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Pharmacokinetics and Pharmacodynamics of DMPA With HIV PrEP (DynamoPrEP)

Primary Purpose

HIV/AIDS, Contraception

Status

Completed

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

tenofovir/emtricitabine

DMPA

About this trial

This is an interventional other trial for HIV/AIDS

Eligibility Criteria

18 Years - 45 Years (Adult)FemaleAccepts Healthy Volunteers

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

Sites / Locations

Magee-Womens Hospital of UPMC

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

DMPA with tenofovir/emtricitabine PrEP

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Ex vivo HIV replication in cervical tissue and cervicovaginal fluid

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

Full Information

NCT ID

NCT03197961

First Posted

June 21, 2017

Last Updated

December 1, 2020

Sponsor

Sharon Achilles

1. Study Identification

Unique Protocol Identification Number

NCT03197961

Brief Title

Pharmacokinetics and Pharmacodynamics of DMPA With HIV PrEP

Acronym

DynamoPrEP

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2020

Overall Recruitment Status

Completed

Study Start Date

November 17, 2017 (Actual)

Primary Completion Date

April 18, 2018 (Actual)

Study Completion Date

December 1, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Sharon Achilles

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV/AIDS, Contraception

7. Study Design

Primary Purpose

Other

Study Phase

Early Phase 1

Interventional Study Model

Sequential Assignment

Model Description

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.

Masking

None (Open Label)

Allocation

N/A

Enrollment

15 (Actual)

8. Arms, Groups, and Interventions

Arm Title

DMPA with tenofovir/emtricitabine PrEP

Arm Type

Experimental

Arm Description

Intervention Type

Combination Product

Intervention Name(s)

tenofovir/emtricitabine

Other Intervention Name(s)

Truvada®

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

DMPA

Other Intervention Name(s)

Depot-Medroxyprogestereone Acetate

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

Time Frame

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

Secondary Outcome Measure Information:

Title

Ex vivo HIV replication in cervical tissue and cervicovaginal fluid

Description

Time Frame

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

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

45 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jessica Tarleton, MD, MPH

Organizational Affiliation

Clinical Instructor

Official's Role

Principal Investigator

Facility Information:

Facility Name

Magee-Womens Hospital of UPMC

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15213

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

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Pharmacokinetics and Pharmacodynamics of DMPA With HIV PrEP

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