NCT01944189

Brief 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. 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. 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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
70

participants targeted

Target at P25-P50 for phase_4

Timeline
Completed

Started Sep 2013

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2013

Completed
3 days until next milestone

First Submitted

Initial submission to the registry

September 4, 2013

Completed
13 days until next milestone

First Posted

Study publicly available on registry

September 17, 2013

Completed
12 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2014

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2015

Completed
Last Updated

May 28, 2014

Status Verified

May 1, 2014

Enrollment Period

1 year

First QC Date

September 4, 2013

Last Update Submit

May 27, 2014

Conditions

Malaria, Falciparum

Keywords

lumefantrine pharmacokinetics & bioavailability

Outcome Measures

Primary Outcomes (1)

  • Pharmacokinetic (PK) exposure parameters of lumefantrine

    Sparse pharmacokinetic data will be pooled for evaluation of both individual and population PK parameter estimates of lumefantrine using Non linear mixed effect model. Pharmacokinetic exposure will be depicted principally by area under the concentration-time curves following the last dose through to 28 days of follow up (AUC0-28). Other PK parameters portraying exposure will also be assessed alongside. These include half life (t1/2), peak concentrations (Cmax) and time to reach Cmax (Tmax), apparent clearance and volumes of distribution.

    28 days

Secondary Outcomes (1)

  • Relative Oral Bioavailability of lumefantrine

    8 h after the first dose

Other Outcomes (2)

  • Malaria treatment outcome (clinical and parasitological response)

    28 days

  • Adverse events

    28 days

Study Arms (2)

Food Supplement

EXPERIMENTAL

Population PK Study will enroll 70 children receiving standard AL dose at 0, 8, 24, 36, 48, 60 hour with recommended milk or maize porridge plus oil. Both foods contain sufficient fat therefore will contribute to pool evaluations as a single cohort. A subset, 48 children will have participated in nested comparative bio-availability study as follows Standard arm children receiving single dose with milk (12) Standard arm children receiving double dose with milk (12) Experimental arm children receiving single dose with maize porridge plus oil (12) Experimental arm children receiving double dose with maize porridge plus oil (12) The rest, 22 children will have participated exclusively in PPK, receiving appropriate single or double dose with milk similar to those in standard arm

Dietary Supplement: Food

Food Supplement Arm

EXPERIMENTAL

Population PK Study will enroll 70 children receiving standard AL dose at 0, 8, 24, 36, 48, 60 hour with recommended milk or maize porridge plus oil. Both foods contain sufficient fat therefore will contribute to pool evaluations as a single cohort. A subset, 48 children will have participated in nested comparative bio-availability study as follows Standard arm children receiving single dose with milk (12) Standard arm children receiving double dose with milk (12) Experimental arm children receiving single dose with maize porridge plus oil (12) Experimental arm children receiving double dose with maize porridge plus oil (12) The rest, 22 children will have participated exclusively in PPK, receiving appropriate single or double dose with milk similar to those in standard arm

Dietary Supplement: Food

Interventions

FoodDIETARY_SUPPLEMENT

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)

Also known as: Coartem Dispersible 20/120 mg, NAFDAC REG.NO.: A4-1680
Food SupplementFood Supplement Arm

Eligibility Criteria

Age6 Months - 5 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • Diagnosis of uncomplicated falciparum malaria
  • Age ≥ 6 months to ≤5 years.
  • For nested comparative bioavailability study, age \>1 to ≤5 years of age, to avoid intense blood draws from younger children
  • Weight ≥5 kg.
  • For nested comparative bioavailability study, restrict evaluation to 2 weight/dose groups \>5 to \< 15kg and 15 to \< 25kg
  • Within 10 km radius from recruitment site
  • Informed consent from parent or guardian
  • Willingness to adherence to study procedures

You may not qualify if:

  • Severe or complicated malaria "Danger signs"
  • Mixed plasmodial infection
  • Hemoglobin \< 5 mg/dl
  • Weight \< 5kg
  • Allergy to study medication or milk
  • Medication which known to inhibit or induce CYP3A4/5 examples ketoconazole, erythromycin, steroids, antidepressants, anticonvulsants, antiretroviral drugs.
  • Receipt of artemisinin containing compounds in the past 7 days or lumefantrine in the past 28 days

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Department of Pharmacology & Therapeutics, MakCHS, Mulago Hospital Complex

Kampala, 256, Uganda

RECRUITING

Related Publications (1)

  • Mwebaza N, Jerling M, Gustafsson LL, Obua C, Waako P, Mahindi M, Ntale M, Beck O, Hellgren U. Comparable lumefantrine oral bioavailability when co-administered with oil-fortified maize porridge or milk in healthy volunteers. Basic Clin Pharmacol Toxicol. 2013 Jul;113(1):66-72. doi: 10.1111/bcpt.12065. Epub 2013 Apr 6.

    PMID: 23480875BACKGROUND

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

FoodArtemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

MalariaProtozoan InfectionsParasitic DiseasesInfectionsMosquito-Borne DiseasesVector Borne Diseases

Intervention Hierarchy (Ancestors)

Diet, Food, and NutritionPhysiological PhenomenaFood and BeveragesArtemetherArtemisininsReactive Oxygen SpeciesFree RadicalsInorganic ChemicalsOrganic ChemicalsLumefantrineFluorenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsSesquiterpenesTerpenesPolycyclic CompoundsDrug CombinationsPharmaceutical Preparations

Study Officials

  • Norah Mwebaza, MBChB M Sc

    • Department of Pharmacology and Therapeutics, Makerere University College of Health Sciences (MakCHS), Uganda

    PRINCIPAL INVESTIGATOR

  • Urban Hellgren, MD PhD

    Div Infectious Diseases, Karolinska Institutet (KI) , Sweden

    STUDY CHAIR

  • Lars L Gustaffson, MD PhD

    Dep Lab Medicine, Div Clinical Pharmacology, KI

    STUDY CHAIR

  • Paul Waako, PhD

    Department of Pharmacology and Therapeutics, MakCHS, Kampala, Uganda

    STUDY CHAIR

  • Celestino Obua, PhD

    Department of Pharmacology and Therapeutics, MakCHS, Kampala, Uganda

    STUDY CHAIR

Central Study Contacts

Norah Mwebaza, MBChB M Sc

CONTACT

+256 711589889mwebno@yahoo.com

Paul Waako, PhD

CONTACT

+256 772468458pwaako@chs.mak.ac.ug

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
SUPPORTIVE CARE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Dr Norah Mwebaza

Study Record Dates

First Submitted

September 4, 2013

First Posted

September 17, 2013

Study Start

September 1, 2013

Primary Completion

September 1, 2014

Study Completion

March 1, 2015

Last Updated

May 28, 2014

Record last verified: 2014-05

Locations

UG(1)