A Phase II Study To Assess Safety and Efficacy Of Short-Course Regimens Of Amphotericin B Emulsion In Kala-Azar

A Prospective, Single Center, Open-Label, Dose-Escalation Phase II Study To Assess Safety and Efficacy Of Short-Course Regimens Of Amphotericin B Emulsion In Treatment Naïve Or Resistant Cases Of Visceral Leishmaniasis (Kala-Azar).

The purpose of this study is:

1. To evaluate the Safety and Efficacy of four different short-course regimens of Amphotericin B emulsion in treatment of Kala-azar (visceral leishmaniasis) subjects who are either treatment naive or treatment resistant to other antileishmanial drugs except amphotericin B containing preparations.
2. To assess the safety and efficacy of single-bolus infusion of Amphotericin B emulsion in treatment of Kala-azar.

Study Overview

• Status: Completed
• Conditions: Visceral Leishmaniasis
• Intervention / Treatment: Drug: Amphotericin B fat emulsion in visceral leishmaniasis; Drug: Amphotericin B fat emulsion; Drug: Amphotericin B in fat emulsion

Detailed Description

1. To evaluate the Safety and Efficacy of four different short-course regimens of Amphotericin B emulsion in treatment of Kala-azar (visceral leishmaniasis) subjects who are either treatment naive or treatment resistant to other antileishmanial drugs except amphotericin B containing preparations.
2. To assess the safety and efficacy of single-bolus infusion of Amphotericin B emulsion in treatment of Kala-azar.

Subjects will be administered the study drug in either of the following four dose levels in an ascending manner, starting with the first dosage regimen:

• 7.5 mg/kg on day 1 and day3 (Regimen 1)
• 10 mg/kg on day 1, followed by 5 mg/kg on day 3 (Regimen 2)
• 12.5 mg/kg on day 1, followed by 2.5 mg/kg on day 3 (Regimen 3)
• Single-bolus infusion of 15 mg/kg over 2-4 hours on day 1 (Regimen 4)

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• India
  • Bihar
    • Muzaffarpur, Bihar, India, 842001
      • Kala-azar Medical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female subjects between 18 years and 65 years of age (both inclusive).
2. Subject/subject's legally acceptable representative is willing and able to give written informed consent to participate in the study.
3. Treatment naive subjects having symptoms and/or signs of visceral leishmaniasis with parasitological confirmation of Kala-azar (by splenic or bone marrow aspirate smear examination).

If subjects are previously treated with other antileishmanial drugs except amphotericin B containing preparations, they will be enrolled in the study only after clinical and parasitological evidence that the disease is unresponsive to adequate treatment with other drugs, and after an appropriate wash out period

Exclusion Criteria:

1. Subjects with past history of treatment with Amphotericin B for Kala-azar.
2. Subjects positive for HIV infection.
3. Concomitant life threatening or serious disease.
4. Concurrent malaria (malarial parasite test to be negative prior to study treatment administration), tuberculosis or bacterial pneumonia.
5. Haemoglobin < 6 gm/dl, total leukocyte count < 1,500/cmm, platelet count < 50,000/cmm
6. Abnormal liver and renal functions (BUN and serum creatinine > 1.5 times upper limit of normal (ULN), AST/ALT > 2.5 times ULN, and bilirubin > 1.5 times ULN).
7. Pregnant or nursing women.
8. Known hypersensitivity to Amphotericin B or inactive ingredients of study drug formulation.
9. Subjects receiving any of the medications prohibited by the study protocol.
10. Evidence of significant haematological, cardiac, hepatic, renal, respiratory, neurological or metabolic disease or any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives.
11. Simultaneous participation in another trial or received any investigational product < 30 days prior to enrolment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; Amphotericin B in fat emulsion (Amphomul) 7.5 mg/kg on day 1 and 3	Drug: Amphotericin B fat emulsion in visceral leishmaniasis; Amphotericin B in fat emulsion (Amphomul) 7.5 mg/kg on day 1 & 3 in group A Amphotericin B in fat emulsion (Amphomul) 10 & 5 mg/kg on day 1 & 3 in group B Amphotericin B in fat emulsion (Amphomul) 12.5 & 2.5 mg/kg on day 1 & 3 in group C Amphotericin B in fat emulsion (Amphomul) 15 mg/kg on day 1 in group D; Other Names: Amphomul; Drug: Amphotericin B fat emulsion; Starting with 7.5 mg/kg on day 1 and 3, 10 and 5 mg/kg on day 1 and 3, 12.5 and 2.5 mg/kg on day 1 and 3 and finally 15 mg/kg on day 1; Other Names: Amphomul; Drug: Amphotericin B in fat emulsion; Starting with 7.5 mg/kg on day 1 and 3, 10 and 5 mg/kg on day 1 and 3, 12.5 and 2.5 mg/kg on day 1 and 3 and finally 15 mg/kg on day 1; Other Names: Amphomul
Experimental: B; Amphotericin B in fat emulsion (Amphomul) 10 mg/kg on day 1 and 5 mg/kg on day 3	Drug: Amphotericin B fat emulsion in visceral leishmaniasis; Amphotericin B in fat emulsion (Amphomul) 7.5 mg/kg on day 1 & 3 in group A Amphotericin B in fat emulsion (Amphomul) 10 & 5 mg/kg on day 1 & 3 in group B Amphotericin B in fat emulsion (Amphomul) 12.5 & 2.5 mg/kg on day 1 & 3 in group C Amphotericin B in fat emulsion (Amphomul) 15 mg/kg on day 1 in group D; Other Names: Amphomul; Drug: Amphotericin B fat emulsion; Starting with 7.5 mg/kg on day 1 and 3, 10 and 5 mg/kg on day 1 and 3, 12.5 and 2.5 mg/kg on day 1 and 3 and finally 15 mg/kg on day 1; Other Names: Amphomul; Drug: Amphotericin B in fat emulsion; Starting with 7.5 mg/kg on day 1 and 3, 10 and 5 mg/kg on day 1 and 3, 12.5 and 2.5 mg/kg on day 1 and 3 and finally 15 mg/kg on day 1; Other Names: Amphomul
Experimental: C; Amphotericin B in fat emulsion (Amphomul) 12.5 mg/kg on day 1 and 2.5 mg/kg on day 3	Drug: Amphotericin B fat emulsion in visceral leishmaniasis; Amphotericin B in fat emulsion (Amphomul) 7.5 mg/kg on day 1 & 3 in group A Amphotericin B in fat emulsion (Amphomul) 10 & 5 mg/kg on day 1 & 3 in group B Amphotericin B in fat emulsion (Amphomul) 12.5 & 2.5 mg/kg on day 1 & 3 in group C Amphotericin B in fat emulsion (Amphomul) 15 mg/kg on day 1 in group D; Other Names: Amphomul; Drug: Amphotericin B fat emulsion; Starting with 7.5 mg/kg on day 1 and 3, 10 and 5 mg/kg on day 1 and 3, 12.5 and 2.5 mg/kg on day 1 and 3 and finally 15 mg/kg on day 1; Other Names: Amphomul; Drug: Amphotericin B in fat emulsion; Starting with 7.5 mg/kg on day 1 and 3, 10 and 5 mg/kg on day 1 and 3, 12.5 and 2.5 mg/kg on day 1 and 3 and finally 15 mg/kg on day 1; Other Names: Amphomul
Experimental: D; Amphotericin B in fat emulsion (Amphomul) 15 mg/kg in a single dose administration on day 1	Drug: Amphotericin B fat emulsion in visceral leishmaniasis; Amphotericin B in fat emulsion (Amphomul) 7.5 mg/kg on day 1 & 3 in group A Amphotericin B in fat emulsion (Amphomul) 10 & 5 mg/kg on day 1 & 3 in group B Amphotericin B in fat emulsion (Amphomul) 12.5 & 2.5 mg/kg on day 1 & 3 in group C Amphotericin B in fat emulsion (Amphomul) 15 mg/kg on day 1 in group D; Other Names: Amphomul; Drug: Amphotericin B fat emulsion; Starting with 7.5 mg/kg on day 1 and 3, 10 and 5 mg/kg on day 1 and 3, 12.5 and 2.5 mg/kg on day 1 and 3 and finally 15 mg/kg on day 1; Other Names: Amphomul; Drug: Amphotericin B in fat emulsion; Starting with 7.5 mg/kg on day 1 and 3, 10 and 5 mg/kg on day 1 and 3, 12.5 and 2.5 mg/kg on day 1 and 3 and finally 15 mg/kg on day 1; Other Names: Amphomul

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Clinical and parasitological cure at end of treatment and final cure (no relapse) at six months, no hematological, hepatic or renal toxicity	one year

Collaborators and Investigators

• Sponsor: Banaras Hindu University
• Investigators: Principal Investigator: Shyam Sundar, Banaras Hindu University

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: July 5, 2007
• First Submitted That Met QC Criteria: July 5, 2007
• First Posted (Estimate): July 6, 2007

Study Record Updates

• Last Update Posted (Estimate): September 12, 2008
• Last Update Submitted That Met QC Criteria: September 11, 2008
• Last Verified: September 1, 2008

More Information

Terms related to this study

• Keywords: Amphotericin B; Visceral Leishmaniasis; Fat emulsion
• 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; Antifungal Agents; Antiprotozoal Agents; Antiparasitic Agents; Pharmaceutical Solutions; Amebicides; Parenteral Nutrition Solutions; Fat Emulsions, Intravenous; Soybean oil, phospholipid emulsion; Amphotericin B; Liposomal amphotericin B
• Other Study ID Numbers: BSV-AMBE II-KA-706