Safety and Efficacy Study of Paromomycin to Treat Visceral Leishmaniasis

• (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.

• - 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

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.

• Drug: Paromomycin sulfate
• Drug: Amphotericin B

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.