Pharmacokinetics and Pharmacodynamics of DMPA With HIV PrEP

NCT03197961 | Completed Early Phase 1 FDA Drug

• 1 other identifier: PRO17010089
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a biphasic steady state pharmacokinetic and pharmacodynamic study of TFV and FTC in healthy women comparing the drug levels and activity in the absence (first phase) and then the presence (second phase) of DMPA. The investigators will recruit 12 healthy women aged 18-45 who are HIV-negative and at low risk for acquiring HIV.

Conditions

HIV/AIDS; Contraception

Outcome Measures

Primary Outcomes (1)

• Tenofovir and emtricitabine levels in the female genital tract, blood, and rectum

  The concentrations of tenofovir and emtricitabine in plasma, cervicovaginal fluid, and rectal fluid will be compared in women who are concomitantly using tenofovir/emtricitabine and DMPA as compared to using tenofovir/emtricitabine alone.

  Two weeks after daily dosing of tenofovir/emtricitabine; before and after administration of depot medroxyprogesterone acetate

Secondary Outcomes (1)

• Ex vivo HIV replication in cervical tissue and cervicovaginal fluid

  Before tenofovir/emtricitabine and two weeks after daily dosing of tenofovir/emtricitabine both before and after administration of depot medroxyprogesterone acetate

Study Arms (1)

DMPA with tenofovir/emtricitabine PrEP

EXPERIMENTAL

the drug combination of tenofovir disoproxil fumarate 300mg and emtricitabine 200mg which is known as Truvada® will be taken orally once daily for 14 days by all participants. Drug concentrations will be measured (blood sampling) and one dose of Depot medroxyprogesterone acetate (DMPA) 150mg will be administered to each participant as an intramuscular injection after the first course of tenofovir disoproxil fumarate/emtricitabine is completed. Then, a second round of the combination of tenofovir disoproxil fumarate 300mg and emtricitabine 200mg (Truvada®) will be taken orally once daily for 14 days by all participants.

Combination Product: tenofovir/emtricitabine; Drug: DMPA

Interventions

tenofovir/emtricitabine COMBINATION_PRODUCT

At the enrollment visit, participants will be given a 14-day supply of tenofovir/emtricitabine 200mg/300mg to take once daily for 14 days. Drug concentrations will be measured as outlined in the outcomes section at the end of the two week period. The tenofovir/emtricitabine 200mg/300mg course will be repeated approximately 2 to 6 weeks later to allow washout of tenofovir/emtricitabine.

Also known as: Truvada®

DMPA with tenofovir/emtricitabine PrEP

DMPA DRUG

After completion of the first 14 day course of tenofovir/emtricitabine depot medroxyprogesterone acetate 150 mg will be administered as intramuscular injection.

Also known as: Depot-Medroxyprogestereone Acetate

DMPA with tenofovir/emtricitabine PrEP

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Women aged 18-45 at screening
• In general good health and without any clinically significant systemic disease by history and per investigator judgement
• HIV negative at screening
• Heterosexually abstinent, consistent use of condoms, or female or male partner sterilization
• Currently having regular menstrual cycles (defined as cycles lasting 21-35 days by participant report)
• Agree not to participate in any other clinical trials involving drugs or medical devices during the study period
• Willing to comply with the study protocol

You may not qualify if:

• Currently or recently pregnant or breastfeeding (defined as pregnancy or breastfeeding in the last 3 months)
• Desiring pregnancy in the next 9 months
• Use of copper intrauterine device or other method of hormonal contraception
• Status post hysterectomy and/or bilateral oophorectomy
• Positive test for Hepatitis B surface antigen at screening
• Positive for Neisseria gonorrhea, Chlamydia trachomatis, or Trichomonas vaginalis at screening
• Positive syphilis screening test at screening
• Symptomatic bacterial vaginosis, defined as vaginal symptoms with Nugent score ≥ 7. (If symptomatic bacterial vaginosis is treated at screening and asymptomatic at enrollment, the participant may enroll.)
• Renal impairment (defined as creatinine clearance \<60 ml/minute)
• Known bleeding disorder
• Daily use of NSAIDs
• Systemic use in the last two weeks or anticipated use during the study of any of the following: corticosteroids, antibiotics, anticoagulants, antifungals, antivirals, antiretrovirals, or other drugs known to prolong bleeding and/or clotting,
• Use of DMPA in the 6 months prior to screening
• Use of other hormonal contraception (including any contraceptive pill, patch, ring, implant, or levonorgestrel intrauterine device) in the 28 days prior to screening.
• Surgery requiring inpatient admission, or any abdominal surgery \<30 days prior to enrollment

Sponsors & Collaborators

• Sharon Achilles: lead

Study Sites (1)

Magee-Womens Hospital of UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Tenofovir; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; N,N-dimethyl-4-anisidine; Medroxyprogesterone Acetate

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations; Medroxyprogesterone; Hydroxyprogesterones; Progesterone; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Jessica Tarleton, MD, MPH

  Clinical Instructor

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Model Details: This is a biphasic steady state pharmacokinetic and pharmacodynamic study of healthy women to evaluate the concentrations and activity of tenofovir and emtricitabine in different compartments before and after the administration of DMPA. Each participant will receive the study medications in the same order, i.e. TDF/FTC alone for 14 days followed by TDF/FTC for 14 days after having received DMPA.

Study Record Dates

• First Submitted: June 21, 2017
• First Posted: June 23, 2017
• Study Start: November 17, 2017
• Primary Completion: April 18, 2018
• Study Completion: December 1, 2020
• Last Updated: December 3, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)