Artemether/ Lumefantrine: A Study of the Effect of Local Food on Pharmacokinetics and Population Pharmacokinetics

Summary

Despite preventive programs, effective case management is still the cornerstone in malaria control.

This study is as a strategy towards improved recommendations in resource limited countries during artemether -lumefantrine (AL) treatment in order to maximize the public health benefits.

This is observational population pharmacokinetics study with a nested comparative bioavailability study.The study is intended to describe the variability in lumefantrine blood levels among under five year old Ugandan children with uncomplicated falciparum malaria receiving current standard artemether-lumefantrine dose regimens. Findings will form a basis for development of rational dosage recommendations. The nested comparative bioavailability study will explore effect of profiled local food intake (maize porridge plus vegetable oil versus milk) on lumefantrine uptake. As a strategy towards improved recommendations in resource limited countries during AL treatment in order to maximize the public health benefits. As a secondary objective we will correlate the variability in lumefantrine uptake to malaria treatment outcome and safety profile in this population.

Research hypotheses

1. The population pharmacokinetic profile of lumefantrine among under five year old children in Uganda with uncomplicated falciparum malaria is not affected by demographic factors.
2. There is no difference in the bioavailability of lumefantrine when artemether-lumefantrine is received with maize porridge plus vegetable oil versus milk among under five year old Ugandan children treated for uncomplicated falciparum malaria.

Conditions

• Malaria, Falciparum

Interventions

DIETARY_SUPPLEMENT

Food

Nested comparative bioavailability study: 48 out of 70 children randomized to 2 food arms under 2 dose groups of artemether lumefantrine (20mg /120 mg) treatment according to standard care weight based dose groups (\> 5 to \>15 kg receive 1 tablet and 15 to \> 25 kg receive 2 tablets) Food arms: Standard arm = Milk Experimental arm = maize porridge plus oil Groups include Single dose group= 1 tablet of artemether lumefantrine (20/120 mg) and Double dose group= 2 tablet of artemether lumefantrine (20/120 mg) Standard arm children receiving milk and single dose(12) Standard arm children receiving milk and double dose(12) Experimental arm children receiving maize porridge plus oil and single dose(12) Experimental arm children receiving maize porridge plus oil and double dose (12)

Sponsors & Collaborators

• Karolinska Institutet

  collaborator OTHER

• Swedish International Development Cooperation Agency (SIDA)

  collaborator OTHER_GOV

• Makerere University

  lead OTHER

Principal Investigators

• Norah Mwebaza, MBChB M Sc · • Department of Pharmacology and Therapeutics, Makerere University College of Health Sciences (MakCHS), Uganda

• Urban Hellgren, MD PhD · Div Infectious Diseases, Karolinska Institutet (KI) , Sweden

• Lars L Gustaffson, MD PhD · Dep Lab Medicine, Div Clinical Pharmacology, KI

• Paul Waako, PhD · Department of Pharmacology and Therapeutics, MakCHS, Kampala, Uganda

• Celestino Obua, PhD · Department of Pharmacology and Therapeutics, MakCHS, Kampala, Uganda

Study Design

Allocation

RANDOMIZED

Purpose

SUPPORTIVE_CARE

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

6 Months

Max Age

5 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2013-09-30

Primary Completion

2014-09-30

Completion

2015-03-31

Countries

• Uganda

Study Locations