HIV Pre-exposure Prophylaxis During BreastfeedingPhase 2/3NCT02776748
PrEP in Breastfeeding Study
A Phase 2/3 study testing FTC/TDF PrEP in people with HIV Pre-exposure Prophylaxis During Breastfeeding, run by University of Washington at 2 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- HIV Pre-exposure Prophylaxis During Breastfeeding
- What is being tested?
- FTC/TDF PrEP
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Jan 2015to Dec 2015
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 15Show fewer
- 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
Who cannot join
- Women breastfeeding more than one child
- Preterm babies or infants with low birth weight (i.e. ≤2000mg)
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
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
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.
Read the 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.
- Being tested
- FTC/TDF PrEP
- Keywords
- Tenofovir disoproxil, Pre-exposure prophylaxis, Breastfeeding, Emtricitabine, Tenofovir, Post-partum, HIV prevention, Women, Pharmacokinetics
- Medical subject headings
- Breast Feeding
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FTC/TDF PrEPDrug
Also called Truvada PrEP
Daily oral directly observed FTC/TDF PrEP administered to breastfeeding HIV-uninfected women
| Study group | Role | What they receive |
|---|---|---|
| FTC-TDF | Other | Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) PrEP: 200mg FTC /300 mg TDF Receives: Drug: FTC/TDF PrEP |
What is being measured
The primary outcome is the main question the study is designed to answer.
Steady state plasma concentrations of emtricitabine and tenofovir in the infants of breastfeeding women using PrEP: Quantity of PrEP medications in the infant plasma.
Infant exposure measured as median (interquartile range) concentrations of emtricitabine and tenofovir infant plasma.
Measured: Time averaged: 10 days
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.
Measure the proportion of infant plasma samples with concentrations of emtricitabine and tenofovir below the assay lower limit of quantification.
Measured: Time averaged: 10 days
Steady state concentrations of emtricitabine and tenofovir in plasma of HIV-uninfected women using PrEP.
Measure median (interquartile range) concentrations of emtricitabine and tenofovir in maternal plasma.
Measured: Time averaged: 10 days
Steady state concentrations of emtricitabine and tenofovir in breastmilk of HIV-uninfected women using PrEP.
Measure median (interquartile range) concentrations of emtricitabine and tenofovir in breast milk.
Measured: Time averaged: 10 days
Infant plasma-to-maternal breast milk emtricitabine and tenofovir concentration ratios.
Measure median (interquartile range) infant plasma-to-maternal breast milk emtricitabine and tenofovir concentration ratios.
Measured: Time averaged: 10 days
Infant daily dose of tenofovir and emtricitabine received from breastmilk
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.
Measured: Time averaged: 10 days
Infant dose fraction for tenofovir and emtricitabine.
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.
Measured: Time averaged: 10 days
Maternal breastmilk emtricitabine and tenofovir to plasma concentration ratios.
Measure median (interquartile range) of maternal breastmilk emtricitabine and tenofovir to plasma concentration ratios.
Measured: Time averaged: 10 days
Serious adverse events in infants of breastfeeding HIV-uninfected women using PrEP.
Number of infants with serious adverse effects.
Measured: Time averaged: 10 days
Serious adverse events in breastfeeding HIV-uninfected women using PrEP.
Number of women with serious adverse effects.
Measured: Time averaged: 10 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2016 (estimated)
- Study startJan 2015
- Primary completionMay 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV Pre-exposure Prophylaxis During BreastfeedingStudies of the same condition, open and under way.
- More trials run by University of WashingtonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Collaborators
- Bill and Melinda Gates Foundation
- Responsible party
- Principal investigator, Jared Baeten, University of Washington
- Investigators
- Jared M Baeten, MD, PhD, Principal investigator, University of WashingtonKenneth K Mugwanya, MBChB, MS, Study director, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02776748
- Sponsor's protocol ID
- 46363
- Status last verified
- Sep 2021
- First submitted
- 15 May 2016
- Last updated
- 21 Sep 2021
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: Data from the PrEP in Breastfeeding Study are available by contacting the International Clinical Research Center at the University of Washington (icrc@uw.edu).
Publications
Mugwanya KK, Hendrix CW, Mugo NR, Marzinke M, Katabira ET, Ngure K, Semiyaga NB, John-Stewart G, Muwonge TR, Muthuri G, Stergachis A, Celum CL, Baeten JM. Pre-exposure Prophylaxis Use by Breastfeeding HIV-Uninfected Women: A Prospective Short-Term Study of Antiretroviral Excretion in Breast Milk and Infant Absorption. PLoS Med. 2016 Sep 27;13(9):e1002132. doi: 10.1371/journal.pmed.1002132. eCollection 2016 Sep.
PubMed 27676257
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02776748
- Acronym / sponsor ID
- 46363
- Keywords
- Tenofovir disoproxil, Pre-exposure prophylaxis, Breastfeeding, Emtricitabine, Tenofovir, Post-partum, HIV prevention, Women
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Collaborators
- Bill and Melinda Gates Foundation
- Study start
- Jan 2015
- Primary completion
- May 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 18 May 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| FTC-TDF | Other | Drug: FTC/TDF PrEPEmtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) PrEP: 200mg FTC /300 mg TDF |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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
- Willing to provide breast milk samples and breastfeed during the duration of the study 0-24 weeks postpartum
- Breastfeeding an infant
Key exclusion criteria (2 listed)
- Women breastfeeding more than one child
- Preterm babies or infants with low birth weight (i.e. ≤2000mg)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FTC/TDF PrEPAlso: Truvada PrEPDaily oral directly observed FTC/TDF PrEP administered to breastfeeding HIV-uninfected women | Drug | FTC-TDF |
Primary outcome
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.
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.
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.
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.
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.
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.
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.
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.
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.
Serious adverse events in breastfeeding HIV-uninfected women using PrEP.
Time frame: Time averaged: 10 days
Number of women with serious adverse effects.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2021.
- Derived from this study: PubMed 27676257Mugwanya KK, Hendrix CW, Mugo NR, Marzinke M, Katabira ET, Ngure K, Semiyaga NB, John-Stewart G, Muwonge TR, Muthuri G, Stergachis A, Celum CL, Baeten JM. Pre-exposure Prophylaxis Use by Breastfeeding HIV-Uninfected Women: A Prospective Short-Term Study of Antiretroviral Excretion in Breast Milk and Infant Absorption. PLoS Med. 2016 Sep 27;13(9):e1002132. doi: 10.1371/journal.pmed.1002132. eCollection 2016 Sep.
- Individual participant dataSharing planned: Yes. Data from the PrEP in Breastfeeding Study are available by contacting the International Clinical Research Center at the University of Washington (icrc@uw.edu).
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jared M Baeten, MD, PhD principal investigator
University of Washington
Kenneth K Mugwanya, MBChB, MS study director
University of Washington
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing FTC/TDF PrEP in people with HIV Pre-exposure Prophylaxis During Breastfeeding, run by University of Washington at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Kenya, Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02776748, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2021.