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

NCT ID: NCT04283656

Last Updated: 2025-03-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-04
• Study Completion Date: 2022-12-30

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

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment A

Single-dose oral Doravirine/lamivudine/tenofovir disoproxil

Group Type: EXPERIMENTAL

Doravirine/Lamivudine/Tenofovir

Intervention Type: DRUG

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

Treatment B

Single-dose estradiol and spironolactone co-administered with placebo

Group Type: EXPERIMENTAL

Spironolactone 100mg

Intervention Type: DRUG

200mg orally for two doses, twice-daily

Estradiol 2mg

Intervention Type: DRUG

4mg orally for two doses, twice-daily

Placebo

Intervention Type: OTHER

Placebo for one dose, daily

Treatment C

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

Group Type: EXPERIMENTAL

Doravirine/Lamivudine/Tenofovir

Intervention Type: DRUG

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

Spironolactone 100mg

Intervention Type: DRUG

200mg orally for two doses, twice-daily

Estradiol 2mg

Intervention Type: DRUG

4mg orally for two doses, twice-daily

Interventions

Doravirine/Lamivudine/Tenofovir

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

Intervention Type: DRUG

Spironolactone 100mg

200mg orally for two doses, twice-daily

Intervention Type: DRUG

Estradiol 2mg

4mg orally for two doses, twice-daily

Intervention Type: DRUG

Placebo

Placebo for one dose, daily

Intervention Type: OTHER

Other Intervention Names

Delstrigo; Aldactone

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Thomas Jefferson University

OTHER

Sponsor Role: lead

Responsible Party

Walter K. Kraft

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Walter K Kraft, MD

Role: PRINCIPAL_INVESTIGATOR

Thomas Jefferson University

Locations

Clinical Research Unit at Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 38421210 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

15431

Identifier Type: -

Identifier Source: org_study_id