Assessment of Drug-drug Interactions Between Masculinizing Hormone Therapy and Antiretroviral Agents Concomitantly for Pre-exposure Prophylaxis Among Transgender Men

Institute of HIV Research and Innovation (IHRI)

There are currently no published studies addressing drug-drug interactions (DDI) between masculinizing hormone therapy (MHT) and pre-exposure prophylaxis (PrEP) among transgender men (TGM). This could lead to concerns and subsequent prioritizing MHT over PrEP among TGM. Because tenofovir alafenamide (TAF) can achieve higher intracellular tenofovir diphosphate (TFV-DP) levels with lower tenofovir plasma concentrations, it is promising that both plasma tenofovir (TFV) and intracellular TFV-DP levels might not be significantly affected by MHT. The current study aims to determine the pharmacokinetics (PK) DDI between MHT and daily PrEP among TGM.

Study Overview

• Status: Recruiting
• Conditions: Drug Interaction
• Intervention / Treatment: Drug: Emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg (F/TDF) and emtricitabine 200 mg/tenofovir alafenamide 25 mg (F/TAF)

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nittaya Phanuphak, MD, PhD; Phone Number: 881 8253544; Email: nittaya.p@ihri.org
• Study Contact Backup: Name: Rena Janamnuaysook, MBA; Phone Number: +662 2530996; Email: rena.j@ihri.org

Study Locations

• Thailand
  • Pathumwan
    • Bangkok, Pathumwan, Thailand, 10330
      • Recruiting
      • Institute of HIV Research and Innovation (IHRI)
      • Contact: Nittaya Phanuphak, MD, PhD; Phone Number: +662253 0996; Email: nittaya.p@ihri.org
      • Contact: Rena Janamnuaysook, MBA; Phone Number: +662253 0996; Email: rena.j@ihri.org
      • Principal Investigator: Nittaya Phanuphak, MD,PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Thai nationality
2. Age 18-40 years old
3. Female-to-Male transgender individual
4. HIV-negative
5. Body mass index 18.5-24.9 kg/m2
6. Negative urine pregnancy test
7. Calculated creatinine clearance (CrCl) ≥60 mL/min, as estimated by the Cockcroft-Gault equation
8. Alanine aminotransferase (ALT) ≤2.5 x ULN
9. Signed the informed consent form

Exclusion Criteria:

1. Known history of allergy to hormonal component to be used in the study
2. Use of pre-exposure prophylaxis or post-exposure prophylaxis in the past 30 days
3. Use of injectable MHT in the past 3 months
4. Evidence of current hepatitis B virus infection (HBV) - i.e. hepatitis B surface antigen [HBsAg] positive
5. Evidence of current hepatitis C virus infection (HCV) - i.e. HCV antibody positive
6. History of myocardial infarction or coronary artery disease

7. Current use of any of the following:

   • Anticonvulsants: carbamazepine, oxcarbazepine, phenytoin, or phenobarbital
   • Herbs: gingko biloba, St John's wort or milk thistle
   • Anti-infective agents: protease inhibitors, rifampicin or rifabutin
8. History of gastrointestinal tract surgery that alter gastrointestinal tract and/or drug absorption
9. Alcohol or drug use that, in the opinion of the investigator, would interfere with completion of study procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 20 HIV-negative TGM will take daily TDF/FTC-based PrEP; MHT will be initiated on week 0 and will be last administered on week 12. PrEP will be initiated on week 6 and continued without interruption. MHT: Intramuscular testosterone enanthate 200 mg bi-weekly, which is the treatment of choice for MHT in the Pribta Clinic, will be provided to all participants. PrEP: Fixed-dose combination of emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg (F/TDF) and emtricitabine 200 mg/tenofovir alafenamide 25 mg (F/TAF) will be provided for arm 1 and 2, respectively. Pharmacokinetic measurement of study drug Two full pharmacokinetic (PK) measurements will be performed. Samples collected will include: plasma for testosterone, emtricitabine (FTC) and tenofovir (TFV), with an additional tenofovir alafenamide (TAF).	Drug: Emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg (F/TDF) and emtricitabine 200 mg/tenofovir alafenamide 25 mg (F/TAF); The first full PK measurement of MHT will be performed starting at week 4 and end at week 6 to assess the steady-state plasma PK of testosterone in the absence of PrEP. The second PK measurement of MHT will be performed starting at week 12 and end at week 14 to assess plasma PK of testosterone in the presence of both MHT and PrEP. The first full PK measurement of PrEP will be performed at week 12 to assess the steady-state plasma PK of FTC, TFV, and TAF; and intracellular PBMC FTC-TP and TFV-DP in the presence of both MHT and PrEP. The second measurement of PrEP will be performed at week 16 to assess plasma PK of FTC, TFV, and TAF; and intracellular PBMC FTC-TP and TFV-DP in the absence of MHT.
EXPERIMENTAL: 20 HIV-negative TGM will take daily F/TAF-based PrEP; MHT will be initiated on week 0 and will be last administered on week 12. PrEP will be initiated on week 6 and continued without interruption. MHT: Intramuscular testosterone enanthate 200 mg bi-weekly, which is the treatment of choice for MHT in the Pribta Clinic, will be provided to all participants. PrEP: Fixed-dose combination of emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg (F/TDF) and emtricitabine 200 mg/tenofovir alafenamide 25 mg (F/TAF) will be provided for arm 1 and 2, respectively. Pharmacokinetic measurement of study drug Two full pharmacokinetic (PK) measurements will be performed. Samples collected will include: arm 2, measurement; and peripheral blood mononuclear cells (PBMC) for emtricitabine-triphosphate (FTC-TP) and tenofovir-diphosphate (TFV-DP) intracellular quantification.	Drug: Emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg (F/TDF) and emtricitabine 200 mg/tenofovir alafenamide 25 mg (F/TAF); The first full PK measurement of MHT will be performed starting at week 4 and end at week 6 to assess the steady-state plasma PK of testosterone in the absence of PrEP. The second PK measurement of MHT will be performed starting at week 12 and end at week 14 to assess plasma PK of testosterone in the presence of both MHT and PrEP. The first full PK measurement of PrEP will be performed at week 12 to assess the steady-state plasma PK of FTC, TFV, and TAF; and intracellular PBMC FTC-TP and TFV-DP in the presence of both MHT and PrEP. The second measurement of PrEP will be performed at week 16 to assess plasma PK of FTC, TFV, and TAF; and intracellular PBMC FTC-TP and TFV-DP in the absence of MHT.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in plasma TFV level	Changes in plasma testosterone levels [Time Frame: Measured at week 4 and week 12 of the study period]; Changes in plasma TFV levels [Time Frame: Measured at week 12 and week 16 of the study period]; Changes in plasma emtricitabine (FTC) levels [Time Frame: Measured at week 12 and week 16 of the study period]; Changes in plasma TAF levels [Time Frame: Measured at week 12 and week 16 of the study period]; Changes in peripheral blood mononuclear cell TFV-DP levels [Time Frame: Measured at week 12 and week 16 of the study period]; Changes in peripheral blood mononuclear cell (PBMC) emtricitabine triphosphate (FTC-TP) levels [Time Frame: Measured at week 12 and week 16 of the study period]	2 years

Collaborators and Investigators

• Sponsor: Thai Red Cross AIDS Research Centre

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2020
• Primary Completion (ANTICIPATED): October 1, 2023
• Study Completion (ANTICIPATED): October 1, 2025

Study Registration Dates

• First Submitted: October 14, 2020
• First Submitted That Met QC Criteria: October 19, 2020
• First Posted (ACTUAL): October 20, 2020

Study Record Updates

• Last Update Posted (ACTUAL): April 25, 2022
• Last Update Submitted That Met QC Criteria: April 21, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir; Emtricitabine
• Other Study ID Numbers: iMACT

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No