Phase 1
N=8
Evaluating Drug Interactions Between Doravirine With Estradiol and Spironolactone in Healthy Transgender Women
Transgender Health · Gender Dysphoria · Transgender Women · Human Immunodeficiency Virus
Bottom Line
View on ClinicalTrials.gov: NCT04283656 ↗Enrolled (actual)
8
Serious AEs
0.0%
Results posted
Mar 2025
Primary outcome: Primary: Doravirine Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞) — 17798.14; 18413.21 hr*ng/mL
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Doravirine/Lamivudine/Tenofovir (Drug); Spironolactone 100mg (Drug); Estradiol 2mg (Drug); Placebo (Other)
- Age
- Adult · 18+ yrs
- Sex
- Female
- Sponsor
- Thomas Jefferson University
- Primary completion
- Oct 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Doravirine Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞) |
17798.14; 18413.21 | — |
| PRIMARY Doravirine Maximum Concentration (Cmax) |
745.46; 799.67 | — |
| PRIMARY Doravirine Trough Concentration (C24) |
283.74; 292.89 | — |
| PRIMARY Tenofovir Disoproxil Fumarate Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞) |
2370.6; 2031.84 | — |
| PRIMARY Tenofovir Disoproxil Fumarate Maximum Concentration (Cmax) |
178.84; 129.95 | — |
| PRIMARY Tenofovir Disoproxil Fumarate Trough Concentration (C24) |
29.59; 26 | — |
| PRIMARY Estradiol Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞) |
9370.25; 9677.31 | — |
| PRIMARY Estradiol Maximum Concentration (Cmax) |
118.08; 105.14 | — |
| PRIMARY Estradiol Trough Concentration (C12) |
100.26; 92.01 | — |
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.
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
Data sourced from ClinicalTrials.gov (NCT04283656). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.