Clinical Trials

MainTitle

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

This study is currently recruiting participants. (see Contacts and Locations)

Verified February 2020 by Walter K. Kraft, Thomas Jefferson University

Sponsor
Thomas Jefferson University


Information provided by (Responsible Party)
Walter K. Kraft, Thomas Jefferson University

ClinicalTrials.gov Identifier
NCT04283656

First received: February 22, 2020
Last updated: February 24, 2020
Last Verified: February 2020
History of Changes
Purpose

Purpose

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 Intervention Phase
Transgender Health
Gender Dysphoria
Transgender Women
Human Immunodeficiency Virus

Drug : Doravirine/Lamivudine/Tenofovir
Drug : Spironolactone 100mg
Drug : Estradiol 2mg
Other : Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Three 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

Further study details as provided by Walter K. Kraft, Thomas Jefferson University:

Primary Outcome Measures

  • Doravirine area under the plasma concentration versus time curve from 0 hours to infinity (AUC0-∞) [ Time Frame: Pre-dose, 0.5, 1, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants ]
    Doravirine AUC derived from plasma sampling
  • Doravirine maximum concentration (Cmax) [ Time Frame: 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
  • Doravirine trough concentration (C24) [ Time Frame: 24 hours post-dose for all participants ]
    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-∞) [ Time Frame: Pre-dose, 0.5, 1, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants ]
    Tenofovir AUC derived from plasma sampling
  • Tenofovir disoproxil fumarate maximum concentration (Cmax) [ Time Frame: 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
  • Tenofovir disoproxil fumarate trough concentration (C24) [ Time Frame: 24 hours post-dose for all participants ]
    Tenofovir observed trough concentration during the dosing interval
  • Estradiol area under the plasma concentration versus time curve from 0 hours to infinity (AUC0-∞) [ Time Frame: Pre-dose, 0.5, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants ]
    Estradiol AUC derived from plasma sampling
  • Estradiol maximum concentration (Cmax) [ Time Frame: 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
  • Estradiol trough concentration (C12) [ Time Frame: 12 hours post-dose for all participants ]
    Estradiol observed trough concentration during the dosing interval

Estimated Enrollment: 12
Study Start Date: April 2020
Estimated Study Completion Date: July 2020
Estimated Primary Completion Date: June 2020 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
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 Name: Delstrigo
Drug: Spironolactone 100mg

200mg orally for two doses, twice-daily

Other Name: 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 Name: 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 Name: Delstrigo
Drug: Spironolactone 100mg

200mg orally for two doses, twice-daily

Other Name: Aldactone
Drug: Estradiol 2mg

4mg orally for two doses, twice-daily

Eligibility

Eligibility

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

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

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT04283656

Contacts

Contact:   Edwin Lam, PharmD (215) 955-9076 edwin.lam@jefferson.edu

Locations

United States, Pennsylvania
Clinical Research Unit at Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Angela C Pallotto, RN, BSN

Sponsors and Collaborators

Thomas Jefferson University

Investigators

Principal Investigator: Walter K Kraft, MD Thomas Jefferson University
More Information

More Information


Responsible Party: Walter K. Kraft, Principal Investigator, Thomas Jefferson University  
ClinicalTrials.gov Identifier: NCT04283656   History of Changes  
Other Study ID Numbers: 15431  
Study First Received: February 22, 2020  
Last Updated: February 24, 2020  
Individual Participant Data    
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

ClinicalTrials.gov processed this data on May 24, 2020
This information is provided by ClinicalTrials.gov.