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

This study has been terminated.
(This study was closed due to lack of enrollment (only one subject enrolled))
Sponsor:
Collaborators:
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
ClinicalTrials.gov Identifier:
NCT01140191
First received: June 7, 2010
Last updated: June 4, 2015
Last verified: June 2015
  Purpose

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 Intervention Phase
Leishmaniasis, Cutaneous
Drug: WR 279,396
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by U.S. Army Medical Research and Materiel Command:

Primary Outcome Measures:
  • Number of adverse events [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    Application site reactions including elicited question about pain, and clinician examination for erythema/redness and swelling/edema Blood chemistries and hematology Vital signs

  • Number of initial clinical cures [ Time Frame: Day 60 ] [ Designated as safety issue: No ]
    100% re-epithelialization of index lesion by nominal Day 60

  • Number of initial clinical improvements [ Time Frame: 60-100 days ] [ Designated as safety issue: No ]
    > 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 no relapses of index lesion between nominal Day 60 and nominal Day 100 [ Time Frame: 60-100 days ] [ Designated as safety issue: No ]
    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% reepithelialization of the index lesion at nominal Day 60 or before


Secondary Outcome Measures:
  • Number of cures of all other lesions [ Time Frame: 100 days ] [ Designated as safety issue: No ]
    100% re-epithelialization of all ulcerated lesions and resolution of all other types of lesions

  • Area of ulceration of the index lesion [ Time Frame: 0-100 days ] [ Designated as safety issue: No ]
  • Area of ulceration of all treated lesions [ Time Frame: 0-100 days ] [ Designated as safety issue: No ]
  • Number of ulcerated lesion complete cure rate [ Time Frame: 0-100 days ] [ Designated as safety issue: No ]
    complete cure is defined as 100% reepithelialization of an ulcerated lesion


Enrollment: 1
Study Start Date: July 2010
Study Completion Date: September 2014
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01140191

Locations
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)
Investigators
Principal Investigator: Timothy Whitman, DO, USN Walter Reed Army Medical Center
  More Information

No publications provided

Responsible Party: U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier: NCT01140191     History of Changes
Other Study ID Numbers: A-16049; S-10-0007, USAMMDA Protocol Number
Study First Received: June 7, 2010
Last Updated: June 4, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by U.S. Army Medical Research and Materiel Command:
leishmaniasis
cutaneous
WR 279,396
paromomycin
gentamicin
pharmacokinetics
safety
efficacy
military

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

ClinicalTrials.gov processed this record on September 02, 2015