Assessment of Drug-drug Interactions Between Feminizing Hormone Therapy and Emtricitabine/Tenofovir Alafenamide Concomitantly for Pre-exposure Prophylaxis Among Transgender Women

Drug Interaction Clinical Trial

Official title:

Institute of HIV Research and Innovation (IHRI)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04590417
• Other study ID #: iFACT 3
• Status: Active, not recruiting
• Phase: N/A
• Start date: October 1, 2020
• Est. completion date: October 1, 2025

Study information

• Verified date: April 2022
• Source: Thai Red Cross AIDS Research Centre
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Recent studies have showed that there were significant drug-drug interactions (DDI) from feminizing hormone therapy (FHT) towards emtricitabine/tenofovir disoproxil fumarate (F/TDF)-based pre-exposure prophylaxis (PrEP) among transgender women (TGW). New strategies for PrEP among TGW who use FHT are urgently needed. Because tenofovir alafenamide (TAF) can achieve higher intracellular TFV-DP levels with lower tenofovir plasma concentrations, it is promising that both plasma TFV and intracellular TFV-DP levels might not be significantly affected by FHT. The current study aims to determine the pharmacokinetics DDI between FHT and F/TAF-based PrEP among TGW.

Description:

Two full pharmacokinetic (PK) measurements will be performed. Samples collected will include: plasma for estradiol (E2), emtricitabine (FTC), tenofovir (TFV), and tenofovir alafenamide (TAF) measurement; and peripheral blood mononuclear cells (PBMC) for emtricitabine-triphosphate (FTC-TP) and tenofovir-diphosphate (TFV-DP) intracellular quantification.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 20
• Est. completion date: October 1, 2025
• Est. primary completion date: October 1, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

1. Thai nationality

2. Age 18-40 years old

3. Transgender women

4. HIV-negative

5. Body mass index 18.5-24.9 kg/m2

6. Calculated creatinine clearance (CrCl) =60 mL/min, as estimated by the Cockcroft-Gault equation

7. Alanine aminotransferase (ALT) =2.5 x ULN

8. Signed the informed consent form

Exclusion Criteria:

1. Known history of allergy to hormonal component to be used in the study

2. Male-to-female transgender who underwent orchiectomy

3. Use of pre-exposure prophylaxis or post-exposure prophylaxis in the past 30 days

4. Use of injectable FHT in the past 3 months

5. Evidence of current hepatitis B virus infection (HBV) - i.e. hepatitis B surface antigen (HBsAg) positive

6. Evidence of current hepatitis C virus infection (HCV) - i.e. HCV antibody positive

7. Current use of any of the following:

• Anticonvulsants: carbamazepine, felbamate, oxcarbazepine, phenytoin, phenobarbital, primidone or topiramate

• Herbs: gingko biloba, St John's wort or milk thistle

• Anti-infective agents: azole antifungals, macrolides, griseofulvin, protease inhibitors, rifampicin or rifabutin

8. Participant-reported active rectal infection requiring treatment

9. History of gastrointestinal tract surgery that alter gastrointestinal tract and/or drug absorption

10. Alcohol or drug use that, in the opinion of the investigator, would interfere with completion of study procedures

Related Conditions & MeSH terms

• Drug Interaction

Intervention

Drug:
• Estradiol valerate 2 mg, cyproterone acetate 25 mg
The entire study period will be approximately 1 year, which will include around 2 months of document preparation, 5 months of recruitment, 3 months of follow-up, and 2 months of data analysis.

Locations

Country	Name	City	State
Thailand	Institute of HIV Research and Innovation (IHRI)	Bangkok	Pathumwan

Sponsors (1)

Lead Sponsor	Collaborator
Thai Red Cross AIDS Research Centre

Country where clinical trial is conducted

Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in plasma estradiol levels		Measured at week 3 and week 9 of the study period
Primary	Changes in plasma PrEP levels	Plasma TFV; Plasma FTC; Plasma TAF	Week 9 through 12
Primary	Changes in intracellular PrEP levels	PBMC TFV-DP levels; PBMC FTC-TP levels	Week 9 through 12
Secondary	Changes in plasma testosterone levels		Week 3 through 9