Expand Access/Assess Safety and Efficacy of Paromomycin IM Injection for the Treatment of Visceral Leishmaniasis

• M1: Safety as measured by adverse events, serious adverse events, vital signs, and laboratory parameters. [ Time Frame: M1: Approximately 6 months ] [ Designated as safety issue: Yes ]
  
• M2&3: Program effectiveness as measured by specific criteria for healthcare workers, patients, and operational systems. [ Time Frame: approximately 2.5 years ] [ Designated as safety issue: No ]
  

• M1: Clinical cure as measured by temperature/hx of fever, spleen size decrease by at least 33% from baseline, and clinical assessment of treating physician. [ Time Frame: M1: Approximately 6 months ]
  
• M2 and M3: Clinical cure as measured by temperature/hx of fever, spleen size decrease, and clinical assessment of treating physician. [ Time Frame: approximately 6 months ] [ Designated as safety issue: No ]
  

Safe, effective, and affordable treatments for visceral leishmaniasis (VL) that are widely available to the poorest population of rural India where the disease is endemic are urgently needed. Resistance to antimonials, which have historically been the first line of treatment for VL in Bihar and adjoining states, is a major problem. Other available treatments are limited by their high cost, toxicity, or contraindications in certain populations. Paromomycin IM Injection was approved for the treatment of VL in August 2006 by the Drug Controller General of India (DCGI).

The study is designed to establish a Phase 4 Access Program in a modular, stepwise fashion (Modules 1 to 3). The study will first confirm the safety and efficacy of Paromomycin IM Injection in an expanded VL population treated as an outpatient in experienced centers (Module 1); and then progressively extend the network of treatment facilities, the number and reach of the trained staff, and the implementation of the requisite logistics systems to rural Bihar (Modules 2 and 3). An expanded network of healthcare workers will be trained and supervised to make a preliminary diagnosis of VL; to make appropriate referrals to confirm the diagnosis of VL; to treat with Paromomycin IM Injection; and to assess patient safety and clinical response on an outpatient basis.