drug: Dilatrend IR tablet 25mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Between 20 aged and 35aged in healthy male Body Weight more than 50kg, and within 20% of ideal body weight(IBW). IBW(kg) = {height(cm)-100}*0.9 Have not any congenital or chronic disease and medical symptoms. Suitable results of inspections(laboratory test, ECG, etc) within 21 days before IP administration. Agreement with written informed consent Exclusion Criteria: Subject has hypersensitivity reaction or clinically significant history about carvedilol or investigator drug. Clinically significant cardiovascular system, respiratory system, liver, kidney, endocrine system, gastrointestinal system, central nervous system, blood tumor, mental disease, skin disease, otorhinolaryngologic diseases and so on. Hypotension(SBP < 105mmHg or DBP < 65mmHg), Hypertension(SBP > 150mmHg or DBP > 100mmHg) Heart rate < 50times/minute Active liver disease or AST, ALT > 1.5*upper limit of normal range Creatinine clearance < 80mL/min Subject has a disease affecting drug's ADME or gastrointestinal surgery. Subject with symptoms of injured or acute disease within 28days before the first IP administration. Subject has a history of drug abuse or a positive reaction for drug abuse at the screening test for urine. Taking ETC medicine including oriental medicine within 14days before the first IP administration or Taking OTC medicine within 7days Subject takes an abnormal meal which affect the ADME of drug. Previously participate in other trial within 90days. Previously make whole blood donation within 60days or component blood donation within 30days before the first IP administration. Continued to be taking caffeine(caffeine > 5cup/day), drinking(alcohol > 21unit/week, 1unit = 10g = 12.5mL of pure alcohol) or during clinical trials can not be drunk or severe heavy smoker(cigarette > 10cigarettes/day). Subject with positive reaction about serum test(HBsAg, HCV Ab, HIV Ag/Ab, VDRL) Genetic problems such as galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption. An impossible one who participates in clinical trial by investigator's decision including for reason of laboratory test result.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dilatrend SR capsule 32mg<br> | Drug: Dilatrend SR capsule 32mg<br>* 1 capsule, oral, once daily, 7days over the period I&II(crossover)<br>|
| Active Comparator: Dilatrend IR tablet 25mg<br> | Drug: Dilatrend IR tablet 25mg<br>* 1 tablet, oral, once daily, 7days over the period I&II(crossover)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In the steady state Dilatrend SR Capsule 32mg and Dilatrend tablet 25mg AUCtau | AUCtau: Area under the plasma concentration-time curve for each dosing interval (from time 0 to 48 hours sample) determined using the linear trapezoidal rule | 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48hr post-dose (on last day of each period) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In the steady state Dilatrend SR Capsule 32mg and Dilatrend tablet 25mg AUCinf | AUCinf: Area Under the Concentration time curve with the last concentration extrapolated based on the elimination rate constant Kel | 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48hr post-dose (on last day of each period) | 
| In the steady state Dilatrend SR Capsule 32mg and Dilatrend tablet 25mg Css,max | Css,max : Maximum drug concentration in plasma determined directly from individual concentration-time data | 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48hr post-dose (on last day of each period) | 
| In the steady state Dilatrend SR Capsule 32mg and Dilatrend tablet 25mg Css,min | Css,min : Minimum drug concentration in plasma determined directly from individual concentration-time data | 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48hr post-dose (on last day of each period) | 
| In the steady state Dilatrend SR Capsule 32mg and Dilatrend tablet 25mg Tss,max | Tss,max : Time to reach maximum drug concentration in plasma calculated from [plasma] versus time profiles | 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48hr post-dose (on last day of each period) | 
| In the steady state Dilatrend SR Capsule 32mg and Dilatrend tablet 25mg t½ | t½ : Observed terminal elimination half-life | 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48hr post-dose (on last day of each period) | 
| Number of participants with adverse events | Evaluated safety parameters included: physical examination, vital sign, laboratory test, ECG adverse event monitoring | From 1day to 37 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Carvedilol, Dilatrend SR capsule, Dilatrend Tablet, Pharmacokinetics, Healthy male subjects