Effectiveness Study of Paromomycin IM Injection (PMIM) for the Treatment of Visceral Leishmaniasis (VL) in Bangladesh

Background: This study was conducted in Bangladeshi patients in an outpatient setting to support registration of Paromomycin Intramuscular Injection (PMIM) as a low-cost treatment option in Bangladesh. Methodology: This Phase IIIb, open-label, multi-center, single-arm trial assessed the efficacy and safety of PMIM administered at 11 mg/kg (paromomycin base) intramuscularly once daily for 21 consecutive days to children and adults with VL in a rural outpatient setting in Bangladesh. Patients ≥5 and ≤55 years were eligible if they had signs and symptoms of VL (intermittent fever, weight loss/decreased appetite, and enlarged spleen), positive rK39 test, and were living in VL-endemic areas. Compliance was the percentage of enrolled patients who received 21 daily injections over no more than 22 days. Efficacy was evaluated by initial clinical response, defined as resolution of fever and reduction of splenomegaly at end of treatment, and final clinical response, defined as the absence of new clinical signs and symptoms of VL 6 months after end of treatment. Safety was assessed by evaluation of adverse events. Principal Findings: A total of 120 subjects (49% pediatric) were enrolled. Treatment compliance was 98.3%. Initial clinical response in the Intent-to-Treat population was 98.3%, and final clinical response 6 months after end of treatment was 94.2%. Of the 119 subjects who received ≥1 dose of PMIM, 28.6% reported at least one adverse event. Injection site pain was the most commonly reported adverse event. Reversible renal impairment and/or hearing loss were reported in 2 subjects. Conclusions/Significance: PMIM was an effective and safe treatment for VL in Bangladesh. The short treatment duration and lower cost of PMIM compared with other treatment options may make this drug a preferred treatment to be investigated as part of a combination therapy regimen. This study supports the registration of PMIM for use in government health facilities in Bangladesh. Trial Registration: ClinicalTrials.gov identifier: NCT01328457 Author Summary: Effective and safe therapies for visceral leishmaniasis (VL), also known as kala-azar, at an affordable cost are urgently needed in Bangladesh. Although sodium stibogluconate, miltefosine, and paromomycin are included in the National Essential Drug List for VL, only miltefosine is currently registered in Bangladesh. Paromomycin is a low-cost drug that was demonstrated to be an efficacious and safe treatment for VL in endemic areas of India, which led to approval of paromomycin IM injection (PMIM) for the treatment of VL in India in 2006 and inclusion of PMIM in the WHO Essential Medicines List in 2007. A subsequent Phase IV trial in India revealed a similarly high efficacy and safety profile coupled with high treatment compliance in a rural outpatient setting. We confirmed the effectiveness, safety, and high compliance of PMIM when used in an outpatient setting in Bangladesh. This study supports the registration of PMIM as a low-cost treatment option for VL in Bangladesh.