Safety, Efficacy, and PK of Topical Paromomycin/Gentamicin Cream for Treatment of Cutaneous Leishmaniasis
Condition: Leishmaniasis, Cutaneous
MeSH terms: Leishmaniasis; Leishmaniasis, Cutaneous
Intervention: WR 279,396
Intervention description: Topical application of WR 279,396 cream (15% paromomycin + 0.5% gentamicin)once daily for 20 days
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
Healthy volunteers: No
Keywords: leishmaniasis; cutaneous; WR 279,396; paromomycin; gentamicin; pharmacokinetics; safety; efficacy; military

Summary:

      The objectives of the study are to evaluate the safety, pharmacokinetics (PK), and efficacy
      of open label treatment with WR 279,396 (Topical Paromomycin/Gentamicin Cream)in subjects
      with cutaneous leishmaniasis (CL).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects must be male or female military health care beneficiary of any race or
             ethnicity and at least 18 years of age

          -  Subjects must give written informed consent.

          -  Subjects must have a diagnosis of CL in at least one lesion by at least one of the
             following methods: 1) positive culture for promastigotes; 2) microscopic
             identification of amastigotes in stained lesion tissue; 3) positive polymerase chain
             reaction (PCR) assay; and/or 4) prior diagnosis of CL within 14 days of the start of
             treatment.

          -  Subjects must have at least one ulcerative lesion ≥ 1 cm and < 5 cm, that meets the
             criteria for an index lesion (Larger lesions will be accepted for treatment, but these
             will not be included in the primary evaluation of efficacy).

          -  Subjects must be willing to forego other forms of treatments for CL including other
             investigational treatment during the study.

          -  Subjects must be capable of understanding and complying with the protocol (in the
             opinion of the investigator).

          -  Subjects must expect to be located in the Washington DC metropolitan area for at least
             the duration of the screening, 20-day treatment period, and Day 28 +/- 2 days
             follow-up visit.

          -  Subjects who are female and of child-bearing potential, must have a negative pregnancy
             test during screening and agree to use an acceptable method of birth control during
             the treatment phase and for 1 month after treatment is completed.

          -  Subject has adequate venous access for blood draws, if consented to the PK part of
             study.

        Exclusion Criteria:

          -  Subject has had a prior diagnosis of leishmaniasis where all lesions had healed.

          -  Subject has only a single lesion whose characteristics include any of the following:
             verrucous or nodular lesion (non-ulcerative), lesion <1 cm in its greatest diameter,
             lesion in a location that in the opinion of the Investigator is difficult to maintain
             application of study drug topically.

          -  Subject has a lesion due to Leishmania that involves the mucosa or palate.

          -  Subject has signs and symptoms of disseminated disease.

          -  Subject is a female who is breast-feeding.

          -  Subject has an active malignancy or history of solid, metastatic or hematologic
             malignancy with the exception of basal or squamous cell carcinoma of the skin that has
             been removed.

          -  Subject has significant organ abnormality, chronic disease such as diabetes, severe
             hearing loss, evidence of renal or hepatic dysfunction, or creatinine, AST, or ALT
             greater than the upper limit of normal as defined by the clinical laboratory normal
             ranges.

          -  Subject has received treatment for leishmaniasis including thermosurgery (ThermoMed™)
             or any medication with pentavalent antimony including sodium stibogluconate
             (Pentostam), meglumine antimoniate (Glucantime); amphotericin B (including liposomal
             amphotericin B and amphotericin B deoxycholate); WR 279,396; or other medications
             containing paromomycin (administered parenterally or topically) or methylbenzethonium
             chloride (MBCL); gentamicin; fluconazole; ketoconazole; pentamidine; or allopurinol
             within 4 weeks of starting study treatment.

          -  Subject has a history of known or suspected hypersensitivity or idiosyncratic
             reactions to aminoglycosides.

          -  Subject has any other topical disease/condition which interferes with the objectives
             of this study.