Clinical trial NCT04862975: Pharmacokinetics of Antiretroviral Drugs in Lactating Women and Breastmilk Fed Infants Under 6 Months of Age in Botswana
Official title: Pharmacokinetics of Antiretroviral Drugs in Lactating Women and Breastmilk Fed Infants Under 6 Months of Age in Botswana
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Lactating Women on Select DOI
Breastmilk Fed Infants of Mothers on Select DOI
HIV Infections
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: The Emmes Company, LLC
First posted: 2021-04-28
Enrollment: 164
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Approximately 50 eligible lactating women and their breastmilk fed infants per DOI will be co-enrolled. Participants may be enrolled for one or more DOIs with a single consent. The co-enrollment of mothers and more than 1 infant (multiple birth) is permitted.

Brief summary: The purpose of this study is to characterize the pharmacokinetics (PK) of understudied drugs administered to lactating women, receiving antiretroviral drugs per SOC as prescribed by their healthcare provider, and their co-enrolled infants ≤180 days of age who receive maternal breastmilk.

Detailed description: Prospective, single-site, open label, PK and safety study. Co-enrollment of lactating women ≥18 years of age receiving drugs of interest (DOIs) per standard of care (SOC), as prescribed by their healthcare providers, and their infants who receive maternal breastmilk ≤180 days postpartum.

To understand drug transfer into breastmilk and determine subsequent infant exposure, biological samples will be collected from lactating women (blood and breastmilk) and infants (blood). The opportunistic design of this study will allow for a minimal risk study, an expanded enrollment net, evaluation of antiretroviral drugs, and capitalization of procedures performed per SOC to maximize study efficiency and data collection and minimize potential risk to participants. The data collected through this initiative will provide valuable PK, dosing, and safety information for drugs in this vulnerable population in order to inform public health.

Eligibility criteria: Inclusion Criteria Mothers/Infants:

1. Lactating women ≥18 years of age 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.
2. Informed consent, according to local IRB/REB/IEC guidelines, prior to any study-related procedures.
3. If the mother is receiving more than one DOI, the mother must have taken all DOIs that she is receiving concomitantly for the 6 doses prior to sample collection.
4. Mother participant is fluent in English or Setswana.
5. Willing to provide at least 1 of the below required samples between the co-enrolled mother/infant pair:

   * Maternal breastmilk
   * Infant blood

Exclusion Criteria Mothers/Infants:

1. Any concomitant condition which, in the opinion of the participant's healthcare provider, the site principal investigator (PI), a research nurse, or designee conducting the study, would preclude participation in the study.
2. Known pregnancy of mother during sample collection.
3. Mother has pumped any breastmilk at all in between the last 6 direct infant feedings prior to sample collection.
4. Infant was fed breastmilk in any manner besides nursing at mother's breast for any of the last 6 feedings prior to sample collection.
5. Previous enrollment on this study.

Primary outcomes:
measure: Drug concentration in maternal plasma
timeFrame: Baseline
measure: Drug concentration in maternal breastmilk
timeFrame: Baseline
measure: Drug concentration in infant plasma
timeFrame: Baseline
measure: Milk/Plasma ratio
timeFrame: Baseline
measure: Estimated daily infant dose
timeFrame: Baseline
measure: Relative infant dose
timeFrame: Baseline
measure: Infant/maternal exposure ratio
timeFrame: Baseline
Secondary outcomes:
Other outcomes:
measure: PK of selected DOIs in lactating women and breastmilk fed infants as measured by Clearance (CL) or apparent clearance (CL/F).
timeFrame: Baseline
measure: PK of selected DOIs in lactating women and breastmilk fed infants as measured by volume of distribution (V) or apparent volume of distribution (V/F)
timeFrame: Baseline
measure: PK of selected DOIs in lactating women and breastmilk fed infants as measured by elimination Half-life (t1/2).
timeFrame: Baseline
measure: PK of selected DOIs in lactating women and breastmilk fed infants as measured by absorption rate constant (ka).
timeFrame: Baseline
measure: PK of selected DOIs in lactating women and breastmilk fed infants as measured by area under the curve (AUC).
timeFrame: Baseline
measure: PK of selected DOIs in lactating women and breastmilk fed infants as measured by elimination rate constant (kel).
timeFrame: Baseline
measure: PK of selected DOIs in lactating women and breastmilk fed infants as measured by maximum concentration (CMAX).
timeFrame: Baseline
measure: PK of selected DOIs in lactating women and breastmilk fed infants as measured by time to reach maximum concentration (TMAX).
timeFrame: Baseline
measure: Correlation of PK parameters (drug concentration in maternal breastmilk) with maternal BMI
timeFrame: Baseline
measure: Correlation of PK parameters (drug concentration in maternal plasma) with maternal BMI
timeFrame: Baseline
measure: Correlation of PK parameters (drug concentration in infant plasma) with maternal BMI
timeFrame: Baseline
measure: Correlation of PK parameters (milk/plasma ratio) with maternal BMI
timeFrame: Baseline
measure: Correlation of PK parameters (estimated daily infant dose) with maternal BMI
timeFrame: Baseline
measure: Correlation of PK parameters (relative infant dose) with maternal BMI
timeFrame: Baseline
measure: Correlation of PK parameters (infant/maternal exposure ratio) with maternal BMI
timeFrame: Baseline
measure: Safety ESIs for infants
timeFrame: Baseline
Locations:
city: Botswana
country: South Africa
facility: Botswana-UPenn Partnership
state: Gaborone
city: Botswana
country: South Africa
facility: Lesirane Clinic
state: Gaborone
city: Botswana
country: South Africa
facility: Mogoditshane Clinic KDC
state: Gaborone
city: Botswana
country: South Africa
facility: Old Naledi Clinic
state: Gaborone
Study officials:
affiliation: Duke University
name: Matt Kelly, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Utah
name: Kevin Watt, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Stephen Balevic, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Angelique Boutzoukas, MD
role: PRINCIPAL_INVESTIGATOR
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