Topical Treatment of Cutaneous Leishmaniasis With WR 279,396: A Phase 2 Study in the Old World

Phase 2

Completed

Conditions: Cutaneous Leishmaniasis

Interventions: Drug: Placebo
Drug: WR 279,396

Registration Number: NCT00703924

Lead Sponsor: U.S. Army Medical Research and Development Command

Brief Summary: This study is to determine the effectiveness and safety of WR 279,396, a topical cream for the treatment of cutaneous leishmaniasis. This study is to be conducted with a placebo control under double-blind conditions in a local population group in Tunisia where leishmaniasis is endemic.

Detailed Description: WR 279,396 is a paromomycin-based topical cream that has shown some suggestion of being effective for the treatment of non-serious, non-complicated cutaneous leishmaniasis in previous clinical studies. The goal of this study is to expand those observations in a larger, more rigorous study to clearly define the efficacy of this product and collect information about adverse effects. Subjects will be randomized to receive either WR 279,396 or vehicle placebo; applied twice a day for 20 days.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 92

Inclusion Criteria

Age 5-75 years
Lesions must measure at least 1 cm and be primarily ulcerative
Have cutaneous leishmaniasis proven parasitologically in the lesion selected for study
Must have given written informed consent to participate in the study

Exclusion Criteria

Known drug intolerance to aminoglycosides in the patient or immediate family
Previous use of antileishmanial drugs (within 3 months) or present use of routinely nephrotoxic or ototoxic drugs
Patients with tuberculosis under treatment
Potential for follow-up: have less than 7 months time remaining in present address and/or plan to leave the area for more than 30 days
Extent of disease: more than 5 lesions or lesion equal to or greater than 5 cm or a lesion less than 5 cm from the eye, or a lesion in the face that, in the opinion of the attending dermatologist could potentially cause significant disfigurement
Location of disease: mucosal involvement
Disseminated disease: clinically significant lymphadenitis with nodules that are painful and greater than 1 cm in size in the lymphatic drainage of the ulcer
Concomitant medical problems: significant medical problems of the kidney or liver as determined by history and by the following laboratory studies:
Hearing abnormality
Ongoing pregnancy or have plans to become pregnant
Females of child bearing age (Tunisia Only)
Signs or symptoms of peripheral neuropathy

Kidney: clinically significant abnormalities of urine analysis, serum levels of creatinine, BUN, total proteins greater than the upper limit of normal for the laboratory.

Liver: AST or ALT greater than the upper limit of normal for the laboratory General: glucose, Na+, or K+ greater than the upper limit of normal for the laboratory

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Topical cream vehicle containing all of the components in WR 279,396 except the active ingredients.
WR 279,396	WR 279,396	WR 279,396 is a topical antibiotic cream containing paromomycin and gentamicin

Primary Outcome Measures

Name	Time	Method
Complete Clinical Response (CCR) of Lesion at Days 50, 100 and 180 (+7 Days)	180 days	CCR is defined as at least 50% reduction, from baseline, in index lesion area of ulceration at study days 50, 100 and 180 (+ 7 days). Randomized subjects were compared using the uncorrected Fisher's exact test. Confidence intervals (95%) were constructed on the difference between the two group proportions. The log-rank test was used to compare the time to complete re-epithelialization of the index lesion without relapse. Cure of all subjects lesions was also compared using the Fisher's exact test. To adjust for baseline differences in the treatment groups, a linear model for the proportion of subjects achieving CCR was fit for each baseline variable of interest with covariates for treatment group and the baseline variable. The Breslow-Day test was used to examine whether the effect of WR 279,396 varied between subgroups
Safety of WR 279,396 (AEs and SAEs)	180 days	Safety was evaluated on each day during daily administration of the topical products. Subjects were observed and questioned for the occurrence of solicited local side effects (eg, pain, erythema, edema) and solicited systemic side effects (eg, vertigo, tinnitus, diminished hearing). Non-solicited AE evaluations included spontaneous reports from subjects and clinical observations.

Secondary Outcome Measures

Name	Time	Method
Time to Complete Re-epithelialization of the Index Lesion Ulcer Without Relapse	180 days	100% re-epithelialization of the index lesion without having had a relapse. The log-rank test was used to compare the time to complete re-epithelialization.
Final Cure Rate by Subject of All Lesions	180 days	Final cure rate by subject was determined using the Fisher's exact test. To adjust for baseline differences in the treatment groups, a linear model for the proportion of subjects achieving CCR was fit for each baseline variable of interest with covariates for treatment group and the baseline variable.
Rate of Relapse	180 days	Relapse is defined as enlargement of the index lesion compared to previous measurement at any time after day 50 (+ 7 days) or not demonstrating CCR by study day 180. CCR was compared using uncorrected Fisher's exact test. Confidence intervals (95%) were constructed on the difference between the two group proportions. The log-rank test was used to compare the time to complete re-epithelialization of the index lesion without relapse. Cure of all subjects lesions was also compared using the Fisher's exact test. To adjust for baseline differences in the treatment groups, a linear model for the proportion of subjects achieving CCR was fit for each baseline variable of interest with covariates for treatment group and the baseline variable.