Pharmacokinetics of Antimalarials in Breastfeeding Ugandan Mother-infant Pairs

Active, not recruiting

• Conditions: Malaria,Falciparum
• Interventions: Drug: Artemether-lumefantrine

• Registration Number: NCT05676645
• Lead Sponsor: University of Liverpool

Brief Summary

Lactating women requiring treatment for uncomplicated malaria will be identified and invited for sampling. The decision to treat them with first-line treatment will have been made by the clinician, not by a member of the study team. The study team will not make any adjustments to the prescribed treatment. Artemether-lumefantrine comprises six doses of medication, with the initial two doses given 8 hours apart on Day 1, and dosing 12-hourly on Day 2 and Day 3. Intensive pharmacokinetic sampling will be undertaken after Dose 5, as indicated in the schema under Section 5: plasma and breastmilk samples will be obtained pre-dose and at 2, 4, 6, 8 hours after dose. In addition, sparse sampling will be undertaken on either of these occasions; at pre-dose and between 1 to 6 hours after the first dose; a trough (pre-dose) sample after the Dose 3 or Dose 4 and lastly at 5, 7, and up to 14-days after the first dose. A heelprick sample will also be obtained from the breastfed infants at maternal trough (prior to maternal dose) and at a random timepoint (once per infant) over the 8-hour pharmacokinetic sampling visit to characterize concentrations of these drugs over an 8-hour dosing interval. In addition, a single heelprick sample will be obtained from the infant whenever the mother returns after treatment for the late sampling time points (5, 7, and 14 days post the first dose). Due to the long half-life of lumefantrine of approximately 6 days plasma sampling will be performed up to day 14 to characterise the terminal elimination of the drug. Concentrations of total plasma and breastmilk lumefantrine and desbutyl-lumefantrine will be determined.

Detailed Description

The endpoints of this study relate to the amount of antimalarial drug present in maternal blood, breastmilk and infant blood. The study is not powered for antimalarial efficacy, and therefore formal assessment of parasitological clearance is not required. The participants will be followed up until 30-40 days after completion of antimalarial therapy, and if recurrent symptoms occur, management will be as clinically indicated. Details regarding further clinical investigations and management required by either mother or infant during the follow-up period will be recorded on the CRF.

Study Timeline

• Study First Submitted: 2022-12-13
• Study First Submitted QC: 2023-01-04
• Study First Posted: 2023-01-09
• Study Start: 2023-03-20
• Primary Completion: 2024-12-10
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-25
• Last Update Posted: 2025-02-26
• Study Completion: 2026-12-25

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 30

Inclusion Criteria

1. A personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study.
2. Participants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
3. Woman is aged 18 years or older, and mothers between the age of 14-17, who are considered emancipated minors.
4. Receiving treatment for uncomplicated malaria
5. Breastfeeding at enrolment

Exclusion Criteria

1. Severe maternal or infant illness which in the opinion of the patient's clinician would interfere with her participation in the study
2. Breastfed infant is aged over 12 months
3. Partner objection to participate in the study
4. Maternal objection to infant participation

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Participants	Artemether-lumefantrine	Breastfeeding women who have been prescribed (by a clinician independent from the study team) artemether-lumefantrine to treat uncomplicated malaria

Primary Outcome Measures

Name	Time	Method
AUC0-24 of lumefantrine breastmilk	0-24 hours after dose	Breastmilk exposure of lumefantrine
AUC0-24 of lumefantrine in maternal plasma and breastmilk	0-24 hours after dose	Maternal plasma exposure of lumefantrine
Milk to plasma ratio of lumefantrine	0-24 hours after dose	Ratio of AUC in breastmilk to maternal plasma

Secondary Outcome Measures

Name	Time	Method
Infant development	0-1 year old	Infant assessment using Gross Motor Development Score (IGMDS)
Infant concentration desbutyl-lumefantrine	0-8 hours after maternal dose	Infant exposure to active metabolite
AUC desbutyl-lumefantrine plasma	0-24 hours after dose	Plasma exposure of active metabolite
Milk to plasma ratio of desbutyl-lumefantrine	0-24 hours after dose	Ratio of breastmilk to maternal plasma of active metabolite
Infant concentration lumefantrine	0-8 hours after maternal dose	Infant lumefantrine exposure
Depression and anxiety in mothers	0-1 year postpartum	General Anxiety Disorder (GAD7)
AUC desbutyl-lumefantrine breastmilk	0-24 hours after dose	Breastmilk exposure of active metabolite
Maternal beliefs about medicines	0-1 year postpartum	Beliefs about Medicines questionnaire (BMQ)

Trial Locations

Locations (1)

Infectious Diseases Institute; 🇺🇬 Kampala, Uganda