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

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

The purpose of this study is to evaluate the effectiveness of treatment with PMIM in patients with visceral leishmaniasis within the VL-endemic region of Bangladesh at EOT (21/22 days after treatment begins), and at 6 months after end of treatment (Day 202/203, -15 to +30 days).

Safe, effective and affordable treatments for visceral leishmaniasis (VL) that are widely available to the poorest populations are urgently needed in Bangladesh in areas where the disease is endemic. Paromomycin IM Injection (PMIM) was approved for the treatment of VL in August 2006 by the Drugs Controller General of India (DCGI), and it offers an attractive alternative to treatments that are currently available.

Inclusion Criteria:

1. Signs and symptoms of VL including:

   • History of intermittent fever for at least two weeks
   • History of weight loss and/or decrease in appetite
   • Enlarged spleen

2. VL serologically confirmed using the rK39 test:

3. Willingness / ability to understand and provide informed consent prior to participation in this study:

4. Age ≥ five years and ≤ 55 years, and weighing at least five kg

5. Adequately hydrated as assessed by clinical criteria and able to maintain adequate hydration on an outpatient basis through oral intake of fluids

6. Clinically stable and appropriate for treatment with PMIM as an outpatient, if possible (subjects may be hospitalized to receive 21-day dosing at the discretion of the investigator)

7. Living in the VL-endemic areas in Bangladesh

Exclusion Criteria:

1. Active tuberculosis or taking anti-tuberculosis medications
2. Previous treatment with Paromomycin IM Injection (PMIM)
3. Clinically significant severe anemia as determined by the investigator
4. Clinically significant renal or hepatic dysfunction as determined by the investigator, or history of clinically significant renal or hepatic dysfunction
5. History of Hepatitis B or C; or known HIV positive
6. History of hearing loss
7. Other serious illness or medical condition that, in the opinion of the doctor, would interfere with the patient's ability to receive PMIM treatment or comply with the study procedures, or that could obscure toxicity of or response to PMIM
8. Major surgery within 30 days prior to first dose of PMIM
9. History of hypersensitivity to aminoglycosides or to any of the components of PMIM, including sulfite
10. Any history of VL or treatment of VL at any time
11. Patients who have received any investigational (unlicensed) drug within the last six months
12. Concomitant use of other aminoglycosides (e.g., gentamicin, tobramycin, amikacin), nephrotoxic and ototoxic drugs, or immunosuppressive drugs
13. Proteinuria (results > 1+ ) on urine dipstick analysis at screening visit and/or
14. Serum creatinine above the upper limit of normal (ie, serum creatinine >1.1 mg/dl in males and >0.9 mg/dl in females
15. Pregnant or lactating women