While there are indications that 28 days of miltefosine is not sufficient for treating CL by L. aethiopica, a better understanding of what happens in terms of parasite clearance and drug dosing is lacking. In this study, longitudinal measurements of parasite and drug concentrations during treatment are done to monitor parasite kinetics as well as pharmacokinetics. This data will be crucial to provide more information on duration and dosing of miltefosine in CL patients globally, and in Ethiopia and pediatric patients in particular.
In this project, parasite dynamics and miltefosine pharmacokinetics in the skin and blood during routine durations of miltefosine treatment (4-8 weeks) are studied with the aim to provide evidence to optimize miltefosine dosing for treatment of CL. By also studying these factors in children who get allometric miltefosine dosing, data which can be used to adapt the current allometric dosing scheme specifically to children with CL will be produced. Exploratory objectives will look into searching for more objective outcome assessment measures, resistance, helminth infection and nutritional status as potential factors affecting treatment response.
Study Type
OBSERVATIONAL
Enrollment
80
Miltefosine will be prescribed by the treating physician for a minimum of 4 weeks. If treatment response is not sufficient, treatment extension could be decided by the treating physician up to 8 weeks
Africa Leprosy, Tuberculosis, Rehabilitation and Training (ALERT) Hospital
Addis Ababa, Ethiopia
RECRUITINGMiltefosine plasma concentrations - Area under the plasma concentration versus time curve (AUC)
Determined by LC-MS/MS, miltefosine pharmacokinetics are assessed through calculation of the area under the plasma concentration-time curve from start of treatment until end of treatment (AUC0-EoT), stratified by whether patients received allometric dosing or not.
Time frame: Day 0, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42/Day 56, Day 90, Day 180
Miltefosine plasma concentrations - Maximum plasma concentration (Cmax)
Determined by LC-MS/MS, stratified by whether patients received allometric dosing or not.
Time frame: Day 0, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42/Day 56, Day 90, Day 180
MIltefosine plasma concentrations - Time of maximum concentration (Tmax)
Determined by LC-MS/MS, stratified by whether patients received allometric dosing or not.
Time frame: Day 0, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42/Day 56, Day 90, Day 180
Parasite kinetics in blood and skin
To determine parasite kinetics in terms of Ct-values in blood and skin (microbiopsy sample) measured by quantitative PCR
Time frame: Day 0, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42/Day 56, Day 90, Day 180
Adapted allometric dosing scheme specifically for children with CL
Population PK and PK-PD analysis of the relationship between miltefosine exposure and parasite kinetics will be done at UU, based on results from miltefosine plasma concentrations. Structural pharmacokinetic modelling will be used to develop and simulate alternative dosing schemes for children with CL, using Monte Carlo simulations.
Time frame: Day 0, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42/Day 56, Day 90, Day 180
Treatment outcomes of patients on miltefosine treatment
Clinical cure rate determined by complete flattening, complete reepithelization and absence of erythema, crustation, and swelling
Time frame: Day 28, day 90 and day 180
Assess safety of miltefosine
Side-effects: number and proportion of patients with adverse events
Time frame: Day 28
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