Phase 3 Study to Evaluate WR 279,396 vs. Paromomycin Alone to Treat Cutaneous Leishmaniasis (in Tunisia) - Full Text View

Sponsor:	U.S. Army Medical Research and Materiel Command
Collaborators:	Walter Reed Army Institute of Research (WRAIR) Institute of Pasteur- Tunis Institute of Pasteur- Paris
Information provided by (Responsible Party):	U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier:	NCT00606580

Purpose

This study will test the ability of the topical cream WR 279,396 to treat the skin lesions caused by the parasite called leishmania. WR 279,396 is an antibiotic preparation that contains paromomycin + gentamicin. This cream will be compared to the effect of a topical cream containing paromomycin alone and to a placebo cream that contains no antibiotics. Therefore, this study will have three groups of patients, and they will be assigned to one of these treatments randomly. The study will be carried out without the patient or the physician knowing which cream is being used for which patient. The goal is to determine if WR 279,396 cream or the paromomycin cream is better than placebo, and if WR 279,396 is better than paromomycin alone.

Condition	Intervention	Phase
Cutaneous Leishmaniasis	Drug: WR 279,396 topical cream Drug: Paromomycin Alone topical cream Drug: Vehicle placebo cream	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
Official Title:	A Pivotal, Randomized, Double-blind, Vehicle-controlled Study to Evaluate WR 279,396 and Paromomycin Alone to Treat Cutaneous Leishmaniasis (in Tunisia)

Resource links provided by NLM:

MedlinePlus related topics: Antibiotics Leishmaniasis

Drug Information available for: Paromomycin 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 rate for the index lesion: initial clinical improvement [ Time Frame: day 42 ] [ Designated as safety issue: No ]
Initial Clinical Improvement: At least 50% to 99% reduction in the size of the measured lesion from the baseline measurement by the Day 42 evaluation.
final clinical cure rate for the index lesion: initial clinical cure [ Time Frame: Day 42, Day 98 ] [ Designated as safety issue: No ]
Initial clincial cure: 100% reepithelialization (ie, a 0 x 0 length x width measurement) of the lesion at the nominal Day 42 evaluation, or initial clinical improvement followed by 100% reepithelialization by Day 98
final clinical cure rate for the index lesion: Relapse [ Time Frame: Day 168 ] [ Designated as safety issue: No ]
Relapse: Initial clinical cure followed by re-ulceration by Day 168, or initial clinical improvement followed by lesion enlargement by Day 168.
final clinical cure rate for the index lesion [ Time Frame: Day 168 ] [ Designated as safety issue: No ]
Initial clinical cure without relapse

Secondary Outcome Measures:

Time to Clinical Cure of CL lesions [ Time Frame: Days 28, 42, 49, 98 and 168 ] [ Designated as safety issue: No ]
proportion of index lesions achieving re-epithelialization without relapse by Day 42; proportion acheiving 100% re-epithelilization without subsequent relapse; and proportion acheiving 100% reepithelialization of all treated lesions without subsequent relapse
Measures of Clinical Improvement [ Time Frame: Day 42 ] [ Designated as safety issue: No ]
Proportion of subjects: 1) achieving 100% reepithelialization of all treated baseline lesions at Day 42 without subsequent relapse, 2) achieving initial clinical improvement; 3) who ever have a relapse on or after Day 42; 4) achieving 100% reepithelialization of the index lesion by Day 42 without subsequent relapse from Day 42 onward; 5) all lesions achieving 100% reepithelialization by Day 42.
Change in the area of ulceration over time [ Time Frame: Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 28, 42, 49, 98, 168 ] [ Designated as safety issue: No ]
Area of ulceration of the index lesion at each measurement timepoint; and, area of ulceration of all ulcerated lesions at each measurement timepoint.

Enrollment:	375
Study Start Date:	January 2008
Study Completion Date:	July 2011
Primary Completion Date:	July 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: WR 279,396 Topical Treament 125 subjects will be randomized to this arm to receive WR 279,396 topical cream	Drug: WR 279,396 topical cream WR 279,396 is a topical antibiotic cream containing 15% paromomycin and 0.5% gentamicin that will be applied to each lesion once a day and covered with a sterile gauze and tape dressing.
Experimental: Paromomycin Alone Topical treatment 125 subjects in this arm will receive the topical cream containing 15% paromomycin alone	Drug: Paromomycin Alone topical cream The antibiotic paromomycin 15% in the same topical cream used in arm 1 will be applied to lesions daily and covered with a protective sterile gauze and tape dressing.
Placebo Comparator: Vehicle Placebo Cream 125 subjects in this arm will receive the vehicle placebo cream. In this cream, se, the antibiotics have been removed. The placebo will also be applied daily to cutaneous leishmaniasis lesions daily and covered with a protective, sterile gauze dressing.	Drug: Vehicle placebo cream Applied daily to cutaneous leishmaniasis lesions, primarily ulcerative, and covered with a protective, sterile gauze and tape dressing.

Detailed Description:

This is an efficacy study to test the ability of WR 279,396 topical cream to treat uncomplicated cutaneous leishmaniasis caused primarily by Leishmania major in adults and children in Tunisia where the disease in endemic. A total of 375 volunteers will be randomized to the three arms described above to determine product efficacy. Safety data in all three arms will also be collected.

Eligibility

Ages Eligible for Study:	5 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

The subject was age 5 years or older, but less than 65 years.
The subject was able to understand the information provided to him/her and give written informed consent. Consent was obtained from the parent/guardian of subjects who were < 18 years old. Children 12 to < 18 years old were asked to sign the written assent form. Witnessed verbal assent was obtained from subjects 5 to 11 years old.
The subject was a male or female who was generally healthy.
The subject had cutaneous lesions diagnosed as leishmaniasis in the index lesion by: (1) the identification of promastigotes in a culture of an aspirated lesion, or (2) the microscopic identification of Leishmania amastigotes on a DifQuik or Giemsa stained smear obtained from a lesion scraping.
The subject had five or fewer cutaneous lesions.
The subject had one lesion, which would be designated as the index lesion, that was ≥ 1 and < 5 cm in its greatest diameter and primarily ulcerative, ie, not purely verrucous or nodular.
The subject was willing to forego other forms of treatment for CL, including other investigational treatment during the study.
In the opinion of the principal investigator, the subject or subject's parent/guardian was capable of understanding and complying with the protocol

Exclusion Criteria

The subject received previous treatment for leishmaniasis (including WR 279,396) within the last 6-months, with the exception of mercurochrome.
The subject had difficulty complying with instructions on maintaining the dressing, eg, due to life style activities or age.
The subject had only a single lesion whose characteristics included any of the following: verrucous or nodular lesion, ≥ 5 cm in its greatest diameter, < 1 cm or located on the ear, or other location that in the opinion of the principal investigator would be difficult to maintain application of study drug topically.
The subject had a lesion due to Leishmania that involved the mucosa.
The subject had signs or symptoms of disseminated disease, ie, clinically significant lymphadenitis with nodules that were painful and > 1 cm in the lymphatic drainage of the ulcer.
The subject was a female with a positive urine pregnancy test, or who was breast feeding or lactating.
The subject had an active malignancy or had a history of a solid, metastatic or hematologic malignancy, with the exception of a basal or squamous cell carcinoma of the skin that had been removed.
The subject had a significant organ abnormality or chronic disease that, in the opinion of the investigator, would warrant exclusion of the subject from the study or would prevent the subject from completing the study.
The subject was receiving any of the following medications: any medication containing pentavalent antimony, including stibogluconate sodium (Pentostam®) and meglumine antimoniate (Glucantime®); amphotericin B, including liposomal amphotericin B and amphotericin B deoxycholate; other medications containing paromomycin (administered IV or topically); methylbenzethonium chloride, fluconazole, ketoconazole, itraconazole; pentamidine; or allopurinol.
The subject or the subject's parent/guardian was unable to understand verbal and/or written Arabic, English, or French (languages in which certified translations of the informed consent were available).
The subject presented with an immuno-compromising condition, including recidivant leishmaniasis (during the past 2 years), or diabetes.
The subject had a history of known or suspected idiosyncratic reactions or hypersensitivity to aminoglycosides.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00606580

Locations

Tunisia
Central Clinic-Sidi Bouzid
Tunis, Tunisia

Sponsors and Collaborators

U.S. Army Medical Research and Materiel Command

Walter Reed Army Institute of Research (WRAIR)

Institute of Pasteur- Tunis

Institute of Pasteur- Paris

Investigators

Principal Investigator:

Afif Ben Salah, M.D., Ph.D.

Institute Pasteur Tunisia

More Information

No publications provided

Responsible Party:	U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier:	NCT00606580 History of Changes
Other Study ID Numbers:	A-14134
Study First Received:	January 21, 2008
Last Updated:	January 4, 2012
Health Authority:	United States: Food and Drug Administration

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

cutaneous leishmaniasis, topical treatment, Tunisia

Additional relevant MeSH terms:

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

Paromomycin
Amebicides
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on February 12, 2012