Phase 3 Study of Walter Reed (WR) 279,396 and Paromomycin Alone for the Treatment of Cutaneous Leishmaniasis in Panama - Full Text View

Purpose

This study is a pivotal Phase 3, randomized, double-blind, 3-site, two-group trial assessing the efficacy and safety of WR 279,396 Topical Cream and Paromomycin Alone Topical Cream in subjects with CL in Panama. The primary objective of this study is to determine if WR 279,396 results in statistically superior final clinical cure rates of an index lesion when compared with Paromomycin Alone for the treatment of CL in Panama expected to be caused by L panamensis.

Condition	Intervention	Phase
Cutaneous Leishmaniasis Caused by Leishmania Panamensis	Drug: WR 279,396 Drug: Paromomycin	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	A Randomized, Double-blind, Pivotal Phase 3 Study of WR 279,396 (Paromomycin + Gentamicin Topical Cream) and Paromomycin Alone Topical Cream for the Treatment of Cutaneous Leishmaniasis in Panama

Resource links provided by NLM:

MedlinePlus related topics: Leishmaniasis

Drug Information available for: Paromomycin sulfate Gentamicin Gentamicin sulfate Paromomycin

U.S. FDA Resources

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

Primary Outcome Measures:

final clinical cure change from baseline [ Time Frame: baseline (before the start of treatment), and on Study Days 20, 35 ± 2 days, 49 ± 4 days, 63 ± 7 days, 100 ± 14 days, and 168 ± 14 days ] [ Designated as safety issue: No ]
The primary efficacy endpoint is percentage of subjects with final clinical cure. Final clinical cure is defined as follows:
- Subject has initial clinical cure (100% re-epithelialization of index lesion by nominal Day 63); OR,
- Subject has initial clinical improvement (> 50% re-epithelialization of index lesion by nominal Day 63) followed by 100% re-epithelialization of the index lesion on or before nominal Day 100; AND,
- Subject has no relapse of index lesion.

Secondary Outcome Measures:

Percentage of subjects with all lesions cured [ Time Frame: baseline (before the start of treatment), and on Study Days 20, 35 ± 2 days, 49 ± 4 days, 63 ± 7 days, 100 ± 14 days, and 168 ± 14 days ] [ Designated as safety issue: No ]
• Percentage of subjects with all lesions cured, defined as: Final clinical cure as defined in primary objective (which is based solely on the index lesion); AND, Cure of all other lesions by nominal Day 100 (100% re-epithelialization of all ulcerated lesions and resolution of all other types of lesions)
Percentage of all lesions cured at Day 168 (ignores per subject cure rate) [ Time Frame: Day 168 ] [ Designated as safety issue: No ]
Area of ulceration of the index lesion at each measurement time point [ Time Frame: baseline (before the start of treatment), and on Study Days 20, 35 ± 2 days, 49 ± 4 days, 63 ± 7 days, 100 ± 14 days, and 168 ± 14 days ] [ Designated as safety issue: No ]
Area of ulceration all treated lesions at each measurement time point [ Time Frame: baseline (before the start of treatment), and on Study Days 20, 35 ± 2 days, 49 ± 4 days, 63 ± 7 days, 100 ± 14 days, and 168 ± 14 days ] [ Designated as safety issue: No ]
Ulcerated lesion cure rate at each measurement time point [ Time Frame: baseline (before the start of treatment), and on Study Days 20, 35 ± 2 days, 49 ± 4 days, 63 ± 7 days, 100 ± 14 days, and 168 ± 14 days ] [ Designated as safety issue: No ]
(cure is defined as 100% re-epithelialization of an ulcerated lesion)
Median time to initial clinical cure [ Time Frame: to be determined ] [ Designated as safety issue: No ]
(100% re-epithelialization of the index lesion)
adverse events (AEs) /serious adverse events (SAEs) (clinical signs and symptoms) [ Time Frame: AEs will be assessed at baseline, days 2-9 daily, day 20, day 35, 49, 63, 100, and 168 (if applicable) ] [ Designated as safety issue: Yes ]
AEs including application site reactions including elicited examination for pain, and clinician examination for erythema/redness, swelling/edema, and vesicles. Physical examination findings of evidence of mucosal leishmaniasis will be reported as an AE
Significant lab abnormalities [ Time Frame: baseline screening and day 20 ] [ Designated as safety issue: Yes ]
Any clinically significant changes in lab values from baseline

Estimated Enrollment:	300
Study Start Date:	March 2013
Estimated Study Completion Date:	June 2014
Estimated Primary Completion Date:	June 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: WR 279,396 (Paromomycin and Gentamicin Topical Cream)	Drug: WR 279,396 WR 279,396 is a topical cream of paromomycin 15% and gentamicin 0.5% Other Name: Paromomycin/Gentamicin topical cream
Experimental: Paromomycin Paromomycin alone	Drug: Paromomycin Paromomycin alone

Eligibility

Ages Eligible for Study:	5 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male or female at least 5 years-of-age
Subject or legal guardian able to give written informed consent or assent, as appropriate
Diagnosis of CL in at least one lesion by at least one of the following methods: 1) positive culture for promastigotes or 2) microscopic identification of amastigotes in stained lesion tissue
At least one ulcerative lesion ≥ 1 cm and ≤ 5 cm that has a diagnosis of CL
Willing to forego other forms of treatments for CL including other investigational treatments during the study
In the opinion of the investigator, subject (or their legal guardian), subject is capable of understanding and complying with the protocol
If female and of child-bearing potential, must have a negative serum pregnancy test during screening and agree to use an acceptable method of birth control during the treatment phase and for 1 week after treatment is completed

Exclusion Criteria:

Lesion due to leishmania that involves the nasal or oral mucosa or any signs of mucosal disease that might be due to Leishmania
Only a single lesion on the ear with erosive cartilage
Signs and symptoms of disseminated disease in the opinion of the investigator
More than 10 lesions
Female who is breast-feeding
Significant organ abnormality, chronic disease such as diabetes, severe hearing loss, evidence of renal or hepatic dysfunction, or creatinine, aspartate aminotransferase (AST), or alanine aminotransferase (ALT) greater than 15% above the upper limit of normal (ULN) as defined by the clinical laboratory defined normal ranges
Received treatment for leishmaniasis including any medication with pentavalent antimony including sodium stibogluconate (Pentostam™), meglumine antimoniate (Glucantime™); amphotericin B (including liposomal amphotericin B and amphotericin B deoxycholate); or other medications containing paromomycin (administered parenterally or topically) or methylbenzethonium chloride (MBCL); gentamicin; fluconazole; ketoconazole; pentamidine; miltefosine, azithromycin or allopurinol that was completed within 56 days of starting study treatments
History of known or suspected hypersensitivity or idiosyncratic reactions to aminoglycosides

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01790659

Locations

Panama
Instituto Conmemorativo Gorgas de Estudios de la Salud,	Not yet recruiting
Panama City, Panama
Contact: Zeus Capitan, MSc 507-527-4815
Contact: Vanessa Almengor, MSc 507-527-4815

Sponsors and Collaborators

U.S. Army Medical Research and Materiel Command

Investigators

Principal Investigator:

Nestor Sosa, MD, FACP

Instituto Conmemorativo Gorgas de Estudios de la Salud

More Information

No publications provided

Responsible Party:	U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier:	NCT01790659 History of Changes
Other Study ID Numbers:	S-12-21
Study First Received:	February 5, 2013
Last Updated:	February 11, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by U.S. Army Medical Research and Materiel Command:

leishmaniasis
cutaneous leishmaniasis
Leishmania panamensis

L panamensis
Paromomycin
Paromomycin/Gentamicin

Additional relevant MeSH terms:

Leishmaniasis
Leishmaniasis, Cutaneous
Euglenozoa Infections
Protozoan Infections
Parasitic Diseases
Skin Diseases, Parasitic
Skin Diseases, Infectious
Skin Diseases
Gentamicins
Paromomycin

Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Amebicides
Antiprotozoal Agents
Antiparasitic Agents

ClinicalTrials.gov processed this record on May 19, 2013