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

A Phase 4 Study to Expand Access Program While Assessing the Safety and Efficacy of Paromomycin IM Injection in an Outpatient Setting for the Treatment of Visceral Leishmaniasis

This modular Program will first confirm the safety and efficacy of Paromomycin IM Injection when given to an expanded population in the outpatient setting in experienced VL centers and subsequently evaluate the effectiveness of an expanded access model of providing Paromomycin IM Injection to progressively more resource-constrained clinics in Bihar, India.

Study Overview

• Status: Completed
• Conditions: Visceral Leishmaniasis
• Intervention / Treatment: Drug: Paromomycin sulfate

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 2000
• Phase: Phase 4

Contacts and Locations

Study Locations

• India
  • Bihar
    • Agam Kuan, Patna, Bihar, India, 800 007
      • Rajendra Memorial Research Institute of Medical Sciences
    • Azad Nagar, Balua Tal, Motihari, Bihar, India, 845 401
      • Shrimati Hazari Maternity and Medical Care
    • Bengali Tola, Samastipur, Bihar, India, 848 101
      • Research Centre for Diabetes, Hypertension and Obesity
    • East of Bhola Talkies, Samastipur, Bihar, India, 848 101
      • Dr. A.K. Aditya Clinic
    • Patna, Bihar, India, 800 001
      • Kala-zar Research Centre
    • Rambagh Road, Muzaffarpur, Bihar, India, 842 001
      • Kala-azar Medical Research Centre
  • Muzaffarpur, Bihar
    • Brahmpura, Muzaffarpur, Bihar, India, 842 003
      • Kalazar Research Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 months to 53 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Confirmed, newly diagnosed or relapsed visceral leishmaniasis

Exclusion Criteria:

• HIV infection, tuberculosis
• Significant hematologic, renal or liver dysfunction
• Malaria
• Those unable to be treated as an outpatient.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; Paromomycin IM Injection (approved product in India)	Drug: Paromomycin sulfate; Paromomycin will be administered intramuscularly at 11 mg/kg, once a day, for 21 consecutive days; Other Names: Paromomycin IM Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
M1: Safety as measured by adverse events, serious adverse events, vital signs, and laboratory parameters.	M1: Approximately 6 months
M2&3: Program effectiveness as measured by specific criteria for healthcare workers, patients, and operational systems.	approximately 2.5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
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.	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.	approximately 6 months

Collaborators and Investigators

• Sponsor: PATH
• Investigators: Principal Investigator: P K Sinha, MD, Rajendra Memorial Research Institute of Medical Sciences; Principal Investigator: T K Jha, MD, Kalazar Research Centre; Principal Investigator: C P Thakur, MD, Kala-azar Research Centre; Principal Investigator: Shyam Sundar, MD, Kala-azar Medical Research Centre; Principal Investigator: Devendra Nath, MD, Shrimati Hazari Maternity and Medical Care; Principal Investigator: Supriyo Mukherjee, MD, Research Centre for Diabetes, Hypertension and Obesity; Principal Investigator: Amrendra K Aditya, MD, Dr. A.K. Aditya Clinic

Publications and helpful links

General Publications

• 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. doi: 10.1056/NEJMoa066536.

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: January 17, 2008
• First Submitted That Met QC Criteria: January 29, 2008
• First Posted (Estimate): January 30, 2008

Study Record Updates

• Last Update Posted (Estimate): October 3, 2014
• Last Update Submitted That Met QC Criteria: October 2, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: visceral leishmaniasis; kala-azar; Bihar, India
• Additional Relevant MeSH Terms: Skin Diseases; Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Skin Diseases, Parasitic; Skin Diseases, Infectious; Euglenozoa Infections; Leishmaniasis; Leishmaniasis, Visceral; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Paromomycin
• Other Study ID Numbers: VLPM03