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

NCT02431143 | Completed Phase 2

• 1 other identifier: LEAP 0714
• Study Type: interventional
• Target: 30
• Locations: 2 countries
• Sites: 2

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.

Conditions

Visceral Leishmaniasis

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (1)

Miltefosine

EXPERIMENTAL

allometric dosing

Drug: Miltefosine

Interventions

Miltefosine DRUG

Miltefosine

Eligibility Criteria

• Age: 4 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Drugs for Neglected Diseases: lead

Study Sites (2)

Kacheliba Hospital

Kacheliba, Rift Valley, West Pokot, 30601, Kenya

Location

Amudat Hospital

Amudat, Karamoja, Uganda

Location

Related Publications (1)

• 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.

  PMID: 30188978 DERIVED

MeSH Terms

Conditions

Leishmaniasis, Visceral

Interventions

miltefosine

Condition Hierarchy (Ancestors)

Leishmaniasis; Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Vector Borne Diseases

Study Officials

• Dr. Rashid Juma, MD

  Kenya Medical Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2015
• First Posted: April 30, 2015
• Study Start: May 1, 2015
• Primary Completion: April 1, 2016
• Study Completion: September 1, 2016
• Last Updated: October 11, 2016

Record last verified: 2016-10

Locations

KE (1); UG (1)