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

• Status: Not yet recruiting
• Trial end date: 2022-07-30
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Thomas Jefferson University
• Treatments: Estradiol; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Lamivudine; Polyestradiol phosphate; Spironolactone; Tenofovir

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
• 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