Pharmacokinetics and Pharmacodynamics of DMPA With HIV PrEP (DynamoPrEP)

December 1, 2020 updated by: Sharon Achilles

The Pharmacokinetic and Pharmacodynamic Impacts of Depot Medroxyprogesterone Acetate on HIV Pre-exposure Prophylaxis (PrEP)

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The investigators hypothesize that a drug interaction exists between DMPA and tenofovir/emtricitabine, such that levels of tenofovir (TFV) and emtricitabine (FTC) in cervicovaginal fluid, rectal fluid, and blood plasma, and levels of the active metabolites of TFV and FTC in cervical tissue and peripheral blood mononuclear cells will be significantly lower when women are using DMPA than when they are using no hormonal contraception. The investigators secondarily hypothesize that ex vivo HIV replication will be less suppressed in cervical tissue and cervicovaginal fluid when women are using the co-formulated pre-exposure prophylaxis oral pill containing tenofovir disoproxil fumarate (TDF), the prodrug of tenofovir, and FTC concurrently with the contraceptive injection DMPA as compared to when they are on TDF/FTC alone. 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. Participants will take TDF/FTC for 14 days, after which drug levels will be measured and DMPA administered. After at least a 2 week washout period for TDF/FTC, participants will again take TDF/FTC for 14 days, and drug levels will be measured again. HIV replication activity will also be measured in cervicovaginal fluid and cervical tissue at baseline before starting TDF/FTC, after 14 days of TDF/FTC, and then after the second 14 days of TDF/FTC in the presence of DMPA.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
15

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • Magee-Womens Hospital of UPMC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 41 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • Recreational or non-medical injection drug use in the 12 months prior to screening
  • In a sexual relationship with a partner known to be HIV-positive or at high-risk of HIV (e.g. known recreational injection drug user, incarcerated in the 12 months prior to screening, etc.)
  • Has any other condition that, in the opinion of the investigator, would preclude informed consent, make study participation unsafe, or complicate the interpretation of the study outcome data, or otherwise interfere with achieving the study objectives

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: DMPA with tenofovir/emtricitabine PrEP
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
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.
Other Names:
  • Truvada®
Drug: DMPA
After completion of the first 14 day course of tenofovir/emtricitabine depot medroxyprogesterone acetate 150 mg will be administered as intramuscular injection.
Other Names:
  • Depot-Medroxyprogestereone Acetate

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Tenofovir and emtricitabine levels in the female genital tract, blood, and rectum
Time Frame: Two weeks after daily dosing of tenofovir/emtricitabine; before and after administration of depot medroxyprogesterone acetate
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Ex vivo HIV replication in cervical tissue and cervicovaginal fluid
Time Frame: Before tenofovir/emtricitabine and two weeks after daily dosing of tenofovir/emtricitabine both before and after administration of depot medroxyprogesterone acetate
Ex vivo HIV replication in cervical tissue and cervicovaginal fluid will be compared in women who are concomitantly using tenofovir/emtricitabine and DMPA as compared to using tenofovir/emtricitabine alone
Before tenofovir/emtricitabine and two weeks after daily dosing of tenofovir/emtricitabine both before and after administration of depot medroxyprogesterone acetate

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Sharon Achilles

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jessica Tarleton, MD, MPH, Clinical Instructor

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 17, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 18, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 21, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 21, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 23, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 3, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 1, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PRO17010089

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

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.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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