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

NCT04283656 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 15431
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Transgender Health; Gender Dysphoria; Transgender Women; Human Immunodeficiency Virus

Outcome Measures

Primary Outcomes (9)

• 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

Study Arms (3)

Treatment A

EXPERIMENTAL

Single-dose oral Doravirine/lamivudine/tenofovir disoproxil

Drug: Doravirine/Lamivudine/Tenofovir

Treatment B

EXPERIMENTAL

Single-dose estradiol and spironolactone co-administered with placebo

Drug: Spironolactone 100mg; Drug: Estradiol 2mg; Other: Placebo

Treatment C

EXPERIMENTAL

Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone

Drug: Doravirine/Lamivudine/Tenofovir; Drug: Spironolactone 100mg; Drug: Estradiol 2mg

Interventions

Doravirine/Lamivudine/Tenofovir DRUG

100mg/300mg/300mg orally for one dose, daily

Also known as: Delstrigo

Treatment A; Treatment C

Spironolactone 100mg DRUG

200mg orally for two doses, twice-daily

Also known as: Aldactone

Treatment B; Treatment C

Estradiol 2mg DRUG

4mg orally for two doses, twice-daily

Treatment B; Treatment C

Placebo OTHER

Placebo for one dose, daily

Treatment B

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: Transgender Female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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
• Recent significant blood or plasma donation

Sponsors & Collaborators

• Thomas Jefferson University: lead

Study Sites (1)

Clinical Research Unit at Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (1)

• 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.

  PMID: 38421210 RESULT

MeSH Terms

Conditions

Gender Dysphoria; Acquired Immunodeficiency Syndrome

Interventions

doravirine; Canrenoic Acid; Spironolactone; Estradiol

Condition Hierarchy (Ancestors)

Sexual Dysfunctions, Psychological; Mental Disorders; HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Lactones; Organic Chemicals; Pregnenes; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Dr. Walter K. Kraft
• Organization: Thomas Jefferson University

Walter.Kraft@jefferson.edu

(215) 955-9077

Study Officials

• Walter K Kraft, MD

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Three period crossover

Study Record Dates

• First Submitted: February 22, 2020
• First Posted: February 25, 2020
• Study Start: January 4, 2022
• Primary Completion: October 25, 2022
• Study Completion: December 30, 2022
• Last Updated: March 26, 2025
• Results First Posted: March 26, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)