Pharmacokinetics and Safety of Commonly Used Drugs in Lactating Women and Breastfed Infants

Recruiting

• Conditions: Breastfed Infants of Mothers on Select DOI; Lactating Women on Select DOI
• Interventions: Drug: Tranexamic acid (TXA); Drug: Hydrocodone; Drug: labetalol; Drug: metformin; Drug: nifedipine; Drug: oxycodone; Drug: clindamycin; Drug: azithromycin; Drug: escitalopram; Drug: sertraline; Drug: Ciprofloxacin; Drug: ondansetron; Drug: Doxycycline; Drug: Levofloxacin; Drug: Methylphenidate; Drug: Citalopram; Drug: Sumatriptan; Drug: Cyclobenzaprine; Drug: Furosemide; Drug: Rosuvastatin; Drug: Gabapentin; Drug: Hydrochlorothiazide; Drug: Hydroxyurea; Drug: Trazodone; Drug: Topiramate; Drug: Valganciclovir; Drug: Remdesivir; Drug: Venlafaxine; Drug: Verapamil; Drug: Fluvoxamine; Drug: Anakinra; Drug: Tocilizumab; Drug: Amoxicillin; Drug: Bupropion; Drug: Buprenorphine; Drug: Levetiracetam; Drug: Paroxetine; Drug: Duloxetine

• Registration Number: NCT03511118
• Lead Sponsor: Duke University

Brief Summary

Over half of women in the US who are breastfeeding their infants take prescription drugs. You are being asked to participate in this study because you are breastfeeding your infant and are currently taking, as part of your medical care, at least one of the drugs we are studying. We are interested in studying drugs commonly prescribed to women who are breastfeeding so we can learn more about the amount of drug that is transferred to breastmilk and estimate how much of drug that is consumed by breastfed infants.

Detailed Description

The purpose of this study is to understand if the study drugs of interest are found in breastmilk and how much; to estimate the amount of drug that is consumed by breastfed infants and what effect this may have on infants; and to share what we learn with other researchers. The study drugs of interest have Food and Drug Administration (FDA) approval, but there is little or no information about the amount of drug found in the breastmilk of mothers who take them; the amount of drug that may be transferred to their infant's through breastmilk; or the effects this transfer may have on their infants. During this study we will ask to collect breastmilk and blood from mothers, and blood from infants, to measure the amount of study drug of interest in these body fluids. Results from this study will help researchers better understand how much of the study drug of interest is in your blood and breastmilk, and how much of the study drug of interest may be in your infant's blood because of breastfeeding.

Study Timeline

• Study First Submitted: 2018-04-23
• Study First Submitted QC: 2018-04-23
• Study First Posted: 2018-04-27
• Study Start: 2018-10-04
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-12
• Last Update Posted: 2024-12-17
• Primary Completion: 2026-07-23
• Study Completion: 2027-07-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1600

Inclusion Criteria

• Lactating women who are receiving at least one DOI per SOC who are ≤180 days postpartum, and their infants (≤180 days of age) who receive maternal breastmilk.
• Informed consent/HIPAA obtained, according to local IRB/REB/IEC guidelines, prior to any study-related procedures. Lactating women who are not legal adults and their breastfed infants may be enrolled if they assent to participate in the study and consent is obtained from their legal guardian according to local IRB/REB/IEC guidelines.

Exclusion Criteria

• Any concomitant condition which, in the opinion of the physicians providing patient care or the principal investigator conducting the study, would preclude a subject's participation in the study.
• Known pregnancy during PK sampling.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Tranexamic acid (TXA)	Tranexamic acid (TXA)	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
Hydrocodone	Hydrocodone	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
labetalol	labetalol	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
metformin	metformin	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
nifedipine	nifedipine	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
oxycodone	oxycodone	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
clindamycin	clindamycin	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
azithromycin	azithromycin	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
escitalopram	escitalopram	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
sertraline	sertraline	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
Ciprofloxacin	Ciprofloxacin	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
ondansetron	ondansetron	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
Doxycycline	Doxycycline	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
Levofloxacin	Levofloxacin	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
Methylphenidate	Methylphenidate	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
Citalopram	Citalopram	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
Sumatriptan	Sumatriptan	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
Cyclobenzaprine	Cyclobenzaprine	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
Furosemide	Furosemide	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
Rosuvastatin	Rosuvastatin	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
Gabapentin	Gabapentin	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
Hydrochlorothiazide	Hydrochlorothiazide	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
Hydroxyurea	Hydroxyurea	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
Trazodone	Trazodone	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
Topiramate	Topiramate	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
Valganciclovir	Valganciclovir	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
Remdesivir	Remdesivir	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
Venlafaxine	Venlafaxine	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
Verapamil	Verapamil	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
Fluvoxamine	Fluvoxamine	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
Anakinra	Anakinra	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
Tocilizumab	Tocilizumab	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
Amoxicillin	Amoxicillin	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
Bupropion	Bupropion	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
Buprenorphine	Buprenorphine	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
Levetiracetam	Levetiracetam	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
Paroxetine	Paroxetine	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.
Duloxetine	Duloxetine	No intervention, observational study and PK collections The study objectives are to characterize the PK and safety profile of DOIs that are commonly administered to lactating women. The primary focus of this analysis will be to determine drug concentrations in breastmilk and to estimate the relative infant dose.

Primary Outcome Measures

Name	Time	Method
M/P ratio	Until the infant becomes 180 days of age	Characterize the pharmacokinetics using maternal milk/plasma exposure ratio is calculated by dividing the BMS01 drug of interest breastmilk concentration by the BMS01 drug of interest in maternal plasma concentration.
RID	Until the infant becomes 180 days of age	Pharmacokinetics is characterized by relative infant dose is a method of relating the potential dose of the drug delivered to the infant to the typical therapeutic dose given to the mother.
I/M ratio	Until the infant becomes 180 days of age	Pharmacokinetics is characterized using infant maternal/exposure ratio. IM ratio is calculated using the average infant plasma concentration of the BMS01 drug of interest and historical value of clearance in infants.
DID	Until the infant becomes 180 days of age	Pharmacokinetics is characterized by estimated daily infant dose-daily infant dose which estimates the quantity of drug delivered to an infant via breastmilk in a given day.

Secondary Outcome Measures

Name	Time	Method
AE	Up until 180 days of age	Safety profile of commonly used drugs in infants exposed to drugs in breastmilk is characterized by Adverse Events(AE) which are collected at each time point when the study-specific procedure occurred and up until 1 hour after.
ESI	Until the infant becomes 180 days of age	Safety profile of commonly used drugs in infants exposed to drugs in breastmilk is characterized by Events of Special Interest(ESI) which include any pre-specified safety event that could be related to BMS01 drug of interest exposure. ESI's are only assessed for infants and only at study visits from the time the BMS01 DOI was initiated in mother and infant began breast milk feeding through the end of the study / infant age ≤ 180 days
Safety profile of commonly used drugs in infants exposed to drugs in breastmilk	Until the infant becomes 180 days of age	see Cohort 1-31 for listing of drugs
SAE	Up until 180 days of age	Safety profile of commonly used drugs in infants exposed to drugs in breastmilk is characterized by Serious Adverse Events which are directly related to study procedures and were recorded from participants (infant or mother) at each time point when the study-specific procedure occurred and up until 1 hour after.

Trial Locations

Locations (22)

Northwestern University; 🇺🇸 Chicago, Illinois, United States

Ann and Robert H. Lurie Childrens Hospital of Chicago; 🇺🇸 Chicago, Illinois, United States

Loma Linda University Health; 🇺🇸 Loma Linda, California, United States

University of Pittsburgh School of Medicine; 🇺🇸 Pittsburgh, Pennsylvania, United States

University of Texas Medical Branch - Galveston; 🇺🇸 Galveston, Texas, United States

University of Washington; 🇺🇸 Seattle, Washington, United States

University of Texas Health Science Center at Houston; 🇺🇸 Houston, Texas, United States

The Women's Hospital of Texas; 🇺🇸 Houston, Texas, United States

Duke University Maternal and Fetal Medicine; 🇺🇸 Durham, North Carolina, United States

University of Texas Health Science Center; 🇺🇸 San Antonio, Texas, United States

University of Utah; 🇺🇸 Salt Lake City, Utah, United States

University of New Mexico, Health Sciences Center; 🇺🇸 Albuquerque, New Mexico, United States

University of Iowa Hospitals and Clinics; 🇺🇸 Iowa City, Iowa, United States

Texas Tech University Health Sciences Center School of Medicine.; 🇺🇸 Amarillo, Texas, United States

Indiana University Health; 🇺🇸 Indianapolis, Indiana, United States

Children's Hospital and Clinics - Minneapolis; 🇺🇸 Minneapolis, Minnesota, United States

Centre Hospitalier Universitaire Sainte-Justine; 🇨🇦 Montréal, Quebec, Canada

University of California-San Diego Medical Center; 🇺🇸 La Jolla, California, United States

Hospital of the University of Pennsylvania Department of Maternal Fetal Medicine; 🇺🇸 Philadelphia, Pennsylvania, United States

Lawson Health Research Institute; 🇨🇦 London, Ontario, Canada

University of North Carolina Hospital; 🇺🇸 Chapel Hill, North Carolina, United States

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States