Topical Treatment of Cutaneous Leishmaniasis With WR 279,396: A Phase 2 Study in the Old World

Topical Treatment of Cutaneous Leishmaniasis With WR 279,396: a Phase 2 Study in the Old World

This study is to determine the effectiveness and safety of WR 279,396, a topical cream for the treatment of cutaneous leishmaniasis. This study is to be conducted with a placebo control under double-blind conditions in a local population group in Tunisia where leishmaniasis is endemic.

WR 279,396 is a paromomycin-based topical cream that has shown some suggestion of being effective for the treatment of non-serious, non-complicated cutaneous leishmaniasis in previous clinical studies. The goal of this study is to expand those observations in a larger, more rigorous study to clearly define the efficacy of this product and collect information about adverse effects. Subjects will be randomized to receive either WR 279,396 or vehicle placebo; applied twice a day for 20 days.

Inclusion Criteria:

• Age 5-75 years
• Lesions must measure at least 1 cm and be primarily ulcerative
• Have cutaneous leishmaniasis proven parasitologically in the lesion selected for study
• Must have given written informed consent to participate in the study

Exclusion Criteria:

• Known drug intolerance to aminoglycosides in the patient or immediate family
• Previous use of antileishmanial drugs (within 3 months) or present use of routinely nephrotoxic or ototoxic drugs
• Patients with tuberculosis under treatment
• Potential for follow-up: have less than 7 months time remaining in present address and/or plan to leave the area for more than 30 days
• Extent of disease: more than 5 lesions or lesion equal to or greater than 5 cm or a lesion less than 5 cm from the eye, or a lesion in the face that, in the opinion of the attending dermatologist could potentially cause significant disfigurement
• Location of disease: mucosal involvement
• Disseminated disease: clinically significant lymphadenitis with nodules that are painful and greater than 1 cm in size in the lymphatic drainage of the ulcer
• Concomitant medical problems: significant medical problems of the kidney or liver as determined by history and by the following laboratory studies:
• Hearing abnormality
• Ongoing pregnancy or have plans to become pregnant
• Females of child bearing age (Tunisia Only)
• Signs or symptoms of peripheral neuropathy

Kidney: clinically significant abnormalities of urine analysis, serum levels of creatinine, BUN, total proteins greater than the upper limit of normal for the laboratory.

Liver: AST or ALT greater than the upper limit of normal for the laboratory General: glucose, Na+, or K+ greater than the upper limit of normal for the laboratory