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

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ClinicalTrials.gov Identifier: NCT01790659
Recruitment Status : Completed
First Posted : February 13, 2013
Results First Posted : August 23, 2017
Last Update Posted : February 14, 2018
Sponsor:
Information provided by (Responsible Party):
U.S. Army Medical Research and Development Command

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Cutaneous Leishmaniasis
Interventions Drug: WR 279,396
Drug: Paromomycin
Enrollment 399
Recruitment Details Subjects were recruited from three regions in Panama. Subjects were screened over a 28 day period.
Pre-assignment Details  
Arm/Group Title WR 279,396 Paromomycin
Hide Arm/Group Description

(Paromomycin and Gentamicin Topical Cream)

WR 279,396: WR 279,396 is a topical cream of paromomycin 15% and gentamicin 0.5%

Paromomycin alone

Paromomycin: Paromomycin alone

Period Title: Overall Study
Started 201 198
Completed 195 192
Not Completed 6 6
Arm/Group Title WR 279,396 Paromomycin Total
Hide Arm/Group Description

(Paromomycin and Gentamicin Topical Cream)

WR 279,396: WR 279,396 is a topical cream of paromomycin 15% and gentamicin 0.5%

Paromomycin alone

Paromomycin: Paromomycin alone

Total of all reporting groups
Overall Number of Baseline Participants 201 198 399
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 201 participants 198 participants 399 participants
<=18 years
96
  47.8%
88
  44.4%
184
  46.1%
Between 18 and 65 years
105
  52.2%
110
  55.6%
215
  53.9%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 201 participants 198 participants 399 participants
22.9  (16.8) 23.6  (15.1) 23.2  (16.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 201 participants 198 participants 399 participants
Female
76
  37.8%
73
  36.9%
149
  37.3%
Male
125
  62.2%
125
  63.1%
250
  62.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 201 participants 198 participants 399 participants
Hispanic or Latino
201
 100.0%
196
  99.0%
397
  99.5%
Not Hispanic or Latino
0
   0.0%
1
   0.5%
1
   0.3%
Unknown or Not Reported
0
   0.0%
1
   0.5%
1
   0.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 201 participants 198 participants 399 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
0
   0.0%
0
   0.0%
0
   0.0%
More than one race
198
  98.5%
192
  97.0%
390
  97.7%
Unknown or Not Reported
3
   1.5%
6
   3.0%
9
   2.3%
Number of baseline lesions  
Mean (Standard Deviation)
Unit of measure:  Lesions
Number Analyzed 201 participants 198 participants 399 participants
2.27  (1.71) 2.13  (1.63) 2.20  (1.67)
Lesion sizes   [1] 
Mean (Standard Deviation)
Unit of measure:  Mm
Number Analyzed 201 participants 198 participants 399 participants
120  (146) 121  (152) 120  (149)
[1]
Measure Description: Lesion size was calculated in mm
Length of time between initial presence current lesions and treatment   [1] 
Mean (Standard Deviation)
Unit of measure:  Days
Number Analyzed 201 participants 198 participants 399 participants
59.7  (53.6) 62.1  (57.7) 60.9  (55.6)
[1]
Measure Description: Length of time in days before treatment that lesions were first noticed
1.Primary Outcome
Title Percent of Participants With Final Clinical Cure
Hide Description

The primary efficacy endpoint is percent 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.
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
Hide Outcome Measure Data
Hide Analysis Population Description
MITT subjects
Arm/Group Title WR 279,396 Paromomycin
Hide Arm/Group Description:

(Paromomycin and Gentamicin Topical Cream)

WR 279,396: WR 279,396 is a topical cream of paromomycin 15% and gentamicin 0.5%

Paromomycin alone

Paromomycin: Paromomycin alone

Overall Number of Participants Analyzed 201 198
Measure Type: Number
Unit of Measure: percent of participants
78.6 77.8
2.Secondary Outcome
Title Percentage of Subjects With All Lesions Cured
Hide Description • 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)
Time Frame 100 ± 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
MITT subjects
Arm/Group Title WR 279,396 Paromomycin
Hide Arm/Group Description:

(Paromomycin and Gentamicin Topical Cream)

WR 279,396: WR 279,396 is a topical cream of paromomycin 15% and gentamicin 0.5%

Paromomycin alone

Paromomycin: Paromomycin alone

Overall Number of Participants Analyzed 201 198
Measure Type: Number
Unit of Measure: percentage of participants
75.1 76.3
3.Secondary Outcome
Title Percentage of All Lesions Cured at Day 168 (Ignores Per Subject Cure Rate)
Hide Description Percentage of all lesions meeting criteria for clinical cure during the study at 168 day mark for mITT subjects
Time Frame Day 168
Hide Outcome Measure Data
Hide Analysis Population Description
Cure rates of all lesions over time without regard to subject for mITT subjects
Arm/Group Title WR 279,396 Paromomycin
Hide Arm/Group Description:

(Paromomycin and Gentamicin Topical Cream)

WR 279,396: WR 279,396 is a topical cream of paromomycin 15% and gentamicin 0.5%

Paromomycin alone

Paromomycin: Paromomycin alone

Overall Number of Participants Analyzed 201 198
Measure Type: Number
Unit of Measure: percentage of lesions
77.2 83.3
4.Secondary Outcome
Title Area of Ulceration (mm^2) of the Index Lesion at Each Measurement Time Point
Hide Description Area of ulceration (mm^2) of the index lesion at each measurement time point for mITT subjects
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
Hide Outcome Measure Data
Hide Analysis Population Description
mITT subjects
Arm/Group Title WR 279,396 Paromomycin
Hide Arm/Group Description:

(Paromomycin and Gentamicin Topical Cream)

WR 279,396: WR 279,396 is a topical cream of paromomycin 15% and gentamicin 0.5%

Paromomycin alone

Paromomycin: Paromomycin alone

Overall Number of Participants Analyzed 201 198
Mean (Standard Deviation)
Unit of Measure: mm^2
Day 1 153  (137) 165  (167)
Day 20 831  (627) 928  (986)
Change from baseline Day 20 677  (602) 762  (933)
Day 35 68.3  (138) 96.1  (188)
Change from baseline Day 35 -84.1  (156) -69.9  (172)
Day 49 29.4  (87.2) 33.9  (100)
Change from baseline Day 49 -123  (144) -132  (157)
Day 63 29.9  (119) 27.6  (107)
Change from baseline Day 63 -123  (167) -136  (171)
Day 100 12.5  (85.9) 7.41  (56.9)
Change from baseline Day 100 -144  (163) -152  (165)
Day 168 13.3  (111) 1.37  (9.89)
Change from baseline Day 168 -147  (171) -160  (161)
5.Secondary Outcome
Title Area of Ulceration (mm^2) All Treated Lesions at Each Measurement Time Point
Hide Description Area of ulceration (mm^2) of all treated lesions from 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 for mITT subjects. Data presented is as presented in the Final Clinical Study Report; any inconsistencies can't be changed.
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
Hide Outcome Measure Data
Hide Analysis Population Description
All lesions for mITT Subjects
Arm/Group Title WR 279,396 Paromomycin
Hide Arm/Group Description:

(Paromomycin and Gentamicin Topical Cream)

WR 279,396: WR 279,396 is a topical cream of paromomycin 15% and gentamicin 0.5%

Paromomycin alone

Paromomycin: Paromomycin alone

Overall Number of Participants Analyzed 201 198
Overall Number of Units Analyzed
Type of Units Analyzed: Number of lesions
457 422
Mean (Standard Deviation)
Unit of Measure: mm^2
Day 1 115  (152) 115  (149)
Day 20 656  (683) 699  (897)
Change from baseline Day 20 533  (632) 577  (829)
Day 35 53.0  (132) 66.1  (159)
Change from baseline Day 35 -62.8  (167) -51.9  (146)
Day 49 21.4  (76.8) 23.9  (88.2)
Change from baseline Day 49 -93.8  (160) -92.1  (132)
Day 63 19.9  (94.6) 15.8  (82.3)
Change from baseline Day 63 -96.2  (170) -98.7  (142)
Day 100 7.49  (58.8) 4.64  (42.8)
Change from baseline Day 100 -113  (166) -109  (143)
Day 168 9.14  (87.7) 0.83  (7.23)
Change from baseline Day 168 -118  (182) -114  (147)
6.Secondary Outcome
Title Median Time to Initial Clinical Cure for Index Lesions
Hide Description Median time to initial clinical cure for index lesions (100% re-epithelialization of the index lesion)
Time Frame When 100% re-epithelialization of the index lesion is observed at any visit Study Days (20, 35 ± 2 days, 49 ± 4 days, 63 ± 7 days, 100 ± 14 days, and 168 ± 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
MITT subjects
Arm/Group Title WR 279,396 Paromomycin
Hide Arm/Group Description:

(Paromomycin and Gentamicin Topical Cream)

WR 279,396: WR 279,396 is a topical cream of paromomycin 15% and gentamicin 0.5%

Paromomycin alone

Paromomycin: Paromomycin alone

Overall Number of Participants Analyzed 201 198
Median (95% Confidence Interval)
Unit of Measure: Days
36.000
(35 to 49)
48.000
(36 to 49)
Time Frame AE's were assessed at baseline, days 2-9 daily, day 20, 35, 49, 63, 100, and 168 (applicable)
Adverse Event Reporting Description AE's 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.
 
Arm/Group Title WR 279,396 Paromomycin
Hide Arm/Group Description

(Paromomycin and Gentamicin Topical Cream)

WR 279,396: WR 279,396 is a topical cream of paromomycin 15% and gentamicin 0.5%

Paromomycin alone

Paromomycin: Paromomycin alone

All-Cause Mortality
WR 279,396 Paromomycin
Affected / at Risk (%) Affected / at Risk (%)
Total   0/201 (0.00%)      0/198 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
WR 279,396 Paromomycin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/201 (1.00%)      1/198 (0.51%)    
Infections and infestations     
Infection of surgical site * 1  0/201 (0.00%)  0 1/198 (0.51%)  1
Injury, poisoning and procedural complications     
Second degree burn: scalding water * 1  1/201 (0.50%)  1 0/198 (0.00%)  0
Surgical and medical procedures     
Appendectomy * 1  1/201 (0.50%)  1 0/198 (0.00%)  0
Appendectomy * 1  0/201 (0.00%)  0 1/198 (0.51%)  1
1
Term from vocabulary, MedDRA
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
WR 279,396 Paromomycin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   201/201 (100.00%)      198/198 (100.00%)    
Blood and lymphatic system disorders     
Lymphadenitis  1  6/201 (2.99%)  6 6/198 (3.03%)  6
Lymphadenopathy  1  6/201 (2.99%)  6 10/198 (5.05%)  10
Gastrointestinal disorders     
Abdominal pain (upper)  2  5/201 (2.49%)  5 3/198 (1.52%)  3
Diarrhoea  2  8/201 (3.98%)  8 4/198 (2.02%)  4
Gastritis  2  6/201 (2.99%)  6 0/198 (0.00%)  0
Vomiting  2  4/201 (1.99%)  4 2/198 (1.01%)  2
General disorders     
Application site dermatitis  2  21/201 (10.45%)  21 13/198 (6.57%)  13
Application site erosion  2  4/201 (1.99%)  4 7/198 (3.54%)  7
Application site erythema  2  2/201 (1.00%)  2 3/198 (1.52%)  3
Application site injury  2  22/201 (10.95%)  22 38/198 (19.19%)  38
Application site pain  2  14/201 (6.97%)  14 16/198 (8.08%)  16
Application site pruritus  2  11/201 (5.47%)  11 8/198 (4.04%)  8
Mucosal erosion  2  3/201 (1.49%)  3 3/198 (1.52%)  3
Pyrexia  2  3/201 (1.49%)  3 5/198 (2.53%)  5
Infections and infestations     
Conjunctivitis  2  2/201 (1.00%)  2 4/198 (2.02%)  4
Cutaneous Leishmaniasis  2  10/201 (4.98%)  10 12/198 (6.06%)  12
Folliculitis  2  9/201 (4.48%)  9 14/198 (7.07%)  14
Gastroenteritis  2  10/201 (4.98%)  10 9/198 (4.55%)  9
Lymphangitis  2  29/201 (14.43%)  29 16/198 (8.08%)  16
Mucocutaneous Leishmaniasis  2  5/201 (2.49%)  5 7/198 (3.54%)  7
Nasopharyngitis  2  126/201 (62.69%)  126 112/198 (56.57%)  112
Pharyngitis  2  9/201 (4.48%)  9 8/198 (4.04%)  8
Pyoderma  2  3/201 (1.49%)  3 4/198 (2.02%)  4
Rhinitis  2  12/201 (5.97%)  12 13/198 (6.57%)  13
Superinfection bacterial  2  20/201 (9.95%)  20 19/198 (9.60%)  19
Injury, poisoning and procedural complications     
Arthrpod bite  2  21/201 (10.45%)  21 15/198 (7.58%)  15
Contusion  2  4/201 (1.99%)  4 6/198 (3.03%)  6
Limb Injury  2  4/201 (1.99%)  4 2/198 (1.01%)  2
Wound  2  4/201 (1.99%)  4 2/198 (1.01%)  2
Musculoskeletal and connective tissue disorders     
Arthralgia  2  6/201 (2.99%)  6 3/198 (1.52%)  3
Back pain  2  7/201 (3.48%)  7 6/198 (3.03%)  6
Pain in extremity  2  8/201 (3.98%)  8 2/198 (1.01%)  2
Nervous system disorders     
Dizziness  2  5/201 (2.49%)  5 4/198 (2.02%)  4
Headache  2  37/201 (18.41%)  37 22/198 (11.11%)  22
Reproductive system and breast disorders     
Dysmenorrhoea  2  0/201 (0.00%)  0 6/198 (3.03%)  6
Respiratory, thoracic and mediastinal disorders     
Cough  2  3/201 (1.49%)  3 3/198 (1.52%)  3
Rhinitis allergic  2  0/201 (0.00%)  0 6/198 (3.03%)  6
Rhinorrhoea  2  6/201 (2.99%)  6 2/198 (1.01%)  2
Skin and subcutaneous tissue disorders     
Dermatitis allergic  2  3/201 (1.49%)  3 2/198 (1.01%)  2
Dermatitis contact  2  99/201 (49.25%)  99 97/198 (48.99%)  97
Pruritus  1  60/201 (29.85%)  60 53/198 (26.77%)  53
Skin erosion  2  25/201 (12.44%)  25 13/198 (6.57%)  13
Vascular disorders     
Hypertension  2  2/201 (1.00%)  2 5/198 (2.53%)  5
1
Term from vocabulary, MedDRA (Unspecified)
2
Term from vocabulary, MedDRA
Indicates events were collected by systematic assessment
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: Nestor Sosa, MD, FACP
Organization: Instituto Conmemorativo Gorgas de Estudios de la Salud
Phone: 507-527-4950
Responsible Party: U.S. Army Medical Research and Development Command
ClinicalTrials.gov Identifier: NCT01790659     History of Changes
Other Study ID Numbers: S-12-21
First Submitted: February 5, 2013
First Posted: February 13, 2013
Results First Submitted: October 11, 2016
Results First Posted: August 23, 2017
Last Update Posted: February 14, 2018