Clinical trial NCT03304873
Conditions: MRSA
Keywords: rectal MRSA mupirocin-resistant nasal MRSA
Sponsor: NYU Langone Health
Start date: 2017-12-01; Completion date: 2019-03-18
Enrollment: 47 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to investigate the efficacy of retapamulin to reduce carriage of MRSA via a randomized, double-blind, placebo-controlled clinical study testing retapamulin among patients with confirmed mupirocin-resistant nasal and/or rectal MRSA colonization. The sample size will include 27 subjects in each of the two arms of the study (retapamulin versus placebo) for a total of 54 subjects. Participants who are found to be nasal and/or rectal colonized with MRSA will be randomized to receive either retapamulin or placebo applied nasally and rectally for a total of 5 days. Nasal and rectal swabs will be collected at pre-defined time points during study duration (screening swab, swab one week after completion of topical therapy, swab 4 weeks after completion of topical therapy) to assess MRSA colonization status. The colonization rates of both groups will be assessed via Fisher's Exact Test.

Detailed description:

Arms: arm 1: Thin layer of ointment applied twice a day for five days. Study drug will be applied to the nares and peri-rectal area twice a day for 5 consecutive days. arm 2: The placebo used will be a triple purified pharmaceutical grade white petrolatum
Interventions: intervention 1: Retapamulin intervention 2: Placebo Ointment
Intervention descriptions: intervention 1: Retapamulin is a topical antibiotic ointment. The ingredients include retapamulin and white petrolatum as the vehicle. The composition is 10mg retapamulin per 1g of ointment (1%). intervention 2: The placebo that will be used is triple-purified pharmaceutical-grade petrolatum.

Protocol documents:
Prot_SAP_000.pdf: 
 
 
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A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL 
OF THE EFFICACY OF RETAPAMULIN AS A TOPICAL 
DECOLONIZING AGENT FOR MUPIROCIN-RESISTANT METHICILLIN-
RESISTANT STAPHYLOCOCCUS AUREUS (MRSA)  
 
Principal Investigator: 
 
Jennifer Lighter, MD 
Pediatric Infectious Diseases 
NYU School of Medicine 
545 First Avenue 
Greenberg Hall, SC1-174 
New York, NY 10016 
Jennifer.Lighter@nyumc.org  
212-263-5454 
Additional Investigators: 
 
Ami Patel, MD, MPH 
Pediatric Infectious Diseases 
NYU School of Medicine 
545 First Avenue 
Greenberg Hall, SC1-174 
New York, NY 10016 
Ami.Patel@nyumc.org  
718-612-1408 
NYULMC Study Number: 
S17-00907 
NCT 
NCT03304873 
Funding Sponsor: 
Aqua Pharmaceuticals 
707 Eagleview Blvd 
Exton PA, 19341 
610-644-7000 
IND/IDE Number: 
Not applicable (Exempt) 
Regulatory Sponsor:  
Not applicable  
Study Product: 
Retapamulin (Altabax) 
Study Product Provider:  
Aqua Pharmaceuticals 
ClinicalTrials.gov 
Number                 
NCT03304873  
 
Initial version: 09/26/2017 
Amended: 
[10/24/2017] 
Amended: 
[01/07/2018] 
Amended: 
[05/03/2018] 
Amended:  
[06/20/2018] 
 


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Statement of Compliance 
 
This study will be conducted in accordance with the Code of Federal Regulations on the Protection of 
Human Subjects (45 CFR Part 46), 21 CFR Parts 50, 56, 312, and 812 as applicable, any other applicable 
US government research regulations, and institutional research policies and procedures. The International 
Conference on Harmonisation (“ICH”) Guideline for Good Clinical Practice (“GCP”) (sometimes referred to 
as “ICH-GCP” or “E6”) will be applied only to the extent that it is compatible with FDA and DHHS regulations. 
The Principal Investigator will assure that no deviation from, or changes to the protocol will take place 
without prior agreement from the sponsor and documented approval from the Institutional Review Board 
(IRB), except where necessary to eliminate an immediate hazard(s) to the trial participants. All personnel 
involved in the conduct of this study have completed Human Subjects Protection Training.  
 
 


Study number: s17-00907 
 
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Table of Contents 
STATEMENT OF COMPLIANCE ................................................................................................................. II 
LIST OF ABBREVIATIONS......................................................................................................................... VI 
PROTOCOL SUMMARY .............................................................................................................................. 1 
SCHEMATIC OF STUDY DESIGN ............................................................................................................... 2 
1 
KEY ROLES ......................................................................................................................................... 3 
2 
INTRODUCTION, BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE ....................... 4 
2.1 
BACKGROUND INFORMATION AND RELEVANT LITERATURE ................................................................ 4 
2.2 
NAME AND DESCRIPTION OF THE INVESTIGATIONAL AGENT .............................................................. 5 
2.2.1 
Preclinical Data........................................................................................................................ 6 
2.2.2 
Clinical Data to Date ................................................................................................................ 6 
2.2.3 
Dose Rationale (if applicable) ................................................................................................. 6 
2.3 
RATIONALE .................................................................................................................................... 6 
2.4 
POTENTIAL RISKS & BENEFITS ........................................................................................................ 7 
2.4.1 
Known Potential Risks ............................................................................................................. 7 
2.4.2 
Known Potential Benefits ........................................................................................................ 7 
3 
OBJECTIVES AND PURPOSE ........................................................................................................... 7 
3.1 
PRIMARY OBJECTIVE ...................................................................................................................... 7 
3.2 
SECONDARY OBJECTIVES (IF APPLICABLE) ...................................................................................... 7 
4 
STUDY DESIGN AND ENDPOINTS .................................................................................................... 8 
4.1 
DESCRIPTION OF STUDY DESIGN .................................................................................................... 8 
4.2 
STUDY ENDPOINTS......................................................................................................................... 8 
4.2.1 
Primary Study Endpoints ......................................................................................................... 8 
4.2.2 
Secondary Study Endpoints .................................................................................................... 8 
4.2.3 
Exploratory Endpoints ............................................................................................................. 8 
5 
STUDY ENROLLMENT AND WITHDRAWAL .................................................................................... 9 
5.1 
INCLUSION CRITERIA ...................................................................................................................... 9 
5.2 
EXCLUSION CRITERIA ..................................................................................................................... 9 
5.3 
VULNERABLE SUBJECTS ................................................................................................................. 9 
5.4 
STRATEGIES FOR RECRUITMENT AND RETENTION ............................................................................ 9 
5.4.1 
Use of DataCore/Epic Information for Recruitment Purposes .............................................. 10 
5.5 
DURATION OF STUDY PARTICIPATION ............................................................................................ 10 
5.6 
TOTAL NUMBER OF PARTICIPANTS AND SITES ................................................................................ 10 
5.7 
PARTICIPANT WITHDRAWAL OR TERMINATION ................................................................................ 10 
5.7.1 
Reasons for Withdrawal or Termination ................................................................................ 10 
5.7.2 
Handling of Participant Withdrawals or Termination ............................................................. 10 
5.8 
PREMATURE TERMINATION OR SUSPENSION OF STUDY .................................................................. 11 
6 
STUDY AGENT (STUDY DRUG, DEVICE, BIOLOGIC, VACCINE ETC.) AND/OR PROCEDURAL 
INTERVENTION ......................................................................................................................................... 11 
6.1 
STUDY AGENT(S) AND CONTROL DESCRIPTION .............................................................................. 11 
6.1.1 
Acquisition ............................................................................................................................. 12 
6.1.2 
Formulation, Appearance, Packaging, and Labeling ............................................................ 12 
6.1.3 
Product Storage and Stability ................................................................................................ 12 
6.1.4 
Preparation ............................................................................................................................ 12 
6.1.5 
Dosing and Administration .................................................................................................... 12 
6.1.6 
Route of Administration ......................................................................................................... 12 
6.1.7 
Starting Dose and Dose Escalation Schedule ...................................................................... 12 
6.1.8 
Dose Adjustments/Modifications/Delays ............................................................................... 12 


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6.1.9 
Duration of Therapy ............................................................................................................... 13 
6.1.10 
Tracking of Dose ............................................................................................................... 13 
6.1.11 
Device Specific Considerations ........................................................................................ 13 
6.2 
STUDY AGENT ACCOUNTABILITY PROCEDURES ............................................................................. 13 
7 
STUDY PROCEDURES AND SCHEDULE ....................................................................................... 13 
7.1 
STUDY PROCEDURES/EVALUATIONS ............................................................................................. 13 
7.1.1 
Study Specific Procedures .................................................................................................... 13 
7.1.2 
Standard of Care Study Procedures ..................................................................................... 14 
7.2 
LABORATORY PROCEDURES/EVALUATIONS ................................................................................... 14 
7.2.1 
Clinical Laboratory Evaluations ............................................................................................. 14 
7.2.2 
Other Assays or Procedures ................................................................................................. 14 
7.2.3 
Specimen Preparation, Handling, and Storage ..................................................................... 14 
7.2.4 
Specimen Shipment .............................................................................................................. 15 
7.3 
STUDY SCHEDULE ........................................................................................................................ 15 
7.3.1 
Screening .............................................................................................................................. 15 
7.3.2 
Enrollment/Baseline .............................................................................................................. 15 
7.3.3 
Intermediate Visits ................................................................................................................. 15 
7.3.4 
Final Study Visit ..................................................................................................................... 15 
7.3.5 
Withdrawal/Early Termination Visit........................................................................................ 16 
7.3.6 
Unscheduled Visit .................................................................................................................. 16 
7.4 
CONCOMITANT MEDICATIONS, TREATMENTS, AND PROCEDURES .................................................... 16 
7.5 
JUSTIFICATION FOR SENSITIVE PROCEDURES ................................................................................ 16 
7.5.1 
Precautionary Medications, Treatments, and Procedures .................................................... 16 
7.6 
PROHIBITED MEDICATIONS, TREATMENTS, AND PROCEDURES ........................................................ 16 
7.7 
PROPHYLACTIC MEDICATIONS, TREATMENTS, AND PROCEDURES ................................................... 16 
7.8 
RESCUE MEDICATIONS, TREATMENTS, AND PROCEDURES ............................................................. 16 
7.9 
PARTICIPANT ACCESS TO STUDY AGENT AT STUDY CLOSURE ........................................................ 16 
8 
ASSESSMENT OF SAFETY ............................................................................................................. 17 
8.1 
SPECIFICATION OF SAFETY PARAMETERS ...................................................................................... 17 
8.1.1 
Definition of Adverse Events (AE) ......................................................................................... 17 
8.1.2 
Definition of Serious Adverse Events (SAE) ......................................................................... 17 
8.1.3 
Definition of Unanticipated Problems (UP) ............................................................................ 17 
8.2 
CLASSIFICATION OF AN ADVERSE EVENT ....................................................................................... 18 
8.2.1 
Severity of Event ................................................................................................................... 18 
8.2.2 
Relationship to Study Agent .................................................................................................. 18 
8.2.3 
Expectedness ........................................................................................................................ 18 
8.3 
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP .................................... 18 
8.4 
REPORTING PROCEDURES – NOTIFYING THE IRB .......................................................................... 19 
8.4.1 
Adverse Event Reporting ...................................................................................................... 19 
8.4.2 
Serious Adverse Event Reporting ......................................................................................... 19 
8.4.3 
Unanticipated Problem Reporting ......................................................................................... 19 
8.4.4 
Reporting of Pregnancy ......................................................................................................... 20 
8.5 
REPORTING PROCEDURES – NOTIFYING THE STUDY SPONSOR ...................................................... 20 
8.6 
STUDY HALTING RULES ................................................................................................................ 20 
8.7 
SAFETY OVERSIGHT ..................................................................................................................... 20 
9 
CLINICAL MONITORING .................................................................................................................. 21 
10 
STATISTICAL CONSIDERATIONS .................................................................................................. 21 
10.1 
STATISTICAL AND ANALYTICAL PLANS (SAP) ................................................................................. 21 
10.2 
STATISTICAL HYPOTHESES ........................................................................................................... 21 
10.3 
ANALYSIS DATASETS .................................................................................................................... 22 
10.4 
DESCRIPTION OF STATISTICAL METHODS ...................................................................................... 22 
10.4.1 
General Approach ............................................................................................................. 22 
10.4.2 
Analysis of the Primary Efficacy Endpoint(s) .................................................................... 22 


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10.4.3 
Analysis of the Secondary Endpoint(s) ............................................................................. 23 
10.4.4 
Safety Analyses ................................................................................................................ 23 
10.4.5 
Adherence and Retention Analyses .................................................................................. 23 
10.4.6 
Baseline Descriptive Statistics .......................................................................................... 23 
10.4.7 
Planned Interim Analysis .................................................................................................. 23 
10.4.8 
Additional Sub-Group Analyses ........................................................................................ 24 
10.4.9 
Multiple Comparison/Multiplicity ........................................................................................ 24 
10.4.10 
Tabulation of Individual Response Data ........................................................................... 24 
10.4.11 
Exploratory Analyses ........................................................................................................ 24 
10.5 
SAMPLE SIZE ............................................................................................................................... 24 
10.6 
MEASURES TO MINIMIZE BIAS ....................................................................................................... 25 
10.6.1 
Enrollment/Randomization/Masking Procedures .............................................................. 25 
10.6.2 
Evaluation of Success of Blinding ..................................................................................... 25 
10.6.3 
Breaking the Study Blind/Participant Code ....................................................................... 25 
11 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS ................................. 25 
12 
QUALITY ASSURANCE AND QUALITY CONTROL ....................................................................... 26 
13 
ETHICS/PROTECTION OF HUMAN SUBJECTS ............................................................................. 26 
13.1 
ETHICAL STANDARD ..................................................................................................................... 26 
13.2 
INSTITUTIONAL REVIEW BOARD ..................................................................................................... 26 
13.3 
INFORMED CONSENT PROCESS .................................................................................................... 26 
13.3.1 
Consent/Assent and Other Informational Documents Provided to Participants ............... 26 
13.3.2 
Consent Procedures and Documentation ......................................................................... 27 
13.4 
PARTICIPANT AND DATA CONFIDENTIALITY .................................................................................... 28 
13.4.1 
Research Use of Stored Human Samples, Specimens, or Data ...................................... 28 
13.5 
FUTURE USE OF STORED SPECIMENS ........................................................................................... 29 
14 
DATA HANDLING AND RECORD KEEPING ................................................................................... 29 
14.1 
DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES .............................................................. 29 
14.2 
STUDY RECORDS RETENTION ....................................................................................................... 30 
14.3 
PROTOCOL DEVIATIONS ............................................................................................................... 30 
14.4 
PUBLICATION AND DATA SHARING POLICY ..................................................................................... 30 
15 
STUDY FINANCES ............................................................................................................................ 31 
15.1 
FUNDING SOURCE ........................................................................................................................ 31 
15.2 
COSTS TO THE PARTICIPANT ......................................................................................................... 31 
15.3 
PARTICIPANT REIMBURSEMENTS OR PAYMENTS ............................................................................ 31 
16 
STUDY ADMINISTRATION ............................................................................................................... 31 
16.1 
STUDY LEADERSHIP ..................................................................................................................... 31 
17 
CONFLICT OF INTEREST POLICY .................................................................................................. 32 
18 
REFERENCES ................................................................................................................................... 32 
19 
ATTACHMENTS ................................................................................................................................ 34 
19.1 
INFORMED CONSENT .................................................................................................................... 34 
19.2 
ASSENT (AGE 7-11) ..................................................................................................................... 34 
19.3 
ASSENT (AGE 12-14) ................................................................................................................... 34 
19.4 
ASSENT (AGE 15-17) ................................................................................................................... 34 
19.5 
QUESTIONNAIRE - INITIAL .............................................................................................................. 34 
19.6 
QUESTIONNAIRE – FOLLOW UP ..................................................................................................... 34 
19.7 
INSTRUCTIONS ON APPLICATION OF STUDY DRUG AND ENVIRONMENTAL DECOLONIZATION PROTOCOL
 
34 
19.8 
RETAPAMULIN PACKAGE INSERT/PRODUCT INFORMATION .............................................................. 34 
20 
SCHEDULE OF EVENTS .................................................................................................................. 35 


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List of Abbreviations 
AE 
Adverse Event/Adverse Experience 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
CSOC 
Clinical Study Oversight Committee 
DCC 
Data Coordinating Center 
DHHS 
Department of Health and Human Services 
DSMB 
Data and Safety Monitoring Board 
FFR 
Federal Financial Report 
FWA 
Federalwide Assurance 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IDSA 
Infectious Diseases Society of America 
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
MOP 
Manual of Procedures 
MRSA 
Methicillin-Resistant Staphylococcus aureus 
N 
Number (typically refers to participants) 
NIH 
National Institutes of Health 
NYU 
New York University  
OHRP 
Office for Human Research Protections 
OHSR 
Office of Human Subjects Research 
PI 
Principal Investigator 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SOP 
Standard Operating Procedure 
US 
United States 


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Protocol Summary 
Title 
The Efficacy of Retapamulin as a Topical Decolonizing Agent for Mupirocin-
Resistant Methicillin-Resistant Staphylococcus aureus (MRSA) 
Short Title 
Retapamulin as a Decolonizing Agent for MRSA 
Brief Summary 
A randomized, double-blind, placebo-controlled clinical trial to test the 
efficacy of retapamulin to decolonize MRSA in a high risk pediatric group 
aged 9 months-17 years. The sample size will include 27 subjects in each of 
the two arms of the study (retapamulin versus placebo) for a total of 54 
subjects. Participants who are found to be nasal and/or rectal colonized with 
MRSA will be randomized to receive either retapamulin or placebo applied 
nasally and rectally for a total of 5 days. Nasal and rectal swabs will be 
collected at pre-defined time points during study duration (screening swab, 
swab one week after completion of topical therapy, swab 4 weeks after 
completion of topical therapy) to assess MRSA colonization status. The 
colonization rates of both groups will be assessed via Fisher’s Exact Test.  
Phase 
Clinical study phase 3  
Objectives 
To investigate the efficacy of retapamulin to reduce carriage of MRSA via a 
randomized, double-blind, placebo-controlled clinical study testing 
retapamulin among patients with confirmed mupirocin-resistant nasal and/or 
rectal MRSA colonization. 
Methodology 
Randomized, double-blind, placebo-controlled clinical trial  
Endpoint 
Primary Endpoint: Nasal/Rectal MRSA carriage at 1 week following 
decolonization course 
Secondary Endpoint: Nasal/Rectal MRSA carriage at 4 weeks following 
decolonization course 
Study Duration 
2 years 
Participant Duration 
6 weeks 
Duration of IP 
administration 
5 days 
Population 
27 patients per the two arms of the study aged 9 months-17 years for a total 
of 54 participants, of both genders. Patients are required to be colonized with 
a mupirocin-resistant methicillin-resistant strain of Staphylococcus aureus of 
which there is currently an outbreak in a particular high risk geographical 
cluster (children living in Brooklyn NY of Orthodox Jewish descent). The 
patients will be sampled from admitted children who reside in Orthodox 
predominant neighborhoods in Brooklyn NY based on zip code of residence. 
Study Sites 
NYU Langone Medical Center - Tisch Hospital, ODA clinic in Brooklyn 
Number of participants 
54 participants across both arms of the study  
Description of Study 
Agent/Procedure 
Retapamulin is a topical antibiotic ointment. The study drug (and placebo) will 
be used topically in a thin layer to the nares and peri-rectal area twice a day 
for five consecutive days 
Reference Therapy 
Placebo (white petrolatum)  
Key Procedures 
Body surface swabs/cultures 
Statistical Analysis 
Statistical analysis will be performed using Fisher’s exact test (non-
parametric) to evaluate for significant difference in colonization between the 
two groups (retapamulin and placebo).  


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Schematic of Study Design 
  
 
Obtain informed consent. Screen potential subjects by inclusion and exclusion criteria. 
Obtain screening nasal and peri-rectal swabs.  
Randomize Total N (54): nasal and/or 
rectal + for MRSA 
Arm 1        
27 Subjects 
Arm 2        
27 Subjects 
Perform baseline assessments. Obtain initial questionnaire. Administer study 
intervention (retapamulin or placebo) to be used at home for 5 days. 
Study visit for nasal/peri-rectal swabs. Obtain follow up questionnaire. Collect drug 
containers 
Study visit for nasal/peri-rectal swabs. Obtain follow up questionnaire.  
Enrollment 
Visit 1 
Day 1 
Screening 
Visit 
Visit 2 
Day 14 
Visit 3 
Day 35 


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1 Key Roles 
 
Principal Investigator  
Jennifer Lighter Fisher, MD: Hospital Epidemiologist, Assistant Professor of Pediatric Infectious Diseases  
NYU School of Medicine 
545 First Avenue 
Greenberg Hall, SC1-174 
New York, NY 10016 
212-263-5454 
Jennifer.Lighter@nyumc.org 
 
Co-investigator 
Ami Patel, MD, MPH: Pediatric Infectious Diseases Fellow 
NYU School of Medicine 
545 First Avenue 
Greenberg Hall, SC1-174 
New York, NY 10016 
718-612-1408 
Ami.Patel@nyumc.org 
Industry Partner/Industry Sponsor 
Aqua Pharmaceuticals  
Susan Cutler, DMD: Senior Director of Clinical and Medical Affairs 
Stephan Levy, MD: VP of Research and Development  
70 Eagleview Blvd, Suite 200 
Exton, PA 19341 
610-644-7000 
 
Biostatistician  
Anna Stachel, MPH, CIC: Data Analyst  
NYU Langone Medical Center 
545 First Avenue 
Greenberg Hall, SC1-174 
New York, NY 10016 
212-263-5454 
Anna.Stachel@nyumc.org 
 
Research Coordinator 
 
Kristine Smart 
NYU Langone Medical Center 
550 First Avenue, MSB 223 
New York< NY 10016 
646-501-2469 
Kristine.Smart@nyumc.org 
 
Additional Study Team Members  
 
Bo Shopsin, MD, PhD: Assistant Professor of Microbiology and Infectious Diseases 
Shopsin Laboratory  
NYU School of Medicine  
Alexandria Center for Life Sciences West Tower  
430 East 29th Street, Third Floor 
New York, NY 10016 
Bo.Shopsin@med.nyu.edu 


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Rebecca Rosenberg, MD, MPH: Pediatric Hospitalist, Assistant Professor of Pediatrics 
NYU School of Medicine 
550 First Avenue 
New York, NY 10016 
212-263-0959 
Rebecca.Rosenberg@nyumc.org 
 
Israel Rosman, MBA: Patient/Physician Liaison, Network Development 
NYU Langone Medical Center  
545 First Avenue 
New York, NY 10016 
212-263-0816, 917-363-3079 
Israel.Rosman@nyumc.org 
 
Data Safety and Clinical Monitoring  
 
Adam Ratner, MD, MPH: Associate Professor of Pediatrics and Microbiology  
NYU School of Medicine 
550 First Avenue, MSB 223 
New York, NY 10016 
646-501-0044 
Adam.Ratner@nyumc.org  
 
2 Introduction, Background Information and Scientific Rationale 
2.1 Background Information and Relevant Literature 
 
Staphylococcus aureus (S. aureus) is a leading cause of superficial and invasive hospital and community-
acquired infections. It is the most virulent of the Staphylococcus species and can produce systemic 
infections in otherwise healthy adults and children. The anterior nares are a natural reservoir for S. 
aureus, and colonization confers an increased risk of infection. [1] National data indicate that the 
prevalence of asymptomatic colonization with methicillin-sensitive S. aureus ranges from 18 to 38%, and 
with methicillin-resistant S. aureus (MRSA) from 0.8 to 6%.[1] Controlling MRSA colonization and 
preventing its spread is essential, as infection is associated with significant morbidity and mortality. 
Decolonization is an evidence-based intervention that can be used to reduce bacterial burden in order to 
prevent MRSA infections and transmission.[2] Standard decolonization regimens include mupirocin 
ointment to the nares and chlorhexidine wipes or baths for the body. Mupirocin is a topical antibacterial 
agent that is well established in clinical practice and is currently the gold standard therapy for MRSA 
nasal decolonization. [11] However, increasing resistance to mupirocin has been noted with some studies 
showing that MRSA mupirocin resistance (Mup-R) rates are as high as 24% in the US.[3] Emerging 
resistance to mupirocin highlights an urgent need for alternative approaches to MRSA decolonization. 
 
In New York City (NYC), there is a high prevalence of MRSA infections. Over the past several years, 
pediatric clinicians at New York University Langone Medical Center (NYULMC) have observed an 
increased incidence of MRSA infections amongst the pediatric population, specifically among Orthodox 
Jewish children. These observations were confirmed in a 2015 prospective study conducted at NYULMC 
to better understand the epidemiology of Community Acquired MRSA (CA-MRSA) in the pediatric 
population. Children from the Orthodox Jewish community were identified as high risk compared to the 
general pediatric population. Children from the high-risk communities were identified via zip codes as 
described in a publication that determined Orthodox Jewish neighborhoods based on the concentration of 
Jewish establishments such as synagogues, yeshivas, and kosher food retailers.[12] Information was 
collected to ascertain MRSA infection and colonization rates among these two groups. 
 


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Interestingly, no difference in methicillin-susceptible S. aureus (MSSA) colonization prevalence was 
observed between children from high-risk and low-risk communities. However, children from these high-
risk areas were 2.8 times as likely to be colonized with MRSA (prevalence 9% vs 3 % [p=0.04]). Likewise, 
the MRSA infection rate per 1,000 patient days was 36 for children from high-risk areas versus 3.9 in 
children from low-risk areas (p<0.0001).  All isolates from patients in high-risk zip codes analyzed to date 
belong to genotype USA300, the predominant CA-MRSA clone in the US. This data suggests there is a 
geographically defined outbreak of CA-MRSA in children and these isolates form a distinct clade within 
the common USA300 MRSA lineage.  
 
Moreover, the majority of the clinical strains from the outbreak cluster carry the plasmid encoding the 
mupA gene, which confers the mupirocin-resistant (Mup-R) phenotype. Phenotypic analysis confirmed 
mupirocin resistance in 84% (39/55) of the outbreak subclone isolates compared to none (0/17) in the 
USA300 CA-MRSA control isolates. This finding has significant clinical impact, as there are no validated 
approaches to decolonize these children and families, and many such patients are re-hospitalized with 
recurrent infections.  In addition, CA-MRSA transmission in the community is ongoing and transmissions 
have been observed at our institution. Without an adequate way to decolonize Mup-R MRSA-positive 
patients, we risk expansion of the outbreak strain to lower risk patients and to communities outside the 
high risk geographic area.  
 
Retapamulin is a novel topical bacteriostatic pleuromutilin antibiotic, currently used for the treatment of 
impetigo, which has been shown to be effective against S. aureus skin infections. It has excellent in vitro 
and in vivo activity against MRSA and methicillin-sensitive S. aureus (MSSA) strains. An in vitro study to 
determine the activity of retapamulin among 403 MRSA isolates found that 99% of the MRSA isolates 
were susceptible to retapamulin.[4] In a multicenter Global Surveillance Program, S. aureus isolates were 
collected from skin and soft tissue infections of adults and children in hospital and community settings. 
Among MRSA isolates, retapamulin was 128-fold more potent than mupirocin.[3] 
 
Multiple in vitro studies have demonstrated that the likelihood of S. aureus developing resistance to 
retapamulin is low. This is in large part due to the antibiotic’s mechanism of action, inhibition of bacterial 
protein synthesis by binding to and preventing formation of the 50S ribosomal unit. A multi-center study 
was performed by Biedenbach in outpatient dermatology centers to determine the rates of resistance of 
agents against S. aureus isolates collected from skin and soft tissue infections. The rate of mupirocin 
resistant S. aureus isolates was >10%, whereas retapamulin resistance was infrequent (1%). [5] Reduced 
susceptibility to retapamulin can occur via mutations in the cfr and rplC genes. [6, 7] The cfr 
(chloramphenicol-florfenicol resistance) gene encodes an rRNA methylase. The presence of this gene 
may lead to enhanced methylation, which is thought to prevent the antimicrobial from binding to the 
ribosome.[8] For the rplC (ribosomal protein L3) gene, the mechanism of resistance has been identified as 
first-, second-, and third- step rplC mutants of S. aureus. [9] The rplC gene encodes the L3 ribosomal 
protein which is essential for the formation of the peptidyl trasnferase center, the site where retapamulin 
binds. Three mutations are needed to have a notable effect; however each mutation confers a 
considerable fitness cost to the organism, leading to a low probability for the emergence of resistance in 
S. aureus. [10]  
 
Evidence for retapamulin as an effective decolonizing agent against MRSA is sparse, with even more 
limited studies in the pediatric population. There is high prevalence of MRSA in New York City, 
specifically in a geographically defined outbreak of CA-MRSA in children that has resistance to mupirocin, 
the standard of nasal decolonization. This represents a unique opportunity to gain further insight into 
retapamulin susceptibility and its efficacy as an alternative decolonizing agent. We hypothesize that 
retapamulin will be an effective agent to decolonize children harboring mupirocin-resistant MRSA strain.  
2.2 Name and Description of the Investigational Agent  
 
Retapamulin is a topical 1% antibiotic ointment that consists of retapamulin and white petrolatum as the 
vehicle. Retapamulin is a white to pale yellow crystalline solid. It is a bacteriostatic pleuromutilin antibiotic 
which inhibits bacterial protein synthesis by binding to and preventing formation of the 50S ribosomal unit. 


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The recommended dose is a thin layer of ointment applied twice a day for five days. Systemic exposure 
following application to intact skin is generally very low.  
 
It was FDA approved in 2007 for topical use in patients over 9 months of age. It is indicated for impetigo 
and mild secondary skin infections arising from lacerations, abrasions, sutured wounds, psoriasis or 
dermatitis. These infections are mainly caused by Staphylococcus aureus, but can also be due to 
Streptococcus pyogenes. 
 
The drug meets IND exemption criteria as it meets all 6 criteria for IND Exemption in article 312.2(b) of 
the FDA Guidance and IND requirements. Please see attached IND appendix.  
2.2.1 Preclinical Data 
The study drug, retapamulin, was tested in the Shopsin laboratory at NYU by the study team to assess 
susceptibility to the isolates of the strain in question. The initial epidemiologic study in 2015-2016 
conducted by Jennifer Lighter, MD and Bo Shopsin, MD, PhD described the outbreak of MRSA in this 
geographically defined high risk pediatric population. The genotypic and phenotypic analyses 
demonstrated that this MRSA strain is a subclone of the common USA 300 lineage and carries the mupA 
gene which confers resistance to mupirocin.  
 
The isolates from the subjects in the above study were tested via broth dilution to determine minimum 
inhibitory concentration (MIC) of retapamulin to assess susceptibility. This in vitro data shows that all of 
these isolates are susceptible to the study drug, retapamulin.   
2.2.2 Clinical Data to Date 
Multiple in vitro and in vivo studies have been published to date that have demonstrated retapamulin 
activity against MRSA (a few referenced above in the background and listed in the reference section). 
Studies have tested retapamulin in vitro to determine susceptibility and MIC data and have found the drug 
to be effective against MRSA isolates. These studies have also compared these isolates to mupirocin, the 
standard of care in decolonization, to compare efficacy with retapamulin which was shown to be very 
efficacious.   
 
A recent abstract/poster was presented at the Infectious Diseases Society of America (IDSA) 2016 ID 
week. The study was a randomized double-blinded placebo-controlled trial to assess effect of retapamulin 
for nasal decolonization of mupirocin-resistant MRSA nasal carriers. This trial found that nasal 
retapamulin reduced MRSA nasal carriage at 1 week following application of the study drug (84% 
reduction in odds of MRSA carriage compared to placebo) but reductions were not sustained at 6 weeks. 
This study found retapamulin was well tolerated when applied nasally with no reported side effects.[18]  
2.2.3 Dose Rationale (if applicable)  
The recommended dose for retapamulin is a thin layer of ointment applied twice a day for five days. This 
type of dosing is common for MRSA decolonization protocols and guidelines with other topical ointments.  
2.3 Rationale 
 
Methicillin resistant Staphylococcus aureus (MRSA) is an significant pathogen that causes a wide 
spectrum of superficial and invasive hospital and community-acquired infections. Controlling MRSA 
colonization is essential to prevent infections and transmission of the pathogen. At NYU Langone Medical 
Center there is a high prevalence of MRSA infections, specifically within a geographically defined 
community. Genotypic and phenotypic analysis of isolates from these patients demonstrates that the 
majority are resistant to mupirocin, the standard of care for decolonization. There is limited evidence of 
other alternative topical decolonizing strategies. In this study we will investigate the efficacy of 
decolonization in this pediatric population with a novel topical antibiotic, retapamulin which has been 
shown in a limited number of previous studies to be effective against MRSA.  
 


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Study Aim: 
To investigate the efficacy of retapamulin to reduce carriage of MRSA via a randomized, double-blind, 
placebo-controlled clinical trial testing retapamulin among pediatric patients with confirmed mupirocin-
resistant nasal and/or rectal MRSA colonization.  
 
Hypothesis:  
Retapamulin will be an effective way to decolonize children harboring mupirocin-resistant CA-MRSA 
strain compared to placebo at 1 week and 4 weeks post treatment. Specifically, we hypothesize 
retapamulin will reduce MRSA carriage by 60%. 
2.4 Potential Risks & Benefits 
2.4.1 Known Potential Risks 
Known risks or adverse reactions from this drug use are minimal and include local application site 
irritation (pruritus, erythema, stinging). In clinical studies, this was found to occur in less than 2% of 
patients. Retapamulin has not yet been widely evaluated for use on mucosal surfaces. This information is 
listed in the package insert for retapamulin. 
 
We do not anticipate that this research study will pose greater than minimal risk to participants. Side 
effects of Retapamulin not commonly expected and should subside with the discontinuation of the drug 
without expected long term risks. Serious side effects are rare and can include allergic reaction.  
 
All efforts will be made to minimize risk for participants in this study. Study staff have been trained in 
human subjects’ research and protection. The subjects will be instructed on proper use (amount, 
technique, duration) of the study drugs and potential effects to monitor for. If a side effect were to occur or 
there are any concerns, the subjects will be advised to call the research staff immediately and guidance 
or treatment will be offered as needed. Immediate necessary care for adverse events will be provided at 
NYULMC. Subjects will be monitored for side effects at each study visit and check-in via telephone to 
parent/guardian. If subjects experience serious adverse events or side effects to the study drug they will 
be withdrawn from the study.  
2.4.2 Known Potential Benefits 
Successful decolonization with retapamulin may prevent future MRSA infections in subjects and 
transmission to family members. The findings will also advance our understanding of the efficacy of 
retapamulin as a novel decolonization strategy for mupirocin-resistant MRSA. If efficacious, this therapy 
will have a significant clinical impact upon general practice for control of MRSA colonization and 
infections within this outbreak community. This is especially important in the study group and strain we 
are investigating as it has been found to be resistant to the standard of care for decolonization.  
 
3 Objectives and Purpose 
3.1 Primary Objective 
To assess the efficacy of retapamulin to reduce carriage of MRSA via a randomized, double-blind, 
placebo-controlled clinical trial testing retapamulin among pediatric patients with confirmed mupirocin-
resistant nasal and/or rectal MRSA colonization. This study will investigate the efficacy of retapamulin to 
reduce MRSA colonization 1 week post therapy by 60% compared to placebo, assuming a 15% 
spontaneous decolonization rate. 
3.2 Secondary Objectives (if applicable) 
To assess the efficacy of retapamulin to reduce MRSA colonization 4 weeks post therapy. 
 


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4 Study Design and Endpoints 
4.1 Description of Study Design 
The proposed study will be a randomized, double-blind, placebo-controlled clinical trial. Subjects who are 
positive for mupirocin-resistant methicillin-resistant Staphylococcus aureus (MRSA) based on nasal or 
rectal culture will be recruited. They will be randomized into one of the two arms to the study – 
retapamulin or placebo. They will be advised to apply the study drug to the nares and peri-rectal area 
twice a day for 5 consecutive days. Nasal and rectal colonization of MRSA will be observed at pre-
determined points within the study timeframe as described below via nasal and peri-rectal culture. The 
participants will be cultured before and after the interventional drug and a final culture to assess long-term 
decolonization status. The primary outcome measures are nasal and/or rectal MRSA carriage at 1 week 
and 4 weeks post decolonization with retapamulin.  
 
The participants will be recruited from NYU Langone Medical Center, specifically from Hassenfeld 
Children’s Hospital’s general pediatric and pediatric intensive care units (PICU). Hassenfeld Children’s 
Hospital at New York University Langone Health consists of 4 inpatient units totaling 109 beds within a 
larger 1069-bed tertiary care academic medical center. There are 33 beds in our general pediatric ward 
and 14 PICU beds.  Patients admitted from zip codes that are classified as Orthodox-predominant 
neighborhoods in Brooklyn will be recruited. As described in the background, a reference identified 
neighborhoods in Brooklyn determined to be mainly Orthodox based on the number of Jewish 
establishments (synagogues, yeshivas, and kosher food retailers) in the area.[12] A report will be 
generated daily through the Infection Prevention database that identifies patients admitted from these zip 
codes. These patients, regardless of reason for admission except as noted in exclusion criteria, will be 
recruited by the study team.  
 
Participants will also be recruited from the ODA clinic on Park Aveunue in Williamsburg Brooklyn. Study 
team members will be going to the clinic for scheduled visits where participants can be screened for 
inclusion into study. These participants will be referred by their pediatricians, the members of the clinic, or 
by word of mouth. Additionally, participants who are recruited at NYU Langone can come to the ODA 
clinic for follow up visits for ease to the participants.  
4.2 Study Endpoints 
4.2.1 Primary Study Endpoints 
The primary endpoint is % change in nasal/rectal colonization of MRSA from baseline to 1 week after 
completion of decolonization protocol with retapamulin compared to placebo.  
 
This endpoint is important to determine the short term efficacy of the study drug to decolonize patients 
with MRSA.  
4.2.2 Secondary Study Endpoints 
The secondary endpoint is % change in nasal/rectal colonization of MRSA from baseline to 4 weeks after 
completion of decolonization protocol with retapamulin compared to placebo.  
 
This endpoint is important to determine the long term efficacy of the study drug to decolonize patients 
with MRSA.  
4.2.3 Exploratory Endpoints 
Exploratory endpoints include: efficacy of decolonization per body site (nasal versus rectal), adverse 
events related to retapamulin use, and MRSA infections while on study/decolonization protocol. 
 


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5 Study Enrollment and Withdrawal 
5.1 Inclusion Criteria 
In order to be eligible to participate in this study, an individual must meet all of the following criteria: 
 
1. Admission to the general pediatric floor and pediatric intensive care units at NYU Langone Medical 
Center or visit to study team members at ODA clinic (Park Ave locations) in Williamsburg Brooklyn. 
2. Ages 9 months to 17 years  
3. Residing in the zip codes which reflect Orthodox Jewish neighborhoods where there is a current 
outbreak of this strain of MRSA.  
4. Nasal and/or rectal culture positive for mupirocin-resistant methicillin-resistant Staphylococcus aureus 
(MRSA) 
 
5.2 Exclusion Criteria 
An individual who meets any of the following criteria will be excluded from participation in this study: 
 
1. Pregnant or lactating  
2. Unable to appropriately consent 
3. Open sores in either of the study sites (nares or rectum) 
4. Recent surgical procedure to either study site (nares or rectum) 
5. Concurrent use of Rifampin or Trimethoprim/Sulfamethoxazole  
6. Current active MRSA infection 
7. Immunocompromised  
8. Presence of endotracheal tube, tracheostomy tube or other foreign body in upper airway  
5.3 Vulnerable Subjects 
This study will enroll children as we have established that we have a unique high risk pediatric population 
that has a high prevalence of mupirocin-resistant MRSA colonization and infections. These are no current 
studies on the use of the study drug, retapamulin, in the pediatric population for this indication. Please 
see attached Appendix: Children. 
 
5.4 Strategies for Recruitment and Retention 
We will recruit 54 total participants from ages 9 months – 17 years of age from the inpatient pediatric units 
at Tisch Hospital or ODA clinic. Our sample size calculation determined 22 participants in each arm (drug 
vs placebo) of the study to see a 60% reduction in MRSA colonization at a power level of 80%. We 
anticipated a 20% drop out rate based on prior studies of retention and therefore an additional 5 patients 
were added per arm of study. 
 
Patients admitted to the general inpatient or pediatric intensive care units at NYU Langone Medical 
Center Tisch hospital will be recruited if they reside in a pre-defined zip code that is identified as an 
Orthodox predominant neighborhood. A daily report will be generated for patients admitted from these zip 
codes and sent to the Infection Prevention and Control team (specifically the PI Jennifer Lighter). 
Recruitment will be conducted by either the PI and co-investigator or study team members. The children 
will not necessarily be under the care of the PI or co-investigators, or some instances they may be if they 
are admitted with an infection that requires a Pediatric Infectious Diseases consult and the PI and co-
investigator are the physicians who are covering the service. Otherwise, when patients from the defined 
zip-codes are admitted, a report that captures these patients will be created and sent to the PI and co-
investigator. The study team will approach the parent/guardian explaining how they were identified for the 
potential study. It will be explained that the research team is not aware of their current reason for 
admission and will not access their Epic chart for this reason. Once permission is obtained from the 


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parent/guardian, then the child will be approached to discuss the study. Participants will also be recruited 
at the ODA clinic (Park Ave location) In Brooklyn. These participants will be referred for screening by 
clinic members, pediatricians in the community, or by word of mouth. 
 
After informed consent, and assent when appropriate is obtained, screening nasal and peri-rectal cultures 
will be performed on these participants to determine if they are eligible to enroll. Eligibility includes either 
nasal or rectal positive for MRSA. Informed consent will take place either at NYULMC on the inpatient 
ward while they are admitted, at ODA clinic  during time of screening, or at Fink Children’s Ambulatory 
Center when present for a routine follow up visit. Participants will be asked to fill out a study questionnaire 
which asks about medical history, medication use, history of MRSA infections and prior use of antibiotics 
and specific MRSA medications. The study team will ask participants for this information via questionnaire 
only; it will not be gathered from their medical records. They study team will not access medical records 
or charts for participants.  
 
The participants will be required to follow up at pre-defined time points throughout the 6 weeks study 
period to obtain follow up swabs, complete questionnaires regarding interim change in medical history or 
side effects experienced, and to collect containers from study drugs. Retention will be enhanced through 
telephone reminders of study visit appointments as well as payments for participation in the study. In 
addition, follow up for study visits for the participants recruited at NYULMC will occur at NYU Pediatric 
Infectious Diseases outpatient clinic as per routine medical management,at NYU Langone Main 
Campus,Greenberg Hall, or at ODA clinic (Park Ave location) in Brooklyn.  
5.4.1 Use of DataCore/Epic Information for Recruitment Purposes 
DataCore/Epic will not be utilized for study purposes 
5.5 Duration of Study Participation 
The duration of study participation including screening, both intervention study and follow up is about 6 
weeks.  
5.6 Total Number of Participants and Sites  
The total number of participants enrolled will be 54 subjects. 27 in each of the two arms of the study. 
 
Recruitment will end when approximately 54 participants are enrolled and have completed the study 
protocol. It is expected that approximately 54 participants will be enrolled in order to produce 44 evaluable 
participants as we estimate a 20% drop out rate. The participants will be recruited at NYULMC Tisch 
Hospital or ODA clinic in Brooklyn. 
 
5.7 Participant Withdrawal or Termination 
5.7.1 Reasons for Withdrawal or Termination 
 
Participants are free to withdraw from participation in the study at any time upon request. An investigator 
may terminate participation in the study if: 
 
Any clinical adverse event (AE), laboratory abnormality, or other medical condition or situation 
occurs such that continued participation in the study would not be in the best interest of the 
participant 
 
The participant meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation 
5.7.2 Handling of Participant Withdrawals or Termination 
For patients who have withdrawn or terminated from the study, follow up telephone calls will be 
conducted to assess for side effects. One phone call two weeks after the patient has been declared 


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withdrawn or terminated will be conducted. For patients who remain in the study, but discontinue the 
study agent, they will be asked to complete the follow up questionnaire when they present for study visits 
to assess for adverse reactions or side effects. Adverse events from the drug are local at the site of 
application and should subside with the discontinuation of the product. Therefore, long term follow up for 
adverse events is deemed unnecessary.  
 
A participant will be stated as lost to follow-up (and therefore withdrawn/terminated) if: they have missed 
all three study visits, the study team has attempted weekly phone calls to parent/guardian for three weeks 
without answer or success of having the participant return for study visit.  
5.8 Premature Termination or Suspension of Study 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable 
cause. Written notification, documenting the reason for study suspension or termination, will be provided 
by the study investigators to the study team members, partnering sites, industry partner, and the IRB. If 
the study is prematurely terminated or suspended, the PI will promptly inform the IRB and will provide the 
reason(s) for the termination or suspension. 
Circumstances that may warrant termination or suspension include, but are not limited to: 
 
Determination of unexpected, significant, or unacceptable risk to participants 
 
Demonstration of efficacy that would warrant stopping 
 
Insufficient compliance to protocol requirements 
 
Data that are not sufficiently complete and/or evaluable 
 
Determination of futility 
 
Study may resume once concerns about safety, protocol compliance, data quality are addressed and 
satisfy the sponsor, IRB and/or FDA. 
 
6 Study Agent (Study drug, device, biologic, vaccine etc.) and/or 
Procedural Intervention  
6.1 Study Agent(s) and Control Description 
Retapamulin is a topical antibiotic ointment. The ingredients include retapamulin and white petrolatum as 
the vehicle. The composition is 10mg retapamulin per 1g of ointment (1%). The placebo that will be used 
is triple-purified pharmaceutical-grade petrolatum.  
 
The study is IND exempt as it meets all 6 criteria for IND Exemption in article 312.2(b) of the FDA 
Guidance and IND requirements listed below. Please see attached Appendix: IND Recruitments 
Exemption. 
 
1. The drug product is lawfully marketed in the United States. 
2. The investigation is not intended to be reported to FDA as a well-controlled study in support of a new 
indication and there is no intent to use it to support any other significant change in the labeling of the 
drug. 
3. In the case of a prescription drug, the investigation is not intended to support a significant change in 
the advertising for the drug. 
4. The investigation does not involve a route of administration, dose, patient population, or other factor 
that significantly increases the risk (or decreases the acceptability of the risk) associated with the use of 
the drug product (21 CFR 312.2(b)(1)(iii)). 
5. The investigation is conducted in compliance with the requirements for review by an IRB (21 CFR part 
56) and with the requirements for informed consent (21 CFR part 50).  
6. The investigation is conducted in compliance with the requirements of § 312.7 (i.e., the investigation is 
not intended to promote or commercialize the drug product).  


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6.1.1 Acquisition 
The study drug will be acquired directly from the drugs distributor, Aqua Pharmaceuticals. Aqua 
Pharmaceuticals will ship the drug directly to the NYU Investigational Research Pharmacy. 
 
The placebo control will be acquired from the distributor and also shipped directly to the NYU 
Investigational Research Pharmacy. 
6.1.2 Formulation, Appearance, Packaging, and Labeling 
Retapamulin is a 1% ointment that consists of retapamulin and white petrolatum as the vehicle. 
Retapamulin is a white to pale yellow crystalline solid that is packaged by the manufacturer in 15g/30g 
tubes and commercially available for human use in this form.  
 
GlaxoSmithKline (GSK) is the manufacturer of the study agent, Aqua Pharmaceuticals is the distributor of 
the study agent and acquired its US rights in 2015. As supplied, it is labeled under the brand name 
Altabax.The package insert of the product is attached in the appendix. 
 
The placebo used will be a triple purified pharmaceutical grade white petrolatum. White petrolatum is the 
vehicle in the Altabax ointment which consists of retapamulin and white petrolatum. The petrolatum is 
Ultimate EP White PET UP (code: 130985), Product Code: PEN1702-02-C-DR, manufactured by Calumet 
Specialty Products. It is a topical ointment that is colorless to white ointment. It will be purchased in bulk 
in jar containers or tubes but will be distributed to the subjects weighed into unlabeled containers.  
6.1.3 Product Storage and Stability 
The study agents are stored at room temperature. Per package insert - store at 25°C (77°F) with 
excursions permitted to 15°-30°C (59°-86°F). The product can be used after opening or further dispensed 
after seal is broken until the expiration date on package.  
6.1.4 Preparation 
The study drug and placebo will be dispensed by the NYULMC Investigational Research Pharmacy.  Both 
will be handled in the same manner. The drug (retapamulin) and placebo (white petrolatum) will be 
removed from their original packaging and packaged into standard unlabeled containers for the blinding 
process. The drug and placebo will be aliquoted and distributed in 15g amounts throughout the study. 
The study agents are ready for use from the package and do not require additional preparation. The 
NYULMC Investigational Research Pharmacy will receive, store, and dispense all study drug and placebo 
for this study’s use. The contact for the NYULMC Investigational Research Pharmacy is Kanika Ballani, 
Pharm.D, Assistant Director of Pharmacy, Clinical Trials, 212-263-5039. 
6.1.5 Dosing and Administration 
Retapamulin is a topical drug. Each participant will be advised to apply a thin layer of the ointment using a 
cotton swab or finger to both nares and peri-rectal area twice a day (morning and evening) for 5 
consecutive days.  
6.1.6 Route of Administration 
Topical 
6.1.7 Starting Dose and Dose Escalation Schedule 
Not applicable. Each participant will receive the same drug concentration and dose. 15g of ointment will 
be distributed and the subjects will be instructed to apply a small pea size layer topically using a cotton 
swab or tip of finger to both nares and peri-rectal area. 
6.1.8 Dose Adjustments/Modifications/Delays 
Not applicable  


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6.1.9 Duration of Therapy 
Each ointment will be applied for five consecutive days. The five days is necessary for an ‘evaluable’ 
participant 
6.1.10 Tracking of Dose 
Participants will be advised on correct application and dosing at each study visit. They will be required to 
return the containers were dispensed in to monitor use. Participants will be asked to fill a questionnaire at 
each visit regarding the use of the medications (frequency of application, doses/days missed, etc).  
6.1.11 Device Specific Considerations 
Not applicable 
6.2 Study Agent Accountability Procedures 
The study agents will be allocated and dispensed by the NYULMC Investigational Research Pharmacy. 
The pharmacy and research pharmacist will receive shipment of the agents, allocated into individual un-
identifiable container and be responsible for the blinding of the agents. The dispensed drugs will be given 
to the PI or co-investigator in blinded fashion by the Investigational Pharmacy for enrolled patients at the 
time of enrollment visit. The PI/co-investigator will distribute the agents to the participants at study visit 1. 
The handling and distribution will be documented by the PI/co-investigator in locked and de-identified 
official study records. The participants will be asked to return containers at study visit 2 after completing 
the 5 day decolonization process at home. This will allow for drug reconciliation checks to document drug 
assigned, drug consumed and drug remaining. This reconciliation will be logged on the drug reconciliation 
form and signed and date by the study team. The returned containers will be collected by the study team 
and then returned to the NYULMC Investigational Research Pharmacy for final reconciliation and 
destruction on site.  
 
7 Study Procedures and Schedule 
7.1 Study Procedures/Evaluations 
7.1.1 Study Specific Procedures 
 
 
History 
o 
Medical history: list of chronic medical conditions, history of MRSA infections to be 
obtained from initial study questionnaire  
o 
Medication history: list of daily medications use, antibiotic use in the past 6 months, as 
well as interim antibiotic use while on study. This will be obtained from study 
questionnaires. Medication use does not affect assessment of eligibility.  
 
Physical Exam 
o 
A physical exam of the nares and peri-rectal area will be conducted at screening, 
enrollment and each follow up visit to assess area, integrity of skin/mucosa and evaluate 
for side effects. The exam will be documented by study team in the subject’s study chart.  
 
Biological specimen collection and laboratory evaluations:  
o 
Specimen collection: Nasal and peri-rectal cultures via cotton swab will be obtained at 
screening visit and each subsequent study visit to assess MRSA colonization. Samples 
will be collected by surface swabs for MRSA culture using cotton swabs. Swabs will be 
collected from both of the anterior nares. Separate swabs will be collected from the peri-
rectal area.  
o 
Specimen processing: Samples will all be processed in Shopsin laboratory at NYU by the 
study investigators. Cultures of the swabs will be performed within one day of collection 
on chromagar MRSA culture plates to identify MRSA positive isolates. The initial 
screening isolates will them undergo susceptibility testing via E-test to determine 


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mupirocin resistance. Rapid MRSA identification will also be performed via PCR testing. 
Specimens collected at follow up visits post decolonization that are positive for MRSA will 
also be analyzed via PCR to determine if resistance mutations (specifically in the rplC 
gene) are present after use of the drug.  
 
Study Drug Agent 
o 
Study drug monitoring: The study drug will be prepared by the Investigational Pharmacy 
at NYU. The medications will be weighed, aliquoted and prepared for distribution by the 
research pharmacist. The subjects will be required to return all left over medication and 
containers to the researchers. The research pharmacist at the Investigational Pharmacy 
will verify amount and contents prior to discarding the drug. 
o 
Assessment of study agent adherence will occur at each study visit based on 
questionnaires completed by the participants and assessment of study drug containers 
returned by participants to study team members after use. 
 
Decolonization: Subjects will all be instructed to performed the following decolonization protocol 
at home: 
o 
Apply the study drug topically to their nares and peri-rectal area twice daily (morning and 
night) for 5 consecutive days.  
o 
Perform environmental procedures to help eradicate MRSA from the home and prevent 
recolonization which includes washing all towels and linens with hot water and cleaning all 
frequently touched surfaces with bleach.  
 
Administration of questionnaires will occur at each study visit to assess change in medical history, 
change in infectious history, use of antibiotics, adherence to study drug agents and assessments 
of side effects 
 
A discussion of results of any study specific procedures will be provided to participant at the end 
of the study period after blinding has been lifted. 
7.1.2 Standard of Care Study Procedures 
All planned procedures completed during the study are investigational. The environmental procedures to 
be completed at home by participants to aid in eradication of MRSA in the home is regular standard to 
care for decolonization protocols.  
7.2 Laboratory Procedures/Evaluations 
7.2.1 Clinical Laboratory Evaluations 
Screening and post enrollment microbiology evaluations: Nasal and peri-rectal culturesand PCR testing to 
determine MRSA colonization. All samples will be processed by the study team at Shopsin Laboratory. 
7.2.2 Other Assays or Procedures 
The assay includes bacterial cultures and PCR testing on the samples. MRSA will be determined via 
chromagar MRSA culture plates to identify MRSA positive isolates. MRSA PCR testing will be performed 
if rapid MRSA detection is needed. In addition, follow up specimens that are positive for MRSA after 
decolonization will undergo PCR testing to detect acquisition of resistant mutations.  All will be processed 
at Shopsin Laboratory by study team members. 
7.2.3 Specimen Preparation, Handling, and Storage 
Specimens will be obtained from participants at each study visit. These include nasal specimen using 
cotton culture swabs and peri-rectal specimen using separate cotton culture swabs. These specimens will 
be stored at room temperature and then processed within one day of collection. Storage and processing 
of the specimen will occur by the study investigators at Shopsin Laboratory. Processing of the specimens 
includes culturing on chromagar MRSA culture plates and/or PCR testing. Originally cotton swabs and 
plates will be labeled with the participants study code number. Original cotton swabs will be discarded 
after processing. If culture plates are positive for MRSA, the isolates will be stored in -80C freezer in 
Shopsin Laboratory for further testing as needed. The stored isolates will be labeled with the study code 
number, not with patient identifier.  


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7.2.4 Specimen Shipment 
The cotton swab specimens will be transported by hand by study investigators at room temperature from 
site of collection (NYULMC) to Shopin Laboratory on day of collection.  
7.3 Study Schedule 
7.3.1 Screening  
 
Screening  
 
Admitted patients from an Orthodox predominant neighborhood based on zip code of residence 
will be approached regarding the study for recruitment 
 
Informed consent (and assent when appropriate) of a potential participant will be obtained and 
verified by signature on written informed consent form 
 
Review eligibility based on inclusion/exclusion criteria 
 
Perform physical examination  
 
Collect and nasal peri-rectal culture specimens 
 
Schedule study visits for participants who are eligible and available for the duration of the study. 
7.3.2 Enrollment/Baseline 
 
Enrollment/Baseline Visit (Visit 1, Day 0) 
 
Verify inclusion/exclusion criteria. 
 
Obtain demographic information, medical history, medication history, infection history from initial 
study questionnaire. 
 
Perform physical examination  
 
Subject randomization 
 
Provide study drug at this visit for home use.  
 
Instructions provided to the participants: The subjects will apply study drug topically inside the 
anterior nares and peri-rectal area twice a day (morning and night) for five consecutive days. 
They will also follow the environmental procedures in the attached instructions to help eradicate 
MRSA from the home. 
7.3.3 Intermediate Visits 
7.3.3.1 
Visit 2 
 
Visit 2 (Day 14 +/- 5)  
 
This visit will occur about one week after completion of 5 days of the study drug  
 
Record adverse events as reported by participant on follow up study questionnaire  
 
Record change in medical history, recent infections or antibiotic use on follow up study 
questionnaire  
 
Record participant’s adherence to protocol via follow-up study questionnaire  
 
Perform physical examination  
 
Collect samples for MRSA culture using cotton swabs to culture the anterior nares and peri-rectal 
area 
 
Collect study drug containers from participants  
7.3.4 Final Study Visit 
 
Final Study Visit (Visit 3, Day 35 +/- 15)  
 
This visit will occur about four weeks after completion of the study agent 
 
Record adverse events as reported by participant on follow up study questionnaire  


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 
Record change in medical history, recent infections or antibiotic use on follow up study 
questionnaire  
 
Perform physical examination 
 
Collect samples for MRSA culture using cotton swabs to culture the anterior nares and peri-rectal 
area 
7.3.5 Withdrawal/Early Termination Visit 
If a participant withdraws from the study or early termination occurs, a final nasal and peri-rectal swab will 
attempted to be collected. The participant will also be asked to fill out one final follow up questionnaire to 
assess use of the study agents and any adverse reactions. Participants will be asked to return all study 
agents containers at the time of withdrawal.  
7.3.6 Unscheduled Visit 
Unscheduled visits are not anticipated. If an unscheduled visit is required for unanticipated or serious 
adverse reaction, the participant will meet with a study team member and appropriate care will be offered. 
The study visit will be documented in the participants study chart and adverse reaction reported to the 
IRB. Any other unscheduled visit will be documented accordingly in the patients study chart.  
7.4 Concomitant Medications, Treatments, and Procedures 
All concomitant antibiotic use during study participation will be obtained via study questionnaires and 
recorded in the participant’s study charts. No concomitant medications, treatment, and/or procedures are 
restricted while on study. Information about concomitant antibiotic use will be collected at each study visit 
via questionnaire. Concomitant antibiotic use information is collected to assess if the antibiotic is being 
used to treat a MRSA infection or could potentially impact colonization with MRSA.  
7.5 Justification for Sensitive Procedures 
A placebo is used to assess the true efficacy of retapamulin compared to no medication or spontaneous 
decolonization. The study is blinded to both the researchers and the participants to minimize any bias 
with study drug use.   
7.5.1 Precautionary Medications, Treatments, and Procedures 
There are no medication precautions, interactions or toxicities known with the study agent. Therefore, 
there are no instructions for medication or therapy avoidance or modification as part of this protocol. 
7.6 Prohibited Medications, Treatments, and Procedures 
There are no medications, treatments or procedures that are not permitted on study 
7.7 Prophylactic Medications, Treatments, and Procedures 
There will be no prophylactic medications, treatments or procedures provided as prophylaxis on study 
7.8 Rescue Medications, Treatments, and Procedures 
There will be no rescue medications, treatments or procedures provided as rescue on study 
7.9 Participant Access to Study Agent at Study Closure 
Participants who remain positive for MRSA colonization after their completion of study related procedures 
will be offered access to the study agent via open label through the NYU Investigational Pharmacy.. Once 
subjects have completed study visit #3 and the follow up cultures one month post decolonization are 
collected, if they remain positive the researchers will offer the study agent directly via the NYU 
Investigational Pharmacy The participants that remain positive for colonization will be advised to use the 
ointment again twice a day for 5 days to the nares and peri-rectal area. 


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After the final study closure has been completed, there will not be continued access to study agent. The 
study drug is commercially available through physician prescription.   
 
8 Assessment of Safety 
8.1 Specification of Safety Parameters  
Safety parameters and adverse reactions/side effects will be recorded in the participants chart in the 
study database. No more than minimal adverse effects (local application site irritation) are anticipated 
from using the study agent. If adverse effects are encountered by participants and considered to be more 
than minimal affect it would be considered a study endpoint and adverse effects should subside with 
withdrawal of study agent. If more than minimal adverse effect is experienced (eg anaphylaxis or allergic 
reaction) it will be reported to the industry partner and the IRB. 
 
If subject develops MRSA active clinical infection while on study protocol, they will be cared for per 
routine medical management for such infections. This is anticipated to be rare. This development of 
disease while on protocol will be reported to the IRB and industry sponsor. If available, the isolates from 
these cases of active disease will be collected and analyzed by study team members and Shopsin 
laboratory to assess the bacterium and resistance determinants. Bacterial strain isolates will be stored. 
No material containing subject DNA will be collected or stored.  
8.1.1 Definition of Adverse Events (AE) 
An adverse event (AE) is any symptom, sign, illness or experience that develops or worsens in severity 
during the course of the study.  Intercurrent illnesses or injuries should be regarded as adverse events.  
Abnormal results of diagnostic procedures are considered to be adverse events if the abnormality: 
 results in study withdrawal 
 is associated with a serious adverse event 
 is associated with clinical signs or symptoms 
 leads to additional treatment or to further diagnostic tests 
 is considered by the investigator to be of clinical significance 
8.1.2 Definition of Serious Adverse Events (SAE) 
 
Serious Adverse Event 
Adverse events are classified as serious or non-serious.  A serious adverse event is any AE that is:  
 fatal 
 life-threatening 
 requires or prolongs hospital stay 
 results in persistent or significant disability or incapacity 
 an important medical event 
 
Important medical events are those that may not be immediately life threatening, but are clearly of major 
clinical significance. They may jeopardize the subject, and may require intervention to prevent one of the 
other serious outcomes noted above..  
 
All adverse events that do not meet any of the criteria for serious should be regarded as non-serious 
adverse events.  
8.1.3 Definition of Unanticipated Problems (UP) 
 
Unanticipated Problems Involving Risk to Subjects or Others 
Any incident, experience, or outcome that meets all of the following criteria:  


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 Unexpected in nature, severity, or frequency  (i.e. not described in study-related documents such 
as the IRB-approved protocol or consent form, the investigators brochure, etc) 
 Related or possibly related to participation in the research (i.e. possibly related means there is a 
reasonable possibility that the incident experience, or outcome may have been caused by the 
procedures involved in the research) 
 Suggests that the research places subjects or others at greater risk of harm (including physical, 
psychological, economic, or social harm). 
8.2 Classification of an Adverse Event 
8.2.1 Severity of Event 
 
For AEs not included in the protocol defined grading system, the following guidelines will be used to 
describe severity. 
 
 Mild – Events require minimal or no treatment and do not interfere with the participant’s daily 
activities. 
 Moderate – Events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning. 
 Severe – Events interrupt a participant’s usual daily activity and may require systemic drug 
therapy or other treatment. Severe events are usually potentially life-threatening or incapacitating. 
8.2.2 Relationship to Study Agent 
 
The clinician’s assessment of an AE's relationship to study agent is part of the documentation process, 
but it is not a factor in determining what is or is not reported in the study. If there is any doubt as to 
whether a clinical observation is an AE, the event should be reported. All AEs must have their relationship 
to study agent assessed. In a clinical trial, the study product must always be suspect. To help assess, the 
following guidelines are used. 
 
 Related – The AE is known to occur with the study agent, there is a reasonable possibility that the 
study agent caused the AE, or there is a temporal relationship between the study agent and event. 
Reasonable possibility means that there is evidence to suggest a causal relationship between the 
study agent and the AE. 
 Not Related – There is not a reasonable possibility that the administration of the study agent 
caused the event, there is no temporal relationship between the study agent and event onset, or 
an alternate etiology has been established. 
8.2.3 Expectedness 
 
The PI and essential study team members will be responsible for determining whether an AE is expected 
or unexpected. An AE will be considered unexpected if the nature, severity, or frequency of the event is 
not consistent with the risk information previously described for the study agent. 
8.3 Time Period and Frequency for Event Assessment and Follow-Up 
 
The occurrence of an AE or SAE may come to the attention of study personnel during study visits and 
interviews of a study participant presenting for medical care, or upon review by a study monitor. All AEs 
including local and systemic reactions not meeting the criteria for SAEs will be captured on the 
appropriate RF. Information to be collected includes event description, time of onset, clinician’s 
assessment of severity, relationship to study product (assessed only by those with the training and 
authority to make a diagnosis), and time of resolution/stabilization of the event. All AEs occurring while on 


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study must be documented appropriately regardless of relationship. All AEs will be followed to adequate 
resolution. 
 
Any medical condition that is present at the time that the participant is screened will be considered as 
baseline and not reported as an AE. However, if the study participant’s condition deteriorates at any time 
during the study, it will be recorded as an AE. UPs will be recorded in the data collection system 
throughout the study. 
 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the event 
at each level of severity to be performed. AEs characterized as intermittent require documentation of 
onset and duration of each episode. 
 
The PI will record all reportable events with start dates occurring any time after informed consent is 
obtained until 7 (for non-serious AEs) or 30 days (for SAEs) after the last day of study participation. At 
each study visit, the investigator will inquire about the occurrence of AE/SAEs since the last visit. Events 
will be followed for outcome information until resolution or stabilization. 
 
All unresolved adverse events should be followed by the investigator until the events are resolved, the 
subject is lost to follow-up, or the adverse event is otherwise explained.  At the last scheduled visit, the 
investigator should instruct each subject to report any subsequent event(s) that the subject, or the 
subject’s personal physician, believes might reasonably be related to participation in this study.  The 
investigator should notify the study sponsor of any death or adverse event occurring at any time after a 
subject has discontinued or terminated study participation that may reasonably be related to this study.  
The sponsor should also be notified if the investigator should become aware of the development of 
cancer or of a congenital anomaly in a subsequently conceived offspring of a subject that has participated 
in this study.  
8.4 Reporting Procedures – Notifying the IRB  
8.4.1 Adverse Event Reporting 
Adverse Events will be reported by the PI/co-investigator to the IRB and industry partner (Aqua 
Pharmaceuticals). Serious adverse events will be reported within 7 days. Minor/minimal adverse events 
(local application site irritation) will be reported at the completion of the study. 
8.4.2 Serious Adverse Event Reporting 
Serious Adverse Events will be reported in written format by the PI/co-investigator to the IRB and the 
industry partner within 7 days. The PI will be responsible for completing and signing off on the SAE 
reports.  
8.4.3 Unanticipated Problem Reporting 
Incidents or events that meet the OHRP criteria for UPs require the creation and completion of an UP 
report form. It is the site investigator’s responsibility to report UPs to their IRB and to the DCC/study 
sponsor. The UP report will include the following information: 
 
 Protocol identifying information: protocol title and number, PI’s name, and the IRB project number; 
 A detailed description of the event, incident, experience, or outcome; 
 An explanation of the basis for determining that the event, incident, experience, or outcome 
represents an UP; 
 A description of any changes to the protocol or other corrective actions that have been taken or 
are proposed in response to the UP. 
 
To satisfy the requirement for prompt reporting, UPs will be reported using the following timeline: 
 


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 UPs that are SAEs will be reported to the IRB and to the DCC/study sponsor within 7 days of the 
investigator becoming aware of the event. 
 Any other UP will be reported to the IRB and to the DCC/study sponsor within 30 days of the 
investigator becoming aware of the problem. 
 All UPs should be reported to appropriate institutional officials (as required by an institution’s 
written reporting procedures), the supporting agency head (or designee), and OHRP within 30 
days of the IR’s receipt of the report of the problem from the investigator. 
8.4.4 Reporting of Pregnancy 
If pregnancy were to occur while participants are on study protocol, they will be withdrawn from the study 
and study drug use will be discontinued. The pregnancy will be reported in written format to the IRB and 
the industry partner by the PI. 
8.5 Reporting Procedures – Notifying the Study Sponsor 
The study clinician will complete a SAE Form within the following timelines: 
 
 All deaths and immediately life-threatening events, whether related or unrelated, will be recorded 
on the SAE Form and submitted to the DCC/study sponsor within 24 hours of site awareness. See 
Section 1, Key Roles for contact information. 
 Other SAEs regardless of relationship will be submitted to the DCC/study sponsor within 72 hours 
of site awareness. 
 
All SAEs will be followed until satisfactory resolution or until the site investigator deems the event to be 
chronic or the adherence to be stable. Other supporting documentation of the event may be requested by 
the DCC/study sponsor and should be provided as soon as possible.  
 
As a follow-up to the initial report, within the following 48 hours of awareness of the event, the investigator 
shall provide further information, as applicable, on the unanticipated event or the unanticipated problem in 
the form of a written narrative.  This should include a copy of the completed Unanticipated Problem form, 
and any other diagnostic information that will assist the understanding of the event.  Significant new 
information on ongoing unanticipated adverse effects shall be provided promptly to the study sponsor. 
8.6 Study Halting Rules 
Administration of study agent will be halted when three grade 3 AEs determined to be “probably related” 
are reported to the DCC. In the case of this study agent, retapamulin, that would likely be serious allergic 
reaction or anaphylaxis. The DCC will notify the study sponsor and investigators immediately when the 
third grade 3 event is reported and enrollment screens will stop accepting new study participants. The 
study sponsor will inform the DSMB members within 24 hours of this occurrence and will provide the 
DSMB with AE listing reports. The DSMB will convene an ad hoc meeting by teleconference or in writing 
as soon as possible. The DSMB will provide recommendations for proceeding with the study to the study 
sponsor/NIH. The study sponsor will inform the FDA of the temporary halt and the disposition of the 
study. 
8.7 Safety Oversight 
 
It is the responsibility of the Principal Investigator to oversee the safety of the study.  This safety 
monitoring will include careful assessment and appropriate reporting of adverse events as noted above, 
as well as the construction and implementation of a site data and safety-monitoring plan. Medical 
monitoring will include a regular assessment of the number and type of serious adverse events. The 
safety oversight will be conducted via a single medical monitor. It is felt that this is sufficient for this trial as 
the overall risk to the subjects is very low based on the number of subjects to be recruited, the type of 
non-invasive monitoring to be performed, and the safety profile of the drug to be studied. 
 


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Safety oversight will be under the direction of a medical monitor with appropriate expertise, Adam Ratner, 
MD, MPH. Dr Ratner is a Pediatric Infectious Diseases physician and Microbiologist at NYU with 
expertise in both of these fields. The medical monitor will meet with the PI and co-investigator at least 
semiannually to assess safety and efficacy data on each arm of the study. Data collected to date will be 
reviewed including participants’ demographics, any significant history or illnesses, % change in 
colonization for nose and peri-rectal area, and answers to questionnaires. Safety data will also be 
reviewed including any adverse effects that have occurred, side effects reports and retention/dropout 
rate. The medical monitor will provide its input to the PI, IRB and industry partner.  
 
9 Clinical Monitoring 
 
Clinical site monitoring is conducted to ensure that the rights and well-being of human subjects are 
protected, that the reported trial data are accurate, complete, and verifiable, and that the conduct of the 
trial is in compliance with the currently approved protocol/amendment(s), with GCP, and with applicable 
regulatory requirement(s). 
 
 Monitoring for this study will be performed by Adam Ratner, MD, MPH. 
 Monitoring will be centralized at NYULMC and will occur at the initiation of the study and semi-
annually throughout the duration of the study. On-site monitoring of Tisch Hospital will occur once 
at the initiation of the study. Targeted, random review of data collection, data recording, data 
handling, data analysis, study-related procedures, and safety monitoring will be performed. The 
monitoring reports will be distributed to the PI, co-investigators and the IRB within 30 days.  
 Independent audits will not be conducted at this trial does not involve numerous sites 
 Internal quality management of study conduct, data collection, documentation and completion will 
be performed centrally.  
 
10 Statistical Considerations 
10.1 Statistical and Analytical Plans (SAP) 
There will be a formal Statistical and Analytical Plan (SAP). Partial details as outlined in the below 
sections, with full SAP created by study biostatistician being part of a stand-alone document. Key 
elements of the analysis plan are described below.  
10.2 Statistical Hypotheses 
Primary endpoint  
The percent change in nasal/rectal colonization of MRSA from baseline to 1 week after completion of 
decolonization protocol with retapamulin compared to placebo 
Null hypothesis: There will be no difference in reduction of nasal/rectal colonization of MRSA from 
baseline to 1 week after completion of decolonization protocol between retapamulin compared to 
placebo 
Alternative hypothesis: There will be a 45% difference in reduction in nasal/rectal colonization of 
MRSA from baseline to 1 week after completion of decolonization protocol with retapamulin 
compared to placebo 
 
Secondary endpoint 
The percent change in nasal/rectal colonization of MRSA from baseline to 4 weeks after completion of 
decolonization protocol with retapamulin compared to placebo 
Null hypothesis: There will be no difference in reduction of nasal/rectal colonization of MRSA from 
baseline to 4 weeks after completion of decolonization protocol between retapamulin compared to 
placebo 


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Alternative hypothesis: There will be a 45% difference in reduction in nasal/rectal colonization of 
MRSA from baseline to 4 weeks after completion of decolonization protocol with retapamulin 
compared to placebo 
 
This analysis will be a superiority trial. 
10.3 Analysis Datasets 
This will be a triple-blinded randomized Intent to Treat (ITT) clinical trial to assess the effectiveness of 
retapamulin in children colonized with MRSA under the age of 18 from a pre-specified community in 
Brooklyn. Participants living in the following zip codes will be eligible: 11024, 11205, 11206, 11211, 
11213, 11214, 11218, 11219, 11225, 11230, 11249. Neither the treatment team nor the subject will know 
the treatment assignments.  The outcome will be a dichotomous variable (1 = Yes, patient’s swab 
negative for MRSA, 0 = No, Patient’s swab positive for MRSA).  We will analyze additional co-variables 
collected on the data collection form such as age, gender, history of MRSA infections, history of chronic 
medical conditions/chronic skin conditions, etc. (see Data Collection Form in appendix uploaded into 
study-related documents). 
 
Information from the data collection form will be entered into an Access database designed for this study 
to provide a readily electronic version dataset to analyze. The following variables will be included: 
Assigned group (blinded treatment arm, A/B), age, gender, side effects, application day 1 (Y/N), 
application day 2 (Y/N), application day 3 (Y/N), application day 4 (Y/N), application day 5 (Y/N), 
environmental clean (Y/N), history of medical conditions or chronic skin conditions, history of MRSA, 
history of MRSA in family, recent or concomitant antibiotic use, prior retapamulin use etc. Variables 
related to safety will also be recorded in the database. 
 
In addition to the ITT analysis, we will conduct a per-protocol analysis of those who completed 4 or 5 days 
of treatment and analyze similar to the ITT analysis. 
10.4 Description of Statistical Methods 
10.4.1 General Approach 
The design of the study is a randomized, double-blind, placebo-controlled clinical trial. Schematic of 
Study design on page 2 of this document illustrates further. 
 
This will be a double-blinded randomized Intent to Treat (ITT) clinical trial to assess the effectiveness of 
retapamulin in children colonized with MRSA under the age of 18 from a pre-specified community in 
Brooklyn. The outcome will be a dichotomous variable (1 = Yes, patient’s swab negative for MRSA, 0 = 
No, Patient’s swab positive for MRSA).  We will analyze additional co-variables collected on the data 
collection form such as age, gender, history of MRSA infections, history of chronic medical 
conditions/chronic skin conditions, etc. (see Data Collection Form in appendix uploaded into study-related 
documents).These will be presented as descriptive statistics between Retapamulin and Placebo groups 
and assessed for potential statistical differences between the groups.  Chi-square will be used for 
dichotomous variables and a T-test will be used for continuous variables (if normally distributed otherwise 
Mann-Whitney).   
10.4.2 Analysis of the Primary Efficacy Endpoint(s) 
To assess the primary dichotomous endpoint, the change in nasal/rectal colonization of MRSA from 
baseline to 1 week after completion of decolonization protocol with retapamulin compared to placebo, we 
will use a fisher exact (non-parametric) to evaluate for significant difference in colonization after 1 week 
between the two groups.  We will provide the difference in decolonization rates with an odd ratio, 95% 
confidence interval and p-value. Participants will be selected to treatment group at random, therefore 
baseline characteristics should not significantly differ.  However if the two treatment groups have 
covariates that are significantly different, we will consider a logistic regression to adjust for the difference 


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in population.   Before we analyze with a logistic regression, we will test for normality to assure that all 
apriori statistical assumptions are met. 
10.4.3 Analysis of the Secondary Endpoint(s) 
To assess the secondary dichotomous endpoint, the change in nasal/rectal colonization of MRSA from 
baseline to 4 week after completion of decolonization protocol with retapamulin compared to placebo, we 
will use a fisher exact (non-parametric) to evaluate for significant difference in colonization after 4 week 
between the two groups.  We will provide the difference in decolonization rates with an odd ratio, 95% 
confidence interval and p-value. Participants will be selected to treatment group at random, therefore 
baseline characteristics should not significantly differ.  However if the two treatment groups have 
covariates that are significantly different, we will consider a logistic regression to adjust for the difference 
in population.   Before we analyze with a logistic regression, we will test for normality to assure that all 
apriori statistical assumptions are met. 
 
10.4.4 Safety Analyses 
Patients will be monitored for the occurrence of possible adverse events using a standardized data 
collection form prior to hospital discharge.   All serious events which many potentially be adverse 
reactions (anaphylaxis, serious rash or death) will be assessed by the primary investigator.  The study 
team and the NYU SOM Institutional Review Board will be notified within one day of identification of the 
event by study personnel. 
10.4.5 Adherence and Retention Analyses 
Adherence to the protocol will be collected and documented using the data collection form (in appendix 
uploaded into study-related documents). Subjects will be asked to report the use of the provided ointment 
in follow-up questionnaire which will be administered at the follow-up study visit conducted one week after 
completion of study decolonization protocol. The subjects will receive phone calls from study team 
members as reminders to use the study drug provided. Additionally, containers from the drug provided 
will be collected at the same follow-up study visit to assess use. Subject retention/follow up will be 
assessed via phone call when subject fails to return for study visit within three weeks of completion of 
decolonization protocol. Additional comments due to loss to follow-up will be recorded after scheduled 
phone call. Discontinuation of intervention will occur if serious side effect (anaphylaxis) occurs. 
10.4.6 Baseline Descriptive Statistics 
We will assess differences in baseline descriptive statistics between the intervention groups.  These 
variables include age, sex, history of MRSA infections, history of chronic skin conditions, and recent 
antibiotic use. 
10.4.7 Planned Interim Analysis 
Not applicable 
10.4.7.1 Safety Review 
Study enrollment and administration of study drug will be halted if serious adverse events are noted 
across multiple participants. If it was deemed that enrollment and administration of drug needed to be 
stopped, it would pertain to the entire study including participants in both arms. 
10.4.7.2 Efficacy Review 
Study enrollment and administration of study drug will be halted if serious adverse events are noted 
across multiple participants. If it was deemed that enrollment and administration of drug needed to be 
stopped, it would pertain to the entire study including participants in both arms. Interim analysis is not 
planned for efficacy review.  


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10.4.8 Additional Sub-Group Analyses 
We will assess differences in baseline descriptive statistics between the intervention groups.  These 
variables include age, gender, history of MRSA infections, history of chronic skin conditions, and recent 
antibiotic use. 
10.4.9 Multiple Comparison/Multiplicity 
Not applicable  
10.4.10 
Tabulation of Individual Response Data 
De-identified patient data will be listed measure (blinded) and pre-defined study follow up time points as 
illustrated in the Schematic of Study design on page 2 of this document. . 
 
10.4.11 
Exploratory Analyses 
None planned 
10.5 Sample Size 
The table below presents ranges of the required sample size based on the primary trial endpoint of the 
change in nasal/rectal colonization of MRSA from baseline to 1 week after completion of decolonization 
protocol at approximately 80% power.  It provides a range of sample size depending on the potential 
effectiveness of retapamulin.    
 
Computed N Per Group 
Proportion 
Diff 
Actual Power N Per Group 
0.30 
0.809 
42 
0.35 
0.801 
32 
0.40 
0.807 
26 
0.45 
0.822 
22 
0.50 
0.811 
18 
0.55 
0.802 
15 
0.60 
0.808 
13 
0.65 
0.841 
12 
 
The sample size calculation was based on prior literature indicating a 60% decolonization rate; a 45% 
difference in decolonization between groups (60% retapamulin vs 15% placebo/spontaneous 
decolonization) at 80% power. This is taken into account a 15% spontaneous decolonization rate as 
reported in the literature. Power calculation analyses were performed in SAS 9.3 (SAS Institute, Cary NC) 
using fisher’s exact conditional test for two proportions (Walters normal approximation with exact 
conditional distribution). A 20% lost to follow up was estimated and added to the final sample size 
number. Therefore, the total number of participants enrolled will be 54 subjects – 27 in each of the two 
arms of the study.   
 
It is estimated that 0.8-6% of the general population is colonized with MRSA. Colonization in persons with 
previous infection is estimated to be 20%. We suspect this percent is higher in the particular population 
we aim to study as it is a high risk population for MRSA colonization and infection. Therefore we estimate 
screening 500 participants to meet the sample size goal of our study. 


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We will use fisher exact test at alpha .05 to determine a significant difference between treatment groups 
(retapamulin vs placebo). Participants who withdraw before the 1 week primary endpoint will be excluded 
from analysis as the primary end point will not be recorded.   
10.6 Measures to Minimize Bias 
10.6.1 Enrollment/Randomization/Masking Procedures 
In order to produce treatment groups in which the distributions of prognostic factors, known and unknown, 
are similar and minimize bias, we will randomize participants to treatment groups. We will generate a 
randomization schedule using SAS 9.3 (SAS Institute, Cary NC).  Additionally, participants, investigator, 
treatment team and analyst will be blinded to treatment group.  The generated randomization schedule 
will be provided to the research pharmacy who will assign which arm is the treatment groups and reveal 
assignment after analysis is complete. The pharmacy will carry out the blinding as the drugs (ointments) 
will be aliquoted into unmarked containers labeled with the arm (A or B). The research pharmacy will 
provided drug to the investigators when a subject is enrolled in blinded form. The A/B group identifier 
(retapamulin vs placebo) will not be revealed until the study is completed and data analyzed. There are 
no anticipated obvious drug effects from the retapamulin or placebo that would imperfect blinding.  
10.6.2 Evaluation of Success of Blinding 
If treatment group assignment is unknown to all subjects, investigators, treatment team and analyst for 
the duration of the study, blinding will be considered a success. 
10.6.3 Breaking the Study Blind/Participant Code 
Criteria to break the study blind for an individual include serious adverse events such as anaphylaxis in 
the particular patient. Study blind would be broken for all participants if recurrent serious adverse events 
are observed among numerous participants. Serious adverse effects are not expected with the use of this 
study drug. Intentional and unintentional breaking of the blind will be reported by the PI/co-investigator to 
all members of the study team, the IRB, and the industry sponsor.  
 
11 Source Documents and Access to Source Data/Documents 
Source data is all information, original records of clinical findings, observations, or other activities in a 
clinical trial necessary for the reconstruction and evaluation of the trial.  Source data are contained in 
source documents.  Examples of these original documents, and data records include: hospital records, 
clinical and office charts, laboratory notes, memoranda, subjects’ diaries or evaluation checklists, 
pharmacy dispensing records, recorded data from automated instruments, copies or transcriptions 
certified after verification as being accurate and complete, microfiches, photographic negatives, microfilm 
or magnetic media, x-rays, subject files, and records kept at the pharmacy, at the laboratories, and at 
medico-technical departments involved in the clinical trial. It is acceptable to use CRFs as source 
documents. If this is the case, it should be stated in this section what data will be collected on CRFs and 
what data will be collected from other sources. 
 
The study case report form (CRF) is the primary data collection instrument for the study.  All data 
requested on the CRF must be recorded.  All missing data must be explained.  If a space on the CRF is 
left blank because the procedure was not done or the question was not asked, write “N/D”.  If the item is 
not applicable to the individual case, write “N/A”.  All entries should be printed legibly in black ink.  If any 
entry error has been made, to correct such an error, draw a single straight line through the incorrect entry 
and enter the correct data above it.  All such changes must be initialed and dated.  DO NOT ERASE OR 
WHITE OUT ERRORS.  For clarification of illegible or uncertain entries, print the clarification above the 
item, then initial and date it. 
 
Access to study records will be limited to IRB-approved members of the study team. The investigator will 
permit study-related monitoring, audits, and inspections by the IRB/EC, the sponsor, government 


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regulatory bodies, and University compliance and quality assurance groups of all study related 
documents (e.g. source documents, regulatory documents, data collection instruments, study data etc.).  
The investigator will ensure the capability for inspections of applicable study-related facilities (e.g. 
pharmacy, diagnostic laboratory, etc.). 
 
Participation as an investigator in this study implies acceptance of potential inspection by government 
regulatory authorities and applicable University compliance and quality assurance offices. 
 
12 Quality Assurance and Quality Control 
 
QA/QC will be monitored by Adam Ratner, MD, MPH. All planned study related procedures, data handling 
and analysis will be assessed at the initiation of the trial and semiannually to ensure the trial is performed 
and data is generated, documented and reported in compliance with GCP and the applicable regulatory 
requirements. QC procedures will be implemented beginning with the data entry system and data QC 
checks that will be run on the database will be generated. Any missing data or data anomalies will be 
communicated to the PI for clarification/resolution. 
 
Following written SOPs, the monitors will verify that the clinical trial is conducted and data are generated, 
documented (recorded), and reported in compliance with the protocol, GCP, and the applicable regulatory 
requirements (e.g., Good Laboratory Practices (GLP), Good Manufacturing Practices (GMP)). 
 
The investigational site will provide direct access to all trial related sites, source data/documents, and 
reports for the purpose of monitoring and auditing. 
 
13 Ethics/Protection of Human Subjects 
13.1 Ethical Standard 
The investigator will ensure that this study is conducted in full conformity with Regulations for the 
Protection of Human Subjects of Research codified in 45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 
and/or the ICH E6. 
13.2 Institutional Review Board 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the IRB for review and approval. Approval of both the protocol and the consent form must be 
obtained before any participant is enrolled. Any amendment to the protocol will require review and 
approval by the IRB before the changes are implemented to the study. All changes to the consent form 
will be IRB approved; a determination will be made regarding whether previously consented participants 
need to be re-consented. 
13.3 Informed Consent Process 
13.3.1 Consent/Assent and Other Informational Documents Provided to Participants 
 
Consent forms describing in detail the study agent, study procedures, and risks are given to the 
participant and written documentation of informed consent is required prior to starting 
intervention/administering study product.  
 
The following consent materials are submitted with this protocol in the appendix:  
 
Informed Consent 
Assent (Age 7-11) 


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Assent (Age 12-14) 
Assent (Age 15-17) 
13.3.2 Consent Procedures and Documentation 
 
Informed consent and assent will be obtained from all subjects by the PI and trained study co-
investigators. The consent forms (informed consent, and age specific assents) are included in the 
appendix. Informed consent will be obtained from the participant’s parent/legal guardian and assent will 
be obtained if able from the participant. The study staff will explain the study rationale, procedures, risks 
and benefits. Subjects will be given ample time to read and review the consent/assent forms and to ask 
questions to ensure comprehension of the consent/assent, the scientific background of the study, and the 
procedures required of them.  
 
Since the population being studied may not be able to provide informed consent in English, the informed 
consent and assent forms will be translated into the subject’s preferred language and submitted to the 
IRB for review before a non-English speaking subject is enrolled. A translator will be used when a non-
English speaking subject is taken through the informed consent and assent process. For non-English 
speaking children capable of providing assent, assent will be obtained verbally and documented 
accordingly in the research record. For English speaking children capable of providing assent, the age-
appropriate assent will be signed.  
 
 
The following individuals are authorized to obtain consent: 
Ami Patel, M.D.,M.P.H. – Co-investigator  
Jennifer Lighter, M.D. – Principal Investigator 
Israel Rosman, MBA 
Rebecca Rosenberg, MD, MPH 
 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the study 
and continues throughout the individual’s study participation. Extensive discussion of risks and possible 
benefits of participation will be provided to the participants and their families. Consent forms will be IRB-
approved and the subject’s parent/guardian will be asked to read and review the document while children 
will be asked to review the age-appropriate assent form. The investigator will explain the research study 
to the participant and the parent/guardian and answer any questions that may arise. All participants and 
parent/guardians will receive a verbal explanation in terms suited to their comprehension of the purposes, 
procedures, and potential risks of the study and of their rights as research participants. Participants’ 
parents/guardians will have the opportunity to carefully review the written consent form and ask questions 
prior to signing and the children will in turn have the opportunity to review the assent form and ask 
questions. The participants and their parent/guardian should have the opportunity to discuss the study 
with their families or doctors or think about it prior to agreeing to participate. The participants’ 
parent/guardian will sign the informed consent document prior to any procedures being done specifically 
for the study and the children will sign the appropriate assent form. The participants’ parent/guardian may 
withdraw consent at any time throughout the course of the trial. A copy of the signed informed consent 
and assent document will be given to the participants’ parent/guardian for their records. The rights and 
welfare of the participants will be protected by emphasizing to them that the quality of their medical care 
will not be adversely affected if they decline to participate in this study. 
 
A copy of the signed informed consent document and assent form will be stored in the subject’s research 
record. The consent and assent process, including the name of the individual obtaining consent and 
assent, will be thoroughly documented in the subject’s research record. Any alteration to the standard 
consent process (e.g. use of a translator, consent document presented orally, etc.) and the justification for 
such alteration will likewise be documented.  


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13.4 Participant and Data Confidentiality 
 
Data will be kept secure and minimal personal identification information will be collected which will then 
be de-identified in the study database. Each subject enrolled in the study will be assigned a unique code. 
All samples and data collected will be labeled with the subject’s assigned code. No other names or 
identifiers will be on these samples or data. A file linking the study code to the patient will be maintained 
by the study PI and co--investigator to enable retrieval of additional information if needed. This file will be 
store in a locked cabinet and password protected database created specifically for this study. Only the PI 
and essential research personnel will have access to the cabinet and database. No individual identifiable 
information from the data collected will be published. Only aggregate data will be presented publicly to 
avoid identification of any individual subject. Project staff will verify that all research materials are 
collected before leaving a research site. 
 
Information about study subjects will be kept confidential and managed according to the requirements of 
the Health Insurance Portability and Accountability Act of 1996 (HIPAA).  Those regulations require a 
signed subject authorization informing the subject of the following:  
 What protected health information (PHI) will be collected from subjects in this study 
 Who will have access to that information and why 
 Who will use or disclose that information  
 The rights of a research subject to revoke their authorization for use of their PHI.  
 
In the event that a subject revokes authorization to collect or use PHI, the investigator, by regulation, 
retains the ability to use all information collected prior to the revocation of subject authorization.  For 
subjects that have revoked authorization to collect or use PHI, attempts should be made to obtain 
permission to collect at least vital status (i.e. that the subject is alive) at the end of their scheduled study 
period. 
 
Participant confidentiality is strictly held in trust by the participating investigators, their staff, and the 
sponsor(s) and their agents. This confidentiality is extended to cover testing of biological samples and 
genetic tests in addition to the clinical information relating to participants. Therefore, the study protocol, 
documentation, data, and all other information generated will be held in strict confidence. No information 
concerning the study or the data will be released to any unauthorized third party without prior written 
approval of the sponsor. 
 
The study monitor, other authorized representatives of the sponsor, representatives of the IRB or 
pharmaceutical company supplying study product may inspect all documents and records required to be 
maintained by the investigator, including but not limited to, medical records (office, clinic, or hospital) and 
pharmacy records for the participants in this study. The clinical study site will permit access to such 
records. 
 
The study participant’s contact information will be securely stored at each clinical site for internal use 
during the study. At the end of the study, all records will continue to be kept in a secure location for as 
long a period as dictated by local IRB and Institutional regulations. 
 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will 
be transmitted to and stored at NYU Langone Medical Center. This will not include the participant’s 
contact or identifying information. Rather, individual participants and their research data will be identified 
by a unique study identification number. The study data entry and study management systems used by 
clinical sites and by NYU Langone Medical Center research staff will be secured and password protected. 
At the end of the study, all study databases will be de-identified and archived at the NYU Langone 
Medical Center. 
13.4.1 Research Use of Stored Human Samples, Specimens, or Data 
 
 


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 Intended Use: Samples and data collected under this protocol may be used to study MRSA 
infections, the bacterium, risk factors, complications, potential subsequent microbiome analysis, or 
potential therapies. No genetic testing will be performed. 
 Storage: The isolates from the surface swabs will be retained at Shopsin laboratory. Access to 
stored samples will be limited to study team members. Samples and data will be stored using 
codes assigned by the investigators. Data will be kept in password-protected computers. Only 
investigators will have access to the samples and data. 
 Tracking: Data will be tracked using basic electronic logging/tracking methods (Microsoft word and 
excel). 
o 
Disposition at the completion of the study: All stored samples will be stored at Shopsin 
Laboratory. Study participants who request destruction of samples will be notified of 
compliance with such request and all supporting details will be maintained for tracking. 
 
13.5 Future Use of Stored Specimens 
 
With the approval of the local IRB, de-identified biological samples of MRSA isolates will be stored at the 
Shopsin Laboratory in the Alexandria building at NYU for future research into MRSA and to improve 
treatment. Banking of the isolates is required indefinitely because if the patient/isolates develop 
resistance to the study drug, we would want to find the mechanistic basis of the resistance through 
genotypic and phenotypic analysis. This work can take years to accomplish. The sample from the swabs 
stored will be bacterial strain isolates, no material containing patient DNA is saved. 
 
The banked isolates will be identified via a code. The PI will hold the code-link that will allow linking the 
biological specimens with the phenotypic data from each participant, maintaining the masking of the 
identity of the participant. If future studies are conducted with these isolates, they will be reviewed by the 
site’s IRB under a new protocol or addendum to existing approved protocol. 
 
14 Data Handling and Record Keeping 
14.1 Data Collection and Management Responsibilities 
 
Data collection is the responsibility of the clinical trial PI and co-investigator. The investigators are 
responsible for ensuring the accuracy, completeness, legibility, and timeliness of the data reported. 
 
Data capture will be paper (study related questionnaire, tracking of sample collection, results of sample 
processing, and tracking of study agents) and will be transferred to an electronic database in an ongoing 
fashion by study PI and co-investigator. These paper source documents will be kept in the participants 
study charts that will be kept in a locked cabinet accessible to PI and co-investigator.  
 
All source documents should be completed in a neat, legible manner to ensure accurate interpretation of 
data. Black ink is required to ensure clarity of reproduced copies. When making changes or corrections, 
cross out the original entry with a single line, and initial and date the change. DO NOT ERASE, 
OVERWRITE, OR USE CORRECTION FLUID OR TAPE ON THE ORIGINAL. 
 
Copies of the electronic CRF (eCRF) will be provided for use as source documents and maintained for 
recording data for each participant enrolled in the study. Data reported in the eCRF derived from source 
documents should be consistent with the source documents or the discrepancies should be explained 
and captured in a progress note and maintained in the participant’s official electronic study record. 
 
Clinical data (including AEs, concomitant medications, and expected adverse reactions data) and clinical 
laboratory data will be entered into the subject’s chart and Microsoft word or excel. The data system 
includes password protection and internal quality checks, such as automatic range checks, to identify 


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data that appear inconsistent, incomplete, or inaccurate. Clinical data will be entered directly from the 
source documents. 
14.2 Study Records Retention 
 
Study documents will be retained for the longer of 3 years after close-out, 5 years after final 
reporting/publication, or 2 years after the last approval of a marketing application is approved for the drug 
for the indication for which it is being investigated or 2 years after the investigation is discontinued and 
FDA is notified if no application is to be filed or if the application has not been approved for such 
indication.  
14.3 Protocol Deviations 
 
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or Manual of Procedures 
(MOP) requirements. The noncompliance may be either on the part of the participant, the investigator, or 
the study site staff. As a result of deviations, corrective actions are to be developed by the site and 
implemented promptly. 
 
These practices are consistent with ICH E6: 
 4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3 
 5.1 Quality Assurance and Quality Control, section 5.1.1 
 5.20 Noncompliance, sections 5.20.1, and 5.20.2. 
 
It is the responsibility of the site PI to use continuous vigilance to identify and report deviations within 14 
working days of identification of the protocol deviation, or within 30 working days of the scheduled 
protocol-required activity. 
 
All protocol deviations must be addressed in study source documents, reported to QA/QC and safety 
monitor Adam Ratner, MD, MPH and the IRB by the study PI.  
 
14.4 Publication and Data Sharing Policy 
 
This study will comply with the NIH Public Access Policy, which ensures that the public has access to the 
published results of NIH funded research. It requires scientists to submit final peer-reviewed journal 
manuscripts that arise from NIH funds to the digital archive PubMed Central upon acceptance for 
publication. 
 
The PI and co-investigator will be responsible for developing publishing procedures and resolving 
authorship issues. The study will be registered and updated onto ClinicalTrials.gov.  
 
The International Committee of Medical Journal Editors (ICMJE) member journals have adopted a clinical 
trials registration policy as a condition for publication. The ICMJE defines a clinical trial as any research 
project that prospectively assigns human subjects to intervention or concurrent comparison or control 
groups to study the cause-and-effect relationship between a medical intervention and a health outcome. 
Medical interventions include drugs, surgical procedures, devices, behavioral treatments, process-of-care 
changes, and the like. Health outcomes include any biomedical or health-related measures obtained in 
patients or participants, including pharmacokinetic measures and adverse events. The ICMJE policy, and 
the Section 801 of the Food and Drug Administration Amendments Act of 2007, requires that all clinical 
trials be registered in a public trials registry such as ClinicalTrials.gov, which is sponsored by the National 
Library of Medicine. Other biomedical journals are considering adopting similar policies. For interventional 
clinical trials performed under NIH IC grants and cooperative agreements, it is the grantee’s responsibility 
to register the trial in an acceptable registry, so the research results may be considered for publication in 
ICMJE member journals. The ICMJE does not review specific studies to determine whether registration is 


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necessary; instead, the committee recommends that researchers who have questions about the need to 
register err on the side of registration or consult the editorial office of the journal in which they wish to 
publish. 
 
FDAAA mandates that a "responsible party" (i.e., the sponsor or designated principal investigator) register 
and report results of certain "applicable clinical trials": 
 
 Trials of Drugs and Biologics: Controlled, clinical investigations, other than Phase I investigations 
of a product subject to FDA regulation; 
 Trials of Devices: Controlled trials with health outcomes of a product subject to FDA regulation 
(other than small feasibility studies) and pediatric postmarket surveillance studies. 
 NIH grantees must take specific steps to ensure compliance with NIH implementation of FDAAA. 
 
15 Study Finances 
15.1 Funding Source 
The study is partially financed through an investigator-initiated grant from Aqua Pharmaceuticals and a 
monetary donation made to the PI for academic/research purposes. The study drug is provided by Aqua 
Pharmaceuticals.  
15.2 Costs to the Participant 
There will be no cost to the subjects for participation in this study. The study is being sponsored by a 
grant from Aqua Pharmaceuticals, the company that distributes Retapamulin. All study related costs will 
be paid through this grant. 
15.3 Participant Reimbursements or Payments 
The subjects will receive $100 for their participation in this study. The full compensation will be provided 
upon completion of the study protocol. If subjects were to withdraw prior to the completion of the study, 
they will be eligible for $25 compensation per visit completed. The compensation will be provided to the 
parent/guardian of the participants.  
 
16 Study Administration 
16.1 Study Leadership 
 
The study will be led by the PI (Jennifer Lighter) and co-investigator (Ami Patel). They are responsible for 
participant recruitment, consent, specimen collection and processing, data handling, data analysis, and 
safety monitoring. The main study decisions will be led by them. They will be in continuous 
communication during the duration of the study with weekly meetings.  
 
Other study team members include: Israel Roman, Bo Shopin, MD PhD, Rebecca Rosenberg, MD, MPH 
who will provide guidance on details of study design, subject recruitment and retention, assistance with 
microbiologic procedures and provide general oversight. Anna Stachel, MPH will provide guidance on 
study design, data handling, and will conduct study related statistical analysis. Adam Ratner, MD, MPH 
will provide oversight to the study including QA/QC and safety and clinical monitoring.  
 
All study team members will meet on a semi-annual basis and more frequently as needed to discuss 
study progress. Progress will be communicated and reported in both verbal and written formats.   
 


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17 Conflict of Interest Policy 
 
The independence of this study from any actual or perceived influence, such as by the pharmaceutical 
industry, is critical. Therefore any actual conflict of interest of persons who have a role in the design, 
conduct, analysis, publication, or any aspect of this trial will be disclosed and managed. Furthermore, 
persons who have a perceived conflict of interest will be required to have such conflicts managed in a 
way that is appropriate to their participation in the trial. The study leadership has established policies and 
procedures for all study group members to disclose all conflicts of interest and will establish a mechanism 
for the management of all reported dualities of interest.  
 
Any investigator who has a conflict of interest with this study (patent ownership, royalties, or financial gain 
greater than the minimum allowable by their institution, etc.) must have the conflict reviewed by the NYU 
Langone Conflict of Interest Management Unit (CIMU) with a Committee-sanctioned conflict management 
plan that has been reviewed and approved by the study sponsor prior to participation in this study. All 
NYULMC investigators will follow the applicable conflict of interest policies. 
 
 
18 References 
 
1. 
McConeghy, K.W., D.J. Mikolich, and K.L. LaPlante, Agents for the decolonization of methicillin-resistant 
Staphylococcus aureus. Pharmacotherapy, 2009. 29(3): p. 263-80. 
2. 
Septimus, E.J. and M.L. Schweizer, Decolonization in Prevention of Health Care-Associated Infections. Clin 
Microbiol Rev, 2016. 29(2): p. 201-22. 
3. 
Weinberg, J.M. and S.K. Tyring, Retapamulin: an antibacterial with a novel mode of action in an age of 
emerging resistance to Staphylococcus aureus. J Drugs Dermatol, 2010. 9(10): p. 1198-204. 
4. 
Harrington, A.T., J.A. Black, and J.E. Clarridge, 3rd, In Vitro Activity of Retapamulin and Antimicrobial 
Susceptibility Patterns in a Longitudinal Collection of Methicillin-Resistant Staphylococcus aureus Isolates from a 
Veterans Affairs Medical Center. Antimicrob Agents Chemother, 2015. 60(3): p. 1298-303. 
5. 
Biedenbach, D.J., et al., Susceptibility of Staphylococcus aureus to topical agents in the United States: a 
sentinel study. Clin Ther, 2014. 36(6): p. 953-60. 
6. 
Traczewski, M.M. and S.D. Brown, Proposed MIC and disk diffusion microbiological cutoffs and spectrum of 
activity of retapamulin, a novel topical antimicrobial agent. Antimicrob Agents Chemother, 2008. 52(11): p. 3863-7. 
7. 
Toh, S.M., et al., Acquisition of a natural resistance gene renders a clinical strain of methicillin-resistant 
Staphylococcus aureus resistant to the synthetic antibiotic linezolid. Mol Microbiol, 2007. 64(6): p. 1506-14. 
8. 
Schwarz, S., et al., Lincosamides, Streptogramins, Phenicols, and Pleuromutilins: Mode of Action and 
Mechanisms of Resistance. Cold Spring Harb Perspect Med, 2016. 6(11). 
9. 
Scangarella-Oman, N.E., et al., Microbiological profile of a new topical antibacterial: retapamulin ointment 
1%. Expert Rev Anti Infect Ther, 2009. 7(3): p. 269-79. 
10. 
Paukner, S. and R. Riedl, Pleuromutilins: Potent Drugs for Resistant Bugs-Mode of Action and Resistance. 
Cold Spring Harb Perspect Med, 2016. 
11.     Liu, C, et al, Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of 
Methicillin-Resistant Staphylococcus aureus Infections in Adults and Children. IDSA Guidelines. 2011 
12.     Gallagher, P, Identification and Analysis of Orthodox Jewish Enclaves in Brooklyn, New York: A GIS Based 
Approach. Middle States Geographer 2009;42:83-9. 
13.           Singh, R et al, (October 2016). Randomized Double-Blinded Placebo-Controlled Trial of Retapamulin for 
Nasal Decolonization of Mupirocin-Resistant MRSA Carriers. Poster abstract session presented at ID week. New 
Orleans, LA. 
14.   
  Pankuch et al, Activity of Retapamulin against Streptococcus pyogenes and Staphylococcus aureus 
Evaluated by Agar Dilution, Microdilution, E-test, and Disk Diffusion Methodologies. Antimicrob Agents Chemother, 
2006. 50(5):p.1727-1739. 


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15.   
 Ross et al, Quality Control Guidelines for Susceptibility Testing of Retapamulin (SB-275833) by Reference 
Standard Methods, J Clin Microbiol 2005.43(12): p 6212-6213. 
16.  
 Harbarth et al, Randomzied, placebo-controlled, double blin trial to evaluate the efficacy of mupirocin for 
eradicating carriage of methicillin-resistant Staphylocccus aureus. Antimicrob Agents Chemother, 1999. 
43(6):p.1412-6. 
17. 
  Mody et al, Mupirocin-based decolonization of Staphylococcus aureus carriers in residents of 2 long-term 
care facilities: a randomized, double-blind, placebo-controlled trial. Clin Infect Dis, 2003. 37(11):p.1467-74. 
18.  
Singh et al, Rendomized Double-Blinded Placebo-Controlled Trial of Retapamulin for Nasal Decolonization 
of Mupiocin-Resistant MRSA Carriers. ID Week. Infectious Diseases Society of America. New Orleans. 27 October 
2016. Poster presentation. 
 
 


Study number: s17-00907 
 
Page 34 
Version: 8.0 06/20/2018 
 
 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as 
authorized in writing by the study sponsor 
Interventional Template Version: 28 APR 2017 
19 Attachments 
These documents are relevant to the protocol, but they are not considered part of the protocol.  They are 
stored and modified separately. As such, modifications to these documents do not require protocol 
amendments. 
 
19.1 Informed Consent 
19.2 Assent (Age 7-11) 
19.3 Assent (Age 12-14) 
19.4 Assent (Age 15-17) 
19.5 Questionnaire - Initial 
19.6 Questionnaire – Follow Up 
19.7 Instructions on application of study drug and environmental decolonization protocol  
19.8 Retapamulin Package Insert/Product Information  
 
19.9   Data Collection Form  
 
19.10  Study handout 
 
 
 
 


Study number: s17-00907 
 
Page 35 
Version: 8.0 06/20/2018 
 
 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as authorized in writing by the study sponsor 
Interventional Template Version: 05 JAN 2017 
 
20 Schedule of Events 
 
 
 
 
Screening 
Visit 1 
Decolonization at home 
Visit 2 
Visit 3 
 
Screening visit  
Enrollment 
 
Retapamulin vs placebo 
1 week post-
decolonization 
4 weeks post-decolonization 
Consent/ Assent 
X 
 
 
 
 
Randomization 
 
X 
 
 
 
Demographics  
 
X 
 
 
 
Medical History 
 
X 
 
X 
X 
Physical Examination  
 
X 
 
X 
X 
Questionnaire 
 
X 
 
X 
X 
Nasal/Peri-rectal Swabs 
X 
 
 
X 
X 
Study drug dispensation  
 
X 
 
 
 
Participant study drug 
compliance check 
 
 
 
X 
 
Participant Adverse 
Events check 
 
 
 
X 
X