Optimisation of treatments for oral Neisseria gonorrhoeae infection: Pharmacokinetics Study (STI-PK project) – study protocol for non-randomised clinical trial
Eric P F Chow,
Christopher K Fairley,
Deborah A Williamson,
Jane S Hocking,
Magnus Unemo,
David A Lewis,
Steven C Wallis,
Jason A Roberts,
Fabian Y S Kong,
Shueh H Lim,
Ngaire Latch,
Suzanne L Parker,
Cornelia B Landersdorfer,
Tami Yap,
Mohamed A Hammoud
Affiliations
Eric P F Chow
Melbourne Sexual Health Centre, Alfred Health, Carlton, Victoria, Australia
Christopher K Fairley
Melbourne Sexual Health Centre, Alfred Health, Carlton, Victoria, Australia
Deborah A Williamson
Department of Infectious Diseases, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia
Jane S Hocking
Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia
Magnus Unemo
WHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for Sexually Transmitted Infections, Department of Laboratory Medicine, Microbiology, Örebro University, Orebro, Sweden
David A Lewis
Westmead Clinical School and Sydney Institute for Infectious Diseases, The University of Sydney, Sydney, New South Wales, Australia
Steven C Wallis
The University of Queensland Centre for Clinical Research, Brisbane, Queensland, Australia
Jason A Roberts
The University of Queensland Centre for Clinical Research, Brisbane, Queensland, Australia
Fabian Y S Kong
Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia
Shueh H Lim
Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia
Ngaire Latch
Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia
Suzanne L Parker
The University of Queensland Centre for Clinical Research, Brisbane, Queensland, Australia
Cornelia B Landersdorfer
Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia
Tami Yap
Melbourne Dental School, The University of Melbourne, Melbourne, Victoria, Australia
Mohamed A Hammoud
Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia
Introduction Neisseria gonorrhoeae infections are common and incidence increasing. Oropharyngeal infections are associated with greater treatment failure compared with other sites and drive transmission to anogenital sites through saliva. Gonococcal resistance is increasing and new treatments are scarce, therefore, clinicians must optimise currently available and emerging treatments in order to have efficacious therapeutic options. This requires pharmacokinetic data from the oral cavity/oropharynx, however, availability of such information is currently limited.Methods and analysis Healthy male volunteers (participants) recruited into the study will receive single doses of either ceftriaxone 1 g, cefixime 400 mg or ceftriaxone 500 mg plus 2 g azithromycin. Participants will provide samples at 6-8 time points (treatment regimen dependent) from four oral sites, two oral fluids, one anorectal swab and blood. Participants will complete online questionnaires about their medical history, sexual practices and any side effects experienced up to days 5–7. Saliva/oral mucosal pH and oral microbiome analysis will be undertaken. Bioanalysis will be conducted by liquid chromatography-mass spectrometry. Drug concentrations over time will be used to develop mathematical models for optimisation of drug dosing regimens and to estimate pharmacodynamic targets of efficacy.Ethics and dissemination This study was approved by Royal Melbourne Hospital Human Research Ethics Committee (60370/MH-2021). The study results will be submitted for publication in peer-reviewed journals and reported at conferences. Summary results will be sent to participants requesting them. All data relevant to the study will be included in the article or uploaded as supplementary information.Trial registration number ACTRN12621000339853.
