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Pharmacokinetics of Miltefosine in Children and Adults (PK)

Primary Purpose

Cutaneous Leishmaniasis

Status
Completed
Phase
Phase 4
Locations
Colombia
Study Type
Interventional
Intervention
Miltefosine
Sponsored by
Centro Internacional de Entrenamiento e Investigaciones Médicas
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cutaneous Leishmaniasis focused on measuring Miltefosine, pharmacokinetics, cutaneous leishmaniasis

Eligibility Criteria

2 Years - 60 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Corporación Centro Internacional de entrenamiento e Investigaciónes Médicas

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Miltefosine

Arm Description

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

Outcomes

Primary Outcome Measures

Intracellular and plasma concentration of miltefosine
Parasite burden in lesions and extralesional tissues.

Secondary Outcome Measures

Full Information

First Posted
October 25, 2011
Last Updated
August 18, 2016
Sponsor
Centro Internacional de Entrenamiento e Investigaciones Médicas
Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
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1. Study Identification

Unique Protocol Identification Number
NCT01462500
Brief Title
Pharmacokinetics of Miltefosine in Children and Adults
Acronym
PK
Official Title
Pharmacokinetics of Miltefosine in Children and Adults: Implications for the Treatment of Cutaneous Leishmaniasis in Colombia.
Study Type
Interventional

2. Study Status

Record Verification Date
August 2016
Overall Recruitment Status
Completed
Study Start Date
October 2011 (undefined)
Primary Completion Date
May 2014 (Actual)
Study Completion Date
December 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centro Internacional de Entrenamiento e Investigaciones Médicas
Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cutaneous Leishmaniasis
Keywords
Miltefosine, pharmacokinetics, cutaneous leishmaniasis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Miltefosine
Arm Type
Experimental
Arm Description
Miltefosine PO at a dose of 1.8-2.5 mg/kg/day for 28 days
Intervention Type
Drug
Intervention Name(s)
Miltefosine
Other Intervention Name(s)
pharmacokinetic
Intervention Description
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.
Primary Outcome Measure Information:
Title
Intracellular and plasma concentration of miltefosine
Time Frame
Participants will be followed up to 26 weeks.
Title
Parasite burden in lesions and extralesional tissues.
Time Frame
Participants will be followed up to 26 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nancy C Saravia, PhD
Organizational Affiliation
Centro Internacional de Entrenamiento e Investigaciones Médicas, CIDEIM
Official's Role
Principal Investigator
Facility Information:
Facility Name
Corporación Centro Internacional de entrenamiento e Investigaciónes Médicas
City
Cali
State/Province
Valle
ZIP/Postal Code
5930
Country
Colombia

12. IPD Sharing Statement

Citations:
PubMed Identifier
16730362
Citation
Sindermann H, Engel J. Development of miltefosine as an oral treatment for leishmaniasis. Trans R Soc Trop Med Hyg. 2006 Dec;100 Suppl 1:S17-20. doi: 10.1016/j.trstmh.2006.02.010. Epub 2006 May 26.
Results Reference
background
PubMed Identifier
18519729
Citation
Dorlo TP, van Thiel PP, Huitema AD, Keizer RJ, de Vries HJ, Beijnen JH, de Vries PJ. Pharmacokinetics of miltefosine in Old World cutaneous leishmaniasis patients. Antimicrob Agents Chemother. 2008 Aug;52(8):2855-60. doi: 10.1128/AAC.00014-08. Epub 2008 Jun 2.
Results Reference
background
PubMed Identifier
16807730
Citation
Anderson BJ, Allegaert K, Holford NH. Population clinical pharmacology of children: general principles. Eur J Pediatr. 2006 Nov;165(11):741-6. doi: 10.1007/s00431-006-0188-y. Epub 2006 Jun 29.
Results Reference
background
PubMed Identifier
18721114
Citation
Berman JJ. Treatment of leishmaniasis with miltefosine: 2008 status. Expert Opin Drug Metab Toxicol. 2008 Sep;4(9):1209-16. doi: 10.1517/17425255.4.9.1209.
Results Reference
background
PubMed Identifier
28379954
Citation
Castro MDM, Cossio A, Velasco C, Osorio L. Risk factors for therapeutic failure to meglumine antimoniate and miltefosine in adults and children with cutaneous leishmaniasis in Colombia: A cohort study. PLoS Negl Trop Dis. 2017 Apr 5;11(4):e0005515. doi: 10.1371/journal.pntd.0005515. eCollection 2017 Apr.
Results Reference
derived
PubMed Identifier
27956421
Citation
Castro MD, Gomez MA, Kip AE, Cossio A, Ortiz E, Navas A, Dorlo TP, Saravia NG. Pharmacokinetics of Miltefosine in Children and Adults with Cutaneous Leishmaniasis. Antimicrob Agents Chemother. 2017 Feb 23;61(3):e02198-16. doi: 10.1128/AAC.02198-16. Print 2017 Mar.
Results Reference
derived

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Pharmacokinetics of Miltefosine in Children and Adults

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