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

Visceral Leishmaniasis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01328457
• Other study ID #: VLPMIM402
• Status: Completed
• Phase: N/A
• First received: January 21, 2011
• Last updated: April 2, 2014
• Start date: January 2011
• Est. completion date: June 2012

Study information

• Verified date: August 2012
• Source: PATH
• Contact: n/a
• Is FDA regulated: No
• Health authority: Bangladesh: Directorate of Drug Administration
• Study type: Interventional

Clinical Trial Summary

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).

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: June 2012
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 5 Years to 55 Years

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leishmaniasis
• Leishmaniasis, Visceral
• Visceral Leishmaniasis

Intervention

Drug:
• Paromomycin sulfate
Paromomycin IM Injection, 11 mg/kg as the base, intramuscular, once a day on 21 consecutive days (or no more than 22 days if one injection is missed during the treatment period).

Locations

Country	Name	City	State
Bangladesh	Bhaluka Upazila Health Complex	Bhaluka	Mymensingh District
Bangladesh	Icddr,B	Dhaka
Bangladesh	Trishal Upazila Health Complex	Trishal	Mymensingh District

Sponsors (4)

Lead Sponsor	Collaborator
PATH	GVK Biosciences Private Limited, Gurgaon, India, International Centre for Diarrhoeal Disease Research, Bangladesh, Shaheed Suhrawardy Medical College Hospital, Dhaka, Bangladesh

Country where clinical trial is conducted

Bangladesh, 

References & Publications (2)

Kanyok TP, Killian AD, Rodvold KA, Danziger LH. Pharmacokinetics of intramuscularly administered aminosidine in healthy subjects. Antimicrob Agents Chemother. 1997 May;41(5):982-6. — View Citation

Sundar S, Jha TK, Thakur CP, Sinha PK, Bhattacharya SK. Injectable paromomycin for Visceral leishmaniasis in India. N Engl J Med. 2007 Jun 21;356(25):2571-81. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Final cure rate	Criteria evaluated (binary fashion): Patient's temperature less than 99.4°F in clinic at EOT visit? (Y/N); Patient reported resolution of fever and NO fever within the last 5 days? (Y/N); Spleen size decreased from screening value? (Y/N); Is the clinical impression of the treating physician that of an adequate clinical response? (Y/N); The patient is deemed to have achieved final cure if answers to a, b, c, AND d are all "Yes" OR if one answer (a, b, or c) is "No" but all others and "d" are "Yes". In addition, the clinician will inquire about pregnancy status for female patients.	6 months after end of treatment (Day 202/203, -15 to +30 days)	No
Secondary	Initial clinical response rate	Criteria evaluated (binary fashion): Patient's temperature less than 99.4°F in clinic at EOT visit? (Y/N); Patient reported resolution of fever / NO fever within the last 5 days? (Y/N); Spleen size decreased from screening value? (Y/N); Is clinical impression of the treating physician that of an adequate clinical response? (Y/N); The patient is deemed to achieve an initial clinical response if answers to a, b, c, AND d are all "Yes" OR if one answer (a, b, or c) is "No" but all others and "d" are "Yes". Also, the clinician will inquire re: pregnancy status for female patients.	End of treatment (21/22 days after treatment begins)	No
Secondary	Patient compliance with PMIM treatment	Proportion of patients complying with prescribed 21 daily injections over no more than 22 days.	22 days	No
Secondary	Safety of PMIM in the study population based on clinical assessment by the study physician at the Upazilla Health Centre.	All serious adverse events (SAEs), regardless of causality, from time of first administration of PMIM through 30 days post-EOT.; All adverse events (AEs), regardless of causality, from time of first dose through 30 days post-EOT.; Vital signs on Study Days 1 to 21/22 (or early termination), any unscheduled visit after EOT, 30 days after EOT, and 6 months after EOT.; Patients who become pregnant during treatment/within 30d following EOT will be included in the safety population. Offspring from pregnancies will be followed for safety under a separate study for a period up to 3 yrs after birth.	6 months after end of treatment	Yes
Secondary	To introduce PMIM in government health facilities in rural Bangladesh.	Training study staff to provide treatment with PMIM at selected Upazila level health complexes in rural Bangladesh.	October 2011	Yes