Pharmacokinetics of Miltefosine in Children and Adults

Cutaneous Leishmaniasis Clinical Trial

— PK  

Official title:

Pharmacokinetics of Miltefosine in Children and Adults: Implications for the Treatment of Cutaneous Leishmaniasis in Colombia.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01462500
• Other study ID #: 2229-519-28930
• Status: Completed
• Phase: Phase 4
• First received: October 25, 2011
• Last updated: August 18, 2016
• Start date: October 2011
• Est. completion date: December 2015

Study information

• Verified date: August 2016
• Source: Centro Internacional de Entrenamiento e Investigaciones Médicas
• Contact: n/a
• Is FDA regulated: No
• Health authority: Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: December 2015
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 60 Years

Eligibility

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

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cutaneous Leishmaniasis
• Leishmaniasis
• Leishmaniasis, Cutaneous

Intervention

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.

Locations

Country	Name	City	State
Colombia	Corporación Centro Internacional de entrenamiento e Investigaciónes Médicas	Cali	Valle

Sponsors (2)

Lead Sponsor	Collaborator
Centro Internacional de Entrenamiento e Investigaciones Médicas	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Country where clinical trial is conducted

Colombia, 

References & Publications (4)

Anderson BJ, Allegaert K, Holford NH. Population clinical pharmacology of children: general principles. Eur J Pediatr. 2006 Nov;165(11):741-6. Epub 2006 Jun 29. Review. — View 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. Review. — View 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. — View 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. Epub 2006 May 26. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Intracellular and plasma concentration of miltefosine		Participants will be followed up to 26 weeks.	No
Primary	Parasite burden in lesions and extralesional tissues.		Participants will be followed up to 26 weeks	No