Evaluation of Doxycycline Monohydrate Postexposure Prophylaxis on Antimicrobial Resistance in Bacterial Sexually Transmitted Infections

The primary objective of this study is to assess if **doxycycline** post-exposure prophylaxis (PEP) can result in reduced susceptibility to doxycycline in rectal **Escherichia coli** on day 180. This is clinically relevant as it evaluates the potential impact of doxycycline PEP on antimicrobial resistance, which is a significant concern in the treatment of bacterial sexually transmittable diseases such as chlamydia, gonorrhea, and syphilis.

Secondary objectives include assessing if doxycycline PEP can result in reduced susceptibility to various antibiotics in different bacterial species on day 180. These include:

• Reduced susceptibility to ceftriaxone and ciprofloxacin in rectal E. coli.
• Reduced susceptibility to doxycycline, ceftriaxone, and ciprofloxacin in rectal **Klebsiella pneumoniae**.
• Reduced susceptibility to doxycycline, ceftriaxone, and ciprofloxacin in oral streptococci.
• Reduced susceptibility to doxycycline, ceftriaxone, and ciprofloxacin in oral **Staphylococcus aureus**.
• Reduced susceptibility to doxycycline, ceftriaxone, and ciprofloxacin in oral commensal **Neisseria** spp.
• Assessing the effect of doxycycline PEP on susceptibility to all the above antibiotics and bacterial combinations, adjusting for doxycycline consumption, antibiotic use, and other confounders.

The clinical trial focuses on **bacterial sexually transmittable diseases** such as chlamydia, gonorrhea, and syphilis. The study population comprises male participants, aged 18 years and older, who are eligible to take HIV PrEP. Participants must be able and willing to provide written informed consent. The trial does not include female subjects or vulnerable populations. The sponsor has not provided information regarding the total number of participants. The selection criteria emphasize the inclusion of individuals who were male at birth, ensuring a specific focus on this demographic group. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed as a **pilot single-center, open-label** study to evaluate the impact of **doxycycline** post-exposure prophylaxis on antimicrobial resistance. The primary objective is to assess whether doxycycline prophylaxis can lead to reduced susceptibility to doxycycline in rectal **E. coli** on day 180. The trial will involve male participants aged 18 years or older who are eligible to take HIV PrEP and are able and willing to provide written informed consent. The study will focus on bacterial sexually transmittable diseases, including chlamydia, gonorrhea, and syphilis.

The trial will commence with a screening visit to confirm eligibility based on the inclusion criteria. Participants will then be enrolled and receive the study medication, **Doxycycline EG 200 mg Tabletten**, administered orally. The maximum daily dose is 200 mg, with a total treatment period of up to six months. The trial will include follow-up visits to monitor the participants' health and collect data on the minimum inhibitory concentration (MIC) of doxycycline and other antibiotics in various bacterial strains, including **K. pneumoniae**, **S. aureus**, oral streptococci, and oral commensal **Neisseria spp.** The primary endpoint is the shift in the distribution of MIC of doxycycline in rectal E. coli on day 180, with secondary endpoints assessing similar shifts for other antibiotics and bacterial strains.

The estimated recruitment start date is November 1, 2023, with the trial expected to conclude by September 30, 2024. Participants will be involved in the study for the duration of the treatment period, with regular follow-up visits scheduled to ensure compliance and monitor any adverse effects. Conditions that may lead to early termination from the study include non-compliance with the study protocol, withdrawal of consent, or any adverse events that compromise participant safety. The trial is categorized as a low-intervention Phase 4 study, focusing on the potential impact of doxycycline prophylaxis on antimicrobial resistance patterns.

The clinical trial involves the administration of **Doxycycline EG 200 mg Tabletten** as the experimental medication. This pharmaceutical product is formulated as a **tablet** and contains the active substance **doxycycline monohydrate**. The medication is administered **orally** with a maximum daily dose of **200 mg**. The total maximum dose over the course of the treatment is **24,000 mg**, with the treatment period extending up to **6 months**. The product is manufactured by EUROGENERICS N.V./S.A. and is not a pediatric formulation. The trial aims to assess the impact of doxycycline postexposure prophylaxis on antimicrobial resistance, specifically focusing on the susceptibility of rectal **E. coli** to doxycycline on day 180.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified for this study. The trial is designed as a single-center, open-label study, and participant compliance with the dosing schedule will be monitored throughout the trial period. The study does not involve any orphan drug designation or pediatric formulations, and the product's authorization status is confirmed for use in the trial.

Efficacy in this clinical trial will be assessed by evaluating the impact of doxycycline postexposure prophylaxis (PEP) on antimicrobial resistance. The primary endpoint is the shift in the distribution of the **minimum inhibitory concentration (MIC)** of doxycycline in rectal *E. coli* on day 180. Secondary endpoints include shifts in the distribution of MICs for ceftriaxone and ciprofloxacin in rectal *E. coli*, as well as similar assessments for rectal *K. pneumoniae*, oral streptococci, oral *S. aureus*, and oral commensal *Neisseria* spp. on day 180. These endpoints will be measured using laboratory tests to determine the MIC values, which will provide insights into changes in bacterial susceptibility to these antibiotics. The trial is designed to determine if doxycycline PEP can lead to reduced susceptibility to tetracyclines, cephalosporins, and fluoroquinolones in the specified bacterial species. The assessments will be conducted at the specified timepoint of day 180, ensuring a comprehensive evaluation of the prophylactic impact on antimicrobial resistance. The trial is categorized as a low-intervention Phase 4 study, focusing on the potential changes in antibiotic susceptibility profiles.