Pharmacokinetics/Safety of Miltefosine Allometric Dose for the Treatment of Visceral Leishmaniasis in Children in Eastern Africa

Study Overview
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Brief Summary
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This is a multicenter, non-comparative, open-label clinical trial to assess the Pharmacokinetics (PK) and safety of miltefosine using an allometric dose algorithm in the treatment of children with primary Visceral Leishmaniasis (VL) in eastern Africa. Efficacy and Pharmacodynamics (PD) will be assessed as secondary outcomes. The proposed study aims to assess whether drug exposure in children can be increased to equivalent adult drug exposure by using the miltefosine allometric dose given BID for 28 days in paediatric VL patients aged 4-12y and whether this dose is tolerable. The present study is also expected to provide the basis for minimum time to reach sufficient drug exposure for miltefosine activity to guide optimal treatment duration to be used in combination therapy for visceral leishmaniasis. The PK data will be assessed in this trial using a compartmental population PK approach.

Official Title
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An Open-label Clinical Trial to Assess the Pharmacokinetics and Safety of Miltefosine Allometric Dose for the Treatment of Children With Primary Visceral Leishmaniasis in Eastern Africa

Conditions
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Visceral Leishmaniasis

Intervention / Treatment
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* Drug: Miltefosine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with clinical signs and symptoms of VL and confirmatory parasitological microscopic diagnosis Patients aged > 4 to < 12 years who are able to comply with the study protocol. Patients for whom written informed consent has been signed by parents(s) or legal guardian Weight < 30 kg Exclusion Criteria: Patients who are relapse cases Patients who have received any anti-leishmanial drugs in the last 6 months Patients with severe malnutrition (for children aged <5 years, weight-for-height WHO reference curves by gender, z score <-3; for children 5-12 years, BMI-for-age WHO reference curves for gender, z score < -3) Patients with positive HIV diagnosis Patients with previous history of hypersensitivity reaction to miltefosine Patients suffering from a concomitant severe infection such as Tuberculosis (TB) or any other serious underlying disease (cardiac, renal, hepatic) which would preclude evaluation of the patient's response to study medication Patients suffering from other conditions associated with splenomegaly such as schistosomiasis Pregnant or lactating women or female patient in childbearing age (reached menarche) Patients with haemoglobin < 5g/dl Patients with White Blood Cells (WBC) < 1 x 10³/mm³ Patients with platelets < 40,000/mm³ Patients with abnormal liver function (ALT and AST) tests of more than three times the normal range. Patients with bilirubin more than 1.5 times the upper normal range Patients with serum creatinine above the upper limit of normal (ULN) for age and gender. Patients with clinical signs of severe VL disease such as jaundice and bleeding Patients who cannot comply with the planned scheduled visits and procedures of the study protocol

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Miltefosine<br>allometric dosing | Drug: Miltefosine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics Parameters (Area Under the Curve (AUC) - composite outcome) | Area Under the Curve calculation is based on several timepoints from first drug intake up to complete elimination of the drug. | During treatment, at 1 and 6 months follow-up | 
| Safety (composite outcome) adverse events | 1. Frequency of Serious Adverse Events (SAEs) and Adverse Events (AEs) requiring treatment discontinuation, 2. Frequency and severity of adverse events | until day 210 | 
| Pharmacokinetics Parameters (Css/Cmax) |  | Day 28 |