Cutaneous LeishmaniasisPhase 4PKNCT01462500
Pharmacokinetics of Miltefosine in Children and Adults
A Phase 4 study testing Miltefosine in people with Cutaneous Leishmaniasis, run by Centro Internacional de Entrenamiento e Investigaciones Médicas at 1 site in Colombia.
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. Read more about this study
- Who is it for?
- Ages 2 to 60 years
- Conditions the study is for
- Cutaneous Leishmaniasis
- What is being tested?
- Miltefosine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteColombia
- Study dates
- Oct 2011to Dec 2015
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Colombia1 site
Corporación Centro Internacional de entrenamiento e Investigaciónes Médicas
Cali, Valle del Cauca Department, 5930
About this study
Official title: Pharmacokinetics of Miltefosine in Children and Adults: Implications for the Treatment of Cutaneous Leishmaniasis in Colombia.
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.
Read the 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.
- Conditions
- Cutaneous Leishmaniasis
- Being tested
- Miltefosine
- Keywords
- Miltefosine, pharmacokinetics, cutaneous leishmaniasis
- Medical subject headings
- Leishmaniasis, Cutaneous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MiltefosineDrug
Also called pharmacokinetic
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.
| Study group | Role | What they receive |
|---|---|---|
| Miltefosine | Experimental | Miltefosine PO at a dose of 1.8-2.5 mg/kg/day for 28 days Receives: Drug: Miltefosine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intracellular and plasma concentration of miltefosine
Measured: Participants will be followed up to 26 weeks.
Parasite burden in lesions and extralesional tissues.
Measured: Participants will be followed up to 26 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2011 (estimated)
- Study startOct 2011
- Primary completionMay 2014
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Cutaneous LeishmaniasisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centro Internacional de Entrenamiento e Investigaciones Médicas
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nancy C Saravia, PhD, Principal investigator, Centro Internacional de Entrenamiento e Investigaciones Médicas, CIDEIM
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01462500
- Sponsor's protocol ID
- 2229-519-28930
- Acronym
- PK
- Status last verified
- Aug 2016
- First submitted
- 25 Oct 2011
- Last updated
- 22 Aug 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 16730362Dorlo 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.
PubMed 18519729Anderson 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.
PubMed 16807730Berman 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.
PubMed 18721114Castro 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.
PubMed 28379954Castro 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.
PubMed 27956421
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics of Miltefosine in Children and Adults: Implications for the Treatment of Cutaneous Leishmaniasis in Colombia.
- ClinicalTrials.gov ID
- NCT01462500
- Acronym / sponsor ID
- PK / 2229-519-28930
- Conditions
- Cutaneous Leishmaniasis
- Keywords
- Miltefosine, pharmacokinetics, cutaneous leishmaniasis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Centro Internacional de Entrenamiento e Investigaciones MédicasUniversity, hospital or other
- Collaborators
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Study start
- Oct 2011
- Primary completion
- May 2014 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 31 Oct 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Miltefosine | Experimental | Drug: MiltefosineMiltefosine PO at a dose of 1.8-2.5 mg/kg/day for 28 days |
Who may qualify
- Ages
- 2 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MiltefosineAlso: pharmacokineticChildren (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. | Drug | Miltefosine |
Primary outcome
Intracellular and plasma concentration of miltefosine
Time frame: Participants will be followed up to 26 weeks.
Parasite burden in lesions and extralesional tissues.
Time frame: Participants will be followed up to 26 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2016.
- Background: PubMed 16730362Sindermann 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.
- Background: PubMed 18519729Dorlo 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.
- Background: PubMed 16807730Anderson 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.
- Background: PubMed 18721114Berman 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.
- Derived from this study: PubMed 28379954Castro 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.
- Derived from this study: PubMed 27956421Castro 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nancy C Saravia, PhD principal investigator
Centro Internacional de Entrenamiento e Investigaciones Médicas, CIDEIM
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Miltefosine in people with Cutaneous Leishmaniasis, run by Centro Internacional de Entrenamiento e Investigaciones Médicas at 1 site in Colombia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Colombia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Intracellular and plasma concentration of miltefosine (time frame: Participants will be followed up to 26 weeks.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01462500, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2016.