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

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

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.

Study Overview

• Status: Completed
• Conditions: Visceral Leishmaniasis
• Intervention / Treatment: Drug: Miltefosine

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Kenya
  • Rift Valley, West Pokot
    • Kacheliba, Rift Valley, West Pokot, Kenya, 30601
      • Kacheliba Hospital
• Uganda
  • Karamoja
    • Amudat, Karamoja, Uganda
      • Amudat Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Miltefosine; allometric dosing	Drug: Miltefosine

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Drugs for Neglected Diseases
• Investigators: Principal Investigator: Dr. Rashid Juma, MD, Kenya Medical Research Institute

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: April 20, 2015
• First Submitted That Met QC Criteria: April 29, 2015
• First Posted (Estimate): April 30, 2015

Study Record Updates

• Last Update Posted (Estimate): October 11, 2016
• Last Update Submitted That Met QC Criteria: October 10, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Skin Diseases, Parasitic; Skin Diseases, Infectious; Euglenozoa Infections; Leishmaniasis; Leishmaniasis, Visceral; Anti-Infective Agents; Antineoplastic Agents; Antifungal Agents; Antiprotozoal Agents; Antiparasitic Agents; Miltefosine
• Other Study ID Numbers: LEAP 0714