Pharmacokinetics of Miltefosine in Children and Adults

Phase 4

Completed

• Conditions: Cutaneous Leishmaniasis
• Interventions: Drug: Miltefosine

• Registration Number: NCT01462500
• Lead Sponsor: Centro Internacional de Entrenamiento e Investigaciones Médicas

Brief Summary

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.

Detailed Description

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 Peripheral Blood Mononuclear Cell (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 Nonlinear Mixed-effects Model (NONMEM), R and Piranha. Parasite burden will be determined by 7SLRNA Quantitative Polymerase Chain Reaction (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.

Study Timeline

• Study Start: 2011-10
• Study First Submitted: 2011-10-25
• Study First Submitted QC: 2011-10-27
• Study First Posted: 2011-10-31
• Primary Completion: 2014-05
• Study Completion: 2015-12
• Status Verified: 2016-08
• Last Update Submitted: 2016-08-18
• Last Update Posted: 2016-08-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• Age: 2-12 years of age, or 18-60 years of age
• Weight greater than 10 kg
• Parasitologic confirmation of cutaneous leishmaniasis
• Normal hepatic and kidney function

Exclusion Criteria

• Pregnant or lactating women, and women who are planning to conceive during the study or that reject the use of birth control methods.
• Use of drugs with antileishmanial potential during the previous 6 months, including pentavalent antimonials, amphotericin B, miltefosine, and pentamidine
• Mucocutaneous or visceral leishmaniasis
• For female children, menses or other evidence of reproductive maturity

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Miltefosine	Miltefosine	Miltefosine PO at a dose of 1.8-2.5 mg/kg/day for 28 days

Primary Outcome Measures

Name	Time	Method
Parasite burden in lesions and extralesional tissues.	Participants will be followed up to 26 weeks
Intracellular and plasma concentration of miltefosine	Participants will be followed up to 26 weeks.

Trial Locations

Locations (1)

Corporación Centro Internacional de entrenamiento e Investigaciónes Médicas; 🇨🇴 Cali, Valle, Colombia