Optimisation of treatments for oral Neisseria gonorrhoeae infection: Pharmacokinetics Study (STI-PK project) – study protocol for non-randomised clinical trial
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 sc...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2022-11-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/12/11/e064782.full |
| _version_ | 1798019197392912384 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Eric P F Chow |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T16:36:39Z |
| format | Article |
| id | doaj.art-2379e80f12214392851657a2b3e002e0 |
| institution | Directory Open Access Journal |
| issn | 2044-6055 |
| language | English |
| last_indexed | 2024-04-11T16:36:39Z |
| publishDate | 2022-11-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj.art-2379e80f12214392851657a2b3e002e02022-12-22T04:13:48ZengBMJ Publishing GroupBMJ Open2044-60552022-11-01121110.1136/bmjopen-2022-064782Optimisation of treatments for oral Neisseria gonorrhoeae infection: Pharmacokinetics Study (STI-PK project) – study protocol for non-randomised clinical trialEric P F Chow0Christopher K Fairley1Deborah A Williamson2Jane S Hocking3Magnus Unemo4David A Lewis5Steven C Wallis6Jason A Roberts7Fabian Y S Kong8Shueh H Lim9Ngaire Latch10Suzanne L Parker11Cornelia B Landersdorfer12Tami Yap13Mohamed A Hammoud14Melbourne Sexual Health Centre, Alfred Health, Carlton, Victoria, AustraliaMelbourne Sexual Health Centre, Alfred Health, Carlton, Victoria, AustraliaDepartment of Infectious Diseases, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, AustraliaCentre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, AustraliaWHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for Sexually Transmitted Infections, Department of Laboratory Medicine, Microbiology, Örebro University, Orebro, SwedenWestmead Clinical School and Sydney Institute for Infectious Diseases, The University of Sydney, Sydney, New South Wales, AustraliaThe University of Queensland Centre for Clinical Research, Brisbane, Queensland, AustraliaThe University of Queensland Centre for Clinical Research, Brisbane, Queensland, AustraliaCentre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, AustraliaCentre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, AustraliaCentre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, AustraliaThe University of Queensland Centre for Clinical Research, Brisbane, Queensland, AustraliaMonash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, AustraliaMelbourne Dental School, The University of Melbourne, Melbourne, Victoria, AustraliaKirby Institute, University of New South Wales, Sydney, New South Wales, AustraliaIntroduction 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.https://bmjopen.bmj.com/content/12/11/e064782.full |
| spellingShingle | 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 Optimisation of treatments for oral Neisseria gonorrhoeae infection: Pharmacokinetics Study (STI-PK project) – study protocol for non-randomised clinical trial BMJ Open |
| title | Optimisation of treatments for oral Neisseria gonorrhoeae infection: Pharmacokinetics Study (STI-PK project) – study protocol for non-randomised clinical trial |
| title_full | Optimisation of treatments for oral Neisseria gonorrhoeae infection: Pharmacokinetics Study (STI-PK project) – study protocol for non-randomised clinical trial |
| title_fullStr | Optimisation of treatments for oral Neisseria gonorrhoeae infection: Pharmacokinetics Study (STI-PK project) – study protocol for non-randomised clinical trial |
| title_full_unstemmed | Optimisation of treatments for oral Neisseria gonorrhoeae infection: Pharmacokinetics Study (STI-PK project) – study protocol for non-randomised clinical trial |
| title_short | Optimisation of treatments for oral Neisseria gonorrhoeae infection: Pharmacokinetics Study (STI-PK project) – study protocol for non-randomised clinical trial |
| title_sort | optimisation of treatments for oral neisseria gonorrhoeae infection pharmacokinetics study sti pk project study protocol for non randomised clinical trial |
| url | https://bmjopen.bmj.com/content/12/11/e064782.full |
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