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

Phase 2

Terminated

• Conditions: Visceral Leishmaniasis
• Interventions: Drug: Liposomal amphotericin B (Ambisome)

• Registration Number: NCT00832208
• Lead Sponsor: Drugs for Neglected Diseases

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2009-01-29
• Study First Submitted QC: 2009-01-29
• Study First Posted: 2009-01-30
• Study Start: 2009-04
• Primary Completion: 2010-09
• Study Completion: 2011-03
• Status Verified: 2016-01
• Last Update Submitted: 2016-01-20
• Last Update Posted: 2016-01-21

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 124

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ambisome control:	Liposomal amphotericin B (Ambisome)	Ambisome, Total dose 21.0 mg given as 7 x 3mg on days 1,2,3,4,5, and 14 and 21
Ambisome test	Liposomal amphotericin B (Ambisome)	Single dose Ambisome in sequence(7.5 / 10.0/ 12.5 / 15.0mg)

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Parasitological clearance at day 30.	Day 30

Trial Locations

Locations (3)

Gondar; 🇪🇹 Gondar, Ethiopia

Arba Minch LRTC; 🇪🇹 Arba Minch, Ethiopia

Kassab Hospital; 🇸🇩 Kassab, Gedarif, Sudan