Safety and Efficacy Study of Paromomycin to Treat Visceral Leishmaniasis

Study Overview
=================
Brief Summary
-----------------
Symptomatic Visceral Leishmaniasis(VL)is fatal; Due to the increasing resistance to standard therapy with antimonials, there is a need for new safe, efficacious, low-cost therapies for the treatment of VL. Paromomycin is an off-patent aminoglycoside antibiotic with anti-leishmaniasis activity. This study will test the safety and efficacy of paromomycin in the treatment of patients with VL in India.

Official Title
-----------------
A Phase 3 Multicenter, Randomized, Controlled, Clinical Trial to Assess the Safety and Efficacy of Injectable Paromomycin in Patients With Visceral Leishmaniasis

Conditions
-----------------
Visceral Leishmaniasis

Intervention / Treatment
-----------------
* Drug: Paromomycin sulfate
* Drug: Amphotericin B


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age between 5-55 years (inclusive) of either gender. Newly diagnosed VL or VL treatment failure confirmed by spleen or bone marrow aspirate. Clinical signs and symptoms compatible with VL: fever of over two weeks duration and splenomegaly. Biochemical and haematological test values as follows: Haemoglobin > 5.0g/100mL White blood cell count > 1 x109/L Platelet count > 50 x 109/L AST, ALT and alkaline phosphatase < 3 times upper normal limit Prothrombin time < 5 seconds above control Serum creatinine levels within normal limits Serum potassium levels within normal limits HIV negative Exclusion Criteria: A history of intercurrent or concurrent diseases (e.g. chronic alcohol consumption or drug addiction; renal, hepatic, cardiovascular or central nervous system disease; diabetes; tuberculosis or other infectious or major psychiatric diseases) that may introduce variables affecting the outcome of the study. Any condition which the investigator thinks may prevent the patient from completing the study therapy and subsequent follow-up. An abnormal baseline audiogram (presentation with 75 dB or higher at 8KHz or below) and/or a history of significant vestibular or auditory dysfunction. Proteinuria (> 2+). A history of allergy or hypersensitivity to aminoglycosides. A history of major surgery within the last two weeks. Pregnancy or lactation. [Note: women of childbearing age must use an adequate form of contraception (documented) or agree to a period of sexual abstinence during the treatment phase of the study.] Previous treatment for VL within two weeks of enrolment into the study. Prior treatment failures with paromomycin or amphotericin B.

Ages Eligible for Study
-----------------
Minimum Age: 5 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Paromomycin sulfate|nan|
|Drug: Amphotericin B|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| (1) To compare the safety of injectable paromomycin to amphotericin B when administered in the proposed dosage regimens. |  |  | 
| (2) To compare the efficacy of injectable paromomycin to amphotericin B with regards to final cure rates. |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| - Characterization of the pharmacokinetics of injectable paromomycin in adults and children with VL |  |  | 
| - Comparison of initial cure rates for the two regimens |  |  | 
| - Comparison of clinical improvement rates for the two regimens |  |  |