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

Sexually Transmitted Diseases Clinical Trial

— DOXY-PK  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06007534
• Other study ID #: APHP221156
• Status: Recruiting
• Phase: N/A
• Start date: October 25, 2023
• Est. completion date: April 25, 2025

Study information

• Verified date: April 2024
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Lauriane GOLDWIRT, Dr
• Phone: +33142494325
• Email: lauriane.goldwirt[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 25
• Est. completion date: April 25, 2025
• Est. primary completion date: April 25, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

• Adult male patient
• Men who have Sex with Men (MSM) on PrEP or HIV-infected 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

Related Conditions & MeSH terms

• Post-exposure Prophylaxis
• Sexually Transmitted Diseases

Intervention

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

Locations

Country	Name	City	State
France	Hôpital Lariboisière AP-HP	Paris
France	Hôpital Saint Louis AP-HP	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Concentration of doxycycline in urine		At Day 90
Secondary	Concentration of doxycycline in plasma		Before the single intake of doxycycline
Secondary	Concentration of doxycycline in plasma		2 hours after doxycycline intake
Secondary	Concentration of doxycycline in plasma		24 hours after doxycycline intake
Secondary	Concentration of doxycycline in plasma		48 hours after doxycycline intake
Secondary	Concentration of doxycycline in plasma		7 days after doxycycline intake
Secondary	Concentration of doxycycline in plasma		14 days after doxycycline intake
Secondary	Concentration of doxycycline in plasma		30 days after doxycycline intake
Secondary	Concentration of doxycycline in plasma		60 days after doxycycline intake
Secondary	Concentration of doxycycline in plasma		90 days after doxycycline intake
Secondary	Concentration of doxycycline in whole blood		Before the single intake of doxycycline
Secondary	Concentration of doxycycline in whole blood		2 hours after doxycycline intake
Secondary	Concentration of doxycycline in whole blood		24 hours after doxycycline intake
Secondary	Concentration of doxycycline in whole blood		48 hours after doxycycline intake
Secondary	Concentration of doxycycline in whole blood		7 days after doxycycline intake
Secondary	Concentration of doxycycline in whole blood		14 days after doxycycline intake
Secondary	Concentration of doxycycline in whole blood		30 days after doxycycline intake
Secondary	Concentration of doxycycline in whole blood		60 days after doxycycline intake
Secondary	Concentration of doxycycline in whole blood		90 days after doxycycline intake
Secondary	Concentration of doxycycline in Dried Blood Spot (DBS)		Before the single intake of doxycycline
Secondary	Concentration of doxycycline in Dried Blood Spot (DBS)		2 hours after doxycycline intake
Secondary	Concentration of doxycycline in Dried Blood Spot (DBS)		24 hours after doxycycline intake
Secondary	Concentration of doxycycline in Dried Blood Spot (DBS)		48 hours after doxycycline intake
Secondary	Concentration of doxycycline in Dried Blood Spot (DBS)		7 days after doxycycline intake
Secondary	Concentration of doxycycline in Dried Blood Spot (DBS)		14 days after doxycycline intake
Secondary	Concentration of doxycycline in Dried Blood Spot (DBS)		30 days after doxycycline intake
Secondary	Concentration of doxycycline in Dried Blood Spot (DBS)		60 days after doxycycline intake
Secondary	Concentration of doxycycline in Dried Blood Spot (DBS)		90 days after doxycycline intake
Secondary	Concentration of doxycycline in urine		Before the single intake of doxycycline
Secondary	Concentration of doxycycline in urine		2 hours after doxycycline intake
Secondary	Concentration of doxycycline in urine		24 hours after doxycycline intake
Secondary	Concentration of doxycycline in urine		48 hours after doxycycline intake
Secondary	Concentration of doxycycline in urine		7 days after doxycycline intake
Secondary	Concentration of doxycycline in urine		14 days after doxycycline intake
Secondary	Concentration of doxycycline in urine		30 days after doxycycline intake
Secondary	Concentration of doxycycline in urine		60 days after doxycycline intake
Secondary	Concentration of doxycycline in oropharyngeal secretions		Before the single intake of doxycycline
Secondary	Concentration of doxycycline in oropharyngeal secretions		2 hours after doxycycline intake
Secondary	Concentration of doxycycline in oropharyngeal secretions		24 hours after doxycycline intake
Secondary	Concentration of doxycycline in oropharyngeal secretions		48 hours after doxycycline intake
Secondary	Concentration of doxycycline in oropharyngeal secretions		7 days after doxycycline intake
Secondary	Concentration of doxycycline in oropharyngeal secretions		14 days after doxycycline intake
Secondary	Concentration of doxycycline in oropharyngeal secretions		30 days after doxycycline intake
Secondary	Concentration of doxycycline in oropharyngeal secretions		60 days after doxycycline intake
Secondary	Concentration of doxycycline in oropharyngeal secretions		90 days after doxycycline intake
Secondary	Doxycycline concentration in hair		Before the single intake of doxycycline
Secondary	Doxycycline concentration in hair		1 month after doxycycline intake
Secondary	Doxycycline concentration in hair		3 months after doxycycline intake
Secondary	Number of biological matrix(es) associated with a quantifiable doxycycline dosage	Determine the biological matrix(es) associated with a quantifiable doxycycline dosage in more than 90% of the samples collected during the study.	Up to 15 days
Secondary	Number of biological matrix(es) associated with a quantifiable doxycycline dosage	Determine the biological matrix(es) associated with a quantifiable doxycycline dosage in more than 90% of the samples collected during the study.	Up to 30 days
Secondary	Number of biological matrix(es) associated with a quantifiable doxycycline dosage	Determine the biological matrix(es) associated with a quantifiable doxycycline dosage in more than 90% of the samples collected during the study.	Up to 60 days
Secondary	Number of biological matrix(es) associated with a quantifiable doxycycline dosage	Determine the biological matrix(es) associated with a quantifiable doxycycline dosage in more than 90% of the samples collected during the study.	Up to 90 days
Secondary	Cmax (maximum concentration) in plasma		Until day 90
Secondary	Cmax (maximum concentration) in whole blood		Until day 90
Secondary	Cmax (maximum concentration) in Dried Blood Spot (DBS)		Until day 90
Secondary	Cmax (maximum concentration) in urine		Until day 90
Secondary	Cmax (maximum concentration) in hair		Until day 90
Secondary	AUC (area under the curve) in plasma		Until day 90
Secondary	AUC (area under the curve) in whole blood		Until day 90
Secondary	AUC (area under the curve) in Dried Blood Spot (DBS)		Until day 90
Secondary	AUC (area under the curve) in urine		Until day 90
Secondary	AUC (area under the curve) in hair		Until day 90
Secondary	Elimination clearance in plasma		Until day 90
Secondary	Elimination clearance in whole blood		Until day 90
Secondary	Elimination clearance in Dried Blood Spot (DBS)		Until day 90
Secondary	Elimination clearance in urine		Until day 90
Secondary	Elimination clearance in hair		Until day 90
Secondary	Half-life in plasma		Until day 90
Secondary	Half-life in whole blood		Until day 90
Secondary	Half-life in Dried Blood Spot (DBS)		Until day 90
Secondary	Half-life in urine		Until day 90
Secondary	Half-life in hair		Until day 90
Secondary	Mean residence time in plasma		Until day 90
Secondary	Mean residence time in whole blood		Until day 90
Secondary	Mean residence time in Dried Blood Spot (DBS)		Until day 90
Secondary	Mean residence time in urine		Until day 90
Secondary	Mean residence time in hair		Until day 90
Secondary	Volume of distribution in plasma		Until day 90
Secondary	Volume of distribution in whole blood		Until day 90
Secondary	Volume of distribution in Dried Blood Spot (DBS)		Until day 90
Secondary	Volume of distribution in urine		Until day 90
Secondary	Volume of distribution in hair		Until day 90