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

Study Overview
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Brief Summary
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The purpose of this study is: 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. To assess the safety and efficacy of single-bolus infusion of Amphotericin B emulsion in treatment of Kala-azar.

Detailed Description
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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. 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)

Official Title
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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).

Conditions
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Visceral Leishmaniasis

Intervention / Treatment
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* Drug: Amphotericin B fat emulsion in visceral leishmaniasis
* Drug: Amphotericin B fat emulsion
* Drug: Amphotericin B in fat emulsion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects between 18 years and 65 years of age (both inclusive). Subject/subject's legally acceptable representative is willing and able to give written informed consent to participate in the study. 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: Subjects with past history of treatment with Amphotericin B for Kala-azar. Subjects positive for HIV infection. Concomitant life threatening or serious disease. Concurrent malaria (malarial parasite test to be negative prior to study treatment administration), tuberculosis or bacterial pneumonia. Haemoglobin < 6 gm/dl, total leukocyte count < 1,500/cmm, platelet count < 50,000/cmm 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). Pregnant or nursing women. Known hypersensitivity to Amphotericin B or inactive ingredients of study drug formulation. Subjects receiving any of the medications prohibited by the study protocol. 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. Simultaneous participation in another trial or received any investigational product < 30 days prior to enrolment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Amphotericin B in fat emulsion (Amphomul) 7.5 mg/kg on day 1 and 3 | Drug: Amphotericin B fat emulsion in visceral leishmaniasis<br>* 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<br>* Other names: Amphomul;Drug: Amphotericin B fat emulsion<br>* 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<br>* Other names: Amphomul;Drug: Amphotericin B in fat emulsion<br>* 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<br>* Other names: Amphomul;|
| Experimental: B<br>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<br>* 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<br>* Other names: Amphomul;Drug: Amphotericin B fat emulsion<br>* 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<br>* Other names: Amphomul;Drug: Amphotericin B in fat emulsion<br>* 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<br>* Other names: Amphomul;|
| Experimental: C<br>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<br>* 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<br>* Other names: Amphomul;Drug: Amphotericin B fat emulsion<br>* 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<br>* Other names: Amphomul;Drug: Amphotericin B in fat emulsion<br>* 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<br>* Other names: Amphomul;|
| Experimental: D<br>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<br>* 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<br>* Other names: Amphomul;Drug: Amphotericin B fat emulsion<br>* 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<br>* Other names: Amphomul;Drug: Amphotericin B in fat emulsion<br>* 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<br>* Other names: Amphomul;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Visceral Leishmaniasis, Amphotericin B, Fat emulsion