Safety, Efficacy and Pharmacokinetics (PK) Study of WR 279,396 Versus Paromomycin for Treatment of Cutaneous Leishmaniasis (Peru-PK)
Condition: Leishmaniasis, Cutaneous
MeSH terms: Leishmaniasis; Leishmaniasis, Cutaneous
Intervention: WR 279,396 (15% paromomycin + 0.5% gentamicin topical cream); Paromomycin Alone Cream (15% paromomycin topical cream)
Intervention description: topical application to CL lesions once daily for 20 days; topical application to CL lesions once daily for 20 days
Intervention MeSH terms: Gentamicins; Paromomycin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 30.0
Sex: All
Minimum age: 5 Years
Healthy volunteers: No
Keywords: leishmaniasis; cutaneous; WR 279,396; paromomycin; gentamicin; pharmacokinetics; safety; efficacy

Summary:

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

Eligibility criteria:

        Inclusion Criteria:

          -  To be eligible for the study, the following must be answered "YES" or not applicable,
             as appropriate for the study subject:

               1. Is the subject a male or female at least 5 years-of-age?

               2. Is the subject or legal guardian able to give written informed consent or assent,
                  as appropriate?

               3. Does the subject have a diagnosis of CL in at least one lesion by at least one of
                  the following methods: 1) positive culture for promastigotes, or 2) microscopic
                  identification of amastigotes in stained lesion tissue.

               4. Does the subject have at least one ulcerative lesion ≥ 1 cm and ≤ 5 cm, that
                  meets the criteria for an index lesion?

               5. Is the subject willing to forego other forms of treatments for CL including other
                  investigational treatments during the study?

               6. In the opinion of the investigator, is the subject (or their legal guardian)
                  capable of understanding and complying with the protocol?

               7. If female and of child-bearing potential, did the subject 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?

               8. Does the subject have adequate venous access for blood draws?

        Exclusion Criteria:

        To be eligible for the study, the following must be answered "NO" or not applicable as
        appropriate for the study subject:

          1. Does the subject have 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 drugs topically?

          2. Does the subject have a lesion due to leishmania that involves the mucosa or palate or
             any signs of mucosal disease that might be due to leishmania?

          3. Does the subject have signs and symptoms of disseminated disease in the opinion of the
             Principal Investigator?

          4. Does the subject have > 10 lesions?

          5. Is the subject a female who is breast-feeding?

          6. Does the subject have 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?

          7. Does the subject have significant organ abnormality, chronic disease such as diabetes,
             severe hearing loss, evidence of renal or hepatic dysfunction, or creatinine greater
             than 15%, or aspartate aminotransferase (AST), or alanine aminotransferase (ALT)
             greater than 1.5 times the above the upper limit of normal (ULN) as defined by the
             clinical laboratory defined normal ranges?

          8. Has the subject received treatment for leishmaniasis including any medication with
             pentavalent antimony including sodium stibogluconate (Pentostam), meglumine
             antimoniate (Glucantime); amphotericin B (including liposomal amphotericin B and
             amphotericin B deoxycholate); or other medications containing paromomycin
             (administered parenterally or topically) or methylbenzethonium chloride (MBCL);
             gentamicin; fluconazole; ketoconazole; pentamidine; miltefosine, azithromycin or
             allopurinol that was completed within 8 weeks of starting study treatments?

          9. Does the subject have a history of known or suspected hypersensitivity or
             idiosyncratic reactions to aminoglycosides?

         10. Does the subject have any other topical disease/condition which would interfere with
             the objectives of this study?