A Pharamcogenomic Study for Isoniazid According to NAT2 Polymorphism Status

Clinical Trial to Investigate the Appropriate Dose of Isoniazid According to NAT2 Polymorphism Status in Korean Subjects

A clinical trial to investigate the appropriate dose of isoniazid according to NAT2 polymorphism status in Korean subjects

Study Overview

• Status: Completed
• Conditions: Tuberculosis; Drug-Induced Liver Injury; Adverse Drug Event
• Intervention / Treatment: Drug: Isoniazid

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Hospital Clinical Trials Center

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:

• Agreement with written informed consent
• Adult healthy male or female subject age 20 to 45

Exclusion Criteria:

• Clinically significant, active gastrointestinal system, cardiovascular system, pulmonary system, renal system, endocrine system, blood system, digestive system, central nervous system, mental disease or malignancy
• Medication with any drug which may affect the pharmacokinetics of isoniazid within 14 days
• Previously donate whole blood within 30 days or Previously participated in other trial within 60 days
• Subject with known for hypersensitivity reactions to isoniazid
• Subject who can not perform contraception during study periods
• Female woman who are pregnant or are breast feeding
• An impossible one who participates in clinical trial by investigator's decision including laboratory test result

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Rapid metabolizer (Standard treatment); Standard isoniazid dose regimen (300 mg qd)	Drug: Isoniazid; One of the first line anti-tubercolosis drug
Active Comparator: Slow metabolizer (Standard treatment); Standard isoniazid dose regimen (300 mg qd)	Drug: Isoniazid; One of the first line anti-tubercolosis drug
Experimental: Slow metabolizer (PGx treatment); Decreased isoniazid dose regimen (200 mg qd)	Drug: Isoniazid; One of the first line anti-tubercolosis drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liver toxicity	Number of participants with drug-induced liver injury as assessed by below criteria.; AST or ALT > 5 ULN; AST or ALT > 3 ULN and total bilirubin > 2 ULN (Hy's law case); ALT ratio/ALP ratio > 5	up to 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Drug exposure	Plasma isoniazid concentration	Day 1 and day 29 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 post-dose

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Collaborators: Ministry of Health & Welfare, Korea

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2018
• Primary Completion (Actual): December 31, 2018
• Study Completion (Actual): March 31, 2019

Study Registration Dates

• First Submitted: August 21, 2018
• First Submitted That Met QC Criteria: September 7, 2018
• First Posted (Actual): September 11, 2018

Study Record Updates

• Last Update Posted (Actual): February 28, 2020
• Last Update Submitted That Met QC Criteria: February 26, 2020
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Digestive System Diseases; Infections; Liver Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Poisoning; Tuberculosis; Drug-Related Side Effects and Adverse Reactions; Chemical and Drug Induced Liver Injury; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; Anti-Bacterial Agents; Antitubercular Agents; Fatty Acid Synthesis Inhibitors; Isoniazid
• Other Study ID Numbers: INH NAT2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No