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

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

Sponsors

Lead Sponsor: Thomas Jefferson University

Source 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.

Overall Status Recruiting
Start Date April 2020
Completion Date July 2020
Primary Completion Date June 2020
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
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 maximum concentration (Cmax) Pre-dose, 0.5, 1, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants
Doravirine trough concentration (C24) 24 hours post-dose for all participants
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 disoproxil fumarate maximum concentration (Cmax) Pre-dose, 0.5, 1, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants
Tenofovir disoproxil fumarate trough concentration (C24) 24 hours post-dose for all participants
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 maximum concentration (Cmax) Pre-dose, 0.5, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants
Estradiol trough concentration (C12) 12 hours post-dose for all participants
Enrollment 12
Condition
Intervention

Intervention Type: Drug

Intervention Name: Doravirine/Lamivudine/Tenofovir

Description: 100mg/300mg/300mg orally for one dose, daily

Other Name: Delstrigo

Intervention Type: Drug

Intervention Name: Spironolactone 100mg

Description: 200mg orally for two doses, twice-daily

Other Name: Aldactone

Intervention Type: Drug

Intervention Name: Estradiol 2mg

Description: 4mg orally for two doses, twice-daily

Intervention Type: Other

Intervention Name: Placebo

Description: Placebo for one dose, daily

Arm Group Label: Period II

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

- 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

Gender: Female

Gender Based: Yes

Gender Description: Transgender Female

Minimum Age: 18 Years

Maximum Age: 45 Years

Healthy Volunteers: Accepts Healthy Volunteers

Overall Official
Last Name Role Affiliation
Walter K Kraft, MD Principal Investigator Thomas Jefferson University
Overall Contact

Last Name: Edwin Lam, PharmD

Phone: (215) 955-9076

Email: [email protected]

Location
Facility: Status: Contact: Clinical Research Unit at Thomas Jefferson University Angela C Pallotto, RN, BSN
Location Countries

United States

Verification Date

February 2020

Responsible Party

Type: Principal Investigator

Investigator Affiliation: Thomas Jefferson University

Investigator Full Name: Walter K. Kraft

Investigator Title: Principal Investigator

Has Expanded Access No
Condition Browse
Number Of Arms 3
Arm Group

Label: Period I

Type: Other

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

Label: Period II

Type: Other

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

Label: Period III

Type: Other

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

Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Crossover Assignment

Intervention Model Description: Three period crossover

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov