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

Visceral Leishmaniasis Clinical Trial

Official title:

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).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00497601
• Other study ID #: BSV-AMBE II-KA-706
• Status: Completed
• Phase: Phase 2
• First received: July 5, 2007
• Last updated: September 11, 2008
• Start date: February 2007
• Est. completion date: July 2008

Study information

• Verified date: September 2008
• Source: Banaras Hindu University
• Contact: n/a
• Is FDA regulated: No
• Health authority: India: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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.

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: July 2008
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leishmaniasis
• Leishmaniasis, Visceral
• Visceral Leishmaniasis

Intervention

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
• 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
• 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

Locations

Country	Name	City	State
India	Kala-azar Medical Research Center	Muzaffarpur	Bihar

Sponsors (1)

Lead Sponsor	Collaborator
Banaras Hindu University

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical and parasitological cure at end of treatment and final cure (no relapse) at six months, no hematological, hepatic or renal toxicity		one year