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

Thomas Jefferson University

Status and phase: Completed; Phase 1

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

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

Study type: Interventional

Funder types: Other

Identifiers

NCT04283656

15431

Details and patient eligibility

About

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.

Full 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

Enrollment: 8 patients

Sex: Female

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

---

8 participants in 3 patient groups

Treatment A

Experimental group

Description:

Single-dose oral Doravirine/lamivudine/tenofovir disoproxil

Treatment:

Drug: Doravirine/Lamivudine/Tenofovir

Treatment B

Experimental group

Description:

Single-dose estradiol and spironolactone co-administered with placebo

Treatment:

Drug: Spironolactone 100mg

Other: Placebo

Drug: Estradiol 2mg

Treatment C

Experimental group

Description:

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

Treatment:

Drug: Spironolactone 100mg

Drug: Doravirine/Lamivudine/Tenofovir

Drug: Estradiol 2mg