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

Human Immunodeficiency Virus Clinical Trial

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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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04283656
• Other study ID #: 15431
• Status: Completed
• Phase: Phase 1
• Start date: February 14, 2022
• Est. completion date: December 30, 2022

Study information

• Verified date: June 2023
• Source: Thomas Jefferson University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: December 30, 2022
• Est. primary completion date: October 25, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Gender Dysphoria
• HIV Infections
• Human Immunodeficiency Virus
• Transgender Health
• Transgender Women

Intervention

Drug:
• Doravirine/Lamivudine/Tenofovir
100mg/300mg/300mg orally for one dose, daily
• Spironolactone 100mg
200mg orally for two doses, twice-daily
• Estradiol 2mg
4mg orally for two doses, twice-daily

Other:
• Placebo
Placebo for one dose, daily

Locations

Country	Name	City	State
United States	Clinical Research Unit at Thomas Jefferson University	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Thomas Jefferson University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Doravirine area under the plasma concentration versus time curve from 0 hours to infinity (AUC0-8)	Doravirine AUC derived from plasma sampling	Pre-dose, 0.5, 1, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants
Primary	Doravirine maximum concentration (Cmax)	Doravirine 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
Primary	Doravirine trough concentration (C24)	Doravirine observed trough concentration during the dosing interval	24 hours post-dose for all participants
Primary	Tenofovir disoproxil fumarate area under the plasma concentration versus time curve from 0 hours to infinity (AUC0-8)	Tenofovir AUC derived from plasma sampling	Pre-dose, 0.5, 1, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants
Primary	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
Primary	Tenofovir disoproxil fumarate trough concentration (C24)	Tenofovir observed trough concentration during the dosing interval	24 hours post-dose for all participants
Primary	Estradiol area under the plasma concentration versus time curve from 0 hours to infinity (AUC0-8)	Estradiol AUC derived from plasma sampling	Pre-dose, 0.5, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants
Primary	Estradiol maximum concentration (Cmax)	Estradiol maximum observed concentration during the dosing interval	Pre-dose, 0.5, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants
Primary	Estradiol trough concentration (C12)	Estradiol observed trough concentration during the dosing interval	12 hours post-dose for all participants