Pharmacokinetics of Miltefosine in Children and Adults (PK)
The purpose of this study is to determine the pharmacokinetics of miltefosine in children and adults with cutaneous leishmaniasis in plasma and intracellularly, and its relation with the parasitologic response. The results will provide pharmacologic bases to optimize the use of miltefosine for the treatment of cutaneous leishmaniasis, and will provide the knowledge base to assess the impact of pharmacokinetic behavior in children and adults on the emergence of drug resistance.
|Study Design:||Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Pharmacokinetics of Miltefosine in Children and Adults: Implications for the Treatment of Cutaneous Leishmaniasis in Colombia.|
- Intracellular and plasma concentration of miltefosine [ Time Frame: Participants will be followed for 7 months, completing 9 visits. ] [ Designated as safety issue: No ]
- Parasite burden in lesions and extralesional tissues. [ Time Frame: Participants will be followed for 7 months, completing 9 visits ] [ Designated as safety issue: No ]
|Study Start Date:||October 2011|
|Estimated Study Completion Date:||April 2014|
|Estimated Primary Completion Date:||January 2014 (Final data collection date for primary outcome measure)|
Children (2-12 years of age) and adults (18-60 years of age) will receive Miltefosine PO at a dose of 1.8-2.5 mg/kg/day for 28 days.
An open-label phase IV clinical trial of miltefosine, designed to evaluate intracellular and plasma drug pharmacokinetics in children and adults using a population pharmacokinetics design. Two study groups have been defined: 1) children 2-12 years of age (n=30) and 2) adults 18-60 years of age (n=30) with confirmed parasitological diagnosis of cutaneous leishmaniasis. The participants will receive supervised standard treatment with miltefosine: 1.8 - 2.5 mg/Kg of weight for 28 days.
Miltefosine concentration will be determined in plasma and PBMCs, from 3 or 10ml peripheral blood samples in children and adults respectively. Sampling will be conducted pre-dosing at days 0,1,15 and 29 during treatment, and at months 1, 2, 3 and 6 post-treatment.
A population pharmacokinetics analysis will be performed using a non-linear model of mixed effects with the software NONMEM, R and Piranha. Parasite burden will be determined by 7SLRNA qPCR of Leishmania from swab samples of lesions and extralesional tissues before and at the end of treatment. The relationship between pharmacokinetics and parasite persistence/burden will be determined by correlation analysis and pharmacodynamic modeling.
|Contact: Maria A Gomez, PhD||572-5552164 ext firstname.lastname@example.org|
|Contact: Alexandra Cossio, RN, MSc||572-5552164 ext email@example.com|
|Corporación Centro Internacional de entrenamiento e Investigaciónes Médicas|
|Cali, Valle, Colombia, 5930|
|Principal Investigator:||Nancy C Saravia, PhD||Centro Internacional de Entrenamiento e Investigaciones Médicas, CIDEIM|