Clinical Trial: Phase 3 Study to Evaluate WR 279,396 vs. Paromomycin Alone to Treat Cutaneous Leishmaniasis (in Tunisia)

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Pivotal, Randomized, Double-blind, Vehicle-controlled Study to Evaluate WR 279,396 and Paromomycin Alone to Treat Cutaneous Leishmaniasis (in Tunisia)

Brief Summary: This study will test the ability of the topical cream WR 279,396 to treat the skin lesions caused by the parasite called leishmania. WR 279,396 is an antibiotic preparation that contains paromomycin + gentamicin. This cream will be compared to the effect of a topical cream containing paromomycin alone and to a placebo cream that contains no antibiotics. Therefore, this study will have three groups of patients, and they will be assigned to one of these treatments randomly. The study will be carried out without the patient or the physician knowing which cream is being used for which patient. The goal is to determine if WR 279,396 cream or the paromomycin cream is better than placebo, and if WR 279,396 is better than paromomycin alone.

Detailed Summary: This is an efficacy study to test the ability of WR 279,396 topical cream to treat uncomplicated cutaneous leishmaniasis caused primarily by Leishmania major in adults and children in Tunisia where the disease in endemic. A total of 375 volunteers will be randomized to the three arms described above to determine product efficacy. Safety data in all three arms will also be collected.
Sponsor: U.S. Army Medical Research and Materiel Command

Current Primary Outcome: Final Clinical Cure Rate [ Time Frame: Day 42, 98, and 168 ]

Final clinical cure was defined as an index lesion that met the criteria for initial clinical cure without relapse. Definitions for index lesion outcomes were as follows:

  • Initial Clinical Improvement: At least 50% to 99% reduction in the size of the measured lesion from the baseline measurement by the Day 42 evaluation.
  • Initial Clinical Cure: 100% re-epithelialization (ie, a 0 x 0 length x width measurement) of the lesion at the nominal Day 42 evaluation, or initial clinical improvement followed by 100% re-epithelialization by Day 98.
  • Relapse: Initial clinical cure followed by re-ulceration by Day 168, or initial clinical improvement followed by lesion enlargement by Day 168.
  • Final Clinical Cure: Initial clinical cure without relapse through study Day 168.Clinical Failure: Lack of at least initial clinical improvement by Day 42, or relapse.


Original Primary Outcome: WR 279,396 is superior to placebo in lesion healing [ Time Frame: 48 days ]

Current Secondary Outcome:

  • Final Clinical Cure Rate (Per Protocol Dataset) [ Time Frame: Day 42, 98, and 168 ]
    Final clinical cure was defined as an index lesion that met the criteria for initial clinical cure without relapse. Definitions for index lesion outcomes as described in the primary outcome measure.
  • Estimated Percentage Subjects With Re-epithelialization of the Index Lesion Without Relapse [ Time Frame: Day 42 ]
    For the first of the above analyses, subjects were considered to have endpoint events at the first assessment on or before Day 42 where complete re-epithelialization occurred at the index lesion that was not followed by a later assessment where ulceration was present. Subjects who did not have complete re-epithelialization by Day 42 or who relapsed after Day 42 were censored in the analysis at the Day 42 assessment. This analysis was only to be conducted through Day 42.
  • Estimated Percentage of Subjects With Re-epithelialization of the Index Lesion Without Relapse at Various Times of Follow-up [ Time Frame: Days 42, 49, and 98 ]
  • Estimated Percentage of All Treated Ulcerated Lesions Without Relapse at Day 42 [ Time Frame: Days 42 ]
  • Estimated Percentage of All Treated Ulcerated Lesions Without Relapse at Day 49 [ Time Frame: Days 49 ]
  • Estimated Percentage of All Treated Ulcerated Lesions Without Relapse at Day 98 [ Time Frame: Days 98 ]
  • Number of Subjects Achieving Initial Clinical Improvement of the Index Lesion [ Time Frame: Day 42 ]
  • Number of Subjects Achieving Re-epithelialization of the Index Lesion Without Relapse [ Time Frame: Day 168 ]
    Number of Subjects Achieving Re-epithelialization of the Index Lesion by Day 42 without Relapse from Day 42 Onward, Imputing Relapse for any Subject with a Missing Visit after Day 42
  • Number of Subjects Achieving Re-epithelialization of All Treated Ulcerated Lesions Without Subsequent Relapse [ Time Frame: Day 168 ]
    Number of Subjects Achieving Re-epithelialization of All Treated Ulcerated Lesions at Day 42 without Subsequent Relapse from Day 42 Onward,
  • Number of All Ulcerated Lesions Achieving 100% Re-epithelialization by Day 42 [ Time Frame: Day 42 ]
  • Number of Subjects With a Relapse on or After Day 42 [ Time Frame: Day 168 ]


Original Secondary Outcome: Paromomycin topical cream is superior to placebo in lesion healing [ Time Frame: 48 days ]

Information By: U.S. Army Medical Research and Materiel Command

Dates:
Date Received: January 21, 2008
Date Started: January 2008
Date Completion:
Last Updated: June 11, 2014
Last Verified: June 2014