Safety and Efficacy Study of Paromomycin to Treat Visceral Leishmaniasis

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

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.

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.