Safety, Efficacy, and PK of Topical Paromomycin/Gentamicin Cream for Treatment of Cutaneous Leishmaniasis (WRNMMC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01140191
Recruitment Status : Terminated (This study was closed due to lack of enrollment (only one subject enrolled))
First Posted : June 9, 2010
Results First Posted : March 22, 2017
Last Update Posted : March 22, 2017
Walter Reed National Military Medical Center
Walter Reed Army Institute of Research (WRAIR)
Information provided by (Responsible Party):
U.S. Army Medical Research and Materiel Command

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).

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

Detailed Description:

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Leishmaniasis at Walter Reed National Military Medical Center (WRNMMC)
Study Start Date : September 2013
Actual Primary Completion Date : December 2013
Actual Study Completion Date : September 2014

Arm Intervention/treatment
Experimental: WR 279,396
All subjects in this one-arm study will receive topical WR 279,396
Drug: WR 279,396
Topical application of WR 279,396 cream (15% paromomycin + 0.5% gentamicin)once daily for 20 days
Other Name: Topical Paromomycin/Gentamicin Cream

Primary Outcome Measures :
  1. 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

  2. 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

  3. 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;

  4. 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

Secondary Outcome Measures :
  1. 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

  2. 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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Subjects must be male or female military health care beneficiary of any race or ethnicity and at least 18 years of age
  • Subjects must give written informed consent.
  • Subjects must have a diagnosis of CL in at least one lesion by at least one of the following methods: 1) positive culture for promastigotes; 2) microscopic identification of amastigotes in stained lesion tissue; 3) positive polymerase chain reaction (PCR) assay; and/or 4) prior diagnosis of CL within 14 days of the start of treatment.
  • Subjects must have at least one ulcerative lesion ≥ 1 cm and < 5 cm, that meets the criteria for an index lesion (Larger lesions will be accepted for treatment, but these will not be included in the primary evaluation of efficacy).
  • Subjects must be willing to forego other forms of treatments for CL including other investigational treatment during the study.
  • Subjects must be capable of understanding and complying with the protocol (in the opinion of the investigator).
  • Subjects must expect to be located in the Washington DC metropolitan area for at least the duration of the screening, 20-day treatment period, and Day 28 +/- 2 days follow-up visit.
  • Subjects who are female and of child-bearing potential, must have a negative pregnancy test during screening and agree to use an acceptable method of birth control during the treatment phase and for 1 month after treatment is completed.
  • Subject has adequate venous access for blood draws, if consented to the PK part of study.

Exclusion Criteria:

  • Subject has had a prior diagnosis of leishmaniasis where all lesions had healed.
  • Subject has only a single lesion whose characteristics include any of the following: verrucous or nodular lesion (non-ulcerative), lesion <1 cm in its greatest diameter, lesion in a location that in the opinion of the Investigator is difficult to maintain application of study drug topically.
  • Subject has a lesion due to Leishmania that involves the mucosa or palate.
  • Subject has signs and symptoms of disseminated disease.
  • Subject is a female who is breast-feeding.
  • Subject has an active malignancy or history of solid, metastatic or hematologic malignancy with the exception of basal or squamous cell carcinoma of the skin that has been removed.
  • Subject has significant organ abnormality, chronic disease such as diabetes, severe hearing loss, evidence of renal or hepatic dysfunction, or creatinine, AST, or ALT greater than the upper limit of normal as defined by the clinical laboratory normal ranges.
  • Subject has received treatment for leishmaniasis including thermosurgery (ThermoMed™) or any medication with pentavalent antimony including sodium stibogluconate (Pentostam), meglumine antimoniate (Glucantime); amphotericin B (including liposomal amphotericin B and amphotericin B deoxycholate); WR 279,396; or other medications containing paromomycin (administered parenterally or topically) or methylbenzethonium chloride (MBCL); gentamicin; fluconazole; ketoconazole; pentamidine; or allopurinol within 4 weeks of starting study treatment.
  • Subject has a history of known or suspected hypersensitivity or idiosyncratic reactions to aminoglycosides.
  • Subject has any other topical disease/condition which interferes with the objectives of this study.

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 identifier (NCT number): NCT01140191

United States, Maryland
Walter Reed National Military Medical Center (WRNMMC)
Bethesda, Maryland, United States, 20889
Sponsors and Collaborators
U.S. Army Medical Research and Materiel Command
Walter Reed National Military Medical Center
Walter Reed Army Institute of Research (WRAIR)
Principal Investigator: Timothy Whitman, DO, USN Walter Reed Army Medical Center

Responsible Party: U.S. Army Medical Research and Materiel Command Identifier: NCT01140191     History of Changes
Other Study ID Numbers: A-16049; S-10-0007
USAMMDA Protocol Number ( Other Identifier: PG-WRAMC-08-01 )
First Posted: June 9, 2010    Key Record Dates
Results First Posted: March 22, 2017
Last Update Posted: March 22, 2017
Last Verified: February 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by U.S. Army Medical Research and Materiel Command:
WR 279,396

Additional relevant MeSH terms:
Leishmaniasis, Cutaneous
Euglenozoa Infections
Protozoan Infections
Parasitic Diseases
Skin Diseases, Parasitic
Skin Diseases, Infectious
Skin Diseases
Anti-Bacterial Agents
Anti-Infective Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antiprotozoal Agents
Antiparasitic Agents