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Trial record 22 of 1403 for:    Peru

Safety, Efficacy and Pharmacokinetics (PK) Study of WR 279,396 Versus Paromomycin for Treatment of Cutaneous Leishmaniasis (Peru-PK)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01032382
Recruitment Status : Completed
First Posted : December 15, 2009
Results First Posted : August 22, 2014
Last Update Posted : July 16, 2015
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: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Leishmaniasis, Cutaneous
Interventions Drug: WR 279,396 (15% paromomycin + 0.5% gentamicin topical cream)
Drug: Paromomycin Alone Cream (15% paromomycin topical cream)
Enrollment 30
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Paromomycin Alone Treatment WR 279,396
Hide Arm/Group Description Paromomycin Alone Cream (15% paromomycin topical cream): topical application to CL lesions once daily for 20 days WR 279,396 (15% paromomycin + 0.5% gentamicin topical cream): topical application to CL lesions once daily for 20 days
Period Title: Overall Study
Started 16 14
Completed 11 9
Not Completed 5 5
Reason Not Completed
Disease dissemination             1             1
Treatment failure             3             1
Index lesion relapse             1             3
Arm/Group Title Paromomycin Alone Treatment WR 279,396 Total
Hide Arm/Group Description Paromomycin Alone Cream (15% paromomycin topical cream): topical application to CL lesions once daily for 20 days WR 279,396 (15% paromomycin + 0.5% gentamicin topical cream): topical application to CL lesions once daily for 20 days Total of all reporting groups
Overall Number of Baseline Participants 16 14 30
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 16 participants 14 participants 30 participants
20.7  (16.2) 18.2  (15.1) 19.5  (15.5)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 16 participants 14 participants 30 participants
Adults (18+ years) 5 4 9
Children (12 to 17 years) 5 3 8
Children (5 to 11 years) 6 7 13
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 14 participants 30 participants
Female
5
  31.3%
4
  28.6%
9
  30.0%
Male
11
  68.8%
10
  71.4%
21
  70.0%
1.Primary Outcome
Title Final Clinical Cure for Index Lesions
Hide Description

Final clinical cure was defined as follows:

  1. Subject has initial clinical cure (100% re-epithelialization of index lesion by nominal Day 63); OR,
  2. 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,
  3. Subject has no relapse of index lesion by Day 168. Relapse was defined as an index lesion meeting the criteria for initial clinical cure that had any new ulceration/nodule (> 0 x 0 mm measurement) by nominal day 168, or an index lesion meeting the criteria for initial clinical improvement that subsequently enlarged by nominal Day 168.
Time Frame Initial clinical cure by day 63 and no relapse by day 168
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Paromomycin Alone Treatment WR 279,396
Hide Arm/Group Description:
Paromomycin Alone Cream (15% paromomycin topical cream): topical application to CL lesions once daily for 20 days
WR 279,396 (15% paromomycin + 0.5% gentamicin topical cream): topical application to CL lesions once daily for 20 days
Overall Number of Participants Analyzed 16 14
Measure Type: Number
Unit of Measure: participants
11 9
2.Secondary Outcome
Title Detectable Paromomycin Plasma Levels
Hide Description Paromomycin plasma concentrations following administration of paromomycin alone or WR 279,396 in adults
Time Frame Day 4, 7, 12, 17, 20, 28
Hide Outcome Measure Data
Hide Analysis Population Description
Adults (18+ years)
Arm/Group Title Paromomycin Alone Treatment WR 279,396
Hide Arm/Group Description:
Paromomycin Alone Cream (15% paromomycin topical cream): topical application to CL lesions once daily for 20 days
WR 279,396 (15% paromomycin + 0.5% gentamicin topical cream): topical application to CL lesions once daily for 20 days
Overall Number of Participants Analyzed 5 4
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 4 12.1  (27.0) 37.3  (74.5)
Day 7 10.3  (23.1) 17.9  (35.8)
Day 12 36.2  (33.2) 78.9  (81.6)
Day 17 210.0  (327.0) 162.0  (123.0)
Day 20 87.3  (109.0) 128.0  (58.7)
Day 28 0  (0) 0  (0)
3.Secondary Outcome
Title Paromomycin Plasma Concentrations in Children
Hide Description Paromomycin plasma concentrations 4 hours following administration of paromomycin alone or WR 279,396 in children
Time Frame 0 and 4 hours on days 1 and 20
Hide Outcome Measure Data
Hide Analysis Population Description
Children ages 5 to 17 (inclusive)
Arm/Group Title Paromomycin Alone Treatment WR 279,396
Hide Arm/Group Description:
Paromomycin Alone Cream (15% paromomycin topical cream): topical application to CL lesions once daily for 20 days
WR 279,396 (15% paromomycin + 0.5% gentamicin topical cream): topical application to CL lesions once daily for 20 days
Overall Number of Participants Analyzed 11 10
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 1 hour 0 6.2  (20.5) 22.1  (69.9)
Day 1 hour 4 71.2  (88.0) 322.0  (757.0)
Day 20 hour 0 93.8  (59.9) 89.2  (132.0)
Day 20 hour 4 744.0  (503.0) 1030.0  (1460.0)
4.Secondary Outcome
Title Pharmacokinetic Parameter: Cmax
Hide Description Cmax of paromomycin following administration of paromomycin alone or WR 279,396 to adults in Panama
Time Frame 0, 0.5, 1.0, 2.0, 3.0, 4.0, 8.0, 12.0, 24.0 hours on both Days 1 and 20
Hide Outcome Measure Data
Hide Analysis Population Description
Adults (18+ years)
Arm/Group Title Paromomycin Alone Treatment WR 279,396
Hide Arm/Group Description:
Paromomycin Alone Cream (15% paromomycin topical cream): topical application to CL lesions once daily for 20 days
WR 279,396 (15% paromomycin + 0.5% gentamicin topical cream): topical application to CL lesions once daily for 20 days
Overall Number of Participants Analyzed 5 4
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 1 511  (445) 155.0  (139.0)
Day 20 1400  (842) 882  (124)
5.Secondary Outcome
Title Pharmacokinetic Parameter: Tmax
Hide Description Pharmacokinetic Parameter: Tmax
Time Frame 0, 0.5, 1.0, 2.0, 3.0, 4.0, 8.0, 12.0, 24.0 hours on both Days 1 and 20
Hide Outcome Measure Data
Hide Analysis Population Description
Adults (18+ years). On day 1, Paromomycin Alone Treatment group N = 4; WR 279,396 group N = 3.
Arm/Group Title Paromomycin Alone Treatment WR 279,396
Hide Arm/Group Description:
Paromomycin Alone Cream (15% paromomycin topical cream): topical application to CL lesions once daily for 20 days
WR 279,396 (15% paromomycin + 0.5% gentamicin topical cream): topical application to CL lesions once daily for 20 days
Overall Number of Participants Analyzed 5 4
Mean (Standard Deviation)
Unit of Measure: hr
Day 1 2.25  (0.5) 3  (1.73)
Day 20 4.6  (3.13) 3  (1.15)
6.Secondary Outcome
Title Pharmacokinetic Parameter: Area Under the Curve (AUC)
Hide Description Area under the curve (AUC) of paromomycin following administration of paromomycin alone or WR 279,396 to adults in Panama
Time Frame 0, 0.5, 1.0, 2.0, 3.0, 4.0, 8.0, 12.0, 24.0 hours on both Days 1 and 20
Hide Outcome Measure Data
Hide Analysis Population Description
Adults (18+ years)
Arm/Group Title Paromomycin Alone Treatment WR 279,396
Hide Arm/Group Description:
Paromomycin Alone Cream (15% paromomycin topical cream): topical application to CL lesions once daily for 20 days
WR 279,396 (15% paromomycin + 0.5% gentamicin topical cream): topical application to CL lesions once daily for 20 days
Overall Number of Participants Analyzed 5 4
Mean (Standard Deviation)
Unit of Measure: ng*hr/mL
Day 1 3154  (3562) 1228  (1413)
Day 20 13331  (9156) 8955  (1955)
7.Secondary Outcome
Title Pharmacokinetic Parameter: t(1/2)
Hide Description t(1/2) of paromomycin following administration of paromomycin alone or WR 279,396 to adults in Panama
Time Frame 0, 0.5, 1.0, 2.0, 3.0, 4.0, 8.0, 12.0, 24.0 hours on both Days 1 and 20
Hide Outcome Measure Data
Hide Analysis Population Description
Adults (18+ years). WR 279,396 group measurements Day 1 N = 2 and Day 20 N = 4. One study participant in the Paromomycin Alone Treatment was withdrawn at Day 100.
Arm/Group Title Paromomycin Alone Treatment WR 279,396
Hide Arm/Group Description:
Paromomycin Alone Cream (15% paromomycin topical cream): topical application to CL lesions once daily for 20 days
WR 279,396 (15% paromomycin + 0.5% gentamicin topical cream): topical application to CL lesions once daily for 20 days
Overall Number of Participants Analyzed 4 4
Mean (Standard Deviation)
Unit of Measure: hr
Day 1 2.55  (1.23) 4.51  (0.06)
Day 20 7.17  (3.29) 6.81  (3.2)
8.Secondary Outcome
Title Pharmacokinetic Parameter: Cmax/D
Hide Description Maximum observed plasma concentration divide by topical dose (Cmax/D) of paromomycin following administration of paromomycin alone or WR 279,396 to adults in Panama
Time Frame 0, 0.5, 1.0, 2.0, 3.0, 4.0, 8.0, 12.0, 24.0 hours on both Days 1 and 20
Hide Outcome Measure Data
Hide Analysis Population Description
Adults (18+ years)
Arm/Group Title Paromomycin Alone Treatment WR 279,396
Hide Arm/Group Description:
Paromomycin Alone Cream (15% paromomycin topical cream): topical application to CL lesions once daily for 20 days
WR 279,396 (15% paromomycin + 0.5% gentamicin topical cream): topical application to CL lesions once daily for 20 days
Overall Number of Participants Analyzed 5 4
Mean (Standard Deviation)
Unit of Measure: 1/ML
Day 1 185  (144) 45.9  (35.8)
Day 20 368  (196) 283  (118)
9.Secondary Outcome
Title Pharmacokinetic Parameter: AUC/D
Hide Description Area under the plasma concentration-time curve over 24 hrs divided by topical dose (AUC/D) of paromomycin following administration of paromomycin alone or WR 279,396 to adults in Panama
Time Frame Days 1 and 20
Hide Outcome Measure Data
Hide Analysis Population Description
Adults (18+ years)
Arm/Group Title Paromomycin Alone Treatment WR 279,396
Hide Arm/Group Description:
Paromomycin Alone Cream (15% paromomycin topical cream): topical application to CL lesions once daily for 20 days
WR 279,396 (15% paromomycin + 0.5% gentamicin topical cream): topical application to CL lesions once daily for 20 days
Overall Number of Participants Analyzed 5 4
Mean (Standard Deviation)
Unit of Measure: hr/ML
Day 1 996.7  (976.1) 340.5  (368.9)
Day 20 3335  (1482) 3155  (2151)
10.Secondary Outcome
Title Final Clinical Cure on All Lesions Independent of Subjects
Hide Description

Final clinical cure was defined as follows:

  1. Subject has initial clinical cure (100% re-epithelialization of lesion by nominal Day 63); OR,
  2. Subject has initial clinical improvement (> 50% re-epithelialization of lesion by nominal Day 63 followed by 100% re-epithelialization of the lesion on or before nominal Day 100; AND,
  3. Subject has no relapse of lesion by Day 168. Relapse was defined as a lesion meeting the criteria for initial clinical cure that had any new ulceration/nodule (> 0 x 0 mm measurement) by nominal day 168, or a lesion meeting the criteria for initial clinical improvement that subsequently enlarged by nominal Day 168.
Time Frame Initial clinical cure by day 63 and no relapse by day 168
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Paromomycin Alone Treatment WR 279,396
Hide Arm/Group Description:
Paromomycin Alone Cream (15% paromomycin topical cream): topical application to CL lesions once daily for 20 days
WR 279,396 (15% paromomycin + 0.5% gentamicin topical cream): topical application to CL lesions once daily for 20 days
Overall Number of Participants Analyzed 16 14
Overall Number of Units Analyzed
Type of Units Analyzed: Total number of ulerated lesions
22 21
Measure Type: Number
Unit of Measure: Cured ulcerated lesions
12 14
11.Secondary Outcome
Title Number of Index Lesions Meeting Criteria for Clinical Cure During the Study
Hide Description Number of study participants who meet the criteria for clinical cure (100% re-epithelialization) at specified timepoints during the study.
Time Frame Day 1, 4, 7, 12, 17, 20, 28, 35, 42, 49, 56, 63, 100, 168
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Paromomycin Alone Treatment WR 279,396
Hide Arm/Group Description:
Paromomycin Alone Cream (15% paromomycin topical cream): topical application to CL lesions once daily for 20 days
WR 279,396 (15% paromomycin + 0.5% gentamicin topical cream): topical application to CL lesions once daily for 20 days
Overall Number of Participants Analyzed 16 14
Measure Type: Number
Unit of Measure: Lesions meeting clinical cure criteria
Day 1 0 0
Day 4 0 0
Day 7 0 0
Day 12 0 0
Day 17 0 0
Day 20 1 0
Day 28 5 6
Day 35 8 11
Day 42 10 11
Day 49 10 12
Day 56 11 10
Day 63 11 10
Day 100 12 10
Day 168 11 9
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Paromomycin Alone Treatment WR 279,396
Hide Arm/Group Description Paromomycin Alone Cream (15% paromomycin topical cream): topical application to CL lesions once daily for 20 days WR 279,396 (15% paromomycin + 0.5% gentamicin topical cream): topical application to CL lesions once daily for 20 days
All-Cause Mortality
Paromomycin Alone Treatment WR 279,396
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Paromomycin Alone Treatment WR 279,396
Affected / at Risk (%) Affected / at Risk (%)
Total   0/16 (0.00%)   0/14 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Paromomycin Alone Treatment WR 279,396
Affected / at Risk (%) Affected / at Risk (%)
Total   16/16 (100.00%)   14/14 (100.00%) 
Blood and lymphatic system disorders     
Lymph node pain   0/16 (0.00%)  1/14 (7.14%) 
Lymphadenopathy   3/16 (18.75%)  2/14 (14.29%) 
Ear and labyrinth disorders     
Motion sickness   0/16 (0.00%)  1/14 (7.14%) 
Endocrine disorders     
Bleeding anovulatory   0/16 (0.00%)  1/14 (7.14%) 
Eye disorders     
Conjunctivitis allergic   1/16 (6.25%)  1/14 (7.14%) 
Myopia   0/16 (0.00%)  1/14 (7.14%) 
Gastrointestinal disorders     
Diarrhoea   0/16 (0.00%)  2/14 (14.29%) 
Lip dry   0/16 (0.00%)  1/14 (7.14%) 
Abdominal pain upper   2/16 (12.50%)  0/14 (0.00%) 
General disorders     
Application site bleeding   2/16 (12.50%)  2/14 (14.29%) 
Application site erythema   12/16 (75.00%)  9/14 (64.29%) 
Application site induration   2/16 (12.50%)  1/14 (7.14%) 
Application site oedema   6/16 (37.50%)  5/14 (35.71%) 
Application site pain   13/16 (81.25%)  3/14 (21.43%) 
Application site papules   1/16 (6.25%)  1/14 (7.14%) 
Application site pruritus   16/16 (100.00%)  14/14 (100.00%) 
Application site vesicles   2/16 (12.50%)  6/14 (42.86%) 
Injection site extravasation   0/16 (0.00%)  1/14 (7.14%) 
Oedema   0/16 (0.00%)  1/14 (7.14%) 
Vessel puncture site pain   1/16 (6.25%)  0/14 (0.00%) 
Immune system disorders     
Hypersensitivity   12/16 (75.00%)  11/14 (78.57%) 
Infections and infestations     
Application site cellulitis   0/16 (0.00%)  1/14 (7.14%) 
Cutaneous leishmaniasis relapse   2/16 (12.50%)  3/14 (21.43%) 
Gastroenteritis   1/16 (6.25%)  1/14 (7.14%) 
Influenza   1/16 (6.25%)  3/14 (21.43%) 
Nasopharyngitis   1/16 (6.25%)  4/14 (28.57%) 
Oral herpes   0/16 (0.00%)  1/14 (7.14%) 
Otitis media   0/16 (0.00%)  1/14 (7.14%) 
Superinfection bacterial   3/16 (18.75%)  2/14 (14.29%) 
Tooth infection   0/16 (0.00%)  1/14 (7.14%) 
Upper respiratory tract infection   12/16 (75.00%)  9/14 (64.29%) 
Cutaneous leishmaniasis   1/16 (6.25%)  0/14 (0.00%) 
Pneumonia   1/16 (6.25%)  0/14 (0.00%) 
Injury, poisoning and procedural complications     
Head injury   0/16 (0.00%)  1/14 (7.14%) 
Skin injury   1/16 (6.25%)  1/14 (7.14%) 
Arthropod bite   1/16 (6.25%)  0/14 (0.00%) 
Investigations     
Blood triglycerides increased   0/16 (0.00%)  1/14 (7.14%) 
Headache   6/16 (37.50%)  4/14 (28.57%) 
Nervous system disorders     
Hypoaesthesia   2/16 (12.50%)  0/14 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Cough   2/16 (12.50%)  1/14 (7.14%) 
Epistaxis   0/16 (0.00%)  1/14 (7.14%) 
Rhinitis allergic   0/16 (0.00%)  2/14 (14.29%) 
Pharyngolaryngeal pain   1/16 (6.25%)  0/14 (0.00%) 
Skin and subcutaneous tissue disorders     
Burning sensation   0/16 (0.00%)  2/14 (14.29%) 
Dermatitis allergic   2/16 (12.50%)  1/14 (7.14%) 
Dry skin   0/16 (0.00%)  1/14 (7.14%) 
Ecchymosis   0/16 (0.00%)  1/14 (7.14%) 
Erythema   0/16 (0.00%)  1/14 (7.14%) 
Skin hyperpigmentation   1/16 (6.25%)  2/14 (14.29%) 
Pruritus   1/16 (6.25%)  0/14 (0.00%) 
Skin hyperpigmentation   1/16 (6.25%)  0/14 (0.00%) 
Urticaria   1/16 (6.25%)  0/14 (0.00%) 
Vascular disorders     
Lymphoedema   1/16 (6.25%)  1/14 (7.14%) 
Indicates events were collected by systematic assessment
All randomized subjects were included in the mITT analysis. All subjects also met the criteria for the evaluable subset; therefore, no separate analysis of an evaluable subset of subjects was performed.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
Parties agree to keep Referenced Information in strict confidence and not to disclose it to any other party or use Referenced Information for any purpose, other than for the performance of the clinical studies herein described, without prior written consent of the providing party. Parties may disclose the Referenced Information to their employees and consultants, and employees and consultants of their affiliates, who have a need to know such Referenced Information.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Director, Division of Regulated Activites and Compliance
Organization: US Army Medical Materiel Development Activity (USAMMDA)
Phone: 301-619-0197
EMail: usarmy.detrick.medcom-usammda.mbx.usamrmc-regulatory-affairs@mail.mil
Layout table for additonal information
Responsible Party: U.S. Army Medical Research and Development Command
ClinicalTrials.gov Identifier: NCT01032382     History of Changes
Other Study ID Numbers: PG-PERU-08-03, A-15809
First Submitted: December 14, 2009
First Posted: December 15, 2009
Results First Submitted: June 6, 2014
Results First Posted: August 22, 2014
Last Update Posted: July 16, 2015