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

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ClinicalTrials.gov Identifier: NCT00703924
Recruitment Status : Completed
First Posted : June 24, 2008
Results First Posted : February 15, 2017
Last Update Posted : May 30, 2017
Sponsor:
Collaborator:
Walter Reed Army Institute of Research (WRAIR)
Information provided by (Responsible Party):
U.S. Army Medical Research and Materiel 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.

Condition or disease Intervention/treatment Phase
Cutaneous Leishmaniasis Drug: WR 279,396 Drug: Placebo Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 92 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Topical Treatment of Cutaneous Leishmaniasis With WR 279,396: a Phase 2 Study in the Old World
Study Start Date : March 2003
Primary Completion Date : November 2004
Study Completion Date : November 2005

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Leishmaniasis
U.S. FDA Resources

Arm Intervention/treatment
Experimental: WR 279,396
WR 279,396 is a topical antibiotic cream containing paromomycin and gentamicin
Drug: WR 279,396
A topical cream containing 15% paromomycin and 0.5% gentamicin. Approximately 0.0005 mL per mm2 of skin lesion
Other Name: Paromomycin topical cream
Placebo Comparator: Placebo
Topical cream vehicle containing all of the components in WR 279,396 except the active ingredients.
Drug: Placebo
Topical cream vehicle. Approximately 0.0005 mL per mm2 of skin lesion
Other Name: Topical vehicle placebo



Primary Outcome Measures :
  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 Outcome Measures :
  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.




Information from the National Library of Medicine

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Ages Eligible for Study:   5 Years to 75 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00703924


Locations
France
Medical Center Institut Pasteur
Paris, France, 75015
Tunisia
Institue Pasteur
Tunis, Tunisia
Sponsors and Collaborators
U.S. Army Medical Research and Materiel Command
Walter Reed Army Institute of Research (WRAIR)
Investigators
Principal Investigator: Afif Ben Salah, M.D., Ph.D. Institute Pasteur Tunisia

Publications:
Responsible Party: U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier: NCT00703924     History of Changes
Other Study ID Numbers: A-9768.1
IND 50098 ( Other Identifier: FDA )
First Posted: June 24, 2008    Key Record Dates
Results First Posted: February 15, 2017
Last Update Posted: May 30, 2017
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data will be shared with WRAIR

Keywords provided by U.S. Army Medical Research and Materiel Command:
cutaneous leishmaniasis topical treatment safety efficacy

Additional relevant MeSH terms:
Leishmaniasis
Leishmaniasis, Cutaneous
Euglenozoa Infections
Protozoan Infections
Parasitic Diseases
Skin Diseases, Parasitic
Skin Diseases, Infectious
Skin Diseases
Paromomycin
Amebicides
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Anti-Bacterial Agents