Pharmacokinetic Characterization of a Single 200 mg Dose of Doxycycline in Post-exposure Prophylaxis (PEP) of Sexually Transmitted Infections in Different Biological Compartments

Official title

Caractérisation de la pharmacocinétique d'Une Dose Unique de 200 mg de Doxycycline en Prophylaxie Post-exposition (PEP) Des Infections Sexuellement Transmissibles Dans différents Compartiments Biologiques

Overview

Post-exposure prophylaxis (PEP) using doxycycline 200 mg within 24 hours of unprotected sexual intercourse to prevent sexually transmitted infections has demonstrated a reduction in the incidence of chlamydial and syphilis infections and syphilis infection by 70% and 73% in men who have sex with men (MSM) undergoing pre-exposure prophylaxis prophylaxis (PrEP) for HIV. Other studies are underway or in development on doxycycline prophylaxis for bacterial STIs, which are particularly common in this population. Monitoring adherence to PEP is of great interest in guaranteeing the effectiveness of this strategy and to be able to assess the uptake of PEP among PrEP users. Among the many methods for assessing adherence, measuring drug concentrations is a more accurate measure of adherence than self-reporting. The therapeutic monitoring of doxycycline and the assessment of adherence have been described using plasma and hair samples, allowing estimation of intake over the last 3-4 days and 4 months, respectively. Nevertheless, these biological matrices present several limitations for application in clinical practice: reflecting the duration of exposure should be more in line with the frequency of visits (2 months), and the collection of hair samples may be difficult due to refusal or short hair. On the other hand, interpretation of the hair assay is limited by the degradation of doxycycline in this matrix, which could lead to underestimation of drug intake. By Therefore, new biological matrices are needed for more accurate assessment of doxycycline adherence in post-exposure prevention monitoring. The objective is to evaluate the pharmacokinetics of doxycycline in plasma, whole blood, dried blood spots (DBS), urine and hair after a single dose of doxycycline in men using oral doxycycline for post-exposure prophylaxis of sexually transmitted infections (syphilis or Chlamydia trachomatis) and having sex with men.

Interventions

• Other Samples
  Blood samples, urine samples and oropharyngeal swabs before taking 200mg of doxycycline and then 2h, 24h, 48h, 7 days, 14 days, 60 days and 90 days after the single dose of doxycycline Hair samples: at the time of doxycycline administration, 1 month and 3 months after the single dose of doxycycline

Primary outcome measures

• Concentration of doxycycline in urine [Time frame: At Day 90]

Secondary outcome measures (12)

• Concentration of doxycycline in plasma [Time frame: Before the single intake of doxycycline]
• Concentration of doxycycline in plasma [Time frame: 2 hours after doxycycline intake]
• Concentration of doxycycline in plasma [Time frame: 24 hours after doxycycline intake]
• Concentration of doxycycline in plasma [Time frame: 48 hours after doxycycline intake]
• Concentration of doxycycline in plasma [Time frame: 7 days after doxycycline intake]
• Concentration of doxycycline in plasma [Time frame: 14 days after doxycycline intake]
• Concentration of doxycycline in plasma [Time frame: 30 days after doxycycline intake]
• Concentration of doxycycline in plasma [Time frame: 60 days after doxycycline intake]
• Concentration of doxycycline in plasma [Time frame: 90 days after doxycycline intake]
• Concentration of doxycycline in whole blood [Time frame: Before the single intake of doxycycline]
• Concentration of doxycycline in whole blood [Time frame: 2 hours after doxycycline intake]
• Concentration of doxycycline in whole blood [Time frame: 24 hours after doxycycline intake]

Eligibility criteria

Inclusion criteria

• Adult male patient
• Men who have Sex with Men (MSM) on PrEP or HIV-infected patients
• Patients who have not taken doxycycline for at least 3 months
• No symptoms of bacterial STI infection (chlamydia, gonorrhea, Mycoplasma genitalium or syphilis).
• Documented history of bacterial STI infection within the past 12 months
• Having had a risky intercourse within 24 hours and at the latest within 72 hours and for which a prescription of doxycycline in a single dose of 200 mg has been made within the framework of his usual follow-up.
• Free, informed, written consent, signed by the person and the investigator at the latest on the day of inclusion and before any examination carried out within the framework of the study (article L1122-1-1 of the Public Health Code).
• Person affiliated or benefiting from a social security system (article L1121-11 of the Public Health Code)

Exclusion criteria

• Systemic treatment with retinoids (Acnetrait®, Procuta®, Curacné®, Contracné®, ....).
• Treatment with enzyme-inducing anticonvulsants (carbamazepine, phenobarbital, phenytoin, etc.).
• Known allergy to antibiotics of the tetracycline family.
• Known allergy to one of the components of doxycycline tablets.
• Documented esophageal injury
• Ongoing treatment with doxycycline at the time of inclusion.
• Person participating in another research study with an exclusion period still in progress at inclusion.
• Persons under guardianship, conservatorship, or deprived of liberty by judicial or administrative decision.
• Patients on State Medical Aid

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Other

Study locations

France · 2 centers

• Hôpital Lariboisière AP-HP — Paris
• Hôpital Saint Louis AP-HP — Paris

Identifiers

NCT: NCT06007534 · APHP221156

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗