Sample Collection and Analysis to Expand Demographics Diversity of Reference Range for the Final Qualification Package for GLDH Activity as a Biomarker of Drug Induced Liver Injury (DDT-BMQ-000050)

NIH RePORTER · FDA · U01 · $247,269 · view on reporter.nih.gov ↗

Abstract

ABSTRACT This project seeks to increase our understanding of the normal reference range of glutamate dehydrogenase (GLDH) in pediatric, geriatric, and expanded ethnic normal healthy populations, which will address an unmet need in drug development for detecting and monitoring drug-induced liver injury (DILI). The evidence generated by this project is necessary to support the qualification of GLDH by the Food and Drug Administration’s (FDA’s) Biomarker Qualification Program (BQP). This qualification effort is being led by the Predictive Safety Testing Consortium’s Hepatotoxicity Working Group, for which GLDH as a safety biomarker to detect DILI was into the Biomarker Qualification Program. In order to progress to the next stage of qualification, the Hepatotoxicity Working Group must prepare a Final Qualification Package which summarizes the performance of GLDH in the confirmatory studies to support the proposed context of use under consideration by the Biomarker Qualification Program. To date, the Hepatotoxicity Working Group has not defined the normal reference range of GLDH in these populations, nor has it been found in the published literature. To address this gap, the Critical Path Institute (C-Path) proposes the following research aims. Specific Aim 1 will conduct a study to collect samples from healthy individuals spanning additional age groups under-represented in the original studies in 100 normal healthy volunteers (both male and female; 50 pediatric and 50 geriatric), from the United States (US). The study will collect single samples from subjects at the University of Michigan Hospital for routine visits. In addition, Specific Aim 2 is to conduct a study to collect samples from healthy individuals to expand ethnicities under-represented in the original studies, which will support the future submission of a Qualification Plan for DDT# DDTBMQ000050 in order to further the understanding of GLDH in various populations.

Key facts

NIH application ID
10411701
Project number
1U01FD007464-01
Recipient
CRITICAL PATH INSTITUTE
Principal Investigator
Nicholas King
Activity code
U01
Funding institute
FDA
Fiscal year
2021
Award amount
$247,269
Award type
1
Project period
2021-09-01 → 2023-08-31