Bioequivalence Study of Tacrobell Capsule 1mg to Prograf Capsule 1mg

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate bioequivalence between tacrobell capsule 1mg and prograf capsule 1mg.

Detailed Description
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This will be an open label, randomized, single dose, 2-treatment, 2-period crossover study in healthy volunteers.Study treatments will be administered under fasting conditions. Blood samples for the analysis of tacrolimus in blood will be obtained as follows: Predose(immediately prior to dosing), and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours postdose.

Official Title
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An Open Label, Randomized, Single Dose, Crossover Pivotal Bioequivalence Study of Tacrobell Capsule 1mg Versus Prograf Capsule 1mg in Healthy Subjects

Conditions
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Immunosuppression

Intervention / Treatment
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* Drug: Tacrobell capsule 1mg
* Drug: Prograf capsule 1mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed the informed consent from prior to screening test Between 19 years and 55 years in healthy male subject Have not any congenital or chronic disease and medical symptoms Body mass index(BMI) of 18 to 30 and a total body weight ≥ 55kg Appropriate subject for the study judging from investigator Exclusion Criteria: Evidence or history of clinically significant hepatic, renal, neurologic, immune system, respiratory system, endocrine Any condition possibly affecting drug absorption (e.g. gastrectomy) Subject with hypersensitivity to tacrolimus or any excipient Administration of cyclosporin or bosentan Administration of potassium-sparing diuretics Subject with hereditary diseases of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption SBP<90 mmHg or DBP<50 mmHg, SBP>150 mmHg or DBP>100 mmHg at least 3 minutes of rest A positive HBsAg, HCV Ab, HIV Ab, RPR AST, ALT > 1.5*upper limit of normal range at the screening test Subject with a history of drug abuse or a positive reaction for drug abuse at the screening test Taking ETC medicine including oriental medicine within 14days before the first hospitalization or taking OTC medicine, vitamin within 7days Use of any drugs known to significantly induce or inhibit drug-metabolizing enzymes within 30 days prior to initiation test Participating in a bioequivalence study or other clinical study within 3 month preceding the first hospitalization Blood donation or more within 2 month or component blood donation within 1 month prior to the first hospitalization Continued to be drinking(alcohol> 21 units/week, 1 unit=10g of pure alcohol) or during clinical trials can not be drunk Severe heavy smoker(cigarette> 10 cigarettes/day) during 3 months or can not be smoking during the clinical study Continued to be taking caffeine or can not be taken caffeine Continued to be taking grapefruit or can not be taken grapefruit Not use of contraception during the clinical study An impossible one who participates in the clinical trial by investigator's decision including for reason of laboratory test result

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 55 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: Tacrobell capsule 1mg<br>Tacrolimus 1mg / 1 capsule | Drug: Tacrobell capsule 1mg<br>* 1 capsule, oral, over the period I&II(crossover)<br>|
| Active Comparator: Prograf capsule 1mg<br>Tacrolimus 1mg / 1 capsule | Drug: Prograf capsule 1mg<br>* 1 capsule, oral, 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 |
| --- | --- | --- |
| AUClast | AUClast: Area under the blood concentration-time profile from time zero to the time of the last quantifiable concentration | At pre-dose (immediately prior to dosing) and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours postdese | 
| Cmax | Cmax: Maximum blood concentration | At pre-dose (immediately prior to dosing) and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours postdese | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUCinf | ACUinf: Area under the blood concentration-time profile from time zero extrapolated to infinite time | At pre-dose (immediately prior to dosing) and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours postdose | 
| Tmax | Tmax: Time for Cmax | At pre-dose (immediately prior to dosing) and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours postdose | 
| T1/2 | T1/2: Terminal elimination half-life | At pre-dose (immediately prior to dosing) and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours postdose | 
| CL/F | CL/F: Apparent Clearance | At pre-dose (immediately prior to dosing) and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours postdose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tacrolimus, tacrobell capsule, prograf capsule, bioequivalence