Gepotidacin for the treatment of uncomplicated urogenital gonorrhea

A phase 2, randomized, doseranging, single-oral dose evaluation

Stephanie N. Taylor, David H. Morris, Ann K. Avery, Kimberly A. Workowski, Byron Batteiger, Courtney A. Tiffany, Caroline R. Perry, Aparna Raychaudhuri, Nicole E. Scangarella-Oman, Mohammad Hossain, Etienne F. Dumont

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background. In this phase 2 study, we evaluated the efcacy 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 stratifed by gender and randomized 1:1 to receive a 1500-mg or 3000-mg single oral dose of gepotidacin. Results. Te 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% confdence 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. Tere were no treatment-limiting adverse events for either dose. Conclusions. Tis study demonstrated that single, oral doses of gepotidacin were =95% e?ective for bacterial eradication of NG in adult participants with uncomplicated urogenital gonorrhea. Clinical Trials Registration. NCT02294682.

Original languageEnglish (US)
Pages (from-to)504-512
Number of pages9
JournalClinical Infectious Diseases
Volume67
Issue number4
DOIs
StatePublished - Jan 1 2018

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Neisseria gonorrhoeae
Gonorrhea
Therapeutics
Topoisomerase II Inhibitors
Microbial Sensitivity Tests
Clinical Trials
Safety
Mutation
Infection
Population
Genes

Keywords

  • Gepotidacin
  • Gonorrhea
  • Neisseria gonorrhoeae
  • Urogenital

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Gepotidacin for the treatment of uncomplicated urogenital gonorrhea : A phase 2, randomized, doseranging, single-oral dose evaluation. / Taylor, Stephanie N.; Morris, David H.; Avery, Ann K.; Workowski, Kimberly A.; Batteiger, Byron; Tiffany, Courtney A.; Perry, Caroline R.; Raychaudhuri, Aparna; Scangarella-Oman, Nicole E.; Hossain, Mohammad; Dumont, Etienne F.

In: Clinical Infectious Diseases, Vol. 67, No. 4, 01.01.2018, p. 504-512.

Research output: Contribution to journalArticle

Taylor, SN, Morris, DH, Avery, AK, Workowski, KA, Batteiger, B, Tiffany, CA, Perry, CR, Raychaudhuri, A, Scangarella-Oman, NE, Hossain, M & Dumont, EF 2018, 'Gepotidacin for the treatment of uncomplicated urogenital gonorrhea: A phase 2, randomized, doseranging, single-oral dose evaluation', Clinical Infectious Diseases, vol. 67, no. 4, pp. 504-512. https://doi.org/10.1093/cid/ciy145
Taylor, Stephanie N. ; Morris, David H. ; Avery, Ann K. ; Workowski, Kimberly A. ; Batteiger, Byron ; Tiffany, Courtney A. ; Perry, Caroline R. ; Raychaudhuri, Aparna ; Scangarella-Oman, Nicole E. ; Hossain, Mohammad ; Dumont, Etienne F. / Gepotidacin for the treatment of uncomplicated urogenital gonorrhea : A phase 2, randomized, doseranging, single-oral dose evaluation. In: Clinical Infectious Diseases. 2018 ; Vol. 67, No. 4. pp. 504-512.
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abstract = "Background. In this phase 2 study, we evaluated the efcacy 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 stratifed by gender and randomized 1:1 to receive a 1500-mg or 3000-mg single oral dose of gepotidacin. Results. Te 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{\%} confdence 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. Tere were no treatment-limiting adverse events for either dose. Conclusions. Tis study demonstrated that single, oral doses of gepotidacin were =95{\%} e?ective for bacterial eradication of NG in adult participants with uncomplicated urogenital gonorrhea. Clinical Trials Registration. NCT02294682.",
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