Please select the eligibility criteria that correspond to the clinical trial below.
Title: Double-blind, Randomized, Pharmacokinetics, Safety, and Efficacy Trial of WR 279,396 (Paromomycin + Gentamicin Topical Cream) and Paromomycin Topical Cream for the Treatment of Cutaneous Leishmaniasis in Peru
Brief 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).


Options:
A: Inclusion Criteria:

* Newly diagnosed (untreated) cutaneous leishmaniasis with localized lesions and visualization of amastigotes in tissue samples or a positive culture or diagnosed by polymerase chain reaction (PCR) methods or by intradermal skin testing (Montenegro test).
* Number of lesions: 1 to 5 ulcerative lesions.
* Lesion´s diameter: 1 to 5 cm.
* Disease duration: up to three months.

Exclusion Criteria:

Safety concerns:

* Thrombocyte count \<30 x 109/l
* Leukocyte count \<1 x 109/l
* Hemoglobin \<5 g/100 ml
* ASAT, ALAT, AP \>3 times upper limit of normal range
* Bilirubin \>2 times upper limit of normal range
* Serum creatinine or BUN \>1.5 times upper limit of normal range
* Evidence of serious underlying disease (cardiac, renal, hepatic or pulmonary)
* Immunodeficiency or antibody to HIV
* Any non-compensated or uncontrolled condition, such as active tuberculosis, malignant disease, severe malaria, HIV, or other major infectious diseases
* Lactation, pregnancy (to be determined by adequate test) or inadequate contraception in females of childbearing potential for treatment period plus 2 months

Lack of suitability for the trial:

* Negative parasitology (aspirate/smear)or negative Montenegro test
* Any history of prior anti-leishmania therapy
* Any condition which compromises ability to comply with the study procedures
* Concomitant serious infection other than cutaneous

Administrative reasons:

* Lack of ability or willingness to give informed consent (patient and/or parent / legal representative)
* Anticipated non-availability for study visits/procedures
B: 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?
C: Inclusion Criteria:

* Parasitologically proven cases of CL based on positive smear and/or culture.
* Patients belonging to the National Colombian Army.
* Otherwise healthy subjects on the basis of medical history, physical examination and results of blood test (if seemed necessary by the physician)
* Age 18-40 years.
* Willing to participate in the study, sign the informed consent , to go to the scheduled visits and to the follow-up visits.
* Abstain to receive any other treatment for CL during the trial and follow-up periods.
* Non purulent lesions.
* Mentally sane volunteers.
* No Leishmaniasis treatment in the six months prior to the recruitment.
* Number of lesions no more than 5

Exclusion criteria:

* None of the lesions must be close to the anal, oral and nasal mucosa, or next to the urogenital and anal canal.
* Serious systemic illnesses (as judged by the physician)
* Patients with mucosal compromise.
* Patients with diffuse Leishmaniasis ( defined as 10 or more cutaneous lesions and negative Montenegro's test)
D: Inclusion Criteria:

* Newly diagnosed cutaneous leishmaniasis (untreated) with localized lesions ( without maximum 6 injuries ) and Direct Examination positive : amastigotes display in tissue samples ;
* Age: 16-64 years;
* Sex: male and female patients to eligible ;
* Disease Clinical Evolution not longer than 3 months .

Exclusion Criteria:

* AST \> 3 times the upper limit of normal;
* ALT \> 3 times the upper limit of normal;
* Alkaline phosphatase \> 3 times the upper limit of normal;
* Serum creatinine and urea \> 1.5 times the upper limit of normality;
* Blood glucose above 110 mg / dl;
* Evidence of serious underlying disease ( heart , kidney , liver or lung);
* protein and / or caloric severe malnutrition;
* Any uncompensated or uncontrolled condition like active tuberculosis, malignant disease , severe malaria , HIV, leprosy , systemic fungal disease (histoplasmosis, paracoccidioidomycosis) or any other infectious disease;
* Pregnant women or who are breastfeeding;
* Lack of ability or willingness to provide informed consent (patient and / or parent / legal representative); lack of availability for the visits or to comply with study procedures.

Answer: B