About this item:

542 Views | 456 Downloads

Author Notes:

Correspondence: S. N. Taylor, LSU Health Sciences Center, Section of Infectious Diseases, 3308 Tulane Ave., 5th Floor, New Orleans, Louisiana 70119, Staylo2@lsuhsc.edu

Acknowledgments: We thank the participants, clinical staff, and investigators of this study for their participation, specifically Dr Susan Philip who enrolled the highest number of Microbiological Evaluable participants.

We also thank the PPD team for their study contributions and Jodi Stahlman and Monica McGee at PPD for manuscript editorial and writing assistance.

For laboratory contributions, we thank Q2 Solutions and the University of Alabama for their microbiology analyses and the GlaxoSmithKline genetics laboratory for their mutation analyses.

Disclosures: The study was sponsored by GlaxoSmithKline (Collegeville, Pennsylvania).

S. N. T. has received research support from Beckman Coulter, Becton Dickinson, Cepheid, GlaxoSmithKline (along with scientific advisory board and as a consultant), Hologic, Melinta, AstraZeneca, and Roche Molecular.

B. E. B. has received research support from Melinta, AstraZeneca, and Entasis.

C. A. T., N. E. S-O., C. R. P., A. R., M. H., and E. F. D. are employees at GlaxoSmithKline.

Medical writing assistance was provided by PPD and funded by GlaxoSmithKline.

Authors were not paid for their contributions.

All other authors reported no conflicts of interest.

All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.

Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Subjects:

Research Funding:

This work was supported by GlaxoSmithKline.

This work was also supported in whole or in part with federal funds from the Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority, under an Other Transaction Authority Agreement (HHSO100201300011C).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Immunology
  • Infectious Diseases
  • Microbiology
  • gepotidacin
  • urogenital
  • gonorrhea
  • Neisseria gonorrhoeae
  • NEISSERIA-GONORRHOEAE
  • AZITHROMYCIN RESISTANCE
  • UNTREATABLE GONORRHEA
  • UNITED-STATES
  • CEFTRIAXONE
  • SUSCEPTIBILITY
  • EMERGENCE
  • INFECTION
  • FUTURE
  • TRIAL

Gepotidacin for the Treatment of Uncomplicated Urogenital Gonorrhea: A Phase 2, Randomized, Dose-Ranging, Single-Oral Dose Evaluation

Show all authors Show less authors

Tools:

Journal Title:

Clinical Infectious Diseases

Volume:

Volume 67, Number 4

Publisher:

, Pages 504-512

Type of Work:

Article | Final Publisher PDF

Abstract:

Background: In this phase 2 study, we evaluated the efficacy and safety of oral gepotidacin, a novel triazaacenaphthylene bacterial type II topoisomerase inhibitor, for the treatment of uncomplicated urogenital gonorrhea. Methods: Adult participants with suspected urogenital gonorrhea were enrolled and completed baseline (day 1) and test-of-cure (days 4-8) visits. Pretreatment and posttreatment urogenital swabs were collected for Neisseria gonorrhoeae (NG) culture and susceptibility testing. Pharyngeal and rectal swab specimens were collected if there were known exposures. Participants were stratified by gender and randomized 1:1 to receive a 1500-mg or 3000-mg single oral dose of gepotidacin. Results: The microbiologically evaluable population consisted of 69 participants, with NG isolated from 69 (100%) urogenital, 2 (3%) pharyngeal, and 3 (4%) rectal specimens. Microbiological eradication of NG was achieved by 97%, 95%, and 96% of participants (lower 1-sided exact 95% confidence interval bound, 85.1%, 84.7%, and 89.1%, respectively) for the 1500-mg, 3000-mg, and combined dose groups, respectively. Microbiological cure was achieved in 66/69 (96%) urogenital infections. All 3 failures were NG isolates that demonstrated the highest observed gepotidacin minimum inhibitory concentration of 1 µg/mL and a common gene mutation. At the pharyngeal and rectal sites, 1/2 and 3/3 NG isolates, respectively, demonstrated microbiological cure. There were no treatment-limiting adverse events for either dose. Conclusions: This study demonstrated that single, oral doses of gepotidacin were ≥95% effective for bacterial eradication of NG in adult participants with uncomplicated urogenital gonorrhea. Clinical Trials Registration: NCT02294682.

Copyright information:

© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
Export to EndNote