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

NCT01140191 | Terminated Phase 2 Results

• 2 other identifiers: A-16049; S-10-0007USAMMDA Protocol Number
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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).

Conditions

Leishmaniasis, Cutaneous

Keywords

leishmaniasis; cutaneous; WR 279,396; paromomycin; gentamicin; pharmacokinetics; safety; efficacy; military

Outcome Measures

Primary Outcomes (4)

• Number of Adverse Events

  Application site reactions including elicited question about pain, and clinician examination for erythema/redness and swelling/edema Blood chemistries and hematology Vital signs

  3 months

• 100% Re-epithelialization of Index Lesion by Nominal Day 60

  Number of participants with 100% re-epithelialization of index lesion by nominal Day 60

  Day 60

• Number of Participants Demonstrating Initial Clinical Improvements

  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;

  60-100 days

• Number of Participants With No Relapse of Index Lesion Between Nominal Day 60 and 100

  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

  60-100 days

Secondary Outcomes (2)

• Cures of All Other Lesions

  100 days

• Complete Cure of Index Lesion by Day 100

  100 days

Study Arms (1)

WR 279,396

EXPERIMENTAL

All subjects in this one-arm study will receive topical WR 279,396

Drug: WR 279,396

Interventions

WR 279,396 DRUG

Topical application of WR 279,396 cream (15% paromomycin + 0.5% gentamicin)once daily for 20 days

Also known as: Topical Paromomycin/Gentamicin Cream

WR 279,396

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• U.S. Army Medical Research and Development Command: lead
• Walter Reed National Military Medical Center: collaborator
• Walter Reed Army Institute of Research (WRAIR): collaborator

Study Sites (1)

Walter Reed National Military Medical Center (WRNMMC)

Bethesda, Maryland, 20889, United States

Location

MeSH Terms

Conditions

Leishmaniasis, Cutaneous; Leishmaniasis

Interventions

Paromomycin

Condition Hierarchy (Ancestors)

Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Skin Diseases, Parasitic; Vector Borne Diseases; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Aminoglycosides; Glycosides; Carbohydrates

Limitations and Caveats

Only one subject was enrolled in the protocol and treated. Data for this single patient was the only data available for analysis.

Results Point of Contact

• Title: COL Glenn W. Wortman
• Organization: Walter Reed National Military Medical Center (WRNMMC)

glenn.wortmann@amedd.army.mil

301-295-6400

Study Officials

• Timothy Whitman, DO, USN

  Walter Reed Army Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2010
• First Posted: June 9, 2010
• Study Start: September 1, 2013
• Primary Completion: December 1, 2013
• Study Completion: September 1, 2014
• Last Updated: November 22, 2019
• Results First Posted: March 22, 2017

Record last verified: 2019-11

Locations

US (1)