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

Primary Purpose

Visceral Leishmaniasis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Miltefosine
Sponsored by
Drugs for Neglected Diseases
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Visceral Leishmaniasis

Eligibility Criteria

4 Years - 12 Years (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Kacheliba Hospital
  • Amudat Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Miltefosine

Arm Description

allometric dosing

Outcomes

Primary Outcome Measures

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.
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
Pharmacokinetics Parameters (Css/Cmax)

Secondary Outcome Measures

Full Information

First Posted
April 20, 2015
Last Updated
October 10, 2016
Sponsor
Drugs for Neglected Diseases
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1. Study Identification

Unique Protocol Identification Number
NCT02431143
Brief Title
Pharmacokinetics/Safety of Miltefosine Allometric Dose for the Treatment of Visceral Leishmaniasis in Children in Eastern Africa
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2016
Overall Recruitment Status
Completed
Study Start Date
May 2015 (undefined)
Primary Completion Date
April 2016 (Actual)
Study Completion Date
September 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Drugs for Neglected Diseases

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Visceral Leishmaniasis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
4 Years
Maximum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dr. Rashid Juma, MD
Organizational Affiliation
Kenya Medical Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Kacheliba Hospital
City
Kacheliba
State/Province
Rift Valley, West Pokot
ZIP/Postal Code
30601
Country
Kenya
Facility Name
Amudat Hospital
City
Amudat
State/Province
Karamoja
Country
Uganda

12. IPD Sharing Statement

Citations:
PubMed Identifier
30188978
Citation
Mbui J, Olobo J, Omollo R, Solomos A, Kip AE, Kirigi G, Sagaki P, Kimutai R, Were L, Omollo T, Egondi TW, Wasunna M, Alvar J, Dorlo TPC, Alves F. Pharmacokinetics, Safety, and Efficacy of an Allometric Miltefosine Regimen for the Treatment of Visceral Leishmaniasis in Eastern African Children: An Open-label, Phase II Clinical Trial. Clin Infect Dis. 2019 Apr 24;68(9):1530-1538. doi: 10.1093/cid/ciy747.
Results Reference
derived

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

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