Pharmacokinetics of Antimalarials in Breastfeeding Ugandan Mother-infant Pairs

NCT05676645 | Active Not Recruiting

• 1 other identifier: MILK Malaria
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Malaria,Falciparum

Outcome Measures

Primary Outcomes (3)

• AUC0-24 of lumefantrine in maternal plasma and breastmilk

  Maternal plasma exposure of lumefantrine

  0-24 hours after dose

• AUC0-24 of lumefantrine breastmilk

  Breastmilk exposure of lumefantrine

  0-24 hours after dose

• Milk to plasma ratio of lumefantrine

  Ratio of AUC in breastmilk to maternal plasma

  0-24 hours after dose

Secondary Outcomes (9)

• AUC desbutyl-lumefantrine plasma

  0-24 hours after dose

• AUC desbutyl-lumefantrine breastmilk

  0-24 hours after dose

• Milk to plasma ratio of desbutyl-lumefantrine

  0-24 hours after dose

• Infant concentration lumefantrine

  0-8 hours after maternal dose

• Infant concentration desbutyl-lumefantrine

  0-8 hours after maternal dose

Study Arms (1)

Participants

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

Drug: Artemether-lumefantrine

Interventions

Artemether-lumefantrine DRUG

National policy recommendation for treatment of uncomplicated malaria in Uganda

Participants

Eligibility Criteria

• Age: 14 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Ugandan breastfeeding women requiring treatment for uncomplicated malaria

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• University of Liverpool: lead
• Makerere University: collaborator
• Malawi-Liverpool-Wellcome Clinical Research Programme: collaborator

Study Sites (1)

Infectious Diseases Institute

Kampala, Kampala, 22418, Uganda

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma samples will be stored for up to 5 years for analysis of additional measures related to the protocol objectives

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2022
• First Posted: January 9, 2023
• Study Start: March 20, 2023
• Primary Completion: December 10, 2024
• Study Completion (Estimated): December 25, 2026
• Last Updated: May 6, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: After primary publication - intention is to place anonymised data on drug concentrations on an online repository such as Zenodo
• Access Criteria: Weblink not yet available.

Locations

UG (1)