Topical Treatment of Recalcitrant Ulcerative Old World Leishmaniasis With WR 279,396

Up to 10 volunteers, who are military health care beneficiaries, with a diagnosis of Old
World cutaneous leishmaniasis who have failed pentavalent antimony or are not eligible to be
treated with pentavalent antimony, will be treated with WR 279,396 (topical
paromomycin-gentamicin-AQIC) twice a day for 20 days. Primary endpoint will be the appearance
of complete epithelialization of each skin lesion by Day 50+/-2 weeks, or estimated 50%-99%
re-epithelialization by Day 50+/-2 weeks followed by complete epithelialization by Day
100+/-2 weeks,with both categories without relapse by Day 180+/-30 days. Efficacy will be
evaluated by clinical appearance assessed by study investigator and documented with
photographs of the treated skin lesions. Toxicity will be evaluated by local adverse
reactions and by laboratory signs of systemic toxicity.

Inclusion Criteria:

Parasitologically confirmed, primarily ulcerative, Old World CL, in a patient who had
either failed pentavalent antimony treatment, or who was ineligible for pentavalent
antimony therapy.

- Military health care beneficiary 18 years of age or greater, unless active military in
which case, 17 years is the minimum age

- Proven parasitological diagnosis by culture, PCR or microscopy in at least one skin
lesion

- Lesions primarily ulcerative (i.e., not verrucous or nodular)

- Written informed consent to participate in protocol

- Negative pregnancy test within 72 hours of starting protocol

- Agrees to take precautions not to become pregnant or father a child for at least two
months after completion of treatment with WR 279,396

- Cutaneous leishmaniasis acquired in Southwest Central Asia/Middle East*

- Inadequate response to treatment with pentavalent antimony or medical condition that
precludes the use of pentavalent antimony

Exclusion Criteria:

- Drug intolerance: history of known or suspected hypersensitivity or idiosyncratic
reactions to aminoglycosides in the patient

- any leishmanial lesion on mucosal surface

- Presence of signs or symptoms of peripheral neuropathic myasthenia gravis,
neuromuscular block

- Routinely taking nephrotoxic or ototoxic medications

- Disseminated disease defined as clinically significant subcutaneous nodules that are
in the lymphatic drainage tract for the skin lesion with regional adenopathy > 1 cm

- Abnormal Romberg test at baseline

- Clinically significant medical problems of the kidney or liver as determined by
history and by the following laboratory studies:

- Kidney: Creatinine > 2x the upper limit of normal

- Liver: ASTor ALT >4x the upper limit fo normal

- This includes "L. major," "L. tropica," and "L. infantum" with over 98% of
cases in U.S. military in 2002-2004 being "L. major"

- An inadequate response to treatment with pentavalent antimony includes
patients who show no or little improvement during a 15-20 day treatment
course, those that initially epithelialize but later show signs of
breakdown/ ulceration or develop new lesions. In general, for those
with initial treatment response, would recommend waiting for
approximately two months after pentavalent antimony and if lesion is
not epithelialized at that time, consideration for further therapy is
advised.