Clinical trial NCT04155203
Conditions: Secondarily Infected Traumatic Skin Lesions
Sponsor: Padagis LLC
Start date: 2019-10-15; Completion date: 2021-06-01
Enrollment: 657 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
To compare the safety and efficacy of Perrigo's product to an FDA approved product, and to Compare Both Active Treatments to a Vehicle Control in the Treatment of Secondarily Infected Traumatic Skin Lesions

Detailed description:

Arms: arm 1: None arm 2: None arm 3: None
Interventions: intervention 1: Mupirocin Calcium intervention 2: Mupirocin Calcium intervention 3: Vehicle
Intervention descriptions: intervention 1: mupirocin cream intervention 2: Reference mupirocin cream intervention 3: vehicle control cream

Protocol documents:
Prot_000.pdf: 
 
 
NCT04155203 
 
02-25-2019 


 
 
 
 
 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-Group 
Study to Compare Perrigo UK FINCO Limited Partnership’s Mupirocin Cream USP, 
2% to Glenmark Pharmaceuticals Mupirocin Cream USP, 2% and to Compare Both 
Active Treatments to a Vehicle Control in the Treatment of Secondarily Infected 
Traumatic Skin Lesions 
 
 
 
Protocol No.: PRG-NY-19-002 
  
 
 
 
 
 
 
 
 
 
 
Confidential 
 
 
The confidential information provided in this document is for use by parties directly involved in 
this investigation.  By accepting this document, you agree that the information contained herein 
will not be disclosed to any person not directly involved in this investigation without written 
authorization from Perrigo UK FINCO Limited Partnership. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 




Protocol No: PRG-NY-19-002 
 
Page 3 of 45 
 
 
TABLE OF CONTENTS 
TABLE OF CONTENTS ............................................................................................................... 3 
1. 
BACKGROUND ......................................................................................................... 8 
2. 
STUDY OBJECTIVES ................................................................................................... 8 
2.1 
Endpoints ............................................................................................................................... 8 
2.2 
Safety ..................................................................................................................................... 8 
3. 
STUDY DESIGN ......................................................................................................... 9 
3.1 
Type/Design of Study ............................................................................................................. 9 
3.2 
Study Population .................................................................................................................. 10 
4. 
SELECTION OF STUDY SUBJECTS .............................................................................. 10 
4.1 
Inclusion Criteria .................................................................................................................. 10 
4.2 
Exclusion Criteria .................................................................................................................. 11 
4.3 
Prohibited Medications ........................................................................................................ 12 
4.4 
Precautions .......................................................................................................................... 12 
5. 
PROCEDURES .......................................................................................................... 12 
5.1 
Subject Screening and Enrollment ....................................................................................... 12 
5.2 
Assignment of Subject Number ........................................................................................... 13 
5.3 
Demographics/Medical History ........................................................................................... 13 
5.4 
Concomitant Medications .................................................................................................... 13 
5.5 
Physical Examination............................................................................................................ 13 
5.6 
Urine Pregnancy Test ........................................................................................................... 13 
5.7 
Dermatological Examination and Target Lesion Diagnosis .................................................. 14 
5.8 
Skin Infection Rating and Clinical Response ........................................................................ 14 
5.9 
Bacteriology Specimen Collection and Bacteriological Response ....................................... 16 
5.10 
Study Medication Use, Subject Instructions and Diary ........................................................ 16 
5.11 
Visit Specific Procedures ...................................................................................................... 16 
Visit 1/ Day 1 - Baseline ........................................................................................................................ 16 
Visit 2/Day 3 (-1/+ 2 days) – During Treatment ................................................................................... 17 
Visit 3/Day 10 (+ 2 days) – End of Treatment ....................................................................................... 17 
Visit 4/Day 17 (± 4 days) - Follow-up/Early Termination ..................................................................... 18 
Negative Baseline Culture Discontinuation Visit .................................................................................. 18 
Unscheduled Visit ................................................................................................................................. 18 
5.12 
Summary of Assessments .................................................................................................... 20 
5.13 
Screen Failures ..................................................................................................................... 22 
5.14 
Protocol Deviations/Violations ............................................................................................ 22 
5.15 
Subject/Treatment Compliance ........................................................................................... 22 
5.16 
Discontinuation/Withdrawal of Study Subjects ................................................................... 23 
6. 
MATERIALS AND SUPPLIES ...................................................................................... 24 
6.1 
Study Medication ................................................................................................................. 24 
6.2 
Medication Management .................................................................................................... 24 
Labeling, Packaging and Distribution ................................................................................................... 24 
Retention Samples ............................................................................................................................... 25 
Storage and Test Article Accountability ............................................................................................... 25 
Randomization ..................................................................................................................................... 26 


Protocol No: PRG-NY-19-002 
 
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Procedure for Breaking the Blind ......................................................................................................... 26 
7. 
ADVERSE REACTIONS .............................................................................................. 26 
7.1 
Departure from the Protocol for Individual Subjects .......................................................... 26 
7.2 
Definitions ............................................................................................................................ 26 
7.3 
Eliciting and Reporting of Adverse Events ........................................................................... 28 
Expedited Reporting Responsibilities of the Study Center .................................................................. 29 
Submitting an Expedited Safety Report to the IRB .............................................................................. 29 
7.4 
SAE & AEs Requiring Discontinuation of Study Drug, including Pregnancies ...................... 30 
7.5 
Pregnancy ............................................................................................................................. 31 
7.6 
Post Study Adverse Events ................................................................................................... 32 
Non-serious Adverse Events ................................................................................................................. 32 
Serious Adverse Events ........................................................................................................................ 32 
8. 
STATISTICAL ANALYSIS ............................................................................................ 32 
8.1 
Statistical Methods .............................................................................................................. 32 
Analysis Populations ............................................................................................................................. 32 
Planned Analysis ................................................................................................................................... 33 
Sample Size Considerations .................................................................................................................. 33 
Efficacy Measures and Analysis ............................................................................................................ 34 
Safety and Adverse Events Analysis ..................................................................................................... 35 
8.2 
Comparability of Subjects at Baseline.................................................................................. 35 
9. 
CONSENT/ASSENT CONSIDERATIONS AND PROCEDURES ......................................... 35 
9.1 
Subject Confidentiality ......................................................................................................... 36 
10. 
CONDUCT OF STUDY ............................................................................................... 37 
10.1 
Completion of Study ............................................................................................................ 37 
10.2 
Protocol Amendments ......................................................................................................... 37 
11. 
RECORDS MANAGEMENT ........................................................................................ 37 
11.1 
Data Collection ..................................................................................................................... 38 
11.2 
Source Documents ............................................................................................................... 39 
11.3 
File Management at the Study Site ...................................................................................... 39 
11.4 
Records Retention at the Study Site .................................................................................... 39 
12. 
QUALITY CONTROL AND QUALITY ASSURANCE ........................................................ 39 
12.1 
Monitoring ........................................................................................................................... 39 
12.2 
Auditing ................................................................................................................................ 40 
13. 
ETHICS AND RESPONSIBILITY ................................................................................... 40 
14. 
USE OF INFORMATION AND PUBLICATION .............................................................. 40 
15. 
APPENDICES ............................................................................................................ 42 
15.1 
Appendix A: Study Personnel Contacts ................................................................................ 42 
15.2 
Appendix B: Instructions for the Subject ............................................................................. 43 
15.3 
Appendix C: Target Lesion Source Document Example ....................................................... 44 
16. 
REFERENCES ............................................................................................................ 45 


Protocol No: PRG-NY-19-002 
 
Page 5 of 45 
 
 
STUDY SYNOPSIS 
 
Title: 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-
Group Study to Compare Perrigo UK FINCO Limited Partnership’s Mupirocin 
Cream USP, 2% to Glenmark Pharmaceuticals Mupirocin Cream USP, 2% and 
to Compare Both Active Treatments to a Vehicle Control in the Treatment of 
Secondarily Infected Traumatic Skin Lesions 
Study Period: 
17 days 
Study Medication: 
1. Mupirocin Cream USP, 2%, Perrigo UK FINCO Limited Partnership, 
 
2. Mupirocin Cream USP, 2%, manufactured by Glenmark Pharmaceuticals 
3. Vehicle of test product, Perrigo UK FINCO Limited Partnership, 
 
Study Objectives: 
To compare the safety and efficacy profiles of Perrigo UK FINCO Limited 
Partnership’s Mupirocin Cream USP, 2% to Glenmark Pharmaceuticals 
Mupirocin Cream USP, 2%, and to demonstrate the superior efficacy of the 
two active formulations over that of the vehicle in the treatment of subjects 
with secondarily infected traumatic skin lesions. 
Study Design: 
Subjects in this multi-center, double-blind, randomized, vehicle-controlled, 
parallel-group study will be admitted into the study only after written 
informed consent/assent (as applicable) has been obtained and after all 
inclusion/exclusion criteria have been met. Male and female subjects 
18 months or older, with a secondarily infected traumatic skin lesion such as 
a laceration, sutured wound, or abrasion will be eligible for enrollment. 
Study Population: 
Approximately 
 subjects 
 who meet the 
inclusion/exclusion criteria, will be enrolled to obtain approximately 
 
 modified-Intent-To-Treat (mITT) and 
 
 per-protocol (PP) subjects. 
Dosing: 
Subjects will be randomized 
 to the test product, reference 
product, or vehicle treatment group, and will apply 
 the study 
medication to the secondarily infected target lesion 3 times daily for 10 days.  
Study Visits: 
Clinical Evaluations will be performed at: 
1. Visit 1/Day 1 (Baseline)  
2. Visit 2/Day 3 
 (During treatment) 
3. Visit 3/Day 10 
 (End of treatment) 
4. Visit 4/Day 17 
 (Follow-up/Early Termination) 
 
Safety will be assessed by monitoring adverse events at each visit. 
Evaluations: 
To evaluate the clinical response, the Skin Infection Rating Scale (SIRS) will be 
used by investigators to rate the signs of exudate/pus, crusting, 
erythema/inflammation, tissue warmth and tissue edema, and by subjects to 
rate the symptoms of itching and pain. Bacteriological response will also be 
assessed. 


Protocol No: PRG-NY-19-002 
 
Page 6 of 45 
 
 
Endpoints: 
The primary efficacy endpoint is the proportion of subjects in each treatment 
group with clinical cure, defined as a SIRS score of zero “0” or absent for all 
signs and symptoms at Visit 4/Day 17 follow-up visit (7 days after the end of 
treatment).  
 
Secondary efficacy endpoints are the proportion of subjects with clinical cure 
at Visit 3/Day 10 (End of Treatment), bacteriological cure (defined as 
elimination of S. aureus and S. pyogenes or response was such that no culture 
material was available and therefore evidence of pathogen eradication) at 
Visit 3/Day 10 (End of Treatment), and bacteriological cure at Visit 4/Day 17 
(Follow-up).  
Safety: 
The incidence of all adverse events reported during the study will be 
summarized by treatment group. Test and reference product will be 
compared for safety by analyzing nature, severity and frequency of treatment 
emergent adverse events.  


Protocol No: PRG-NY-19-002 
 
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ABBREVIATIONS 
 
AE 
Adverse Event 
CI 
Confidence interval 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
FDA 
US Food and Drug Administration 
GCP  
Good Clinical Practices 
ICH 
International Council for Harmonization 
IRB 
Institutional Review Board 
ITT 
Intent- to-treat (population) 
IUD 
Intra-Uterine Device 
LAR 
Legally authorized representative 
LOCF 
Last Observation Carried Forward 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
Modified Intent-to-Treat (population) 
OTC 
Over the counter 
PP 
Per-protocol (population) 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan  
S. aureus 
Staphylococcus aureus 
SIRS 
Skin Infection Rating Scale 
S. pyogenes 
Streptococcus pyogenes 
WHO 
World Health Organization 
 
 
 


Protocol No: PRG-NY-19-002 
 
Page 8 of 45 
 
 
 
1. 
BACKGROUND 
 
 
 
 
 
 
 
 
. 
 
2. 
STUDY OBJECTIVES 
To compare the safety and efficacy profiles of Perrigo UK FINCO Limited Partnership’s Mupirocin 
Cream USP, 2% to Glenmark Pharmaceuticals Mupirocin Cream USP, 2%, and to demonstrate the 
superior efficacy of the two active formulations over that of the vehicle in the treatment of 
subjects with secondarily infected traumatic skin lesions. 
 
2.1 
Endpoints 
The primary efficacy endpoint is the proportion of subjects in each treatment group with clinical 
cure, defined as a Skin Infection Rating Scale (SIRS) score of zero “0” or absent for all signs and 
symptoms at Visit 4/Day 17 follow-up visit (7 days after the end of treatment).  
 
Secondary efficacy endpoints are the proportion of subjects with clinical cure at Visit 3/Day 10 (End 
of Treatment), bacteriological cure (defined as elimination of S. aureus and S. pyogenes or response 
was such that no culture material was available and therefore evidence of pathogen eradication) at 
Visit 3/Day 10 (End of Treatment), and bacteriological cure at Visit 4/Day 17 (Follow-up). 
 
2.2 
Safety 
Safety of the test and reference products will be compared by evaluating the nature, severity and 
frequency of their adverse event profiles.  All adverse events that occur during the study will be 
recorded whether or not they are considered to be related to the study medication.  Descriptions of 
reactions or complaints will include the approximate date of onset, the date the adverse event 
ended, the severity of the adverse event, and the outcome.  Comparisons between the treatment 
groups will be made by tabulating the frequency of subjects with one or more adverse events 
(classified into MedDRA terms) during the study.  Pearson’s Chi-Square test or Fisher’s Exact test, 
whichever is most appropriate, will be used to compare the proportion of subjects in each treatment 
group with any adverse event.  
 
. 
 
 


Protocol No: PRG-NY-19-002 
 
Page 9 of 45 
 
 
 
3. 
STUDY DESIGN 
 
3.1 
Type/Design of Study 
Subjects in this multi-center, double-blind, randomized, vehicle-controlled, parallel-group study will 
be assigned 
 to test product, reference product, or vehicle, respectively.  Subjects will 
apply 
 the assigned study medication topically to cover the entire secondarily infected 
target lesion 3 times per day for 10 consecutive days. 
 
Subjects will be males and females, 18 months or older, with a secondarily infected traumatic skin 
lesion such as a laceration, sutured wound, or abrasion. Visits to the study site are scheduled at Day 
1 (screening/baseline), Day 3 (during treatment), Day 10 (end of treatment), and Day 17 (follow-up). 
 
At Visit 1/Screening/Baseline informed consent will be obtained.  The subject’s medical history will 
be recorded along with concomitant medications.  A urine pregnancy test will be performed for 
women of childbearing potential.  A brief physical examination will be performed. The diagnosis of a 
secondarily infected traumatic skin lesion will be confirmed.  The dimensions of the secondarily 
infected target lesion will be measured, location will be documented, and the Subject’s Skin Infection 
Rating Scale (SIRS) total score of the secondarily infected target lesion will be evaluated and 
recorded.  A specimen for culture will be prepared from exudates collected from the secondarily 
infected target lesion and a slide will be prepared for Wright stain/Gram stain.  Subjects who meet 
inclusion/exclusion criteria will be dispensed study medication and the site staff will instruct the 
subject on medication application and completion of subject diary.  The first application of study 
medication will be made at the site under supervision of site staff.  
Subjects will return to the office for Visit 2/During Treatment (Day 3 
), Visit 3/End of 
Treatment (Day 10 
) and Visit 4/Follow-up (Day 17 
).  During each visit, SIRS total 
score of the secondarily infected target lesion will be completed, the subject’s concomitant 
medications will be reviewed, and any adverse events will be recorded.  Subjects will return at each 
appropriate visit with study medication and their Subject Diary.  
 
  At Visit 3/End of Treatment 
 
 all study medication will be collected.  At Visit 3/End of Treatment 
 and 
Visit 4/Follow-up 
, bacteriological samples for culture will be obtained.  
If it is necessary to see a subject other than at a scheduled visit date, the Unscheduled Visit 
procedures will be followed (Sections 5.11 and 5.12).  If the investigator decides to discontinue a 
subject at any time during the study, a standard of care treatment may be advised at the 
Investigator’s discretion, and an Early Termination Visit may be performed for this purpose.  If the 
investigator discontinues a subject due to a negative baseline culture, the procedures for the 
Negative Baseline Culture Discontinuation Visit (Sections 5.11 and 5.12) should be performed.  
Early Observation of Subjects: At Visit 2/Day 3 
 or at any time the Investigator 
determines that the infection has become systemic, is not responding to treatment, is not improving, 
or that the study treatment is not sufficient to treat the infected lesion, he or she should discontinue 
the subject from the study and prescribe appropriate approved treatment (e.g. Mupirocin Cream 
USP, 2% or oral therapy) or refer the subject to another physician.  This treatment may be topical or 


Protocol No: PRG-NY-19-002 
 
Page 10 of 45 
 
 
systemic in nature and use of such therapy will be documented in the source documents and 
electronic case report form (eCRF). 
 
3.2 
Study Population 
Male and female subjects, 18 months or older with a secondarily infected traumatic skin lesion such 
as a laceration, sutured wound, or abrasion will be eligible for enrollment.   
 
4. 
SELECTION OF STUDY SUBJECTS 
 
4.1 
Inclusion Criteria 
Subjects must meet all of the following criteria: 
 
1. 
Subjects 18 years or older must sign an Institutional Review Board (IRB)-approved written 
informed consent. Subjects under the age of 18 years must have a parent or legally authorized 
representative provide IRB approved written informed consent. 
 
 
 
 
 
 
 
 
 
2. Subjects must be healthy males or nonpregnant females aged 18 months or older. 
3. Subjects must have a secondarily infected traumatic skin lesion such as a laceration, sutured 
wound, or abrasion. 
 
 
 
 
 
 
4. Subjects must have a positive baseline culture for S. aureus and/or S. pyogenes from a sample 
taken from the secondarily infected traumatic skin lesion. 
5. Subjects must have a positive Gram stain or Wright stain for confirmation of white blood cells in 
the pus/exudate from the secondarily infected traumatic skin lesion. 
6. Subjects must have a Skin Infection Rating Scale (SIRS) total score for the secondarily infected 
traumatic skin lesion of at least 8 at baseline (see Section 5.8 for the scale). 
7. Subjects must be willing and able to understand and comply with the requirements of the study, 
apply the medication as instructed, and be able to complete the study. 
8. Subjects must be in general good health and free from any clinically significant disease, other 
than secondarily infected traumatic skin lesion(s), that might interfere with the study 
evaluations. 
9. 
 
 




Protocol No: PRG-NY-19-002 
 
Page 12 of 45 
 
 
14. 
 
 
15. 
 
. 
16. 
 
 
. 
17. 
 
.  
18. Subjects who, in the opinion of the investigator, are unlikely to be able to follow the restrictions 
of the protocol and complete the study.  
 
4.3 
Prohibited Medications 
The following medications/procedures are prohibited during this study: 
 
 
 
 
 
4.4 
Precautions 
The following precautions are to be taken during this study: 
1. Subjects should use study medication externally only and avoid contact with the eyes, nose, 
mouth, or vagina or mucosal surfaces. 
2. 
. 
3. 
 
. 
4. 
 
 
. 
5. 
 
 
 
 
5. 
PROCEDURES 
 
5.1 
Subject Screening and Enrollment 
The study personnel will review the IRB-approved informed consent form and assent form, if 
applicable, with each subject and give the subject an opportunity to have all questions answered 
before proceeding.  
 
Subjects 18 years or older must sign an Institutional Review Board (IRB)-approved written informed 
consent.  Subjects under the age of 18 years must have a parent or legally authorized representative 
provide IRB approved written informed consent.  In addition, an assent form for minors must be 


Protocol No: PRG-NY-19-002 
 
Page 13 of 45 
 
 
signed by subjects under the legal age of consent and over 6 years of age. 
 
 
 
 
 
 
 
 
 
. 
 
5.2 
Assignment of Subject Number 
Once the subject has consented and met inclusion/ exclusion criteria, the subject will be assigned a 
subject number.  Each subject will be dispensed their respective medication.  The subject number 
will correspond to a computer-generated randomization schedule assigning the number to one of 
the three study treatment groups and will be taken from the study medication kit dispensed to the 
subject at each site.  
 
5.3 
Demographics/Medical History 
A demographic profile and complete medical history will be recorded prior to starting study 
medication. The medical history will include a complete review of all current diseases and their 
respective treatments. 
 
5.4 
Concomitant Medications 
Concomitant medications and any medications taken 
 prior to signing informed 
consent/assent will be recorded as prior/concomitant medications (using their generic name, if 
known) with the corresponding indication.  The medications to be recorded will include prescription 
and over-the-counter (OTC) medications and dietary supplements.  All medications taken on either 
a regular or “prn” basis, including vitamins, aspirin, and acetaminophen, should be recorded on this 
page prior to starting the study medication.  A record of medication taken by the subject during the 
study is to be obtained at each study visit.  
 
5.5 
Physical Examination 
The investigator, sub-investigator, or appropriately delegated and qualified designee will perform a 
brief physical examination prior to the subject starting study medication.  
 
 
 
   
 
5.6 
Urine Pregnancy Test 
A urine pregnancy test will be conducted on women of child-bearing potential at Visit 1/Day 1 (before 
the subject applies the first dose of the study medication at the site) and Visit 4/Day 17 
.  
An investigator may repeat the pregnancy test anytime during the study visit if there is any suspicion 
or possibility that the subject may be pregnant.  
 




Protocol No: PRG-NY-19-002 
 
Page 15 of 45 
 
 
assessed by discussion with the subject at each visit and will be reported as the severity 
experienced at the time of the study visit.  
 
 
.  
 
Clinical cure is defined as a SIRS score of zero “0” or “absent” for all signs and symptoms. 
 
Skin Infection Rating Scale (SIRS): 
Sign/Symptom 
Score 
Definition 
Exudate/pus 
0 =Absent 
1 = Mild 
2 = Moderate 
3 = Severe 
No evidence of exudate or pus 
Small amount of fluid/pus coming from the skin lesion(s) 
Exudate/pus infected area is moderate 
Extensive area of skin lesion is infected and there is draining exudate 
Crusting 
0 =Absent 
1 = Mild 
2 = Moderate 
3 = Severe 
No evidence of crusting 
A few areas have some evidence of crusting lesions 
Crusting is present throughout the infected area 
Thick crusting appears over the entire infected area 
Erythema/ 
inflammation 
0 =Absent 
1 = Mild 
2 = Moderate 
3 = Severe 
Skin tone and color are normal; no signs of erythema or inflammation 
Skin is pink with minimal signs of inflammation 
Skin is red with definite signs of inflammation 
Skin is red and severe inflammation is present 
Tissue edema 
0 =Absent 
1 = Mild 
2 = Moderate 
3 = Severe 
No evidence of tissue edema 
Tissue has mild edema 
Tissue has moderate edema 
Tissue has severe edema 
Tissue warmth 
0 =Absent 
1 = Mild 
2 = Moderate 
3 = Severe 
No evidence of tissue warmth 
Tissue has mild warmth 
Tissue has moderate warmth 
Tissue has severe warmth 
Itching 
0 =Absent 
1 = Mild 
 
2 = Moderate 
3 = Severe 
No itching 
Some evidence of scratching or rubbing the area is evident and subject 
reports minor discomfort 
Evidence of scratching and subject reports bothersome itching 
Evidence of extensive scratching and subject reports itching interferes with 
daily activities or sleep 
Pain 
0 =Absent 
1 = Mild 
2 = Moderate 
 
3 = Severe 
No pain 
Slight pain; not bothersome; no analgesics being taken 
Definite pain; subject reports bothersome pain, without loss of sleep, mild 
analgesic may be taken 
Intense pain that interferes with daily activities or sleep; medication 
required to control pain 


Protocol No: PRG-NY-19-002 
 
Page 16 of 45 
 
 
 
5.9 
Bacteriology Specimen Collection and Bacteriological Response 
A wound exudate sample for culture and sensitivity testing will be taken with a swab from the 
secondarily infected target lesion and sent to a designated laboratory for culture.  A positive culture 
(S. aureus or S. pyogenes) is required for study 
 
 
. Subjects with negative 
baseline cultures are to be discontinued as soon as possible after negative results are received by 
the clinical research site.  
 
 
 
 
 
Bacteriological cure is defined as elimination of S. aureus and S. Pyogenes 
 
. 
 
5.10 
Study Medication Use, Subject Instructions and Diary 
Study personnel will ensure that the subjects can identify the treatment area and know where to 
apply the study medication.  Subjects will be instructed on the correct use of study medication at 
the study site during Visit 1/ Day 1.  
 
  
 
 
 
. 
 
Subjects will be instructed to apply 
 study medication 3 times per day for 10 
consecutive days according to the Subject Instructions 
  The Subject Instructions and 
the Subject Diary will be reviewed with each subject at each visit.  
 
Subjects will be given a Subject Diary card to record study medication applications 
 
 to be used during the study period. 
 
The Subject Diary card will be dispensed to each enrolled subject at Visit 1/Day 1.  The subject will 
be instructed to complete the Subject Diary by recording each application or missed application of 
study medication.  At Visit 2/Day 3 
, study personnel will review the Subject Diary.  At 
Visit 3/Day 10 
, study personnel will collect and review the completed Subject Diary. 
 
5.11 
Visit Specific Procedures 
The following sections outline the procedures required at each visit. 
 
Visit 1/ Day 1 - Baseline 
Prospective subjects will visit the study center and be examined by the study physician who will 
perform the procedures below at this visit.  
 


Protocol No: PRG-NY-19-002 
 
Page 17 of 45 
 
 
The following procedures must be completed and documented on the source document before a 
subject is randomized on the study:  
 
• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
) 
 
Visit 2/Day 3 
 – During Treatment 
• 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
Early Observation of Subjects: At this visit, the Investigator will determine if the infection has become 
systemic, is not responding to treatment, is not improving, or that the study treatment is not sufficient to 
treat the infected lesion, and if any of these conditions are confirmed, the subject should be discontinued 
from the study and be prescribed an appropriate approved treatment (e.g. Mupirocin Cream USP, 2% or oral 
therapy) or refer the subject to another physician.  This treatment may be topical or systemic in nature and 
use of such therapy will be documented in the source documents and electronic case report form (eCRF). 
 
Visit 3/Day 10 
 – End of Treatment 
• 
 
 
 


Protocol No: PRG-NY-19-002 
 
Page 18 of 45 
 
 
• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Visit 4/Day 17 
 - Follow-up/Early Termination  
• 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unscheduled Visit 
An unscheduled visit is allowed at any time if in the investigator’s opinion it is warranted. If the 
investigator assesses the subject’s condition and determines that the subject’s condition has 
worsened to the degree that it is unsafe for the subject to continue in the study, the subject may be 
discontinued from the study as a treatment failure, Early Termination Visit procedures conducted, 
and a standard of care treatment may be advised at the investigator’s discretion.  
 
 
 


Protocol No: PRG-NY-19-002 
 
Page 19 of 45 
 
 
• 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No: PRG-NY-19-002 
 
Page 20 of 45 
 
 
5.12 
Summary of Assessments 
The schedule of visits and procedures to be conducted at each visit are summarized in the Schedule 
of Study Procedures. 
 
 
 




Protocol No: PRG-NY-19-002 
 
Page 22 of 45 
 
 
5.13 
Screen Failures 
Screen failures will not be entered in the database or included in any data analyses. A screen failure 
is a subject who received information about the study, including signing an informed consent/assent, 
and possibly underwent some study-related procedures but was not enrolled, dispensed study 
medication, nor applied the investigational product. 
 
5.14 
Protocol Deviations/Violations 
This study will be conducted as described in this protocol except for an emergency situation in which 
the protection, safety, and well-being of the subject requires immediate intervention, based on the 
judgment of the investigator or a responsible, appropriately trained and credentialed professional(s) 
designated by the investigator.  In the event of a significant deviation from the protocol due to an 
emergency, accident or mistake, the investigator or designee must contact Perrigo /
 contacts 
in Section 15 (Appendix A) of this protocol at the earliest possible time. 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
5.15 
Subject/Treatment Compliance 
Study personnel will ensure that subjects can identify the secondarily infected target lesion they 
will be treating and know where to apply the study medication.  Subjects will be instructed on the 
correct use of study medication at the study site during Visit 1/Day 1.  Subjects will apply the first 
application at the study site under the supervision of site staff. Subjects will be instructed to apply 
 study medication three (3) times per day for ten (10) consecutive days according to 
the Subject Instructions 
  
 
 
 
 
 
 
 
 
 


Protocol No: PRG-NY-19-002 
 
Page 23 of 45 
 
 
 
 
5.16 
Discontinuation/Withdrawal of Study Subjects 
Subjects may be removed from the study for any of the following reasons: 
• Negative baseline culture. 
• The subject withdraws his or her consent for any reason. 
• The subject’s condition has worsened to the degree that the investigator feels it is unsafe for the 
subject to continue in the study or requires an alternative therapy for the treatment of their 
secondarily infected traumatic skin lesion. 
• The subject’s medication code is unblinded. 
• The subject did not meet or no longer meets the entry criteria. 
• An adverse event, including intercurrent illness, occurs for which the subject desires to 
discontinue treatment or the investigator determines that it is in the subject’s best interest to be 
discontinued. 
• A concomitant therapy is reported or required that may interfere with the results of the study. 
• The subject is lost to follow-up. The investigator will document efforts to attempt to reach the 
subject twice by telephone and will send a certified follow-up letter before considering that 
subject lost to follow-up. All attempts must be thoroughly recorded. 
• The subject becomes pregnant during the course of the trial. 
• A lack of treatment response,
 
 
• Investigator discretion (e.g., non-compliant with study protocol requirements). 
 
After a subject has been discontinued, he/she will not be allowed to re-enroll in the study at any 
facility.  
 
The reasons for a subject being discontinued will be documented in the eCRFs and the enrollment 
log. 
 
If a subject is discontinued from the study for any reason, the Visit 4/Day 17 (End of Study Visit/Early 
Termination Visit) procedures should be completed and any outstanding data and study medication 
should be collected.  Data, in addition to the reason for discontinuation and the date of removal, will 
be recorded on the Source Document and End of Study eCRF. 
 
If a subject discontinues from the study at any time due to an adverse event, the reason for 
discontinuation, the nature of the event, and its clinical course must be fully documented.  For such 
a subject, the investigator must strive to follow the subject until the adverse event has resolved, 
become clinically insignificant, is stabilized, or the subject is lost to follow-up. 
 
 
 
 
.  


Protocol No: PRG-NY-19-002 
 
Page 24 of 45 
 
 
 
 
 
6. 
MATERIALS AND SUPPLIES 
 
6.1 
Study Medication 
The study medication supplied by Perrigo will consist of: 
 
Test Product: Mupirocin Cream USP, 2%,  
Perrigo 
 
 
Reference Product: Mupirocin Cream USP, 2% (manufactured by Glenmark Pharmaceuticals) 
 
Vehicle: Vehicle of test product  
Perrigo 
 
 
6.2 
Medication Management 
 
Labeling, Packaging and Distribution 
 
The study medication assigned to each subject number will be determined by a computer-generated 
randomization schedule.  Study medication is labeled and packaged, according to the randomization 
code, so that neither the subject nor the investigator can identify the treatment. 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
The tear-off portion of each kit label contains the identity of the medication in the tube.  The 
investigator will not remove the occluding layer of the label unless absolutely necessary to provide 
medical treatment to a subject in an emergency and preferably with prior authorization from Perrigo 
or designee, whenever possible.  If the occluded portion of the label is removed, each involved 
subject(s) will be discontinued from the study and the reason will be noted on the source documents 
and eCRFs. 


Protocol No: PRG-NY-19-002 
 
Page 25 of 45 
 
 
 
The tear-off portion has an adhesive backing to affix to the study medication dispensing log that will 
be maintained at the investigator site.  THE LOG AND TEAR-OFF LABELS WILL BE STORED SECURELY AT THE STUDY 
SITE AS RECORD OF THE SUBJECT’S INTENDED TREATMENT.  THE STUDY LABEL FORMS AND THE ATTACHED ORIGINAL 
LABELS SHOULD NOT BE REMOVED FROM THE SITE UNTIL PERRIGO HAS NOTIFIED THE SITES, IN WRITING. 
 
 
 
 
  
 
 
 
Retention Samples 
Each investigational site where study medication is dispensed to at least one subject will be required 
to randomly select one block of study medication 
 to be 
maintained as retain samples.  The investigator will maintain one randomly selected block of study 
medication from each shipment of study medication received. As per the Code of Federal Regulations 
Part 21, Section 320.38(e), “Each reserve sample shall be stored under conditions consistent with 
product labeling and in an area segregated from the area where testing is conducted and with access 
limited to authorized personnel (stored between 20° to 25°C (68° to 77°F).; even after the study has 
concluded.  Each reserve sample shall be retained for a period of at least five (5) years following the 
date on which the application or supplemental application is approved, or, if such application or 
supplemental application is not approved, at least five (5) years following the date of completion of 
the bioavailability study in which the sample from which the reserve sample was obtained or was 
used.”  The investigator will store the retain sample study medication until such time as written 
notification is received from Perrigo that the samples are no longer required. 
 
Storage and Test Article Accountability 
Study articles used to conduct this study will be maintained under adequate security by the 
investigator or designee.  Each investigator site will ensure that the temperature of study medication 
is monitored and recorded throughout the study.  The study medication should be stored between 
20° to 25°C (68° to 77°F) and should not be frozen, as recommended in the labeling for Mupirocin 
Cream USP, 2%.  The medication should be kept away from children unless the subject is a child.  The 
investigator will not supply study medication to any person not enrolled in this study, or to any 
physician or scientist except those named as sub-investigators. 
 
The clinic personnel at each investigator site will keep a running inventory of study medication 
dispensed that will include subject numbers assigned and the date each tube of study medication is 
dispensed and returned.  A study medication accountability form will be provided to the investigator 
to document all medications received, dispensed by and used by each subject.  At the conclusion of 
the study all unused, partially used, and empty tubes must be inventoried by the monitor and 
returned to Perrigo, or designee, for destruction, with the exception of retention samples which shall 
remain at the investigator site. 


Protocol No: PRG-NY-19-002 
 
Page 26 of 45 
 
 
 
Randomization 
Randomization will be performed according to a computer-generated randomization scheme where 
the treatment group designation has been assigned to the subject number. The treatment 
designation will remain blinded until the final database is closed. An independent third party will 
hold the randomization code throughout the study. The randomization scheme will be a block 
randomization, with each block of 
 assigned to Test: Reference: Vehicle 
. 
 
Procedure for Breaking the Blind 
The investigator, staff at the study site, study monitors, and data analysis/management personnel 
are blinded to the subject assignment.  In the event of an emergency, the specific subject treatment 
may be identified by removing the overlay of the blinded label for each subject at each investigator 
site, which is attached to the study medication log; however, every effort should be made to maintain 
the blind.  The investigator must not scratch off the occluding layer of the label unless absolutely 
necessary to provide medical treatment to a subject in an emergency situation only and should 
seek prior authorization by Perrigo or designee when possible.  The reason for breaking the blind 
must be clearly documented in the source documentation and eCRF and the subject must be 
discontinued from the study. Perrigo must be notified immediately upon all unblinding situations.  
 
7. 
ADVERSE REACTIONS 
The potential adverse reactions of generic Mupirocin Cream USP, 2%, are anticipated to be similar 
to those observed with Mupirocin Cream USP, 2%.   
 
The adverse reactions reported by at least 1% of 339 subjects in connection with the use of Mupirocin 
Cream USP, 2% in clinical trials were headache (1.7%), rash (1.1%), and nausea (1.1%).  Adverse 
reactions that occurred in less than 1% of subjects were abdominal pain, burning at application site, 
cellulitis, dermatitis, dizziness, pruritus, secondary wound infection, and ulcerative stomatitis. 
 
Systemic allergic reactions, including anaphylaxis, urticaria, angioedema, and generalized rash, have 
been identified during postmarketing use of Mupirocin Cream USP, 2%. Because they are reported 
voluntarily from a population of unknown size, estimates of frequency cannot be made. 
 
Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial 
agents and may range in severity from the mild diarrhea to fatal colitis.  
 
7.1 
Departure from the Protocol for Individual Subjects 
When an emergency occurs requiring a departure from the protocol for a subject, departure will be 
only for that subject.  In such circumstances, the investigator or other physician in attendance will 
contact the Medical Monitor or Perrigo by telephone and follow-up with a written description as 
soon as possible.  The overseeing IRB should also be notified. 
 
7.2 
Definitions 
An adverse event (AE) is defined as any untoward medical occurrence in a subject administered a 
medicinal product and which does not necessarily have to have a causal relationship with this 


Protocol No: PRG-NY-19-002 
 
Page 27 of 45 
 
 
treatment.  An adverse event can therefore be any unfavorable and unintended sign (for example, 
an abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal product, whether or not considered related to this medicinal product. 
 
A serious adverse event (SAE) is an adverse event that results in any of the following outcomes: 
• Death 
• Life-threatening event (e.g., the subject was, in the opinion of the investigator, at immediate 
risk of death from the event as it occurred. It does not include an event that, had it occurred 
in a more severe form, might have caused death) 
• Requires in-subject hospitalization or prolongs hospitalization 
• A persistent or significant disability/incapacity or substantial disruption of the ability to 
conduct normal life functions 
• Congenital anomaly/birth defect 
• Other adverse events that may be considered serious based upon appropriate medical 
judgment, may jeopardize the subject and may require medical or surgical intervention to 
prevent one of the outcomes listed above. 
 
Immediately Reportable Adverse Events (IRAE): Any serious AE or any AE that necessitates 
discontinuation of study medication, including pregnancy. 
 
Unexpected Adverse Event: An unexpected event is any adverse drug experience, the specificity or 
severity of which is not consistent with the current approved product labeling (package insert) for 
the study medication, the Investigator’s Brochure, or as described in the clinical protocol and consent 
materials.  
 
Intensity of Adverse Events: The maximum intensity of an AE during a day should be recorded on the 
eCRF. If the intensity of an AE changes over a number of days, then separate entries should be made 
having distinct onset dates for the changes in severity. 
 
Mild - AEs are usually transient, requiring no special treatment, and do not interfere with 
subject’s daily activities. 
 
Moderate - AEs typically introduce a low level of inconvenience or concern to the subject and 
may interfere with daily activities, but are usually ameliorated by simple therapeutic measures. 
 
Severe - AEs interrupt a subject’s usual daily activity and traditionally require systemic drug 
therapy or other treatment. 
 
Causal Relationship to Study Medication: The following criteria should be used in assessing the 
apparent causal relationship of an AE to study medication.  
 
Definitely - The AE: 
• 
follows a reasonable temporal sequence from study medication administration 
• 
abates upon discontinuation of the study medication (dechallenge) 


Protocol No: PRG-NY-19-002 
 
Page 28 of 45 
 
 
• 
is confirmed by reappearance of the reaction on repeat exposure 
 
Probably - The AE: 
• 
follows a reasonable temporal sequence from study medication administration 
• 
abates upon discontinuation of the study medication (dechallenge) 
• 
cannot be reasonably explained by the known characteristics of the subject’s state. 
 
Possible - The AE: 
• 
follows a reasonable temporal sequence from study medication administration 
• 
but that could readily be produced by a number of other factors. 
 
Unlikely - The AE: 
• follows a reasonable temporal sequence from study medication administration. 
• could have been produced by either the subject’s clinical state or by study medication 
administration. 
 
Not related - The AE: 
• does not have a reasonable temporal association with the administration of study 
medication  
• has some other obvious explanation for the event. 
 
7.3 
Eliciting and Reporting of Adverse Events 
The investigator will periodically assess subjects for the occurrence of adverse events.  
 
 
 
 All adverse events (as defined in Section 7.2), either observed by the investigator 
or one of his/her medical collaborators, or reported by the participant spontaneously, or in response 
to direct questioning, will be reported and documented in the source document and the study 
reporting forms.  When reporting an adverse event, the investigator must assign a severity grade to 
each event and declare an opinion on the relatedness of the event to the study medication or 
procedure.  Serious or unexpected adverse events must be reported to 
 within 24 hours of 
when the investigator first learns of the occurrence of the event.  
 
Adverse events will be documented in the source document and recorded in a timely manner on the 
eCRFs. Adverse events that are identified at the last assessment visit (or the early termination visit) 
must be recorded on the AE eCRF with the status of the AE noted.  
 
Adverse event reporting begins from the signing of informed consent/assent. Adverse events should 
be followed until resolved or 30 days after the final study treatment.  In any case, serious adverse 
events that are not resolved or considered to be chronic within 30 days of the final study treatment 
must be followed by the investigator until they become resolved or are considered to be chronic 
(stabilized for at least 30 days).  All events that are ongoing at this time will be recorded as ongoing 
on the eCRF. 
 


Protocol No: PRG-NY-19-002 
 
Page 29 of 45 
 
 
Expedited Reporting Responsibilities of the Study Center 
For any serious or unexpected adverse event, 
 must be notified within 24 hours of when the 
investigator first learns of the occurrence of the event.  Expedited reporting requirements for serious 
adverse events are described below.  Adequate information must be collected with supporting 
documentation to complete a standard report for submission to Perrigo.  The adverse event term on 
the AE eCRF and the SAE report should agree exactly. Special attention should be given to recording 
hospitalizations and concomitant medications.   
 
Subjects with unresolved adverse event(s) or serious adverse event(s) should be followed by the 
investigator until the events are resolved, events determined to be chronic, or the subject is lost to 
follow-up.  Resolution means the subject has returned to the baseline state of health, or the 
investigator does not expect any further improvement or worsening of the adverse event.  The 
investigator should continue to report any significant follow-up information to the sponsor up to the 
point that the event has resolved.  Any serious adverse event reported by the subject to the 
investigator that occurs within 30 days after the last assessment and is determined by the 
investigator to be reasonably associated with the use of the study medication, should be reported 
to the sponsor within 24 hours of when the investigator first learns of the occurrence of the event.   
 
When reporting an SAE the investigator (or the Study Coordinator) will promptly report any serious 
adverse event or pregnancy by telephone to 
 immediately after the investigator becomes aware of the event.  An SAE form should be 
completed and sent by fax, email, or overnight courier to 
 within 24 hours of knowledge of 
the event by the site. In many cases, only preliminary information will be available.  Appropriate 
follow-up information should be sought (hospital discharge summaries, operative reports, etc.) and 
a follow-up SAE report form submitted.  A designation of causality from the study medication should 
always be included with a follow-up report. Assess and report the causality of the event. 
 
Submitting an Expedited Safety Report to the IRB 
Once 
 receives all supporting documentation for the reported event, the Medical Monitor, in 
conjunction with Perrigo, will determine if the safety report is eligible for expedited review.  
 
will log the initial event and will notify the sponsor that an event has been reported within 1 business 
day after initial receipt.  
 will complete the review of the event.  This form, as well as other 
supporting documentation, will be forwarded to 
 Medical Monitor for review.  
 will 
finalize the report and distribute it to the sponsor within 1 day (one) after initial receipt.  When 
expedited safety reporting to regulatory authorities is indeed required, the investigator should 
review and update any newly available materials at once. Follow-up queries may be sent to the study 
center to further clarify the event. 
 
Each expedited safety report will routinely include a brief cover memorandum, the completed 
report, and any additional pertinent information recommended by 
, Perrigo, or the study 
Medical Monitor.  Once the report is assembled, the Principal Investigator must submit the expedited 
safety report to the IRB within the required reporting timeframe.  Follow-up reports should be 
submitted when requested or when pertinent information becomes available.  
 


Protocol No: PRG-NY-19-002 
 
Page 30 of 45 
 
 
When a Principal Investigator receives an expedited safety report from 
 or the sponsor 
detailing adverse events occurring at other study centers under this protocol, it must be promptly 
submitted to the study center’s IRB.  The Principal Investigator must retain a copy of such reports as 
submitted to his/her IRB in the site’s study Regulatory Binder. 
 
7.4 
SAE & AEs Requiring Discontinuation of Study Drug, including Pregnancies 
ANY SAE THAT OCCURS AFTER A SUBJECT HAS ENTERED THE STUDY, WHETHER OR NOT RELATED TO 
STUDY MEDICATION, MUST BE REPORTED TO 
 IMMEDIATELY (WITHIN 24 HOURS) VIA 
TELEPHONE OR FACSIMILE. IF INITIALLY REPORTED VIA TELEPHONE, THIS MUST BE FOLLOWED-UP 
BY A FACSIMILE OF THE WRITTEN SAE REPORT WITHIN 24 HOURS OF THE CALL TO 
. 
 
Non-serious events that require discontinuation of study medication (including laboratory 
abnormalities) should be reported to 
 immediately and within 1 working day. 
 
Subjects who discontinue due to experiencing adverse events should be followed clinically until their 
health has returned to baseline status or until all parameters have returned to normal.  It is expected 
that the investigator will provide or arrange appropriate supportive care for the subject. 
 
A subject who experiences a severe adverse event related to study drug will be discontinued from 
the study. 
 
The notification about any serious adverse event should be directed to: 
 
 
 
 
 
 
 
 
 
 will report the SAE to the Sponsor: 
 
SPONSOR 
 
 
 
  
  
 
 
 
 
 
   


Protocol No: PRG-NY-19-002 
 
Page 31 of 45 
 
 
 
 
 
 
7.5 
Pregnancy 
At the time the Principal Investigator or site personnel becomes aware that a study participant 
became pregnant during study participation, the Principal Investigator or designee will report the 
pregnancy immediately by phone and/or by faxing a completed Pregnancy Report to 
 within 
1 business day of being notified of the pregnancy report. 
 
The report will include the following elements: 
• Participant (mother’s) coded study identifier; 
• Date of participant’s last menstrual period; 
• Total accumulated dose of study treatment administered to date; 
• Date of study medication administration. 
 
The investigator will follow the subject until completion of the pregnancy and must assess the 
outcome in the shortest possible time but not more than 30 days within completion of the 
pregnancy. 
 
Upon delivery, miscarriage or abortion, the Principal Investigator or designee must forward a follow-
up Pregnancy Report with any relevant information on the present condition of the fetus to the 
, including: 
• Mother’s coded study identifier(s); 
• Gestational age at delivery, miscarriage or abortion; 
• Birth weight, gender, length and head circumference, if available; 
• Apgar scores recorded after birth, if available; 
• Any abnormalities. 
 
If the outcome of the pregnancy meets the criteria for immediate classification of an SAE (e.g., 
spontaneous or therapeutic abortion [any congenital anomaly detected in an aborted fetus is to be 
documented], stillbirth, neonatal death, or congenital anomaly), the investigator will report the 
event by phone and by faxing a completed SAE report form to 
 within 1 working day of being 
notified of the pregnancy report. 
 
If the trial is completed before the outcome of the pregnancy is known, 
 will assume the 
responsibility for following up on the pregnancy.  
 will contact the investigator or Study 
coordinator on or around the potential expected date of delivery to follow-up on the outcome of 
pregnancy and will also check on the status of the infant 8 weeks post-delivery.  Upon awareness of 
the pregnancy outcome and known status of the infant following 8 weeks of delivery, the investigator 
will complete the applicable pregnancy report forms and fax to 
 within 1 day of being notified.  
 


Protocol No: PRG-NY-19-002 
 
Page 32 of 45 
 
 
7.6 
Post Study Adverse Events 
 
Non-serious Adverse Events 
Adverse events that are identified at the last assessment visit (or the early termination visit) must be 
recorded on the AE eCRF with the status of the AE noted.  These adverse events must be followed 
by the investigator until the events are resolved, events determined to be chronic or the subject is 
lost to follow-up.  Resolution means the subject has returned to the baseline state of health or the 
investigator does not expect any further improvement or worsening of the adverse event. 
 
Serious Adverse Events 
Serious adverse events that are identified on the last assessment visit (or the early termination visit) 
must be recorded on the AE eCRF page and reported to Perrigo according to the procedures outlined 
above.  Subjects with unresolved previously reported serious adverse events, or any new serious 
adverse events identified on the last assessment visit, should be followed by the investigator until 
the events are resolved, or the subject is lost to follow-up.  Resolution means the subject has 
returned to the baseline state of health or the investigator does not expect any further improvement 
or worsening of the adverse event.  The investigator should continue to report any significant follow-
up information to Perrigo up to the point that the event has resolved.  Any serious adverse event 
reported by the subject to the investigator that occurs after the last assessment and is determined 
by the investigator to be reasonably associated with the use of the study drug, should be reported 
to Perrigo. 
 
8. 
STATISTICAL ANALYSIS 
The sections that follow highlight sample size determination and the planned analyses for this study. 
A statistical analysis plan (SAP) that describes the statistical methods, models, hypotheses, and 
subject populations to be analyzed will be prepared separately from this protocol.  The SAP will be 
completed and approved before locking the database and unblinding the study and will serve as a 
companion to the protocol and the de facto documentation of the proposed statistical evaluation. 
The SAP will be completed and finalized prior to breaking the blind. 
 
8.1 
Statistical Methods 
 
Analysis Populations 
The following populations are defined for the purpose of analyses: 
 
• Intent-to-Treat (ITT) (safety population): Any subject who was randomized, received and used 
study medication.  
 
• Modified Intent-to-Treat (mITT): Any subject who met the inclusion/exclusion criteria 
(including a positive baseline bacteriological culture), was randomized, received and used the 
study medication, and returned for at least one post-baseline efficacy assessment. 
 
• Per Protocol (PP): Any subject who: 
• met inclusion/exclusion criteria (including a positive baseline bacteriological culture), 




Protocol No: PRG-NY-19-002 
 
Page 34 of 45 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
Efficacy Measures and Analysis 
Clinical Endpoints 
The primary efficacy endpoint is the proportion of subjects in each treatment group with clinical 
cure, defined as a SIRS score of 0 for all signs and symptoms at Visit 4/Follow-up (7 days after the 
end of treatment).  Secondary efficacy endpoints are the proportion of subjects with clinical cure at 
Visit 3/End of Treatment, bacteriological cure (defined as elimination of S. aureus and S. pyogenes or 
response was such that no culture material was available and therefore evidence of pathogen 
eradication) at Visit 3/End of Treatment, and bacteriological cure at Visit 4/Follow-up. 
 
Equivalent efficacy 
The clinical equivalence of the test and reference treatments will be based on the proportions of 
subjects with clinical cure at Visit 4/Day 17 (Follow-up, 7 days after end of treatment).  
 
The hypothesis tested for clinical equivalence between test and reference will be:  
H0: pT - pR < -0.20 or pT - pR > 0.20 versus 
HA: -0.20 ≤ pT – pR ≤ 0.20.  
Where pT and pR were the proportions of subjects with clinical cure at Visit 4/Day 17 for the Test and 
Reference products, respectively.  The Test product would be considered to be clinically equivalent 
to the Reference product if the 90% confidence interval (CI) of the difference between their 
proportions of subjects with clinical cure, calculated by the Wald’s method with Yates’ continuity 
correction, is contained within the limits -20.0% to +20.0%. Rejection of the null hypothesis would 
support the conclusion of therapeutic equivalence between the Test and Reference products for the 
primary efficacy variable. 
 
Analysis in the PP population will be considered definitive and those in the mITT population will be 
considered supportive. 
 
Superiority 
The test of superiority of each active treatment over vehicle will be based on the proportions of 
subjects in each treatment group with clinical cure at the Visit 4/Day 17 
  
 


Protocol No: PRG-NY-19-002 
 
Page 35 of 45 
 
 
The hypotheses tested for superiority of the test and reference products over Vehicle will be:  
H0: pT ≤ pV versus HA: pT > pV  
H0: pR ≤ pV versus HA: pR > pV 
Where pT, pR, and pV are the proportions of subjects with clinical cure at the Visit 4/Day 17 for the 
Test, Reference, and Vehicle products, respectively.  The tests will be conducted independently for 
the Test product and the Reference product using two-sided, α = 0.05, continuity-corrected Z-tests. 
Superiority would be established if the proportion of subjects with clinical cure at the Visit 4/Day17 
in the active treatment group is significantly greater (p < 0.05) than that in the Vehicle group. 
Rejection of the null hypothesis would support the conclusion of superiority of the Test and 
Reference products over the Vehicle for the primary efficacy variable. 
 
Superiority analyses in the mITT population will be considered definitive and those in the PP 
population will be 
considered supportive. 
 
The same tests/methods, including the missing data imputation methods, as for the primary analyses 
will be conducted for the secondary analyses.  
 
Safety and Adverse Events Analysis 
The frequency and percent of subjects with adverse events will be summarized by MedDRA system 
organ class and preferred term and by severity and relationship to study drug for all three treatment 
groups.  
 
.  The comparable safety of the Test and Reference treatments will be evaluated 
by statistical comparison of the proportion of subjects who reported any adverse events.  Safety 
comparisons will be performed on the ITT (safety) population. 
 
8.2 
Comparability of Subjects at Baseline 
Descriptive statistics will be presented, by treatment group, for subject baseline characteristics. The 
significance of any obvious treatment group differences will be discussed in the clinical study report. 
 
9. 
CONSENT/ASSENT CONSIDERATIONS AND PROCEDURES 
It will be made clear to the subject that, for the purposes of the study, they are consenting only for 
topical application of medication or vehicle.  Investigators may discuss the availability of the study 
and the possibility for entry with a potential subject without first obtaining consent/assent.  
However, informed consent/assent must be obtained and documented prior to initiation of any 
procedures that are performed solely for the purpose of determining eligibility for research, 
including withdrawal from current medication(s).  When this is done in anticipation of, or in 
preparation for, the research, it is considered to be part of the research. 
 
The study must be approved in writing by an appropriate IRB as defined by FDA regulations. A copy 
of the Letter of Approval from the IRB, which also contains specific identification of the documents 
approved, must be received by Perrigo, prior to study commencement. 


Protocol No: PRG-NY-19-002 
 
Page 36 of 45 
 
 
 
Periodic status reports must be submitted to the IRB at least annually as required by the site’s IRB, 
as well as notification of completion of the study and a final report within three months of study 
completion or termination.  
 
The investigator(s) has both ethical and legal responsibility to ensure that each subject being 
considered for inclusion in this study is given a full explanation of the protocol.  This shall be 
documented on a written informed consent/assent form, which shall be approved by the same IRB 
responsible for approval of this protocol.  Each informed consent/assent form shall include the 
elements required by FDA regulations in 21 CFR Part 50. The investigator agrees to obtain approval 
from Perrigo of any written informed consent/assent form used in the study, preferably prior to 
submission to the IRB. 
 
Once the appropriate essential information has been provided to the subject and fully explained by 
the investigators (or a qualified designee) and it is felt that the subject understands the implications 
of participating, the IRB-approved written informed consent/assent form shall be signed by the 
subject (or their parent/legally authorized representative) and the person obtaining consent/assent 
(investigator or designee).  The subject shall be given a copy of the signed informed consent/assent 
form and the investigator shall keep the original on file. 
 
If the subject fails to meet the inclusion/exclusion criteria at the conclusion of the screening phase, 
the subject will be withdrawn from screening.  If the subject is re-screened for study participation, a 
new informed consent/assent form must be signed. 
 
9.1 
Subject Confidentiality 
All participants are concerned for the individual subject’s privacy and, therefore, all subject data will 
be identified only by a subject identification number and subject initials.  However, in compliance 
with federal guidelines regarding the monitoring of clinical studies and in fulfillment of his/her 
obligations to Perrigo, it is required that the investigator permit the study monitor, any Perrigo 
authorized representative, and/or FDA representative to review that portion of the subject’s medical 
record that is directly related to the study.  This shall include all study-relevant documentation 
including subject medical histories to verify eligibility, laboratory test result reports to verify 
transcription accuracy, admission/discharge summaries for hospital stays occurring while the subject 
is enrolled in the study, and autopsy reports for deaths occurring during the study. 
 
As part of the required content of informed consent, the subject must be informed that his/her 
medical chart may be reviewed by Perrigo or their authorized representative, or a representative of 
the FDA.  If access to the medical record requires a separate waiver or authorization, it is the 
investigator’s responsibility to obtain such permission from the subject in writing before the subject 
is entered into the study. 
 
To preserve the subject's confidentiality, the data collected will be available only to the investigators 
of the study, their support staff, Perrigo or their authorized representative and possibly the FDA. 
 


Protocol No: PRG-NY-19-002 
 
Page 37 of 45 
 
 
All reports and communications relating to the subject in the study will identify each subject only by 
the subject’s initials and by the subject number.  The investigator agrees to furnish Perrigo with 
complete subject identification, if necessary, on a confidential follow-up form that will be used for 
the purpose of a long-term follow-up, if needed.  This will be treated with strict adherence to 
professional standards of confidentiality and will be filed at Perrigo under adequate security and 
restricted accessibility. 
 
10. 
CONDUCT OF STUDY 
The investigational site is to maintain complete documentation of all events and the times at which 
they occur. 
 
10.1 
Completion of Study 
The investigational site will complete the study and complete all documentation required, in 
satisfactory compliance with the protocol, within 2.5 months of enrollment of the last subject and 
extending beyond as needed to complete necessary data queries. 
 
It is agreed that, for reasonable cause, either the investigator or Perrigo may terminate this study 
before completion provided written notice is submitted at a reasonable time in advance of intended 
termination.  Any extension of this study must be mutually agreed upon in writing by both the 
investigator and Perrigo. 
 
10.2 
Protocol Amendments 
The investigator will not make any changes to this protocol without prior written consent from 
Perrigo and subsequent approval by the IRB.  Any permanent change to the protocol, whether it is 
an overall change or a change for specific study center(s), must be handled as a protocol amendment. 
Any amendment to the protocol that appears indicated as the study progresses will be fully discussed 
between 
 and Perrigo.  If agreement is reached regarding the need for an amendment, 
the amendment will be written by Perrigo or 
.  The written amendment must be submitted 
to the chairman of the IRB identified with this responsibility.  Except for “administrative 
amendments,” investigators must await IRB approval of protocol amendments before implementing 
the change(s).  Administrative amendments are defined to have no effect on the safety of the 
research subjects, scope of the investigation, or quality of the trial. However, a protocol change 
intended to eliminate an apparent immediate hazard to subjects should be implemented 
immediately, and the IRB notified within five days. Perrigo will submit protocol amendments to the 
FDA or other regulatory agencies. 
 
When, in the judgment of the reviewing IRB, the investigators and/or Perrigo, the amendment to the 
protocol substantially alters the study design and/or increases the potential risk to the subject, the 
currently approved written informed consent form will require similar modification.  In such cases, 
repeat informed consent will be obtained from subjects enrolled in the study before expecting 
continued participation. 
 
11. 
RECORDS MANAGEMENT 
 


Protocol No: PRG-NY-19-002 
 
Page 38 of 45 
 
 
11.1 
Data Collection 
 
Database set-up will be performed by 
 in collaboration with the Electronic Data Capture (EDC) 
vendor, using an appropriate fully validated, 21 CFR Part 11 compliant EDC system. eCRFs will be 
provided to each site via a secured web link.  All applicable study data collected on each subject will 
be recorded by approved site personnel into the eCRF.  Only authorized site personnel will be able 
to enter/modify/correct data to the eCRF. 
 
Approved staff at 
 will verify all data entered into eCRFs for completeness and accuracy with 
reference to the source documents and records and will issue manual data queries to correct missing 
data or discrepancies found against the source within the EDC system. 
 
Data validation will consist of automated and manual edit checks that are created directly into EDC. 
Automated edit checks will be executed on all data points defined and documented by the study 
team and data management.  Study metrics will be reported from the EDC system. 
 
After all data have been verified by approved staff at 
, an investigator or sub-investigator 
(listed on Form FDA 1572) is required to review and approve all eCRFs prior to database lock and 
breaking of the blind.  
 
 
 
 
 
 
 
During each subject’s visit to the clinic, a designee participating in the study will record progress 
notes to document all significant observations.  At a minimum, these notes will contain: 
 
a) Documentation of the informed consent process; 
b) The date of the visit and the corresponding Visit or Week in the study schedule; 
c) General subject status remarks, including any significant medical findings. The severity, 
frequency, and duration of any adverse events and the investigator's assessment of 
relationship to study medication must also be recorded. 
d) Any changes in concomitant medications or dosages; 
e) A general reference to the procedures completed; and 
f) The signature (or initials) and date of all clinicians who made an entry in the progress notes. 
 
In addition, any contact with the subject via telephone or other means that provides significant 
clinical information will also be documented in the progress notes as described above. 
 
Any changes to information in the study progress notes and other source documents will be entered 
in black or blue ink, initialed, and dated by the authorized person making the correction/addition. 
Changes will be made by striking a single line through erroneous data, and clearly entering the 


Protocol No: PRG-NY-19-002 
 
Page 39 of 45 
 
 
correct data (e.g., wrong data right data).  Entries may not be erased or masked with white-out fluid. 
If the reason for the change is not apparent, a brief explanation for the change will be written 
adjacent to the change by the clinician. 
 
For transmission to Perrigo, information from the study progress notes and other source documents 
will be promptly entered into the database.  The database also contains a complete audit trail to 
capture all regulatory components of data corrections (e.g. initial entry, new value, initials and date 
of the change). 
 
11.2 
Source Documents 
Source documents are defined as the results of original observations and activities of a clinical 
investigation. Source documents will include, but are not limited to, progress notes and screening 
logs.  All source documents pertaining to this study will be maintained by the investigators and made 
available for inspection by authorized persons.  The original signed informed consent form for each 
participating subject shall be filed with records kept by the investigators and a copy given to the 
subject. 
 
11.3 
File Management at the Study Site 
It is the responsibility of the investigator to ensure that the study center file is maintained in 
accordance with Section 8 of the International Council for Harmonization (ICH) Guideline for Good 
Clinical Practices (GCP). 
 
11.4 
Records Retention at the Study Site 
FDA regulations 21 CFR§312.57 require all investigators participating in clinical drug studies to 
maintain detailed clinical data for one of the following periods: 
 
a) A period of at least two years following the date on which a New Drug Application is approved 
by the FDA; 
b) A period of two years after Perrigo notifies the investigator that no further application is to 
be filed with the FDA. 
 
The investigator must not dispose of any records relevant to this study without either (1) written 
permission from Perrigo or (2) providing an opportunity for Perrigo to collect such records.  The 
investigator shall take responsibility for maintaining adequate and accurate electronic or hard copy 
source documents of all observations and data generated during this study. Such documentation is 
subject to inspection by Perrigo and the FDA. 
 
12. 
QUALITY CONTROL AND QUALITY ASSURANCE 
 
12.1 
Monitoring 
Perrigo has ethical, legal, and scientific obligations to carefully follow this study in a detailed and 
orderly manner in accordance with established research principles and FDA regulations.  All medical 
records (source documents) of the subjects participating in this study must be presented for review 
and verification of eCRFs. 


Protocol No: PRG-NY-19-002 
 
Page 40 of 45 
 
 
 
12.2 
Auditing 
Perrigo (or representative) may conduct audits at the study center(s).  Audits will include, but are 
not limited to, drug supply, presence of required documents, the informed consent process, and 
comparison of electronic case report forms with source documents.  The investigator agrees to 
participate with audits conducted at a reasonable time in a reasonable manner. 
 
Regulatory authorities worldwide may also audit the investigator during or after the study.  The 
investigator should contact Perrigo or 
 immediately if notified of such an audit, and must fully 
cooperate with the audits conducted at a reasonable time in a reasonable manner. 
 
13. 
ETHICS AND RESPONSIBILITY 
This study must be conducted in compliance with the protocol, the United States Food and Drug 
Administration (FDA) regulations, any other countries regulations, and ICH GCP Guidelines. 
 
14. 
USE OF INFORMATION AND PUBLICATION 
All information supplied by Perrigo in connection with this study and not previously published, is 
considered confidential information. This information includes, but is not limited to, data, materials 
(e.g., the clinical protocol, eCRFs), equipment, experience (whether of a scientific, technical, 
engineering, operational, or commercial nature), designs, specifications, know-how, product uses, 
processes, formulae, costs, financial data, marketing plans and direct selling systems, customer lists 
and technical and commercial information relating to customers or business projections used by 
Perrigo in its business.  Any data, inventions, or discoveries collected or developed, as a result of this 
study is considered confidential.  This confidential information shall remain the sole property of 
Perrigo, shall not be disclosed to any unauthorized person or used in any unauthorized manner 
without written consent of Perrigo, and shall not be used except in the performance of the study.  As 
such, confidential study-related information should not be included on the curriculum vitae of any 
participating investigator or study staff. 
 
The information developed during the course of this clinical study is also considered confidential, 
and will be used by Perrigo in connection with the development of the drug.  The information may 
be disclosed as deemed necessary by Perrigo to allow the use of the information derived from this 
clinical study, the investigator is obliged to provide Perrigo with complete test results and all data 
developed in the study.  The information obtained during this study may be made available to other 
investigators who are conducting similar studies. 
 
The investigator shall not make any publication related to this study without the express written 
permission of Perrigo.  
 
 
 
 
 


Protocol No: PRG-NY-19-002 
 
Page 41 of 45 
 
 
INVESTIGATOR AGREEMENT 
 
PROTOCOL NUMBER:  PRG-NY-19-002 
 
PROTOCOL TITLE: 
 
 
A Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Parallel-
Group Study to Compare Perrigo UK FINCO Limited Partnership’s Mupirocin 
Cream USP, 2% to Glenmark Pharmaceuticals Mupirocin Cream USP, 2% and 
to Compare Both Active Treatments to a Vehicle Control in the Treatment of 
Secondarily Infected Traumatic Skin Lesions 
 
 
I have carefully read the foregoing protocol and agree that it contains all the necessary information 
for conducting this study safely. I will conduct this study in strict accordance with this protocol, ICH 
Guidelines for Good Clinical Practices, the Code of Federal Regulations, the Health Insurance 
Portability and Accountability Act (HIPAA) and any local regulatory requirements and will attempt to 
complete the study within the time designated. I will provide access to copies of the protocol and all 
other information relating to pre-clinical and prior clinical experience submitted by Perrigo to all 
personnel responsible to me who participate in the study. I will discuss this information with them 
to assure that they are adequately informed regarding the drug and conduct of the study. I agree to 
keep records on all subject information in accordance with FDA regulations. 
 
 
 
 
 
 
 
 
   Principal Investigator’s Printed Name 
 
 
 
 
 
 
 
 
   Principal Investigator’s Signature 
 
 
 
 
 
 
 
   Date 


Protocol No: PRG-NY-19-002 
 
Page 42 of 45 
 
 
15. 
APPENDICES 
 
15.1 
Appendix A: Study Personnel Contacts 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No: PRG-NY-19-002 
 
Page 43 of 45 
 
 
15.2 
Appendix B: Instructions for the Subject 
 
Check Visit Dispensed: Visit 1:  
      Visit 2:  
        Unscheduled visit:  
   Date: ________ 
 
SUBJECT INITIALS: ___________    SUBJECT NUMBER: ________________ SITE NUMBER: ________ 
 
• 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• 
 
 
 
I am scheduled to return at: 
 
_______________on _________________   During Treatment (Study Day 2-5) 
(Time)     
          (Date) 
 
_______________on _________________   End of Treatment (Study Day 10-12) 
(Time)    
          (Date) 
 
Stop applying study medication on ______________________ 
 
_______________on _________________   Follow-up (Study Day 13-21) 
(Time)    
         (Date) 
 


Protocol No: PRG-NY-19-002 
 
Page 44 of 45 
 
 
ALL APPOINTMENTS ARE IMPORTANT!  IF YOU NEED TO CHANGE YOUR APPOINTMENT, PLEASE CALL YOUR 
STUDY DOCTOR’S OFFICE 
15.3 
 
 
 
 
 
 
 


Protocol No: PRG-NY-19-002 
 
Page 45 of 45 
 
 
 
 
16. 
REFERENCES 
 
1. Mupirocin Cream USP, 2% Cream [package insert]. Glenmark Pharmaceuticals; 7/2017. 
2. OGD Draft Guidance on Mupirocin Calcium (Cream/Topical). Recommended June 2010; 
Revised Oct 2011. 

SAP_001.pdf: 
 
 
NCT04155203 
 
02-24-2021 




Perrigo New York Inc.                                                                                                                  Protocol: PRG-NY-19-002 
 
 
 
       
 
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Table of Contents 
1 
Purpose of Statistical Analysis Plan ........................................................................................................ 4 
2 
Study Objectives ....................................................................................................................................... 4 
3 
Study Design and Sample Size ................................................................................................................ 4 
3.1 
Study Design ..................................................................................................................................................... 4 
3.2 
Sample Size ....................................................................................................................................................... 5 
4 
Analysis Populations ................................................................................................................................ 5 
5 
Planned Analyses ...................................................................................................................................... 6 
5.1 
Methodological Considerations ........................................................................................................................ 6 
5.2 
Handling of Dropouts or Missing Data ............................................................................................................. 7 
5.3 
Demographics and Baseline Characteristics ..................................................................................................... 7 
5.4 
Subject Disposition ........................................................................................................................................... 7 
5.5 
Protocol Deviations ........................................................................................................................................... 7 
5.6 
Study Drug Exposure and Compliance ............................................................................................................. 8 
5.7 
Efficacy Variables and Analyses ...................................................................................................................... 9 
5.7.1 
Primary Endpoint ................................................................................................................................. 9 
5.7.2 
Secondary Endpoints .......................................................................................................................... 10 
5.8 
Safety Variables and Analyses ........................................................................................................................ 10 
6 
Appendices .............................................................................................................................................. 11 
6.1 
Handling of Missing or Incomplete Dates for Adverse Events and Concomitant Medications ...................... 11 
6.2 
Summary of Assessments ............................................................................................................................... 11 
7 
Tables and Listings ................................................................................................................................. 13 
Table 14.1.1 - Subject Final Study Disposition ....................................................................................................... 15 
Table 14.1.2 - Subject Population (General) ........................................................................................................... 16 
Table 14.1.3 - Subject Enrollment by Study Site .................................................................................................... 17 
Table 14.1.4.1 - Demographic Characteristics for Intent-to-Treat Population ........................................................ 18 
Table 14.1.4.2 - Demographic Characteristics for Modified Intent-to-Treat Population ........................................ 19 
Table 14.1.4.3 - Demographic Characteristics for Per-Protocol Population ........................................................... 19 
Table 14.1.5.1- Baseline Vital Signs for Intent-to-Treat Population ....................................................................... 20 
Table 14.1.5.2- Baseline Vital Signs for Modified Intent-to-Treat Population ....................................................... 21 
Table 14.1.5.3- Baseline Vital Signs for Per-Protocol Population .......................................................................... 21 
Table 14.1.6.1 – Culture Result and Subject’s Skin Infection Rating Scale (SIRS) at Baseline for Modified Intent-
to-Treat Population .............................................................................................................................................. 22 
Table 14.1.6.2 - Culture Result and Subject’s Skin Infection Rating Scale (SIRS) at Baseline for Per-Protocol 
Population ............................................................................................................................................................ 24 
Table 14.2.1- Primary Efficacy Analysis: Proportion of Subjects with Clinical Cure at Visit 4/Day 18/Follow-up
 ............................................................................................................................................................................. 25 
Table 14.2.2.1- Secondary Efficacy Analysis: Proportion of Subjects with Clinical Cure at Visit 3/Day 11/End of 
Treatment ............................................................................................................................................................ 26 


Perrigo New York Inc.                                                                                                                  Protocol: PRG-NY-19-002 
 
 
 
       
 
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Table 14.2.2.2- Secondary Efficacy Analysis: Proportion of Subjects with Bacteriological Cure at Visit 4/Day 
18/Follow-up ....................................................................................................................................................... 27 
Table 14.2.2.3- Secondary Efficacy Analysis: Proportion of Subjects with Bacteriological Cure at Visit 3/Day 
11/End of Treatment ............................................................................................................................................ 28 
Table 14.3.1 – Days of Exposure and Medication Compliance Rate for Intent-to-Treat Population ...................... 29 
Table 14.3.2.1 - Overall Summary of Treatment Emergent Adverse Events (TEAEs) for Intent-to-Treat 
Population ............................................................................................................................................................ 30 
Table 14.3.2.2- Summary of Treatment-Emergent Adverse Events (TEAEs) by MedDRA System Organ Class 
and Preferred Term for Intent-to-Treat Population .............................................................................................. 31 
Table 14.3.2.3 – Summary of Treatment-Emergent Adverse Events (TEAEs) by MedDRA System Organ Class, 
Preferred Term, and Severity for Intent-to-Treat Population .............................................................................. 32 
Table 14.3.2.4- Summary of Treatment-Emergent Adverse Events (TEAEs) by MedDRA System Organ Class, 
Preferred Term, and Relationship to Study Medication for Intent-to-Treat Population ...................................... 33 
Table 14.3.2.5 – Common Treatment-Emergent Adverse Events (TEAEs) by MedDRA Preferred Term for Intent-
to-Treat Population .............................................................................................................................................. 34 
Subject Listings ............................................................................................................................................... 35 
Listing 16.2.1.1 – Subject Analysis Status .............................................................................................................. 36 
Listing 16.2.1.2 – Subject End-of-Study Status ...................................................................................................... 37 
Listing 16.2.1.3 – Dates of Visits ............................................................................................................................ 38 
Listing 16.2.2.1 – Protocol Violations and Protocol Deviations ............................................................................. 39 
Listing 16.2.2.2 – Comments .................................................................................................................................. 40 
Listing 16.2.2.3 - Inclusion/Exclusion Criteria ....................................................................................................... 41 
Listing 16.2.3 – Subjects Excluded from Efficacy Analyses .................................................................................. 42 
Listing 16.2.4.1 – Demographics and Informed Consent at Baseline ..................................................................... 43 
Listing 16.2.4.2 – Dermatological Exam and Target Lesion Diagnosis at Baseline ............................................... 44 
Listing 16.2.4.3 – Brief Physical Examination at Baseline ..................................................................................... 45 
Listing 16.2.4.4 – Subject Medical History ............................................................................................................. 46 
Listing 16.2.4.5 – Previous or Concomitant Medications ....................................................................................... 47 
Listing 16.2.4.6 – Vital Signs .................................................................................................................................. 48 
Listing 16.2.5.1 – Study Medication and Diary Card Dispensing at Visit 1/Baseline ............................................ 49 
Listing 16.2.5.2 – Study Medication and Diary Card Dispensing at Post-Baseline Visits ...................................... 50 
Listing 16.2.5.3 – Subject Compliance at Post-Baseline Visits .............................................................................. 51 
Listing 16.2.5.4 – Diary and IP Collection and Rescue Therapy at End of Study .................................................. 52 
Listing 16.2.5.5 – Treatment Record at End of Study ............................................................................................. 53 
Listing 16.2.5.6 – Study Medication Reconciliation ............................................................................................... 54 
Listing 16.2.6.1 – Clinical Evaluation ..................................................................................................................... 55 
Listing 16.2.6.2 – Bacteriology Specimen Collection and Results ......................................................................... 56 
Listing 16.2.6.3 – Derived (LOCF Applied) Primary and Secondary Efficacy Data for Per-Protocol Population . 57 
Listing 16.2.6.4 – Derived (LOCF Applied) Primary and Secondary Efficacy Data for Modified Intent-to-Treat 
Population ............................................................................................................................................................ 57 
Listing 16.2.7.1 – Adverse Events .......................................................................................................................... 58 
Listing 16.2.7.2 – Adverse Events Leading to Study Treatment Interruption Temporarily/ Study Treatment 
Discontinued Permanently ................................................................................................................................... 58 
Listing 16.2.7.3 – Serious Adverse Events.............................................................................................................. 58 
Listing 16.2.8 – Urine Pregnancy Tests (Female Subjects Only) ............................................................................ 59 
Listing 16.2.9.1 – COVID-19 Impact by Visit ........................................................................................................ 60 
Listing 16.2.9.2 – COVID-19 Impact by Assessment ............................................................................................. 61 


Perrigo New York Inc.                                                                                                                  Protocol: PRG-NY-19-002 
 
 
 
       
 
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List of Abbreviations  
AE 
Adverse Event 
ANOVA 
Analysis of Variance 
CI 
Confidence Interval 
CMH 
Cochran–Mantel–Haenszel Test 
ITT 
Intent-to-Treat (Population) 
LOCF 
Last Observation Carried Forward 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
Modified Intent-to-Treat (Population) 
PD 
Protocol Deviation 
PP 
Per-Protocol (Population) 
PV 
Protocol Violation 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan  
S. aureus 
Staphylococcus aureus 
SIRS 
Skin Infection Rating Scale 
S. pyogenes 
Streptococcus pyogenes 
TEAE 
Treatment-Emergent Adverse Event 
TESAE 
Treatment-Emergent Serious Adverse Event 
WHO Drug 
World Health Organization Drug Dictionary 
 
 
 
 
 
 
 












Perrigo New York Inc.                                                                                                                  Protocol: PRG-NY-19-002 
 
 
 
       
 
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5.7 
Efficacy Variables and Analyses 
5.7.1 Primary Endpoint 
The primary efficacy endpoint is the proportion of subjects in each treatment group with clinical 
cure, defined as a SIRS score of 0 for all signs and symptoms at Visit 4/Follow-up (7 days after 
the end of treatment). 
Equivalent Efficacy 
The compound hypothesis to be tested for clinical equivalence between test and reference is:  
H0: pT- pR < -0.20 or pT- pR > 0.20 versus 
HA: -0.20 ≤ pT- pR ≤ 0.20.  
Where pT and pR are the proportions of subjects with clinical cure at Visit 4/Follow-up for the 
test and reference products, respectively. The test product will be considered to be 
therapeutically equivalent to the reference product if the 90% CI on the difference in their 
proportions of subjects with clinical cure, calculated by Wald’s method with Yates’ continuity 
correction, is contained within the limits -0.20 to +0.20. Rejection of the null hypothesis 
supports the conclusion of therapeutic equivalence between the test and reference products for 
the primary efficacy variable.  
The result of the analysis in the PP population will be considered definitive and that in the mITT 
population as supportive. 
Analysis for therapeutic equivalence (i.e. 90% confidence interval) will be performed based on 
the following SAS code (SAS Institute v.9.4) e.g. trt=1 for Test and trt=2 for Reference: 
proc freq data=XX; 
  where trt in (1,2);  
   tables trt* cure /alpha=0.10 riskdiff (CORRECT CL=(WALD));  
run; 
Superiority 
The hypotheses to be tested for superiority of the test and reference products over Vehicle are:  
H0: pT ≤ pV versus HA: pT > pV  
H0: pR ≤ pV versus HA: pR > pV 
Where pT, pR and pV are the proportions of subjects with clinical cure at Visit 4/Follow-up for 
the test, reference and Vehicle products, respectively. The tests will be conducted independently 
for the test product vs. vehicle and the reference product vs. vehicle using two-sided, α = 0.05, 


Perrigo New York Inc.                                                                                                                  Protocol: PRG-NY-19-002 
 
 
 
       
 
10 
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continuity-corrected Z-tests. Superiority will be established if the proportion of subjects with 
clinical cure in the active treatment group is greater than and statistically different (p< 0.05) 
from that in the Vehicle. Rejection of the null hypothesis supports the conclusion of superiority 
of the test and reference products over the Vehicle product for the primary efficacy variable. 
The analyses in the mITT population will be considered definitive and those in the PP population 
as supportive.  
Analysis for superiority (continuity-corrected p-value for treatment comparison) will be 
performed based on the following SAS code (SAS Institute v.9.4) e.g. trt=2 for Reference vs. 
trt=3 for Vehicle: 
proc freq data=XX ; 
where trt in (2,3); 
table trt * cure /chisq ;                                                                                                                         
run; 
5.7.2 Secondary Endpoints  
Secondary efficacy endpoints are: 
- 
 the proportion of subjects with clinical cure at Visit 3/End of Treatment; 
- 
the proportion of subjects with bacteriological cure (defined as elimination of S. aureus and 
S. pyogenes or response was such that no culture material was available and therefore 
evidence of pathogen eradication) at Visit 3/End of Treatment; 
- 
the proportion of subjects with bacteriological cure at Visit 4/Follow-up.    
The same tests/methods, including the missing data imputation methods, as for the primary 
analyses will be conducted for the secondary analyses. 
5.8 
Safety Variables and Analyses 
All safety data will be listed and tabulated. The analysis will be performed on the safety/ITT 
population. Safety parameters include adverse events, vital signs and concomitant  
medications. 
Adverse Events 
Adverse events (AEs) will be coded in MedDRA, version 22.0. Treatment-Emergent Adverse 
Event (TEAE) is defined as any AE occurs on or after application of the first dose of study drug. 
Number and percent of subjects reporting TEAEs will be tabulated by treatment group. 
Summary of TEAEs will be presented by body system and preferred term for the ITT population, 
and further by severity and relationship to study medication. Most common TEAEs will include 
those reported by 5% or more subjects for any treatment group will be summarized by preferred 
term. In the summaries of incidence rates (frequencies and percentages), severity and 
relationship to study drug, subjects who report more than one event that are mapped to the same 
preferred term will be counted only once under the strongest severity and relationship, 
accordingly. The difference between Test and Reference treatments with regard to severity and 


Perrigo New York Inc.                                                                                                                  Protocol: PRG-NY-19-002 
 
 
 
       
 
11 
CONFIDENTIAL 
frequency of their dermatological adverse events will be statistically evaluated using Chi-Square 
or Fisher’s exact test to compare the proportions of subjects of the two active treatment groups 
who report any TEAE. 
Treatment-Emergent Serious Adverse Events (TESAEs) will be discussed within the clinical 
study report. TEAEs, TESAEs and TEAEs that led to treatment interruption temporarily or 
treatment discontinued permanently will be presented in data listings. 
Concomitant Medications and Vitals Signs 
Concomitant medications will be coded using the WHO Drug Dictionary, version March 2019, 
and will be presented in data listings. All vital signs data will be displayed in listings. 
6 
Appendices 
6.1 
Handling of Missing or Incomplete Dates for Adverse Events and Concomitant 
Medications 
Adverse Events 
Handling of partial dates is only considered for the start date. An adverse event with a partial 
start date is considered treatment emergent if: 
- 
only the day is missing and the start month/year is the same or after the month/year of 
the first dose 
- 
the day and month are missing and the start year is the same or greater than the year of 
the first dose date 
- 
the start date is completely missing 
Concomitant Medications 
Handling of partial dates is only considered for the stop date. A medication with a partial stop 
date is considered concomitant if: 
- 
only the day is missing and the stop month/year is the same or after the month/year of 
the first dose 
- 
the day and month are missing and the stop year is the same or greater than the year of 
the first dose date 
- 
the stop date is completely missing or the medication is ongoing 
6.2 
Summary of Assessments 
The schedule of visits and procedures to be conducted at each visit are summarized in the 
Schedule of Study Procedures.