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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04283656
Recruitment Status : Recruiting
First Posted : February 25, 2020
Last Update Posted : February 26, 2020
Sponsor:
Information provided by (Responsible Party):
Walter K. Kraft, Thomas Jefferson University

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
Transgender Health Gender Dysphoria Transgender Women Human Immunodeficiency Virus Drug: Doravirine/Lamivudine/Tenofovir Drug: Spironolactone 100mg Drug: Estradiol 2mg Other: Placebo Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
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
Estimated Study Start Date : April 2020
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : July 2020


Arm Intervention/treatment
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

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

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




Primary Outcome Measures :
  1. 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

  2. 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

  3. Doravirine trough concentration (C24) [ Time Frame: 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-∞) [ 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

  5. 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

  6. Tenofovir disoproxil fumarate trough concentration (C24) [ Time Frame: 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-∞) [ 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

  8. 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

  9. Estradiol trough concentration (C12) [ Time Frame: 12 hours post-dose for all participants ]
    Estradiol observed trough concentration during the dosing interval



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Transgender 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 </= 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04283656


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

Locations
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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
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Principal Investigator: Walter K Kraft, MD Thomas Jefferson University
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Responsible Party: Walter K. Kraft, Principal Investigator, Thomas Jefferson University
ClinicalTrials.gov Identifier: NCT04283656    
Other Study ID Numbers: 15431
First Posted: February 25, 2020    Key Record Dates
Last Update Posted: February 26, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Pharmacokinetic data will be updated in study outcome and results.

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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:
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Acquired Immunodeficiency Syndrome
HIV Infections
Gender Dysphoria
Immunologic Deficiency Syndromes
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Sexual Dysfunctions, Psychological
Mental Disorders
Tenofovir
Lamivudine
Spironolactone
Estradiol
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs