Clinical Trial: Safety, Efficacy, and PK of Topical Paromomycin/Gentamicin Cream for Treatment of Cutaneous Leishmaniasis

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: An Open-Label Clinical Study to Examine the Safety, Efficacy, and Pharmacokinetics of WR 279,396 (Paromomycin + Gentamicin Topical Cream) for the Treatment of Cutaneous Leishmani

Brief Summary: The objectives of the study are to evaluate the safety, pharmacokinetics (PK), and efficacy of open label treatment with WR 279,396 (Topical Paromomycin/Gentamicin Cream)in subjects with cutaneous leishmaniasis (CL).

Detailed Summary:

Subjects will be screened over a period of up to 14 days prior to first treatment, and will receive treatment once daily for 20 days. Safety will be assessed by monitoring AEs, lesion site reactions, vital signs, hematology, and blood chemistry parameters.

Complete cure of ulcerated lesions is defined as 100% re-epithelialization or a measurement of ulceration of 0 x 0 mm. non-ulcerated treated lesions will also be measured to monitor total area of exposure of lesions to study drug and will be evaluated for cure (the absence of raised area on the skin).

Follow-up evaluations will be at 28 +2 days, 60 +7 days and 100 +14 days.


Sponsor: U.S. Army Medical Research and Materiel Command

Current Primary Outcome:

  • Number of Adverse Events [ Time Frame: 3 months ]
    Application site reactions including elicited question about pain, and clinician examination for erythema/redness and swelling/edema Blood chemistries and hematology Vital signs
  • 100% Re-epithelialization of Index Lesion by Nominal Day 60 [ Time Frame: Day 60 ]
    Number of participants with 100% re-epithelialization of index lesion by nominal Day 60
  • Number of Participants Demonstrating Initial Clinical Improvements [ Time Frame: 60-100 days ]
    Number of participants with > 50% re-epithelialization of index lesion by Day 60 followed by complete re-epithelialization of index lesion on or before nominal Day 100;
  • Number of Participants With No Relapse of Index Lesion Between Nominal Day 60 and 100 [ Time Frame: 60-100 days ]
    Number of participants with no relapses of lesion between 60 and 100 days. Relapse is defined as a 10% or greater increase in the area of ulceration of the index lesion or a shift from 100% re-epithelialization to < 100% re-epithelialization of the index lesion at Day 100 for those subjects that had 100% re-epithelialization of the index lesion at nominal Day 60 or before


Original Primary Outcome:

  • PK: Proportion of subjects with any detectable paromomycin or gentamicin plasma levels on a study day when blood for PK is collected. [ Time Frame: Days 1, 20 and 28 (Trough levels on days 2, 4, 7, 12,17, and 2, all with +/- 1) ]

    Determination of PK parameters where data permits including:

    • Cmax: Maximum observed plasma concentration
    • Tmax: Observed time to reach maximum plasma concentration
    • AUC: Area under the plasma-concentration time curve over a specified time period
    • t1/2: Apparent terminal exponential half-life
    • λz: Terminal-phase exponential rate constant
    • Absolute paromomycin and gentamicin bioavailability (based on historical data) if feasible.

    The trough blood draws on Days 2 and 21 will be used for the determination of PK parameters along with the blood collected on Days 1 and 20.

  • Safety: Proportion of subjects with adverse events by type [ Time Frame: Days 1-28 +/- 2 ]
    AEs will be coded using MedDRA terms and grouped by system, organ, and class (SOC). The severity, frequency, and relationship of AEs to study drug will be presented by preferred term by SOC grouping. Laboratory data and vital signs will be presented as summary statistics by Study Day including changes from baseline, and by-subject data listings. The severity and frequency of application site reactions will be presented as summary statistics by Study Day. Clinically significant AEs that are ongoi

    Current Secondary Outcome:

    • Cures of All Other Lesions [ Time Frame: 100 days ]
      Number of participants with 100% re-epithelialization of all ulcerated lesions and resolution of all other types of lesions
    • Complete Cure of Index Lesion by Day 100 [ Time Frame: 100 days ]
      Number of participants with complete cure of index lesion by day 100. Cure rate is defined as 100% re-epithelialization of an ulcerated lesion


    Original Secondary Outcome: Efficacy: All lesions cured [ Time Frame: Days 1-100 ]

    All lesions cured, defined as:

    1. Final clinical cure as defined above; AND,
    2. Cure of all other lesions by nominal Day 100 (100% re-epithelialization of all ulcerated lesions and resolution of all other types of lesions).

    Area of ulceration of the index lesion at each measurement time point.

    Area of ulceration all treated lesions at each measurement time point.

    Ulcerated lesion complete cure rate at each measurement time point (complete cure is defined as 100% re-epithelialization of an ulcerated lesion).



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

    Dates:
    Date Received: June 7, 2010
    Date Started: September 2013
    Date Completion:
    Last Updated: February 1, 2017
    Last Verified: February 2017