Dose Selection for Phase III Clinical Evaluation of Gepotidacin (GSK2140944) in the Treatment of Uncomplicated Urinary Tract Infections

Antibiotics are the current standard-of-care treatment for uncomplicated urinary tract infections (uUTIs). However, increasing rates of bacterial antibiotic resistance necessitate novel therapeutic options. Gepotidacin is a first-in-class triazaacenaphthylene antibiotic that selectively inhibits bac...

Full description

Saved in:
Bibliographic Details
Published in:Antimicrobial agents and chemotherapy 2022-03, Vol.66 (3), p.e0149221
Main Authors: Scangarella-Oman, Nicole E, Hossain, Mohammad, Hoover, Jennifer L, Perry, Caroline R, Tiffany, Courtney, Barth, Aline, Dumont, Etienne F
Format: Article
Language:English
Subjects:
Acenaphthenes - pharmacology
Adolescent
Animals
Anti-Bacterial Agents - pharmacology
Antimicrobial Chemotherapy
Clinical Trials, Phase III as Topic
Editor's Pick
Female
Heterocyclic Compounds, 3-Ring - pharmacology
Humans
Microbial Sensitivity Tests
Minireview
Multicenter Studies as Topic
Randomized Controlled Trials as Topic
Urinary Tract Infections - drug therapy
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Antibiotics are the current standard-of-care treatment for uncomplicated urinary tract infections (uUTIs). However, increasing rates of bacterial antibiotic resistance necessitate novel therapeutic options. Gepotidacin is a first-in-class triazaacenaphthylene antibiotic that selectively inhibits bacterial DNA replication by interaction with the bacterial subunits of DNA gyrase (GyrA) and topoisomerase IV (ParC). Gepotidacin is currently in clinical development for the treatment of uUTIs and other infections. In this article, we review data for gepotidacin from nonclinical studies, including activity, animal efficacy, and pharmacokinetic (PK) and pharmacokinetic/pharmacodynamic (PK/PD) models that informed dose selection for phase III clinical evaluation of gepotidacin. Based on this translational package of data, a gepotidacin 1,500-mg oral dose twice daily for 5 days was selected for two ongoing, randomized, multicenter, parallel-group, double-blind, double-dummy, active-comparator phase III clinical studies evaluating the safety and efficacy of gepotidacin in adolescent and adult female participants with uUTIs (ClinicalTrials.gov identifiers NCT04020341 and NCT04187144).
ISSN:0066-4804
1098-6596
1098-6596
DOI:10.1128/aac.01492-21