Pharmacokinetics of Antiretroviral Drugs in Lactating Women and Breastmilk Fed Infants Under 6 Months of Age in Botswana

HIV Infections Clinical Trial

— BMS02  

Official title:

Pharmacokinetics of Antiretroviral Drugs in Lactating Women and Breastmilk Fed Infants Under 6 Months of Age in Botswana

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04862975
• Other study ID #: Pro00107262
• Secondary ID: HHSN275201800003
• Status: Recruiting
• Start date: January 9, 2024
• Est. completion date: December 31, 2024

Study information

• Verified date: February 2024
• Source: Duke University
• Contact: Jessalyn Byrd, MEd, NCC
• Phone: 919-668-5297
• Email: jessalyn.byrd[@]duke.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HIV Infections
• Lactating Women on Select DOI

Intervention

Drug:
• Dolutegravir
Dolutegravir will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider. Not prescribed for this study.
• Lamivudine
Lamivudine will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider. Not prescribed for this study.
• Emtricitabine
Emtricitabine will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider. Not prescribed for this study.
• Tenofovir Disoproxil Fumarate
Tenofovir Disoproxil Fumarate will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider. Not prescribed for this study.

Locations

Country	Name	City	State
South Africa	Botswana-UPenn Partnership	Botswana	Gaborone
South Africa	Lesirane Clinic	Botswana	Gaborone
South Africa	Mogoditshane Clinic KDC	Botswana	Gaborone
South Africa	Old Naledi Clinic	Botswana	Gaborone

Sponsors (2)

Lead Sponsor	Collaborator
Duke University	The Emmes Company, LLC

Country where clinical trial is conducted

South Africa, 

References & Publications (46)

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* Note: There are 46 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	PK of selected DOIs in lactating women and breastmilk fed infants as measured by Clearance (CL) or apparent clearance (CL/F).	Clearance (CL) or apparent clearance (CL/F)	Baseline
Other	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)	Volume of distribution (V) or apparent volume of distribution (V/F)	Baseline
Other	PK of selected DOIs in lactating women and breastmilk fed infants as measured by elimination Half-life (t1/2).	Elimination Half-life (t1/2)	Baseline
Other	PK of selected DOIs in lactating women and breastmilk fed infants as measured by absorption rate constant (ka).	Absorption rate constant (ka)	Baseline
Other	PK of selected DOIs in lactating women and breastmilk fed infants as measured by area under the curve (AUC).	Area under the curve (AUC)	Baseline
Other	PK of selected DOIs in lactating women and breastmilk fed infants as measured by elimination rate constant (kel).	Elimination rate constant (kel)	Baseline
Other	PK of selected DOIs in lactating women and breastmilk fed infants as measured by maximum concentration (CMAX).	Maximum concentration (CMAX)	Baseline
Other	PK of selected DOIs in lactating women and breastmilk fed infants as measured by time to reach maximum concentration (TMAX).	Time to reach maximum concentration (TMAX)	Baseline
Other	Correlation of PK parameters (drug concentration in maternal breastmilk) with maternal BMI	Correlation of drug concentration of each DOI in maternal breastmilk with maternal BMI	Baseline
Other	Correlation of PK parameters (drug concentration in maternal plasma) with maternal BMI	Correlation of drug concentration of each DOI in maternal plasma with maternal BMI	Baseline
Other	Correlation of PK parameters (drug concentration in infant plasma) with maternal BMI	Correlation of drug concentration of each DOI in infant plasma with maternal BMI	Baseline
Other	Correlation of PK parameters (milk/plasma ratio) with maternal BMI	Correlation of milk/plasma ratio of each DOI with maternal BMI	Baseline
Other	Correlation of PK parameters (estimated daily infant dose) with maternal BMI	Correlation of estimated daily infant dose of each DOI with maternal BMI	Baseline
Other	Correlation of PK parameters (relative infant dose) with maternal BMI	Correlation of relative infant dose of each DOI with maternal BMI	Baseline
Other	Correlation of PK parameters (infant/maternal exposure ratio) with maternal BMI	Correlation of infant/maternal exposure ratio for each DOI with maternal BMI	Baseline
Other	Safety ESIs for infants	Will be collected from the medical record at the time of sample collection	Baseline
Primary	Drug concentration in maternal plasma	Drug concentration of a DOI in maternal plasma	Baseline
Primary	Drug concentration in maternal breastmilk	Drug concentration of a DOI in maternal breastmilk	Baseline
Primary	Drug concentration in infant plasma	Drug concentration of a DOI in infant plasma	Baseline
Primary	Milk/Plasma ratio	The drug exposure of selected DOIs will be evaluated using milk/plasma ratio	Baseline
Primary	Estimated daily infant dose	The drug exposure of selected DOIs will be evaluated using the estimated daily infant dose	Baseline
Primary	Relative infant dose	The drug exposure of selected DOIs will be evaluated using relative infant dose	Baseline
Primary	Infant/maternal exposure ratio	The drug exposure of selected DOIs will be evaluated using infant/maternal exposure ratio	Baseline

External Links

•   FDA: Clinical Lactation Studies: Considerations for Study Design Guidance for Industry
•   UNICEF Botswana Key Demographic Indicators