Phase 3 Study to Evaluate WR 279,396 vs. Paromomycin Alone to Treat Cutaneous Leishmaniasis (in Tunisia)
Condition: Cutaneous Leishmaniasis
MeSH terms: Leishmaniasis; Leishmaniasis, Cutaneous
Intervention: WR 279,396 topical cream; Paromomycin Alone topical cream; Vehicle placebo cream
Intervention description: WR 279,396 is a topical antibiotic cream containing 15% paromomycin and 0.5% gentamicin that will be applied to each lesion once a day and covered with a sterile gauze and tape dressing.; The antibiotic paromomycin 15% in the same topical cream used in arm 1 will be applied to lesions daily and covered with a protective sterile gauze and tape dressing.; Applied daily to cutaneous leishmaniasis lesions, primarily ulcerative, and covered with a protective, sterile gauze and tape dressing.
Intervention MeSH terms: Paromomycin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 375.0
Sex: All
Minimum age: 5 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: cutaneous leishmaniasis, topical treatment, Tunisia

Summary:

      This study will test the ability of the topical cream WR 279,396 to treat the skin lesions
      caused by the parasite called leishmania. WR 279,396 is an antibiotic preparation that
      contains paromomycin + gentamicin. This cream will be compared to the effect of a topical
      cream containing paromomycin alone and to a placebo cream that contains no antibiotics.
      Therefore, this study will have three groups of patients, and they will be assigned to one of
      these treatments randomly. The study will be carried out without the patient or the physician
      knowing which cream is being used for which patient. The goal is to determine if WR 279,396
      cream or the paromomycin cream is better than placebo, and if WR 279,396 is better than
      paromomycin alone.
    

Eligibility criteria:

        Inclusion Criteria:

          -  The subject was age 5 years or older, but less than 65 years.

          -  The subject was able to understand the information provided to him/her and give
             written informed consent. Consent was obtained from the parent/guardian of subjects
             who were < 18 years old. Children 12 to < 18 years old were asked to sign the written
             assent form. Witnessed verbal assent was obtained from subjects 5 to 11 years old.

          -  The subject was a male or female who was generally healthy.

          -  The subject had cutaneous lesions diagnosed as leishmaniasis in the index lesion by:
             (1) the identification of promastigotes in a culture of an aspirated lesion, or (2)
             the microscopic identification of Leishmania amastigotes on a DifQuik or Giemsa
             stained smear obtained from a lesion scraping.

          -  The subject had five or fewer cutaneous lesions.

          -  The subject had one lesion, which would be designated as the index lesion, that was ≥
             1 and < 5 cm in its greatest diameter and primarily ulcerative, ie, not purely
             verrucous or nodular.

          -  The subject was willing to forego other forms of treatment for CL, including other
             investigational treatment during the study.

          -  In the opinion of the principal investigator, the subject or subject's parent/guardian
             was capable of understanding and complying with the protocol

        Exclusion Criteria

          -  The subject received previous treatment for leishmaniasis (including WR 279,396)
             within the last 6-months, with the exception of mercurochrome.

          -  The subject had difficulty complying with instructions on maintaining the dressing,
             eg, due to life style activities or age.

          -  The subject had only a single lesion whose characteristics included any of the
             following: verrucous or nodular lesion, ≥ 5 cm in its greatest diameter, < 1 cm or
             located on the ear, or other location that in the opinion of the principal
             investigator would be difficult to maintain application of study drug topically.

          -  The subject had a lesion due to Leishmania that involved the mucosa.

          -  The subject had signs or symptoms of disseminated disease, ie, clinically significant
             lymphadenitis with nodules that were painful and > 1 cm in the lymphatic drainage of
             the ulcer.

          -  The subject was a female with a positive urine pregnancy test, or who was breast
             feeding or lactating.

          -  The subject had an active malignancy or had a history of a solid, metastatic or
             hematologic malignancy, with the exception of a basal or squamous cell carcinoma of
             the skin that had been removed.

          -  The subject had a significant organ abnormality or chronic disease that, in the
             opinion of the investigator, would warrant exclusion of the subject from the study or
             would prevent the subject from completing the study.

          -  The subject was receiving any of the following medications: any medication containing
             pentavalent antimony, including stibogluconate sodium (Pentostam®) and meglumine
             antimoniate (Glucantime®); amphotericin B, including liposomal amphotericin B and
             amphotericin B deoxycholate; other medications containing paromomycin (administered IV
             or topically); methylbenzethonium chloride, fluconazole, ketoconazole, itraconazole;
             pentamidine; or allopurinol.

          -  The subject or the subject's parent/guardian was unable to understand verbal and/or
             written Arabic, English, or French (languages in which certified translations of the
             informed consent were available).

          -  The subject presented with an immuno-compromising condition, including recidivant
             leishmaniasis (during the past 2 years), or diabetes.

          -  The subject had a history of known or suspected idiosyncratic reactions or
             hypersensitivity to aminoglycosides.