A Clinical Study to Explore Biomarkers for Drug-induced Liver Injury (DILI)

Study Overview
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Brief Summary
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This study has an open-label, one-sequence, multiple drug administration design. The purpose of this study is as follows; To evaluate the change of liver function according to glutathione s-transferase (GST) genotype after the multiple administration of amoxicillin/clavulanate. To evaluate the intrinsic metabolite, human leukocyte antigen (HLA) genotype, and microRNA (miRNA) based on liver function change as the candidate biomarker for DILI.

Official Title
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A Clinical Study to Evaluate the Effect of Glutathion S-transferase Polymorphism on Pharmacokinetics/Pharmacodynamics After Multiple Administration of Amoxicillin/Clavulanate and Explore Biomarkers for Drug-induced Liver Injury (DILI)

Conditions
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Healthy

Intervention / Treatment
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* Drug: Augmentin tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject with sufficient ability to understand the nature of the study and any hazards of participating in it. Provide written informed consent after being fully informed about the study procedures Healthy male of female subjects aged 20 - 45 years Subjects whose body mass index (BMI) in the range 18.5 kg/m2 (inclusive) - 27 kg/m2 (exclusive) Exclusion Criteria: Subject with clinically significant disease in liver, kidney, nerve system, respiratory system, endocrine system, blood, tumor, urinary system, cardiovascular system, mental disease or with medical history Subject who has taken any prescribed drugs, herbal agents or crude drugs within 2 weeks before study drug administration Subject who did blood donation during 1 months before the study or Blood donation during 2 months before the study Subject with presence or history of severe adverse reaction to study drug Subject who cannot prevent pregnancy during the study period. Female subject who are pregnant. Subject who drank over 21 units/week of alcohol or subjects who would not be able to stop drinking alcohol during the hospitalization Subject who are Heavy smoker more than 10 cigarettes/day within 3 months prior to screening or subjects who would not be able to stop smoking during the hospitalization. Subject judged not eligible for study participation by investigator.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Glutathione S-Transferase Theta1(GSTT1)/Mu1(GSTM1) wild/wild<br>Augmentin tablet | Drug: Augmentin tablet<br> <br> * Other names: Augmentin 3 tablets (Amoxicilin:clavualanate=2:1) bid, for 14days;|
| Active Comparator: GSTT1/GSTM1 wild/null type<br>Augmentin tablet | Drug: Augmentin tablet<br> <br> * Other names: Augmentin 3 tablets (Amoxicilin:clavualanate=2:1) bid, for 14days;|
| Active Comparator: GSTT1/GSTM1 null/wild type<br>Augmentin tablet | Drug: Augmentin tablet<br> <br> * Other names: Augmentin 3 tablets (Amoxicilin:clavualanate=2:1) bid, for 14days;|
| Active Comparator: GSTT1/GSTM1 null/null type<br>Augmentin tablet | Drug: Augmentin tablet<br> <br> * Other names: Augmentin 3 tablets (Amoxicilin:clavualanate=2:1) bid, for 14days;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aspartate Aminotransferase (AST) |  | 22 days | 
| Alanine Aminotransferase (ALT) |  | 22 days | 
| Alkaline phosphatase (ALP) |  | 22 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GST, DILI, biomarker