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PrEP in Breastfeeding Study

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02776748
Recruitment Status : Completed
First Posted : May 18, 2016
Last Update Posted : September 21, 2021
Sponsor:
Collaborator:
Bill and Melinda Gates Foundation
Information provided by (Responsible Party):
Jared Baeten, University of Washington

Brief Summary:
The purpose of this study is to quantify the magnitude and extent of infant exposure to daily emtricitabine (FTC) /tenofovir disoproxil fumarate (TDF) via maternal breastmilk when taken pre-exposure prophylaxis (PrEP) by lactating HIV-uninfected women. The primary outcome is the steady state concentrations of emtricitabine and tenofovir in the infant plasma.

Condition or disease Intervention/treatment Phase
HIV Pre-exposure Prophylaxis During Breastfeeding Drug: FTC/TDF PrEP Phase 2 Phase 3

Detailed Description:

This is prospective, short-duration, open-label, single-arm, repeat-dose, pharmacokinetic study of daily FTC/TDF PrEP among HIV-uninfected lactating mother-infant pairs. PrEP will be administered to women through daily directly observed therapy for 10 consecutive days - sufficient to reach steady-state but discontinuing thereafter. No drug will be administered to the infant directly. Co-formulated FTC and TDF were dosed at 200 mg daily and 300 mg daily, respectively. The overall goal is to quantify the magnitude and degree to which breastfeeding infants are exposed to FTC/TDF when used as PrEP by HIV-uninfected lactating women. Maternal blood and breastmilk samples will be obtained concurrently (i.e., within 30 minutes of each other) regardless of the timing of food intake (i.e., non-fasting) on the 7th and 10th day. Peak samples will be obtained 1-2 hours after the maternal directly observed PrEP and trough samples were obtained at the end of the dosing interval (i.e., 23 to 24 hours after directly observed PrEP dose). A single infant blood sample will be obtained after the maternal 7th directly observed PrEP dose.

We will conduct quantitative measurements and analyses of infant plasma drug concentrations, infant-plasma to breastmilk and breastmilk to maternal plasma drug concentration ratios to characterize FTC and TDF transmission to breast feeding infants. Tenofovir and emtricitabine concentrations in plasma and breastmilk will be quantified via previously validated liquid chromatographic-tandem mass spectrometric (LC-MS/MS) methods in accordance with the recommendations included in the US Food and Drug Administration, Guidance for Industry, Bioanalytical Method Validation guidelines.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: An Open-label, Short-duration, Repeat-dose Study of Breastmilk Excretion and Infant Absorption of Daily Oral Tenofovir Disoproxil Fumarate/Emtricitabine When Used by HIV-uninfected Lactating Women
Study Start Date : January 2015
Actual Primary Completion Date : May 2015
Actual Study Completion Date : December 2015


Arm Intervention/treatment
FTC-TDF
Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) PrEP: 200mg FTC /300 mg TDF
Drug: FTC/TDF PrEP
Daily oral directly observed FTC/TDF PrEP administered to breastfeeding HIV-uninfected women
Other Name: Truvada PrEP




Primary Outcome Measures :
  1. Steady state plasma concentrations of emtricitabine and tenofovir in the infants of breastfeeding women using PrEP: Quantity of PrEP medications in the infant plasma. [ Time Frame: Time averaged: 10 days ]
    Infant exposure measured as median (interquartile range) concentrations of emtricitabine and tenofovir infant plasma.

  2. Steady state plasma concentrations of emtricitabine and tenofovir in the infants of breastfeeding women using PrEP: Detectable and quantifiable concentrations of PrEP medications in the infant plasma. [ Time Frame: Time averaged: 10 days ]
    Measure the proportion of infant plasma samples with concentrations of emtricitabine and tenofovir below the assay lower limit of quantification.

  3. Steady state concentrations of emtricitabine and tenofovir in plasma of HIV-uninfected women using PrEP. [ Time Frame: Time averaged: 10 days ]
    Measure median (interquartile range) concentrations of emtricitabine and tenofovir in maternal plasma.

  4. Steady state concentrations of emtricitabine and tenofovir in breastmilk of HIV-uninfected women using PrEP. [ Time Frame: Time averaged: 10 days ]
    Measure median (interquartile range) concentrations of emtricitabine and tenofovir in breast milk.

  5. Infant plasma-to-maternal breast milk emtricitabine and tenofovir concentration ratios. [ Time Frame: Time averaged: 10 days ]
    Measure median (interquartile range) infant plasma-to-maternal breast milk emtricitabine and tenofovir concentration ratios.

  6. Infant daily dose of tenofovir and emtricitabine received from breastmilk [ Time Frame: Time averaged: 10 days ]
    We will compute the infant drug dose received from breastmilk per day (infant Computed as the product of breast milk tenofovir and emtricitabine concentrations and the estimated volume of breast milk consumed by infant daily. We will assume the daily amount of breast milk consumed by the infant to be 150 mL/kg/day, the standardized milk consumption of the average milk intake of a fully breast-fed infant. Measure median (interquartile range) infant daily dose for tenofovir and emtricitabine from breastmilk.

  7. Infant dose fraction for tenofovir and emtricitabine. [ Time Frame: Time averaged: 10 days ]
    Infant dose fraction (i.e., exposure index) represents the daily amount of drug dose an infant would ingest from breast milk as a percentage of the recommended pediatric therapeutic daily dose. Infant dose fraction will be computed as as: infant dose fraction (%) = infant dose from breast milk *100/infant therapeutic dose. Measure median (interquartile range) infant dose fraction.

  8. Maternal breastmilk emtricitabine and tenofovir to plasma concentration ratios. [ Time Frame: Time averaged: 10 days ]
    Measure median (interquartile range) of maternal breastmilk emtricitabine and tenofovir to plasma concentration ratios.

  9. Serious adverse events in infants of breastfeeding HIV-uninfected women using PrEP. [ Time Frame: Time averaged: 10 days ]
    Number of infants with serious adverse effects.

  10. Serious adverse events in breastfeeding HIV-uninfected women using PrEP. [ Time Frame: Time averaged: 10 days ]
    Number of women with serious adverse effects.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

For infant's mother and father

  • Able and willing to provide informed consent for the infant to participate in the study
  • Of legal age ≥18 years to consent

For HIV-uninfected mother, in addition to the criteria noted immediately above:

  • Willing to provide breast milk samples and breastfeed during the duration of the study 0-24 weeks postpartum
  • Breastfeeding an infant
  • HIV-uninfected based on negative HIV rapid tests, both at study screening and at the enrollment visit
  • Adequate renal function, defined by normal creatinine levels and estimated creatinine clearance ≥60 mL/min
  • Not infected with hepatitis B virus, as determined by a negative hepatitis B surface antigen test
  • Not currently using PrEP
  • Note: single mothers will be eligible to participate in this study. Where possible the father's permission was be obtained. When the father is unknown, incompetent, deceased, or not reasonably available, or when only the mother has the legal responsibility for the care and custody of the child, infant participation will be based on the mother's consent and documentation will be added to file.

For infant

  • Infant born to eligible women (both male and female infants will be included)
  • Age 0-24 weeks
  • Otherwise infant has no serious infections or active clinically significant medical problems

Exclusion Criteria:

  • Women breastfeeding more than one child
  • Preterm babies or infants with low birth weight (i.e. ≤2000mg)

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): NCT02776748


Locations
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Kenya
Partners in Prevention-Thika
Thika, Kenya
Uganda
Partners in Prevention-Infectious Diseases Institute LTD
Kampala, Uganda
Sponsors and Collaborators
University of Washington
Bill and Melinda Gates Foundation
Investigators
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Principal Investigator: Jared M Baeten, MD, PhD University of Washington
Study Director: Kenneth K Mugwanya, MBChB, MS University of Washington
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Jared Baeten, Professor, Global Health, Medicine, & Epidemiology, University of Washington
ClinicalTrials.gov Identifier: NCT02776748    
Other Study ID Numbers: 46363
First Posted: May 18, 2016    Key Record Dates
Last Update Posted: September 21, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data from the PrEP in Breastfeeding Study are available by contacting the International Clinical Research Center at the University of Washington (icrc@uw.edu).
Keywords provided by Jared Baeten, University of Washington:
Tenofovir disoproxil
Pre-exposure prophylaxis
Breastfeeding
Emtricitabine
Tenofovir
Post-partum
HIV prevention
Women
Pharmacokinetics
Additional relevant MeSH terms:
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Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Anti-HIV Agents
Anti-Retroviral Agents