Topical 3% Amphotericin B Cream for the Treatment of Cutaneous Leishmaniasis in Colombia

Study Overview
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Brief Summary
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The proposed study encompasses a two-step approach. The first aiming to determine the safety of Topical 3% Amphotericin B Cream when applied three or two times per day for 4 weeks in subjects with un-complicated Cutaneous leishmaniasis (CL) whilst the second focusing in having and indication of the efficacy of the two above mentioned regimens of Topical 3% Amphotericin B Cream For the first step, 30 subjects will be randomly assigned to receive direct observed treatment (DOT) with Topical 3% Amphotericin B Cream applied either three or two times per day for 4 weeks. Enrolment will be temporarily halted until all 30 subjects (15 in each group) have been enrolled and completed the 28 day treatment course. An interim analysis of all safety (Adverse Events, including local reactions and lab parameters) and pharmacokinetics collected on subjects who were randomized will be performed by data safety monitoring board. If no serious adverse events (SAEs) related to the study drug are identified on the first 30 subjects by the end of the treatment course, 50 additional subjects will be randomly allocated to receive Topical 3% Amphotericin B Cream either three or two times per day for 28 days Subjects will have a follow-up visit at the end of therapy, on Day 45± 5 days, Day 63± 5 days and on Days 90± 14 days and on Day 180, minus 14d, plus 4 weeks to assess efficacy, as measured by the number of subjects who fulfil the cure criteria: 100% re-epithelialization of the lesion(s) by Day 90 and no relapse by Day 180. All subjects will be followed up to Day 180 for final analysis of efficacy.

Official Title
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Safety, Pharmacokinetics, and Efficacy of Topical 3% Amphotericin B Cream for the Treatment of Uncomplicated Cutaneous Leishmaniasis in Colombia

Conditions
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Cutaneous Leishmaniasis

Intervention / Treatment
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* Drug: Topical Amphotericin B at 3%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject with a confirmed infection due to L. braziliensis by polymerase chain reaction assay Subject has a lesion that satisfies the following criteria: ulcerative in character ulcer size equal or more than 0.5 cm and 3 cm (Longest diameter) not located on the ear, face, close to mucosal membranes, joints or on a location that in the opinion of the PI is difficult to maintain application of study drug topically. Subject with up to 3 lesions. Duration of lesion less than 3 months by patient history Subject able to give written informed consent and that the opinion of the investigator, the subject is capable of understanding and complying with the protocol Exclusion Criteria: Female with a positive serum pregnancy test at screening or who is breast feeding, lactating or female at fertile age who does not agree to take appropriate contraception during treatment period up to Day 45. History of clinically significant medical problems or treatment that might interact, either negatively or positively, with topical treatment of leishmaniasis including any immunocompromising condition. Within 8 weeks (56 days) of starting study treatments, received treatment for leishmaniasis with any medication including antimonials likely, in the opinion of the PI, to modify the course of the Leishmania infection Has diagnosis or suspected diagnosis of mucocutaneous leishmaniasis based on physical exam. History of known or suspected hypersensitivity or idiosyncratic reactions to amphotericin Has laboratory values at screening as follow: Haemoglobin below 10 grams, Serum creatinine above normal level, alanine aminotransferase and or aspartate aminotransferase 3 times above normal range

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Topical Amphotericin B three times per day<br>Anfoleish applied 3 times per day for 4 weeks (TID group) | Drug: Topical Amphotericin B at 3%<br> <br> * Other names: Anfoleish;|
| Experimental: Topical Amphotericin B two times per day<br>Anfoleish applied 2 times per day for 4 weeks (BID group) | Drug: Topical Amphotericin B at 3%<br> <br> * Other names: Anfoleish;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion and severity of local adverse events of Anfoleish or Vehicle when applied three or two times per day. | Local adverse events including erythema/redness, swelling/oedema, and vesicles will be scored according the following criteria: Grade 1: Visibly present but not associated with any other symptoms. Grade 2: Visibly present, large area around lesion site, and associated with other symptoms such as itching or pain. Medical intervention may be required. Grade 3: Severe symptoms that require medical discontinuation of the study drug. | At the end of treatment (Day 28) | 
| Clinical cure rates in two regimens of Anfoleish: Three times a day and Two times a day | Cure is defined as 100% re-epithelialization of the lesion(s) by Day 90. | Day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of Amphotericin B Cmax and Tmax in subjects treated with Anfoleish three or two times per day. |  | Day 45 | 
| Proportion and severity of laboratory adverse events of Anfoleish or vehicle when applied three or two times per day | Laboratory adverse events are limited to monitoring serum levels of creatinine, alanine aminotransferase and aspartate aminotransferase. | At the end of treatment (Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cutaneous leishmaniasis, Topical treatment, Colombia