PGx7685:Exploratory PGx evaluation of adverse events observed in subjects treated with GSK3342830 in 204847 Part 2

Trial description: GSK3342830 is a novel catechol-cephem antibiotic that is being developed by GlaxoSmithKline (GSK) for the treatment of infections caused by Gram-negative bacteria including multidrug-resistant isolates. Study 204847 is a Phase I, first-time-in-human (FTIH), randomized, double-blind (sponsor un-blinded), single-center, placebo-controlled, dose-escalation study to determine the safety, tolerability, and pharmacokinetic (PK) profile of GSK3342830 after administration of single (Part 1) and repeat (Part 2) intravenous (IV) doses in healthy adult subjects, and a single IV dose in healthy adult Japanese subjects (Part 3).During the conduct of 204847 Part 2 (repeat IV dosing), several subjects treated with GSK3342830 experienced adverse events characterized by headache, neck pain, malaise, and in some instances, fever.The objective of study 207935 is to summarize allele carriage frequencies in Human Leukocyte Antigen (HLA) loci and the COMT V158M variant by the presence or absence of adverse events (headache, neck pain, malaise, fever) in subjects in Study 204847 Part 2 treated with GSK3342830. Descriptive summaries of the genetics data will be produced, including Fisher’s exact test to assess allele carriage frequencies by AE status. This is a descriptive summary and no inferential hypothesis testing will be performed. To provide context, allele carriage frequencies will also be generated pooling subjects in Study 204847 Part 1, regardless of treatment, and Part 2 placebo-treated. An Affymetrix Axiom Genotyping Array in conjunction with the phase 3 haplotype reference panel from the 1000 Genomes Project will be used to impute genetic variants across the genome, including the HLA region. Sequencing based typing will be run concurrently to attempt to generate high resolution (4 digit) HLA genotypes for HLA-A, B, C, DRB1 and DQB1; these data will preferentially be analyzed if available.