Open-Label, Sequential Step, Safety and Efficacy Study to Determine the Optimal Single Dose of Ambisome for Patients With VL

Study Overview
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Brief Summary
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This is a phase II/III open, comparative dose trial to find the lowest single dose of AmBisome for the treatment of primary, symptomatic visceral leishmaniasis(VL), in HIV negative patients. In this trial, the minimum effective dose will be determined in a sequential step, dose escalation design, which minimises the number of patients exposed to low, potentially inadequate doses and provides contemporaneous comparative data against the manufacturer's recommended dose schedule in this indication.

Official Title
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Open-Label, Sequential Step, Safety and Efficacy Study to Determine the Optimal Single Dose of Ambisome for Patients With Visceral Leishmaniasis

Conditions
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Visceral Leishmaniasis

Intervention / Treatment
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* Drug: Liposomal amphotericin B (Ambisome)
* Drug: Liposomal amphotericin B (Ambisome)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female adults and children aged 4 years or older with no upper age limit (in accordance with manufacturer's instructions) Acute, symptomatic, VL proven by parasitological examination of splenic aspirate (or bone marrow aspirate) with initial parasite index of at least 2+ Haemoglobin >4g/dL Fever for more than 2 weeks Living within reachable distance of the trial site to enable attendance for follow-up visits Written informed consent to participate (for children, by parent or guardian) HIV negative status Exclusion Criteria: Patients 'in extremis' with signs/symptoms indicative of severe VL Patients who have received any anti-leishmanial treatment within the last 6 months Patients who have received any investigational (unlicensed) drugs during 6 months before recruitment Known underlying chronic disease, such as severe cardiac, pulmonary, renal, or hepatic impairment. Renal function tests (serum creatinine) outside the normal range Liver function tests more than 3 times the normal range at study entry Platelet count less than 40,000/ mm3 Known alcohol abuse Pregnancy or lactation Concomitant acute drug usage for malaria and bacterial infection, pneumonia within last 7 days Known hypersensitivity to AmBisome or amphotericin B Any other condition which may invalidate the trial

Ages Eligible for Study
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Minimum Age: 4 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ambisome control:<br>Ambisome, Total dose 21.0 mg given as 7 x 3mg on days 1,2,3,4,5, and 14 and 21 | Drug: Liposomal amphotericin B (Ambisome)<br>* 21.0 mg/kg total dose. Given iv as 3mg/kg/day on days 1,2,3,4,5, and 14 and 21<br>* Other names: Ambisome;|
| Experimental: Ambisome test<br>Single dose Ambisome in sequence(7.5 / 10.0/ 12.5 / 15.0mg) | Drug: Liposomal amphotericin B (Ambisome)<br>* liposomal amphotericin b given intravenously as single dose at 7.5 mg/kg increasing to 10, 12.5 and 15.0mg/kg depending on results of interim analyses.<br>* Other names: Ambisome;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary efficacy variable is parasitological clearance with no relapse at 6 months post treatment (ie definitive cure) assessed by clinical status and confirmed by splenic or bone marrow aspiration. |  | at 6 months post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parasitological clearance at day 30. |  | Day 30 |