Topical Treatment of Recalcitrant Ulcerative Old World Leishmaniasis With WR 279,396
Condition: Cutaneous Leishmaniasis
MeSH terms: Leishmaniasis; Leishmaniasis, Cutaneous
Intervention: Paromomycin +Gentamicin topical cream
Intervention description: WR297,396 for treatment of patients with parasitologically confirmed, primarily ulcerative, Old World CL, who had either failed pentavalent antimony treatment, or who where ineligible for pentavalent antimony therapy.
Intervention MeSH terms: Gentamicins; Paromomycin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: leishmaniasis; cutaneous; Old World; Leishmania major; Treatment

Summary:

      The primary objective of this protocol is to treat laboratory confirmed cutaneous
      leishmaniasis with WR 279,396 in military health care beneficiaries. In this study "cutaneous
      leishmaniasis" is defined as Old World Leishmaniasis if acquired in the Southwest Central
      Asia/Middle East.
    

Eligibility criteria:

        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.