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

Primary Purpose

Transgender Health, Gender Dysphoria, Transgender Women

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Doravirine/Lamivudine/Tenofovir
Spironolactone 100mg
Estradiol 2mg
Placebo
Sponsored by
Thomas Jefferson University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Transgender Health

Eligibility Criteria

18 Years - 45 Years (Adult)FemaleAccepts 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

Sites / Locations

  • Clinical Research Unit at Thomas Jefferson University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Other

Other

Other

Arm Label

Period I

Period II

Period III

Arm Description

Sequence E, Treatment A: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate alone Sequence F, Treatment C: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone

Sequence E and F, Treatment B: Single-dose estradiol and spironolactone co-administered with placebo

Sequence E, Treatment C: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone Sequence F, Treatment A: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate alone

Outcomes

Primary Outcome Measures

Doravirine area under the plasma concentration versus time curve from 0 hours to infinity (AUC0-∞)
Doravirine AUC derived from plasma sampling
Doravirine maximum concentration (Cmax)
Doravirine maximum observed concentration during the dosing interval
Doravirine trough concentration (C24)
Doravirine observed trough concentration during the dosing interval
Tenofovir disoproxil fumarate area under the plasma concentration versus time curve from 0 hours to infinity (AUC0-∞)
Tenofovir AUC derived from plasma sampling
Tenofovir disoproxil fumarate maximum concentration (Cmax)
Tenofovir maximum observed concentration during the dosing interval
Tenofovir disoproxil fumarate trough concentration (C24)
Tenofovir observed trough concentration during the dosing interval
Estradiol area under the plasma concentration versus time curve from 0 hours to infinity (AUC0-∞)
Estradiol AUC derived from plasma sampling
Estradiol maximum concentration (Cmax)
Estradiol maximum observed concentration during the dosing interval
Estradiol trough concentration (C12)
Estradiol observed trough concentration during the dosing interval

Secondary Outcome Measures

Full Information

First Posted
February 22, 2020
Last Updated
June 28, 2023
Sponsor
Thomas Jefferson University
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1. Study Identification

Unique Protocol Identification Number
NCT04283656
Brief Title
Evaluating Drug Interactions Between Doravirine With Estradiol and Spironolactone in Healthy Transgender Women
Acronym
IDENTIFY
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
February 14, 2022 (Actual)
Primary Completion Date
October 25, 2022 (Actual)
Study Completion Date
December 30, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Thomas Jefferson University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Transgender Health, Gender Dysphoria, Transgender Women, Human Immunodeficiency Virus

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Model Description
Three period crossover
Masking
None (Open Label)
Allocation
Randomized
Enrollment
7 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Period I
Arm Type
Other
Arm Description
Sequence E, Treatment A: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate alone Sequence F, Treatment C: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone
Arm Title
Period II
Arm Type
Other
Arm Description
Sequence E and F, Treatment B: Single-dose estradiol and spironolactone co-administered with placebo
Arm Title
Period III
Arm Type
Other
Arm Description
Sequence E, Treatment C: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone Sequence F, Treatment A: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate alone
Intervention Type
Drug
Intervention Name(s)
Doravirine/Lamivudine/Tenofovir
Other Intervention Name(s)
Delstrigo
Intervention Description
100mg/300mg/300mg orally for one dose, daily
Intervention Type
Drug
Intervention Name(s)
Spironolactone 100mg
Other Intervention Name(s)
Aldactone
Intervention Description
200mg orally for two doses, twice-daily
Intervention Type
Drug
Intervention Name(s)
Estradiol 2mg
Intervention Description
4mg orally for two doses, twice-daily
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo for one dose, daily
Primary Outcome Measure Information:
Title
Doravirine area under the plasma concentration versus time curve from 0 hours to infinity (AUC0-∞)
Description
Doravirine AUC derived from plasma sampling
Time Frame
Pre-dose, 0.5, 1, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants
Title
Doravirine maximum concentration (Cmax)
Description
Doravirine maximum observed concentration during the dosing interval
Time Frame
Pre-dose, 0.5, 1, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants
Title
Doravirine trough concentration (C24)
Description
Doravirine observed trough concentration during the dosing interval
Time Frame
24 hours post-dose for all participants
Title
Tenofovir disoproxil fumarate area under the plasma concentration versus time curve from 0 hours to infinity (AUC0-∞)
Description
Tenofovir AUC derived from plasma sampling
Time Frame
Pre-dose, 0.5, 1, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants
Title
Tenofovir disoproxil fumarate maximum concentration (Cmax)
Description
Tenofovir maximum observed concentration during the dosing interval
Time Frame
Pre-dose, 0.5, 1, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants
Title
Tenofovir disoproxil fumarate trough concentration (C24)
Description
Tenofovir observed trough concentration during the dosing interval
Time Frame
24 hours post-dose for all participants
Title
Estradiol area under the plasma concentration versus time curve from 0 hours to infinity (AUC0-∞)
Description
Estradiol AUC derived from plasma sampling
Time Frame
Pre-dose, 0.5, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants
Title
Estradiol maximum concentration (Cmax)
Description
Estradiol maximum observed concentration during the dosing interval
Time Frame
Pre-dose, 0.5, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants
Title
Estradiol trough concentration (C12)
Description
Estradiol observed trough concentration during the dosing interval
Time Frame
12 hours post-dose for all participants

10. Eligibility

Sex
Female
Gender Based
Yes
Gender Eligibility Description
Transgender Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Walter K Kraft, MD
Organizational Affiliation
Thomas Jefferson University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Clinical Research Unit at Thomas Jefferson University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Pharmacokinetic data will be updated in study outcome and results.

Learn more about this trial

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

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