Malaria, Falciparum Clinical Trial
Official title:
Artemether/ Lumefantrine: A Study of the Effect of Local Food on Pharmacokinetics of Lumefantrine and Population Pharmacokinetics of Lumefantrine Among Ugandan Children
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.
Status | Recruiting |
Enrollment | 70 |
Est. completion date | March 2015 |
Est. primary completion date | September 2014 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 6 Months to 5 Years |
Eligibility |
Inclusion criteria: - 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 Exclusion criteria: - 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 |
Allocation: Randomized, Endpoint Classification: Bio-availability Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Supportive Care
Country | Name | City | State |
---|---|---|---|
Uganda | Department of Pharmacology & Therapeutics, MakCHS, Mulago Hospital Complex | Kampala |
Lead Sponsor | Collaborator |
---|---|
Makerere University | Karolinska Institutet, Swedish International Development Cooperation Agency (SIDA) |
Uganda,
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. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Malaria treatment outcome (clinical and parasitological response) | Correlation of overall lumefantrine exposure (AUC0-28d and AUC0-8) to clinical and parasitological response to artemether lumefantrine treatment will be explored. | 28 days | No |
Other | Adverse events | To assess the relationship between drug exposure over the time and the safety profile in particular clinical parameters | 28 days | Yes |
Primary | 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 | No |
Secondary | Relative Oral Bioavailability of lumefantrine | Nested Randomized Comparative Bioavailability study: Relative oral bioavailability between the two food arms will be assessed using lumefantrine pharmacokinetic exposure outcomes at 8 h after first dose. Parameters to be considered will be attained peak concentrations (Cmax ) and area under concentration-time curve up to 8h after the first dose (AUC0-8h). Peak concentrations (Cmax) and AUC0-8h will be used for relative bioavailability evaluations using confidence interval approach for average bioequivalence. |
8 h after the first dose | No |
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