Leishmaniasis, Cutaneous Clinical Trial
Official 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
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).
Status | Completed |
Enrollment | 30 |
Est. completion date | July 2011 |
Est. primary completion date | March 2011 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 5 Years and older |
Eligibility |
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? |
Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
Peru | Universidad Peruana Cayetano Heredia (UPCH) | Lima |
Lead Sponsor | Collaborator |
---|---|
U.S. Army Medical Research and Materiel Command |
Peru,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Final Clinical Cure for Index Lesions | Final clinical cure was defined as follows: Subject has initial clinical cure (100% re-epithelialization of index lesion by nominal Day 63); OR, Subject has initial clinical improvement (> 50% re-epithelialization of index lesion by nominal Day 63 followed by 100% re-epithelialization of the index lesion on or before nominal Day 100; AND, Subject has no relapse of index lesion by Day 168. Relapse was defined as an index lesion meeting the criteria for initial clinical cure that had any new ulceration/nodule (> 0 x 0 mm measurement) by nominal day 168, or an index lesion meeting the criteria for initial clinical improvement that subsequently enlarged by nominal Day 168. |
Initial clinical cure by day 63 and no relapse by day 168 | No |
Secondary | Detectable Paromomycin Plasma Levels | Paromomycin plasma concentrations following administration of paromomycin alone or WR 279,396 in adults | Day 4, 7, 12, 17, 20, 28 | No |
Secondary | Paromomycin Plasma Concentrations in Children | Paromomycin plasma concentrations 4 hours following administration of paromomycin alone or WR 279,396 in children | 0 and 4 hours on days 1 and 20 | No |
Secondary | Pharmacokinetic Parameter: Cmax | Cmax of paromomycin following administration of paromomycin alone or WR 279,396 to adults in Panama | 0, 0.5, 1.0, 2.0, 3.0, 4.0, 8.0, 12.0, 24.0 hours on both Days 1 and 20 | No |
Secondary | Pharmacokinetic Parameter: Tmax | Pharmacokinetic Parameter: Tmax | 0, 0.5, 1.0, 2.0, 3.0, 4.0, 8.0, 12.0, 24.0 hours on both Days 1 and 20 | No |
Secondary | Pharmacokinetic Parameter: Area Under the Curve (AUC) | Area under the curve (AUC) of paromomycin following administration of paromomycin alone or WR 279,396 to adults in Panama | 0, 0.5, 1.0, 2.0, 3.0, 4.0, 8.0, 12.0, 24.0 hours on both Days 1 and 20 | No |
Secondary | Pharmacokinetic Parameter: t(1/2) | t(1/2) of paromomycin following administration of paromomycin alone or WR 279,396 to adults in Panama | 0, 0.5, 1.0, 2.0, 3.0, 4.0, 8.0, 12.0, 24.0 hours on both Days 1 and 20 | No |
Secondary | Pharmacokinetic Parameter: Cmax/D | Maximum observed plasma concentration divide by topical dose (Cmax/D) of paromomycin following administration of paromomycin alone or WR 279,396 to adults in Panama | 0, 0.5, 1.0, 2.0, 3.0, 4.0, 8.0, 12.0, 24.0 hours on both Days 1 and 20 | No |
Secondary | Pharmacokinetic Parameter: AUC/D | Area under the plasma concentration-time curve over 24 hrs divided by topical dose (AUC/D) of paromomycin following administration of paromomycin alone or WR 279,396 to adults in Panama | Days 1 and 20 | No |
Secondary | Final Clinical Cure on All Lesions Independent of Subjects | Final clinical cure was defined as follows: Subject has initial clinical cure (100% re-epithelialization of lesion by nominal Day 63); OR, Subject has initial clinical improvement (> 50% re-epithelialization of lesion by nominal Day 63 followed by 100% re-epithelialization of the lesion on or before nominal Day 100; AND, Subject has no relapse of lesion by Day 168. Relapse was defined as a lesion meeting the criteria for initial clinical cure that had any new ulceration/nodule (> 0 x 0 mm measurement) by nominal day 168, or a lesion meeting the criteria for initial clinical improvement that subsequently enlarged by nominal Day 168. |
Initial clinical cure by day 63 and no relapse by day 168 | No |
Secondary | Number of Index Lesions Meeting Criteria for Clinical Cure During the Study | Number of study participants who meet the criteria for clinical cure (100% re-epithelialization) at specified timepoints during the study. | Day 1, 4, 7, 12, 17, 20, 28, 35, 42, 49, 56, 63, 100, 168 | No |
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