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NCT Number: NCT00703924

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

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.

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Key information

Conditions

Cutaneous Leishmaniasis Euglenozoa Infections Infections Leishmaniasis Leishmaniasis, Cutaneous Parasitic Diseases Protozoan Infections Skin Diseases Skin Diseases, Infectious Skin Diseases, Parasitic Skin and Connective Tissue Diseases Vector Borne Diseases

Age range

5 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Medical Center Institut Pasteur, Paris, France

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

WR 279,396

Drug

A topical cream containing 15% paromomycin and 0.5% gentamicin. Approximately 0.0005 mL per mm2 of skin lesion

Other names: Paromomycin topical cream

Placebo

Drug

Topical cream vehicle. Approximately 0.0005 mL per mm2 of skin lesion

Other names: Topical vehicle placebo

Primary outcomes

  1. Complete Clinical Response (CCR) of Lesion at Days 50, 100 and 180 (+7 Days)

    Time frame: 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

  2. Safety of WR 279,396 (AEs and SAEs)

    Time frame: 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 outcomes

  1. Time to Complete Re-epithelialization of the Index Lesion Ulcer Without Relapse

    Time frame: 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.

  2. Final Cure Rate by Subject of All Lesions

    Time frame: 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.

  3. Rate of Relapse

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

U.S. Army Medical Research and Development Command

Fed

Collaborators

  • Walter Reed Army Institute of Research (WRAIR)

Registry information

Important dates

Study start
2003
Primary completion
2004
Study completion
2005
First posted
Jun 24, 2008
Registry last updated
May 30, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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