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

Sponsor
Thomas Jefferson University (Other)
Overall Status
Recruiting
CT.gov ID
NCT04283656
Collaborator
(none)
12
Enrollment
1
Location
3
Arms
5.5
Anticipated Duration (Months)
2.2
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
12 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Intervention Model Description:
Three period crossoverThree period crossover
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Feb 14, 2022
Anticipated Primary Completion Date :
Jun 1, 2022
Anticipated Study Completion Date :
Jul 30, 2022

Arms and Interventions

Arm Intervention/Treatment
Other: Period I

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

Drug: Doravirine/Lamivudine/Tenofovir
100mg/300mg/300mg orally for one dose, daily
Other Names:
  • Delstrigo

    • Drug: Spironolactone 100mg
    200mg orally for two doses, twice-daily
    Other Names:
  • Aldactone

    • Drug: Estradiol 2mg
    4mg orally for two doses, twice-daily
    Other: Period II

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

    Drug: Spironolactone 100mg
    200mg orally for two doses, twice-daily
    Other Names:
  • Aldactone

    • Drug: Estradiol 2mg
    4mg orally for two doses, twice-daily

    Other: Placebo
    Placebo for one dose, daily
    Other: Period III

    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

    Drug: Doravirine/Lamivudine/Tenofovir
    100mg/300mg/300mg orally for one dose, daily
    Other Names:
  • Delstrigo

    • Drug: Spironolactone 100mg
    200mg orally for two doses, twice-daily
    Other Names:
  • Aldactone

    • Drug: Estradiol 2mg
    4mg orally for two doses, twice-daily

    Outcome Measures

    Primary Outcome Measures

    1. Doravirine area under the plasma concentration versus time curve from 0 hours to infinity (AUC0-∞) [Pre-dose, 0.5, 1, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants]

      Doravirine AUC derived from plasma sampling

    2. Doravirine maximum concentration (Cmax) [Pre-dose, 0.5, 1, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants]

      Doravirine maximum observed concentration during the dosing interval

    3. Doravirine trough concentration (C24) [24 hours post-dose for all participants]

      Doravirine observed trough concentration during the dosing interval

    4. Tenofovir disoproxil fumarate area under the plasma concentration versus time curve from 0 hours to infinity (AUC0-∞) [Pre-dose, 0.5, 1, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants]

      Tenofovir AUC derived from plasma sampling

    5. Tenofovir disoproxil fumarate maximum concentration (Cmax) [Pre-dose, 0.5, 1, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants]

      Tenofovir maximum observed concentration during the dosing interval

    6. Tenofovir disoproxil fumarate trough concentration (C24) [24 hours post-dose for all participants]

      Tenofovir observed trough concentration during the dosing interval

    7. Estradiol area under the plasma concentration versus time curve from 0 hours to infinity (AUC0-∞) [Pre-dose, 0.5, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants]

      Estradiol AUC derived from plasma sampling

    8. Estradiol maximum concentration (Cmax) [Pre-dose, 0.5, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants]

      Estradiol maximum observed concentration during the dosing interval

    9. Estradiol trough concentration (C12) [12 hours post-dose for all participants]

      Estradiol observed trough concentration during the dosing interval

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 45 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    Yes
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Clinical Research Unit at Thomas Jefferson University Philadelphia Pennsylvania United States 19107

    Sponsors and Collaborators

    • Thomas Jefferson University

    Investigators

    • Principal Investigator: Walter K Kraft, MD, Thomas Jefferson University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Walter K. Kraft, Principal Investigator, Thomas Jefferson University
    ClinicalTrials.gov Identifier:
    NCT04283656
    Other Study ID Numbers:
    • 15431
    First Posted:
    Feb 25, 2020
    Last Update Posted:
    Feb 21, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    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
    Additional relevant MeSH terms:
    Acquired Immunodeficiency Syndrome
    HIV Infections
    Gender Dysphoria
    Tenofovir
    Lamivudine
    Spironolactone
    Estradiol

    Study Results

    No Results Posted as of Feb 21, 2022