Topical Treatment of Recalcitrant Ulcerative Old World Leishmaniasis With WR 279,396

• ClinicalTrials.gov Identifier: NCT00657917
• Recruitment Status: Terminated
• First Posted: April 14, 2008
• Results First Posted: January 22, 2019
• Last Update Posted: January 22, 2019
• Sponsor: U.S. Army Medical Research and Development Command
• Collaborator: Walter Reed Army Medical Center
• Information provided by (Responsible Party): U.S. Army Medical Research and Development Command

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Cutaneous Leishmaniasis
• Intervention: Drug: Paromomycin +Gentamicin topical cream
• Enrollment: 1

Participant Flow

Recruitment Details	Recruitment was conducted at Walter Reed Army Medical Center, Washington, DC. One subject was enrolled.
Pre-assignment Details

Arm/Group Title	Paromomycin +Gentamicin Topical Cream
Arm/Group Description	WR279,396 topically twice a day for 20 days Paromomycin +Gentamicin topical cream: WR297,396 for treatment of patients with parasitologically confirmed, primarily ulcerative, Old World CL, who had either failed pentavalent antimony treatment, or who where ineligible for pentavalent antimony therapy.
Period Title: Overall Study
Started	1
Completed	1
Not Completed	0

Baseline Characteristics

Arm/Group Title		Paromomycin +Gentamicin Topical Cream
Arm/Group Description		WR279,396 topically twice a day for 20 days Paromomycin +Gentamicin topical cream: WR297,396 for treatment of patients with parasitologically confirmed, primarily ulcerative, Old World CL, who had either failed pentavalent antimony treatment, or who where ineligible for pentavalent antimony therapy.
Overall Number of Baseline Participants		1
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	1 100.0%
	>=65 years	0 0.0%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1 participants
	Female	0 0.0%
	Male	1 100.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1 participants
	American Indian or Alaska Native	0 0.0%
	Asian	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	0 0.0%
	White	1 100.0%
	More than one race	0 0.0%
	Unknown or Not Reported	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	1 participants
		1

Outcome Measures

1. Primary Outcome

Title	The Appearance of Complete Epithelialization of Ulcerative Lesions Caused by Old World Cutaneous Leishmaniasis With no Relapse
Description	Appearance of complete (100%) epithelialization of a skin lesion at day 50+2 weeks, or the estimated 50%-99% re-epithelialization by day 50+2 weeks followed by complete eipithelialization by day 100+2 weeks, with both categories without relapse by day 180+30 days. Ulcer measured in millimeters.
Time Frame	180 days

Outcome Measure Data

Analysis Population Description

Ultimately, the planned statistical analysis could not be performed because only one patient was enrolled in the study.

Arm/Group Title	Paromomycin +Gentamicin Topical Cream
Arm/Group Description:	WR279,396 topically twice a day for 20 days Paromomycin +Gentamicin topical cream: WR297,396 for treatment of patients with parasitologically confirmed, primarily ulcerative, Old World CL, who had either failed pentavalent antimony treatment, or who where ineligible for pentavalent antimony therapy.
Overall Number of Participants Analyzed	1
Measure Type: Number; Unit of Measure: Surface area in millimeters squared
Screening	2,142
Day 20+3	1,488
Day 50+14	1,400
Day 180+30 (photos only)	0

2. Secondary Outcome

Title	Number of Relapses
Description	Evaluate the number of relapses occurring by day 180
Time Frame	180 days

Outcome Measure Data

Analysis Population Description

Ultimately, the planned statistical analysis could not be performed because only one patient was enrolled in the study.

Arm/Group Title	Paromomycin +Gentamicin Topical Cream
Arm/Group Description:	WR279,396 topically twice a day for 20 days Paromomycin +Gentamicin topical cream: WR297,396 for treatment of patients with parasitologically confirmed, primarily ulcerative, Old World CL, who had either failed pentavalent antimony treatment, or who where ineligible for pentavalent antimony therapy.
Overall Number of Participants Analyzed	1
Measure Type: Number; Unit of Measure: Number of relapses
	0

3. Secondary Outcome

Title	Safety and Tolerability (SAE's and AE's)
Description	Evaluate safety and tolerability as measured by completion of a full prescribed treatment course, treatment interruptions, SAE's and AE's
Time Frame	180 days

Outcome Measure Data

Analysis Population Description

Ultimately, the planned statistical analysis could not be performed because only one patient was enrolled in the study.

Arm/Group Title	Paromomycin +Gentamicin Topical Cream
Arm/Group Description:	WR279,396 topically twice a day for 20 days Paromomycin +Gentamicin topical cream: WR297,396 for treatment of patients with parasitologically confirmed, primarily ulcerative, Old World CL, who had either failed pentavalent antimony treatment, or who where ineligible for pentavalent antimony therapy.
Overall Number of Participants Analyzed	1
Measure Type: Number; Unit of Measure: Number of AE's
AEs Considered Related to Study Drug	9
AE's Not Considered Related to Study Drug	23

Adverse Events

Time Frame	180 Days
Adverse Event Reporting Description	Solicited and unsolicited AEs were collected throughout the 20-day treatment period. Follow-up contacts to assess efficacy and safety occurred on study days 50+14, 100+14, and 180+30.
Arm/Group Title	Paromomycin +Gentamicin Topical Cream
Arm/Group Description	WR279,396 topically twice a day for 20 days Paromomycin +Gentamicin topical cream: WR297,396 for treatment of patients with parasitologically confirmed, primarily ulcerative, Old World CL, who had either failed pentavalent antimony treatment, or who where ineligible for pentavalent antimony therapy.
All-Cause Mortality
	Paromomycin +Gentamicin Topical Cream
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Paromomycin +Gentamicin Topical Cream
	Affected / at Risk (%)	# Events
Total	0/1 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Paromomycin +Gentamicin Topical Cream
	Affected / at Risk (%)	# Events
Total	1/1 (100.00%)
Blood and lymphatic system disorders
Lymphadenopathy (right inguinal area) † [1]	1/1 (100.00%)	1
Persistent lymphedema, left lower extremity † [1]	1/1 (100.00%)	1
Cardiac disorders
Intermittent tachycardia † [1]	1/1 (100.00%)	1
Gastrointestinal disorders
Gastroenteritis † [1]	1/1 (100.00%)	1
General disorders
Flu-like symptoms † [1]	1/1 (100.00%)	1
Right gluteal pain † [1]	1/1 (100.00%)	1
Worsening pain at ulcer site † [2]	1/1 (100.00%)	1
Incomplete healing of ulcer/lesion † [3]	1/1 (100.00%)	1
Infections and infestations
Upper respiratory infection † [1]	1/1 (100.00%)	1
Injury, poisoning and procedural complications
Vesicle formation at ulcer site † [3]	1/1 (100.00%)	1
Blister-like formation above border of ulcer/lesion † [1]	1/1 (100.00%)	1
Small cut on left shin † [1]	1/1 (100.00%)	1
Investigations
Elevated BP readings † [1]	1/1 (100.00%)	1
Decreased sodium level † [1]	1/1 (100.00%)	1
Elevated percentage of monocytes in blood † [1]	1/1 (100.00%)	1
Elevated percentage of WBC in urine † [1]	1/1 (100.00%)	1
Metabolism and nutrition disorders
Left foot edema † [1]	1/1 (100.00%)	1
Edema, left leg to mid thigh † [1]	1/1 (100.00%)	1
Musculoskeletal and connective tissue disorders
Left calf pain † [2]	1/1 (100.00%)	1
Nervous system disorders
Burning sensation at site † [2]	1/1 (100.00%)	1
Numbness (slight) above ulcer/lesion † [1]	1/1 (100.00%)	1
Dizziness † [1]	1/1 (100.00%)	1
Respiratory, thoracic and mediastinal disorders
Blood-tinged secretions from nares † [1]	1/1 (100.00%)	1
Rhinorrhea † [1]	1/1 (100.00%)	1
Skin and subcutaneous tissue disorders
Right groin rash † [1]	1/1 (100.00%)	1
Cracked skin surrounding ulcer area † [2]	1/1 (100.00%)	1
Erosive areas around ulcer border † [3]	1/1 (100.00%)	1
Rash above surrounding area of ulcer/lesion † [1]	1/1 (100.00%)	1
Surgical and medical procedures
Increased drainage from wound † [2]	1/1 (100.00%)	1
Vascular disorders
Insufficient hypertension control † [1]	1/1 (100.00%)	1
Hyperemic left leg † [1]	1/1 (100.00%)	1
† Indicates events were collected by systematic assessment; [1] Not related to study drug; [2] Possibly related to study drug; [3] Definitely related to study drug

Limitations and Caveats

Early termination due to only 1 patient enrolled.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: COL Naomi Aronson MC
• Organization: Uniformed Services University of the Heralth Sciences
• Phone: 301-295-3621
• EMail: naronson@usuhs.mil

• Responsible Party: U.S. Army Medical Research and Development Command
• ClinicalTrials.gov Identifier: NCT00657917
• Other Study ID Numbers: A-13225
• First Submitted: February 22, 2008
• First Posted: April 14, 2008
• Results First Submitted: May 2, 2017
• Results First Posted: January 22, 2019
• Last Update Posted: January 22, 2019