Evaluating Drug Interactions Between Doravirine With Estradiol and Spironolactone in Healthy Transgender Women (IDENTIFY)

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

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.

Study Overview

• Status: Completed
• Conditions: Gender Dysphoria; Transgender Women; Transgender Health; Human Immunodeficiency Virus
• Intervention / Treatment: Drug: Doravirine/Lamivudine/Tenofovir; Drug: Spironolactone 100mg; Drug: Estradiol 2mg; Other: Placebo

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

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Clinical Research Unit at Thomas Jefferson University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A; Single-dose oral Doravirine/lamivudine/tenofovir disoproxil	Drug: Doravirine/Lamivudine/Tenofovir; 100mg/300mg/300mg orally for one dose, daily; Other Names: Delstrigo
Experimental: Treatment B; Single-dose estradiol and spironolactone co-administered with placebo	Drug: Spironolactone 100mg; 200mg orally for two doses, twice-daily; Other Names: Aldactone; Drug: Estradiol 2mg; 4mg orally for two doses, twice-daily; Other: Placebo; Placebo for one dose, daily
Experimental: Treatment C; Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone	Drug: Doravirine/Lamivudine/Tenofovir; 100mg/300mg/300mg orally for one dose, daily; Other Names: Delstrigo; Drug: Spironolactone 100mg; 200mg orally for two doses, twice-daily; Other Names: Aldactone; Drug: Estradiol 2mg; 4mg orally for two doses, twice-daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Doravirine Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞)	Doravirine AUC derived from plasma sampling with geometric mean ratio compared between treatment arms	Pre-dose, 0.5, 1, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants
Doravirine Maximum Concentration (Cmax)	Doravirine maximum observed concentration during the dosing interval with geometric mean ratio compared between treatment arms	Pre-dose, 0.5, 1, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants
Doravirine Trough Concentration (C24)	Doravirine observed trough concentration during the dosing interval with geometric mean ratio compared between treatment arms	24 hours post-dose for all participants
Tenofovir Disoproxil Fumarate Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞)	Tenofovir AUC derived from plasma sampling with geometric mean ratio compared between treatment arms	Pre-dose, 0.5, 1, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants
Tenofovir Disoproxil Fumarate Maximum Concentration (Cmax)	Tenofovir maximum observed concentration during the dosing interval	Pre-dose, 0.5, 1, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants
Tenofovir Disoproxil Fumarate Trough Concentration (C24)	Tenofovir observed trough concentration during the dosing interval with geometric mean ratio compared between treatment arms	24 hours post-dose for all participants
Estradiol Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞)	Estradiol area under the plasma concentration versus time curve from 0 hours to infinity (AUC) derived from plasma sampling	Pre-dose, 0.5, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants
Estradiol Maximum Concentration (Cmax)	Estradiol maximum observed concentration during the dosing interval with geometric mean ratio compared between treatment arms	Pre-dose, 0.5, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants
Estradiol Trough Concentration (C12)	Estradiol observed trough concentration during the dosing interval with geometric mean ratio compared between treatment arms	12 hours post-dose for all participants

Collaborators and Investigators

• Sponsor: Thomas Jefferson University
• Investigators: Principal Investigator: Walter K Kraft, MD, Thomas Jefferson University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2022
• Primary Completion (Actual): October 25, 2022
• Study Completion (Actual): December 30, 2022

Study Registration Dates

• First Submitted: February 22, 2020
• First Submitted That Met QC Criteria: February 22, 2020
• First Posted (Actual): February 25, 2020

Study Record Updates

• Last Update Posted (Actual): March 26, 2025
• Last Update Submitted That Met QC Criteria: March 11, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Mental Disorders; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Slow Virus Diseases; Sexual Dysfunctions, Psychological; Gender Dysphoria; HIV Infections; Acquired Immunodeficiency Syndrome; Anti-Infective Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Enzyme Inhibitors; Nucleic Acid Synthesis Inhibitors; Antiviral Agents; Hormone Antagonists; Diuretics; Natriuretic Agents; Reverse Transcriptase Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Estrogens; Tenofovir; Spironolactone; Lamivudine; Estradiol
• Other Study ID Numbers: 15431

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pharmacokinetic data will be updated in study outcome and results.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes