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

NCT ID: NCT00832208

Last Updated: 2016-01-21

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 124 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-04-30
• Study Completion Date: 2011-03-31

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.

Conditions

Visceral Leishmaniasis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ambisome control:

Ambisome, Total dose 21.0 mg given as 7 x 3mg on days 1,2,3,4,5, and 14 and 21

Group Type: ACTIVE_COMPARATOR

Liposomal amphotericin B (Ambisome)

Intervention Type: DRUG

21.0 mg/kg total dose. Given iv as 3mg/kg/day on days 1,2,3,4,5, and 14 and 21

Ambisome test

Single dose Ambisome in sequence(7.5 / 10.0/ 12.5 / 15.0mg)

Group Type: EXPERIMENTAL

Liposomal amphotericin B (Ambisome)

Intervention Type: DRUG

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.

Interventions

Liposomal amphotericin B (Ambisome)

21.0 mg/kg total dose. Given iv as 3mg/kg/day on days 1,2,3,4,5, and 14 and 21

Intervention Type: DRUG

Liposomal amphotericin B (Ambisome)

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.

Intervention Type: DRUG

Other Intervention Names

Ambisome; Ambisome

Eligibility Criteria

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

• Minimum Eligible Age: 4 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Addis Ababa University

OTHER

Sponsor Role: collaborator

Drugs for Neglected Diseases

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sisay Yifru, MD

Role: PRINCIPAL_INVESTIGATOR

Gondar University

Locations

Gondar

Gonder, Gondar, Ethiopia

Arba Minch LRTC

Arba Minch, , Ethiopia

Kassab Hospital

Kassāb, Gedarif, Sudan

Countries

Ethiopia; Sudan

References

Khalil EA, Weldegebreal T, Younis BM, Omollo R, Musa AM, Hailu W, Abuzaid AA, Dorlo TP, Hurissa Z, Yifru S, Haleke W, Smith PG, Ellis S, Balasegaram M, EL-Hassan AM, Schoone GJ, Wasunna M, Kimutai R, Edwards T, Hailu A. Safety and efficacy of single dose versus multiple doses of AmBisome for treatment of visceral leishmaniasis in eastern Africa: a randomised trial. PLoS Negl Trop Dis. 2014 Jan 16;8(1):e2613. doi: 10.1371/journal.pntd.0002613. eCollection 2014.

Reference Type: DERIVED

PMID: 24454970 (View on PubMed)

Edwards T, Omollo R, Khalil EA, Yifru S, Musa B, Musa A, Wasunna M, Smith PG, Royce C, Ellis S, Balasegaram M, Hailu A. Single-dose liposomal amphotericin B (AmBisome(R)) for the treatment of visceral leishmaniasis in East Africa: study protocol for a randomized controlled trial. Trials. 2011 Mar 6;12:66. doi: 10.1186/1745-6215-12-66.

Reference Type: DERIVED

PMID: 21375777 (View on PubMed)

Other Identifiers

AMBI 0106

Identifier Type: -

Identifier Source: org_study_id