Pharmacokinetics of Miltefosine in Children and Adults (PK)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Centro Internacional de Entrenamiento e Investigaciones Médicas
Sponsor:
Collaborator:
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Information provided by (Responsible Party):
Centro Internacional de Entrenamiento e Investigaciones Médicas
ClinicalTrials.gov Identifier:
NCT01462500
First received: October 25, 2011
Last updated: March 11, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Cutaneous Leishmaniasis
Drug: Miltefosine
Phase 4

Study Type: Interventional
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.

Resource links provided by NLM:


Further study details as provided by Centro Internacional de Entrenamiento e Investigaciones Médicas:

Primary Outcome Measures:
  • Intracellular and plasma concentration of miltefosine [ Time Frame: Participants will be followed up to 26 weeks. ] [ Designated as safety issue: No ]
  • Parasite burden in lesions and extralesional tissues. [ Time Frame: Participants will be followed up to 26 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: October 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Miltefosine
Miltefosine PO at a dose of 1.8-2.5 mg/kg/day for 28 days
Drug: Miltefosine
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.
Other Name: pharmacokinetic

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.

  Eligibility

Ages Eligible for Study:   2 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01462500

Contacts
Contact: Maria A Gomez, PhD 572-5552164 ext 213 mgomez@cideim.org.co
Contact: Alexandra Cossio, RN, MSc 572-5552164 ext 114 acossio@cideim.org.co

Locations
Colombia
Corporación Centro Internacional de entrenamiento e Investigaciónes Médicas Recruiting
Cali, Valle, Colombia, 5930
Sponsors and Collaborators
Centro Internacional de Entrenamiento e Investigaciones Médicas
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Investigators
Principal Investigator: Nancy C Saravia, PhD Centro Internacional de Entrenamiento e Investigaciones Médicas, CIDEIM
  More Information

Publications:
Responsible Party: Centro Internacional de Entrenamiento e Investigaciones Médicas
ClinicalTrials.gov Identifier: NCT01462500     History of Changes
Other Study ID Numbers: 2229-519-28930
Study First Received: October 25, 2011
Last Updated: March 11, 2014
Health Authority: Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos

Keywords provided by Centro Internacional de Entrenamiento e Investigaciones Médicas:
Miltefosine
pharmacokinetics
cutaneous leishmaniasis

Additional relevant MeSH terms:
Skin Diseases, Infectious
Leishmaniasis
Leishmaniasis, Cutaneous
Euglenozoa Infections
Protozoan Infections
Parasitic Diseases
Skin Diseases, Parasitic
Skin Diseases
Miltefosine
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents
Antiprotozoal Agents
Antiparasitic Agents

ClinicalTrials.gov processed this record on August 21, 2014