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

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)

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Augmentin tablet

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Jieon Lee

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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
2. Healthy male of female subjects aged 20 - 45 years
3. Subjects whose body mass index (BMI) in the range 18.5 kg/m2 (inclusive) - 27 kg/m2 (exclusive)

Exclusion Criteria:

1. 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
2. Subject who has taken any prescribed drugs, herbal agents or crude drugs within 2 weeks before study drug administration
3. Subject who did blood donation during 1 months before the study or Blood donation during 2 months before the study
4. Subject with presence or history of severe adverse reaction to study drug
5. Subject who cannot prevent pregnancy during the study period.
6. Female subject who are pregnant.
7. Subject who drank over 21 units/week of alcohol or subjects who would not be able to stop drinking alcohol during the hospitalization
8. 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.
9. Subject judged not eligible for study participation by investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Investigators: Principal Investigator: In-Jin Jang, MD, PhD, Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: January 18, 2014
• First Submitted That Met QC Criteria: May 18, 2014
• First Posted (Estimate): May 21, 2014

Study Record Updates

• Last Update Posted (Estimate): December 23, 2014
• Last Update Submitted That Met QC Criteria: December 22, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: GST, DILI, biomarker
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Digestive System Diseases; Liver Diseases; Drug-Related Side Effects and Adverse Reactions; Poisoning; Chemical and Drug Induced Liver Injury; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Amoxicillin-Potassium Clavulanate Combination
• Other Study ID Numbers: DILI_Healthy