Clinical trial NCT04283656: Evaluating Drug Interactions Between Doravirine With Estradiol and Spironolactone in Healthy Transgender Women
Official title: A Prospective, Randomized, Three-period Crossover, Interaction Study to Evaluate the Pharmacokinetics of Doravirine and Tenofovir Disoproxil Fumarate Co-administered With Cross-sex Hormonal Therapy in Adult HIV-negative Transgender Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Transgender Health
Gender Dysphoria
Transgender Women
Human Immunodeficiency Virus
Lead sponsor: Thomas Jefferson University
Sponsor class: OTHER
First posted: 2020-02-25
Enrollment: 8
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Three period crossover
Primary purpose: TREATMENT

Brief summary: Transgender women living with Human Immunodeficiency Virus (HIV) may prioritize gender-affirming hormonal therapy over antiretroviral drug therapy. Hormonal therapy typically consists of oral estradiol and spironolactone, which induce drug-metabolizing enzymes after prolonged administration. This study evaluates the bi-directional potential drug interaction between the antiretroviral drug, doravirine, when co-administered with estradiol and spironolactone.

Detailed description: This study will consist of healthy transgender women volunteers randomized to a 1:1 sequence ("E" or "F") There are three periods and in each period there are one of three treatments

Treatment A: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate alone Treatment B: Single-dose estradiol and spironolactone co-administered with placebo Treatment C: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone

The primary outcome measures are the drug concentrations

The primary comparisons are geometric mean ratios of drugs with potential perpetrators of drug interactions using a crossover method

Eligibility criteria: Inclusion Criteria:

* Healthy self-identified transgender women (male-to-female) between 18-45 years old at the time of screening
* Have not undergone an orchiectomy
* Receiving oral estradiol and spironolactone for \>/= 3 months prior to study entry with a self-reported adherence to prescribed doses of \>/= 90%
* Agree to abstain from alcohol consumption throughout the duration of the study
* Be willing to briefly interrupt hormonal therapy prior to and during the study
* If on pre-exposure prophylaxis (PrEP) therapy containing tenofovir alafenamide or tenofovir disoproxil fumarate, willing to discontinue PrEP at least 2 weeks before study start and for the duration of the study
* Agree to use condoms for all sexual activity prior to the start and throughout the duration of the study
* Evidence of a personal signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study

Exclusion Criteria:

* Presence of clinically significant acute or chronic disease, that in the investigator's opinion, would compromise the participant's safety during the study
* Use of injectable or transdermal estradiol
* Use of any other hormonal replacement therapy, wit h the exception of oral estradiol and spironolactone
* Current use of any antiretroviral drug. This will not be exclusionary if participants reported discontinuing within 30 days of screening
* Creatinine clearance \</= 60 mL/min, as estimated by the Cockcroft-Gault equation
* Known anaphylactic or severe systemic reactions to any components of doravirine, lamivudine, or tenofovir disoproxil fumarate
* Positive HIV, hepatitis B or Hepatitis C virus at screening. Evidence of prior hepatitis B infection and immunity is not exclusionary. Positive hepatitis C antibody with negative viral load or documented antiviral hepatitis C treatment with one post treatment non-detectable hepatitis C viral load is not exclusionary
* Recent significant blood or plasma donation

Primary outcomes:
measure: Doravirine Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞)
timeFrame: Pre-dose, 0.5, 1, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants
measure: Doravirine Maximum Concentration (Cmax)
timeFrame: Pre-dose, 0.5, 1, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants
measure: Doravirine Trough Concentration (C24)
timeFrame: 24 hours post-dose for all participants
measure: Tenofovir Disoproxil Fumarate Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞)
timeFrame: Pre-dose, 0.5, 1, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants
measure: Tenofovir Disoproxil Fumarate Maximum Concentration (Cmax)
timeFrame: Pre-dose, 0.5, 1, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants
measure: Tenofovir Disoproxil Fumarate Trough Concentration (C24)
timeFrame: 24 hours post-dose for all participants
measure: Estradiol Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞)
timeFrame: Pre-dose, 0.5, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants
measure: Estradiol Maximum Concentration (Cmax)
timeFrame: Pre-dose, 0.5, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants
measure: Estradiol Trough Concentration (C12)
timeFrame: 12 hours post-dose for all participants
Secondary outcomes:
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Clinical Research Unit at Thomas Jefferson University
state: Pennsylvania
Study officials:
affiliation: Thomas Jefferson University
name: Walter K Kraft, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lam K, Kraft WK, Zhan T, Lam E. Bidirectional pharmacokinetics of doravirine, tenofovir, and feminizing hormones in transgender women (IDentify): A randomized crossover trial. Clin Transl Sci. 2024 Mar;17(3):e13721. doi: 10.1111/cts.13721.