Conditions: Scabies
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 140
Healthy volunteers: no

Brief summary:
This is a multi-center, double-blind, randomized, two arm parallel design study. This study is comprised of two phases: screening and treatment. The screening period will be up to 5 days, followed by the treatment phase of 28±4 days. During the treatment phase subjects will be randomized to receive either test or reference treatments in a double-blind manner in an outpatient setting. Randomization of subjects will be in a 1:1 ratio for the test and reference drug arms and will be stratified by site.

Screening will begin at visit 1, during which eligibility will be determined and prohibited treatments will be discontinued. Randomization will occur following the confirmation of the eligibility criteria at visit 2 (baseline, Day 1) i.e. initiation of treatment phase. The treatment phase will be 28±4 days in duration wherein subject will receive treatment with investigational product (either test or reference) on Day 1 or Baseline (visit 2). Safety and tolerability assessments will be performed on Day 7 (visit 3). Efficacy, safety and tolerability will be assessed on Day 14 (visit 4) followed by the End of study visit on Day 28 (visit 5). If positive identification of scabies is confirmed at Day 14 (visit 4), the subject will be retreated with the second application of the investigational product.

Detailed description:
Systemic absorption of permethrin cream is limited to 0.5% during the first 48 hours following dermal application. In these settings, a conventional pharmacokinetic human study to demonstrate that Mayne Permethrin cream (5% w/w) is bioequivalent to the Reference Listed Drug \[RLD\] Elimite™ is not appropriate.

This is a clinical endpoint bioequivalence (BE) study for a Permethrin Cream, 5% formulation for the treatment of active scabies in comparison to Elimite™ Permethrin cream (5% w/w).

* Test Product: Permethrin Cream, 5%
* Reference Product: Elimite™ marketed by Prestium Pharma, Inc. ("Prestium"), the branded subsidiary of Renaissance Pharma.

The infested person, as well as household members are treated at the same time to prevent re-infestation. In consideration of this recommendation, the household members of the enrolled subject will be examined and treated at the same time as the enrolled subject with an FDA-approved generic Permethrin Cream, 5%.

Arms:
arm 1: Permethrin Cream 5%, topical cream, 60g, maximum of two doses over 28 day treatment duration. arm 2: Elimite™ 60g, topical, marketed by Prestium Pharma, Inc. ("Prestium"), the branded subsidiary of Renaissance Pharma, maximum of two doses over 28 day treatment duration.

Interventions: intervention 1: Permethrin Cream, 5% intervention 2: Elimite
Intervention descriptions: intervention 1: Subjects on Test product will receive a maximum of two doses, 60 g each, during the study. The first dose will be applied on Day 1 in an outpatient setting, after the visit to the clinical site (preferably in the evening). The second dose will be applied on Day 14±2 only if retreatment is necessary. intervention 2: Subjects on RLD will receive a maximum of two doses, 60 g each, during the study. The first dose will be applied on Day 1 in an outpatient setting, after the visit to the clinical site (preferably in the evening). The second dose will be applied on Day 14±2 only if retreatment is necessary.

Protocol document:
Prot_000.pdf: 
 
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Page 1 of 66 
 
CLINICAL STUDY PROTOCOL 
PROTOCOL NUMBER: MAP-8184 
A MULTI-CENTER, DOUBLE-BLIND, RANDOMIZED, PARALLEL-GROUP 
STUDY COMPARING PERMETHRIN CREAM, 5% (MAYNE PHARMA, INC.) 
WITH ELIMITE™ IN PATIENTS WITH ACTIVE SCABIES 
Sponsor 
Mayne Pharma, Inc. 
1240 Sugg Parkway, 
Greenville, NC 27858 USA 
Phone: +1 (252) 717-1382 
Fax: +1 (252) 758-8522 
Amendment No. 1 Version 2.0 
14 October 2016 
Original Protocol Version 1.0 
18 March 2016 




 
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INVESTIGATOR SIGNATURE PAGE 
The signature below constitutes approval of this protocol and provides the necessary assurance that this 
study will be conducted at his/her investigational site according to all stipulations of the protocol including 
all statements of confidentiality and in accordance with ICH GCP and local regulatory requirements. 
 
Print Name 
 
Title 
 
Address of Institution / 
Site: 
_________________________________________________________ 
_________________________________________________________ 
_________________________________________________________ 
_________________________________________________________ 
Telephone Number: 
 
INVESTIGATOR SIGNATURE: _______________________________   DATE: _______________ 


 
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PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Section 
Description of change 
Principal Contacts 
Biorasi Project Manager changed  
Glossary of Abbreviations 
Updated the Glossary, adding missing entries. Acronyms were updated thorough 
the text 
Section 1.2 Rationale of the 
Study 
Updated a reference to CDC treatment guidance for scabies. 
Section 3.1 Study Design 
Phrase “application of standard of care” for the household members was 
changed to “Household members will receive one 60 g tube of the standard of 
care generic Permethrin Cream, 5% at the Baseline visit, sufficient for two 
applications…”. 
3.2 Number of Subjects 
and Sites 
Changed to 3.2 Number of Subjects. Removed Number of sites from the protocol. 
Changed number of subjects to 140. Added provision that the number of subjects 
may be increased based on the reference product availability 
Section 4.1 Study 
Population 
Changed number of subjects to 140 (per protocol population = 112) as per the 
new Sample Size Determination (see Section 8.2). 
Section 4.2.1 Inclusion 
Criteria #5 
Added that household members will be provided with standard of care 
treatment “if deemed necessary by the Investigator” to match protocol design. 
Section 4.2.1 Inclusion 
Criteria #7 
Added new inclusion criterion: 6.7. Subject must be able to apply study product 
to self. If the subject is a child, then parent/guardian will apply study product to 
him/her. 
Section 4.2.2 Exclusion 
Criteria #3 
Updated the exclusion criteria by replacing the reference to the Section 5.11 with 
the actual list of prohibited medication. 
Section 4.2.2 Exclusion 
Criteria #4 
Updated the exclusion criteria by adding history of seizures. 
Section 4.2.2 Exclusion 
Criteria #8 
Updated an exclusion criterion by adding “…synthetic pyrethroids, pyrethrin, 
chrysanthemums or ragweed”. 
Section 5.5 Reserve Sample 
Retention 
Clarified language. Added a reference to the Pharmacy Manual. 
Section 5.6 Treatment 
Assignment 
(Randomization) 
Updated language as per the vendor specifications. 
Added details on how the randomization code will be supplied with each block of 
the investigational product and moved this paragraph to the next section 
(5.7 Blinding). 
Added Section 5.6.1 Assignment of Retreatment, capturing the process for 
dispensing the investigational product for the retreatment. 
Section 5.7 Blinding 
Deleted that the dispensed investigational product may be opened in front of the 
study pharmacist, or designated study personnel. 
Section 5.8 Treatment 
Administration 
The following phrase has been removed: “Subjects will apply investigational 
product once a week for two weeks, preferably in the evening whether or not 
the area(s) appear clinically healed.” 
Section 5.11 Prior, 
Replaced “Oral corticosteroids” with “Systemic corticosteroids” in the prohibited 


 
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Concomitant and 
Prohibited Therapy 
medication list. 
Section 6.3 Schedule of 
Activities 
Visit 4: added bullet point on reapplication of the standard of care by the 
household members of the participating study subject requiring retreatment 
Visit 5: added “Vital signs” 
Section 8.2 Sample Size 
Determination 
Probability of study success for the sample size being reevaluated, which lead to 
the change in the sample size 
12.2 Appendix B. Schedule 
of Events 
Footnote 5 stating “Vital signs are to be performed if Inclusion/Exclusion Criteria 
are satisfied at Screening” deleted as redundant 
12.3 Appendix C. 
Declaration of Helsinki 
Removed 
12.3 Appendix C. Subject 
Diary 
Added 
12.4 Appendix D. Patient 
Self-Assessment 
Added 
Additional formatting and stylistic adjustments have been made and typographical errors corrected to 
facilitate reading process. 


 
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TABLE OF CONTENTS 
SIGNATURE PAGE ............................................................................................................................2 
INVESTIGATOR SIGNATURE PAGE .....................................................................................................3 
PROTOCOL AMENDMENT SUMMARY OF CHANGES ..........................................................................4 
TABLE OF CONTENTS .......................................................................................................................6 
GLOSSARY OF ABBREVIATIONS ...................................................................................................... 10 
PROTOCOL SYNOPSIS ..................................................................................................................... 12 
PRINCIPAL CONTACTS .................................................................................................................... 18 
1. 
BACKGROUND AND RATIONALE .............................................................................................. 19 
1.1 
Background to the Disease ................................................................................................. 19 
1.2 
Rationale of the Study ....................................................................................................... 20 
2. 
STUDY OBJECTIVES AND ENDPOINTS ...................................................................................... 21 
2.1 
Study Objectives ................................................................................................................ 21 
2.1.1 
Primary Objective ............................................................................................................ 21 
2.1.2 
Secondary Objective ........................................................................................................ 21 
2.2 
Study Endpoints ................................................................................................................ 21 
2.2.1 
Primary Endpoint ............................................................................................................. 21 
2.2.2 
Secondary Endpoint ......................................................................................................... 21 
2.3 
Safety Variables ................................................................................................................. 21 
2.4 
Tolerability Assessments.................................................................................................... 21 
3. 
INVESTIGATIONAL PLAN ......................................................................................................... 22 
3.1 
Study Design ..................................................................................................................... 22 
3.2 
Number of Subjects ........................................................................................................... 23 
4. 
SELECTION AND WITHDRAWAL OF STUDY POPULATION .......................................................... 24 
4.1 
Study Population ............................................................................................................... 24 
4.2 
Eligibility Criteria ............................................................................................................... 24 
4.2.1 
Inclusion Criteria .............................................................................................................. 24 
4.2.2 
Exclusion Criteria ............................................................................................................. 24 
4.2.3 
Criteria for Inclusion of Minor Subjects ........................................................................... 26 
4.3 
Withdrawal and Early Discontinuation ............................................................................... 26 
5. 
INVESTIGATIONAL PRODUCT AND TREATMENT OF SUBJECTS .................................................. 28 
5.1 
Investigational Products [IP] .............................................................................................. 28 


 
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5.1.1 
Test Product ..................................................................................................................... 28 
5.1.2 
Reference Product/Comparator ...................................................................................... 28 
5.2 
Standard of Care [SOC] ...................................................................................................... 28 
5.3 
Packaging and Labeling ...................................................................................................... 28 
5.4 
Storage of investigational product and SOC ........................................................................ 29 
5.5 
Reserve Sample Retention ................................................................................................. 29 
5.6 
Treatment Assignment (Randomization) ............................................................................ 29 
5.6.1 
Assignment of Retreatment ............................................................................................ 29 
5.7 
Blinding ............................................................................................................................. 30 
5.8 
Treatment Administration ................................................................................................. 30 
5.8.1 
Investigational Product Dispensation and Application ................................................... 30 
5.8.2 
Administration of Standard of Care ................................................................................. 31 
5.9 
Treatment Compliance ...................................................................................................... 31 
5.10 
Accountability, Destruction and Return of Study Supplies ................................................... 32 
5.11 
Prior, Concomitant and Prohibited Therapy ........................................................................ 33 
6. 
STUDY PROCEDURES AND SCHEDULE OF ACTIVITIES ................................................................ 34 
6.1 
Administrative Procedures ................................................................................................. 34 
6.1.1 
Subject Informed Consent ............................................................................................... 34 
6.1.2 
Documentation of Screen Failures .................................................................................. 34 
6.1.3 
Contraception and Pregnancy Avoidance Measures ...................................................... 34 
6.2 
Study Procedures and Evaluations ..................................................................................... 35 
6.2.1 
Clinical Evaluations .......................................................................................................... 35 
6.2.1.1 
Subject Demographics ............................................................................................... 35 
6.2.1.2 
Medical history .......................................................................................................... 35 
6.2.1.3 
Physical examination ................................................................................................. 35 
6.2.1.4 
Vital Signs ................................................................................................................... 35 
6.2.1.5 
Visual Examination of Lesions .................................................................................... 35 
6.2.1.6 
Adverse Event Assessments ....................................................................................... 36 
6.2.1.7 
Concomitant Medication Recording .......................................................................... 36 
6.2.2 
Laboratory Evaluations .................................................................................................... 36 
6.2.2.1 
Microscopic Examination of Skin Scraping ................................................................ 36 
6.2.2.2 
Pregnancy test ........................................................................................................... 36 
6.2.3 
Patient Self-Assessment .................................................................................................. 36 


 
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6.2.4 
Subject Diary Compliance Review ................................................................................... 37 
6.3 
Schedule of Activities......................................................................................................... 38 
6.3.1 
Visit 1: Screening Visit (Days -5 to 1) ............................................................................... 38 
6.3.2 
Visit 2: Baseline (Day 1) ................................................................................................... 38 
6.3.3 
Visit 3: Interim Evaluation (Day 7±1 Day) ........................................................................ 39 
6.3.4 
Visit 4: Interim Evaluation (Day 14±2 Day) ...................................................................... 39 
6.3.5 
Visit 5: End of Study / Early Termination, and Final Safety Check (Day 28±4) ................ 40 
6.3.6 
Unscheduled Visit ............................................................................................................ 40 
7. 
SAFETY DATA COLLECTION, RECORDING AND REPORTING ....................................................... 41 
7.1 
Definitions ........................................................................................................................ 41 
7.1.1 
Adverse Event .................................................................................................................. 41 
7.1.2 
Serious Adverse Events.................................................................................................... 41 
7.2 
Adverse Event Severity ...................................................................................................... 42 
7.3 
Causality of Adverse Events ............................................................................................... 42 
7.4 
Adverse Event Collection Period ........................................................................................ 43 
7.5 
Adverse Event Reporting ................................................................................................... 43 
7.6 
Unblinding due to SAE ....................................................................................................... 44 
8. 
DATA ANALYSIS ...................................................................................................................... 45 
8.1 
Subject Population/Data Sets to Be Evaluated .................................................................... 45 
8.2 
Sample Size Determination ................................................................................................ 46 
8.3 
Statistical Analyses ............................................................................................................ 46 
8.3.1 
Subject Disposition and Demography ............................................................................. 46 
8.3.2 
Assessment of Bioequivalence as Primary and Secondary Endpoints ............................ 46 
8.3.3 
Assessment of retreatment ............................................................................................. 47 
8.3.4 
Assessment of Tolerability ............................................................................................... 47 
8.3.5 
Assessment of Safety ....................................................................................................... 47 
9. 
REGULATORY, ETHICAL, AND LEGAL OBLIGATIONS .................................................................. 49 
9.1 
Ethical Conduct of the Study .............................................................................................. 49 
9.2 
Institutional Review Board (IRB) / Independent Ethics Committee (IEC) .............................. 49 
9.3 
Other Required Approvals ................................................................................................. 49 
9.4 
Informed Consent .............................................................................................................. 49 
9.5 
Subject Confidentiality....................................................................................................... 50 
9.6 
Publication ........................................................................................................................ 50 


 
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10. ADMINISTRATIVE OBLIGATIONS ............................................................................................. 51 
10.1 
Source Documentation Forms ............................................................................................ 51 
10.2 
Record Retention .............................................................................................................. 51 
10.3 
Quality Control (QC) and Quality Assurance (QA)................................................................ 52 
10.3.1 
Study Site Monitoring Visits ............................................................................................ 52 
10.3.2 
Protocol Deviations ......................................................................................................... 52 
10.4 
Trial Discontinuation/Investigative Site Termination .......................................................... 53 
10.4.1 
Criteria for Premature Termination or Suspension of the Study .................................... 53 
10.4.2 
Criteria for Premature Termination or Suspension of Investigational Sites ................... 53 
10.4.3 
Procedures for Premature Termination or Suspension of the Study or Investigational 
Site(s) ............................................................................................................................... 53 
11. REFERENCES ........................................................................................................................... 54 
12. APPENDICES ........................................................................................................................... 55 
12.1 
Appendix A. Study Flowchart ............................................................................................. 55 
12.2 
Appendix B. Schedule of Events ......................................................................................... 56 
12.3 
Appendix C. Subject Diary .................................................................................................. 57 
12.4 
Appendix D. Patient Self-Assessment ................................................................................. 65 
 


 
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GLOSSARY OF ABBREVIATIONS 
AE 
Adverse Event 
CRA 
Clinical Research Associate 
eCRF 
Electronic Case Report Form 
EOS 
End of Study 
ET 
Early Termination 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIV 
Human Immunodeficiency Virus 
IB 
Investigator’s Brochure 
ICH 
International Conference On Harmonization 
ID 
Identification 
IEC 
Independent Ethics Committee 
IP 
Investigational Product 
IRB 
Institutional Review Board 
IUD 
Intrauterine Device 
LOCF 
Last Observation Carried Forward 
MedDRA 
Medical Dictionary of Regulatory Activities 
mITT 
Modified Intent-To-Treat 
OTC 
Over-the-Counter 
PD 
Protocol Deviation 
PDRR 
Protocol Deviation Review Request 
PMH 
Past Medical History 
PP 
Per-Protocol 
PRN 
Pro Re Nata (as needed) 
PSA 
Patient Self-Assessment 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event 


 
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SOC 
Standard of Care 
SOP 
Standard Operating Procedures 
SUSAR 
Suspected Unexpected Serious Adverse Reactions 
WHO 
World Health Organization 


 
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PROTOCOL SYNOPSIS 
Sponsor: 
Mayne Pharma, Inc. 
Name of Finished Product: 
Permethrin Cream 
Name of Active Ingredient(s): 
Permethrin, 5% 
Study Title 
A Multi-Center, Double-Blind, Randomized, Parallel-Group Study Comparing Permethrin Cream, 5% 
(Mayne Pharma, Inc.) with Elimite™ in patients with active scabies. 
Type of Study 
Bioequivalence with Clinical Endpoints. 
Objectives 
Primary: To demonstrate bioequivalence between Permethrin Cream, 5% (Mayne Pharma, Inc.) and 
Elimite™ in patients with active scabies. 
Secondary: To demonstrate comparative safety of Permethrin Cream, 5% (Mayne Pharma, Inc.) vs 
Elimite™ and tolerability of Permethrin Cream, 5%. 
Methodology 
This is a multi-center, double-blind, randomized, two arm parallel design study. This study is 
comprised of two phases: screening and treatment. The screening period will be up to 5 days, 
followed by the treatment phase of 28±4 days. During the treatment phase subjects will be 
randomized to receive either test or reference treatments in a double-blind manner in an outpatient 
setting. Randomization of subjects will be in a 1:1 ratio for the test and reference drug arms and will 
be stratified by site. 
Screening will begin at visit 1, during which eligibility will be determined and prohibited treatments 
will be discontinued. Randomization will occur following the confirmation of the eligibility criteria at 
visit 2 (baseline, Day 1) i.e. initiation of treatment phase. The treatment phase will be 28±4 days in 
duration wherein subject will receive treatment with investigational product (either test or 
reference) on Day 1 or Baseline (visit 2). Safety and tolerability assessments will be performed on 
Day 7 (visit 3). Efficacy, safety and tolerability will be assessed on Day 14 (visit 4) followed by the End 
of study visit on Day 28 (visit 5). If positive identification of scabies is confirmed at Day 14 (visit 4), 
the subject will be retreated with the second application of the investigational product. 
Planned Number of Subjects 
Number of subjects to be allocated to treatments according to a 1:1 randomization will depend on 
the limited availability of Reference product. Currently, enough drug is available for  a total of N=140 
(enrolled subjects) to achieve N=112 per protocol population. Should additional Reference product 
become available prior to completion of the clinical phase of the study, enrollment will be increased 


 
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Sponsor: 
Mayne Pharma, Inc. 
Name of Finished Product: 
Permethrin Cream 
Name of Active Ingredient(s): 
Permethrin, 5% 
to a total of up to N = 228 (enrolled subjects) to achieve N = 182 (per protocol) population. 
Eligibility Criteria 
Subjects who satisfy ALL of the following inclusion and have NONE of the following exclusion criteria 
may be enrolled in the study: 
Inclusion Criteria 
1. Male or non-pregnant, non-lactating female subject at least 12 years of age or older. 
2. Subject must have a positive identification for mites, eggs, or mite fecal matter by microscopic 
examination of a skin scraping. 
3. Subjects must have at least two of the three following: a) excoriations and inflammatory 
papules with a typical distribution pattern and localization (webbed spaces of the fingers, 
flexor surfaces of the wrists, elbows, axillae, belt line, feet, skin surface of external genitalia, 
or areolae); b) presence of burrows; c) family or contacts with moderate to severe itching 
which increases during the night. 
4. Subjects must be willing to make every effort to immediately disinfect clothes, towels, and 
linens and all potentially infected household items upon diagnosis of infestation to prevent re-
infestation. 
5. All household members with prolonged physical contact with the subject must be willing to 
attend Baseline visit and receive treatment with standard of care if deemed necessary by the 
Investigator in order to prevent re-infestation of the subject enrolled. 
6. Subject or representative must read and sign an Institutional Review Board/Independent Ethics 
Committee (IRB/IEC) approved Informed Consent Form (ICF); for minor subjects (18 years or 
younger in most states) the parent or legal guardian should sign the ICF and the child will be 
required to sign the Assent Form that will written in such a way as to be understandable to a 
child. 
7. Subject must be able to apply study product to self. If the subject is a child, then 
parent/guardian will apply study product to him/her. 
Exclusion Criteria 
1. Females who are pregnant as shown in a urine pregnancy test at the Baseline visit, prior to 
randomization, or lactating, or of childbearing potential (for purpose of this study a female of 
childbearing potential is considered to be not surgically sterile or postmenopausal for at least 
1 year) who are not using or do not agree to use an acceptable form of contraception (oral 
/implant /injectable /transdermal contraceptives, intrauterine device (IUD), condom, 


 
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Sponsor: 
Mayne Pharma, Inc. 
Name of Finished Product: 
Permethrin Cream 
Name of Active Ingredient(s): 
Permethrin, 5% 
diaphragm, or abstinence) during the study, or who intends to become pregnant during the 
study; contraceptive method must also be consistent throughout the study. 
2. Treatment for scabies <4 weeks prior to enrollment, including permethrin, benzyl alcohol, 
lindane, crotamiton, malathion, and ivermectin. 
3. Use of prohibited medications: 
• 
Topical or oral scabicidal/antiparasitic treatment including: permethrin, benzyl alcohol, 
benzyl benzoate, lindane, crotamiton, malathion, ivermectin, precipitated sulfur, 
albendazole, keratolytic cream, tea tree oil, or oil of the leaves of Lippia multiflora Moldenke 
within 28 days of visit 2. 
• 
Systemic corticosteroids (including inhaled steroids) taken within 14 days of visit 2. 
• 
Topical corticosteroids including hydrocortisone taken within 24 hours of visit 2. 
• 
Topical antipruritics, including antihistamines within 24 hours of any study visits. 
• 
Oral antihistamine including diphenhydramine (Benadryl) taken within 24 hours of any study 
visits. 
• 
Topical antibiotics including mupirocin taken within 24 hours of any study visits. 
4. Patients with immunosuppressive disorders requiring therapy, severe systemic disease, history 
of HIV infection and/or seizures. 
5. Patients with crusted/Norwegian scabies. 
6. Presence of underlying skin disease that would obscure evaluation of the papules and burrows 
associated with scabies infection as determined by the Investigator. 
7. Presence of severe cutaneous bacterial or fungal infections requiring therapy (including 
systemic and topical antibiotics) as determined by the Investigator. 
8. Sensitivity or allergy to Permethrin Cream or any of its components, synthetic pyrethroids, 
pyrethrin, chrysanthemums or ragweed. 
9. A recent (less than 1 year) history of alcoholism, drug abuse, or other problems which would 
likely make the subject unreliable for the study. 
10. Participation in another investigational study or using any investigational product within the 
30 days prior to the Baseline visit. 
11. Participation of family member, or another member of the household (including regular 
bedmates) in the current study. 
12. Total number of bedmates and family members with prolonged physical contact is greater than 
6 (including study subject). 


 
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Sponsor: 
Mayne Pharma, Inc. 
Name of Finished Product: 
Permethrin Cream 
Name of Active Ingredient(s): 
Permethrin, 5% 
13. Any employees of the clinic, investigators, or family members of the study staff. 
14. Patients who in the opinion of the Investigator would be non-compliant with the requirements 
of the study protocol. 
Investigational Products, Dose and Mode of Administration: 
Test Drug: Permethrin Cream, 5%, 60g, topical, manufactured by Mayne Pharma International Pty 
Ltd. 
Reference Product: Elimite™ 60g, topical, marketed by Prestium Pharma, Inc. (“Prestium”), the 
branded subsidiary of Renaissance Pharma. 
Standard of Care (SOC): Generic Permethrin Cream, 5% 60g available in the market will be used for 
treatment of the household members with active scabies or at a “high risk” of the disease. 
Dose During the Active Treatment Period: Subjects will receive a maximum of two doses of the 
investigational product during the study. The first dose will be applied on Day 1 in an outpatient 
setting, after the visit to the clinical site (preferably in the evening). The second dose will be applied 
on Day 14±2 only if retreatment is necessary. Household members will receive one 60 g tube of the 
standard of care generic Permethrin Cream, 5% at the Baseline visit, sufficient for two applications: 
at the time of the Baseline visit of the participating study subject, and in two weeks - if the re-
treatment will be necessary of the standard of care at Baseline visit. 
Route: Topical application, covering the entire area of the skin from the neck down to the feet. 
Study Duration: 28 Days 
Primary Endpoint: The primary endpoint will be the proportion of patients that are identified as 
cured at Study Day 28. Cure is defined as the absence of new lesions and the healing of all old lesions. 
Residual, dry, non-inflammatory papules are not counted as active. 
Secondary Endpoint: The secondary endpoint will be the proportion of patients that are identified 
as cured at Study Day 14. 
Safety: Analysis of safety variables will be based on all adverse event (AE) capture measuring 
severity and duration utilizing MedDRA terminology for consistency. Vital signs will also be 
reviewed and analyzed at the Baseline and at visit 5 (End of Study visit). 
Tolerability: Analysis of tolerability will be based on scores of Stinging/Burning and Itching 
sensations collected during Patient Self-Assessments at visits 2-5 between the test and reference 
treatment groups. 
Statistical Methods: To establish bioequivalence, the continuity-corrected 90% confidence interval 


 
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Sponsor: 
Mayne Pharma, Inc. 
Name of Finished Product: 
Permethrin Cream 
Name of Active Ingredient(s): 
Permethrin, 5% 
of the difference in the proportion of subjects with treatment success (defined as the absence of 
new lesions and the healing of all old lesions) between the test and reference products treatment 
groups at Study Day 28 must be within [-0.20, +0.20]. 
Results in the (Per-Protocol) PP population will be considered definitive and those in the mITT 
population as supportive. 
To assess treatment differences in the secondary endpoint, the proportion of subjects that are 
identified as cured in the test and reference treatment groups at Study Day 14 will be analyzed 
following the same approach as described for Day 28. 
Populations for Analysis 
Safety Population: The safety population is any randomized individual who was enrolled into the 
study, and (b) received at least one dose of study treatment. 
Modified Intent-to-Treat (mITT) Population: A modified intent-to-treat individual is any randomized 
individual who (a) met inclusion/exclusion criteria, (b) was enrolled into the study, (c) received at 
least one dose of the assigned study treatment, and (c) had at least one post-baseline visit. 
Per Protocol (PP) Population: A per-protocol subject is any randomized individual who (a) met 
inclusion/exclusion criteria, (b) was enrolled into the study, (c) received the assigned study 
treatment, (d) had not taken any concomitant medications prohibited by the protocol or experienced 
any major deviations that interfered with or may have interfered with the therapeutic administration 
of the treatment or the precise evaluation of treatment efficacy, and (e) completed the primary 
endpoint evaluation within the designated visit window (±4 days). 
Subjects whose condition worsens and require alternate or supplemental therapy for the treatment 
of scabies during the study will be discontinued, included in both the mITT and PP population 
analyses as treatment failures. Subjects who discontinue early for reasons other than treatment 
failure will be excluded from the PP population, but included in the mITT population, using Last 
Observation Carried Forward (LOCF). 
Efficacy analyses will be performed using the per-protocol population as definitive and the mITT 
population as supportive. Safety analyses will be performed using the Safety population. 
Efficacy 
Primary Endpoint: The proportion of subjects considered to be cured (defined as the absence of new 
lesions and the healing of all old lesions) on Study Day 28. To establish bioequivalence, the continuity-
corrected, 90% confidence interval for the test-to-reference difference in proportions of subjects 
cured must be within the equivalence limits -0.20 to 0.20. Results in the PP population will be 
considered definitive and those in the mITT population as supportive. 


 
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Sponsor: 
Mayne Pharma, Inc. 
Name of Finished Product: 
Permethrin Cream 
Name of Active Ingredient(s): 
Permethrin, 5% 
Secondary Endpoint: The proportion of subjects that are identified as cured at Study Day 14. 
Bioequivalence will be assessed using the same approach as in the primary endpoint. 
Tolerability: Tolerability, including itching and burning, will be assessed by the Patient Self-
Assessment (PSA) for Stinging/Burning and Itching, depicted in Section 6.2.3 of the protocol. 
Descriptive statistics using categorical methods will be used to compare tolerability measures 
between the test and reference treatment groups. 
Safety 
Medical Data Coding of the Verbatim terms provided by the Investigators for AEs and Concomitant 
Medications will be performed using relevant MedDRA and WHO Drug dictionaries respectively. 
Safety Data Analysis will include subjects’ disposition, numbers of completed and discontinued 
subjects, and causalities for early discontinuation. AEs/SAEs data will be summarized and all AEs will 
be listed for individual subjects showing both verbatim and preferred terms. The number and percent 
of subjects taking concomitant medications will be summarized using WHO Drug dictionary 
classifications. 
AEs and SAEs Assessment. All AEs/SAEs will be captured in electronic Case Report Form (eCRF) and 
study logs. Serious Adverse Events will be reported by the Investigators using SAE Report Form during 
the 24-hour interval to Biorasi Safety for future analysis and processing. The occurrence of 
treatment-emergent AEs (TEAEs) will be summarized by treatment group using MedDRA Preferred 
Terms (PTs), System Organ Classifications (SOCs), severity, outcome and causality. Separate 
summaries of treatment-emergent SAEs and AEs related to treatment will be generated. 
Prohibited Medication 
List of prohibited medication is supplied in Section 5.11 of the protocol. 


 
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PRINCIPAL CONTACTS 
CLINICAL PROTOCOL AND CONDUCT 
INQUIRIES 
Michael D. Ruff, PharmD, CPIP 
Clinical Director 
Mayne Pharma, Inc. 
email: mike.ruff@maynepharma.com 
1240 Sugg Parkway, 
Greenville, NC 27858 USA 
Phone: +1 (252) 717-1382 
Fax: +1 (252) 758-8522 
 
Phoevos Hughes, J.D. 
Project Manager 
Biorasi LLC 
email: phughes@biorasi.com 
19495 Biscayne Blvd., Suite #900 
Aventura, FL 33180 
Phone: +1 (786) 888-2245 
CLINICAL SAFETY INQUIRIES 
Sergey Yagoda, MD, PhD 
Medical Monitor 
Biorasi Safety and Pharmacovigilance  
email: syagoda@biorasi.com 
19495 Biscayne Blvd., Suite #900 
Aventura, FL 33180 
Fax: +1 (786) 221-3531 
REPORTING OF SERIOUS ADVERSE EVENTS 
(SAES) AND PROTOCOL DEVIATIONS 
Biorasi Safety and Pharmacovigilance 
email: safety@biorasi.com 
19495 Biscayne Blvd., Suite #900 
Aventura, FL 33180 
Fax: +1 (786) 221-3531 


 
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1. BACKGROUND AND RATIONALE 
1.1 Background to the Disease 
Scabies is a contagious skin disease caused by an infestation of the human scabies mite, Sarcoptes scabiei 
variety hominis. The scabies mite burrows and lives in the superficial layers of the skin and the females 
lay their eggs in tiny burrows, which can be identified as tiny raised and crooked (serpiginous) grayish-
white or skin-colored lines on the skin surface [1]. Mites can only live for 48-72 hours without a human 
host, however they can survive as long as 1-2 months on a human host. The most common symptoms of 
a scabies infestation are a pimple-like (papular) skin rash and intense itching that often increases at night. 
The symptoms are cause by a hypersensitivity of the skin to the mite and mite fecal matter and the rash 
is most commonly seen in areas such as the wrist, elbow, armpit, and webbing between the fingers, breast 
areola, and cutaneous area of external genitalia, waist, belt- line, and buttocks. Generally, the head, face, 
neck, palms, and soles of feet are unaffected areas in older children and adults [2]. 
Scabies is found worldwide, affecting people of all races and social classes. It spreads rapidly among 
people in crowded living conditions, such as extended care facilities and nursing homes, as it is most 
commonly transmitted through direct skin-to-skin contact with another infected person. The common 
symptoms often arise within 2-6 weeks after exposure for a person who has never been affected and as 
soon as 1-4 days after exposure for a person who has previously had scabies. In most cases, between 10 
and 15 mites are present on an affected individual, though severe cases, known as crusted (Norwegian) 
scabies, could involve more than hundreds of mites and generally occurs in individuals with weak immune 
systems such as the elderly, disabled, or debilitated. 
Diagnosis of a scabies infestation is made based on the appearance and distribution of the papular skin 
rash and identification of burrows. It is also common to confirm diagnosis with examination of a skin 
scraping under a microscope to identify the mite, mite eggs, or mite fecal matter (scybala). Treatment for 
scabies includes the use of scabicides, such as permethrin cream, lindane, ivermectin, and crotamiton 
lotion, which act as insect-selective neurotoxins that result in paralysis and eventual death of the itch 
mites. The standard of care is to treat not only the infected individual, but also sexual partners and other 
household members who have had prolonged skin-to-skin contact with the infected individuals (including 
bedmates) at the same time to prevent re-infestation.  
Scabicides should be applied to the entire body from the neck down to the feet and toes (the area of 
application may be extended to the scalp and face if these areas are affected, which was observed in 
infants and immunocompromised individuals). The scabicide should be applied to clean skin and left on 
for the recommended time of application before washing it off. Elimite™ (permethrin) 5% Cream is 
recommended as a single application, which is usually sufficient to eradicate typical scabies, whether a 
symptomatic case or asymptomatic carrier. The usual adult dose is 30 grams. Demonstrable living mites 
after 14 days indicate that retreatment is necessary.  
In addition, the standard of care dictates that all bedding, clothing, and towels that the infected individual 


 
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may have come in contact with should be decontaminated by washing in hot water and drying in a hot 
dryer, by dry-cleaning, or by sealing in a plastic bag for at least 72 hours. 
1.2 Rationale of the Study  
Systemic absorption of permethrin cream is limited to 0.5% during the first 48 hours following dermal 
application [3]. In these settings, a conventional pharmacokinetic human study to demonstrate that 
Mayne Permethrin cream (5% w/w) is bioequivalent to the Reference Listed Drug [RLD] Elimite™ is not 
appropriate. 
Mayne Pharma, Inc. proposes to initiate a clinical endpoint bioequivalence (BE) study for a Permethrin 
Cream, 5% formulation for the treatment of active scabies in comparison to Elimite™ Permethrin cream 
(5% w/w). 
• 
Test Product: Permethrin Cream, 5% manufactured for Mayne Pharma, Inc. by Mayne Pharma 
International Pty Ltd., 1538 Main North Road, Salisbury South SA 5016 Australia 
• 
Reference Product: Elimite™ marketed by Prestium Pharma, Inc. (“Prestium”), the branded 
subsidiary of Renaissance Pharma. 
As per Center of Disease Control (CDC) Suggested General Guidelines on Scabies treatment, infested 
person, as well as household members and sexual contacts, particularly those who have had prolonged 
direct skin-to-skin contact with the infested person should receive an antiparasitic treatment [4]. All 
persons should be treated at the same time to prevent re-infestation. In consideration of this 
recommendation, the household members of the enrolled subject will be examined and treated at the 
same time as the enrolled subject with an FDA-approved generic Permethrin Cream, 5%. The treatment 
received by the household members of the enrolled subject will be referred to as “Standard of Care” 
throughout the study.  


 
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2. STUDY OBJECTIVES AND ENDPOINTS 
2.1 Study Objectives 
2.1.1 Primary Objective 
To demonstrate bioequivalence between Permethrin Cream, 5% (Mayne Pharma, Inc.) and Elimite™ in 
patients with active scabies. 
2.1.2 Secondary Objective 
To demonstrate comparative safety of Permethrin Cream, 5% (Mayne Pharma, Inc.) vs Elimite™ and 
tolerability of Permethrin Cream, 5%. 
2.2 Study Endpoints 
2.2.1 Primary Endpoint 
The primary endpoint will be the proportion of patients that are identified as cured at Study Day 28. Cure 
is defined as the absence of new lesions and the healing of all old lesions. Residual, dry, non-inflammatory 
papules are not counted as active. 
2.2.2 Secondary Endpoint 
The secondary endpoint will be the proportion of patients that are identified as cured at Study Day 14. 
2.3 Safety Variables 
Analysis of safety variables will be based on all adverse event (AE) capture measuring severity and 
duration utilizing MedDRA terminology for consistency. Vital signs will also be reviewed and analyzed at 
the Baseline and at visit 5 (End of Study visit). 
2.4 Tolerability Assessments 
Analysis of tolerability will be based on scores of Stinging/Burning and Itching sensations collected during 
Patient Self-Assessments at visits 2-5 between the test and reference treatment groups. 


 
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3. INVESTIGATIONAL PLAN 
3.1 Study Design 
This is a multi-center, double-blind, randomized, two-arm parallel design study to compare the treatment 
success of the test product, Permethrin Cream, 5% (Mayne Pharma, Inc.), and the Reference product, 
Elimite™ in patients with active scabies. The diagnosis of scabies is made based on the evaluation of 
burrows, inflammatory papules and excoriations and with a typical distribution pattern and localization 
(webbed spaces of the fingers, flexor surfaces of the wrists, elbows, axillae, belt line, feet, skin surface of 
external genitalia, or areolae), presence of family or contacts with moderate to severe itching which 
increases during the night, and positive identification of mites, mite eggs, or mite fecal matter (scybala) 
via microscopic evaluation of skin lesion scrapings [1,2]. Treatment success in this study is based on 
previously published studies of scabies infestations and defined as the absence of new lesions and the 
healing of all old lesions due to scabies mites and eggs within the treatment area [5-7]. The assigned 
investigational product will be applied topically (after washing) preferably in the evening on the day of 
the Baseline visit (Day 1). 
Eligibility criteria requires that all regular bedmates and family members with prolonged physical contact 
with the subject will agree to be assessed by the Investigator for clinical signs of scabies infestation and 
receive treatment with standard of care scabicidal drug, if necessary. This requirement is detailed in 
Section 5.8.2. 
If signs of active scabies infestation are present at visit 4 (Day 14±2), the study subject will be retreated 
with a second application of their assigned IP. Household members of the participating study subject will 
be asked to reapply the standard of care generic Permethrin Cream, 5% at the same visit. 
This study is comprised of two phases: screening and treatment. The screening phase will be up to 5 days 
in duration and treatment phase will be 28±4 days in duration. Approximately 140 subjects (or as many 
as 228 subjects), at least 12 years of age, male or female, of any race, who meet the inclusion and exclusion 
criteria, will be enrolled to achieve the desired per protocol subject number. The double-blind 
randomization of subjects will be in a 1:1 ratio for Test and Reference, and will be stratified by site. 
Screening will begin at visit 1 during which informed consent will be obtained from the subject prior to 
any study-related procedures, and eligibility will be determined by the Investigator. Following receipt of 
informed consent, the subject’s medical history will be recorded along with concomitant medications and, 
at this point, prohibited treatments must be assessed as they should be discontinued according to the 
timeframes outlined in section 5.11. A physical examination will be performed for all subjects and a urine 
pregnancy test will be performed for women of childbearing potential. The subject’s scabies infestation 
will be evaluated for papules and burrows during the visual examination. Presence of acarids, feces, or 
ova will be assessed via microscopic exam of skin lesion scraping. Subjects who meet all 
inclusion/exclusion criteria will return to the office for visit 2 within 5 days.  


 
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At visit 2 (baseline) the subject’s concomitant medications will be updated and any changes to medical 
history will be recorded. Randomization will occur at this visit and subjects will be instructed on 
investigational product application and completion of subject diaries. Visits 1 and 2 can be combined, if 
requirements detailed in Section 6.3.2 are met. All regular bedmates of the subject and individuals with 
prolonged physical contact with the subject will undergo an assessment by the Investigator and receive 
one 60 g tube with standard of care generic Permethrin Cream, 5% during the Baseline visit to prevent 
cross-infestation within the household. 
Subject will return at visit 3 (Day 7±1) with the used investigational product tube and subject diaries. 
Compliance with investigational product applications will be assessed. Safety and tolerability assessments 
will be conducted. 
At visit 4 (Day 14±2), subjects will return for efficacy, safety and tolerability assessments. If signs of active 
scabies infection are present at this visit, the subject will be treated with a 2nd application of their assigned 
investigational product as defined in Section 5.6.  
Final efficacy, safety and tolerability assessments will occur at visit 5 (Day 28±4). If the subject was 
retreated, the used tube of the investigational product will be returned at this visit. The duration of each 
subject’s participation in the study will be a maximum of 37 days. 
The primary endpoint is the proportion of subjects considered to be cured (defined as the absence of new 
lesions and the healing of all old lesions) on Study Day 28. To establish bioequivalence, the continuity-
corrected, 90% confidence interval for the test-to-reference difference in proportions of subjects cured 
must be within the equivalence limits -0.20 to 0.20. The evaluation in the PP population will be definitive 
while that in the mITT population will be considered as supportive. 
The secondary endpoint is the proportion of subjects considered to be cured on Study Day 14. 
Bioequivalence will be assessed using the same approach as in the primary endpoint. 
3.2 Number of Subjects  
Based on the limited availability of Reference product, a total of approximately 140 subjects, at least 12 
years of age, male or female, of any race, who meet the inclusion and exclusion criteria, will be enrolled 
to achieve a per protocol population of approximately 112 across the United States. Should additional 
Reference product become available prior to completion of the clinical phase of the study, enrollment will 
be increased, up to 228, to achieve a per protocol population of up to approximately 182. 


 
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4. SELECTION AND WITHDRAWAL OF STUDY POPULATION 
4.1 Study Population 
Approximately one hundred and forty (140) subjects, and as many as two hundred and twenty-eight 
subjects, of age 12 years and older with clinical and parasitological confirmation of active scabies will be 
enrolled in this multi-center study. 
4.2 Eligibility Criteria 
Subjects who satisfy ALL of the following inclusion and have NONE of the following exclusion criteria may 
be enrolled in the study: 
4.2.1 Inclusion Criteria 
1. 
Male or non-pregnant, non-lactating female subject at least 12 years of age or older. 
2. 
Subject must have a positive identification for mites, eggs, or mite fecal matter by microscopic 
examination of a skin scraping. 
3. 
Subjects must have at least two of the three following: a) excoriations and inflammatory papules 
with a typical distribution pattern and localization (webbed spaces of the fingers, flexor surfaces 
of the wrists, elbows, axillae, belt line, feet, skin surface of external genitalia, or areolae); 
b) presence of burrows; c) family or contacts with moderate to severe itching which increases 
during the night. 
4. 
Subjects must be willing to make every effort to immediately disinfect clothes, towels, and linens 
and all potentially infected household items upon diagnosis of infestation to prevent re-infestation. 
5. 
All household members with prolonged physical contact with the subject must be willing to attend 
Baseline visit and receive treatment with standard of care if deemed necessary by the Investigator 
in order to prevent re-infestation of the subject enrolled. 
6. 
Subject or representative must read and sign an IRB/IEC-approved Informed Consent Form (ICF); 
for minor subjects (18 years or younger in most states) the parent or legal guardian should sign the 
ICF and the child will be required to sign the Assent Form that will written in such a way as to be 
understandable to a child. 
7. 
Subject must be able to apply study product to self. If the subject is a child, then parent/guardian 
will apply study product to him/her. 
4.2.2 Exclusion Criteria 
1. 
Females who are pregnant as shown in a urine pregnancy test at the Baseline visit, prior to 
randomization, or lactating, or of childbearing potential (for purpose of this study a female of 


 
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childbearing potential is considered to be not surgically sterile or postmenopausal for at least 1 
year) who are not using or do not agree to use an acceptable form of contraception (oral /implant 
/injectable /transdermal contraceptives, IUD, condom, diaphragm, or abstinence) during the study, 
or who intends to become pregnant during the study; contraceptive method must also be 
consistent throughout the study. 
2. 
Treatment for scabies <4 weeks prior to enrollment, including permethrin, benzyl alcohol, lindane, 
crotamiton, malathion, and ivermectin. 
3. 
Use of prohibited medications: 
• 
Topical or oral scabicidal/antiparasitic treatment including: permethrin, benzyl alcohol, benzyl 
benzoate, lindane, crotamiton, malathion, ivermectin, precipitated sulfur, albendazole, 
keratolytic cream, tea tree oil, or oil of the leaves of Lippia multiflora Moldenke within 28 days 
of visit 2. 
• 
Systemic corticosteroids (including inhaled steroids) taken within 14 days of visit 2. 
• 
Topical corticosteroids including hydrocortisone taken within 24 hours of visit 2. 
• 
Topical antipruritics, including antihistamines within 24 hours of any study visits. 
• 
Oral antihistamine including diphenhydramine (Benadryl) taken within 24 hours of any study 
visits. 
• 
Topical antibiotics including mupirocin taken within 24 hours of any study visits. 
4. 
Patients with immunosuppressive disorders requiring therapy, severe systemic disease, history of 
HIV infection and/or seizures. 
5. 
Patients with crusted/Norwegian scabies. 
6. 
Presence of underlying skin disease that would obscure evaluation of the papules and burrows 
associated with scabies infection as determined by the Investigator. 
7. 
Presence of severe cutaneous bacterial or fungal infections requiring therapy (including systemic 
and topical antibiotics) as determined by the Investigator. 
8. 
Sensitivity or allergy to Permethrin Cream or any of its components, synthetic pyrethroids, 
pyrethrin, chrysanthemums or ragweed. 
9. 
A recent (less than 1 year) history of alcoholism, drug abuse, or other problems which would likely 
make the subject unreliable for the study. 
10. Participation in another investigational study or using any investigational product within the 30 
days prior to the Baseline visit. 
11. Participation of family member, or another member of the household (including regular bedmates) 
in the current study. 
12. Total number of bedmates and family members with prolonged physical contact is greater than 6 
(including study subject). 


 
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13. Any employees of the clinic, investigators, or family members of the study staff. 
14. Patients who in the opinion of the Investigator would be non-compliant with the requirements of 
the study protocol. 
4.2.3 Criteria for Inclusion of Minor Subjects 
Subjects under the age of 18 must sign the Assent Form that will be written in such a way as to be 
understandable to a child and to obtain parental or legal guardian consent prior to enrollment in this 
study. Subjects aged less than 12 years will not be enrolled. 
4.3 Withdrawal and Early Discontinuation 
In accordance with the Declaration of Helsinki and other applicable regulations, a subject has the right to 
withdraw from the study at any time and for any reason without prejudice to his or her future medical 
care. The Investigator, Sponsor, or Medical Monitor may also withdraw the subject at any time if it is 
medically necessary or in the interest of subject safety.  
A subject will be discontinued from this study if any of the following criteria are met: 
• 
Withdrawal of consent by the subject is received 
• 
In the opinion of the Investigator, it is not in the subject’s best interests to continue in the 
study. 
• 
Occurrence of an AE/SAE, which, in the opinion of the Investigator, warrants 
discontinuation of the subject from the study. 
• 
Pregnancy 
• 
Significant non-compliance with study procedures that would interfere with the study 
results or increase the subject’s risks in the study. This includes known cases of non-
compliance of household members with the standard of care treatment. 
• 
If subject is deemed to be a treatment failure, which is defined as any subject whose 
condition worsens and who requires alternate or supplemental therapy for the treatment 
of scabies during the study. 
Subjects discontinuing, or withdrawing from, the study sooner than their Day 28 visit will undergo the End 
of Study assessments (as detailed in Section 6.3.5). In addition, if the subject is discontinuing the study 
and has not returned the dispensed Investigational Product, then the site will remind the subject to return 
the dispensed investigational product during the End of study visit. In such cases, the Investigational 
Product dispensed to the subject will be collected and Investigational Product accountability will be 
performed as per Section 5.10 during the End of Study visit (see Schedule of Activities in Appendix B). 
After the End of Study visit, the subject may resume dosing with any medication prescribed by the 
subject’s physician, including Prohibited Medications listed in section 5.11. 
If a subject does not return for a scheduled visit, every effort will be made to contact the subject and 


 
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document the End of Study visit assessments. The Investigator must document the primary reason for 
discontinuation of a study subject on the appropriate electronic Case Report Form (CRF). 
Randomized subjects who discontinue due to an adverse event will have all events documented and 
followed to satisfactory resolution, as detailed in Section 7.4.  
 
 
 


 
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5. INVESTIGATIONAL PRODUCT AND TREATMENT OF SUBJECTS 
5.1 Investigational Products [IP]  
5.1.1 Test Product 
The test product is Permethrin Cream 5% w/w manufactured by Mayne Pharma International Pty Ltd., 
supplied in 60 g tubes. The formulation composition of the test product consists of the following 
ingredients: 
Active Ingredient - Each gram contains permethrin 50 mg (5%). 
Inactive Ingredients - Fractionated coconut oil (MCT-NF) [7.5%], Isopropyl myristate NF [0.8%], 
Glyceryl monostearate NF [2.0%], Lanolin alcohols NF [0.2%], Mineral oil NF [0.01%], Butylated 
hydroxytoluene NF (BHT) [2.4%], Polyoxyethylene 2 cetyl ether (ceteth 2) [2.4%], Polyoxyethylene 
10 cetyl ether (ceteth 10) [2.4%], Glycerol NF [0.5%], Water USP [74.96%], Polyoxyethylene 20 
cetyl ether (ceteth 20), [2.0%], Carbomer 974P NF [0.26%], 5% NaOH Aqueous solution [1.6%], 
Formaldehyde solution NF [0.27%]. 
5.1.2 Reference Product/Comparator 
The reference product or comparator is Elimite™ marketed by Prestium Pharma, Inc. (“Prestium”), the 
branded subsidiary of Renaissance Pharma. Elimite™ is supplied in 60 g tubes. The formulation 
composition of the reference product, Permethrin 5% w/w (Elimite™) consists of the following ingredients 
according to the FDA-approved labelling:  
Active Ingredient - Each gram contains permethrin 50 mg (5%). 
Inactive Ingredients - Butylated hydroxytoluene, carbomer homopolymer type B, fractionated 
coconut oil, glycerin, glyceryl monostearate, isopropyl myristate, lanolin alcohols, mineral oil, 
polyoxyethylene cetyl ethers, purified water, and sodium hydroxide. Formaldehyde 1 mg (0.1%) 
is added as a preservative. 
5.2 Standard of Care [SOC] 
Generic Permethrin Cream, 5% available in the market will be supplied by the Sponsor in an open-label 
fashion as a Standard of Care (SOC) to each site and will be used for treatment of the household members. 
To avoid any possible unblinding issues, the SOC supplied by the Sponsor will not be the reference product 
of this study, Elimite™. 
5.3 Packaging and Labeling 
The investigational product tubes to be dispensed to the subject will be packaged in diaper-label to ensure 


 
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blinding. Labeling will be in accordance with Good Manufacturing Practice. The labels on each 
investigational product tube will not provide any information in regards to treatment arm.  
The SOC, Permethrin Cream, 5% available in the market will be supplied in an open-label fashion. 
5.4 Storage of investigational product and SOC  
Study Medication supplies (include investigational product and SOC) will be stored at 20° to 25°C (68° to 
77°F) and protected from moisture. All study medication supplies must be kept in a secure cabinet or 
room. Only the study pharmacist, or designated study personnel will have access to study medication 
supplies.  
5.5 Reserve Sample Retention 
Each shipment of investigational product received by the site will contain investigational product tubes to 
be reserved for retention. When the site receives a shipment of investigational product, study pharmacist, 
or designated study personnel will randomly select one block of the investigational product for retention 
and store them separately. For all subsequent shipments, the same procedure is to be followed. Detailed 
guidance is provided in the study Pharmacy Manual. 
As per the Code of Federal Regulations Part 21, Section 320.38(e), “Each reserve sample shall be stored 
under conditions consistent with the product labeling and in an area segregated from the area where 
testing is conducted and with access limited to authorized personnel. Each reserve sample shall be 
retained for a period of at least 5 years following the date on which the application or supplemental 
application is approved, or, if such application or supplemental application is not approved, at least 5 
years following the date of completion of the clinical study in which the sample from which the reserve 
sample was obtained was used.”  
The Investigator will store the retention sample investigational product until such time or until notification 
is received from the Sponsor that the samples are no longer required and proper instruction of what to 
do with the sample is given by the Sponsor. 
5.6 Treatment Assignment (Randomization) 
The block randomization code will be generated and held by an independent third party throughout the 
conduct of the study in order to minimize bias. Blocks of two (2) tubes will be supplied to the sites. Site’s 
dispensing pharmacist will randomly select a tube with an investigational product from the block for the 
study subject. Next enrolled subject will receive the remaining investigational product from the same 
block until the block is entirely used.  
5.6.1 Assignment of Retreatment 
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a retreatment to the study subject. Only one retreatment is allowed per subject. The retreatment 
assignment must belong to the same treatment arm. In order to dispense the correct treatment, the 
following process is to be followed: 
1. Study pharmacist will contact the Drug Depot, specifying subject’s identifying information. 
2. Drug Depot will specify which kit number shall be dispensed for retreatment. 
Please refer to the study Pharmacy Manual for details. 
5.7 Blinding 
This is a double-blind study, thus all clinic staff, study monitors, and subjects will be blinded to the 
randomization scheme. The packaging of the test and the reference products will be similar in appearance 
to make difference in treatment less obvious to the subjects. To maintain adequate blinding of 
Investigators and subject evaluators, it is recommended that the investigational product dispensation and 
accountability be performed by the study pharmacist, or designated study personnel who will not be 
involved in any other activities of this study. Neither the Investigator nor the patient should be able to 
identify the received treatment. The dispensed investigational product will NOT be opened by the subject 
at the study center. The randomization scheme will not be available to the physician, the study pharmacist 
or designated study personnel for investigational product dispensation and accountability and nursing 
staff or study coordinators involved in the collection, monitoring, revision, or evaluation of adverse events 
or to clinical staff who could have an impact on the outcome of the study.  
A sealed copy of the randomization code will be supplied with each block of the investigational product 
and will be retained at each clinical site. Randomization codes must be available to the FDA or other 
regulatory agency investigators at the time of site inspection to allow for verification of the treatment 
identity of each subject. 
The randomization code must not be broken except in emergency situations for which the identification 
of the study treatment of a subject is required by the Qualified Investigator to complete a serious adverse 
event report or the clinical report. In such situations, the randomization information will be held by 
designated individual(s), and the date and reason for breaking the blind must be recorded. Biorasi Project 
Manager should be contacted by telephone prior to unblinding but no later than 24 hours after unblinding. 
As the study is blinded, the Investigator should promptly document and explain to the Sponsor any 
premature unblinding (e.g., accidental unblinding, unblinding due to a serious adverse event) of the 
investigational product(s). 
5.8 Treatment Administration 
5.8.1 Investigational Product Dispensation and Application 
At visit 2 (Baseline or Day 1), subjects will receive the randomized treatment along with a Subject Diary 
(Appendix C. Subject Diary). Subjects will be instructed to bring the dispensed study medication (used 
tube of investigational product) along with the subject diary for visit 3 (day 7) for investigational product 


 
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accountability. 
Each subject will be instructed (verbally and in form of written instructions) on proper application method, 
clothing and bedding disinfection requirements, subject diary completion, and general instructions 
regarding the study. Subjects will apply investigational product on Day 1 after leaving the study site.  
Subjects will be instructed to cleanse with warm water (but NOT the hot bath due to risk of increased 
adsorption and increased risk of systemic adverse events) and a non-medicated soap and dry thoroughly. 
Nails should be clipped back and any debris must be removed prior to the application. Subjects will apply 
a thin layer of investigational product to the entire surface from the neck down to the soles and bottom 
of the feet (NOT including face and head). Subjects should pay special attention when applying cream to 
the areas between fingers and toes, under nails, wrists, armpits, skin surface of external genitalia, breasts 
and buttocks. The investigational product should be applied at bedtime and kept overnight for a minimum 
of 8 hours and a maximum of 14 hours before washing it off.  
Subjects will be informed that residual itching may persist for several weeks after the successful 
treatment, which does not necessarily indicate treatment failure. Oral or topical antipruritics may me 
prescribed based on the Investigator’s clinical judgement in order to reduce itching, taking into account 
prohibited medication and washout periods detailed in the Section 5.11. 
In general, one application of the Permethrin is curative for scabies. However, in the event that signs of 
active scabies infestation are present at visit 4 (Day 14±2), the subject will be retreated with second 
application of their assigned investigational product. In this case, the subject will follow the same 
application recommendations and will complete the diary, returning the used investigational product tube 
and subject diary to the visit 5 (Day 28±4). 
5.8.2 Administration of Standard of Care 
In the current study, all household members with prolonged physical contact with the subject must agree 
to be assessed by the Investigator. Affected (or “high risk”) household members, as determined by the 
Investigator, must be willing to receive a treatment with an open-label standard of care, which will be 
provided to them on the day of visit 2 (baseline). Providing an antiparasitic treatment to the household 
members of the affected individual is dictated by the clinical and epidemiological necessity due to high 
risk of cross-contamination within the family members. Individuals receiving standard of care will not be 
considered as a part of study population. 
All affected (or “high risk”) household members must receive treatment with the standard of care on the 
same day as the enrolled subject and will follow the same recommendations for disinfection of personal 
clothing and bedding items. Please see Appendix A. Study Flowchart. 
5.9 Treatment Compliance 
Subjects will apply the investigational product after the visit 2 (Day 1), preferably in the evening. 


 
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Subjects will be advised to bring back used investigational product tube during visit 3. The study 
pharmacist, or designated study personnel will perform investigational product accountability to ensure 
that the subject took application of the investigational product. Compliance with the application and 
disinfection requirements will be determined from the Subject Diary, which the subject will be instructed 
to use to record date and time of the application and application removal, as well as confirmation of 
disinfection of clothing and compliance of family members with  SOC treatment.  
Missed applications and deviations from the application instructions (e.g.: if cream was washed with soap 
and water within 8 hours of treatment, cream was not applied to the whole body during each application, 
was not performed prior to application of the investigational product, etc.) will be considered as a 
deviation from the protocol. 
5.10 Accountability, Destruction and Return of Study Supplies 
The Sponsor will supply sufficient quantities of the investigational product for the following:  
(1) completion of this study  
(2) retention, as per applicable regulations 
The study pharmacist or designated study personnel will maintain a Site Investigational Product 
Accountability Log and a Subject Investigational Product Accountability Log itemizing all investigational 
product dispensed to and returned from each subject during the study and the amount of SOC dispensed 
to the household members of each subject. Investigational product compliance check will be performed 
at visit 3 (Day 7) and at visit 5 (Day 28) - for subjects receiving second application of the Investigational 
product. All investigational products must be accounted for, and any discrepancies explained. 
The study pharmacist or designated study personnel is responsible for keeping accurate records of the 
clinical supplies received from the Sponsor, all supplies retained in inventory at the site, and 
investigational product dispensed to or returned from each subject and should accurately reflect the drug 
accountability of the investigational product at all times. 
If any dispensing errors or discrepancies are discovered, the Sponsor must be notified immediately. 
Prior to site closure and at appropriate intervals during the study, a representative from Biorasi or Sponsor 
will perform Investigational Product accountability and reconciliation. At the end of the study, the 
Investigator will retain all the original documentation regarding Investigational Product accountability, 
return, and/or destruction, and copies will be sent to the Sponsor. 
With the exception of retention samples, all unused and used investigational product tubes will be 
retained at the investigative site and must be returned to the Sponsor or its designee for destruction at 
the end of the study.  


 
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5.11 Prior, Concomitant and Prohibited Therapy  
Current medications and any medications taken within the 30 days prior to the start of the study will be 
recorded as prior/concomitant medications (using their generic name, if known) with the corresponding 
indication. The medications to be recorded include prescription and all over-the-counter (OTC) 
medications and all dietary supplements. All medications taken on a regular basis, including aspirin and 
acetaminophen, should be recorded prior to commencing the use of the investigational product. Any 
medications started during the study (including “as needed” medications) will be recorded in the 
concomitant medication list as soon as the Investigational Site will become aware of the medication being 
added.  
If the Investigator becomes aware of a subject having taken a prohibited medication, they will report the 
incident to the Medical Monitor and Biorasi within 24 hours, and the Medical Monitor and/or Sponsor will 
provide written approval of the subject’s continuation or discontinuation in the study.  
Prohibited medications include: 
1. 
Topical or oral scabicidal/antiparasitic treatment including: permethrin, benzyl alcohol, 
benzyl benzoate, lindane, crotamiton, malathion, ivermectin, precipitated sulfur, 
albendazole, keratolytic cream, tea tree oil, or oil of the leaves of Lippia multiflora 
Moldenke within 28 days of visit 2. 
2. 
Systemic corticosteroids (including inhaled steroids) taken within 14 days of visit 2. 
3. 
Topical corticosteroids including hydrocortisone taken within 24 hours of visit 2. 
4. 
Topical antipruritics, including antihistamines within 24 hours of any study visits. 
5. 
Oral antihistamine including diphenhydramine (Benadryl) taken within 24 hours of any 
study visits. 
6. 
Topical antibiotics including mupirocin taken within 24 hours of any study visits. 


 
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6. STUDY PROCEDURES AND SCHEDULE OF ACTIVITIES 
The following sections describe the procedures to be completed during the study. Subjects are to be 
assessed by the same Investigator or site personnel whenever possible. 
6.1 Administrative Procedures  
6.1.1 Subject Informed Consent 
A signed and dated, study-specific, Institutional Review Board (IRB) approved Informed Consent Form 
must be obtained from each subject prior to performing any study related procedures. No study related 
procedures or activities may be performed until each subject is fully informed and the consent form is 
signed and dated. Any subject under the age of 18 must have the signature parent or legal guardian on 
informed consent form. All subjects will be given a copy of the signed and dated consent form. 
Subjects between the age of 12 and 18 must sign the Assent Form that will be written in such a way as to 
be understandable to a child. Parental or legal guardian consent will be obtained prior to enrollment in 
this study.  
6.1.2 Documentation of Screen Failures 
Investigators will maintain documentation of pre-screening activities, to include information on potential 
study candidates evaluated and reasons that patients considered for the study did not qualify. 
Investigators must account for all subjects who sign informed consent and will maintain a log of subjects 
screened and indicate who was enrolled or excluded and the reason why. If the subject is found not to be 
eligible prior to enrollment, the reason(s) for ineligibility must be documented by the Investigator. 
Subject Numbers assigned to subjects who fail Screening will not be re-used. 
6.1.3 Contraception and Pregnancy Avoidance Measures 
The study will require that all subjects must agree to use adequate contraception throughout the study. 
Adequate contraception is defined as follows: 
 
Female subjects must be surgically sterile, postmenopausal (for at least one year). 
 
Female subjects not surgically sterile or postmenopausal (for at least one year), and 
nonvasectomized male subjects, must practice at least one of the following methods of birth 
control: 
o total abstinence from sexual intercourse (minimum one complete menstrual cycle prior 
to Screening visit, throughout the study) 
o a vasectomized partner 
o hormonal contraceptives (oral, parenteral, or transdermal) for at least three months prior 


 
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to study drug administration or intrauterine contraception/device double-barrier method 
(such as male condom, female condom, diaphragm, sponge, or cervical cap together with 
spermicidal foam/gel/film/suppository). 
6.2 Study Procedures and Evaluations 
6.2.1 Clinical Evaluations 
The following clinical evaluations will be conducted during the course of the study: 
6.2.1.1 
Subject Demographics 
Basic demographic information, including date of birth, sex, ethnicity, and race will be recorded at the 
Screening visit. 
6.2.1.2 
Medical history  
Medical history will be collected at the Screening visit and updated at the visit 2. Relevant medical history 
(with particular emphasis on previous scabies infestations, related skin disorders and other medical 
conditions that may lead to exclusion) and significant ongoing medical conditions or diseases will be 
documented.  
6.2.1.3 
Physical examination 
Physical examination, including height, weight, and evaluation of organs and systems (General 
Appearance, Heart/Cardiovascular, Lungs, Gastrointestinal, Ears / Nose / Throat, Extremities, and Skin) 
will be assessed. 
6.2.1.4 
Vital Signs 
Vital signs will be collected at the Screening visit; on the Baseline, and at visit 5 (or upon subject 
discontinuation). Vital signs will include body temperature (oral), heart rate and blood pressure (systolic 
and diastolic). Blood pressure and pulse rate will be measured after the subject has been sitting restfully 
for at least 5 minutes. Any abnormal characteristics will be evaluated by the Investigator from based on 
their significance. Abnormal vital signs will be considered AEs if they require therapeutic medical 
intervention, and/or if the Investigator considers them to be AEs due to the clinical judgement. 
6.2.1.5 
Visual Examination of Lesions 
At the Screening (visit 1) and Baseline (visit 2) visits, visual examination of skin lesions will be performed 
by the Investigational Site. Active lesions, defined as inflammatory papules, excoriations and burrows will 
be assessed and mapped to the body areas (webbed spaces of the fingers, flexor surfaces of the wrists, 
elbows, axillae, belt line, feet, skin surface of external genitalia, areolae and other areas). Residual, dry, 
non-inflammatory papules will not be counted as active. At visits 3, 4 and 5 the examination will be 
repeated, identifying the course of healing of old lesions and identification of new elements. The 
examination results will be captured in the eCRF and in the source documentation.  


 
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6.2.1.6 
Adverse Event Assessments 
Beginning with the first dose/application of the investigational product and through visit 5 (End of Study), 
the Investigator and study personnel will review each subject’s clinical evaluation findings and query the 
subject directly regarding AEs (see Section 7, Safety Data Collection, Recording and Reporting). Subjects 
must be followed for AEs until the final required protocol visit or until all drug-related toxicities and SAEs 
have resolved (or are considered chronic/stable), whichever is later. 
6.2.1.7 
Concomitant Medication Recording 
All medications (both prescription and nonprescription, and including vitamins, herbals, topicals, inhaled, 
and intranasal) taken within 30 days prior to the start of the investigational product and through the final 
study visit will be recorded on the appropriate eCRF (using their generic and brand name, if known) with 
the corresponding indication. At each study visit, subjects will be asked whether they have started or 
discontinued any medication since their previous study visit. This includes single use or PRN (as needed) 
medication use. 
6.2.2 Laboratory Evaluations 
The following laboratory evaluations will be conducted during the course of the study: 
6.2.2.1 
Microscopic Examination of Skin Scraping 
During the Screening visit (Visit 1), the Investigator or designee will perform a scraping of skin lesions in 
order to verify the presence of the mites, eggs, or mite fecal matter (scybala) under the light microscopy. 
This can be done by carefully removing the mite from the end of its burrow using the tip of a needle or by 
obtaining multiple wide superficial scrapings of crusted, papular, or lesioned areas of the skin to examine 
under a microscope for mites, eggs, or mite’s fecal matter.  
New lesions identified at visits 3, 4 or 5 will be confirmed by microscopic evaluation of skin scraping. 
6.2.2.2 
Pregnancy test 
A urine pregnancy test will be performed at Screening and at the End of Study (EOS) visit for females of 
childbearing potential (refer to Section 6.1.3 Contraception and Pregnancy Avoidance Measures for 
definitions). The Screening results must be available and must be negative before the subject takes the 
first dose/first application of Investigational Product. 
6.2.3 Patient Self-Assessment 
Subjects will perform a self-assessments of itching and stinging/burning sensations (Appendix D. Patient 
Self-Assessment) at visits 2, 3, 4 and 5, as detailed in Tables 1 and 2. During each visit, subject will be 
provided with a Patient Self-Assessment Worksheets to record the grading of itching and stinging/burning 
sensations. The Patient Self-Assessment Worksheets will be filed along with the source documentation 
and the self-assessments data provided by the subject will be captured by the Investigational Site in the 
eCRF. Information captured on the Patient Self-Assessment will not be documented as an Adverse Event. 


 
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Table 1: Itching 
Itching – Intense, distracting irritation or tickling sensation in the last 24 hours 
Score Grade 
Definition 
0 
None 
No Itching 
1 
Mild 
Barely perceptible, slightly present itch 
2 
Moderate 
Distinct presence of itch 
3 
Severe 
Marked, intense, yet tolerable itch 
4 
Very Severe 
Unbearable, intense itch 
Table 2: Stinging/Burning 
Stinging/Burning – Sensation of the skin is painfully hot or noticeable tingling sensation in the last 24 hours 
Score 
Grade 
Definition 
0 
None 
Absent 
1 
Mild 
Slight, barely present 
2 
Moderate 
Distinct presence 
3 
Severe 
Marked, intense 
6.2.4 Subject Diary Compliance Review 
Subjects will fill out their diaries upon each treatment application noting the following: 
 
Time and date of application 
 
Time and date of removal (washing off of the study drug) 
 
Confirmation that subject disinfected personal clothes, towels, linens and all potentially infected 
household items 
 
Confirmation that the complete skin surface from the neck down to the soles and bottom of the 
feet has been covered by the application 
Subjects will return their diaries to the clinical site at visit 3 (Day 7±1 Day) for compliance review. The 
Investigator will verify that the subject complied with the application requirements and disinfection 
regimen. Both the subject and the study staff will sign off on completed diary. If the subject has missed a 
treatment application notation, this is considered a protocol deviation and must be reported. Refer to 
Section 5.9 for additional information regarding the treatment compliance.  


 
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6.3 Schedule of Activities  
6.3.1 Visit 1: Screening Visit (Days -5 to 1) 
Subjects will undergo Screening procedures within 1-5 days prior to investigational product 
administration. All Screening procedures will be completed prior to randomization but only after obtaining 
voluntary written informed consent. Subjects satisfying all inclusion and none of the exclusion criteria may 
be enrolled in the study. Screening Procedures include: 
• 
Review and signing the Informed Consent. 
• 
Inclusion/Exclusion Criteria review. 
• 
Demographics. 
• 
Medical history. 
• 
Physical examination. 
• 
Vital signs. 
• 
Visual examination of skin lesions. 
• 
Microscopic examination of skin scraping to identify scabies mites, eggs, or fecal matter (see 
Section 6.2.2.1). 
• 
Assessment of concomitant and prohibited medications. 
• 
Pregnancy test and evaluation of contraception use (for females of child bearing potential). 
• 
Identifying bedmates and family members with prolonged physical contact with the subject. 
These members will be invited to attend Baseline visit and must be willing to undergo clinical 
assessment for scabies infestation followed by antiparasitic treatment with standard of care. 
• 
Baseline visit scheduling. 
6.3.2 Visit 2: Baseline (Day 1) 
The Baseline visit can be performed at the same visit as Screening, or up to 5 days later. However, if visit 
2 is completed on a different day than visit 1, then all visit 2 procedures must be performed regardless of 
any duplicate procedures completed at visit 1. 
If subject’s eligibility can be confirmed at the Screening visit, procedures for visits 1 and 2 can be combined 
and conducted on the same day, which then is Day 1. Following requirements must be met at the day of 
the Screening visit: 
a) all screening procedures are completed and results, such as microscopy of skin scrapings are 
obtained by the Investigational Site; 
b) washout requirements for prohibited medications are fulfilled, as outlined in section 5.11; 
c) regular bedmates of subject and individuals with prolonged physical contact with the subject 
(family members), if identified, are present, and were assessed by the Investigator. Affected (or 
“high risk”) family members / bedmates are willing to receive a treatment with a standard of care 
and the treatment with standard of care is initiated on the same day as the Baseline visit of the 


 
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subject. Study subjects and their bedmates must be on the same schedule of treatment 
applications in order to reduce risk of re-infestation. Otherwise, subjects cannot be enrolled. 
The following procedures will be performed: 
• 
Evaluation of bedmates and family members with prolonged physical contact for clinical signs of 
scabies infestation. 
• 
Changes in medical history. 
• 
Assess concomitant and prohibited medications. 
• 
Visual examination of skin lesions. 
• 
Vital signs. 
• 
Patient Self-Assessment (see Section 6.2.3). 
• 
Confirmation subject still meets all Inclusion/Exclusion Criteria prior to Randomization. 
• 
Randomization of eligible subjects. 
• 
Dispensation of investigational product. 
• 
Dispensation of standard of care antiparasitic treatment to bedmates and family members, 
identified as affected with scabies and at “high risk”. 
• 
Complete the Site Investigational Product Accountability Log and a Subject Investigational Product 
Accountability Log 
• 
Education on application, storage, diary completion, and dispensing of subject diary. 
• 
Visit 3 scheduling. 
6.3.3 Visit 3: Interim Evaluation (Day 7±1 Day) 
The following procedures will be performed: 
• 
Assess adverse events. 
• 
Assess concomitant and prohibited medications. 
• 
Visual examination of skin lesions. 
• 
Patient Self-Assessment (see Section 6.2.3). 
• 
Assess subject compliance by reviewing the subject diary. Subject diary will be returned and filed 
with the subject’s source documents (see Section 6.2.4). Both the subject and the study staff will 
sign off on completed diary. 
• 
Collect the dispensed investigational product and complete the Site Investigational Product 
Accountability Log and a Subject Investigational Product Accountability Log.  
• 
Visit 4 scheduling. 
6.3.4 Visit 4: Interim Evaluation (Day 14±2 Day) 
The following procedures will be performed: 
• 
Assess adverse events. 
• 
Assess concomitant and prohibited medications. 


 
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• 
Visual examination of skin lesions. 
• 
Patient Self-Assessment (see Section 6.2.3). 
• 
For subjects showing active signs of scabies: 
o Assess subject for signs of active scabies and dispense the investigational product for 
second application. Complete the Site Investigational Product Accountability Log and a 
Subject Investigational Product Accountability Log.  
o Education on application, storage, diary completion, and re-dispensing of subject diary. 
o Household members of the participating study subject will be asked to reapply the 
standard of care generic Permethrin Cream, 5%. 
• 
Visit 5 scheduling. 
6.3.5 Visit 5: End of Study / Early Termination, and Final Safety Check (Day 28±4) 
The following procedures will be performed: 
• 
Assess adverse events. 
• 
Assess concomitant and prohibited medications. 
• 
Visual examination of skin lesions. 
• 
Vital signs 
• 
Patient Self-Assessment (see Section 6.2.3). 
• 
Pregnancy Test (for females of childbearing potential). 
• 
For subjects receiving second application of the investigational product: 
o Assess subject compliance by reviewing the subject diary. Subject diary will be returned 
and filed with the subject’s source documents (see Section 6.2.4). Both the subject and 
the study staff will sign off on completed diary. 
o Collect the dispensed investigational product and complete the Site Investigational 
Product Accountability Log and a Subject Investigational Product Accountability Log. 
If the Investigator assesses the subject’s condition at any time and determines that the subject’s condition 
has worsened to the degree that it is unsafe for the subject to continue in the study, the subject may be 
discontinued from the study as treatment failure. Visit 5 Early Termination procedures will be performed, 
and a standard of care treatment may be advised at the Investigator’s discretion. 
Subjects discontinuing from the study sooner than the Day 28 visit will undergo the Early Termination (ET) 
visit at the earliest possible date. If the Investigator decides to discontinue a subject at any time during 
the study, a standard care of treatment may be advised at the Investigator’s discretion, and an EOS/ET 
visit preferably prior to receiving any standard of care treatment. 
6.3.6 Unscheduled Visit 
Subjects will be encouraged to report any complications or adverse effects during their participation. 
Investigator may evaluate the subject at an unscheduled visit, if subject’s condition will be considered as 
worsening. 


 
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7. SAFETY DATA COLLECTION, RECORDING AND REPORTING 
The Investigator will monitor each subject for clinical and laboratory evidence of adverse events on a 
routine basis throughout the study. The Investigator will assess and record any AE in detail including the 
date of onset, description, severity, time course, duration and outcome, relationship of the adverse event 
to study drug, an alternate etiology for events not considered “related” or “probably related” to study 
drug, final diagnosis, if known, and any action(s) taken. For AEs to be considered intermittent, the events 
must be of similar nature and severity and each intermittent AE will be reported separately. AEs and SAEs, 
whether in response to a query, observed by site personnel, or reported spontaneously by the subject will 
be recorded, monitored and followed-up until the resolution (or until the Investigator deems the event to 
be stable/chronic). 
7.1 Definitions 
7.1.1 Adverse Event 
An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product and which does not necessarily have a causal relationship with 
this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal 
(investigational) product, whether or not the event is considered causally related to the use of the 
investigational product. 
Such an event can result from use of the drug as stipulated in the protocol or labeling, as well as from 
accidental or intentional overdose, drug abuse, or drug withdrawal. Any worsening of a pre-existing 
condition or illness is considered an AE. Clinically significant abnormalities are to be followed to resolution 
(i.e. become stable, return to normal, return to Baseline, or become explainable). Laboratory 
abnormalities and changes in vital signs are considered to be AEs only if they necessitate therapeutic 
medical intervention, and/or if the Investigator considers them to be AEs. 
7.1.2 Serious Adverse Events 
If an AE meets any of the following criteria, it is to be reported to the Biorasi Safety and Pharmacovigilance 
as a serious adverse event (SAE) using SAE report form within 24 hours of occurrence or notification to 
the study site: 
Death of Subject 
An event that results in the death of a subject. 
Life-Threatening 
An event that, in the opinion of the Investigator, would have resulted in 
immediate fatality if medical intervention had not been taken. This does not 
include an event that would have been fatal if it had occurred in a more 
severe form. 


 
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Hospitalization 
An event that results in an admission to the hospital for any length of time. 
This does not include an emergency room visit or admission to an out-patient 
facility. 
Prolongation of 
Hospitalization 
An event that occurs while the study subject is hospitalized and prolongs the 
subject's hospital stay. 
Congenital 
Anomaly/birth defect 
An anomaly detected at or after birth or any anomaly that result in fetal loss. 
Persistent or Significant 
Disability/Incapacity 
An event that results in a condition that substantially interferes with the 
activities of daily living of a study subject. Disability is not intended to include 
experiences of relatively minor medical significance such as headache, 
nausea, vomiting, diarrhea, influenza, and accidental trauma (e.g., sprained 
ankle). 
Other Important 
Medical Event 
An important medical event that may not be immediately life-threatening or 
result in death or hospitalization, but based on medical judgment may 
jeopardize the subject and may require medical or surgical intervention to 
prevent any of the outcomes listed above (i.e., death of subject, life- 
threatening, hospitalization, prolongation of hospitalization, congenital 
anomaly, or persistent or significant disability/incapacity). Examples of such 
events include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, blood dyscrasias or convulsions that do not 
result in inpatient hospitalization, or the development of drug dependency or 
drug abuse. 
7.2 Adverse Event Severity 
The Investigator will use the following definitions to rate the severity of each AE and SAE: 
Mild 
The event is transient and easily tolerated by the subject. 
Moderate 
The event causes the subject discomfort and interrupts the subject's 
usual activities. 
Severe 
The event causes considerable interference with the subject's usual 
activities and may be incapacitating or life-threatening. 
7.3 Causality of Adverse Events 
The Investigator will use the following definitions to assess the relationship of the AE/SAE to the use of 


 
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investigational product: 
Definitely Related 
The event occurred within a reasonable time after drug administration or drug 
concentration and body fluids demonstrated that the study drug was present: 
the event could not be reasonably explained by known characteristics including 
concomitant therapies; the adverse event abated after discontinuing the study 
drug. 
Probably Related 
The event has a strong temporal relationship to study drug or recurs on re-
challenge and another etiology is unlikely or significantly less likely. 
Possibly Related 
The event has a strong temporal relationship to the study drug and an 
alternative etiology is equally or less likely compared to the potential 
relationship to study drug. 
Probably Not 
Related 
The event has little or no temporal relationship to the study drug and/or a 
more likely alternative etiology exists. 
Not Related 
The event is due to an underlying or concurrent illness or effect of another drug 
and is not related to the study drug (e.g., has no temporal relationship to study 
drug or has a much more likely alternative etiology). 
If an Investigator's opinion of possibly, probably not, or not related to study drug is given, an alternate 
etiology must be provided by the Investigator for the AE. 
7.4 Adverse Event Collection Period 
Any AE/SAE prior to the Baseline visit will be considered past medical history (PMH). The AE reporting 
period for this study begins upon receiving the first application of investigational product and ends at the 
final protocol required visit. SAE(s) that are observed or spontaneously reported during the subject’s 
participation in the trial will be captured and monitored until the Investigator deems the event to be 
chronic or not clinically significant or the subject to be stable.  
7.5 Adverse Event Reporting 
In the event of a SAE, whether related to study drug or not, the Investigator or representative must make 
an accurate and adequate report consisting of at least the minimum criteria (Site and Subject ID, Date site 
became aware of the event, SAE Term, Seriousness criteria, Study Drug information, Investigator/Reporter 
and site address) within 24 hours by email, fax, or telephone to Biorasi Safety and Pharmacovigilance 
team. Biorasi Safety and Pharmacovigilance team will complete the SAE report onto a MedWatch 3500A 
form for evaluation and convey for review by the Medical Monitor and Sponsor contact. Accurate 
Completion of the MedWatch 3500A form will consist of all data supplied such as Subject’s demography, 
SAE narrative, concomitant medication, laboratory parameters and relevant medical history. 
In addition, if required by the applicable IRB/IEC, the Investigator will submit the SAE reports to the IRB/IEC 
within 15 calendar days of discovering the SAE, or alternatively, within accordance of applicable 


 
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regulations or IRB/IEC requirements. 
Copies of each report with the associated documentation (i.e., queries, medical records, lab records, 
IRB/IEC communications and all source documents) will be kept in the site’s study file. 
 A subject experiencing one or more SAEs will receive treatment and follow-up evaluations by the 
Investigator or may be referred to another appropriate physician for treatment and follow-up. The 
Investigational Site will be responsible for collection and forwarding follow-up SAE information to the 
Biorasi Safety and Pharmacovigilance. 
MEDICAL MONITOR 
Sergey Yagoda, MD, PhD 
Biorasi Safety and Pharmacovigilance  
E-mail : syagoda@biorasi.com 
Address : 19495 Biscayne Blvd., Suite #900, Aventura, FL 33180 
Fax 
: +1 (786) 221-3531 
7.6 Unblinding due to SAE 
Treatment assignment for an individual subject should be unblinded only in an emergency by the 
Investigator, when knowledge of the treatment assignment is urgently needed for the clinical 
management or welfare of the subject. Treatment should be provided in accordance with the medical 
condition and with regard to the information provided in the Investigator’s Brochure. 
The Investigator must document the breaking of the code, and the reasons for doing so on the eCRF, in 
the site file, and in the medical notes. 
The Investigator must notify the Sponsor in writing as soon as possible following the code break detailing 
the necessity of the code break. Subject always to clinical need and where possible, all other members of 
the research team should remain blinded. 


 
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8. DATA ANALYSIS 
The sections below summarize the intended statistical methods and analyses of data for the study. A more 
detailed statistical analysis plan will be written prior to finalization of the clinical trial database. Any 
changes to the planned methods and analyses will be described and justified in the protocol and/or in the 
final clinical study report, as appropriate. 
Descriptive statistical methods will be used to summarize the data from this study, with confidence 
intervals calculated for the primary and secondary efficacy endpoints. Unless stated otherwise, the term 
“descriptive statistics” refers to number of subjects (n), mean, median, standard deviation (SD), minimum, 
and maximum for continuous data and frequencies and proportions for categorical data. The term 
“treatment group” refers to randomized treatment assignment: active-test and active-reference. All data 
collected during the study will be included in data listings. Unless otherwise noted, the data will be sorted 
first by treatment assignment, subject number, and then by date within each subject number. 
Unless specified otherwise, all statistical testing will be two-sided and will be performed using a 
significance (alpha) level of 0.05. 
All statistical analyses will be conducted with the SAS® System, version 9.1.3 or higher. 
8.1 Subject Population/Data Sets to Be Evaluated 
The subject populations are defined as follows: 
1. Safety Population: The safety population is any randomized individual who (a) was enrolled 
into the study, and (b) received at least one dose of study treatment. 
2. Modified Intent-to-Treat (mITT) Population: A modified intent-to-treat subject is any 
randomized individual who (a) met inclusion/exclusion criteria, (b) was enrolled into the study, 
(c) received at least one dose of the assigned study treatment, and (c) had at least one post-
baseline visit. 
3. Per Protocol (PP) Population: A per-protocol subject is any randomized individual who (a) met 
inclusion/exclusion criteria, (b) was enrolled into the study, (c) received the assigned study 
treatment, (d) had not taken any concomitant medications prohibited by the protocol or 
experienced any major deviations that interfered with or may have interfered with the 
therapeutic administration of the treatment or the precise evaluation of treatment efficacy, 
and (e) completed the primary endpoint evaluation within the designated visit window (±4 
days). 
Subjects whose condition worsens and require alternate or supplemental therapy for the treatment of 
scabies during the study will be discontinued, included in both the mITT and PP population analyses as 
treatment failures. Subjects who discontinue early for reasons other than treatment failure will be 
excluded from the PP population, but included in the mITT population, using Last Observation Carried 
Forward (LOCF). 


 
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Efficacy analyses will be performed using the per-protocol population as definitive and the mITT 
population as supportive. Safety analyses will be performed using the Safety population. 
8.2 Sample Size Determination 
Under the assumption that the Reference product has a cure rate of at least 88%, sample size evaluations 
were 
conducted, 
via 
computer 
simulation, to 
determine 
the 
probability 
(power) 
of the 
calculated 90% continuity-corrected confidence 
interval 
on 
the 
Test-to-Reference 
difference 
in cure proportions to be contained in the bioequivalence interval [-0.20, +0.20].  When the Test product 
was assumed to have the same 88% cure rate, the required number of PP subjects in each treatment 
group was determined to be 56 (112 total) for a power ≥0.80.  Allowing for up to 20% of the subjects to 
not qualify for the PP population, 70 subjects in each treatment group (140 total) would be needed. 
If it is assumed that the Test product cure rate might deviate from that of the Reference by as much as 
2% (e.g. 86% instead of 88%) and if a higher power, ≥0.95, was desired, then 91 PP subjects in each 
treatment group (182 total) would be needed.  To allow for up to 20% of the subjects to not qualify for 
the PP population, 114 subjects in each treatment group (228 total) would need to be enrolled.   
8.3 Statistical Analyses 
8.3.1 Subject Disposition and Demography 
Descriptive statistics will be generated by treatment group for selected continuous variables. The number 
and percentage of subjects in each class of categorical demographic and Baseline variables (e.g., gender, 
ethnicity, and race) will be tabulated by treatment group. Individual subject demographic and Baseline 
characteristic data will be listed. 
8.3.2 Assessment of Bioequivalence as Primary and Secondary Endpoints 
Bioequivalence assessment will be evaluated by comparing proportions of patients cured in the test and 
the reference treatment groups. Bioequivalence between the test and the reference product will be 
established if the 90% confidence interval for the difference in proportions cured between test and 
reference treatment is contained within the equivalence limits [-0.20, +0.20]. 
In this case, the compound hypothesis to be tested is: 
H0: pT – pR < -0.20 or pT – pR > 0.20 (meaning test product is not bioequivalent to the reference); 
HA: -0.20 ≤ pT –pR ≤ 0.20 (supporting bioequivalence); 
where pT = cure rate of test treatment, pR = cure rate of reference treatment.  
Let nT = sample size of test treatment group, nR = sample size of reference treatment group and 
se = (𝑝𝑝𝑇𝑇 
ෞ(1 −𝑝𝑝𝑇𝑇 
ෞ) 𝑛𝑛𝑇𝑇+ 
⁄
𝑝𝑝𝑅𝑅 
ෞ(1 −𝑝𝑝𝑅𝑅 
ෞ) 𝑛𝑛𝑅𝑅) 
⁄
1
2. 
The 90% confidence interval will be estimated as follows, using Yates correction: 


 
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L = (𝑝𝑝̂𝑇𝑇−𝑝𝑝̂𝑅𝑅) −1.645 ×  𝑠𝑠𝑠𝑠−(
1
𝑛𝑛𝑇𝑇+ 
1
𝑛𝑛𝑅𝑅) 2
⁄  
U = (𝑝𝑝̂𝑇𝑇−𝑝𝑝̂𝑅𝑅) + 1.645 ×  𝑠𝑠𝑠𝑠+ (
1
𝑛𝑛𝑇𝑇+ 
1
𝑛𝑛𝑅𝑅) 2
⁄  
H0 is rejected if L ≥ -0.20 and U ≤ 0.20 resulting in accepting HA and concluding bioequivalence of the two 
products. 
The primary endpoint is the evaluation at Day 28. The results in the PP population will be considered 
definitive, with those in the mITT population as supportive. 
As a secondary endpoint evaluation, patients’ clinical progress at visit 4 (Day 14) will be assessed and 
proportion of cured patients in each of the treatment arms will be compared using the procedure above. 
8.3.3 Assessment of retreatment 
Proportion of subjects requiring retreatment in each of the treatment groups will be compared 
descriptively. 
8.3.4 Assessment of Tolerability 
Descriptive statistics using categorical methods will be used to compare tolerability measures (scores of 
Stinging/Burning and Itching sensations collected during Patient Self-Assessments) between the test and 
reference treatment groups. 
8.3.5 Assessment of Safety 
The reporting of safety data is descriptive, and will include all subjects who receive at least one dose of 
investigational product. The variables for safety endpoints are AEs and vital signs measurements. AEs will 
be summarized based on the frequency of AEs and their severity for all treated subjects. All AEs will be 
coded using Medical Dictionary for Regulatory Activities (MedDRA) and summarized by treatment group. 
Data will be summarized using preferred term and primary system organ class. 
If a subject experiences multiple events that map to a single preferred term, the greatest severity and 
strongest Investigator assessment of relation to study drug will be assigned to the preferred term for the 
appropriate summaries. Should an event have a missing severity or relationship, it will be classified as 
having the highest severity and/or strongest relationship to study drug. 
Summaries of treatment-emergent AEs will include any AEs reported beginning with the first dose of study 
drug on Day 1. The occurrence of treatment-emergent adverse events will be summarized by treatment 
group using preferred terms, system organ classifications, and severity. Separate summaries of treatment-
emergent serious adverse events, treatment-emergent adverse events related to study drug, and events 
leading to the discontinuation of study drug will be generated. All adverse events reported will be listed 
for individual subjects showing both verbatim and preferred terms. 
Concomitant medications will be coded using the World Health Organization (WHO) drug dictionary. 


 
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These data will be summarized by treatment group. Previous and concomitant medications will be 
presented in a data listing. 


 
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9. REGULATORY, ETHICAL, AND LEGAL OBLIGATIONS 
9.1 Ethical Conduct of the Study  
The study will be conducted in accordance with the Declaration of Helsinki on Ethical Principles for 
Medical Research Involving Human Subjects, adopted by the General Assembly of the World 
Medical Association (2013) (See Appendix C). In addition, the study will be conducted in accordance with 
the protocol, the ICH guideline on 
GCP, and applicable local regulatory requirements and laws.  
9.2 Institutional Review Board (IRB) / Independent Ethics Committee (IEC) 
It is the responsibility of the Investigator to have prospective approval of the study protocol, protocol 
amendments, informed consent forms, and other relevant documents, (e.g., recruitment advertisements, 
if applicable) from the IRB/IEC. All correspondence with the IRB/IEC will be retained in the Investigator 
File. Copies of IRB/IEC approvals should be forwarded to the Sponsor or its designee. 
The only circumstance in which an amendment may be initiated prior to IRB/IEC approval is where the 
change is necessary to eliminate apparent immediate hazards to the subjects. In case of such an event, 
the Investigator must notify the IRB/IEC and the Sponsor in writing immediately after the implementation. 
9.3 Other Required Approvals 
In addition to IRB/IEC approval, all other required approvals (e.g. approval from local Research and 
Development Board or Scientific Committee) required by the individual site for participating in this study 
will be obtained by the Investigator prior to recruitment of subjects into the study and shipment of the 
investigational product(s). It is the responsibility of the Investigator to notify the Sponsor and the CRO of 
the requirement of such approvals prior to participating tin the study. 
9.4 Informed Consent 
It is the responsibility of the Investigator to give each subject (or the subject’s acceptable representative), 
prior to inclusion in the trial, full and adequate verbal and written information regarding the objective and 
procedures of the trial and the possible risks involved. The subjects must be informed about their right to 
withdraw from the trial at any time. 
Furthermore, it is the responsibility of the Investigator, or a person designated by the Investigator, to 
obtain signed informed consent from each subject or the subject’s legally acceptable representative prior 
to inclusion in the trial. The Investigator will retain the original of each subject's signed consent form. 
The informed consent form will be in compliance with ICH GCP, local regulatory requirements, and legal 


 
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requirements. The informed consent form used in this study, and any changes made during the course of 
the study, must be prospectively approved by both the IRB/IEC and the Sponsor before use. 
9.5 Subject Confidentiality 
All parties will ensure protection of subject personal data and will not include subject names on any 
Sponsor forms, reports, publications, or in any other disclosures, except where required by law. In case of 
data transfer, the Sponsor will maintain high standards of confidentiality and protection of subject 
personal data. 
The Sponsor and designees affirm and uphold the principle of the subject’s right to protection against 
invasion of privacy. Throughout this study, a subject’s source data will only be linked to the Sponsor’s 
clinical study database or documentation via a unique identification number. As permitted by all 
applicable laws and regulations, limited subject attributes, such as sex, age, or date of birth, and subject 
initials may be used to verify the subject and accuracy of the subject’s unique identification number. 
To comply with ICH Guidelines for GCP and to verify compliance with this protocol, the Sponsor requires 
the Investigator to permit its monitor or designee’s monitor, representatives from any regulatory 
authority (e.g., FDA), the Sponsor’s designated auditors, and the appropriate IRBs and IECs to review the 
subject’s original medical records (source data or documents), including, but not limited to, laboratory 
test result reports, ECG reports, admission and discharge summaries for hospital admissions occurring 
during a subject’s study participation, and autopsy reports. Access to a subject’s original medical records 
requires the specific authorization of the subject as part of the informed consent process. 
Copies of any subject source documents that are provided to the Sponsor must have certain personally 
identifiable information removed (i.e., subject name, address, and other identifier fields not collected on 
the subject’s CRF). 
9.6 Publication 
No publication or disclosure of study results will be permitted, except under the terms and conditions of 
a separate, written agreement between Sponsor and the Investigator and/or the Investigator’s institution. 
The Sponsor must have the opportunity to review and approve all proposed abstracts, manuscripts, or 
presentations regarding this study prior to submission for publication/presentation. Any information 
identified by the Sponsor as confidential must be deleted prior to submission. 


 
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10. 
ADMINISTRATIVE OBLIGATIONS 
10.1 Source Documentation Forms 
The Investigator/institution will permit study-related monitoring, audits/inspections, IRB/IEC review and 
regulatory inspection providing direct access to source documents, including all medical records or 
pertinent data relevant to the audit/inspection. Source documents will represent a record of the raw data. 
Source document templates may be provided by either the clinical site or the Sponsor. If provided by the 
clinical site, the source document template must be provided to the Sponsor prior to subject recruitment. 
The source documents will become part of the subject's permanent medical record maintained by the 
clinical site. If computerized systems are used to create, modify, maintain, archive, retrieve or transmit 
source data, they must comply with the applicable regulatory regulations and/or guidances (ex. 21 CFR 
Part 11 and 312). 
Electronic CRFs (eCRFs) will be used in this study. eCRFs are required and should be completed for each 
subject participating in the study. eCRFs will contain data captured from subject source documents and 
results of laboratory tests. In most cases, the source documents are contained in the subject’s chart at the 
hospital or the physician's office. In these cases, data collected on the CRFs must match the data in those 
charts. Data must be transcribed from the source documents (e.g. physical exam report, associated 
medical records, date and version of informed consent form) onto the eCRF by clinical site personnel prior 
to data monitoring.  
Any corrections to entries made in the source documents must be dated, initialed and explained (if 
necessary) and should not obscure the original entry. The Investigator has ultimate responsibility for the 
accuracy, authenticity, and timely collection and reporting of all clinical, safety, and laboratory data 
entered on the CRFs and any other data collection forms.  
Investigator will sign eCRFs electronically after completion of data entry, to attest that the data contained 
on the CRFs is complete and accurate. Completed eCRFs are the sole property of the Sponsor and should 
not be made available in any form to third parties, except for authorized representatives of the Sponsor 
or appropriate regulatory authorities, without written permission from the Sponsor. 
10.2 Record Retention 
To enable evaluations and/or audits from regulatory authorities or the Sponsor, the Investigator agrees 
to keep records, including the identity of all participating subjects (sufficient information to link records, 
e.g., CRFs and hospital records), all original signed Informed Consent Forms, copies of all CRFs, SAE forms, 
source documents, detailed records of drug disposition, and adequate documentation of relevant 
correspondence (e.g., letters, meeting minutes, telephone calls reports).  
The records will be retained by the Investigator according to the International Conference on 
Harmonization (ICH), local regulations, or as specified in the Clinical Study Agreement, whichever is longer. 


 
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If the Investigator becomes unable for any reason to continue to retain study records for the required 
period (e.g., retirement, relocation), the Sponsor will be prospectively notified. The study records must 
be transferred to a designee acceptable to the Sponsor, such as another Investigator, another institution, 
or to the Sponsor. The Investigator must obtain Sponsor’s written permission before disposing of any 
records, even if retention requirements have been met. 
10.3 Quality Control (QC) and Quality Assurance (QA) 
10.3.1 Study Site Monitoring Visits 
During study conduct, the Sponsor or its designee will conduct periodic monitoring visits to ensure that 
the protocol and Good Clinical Practice (GCP) are being followed. The monitors will review source 
documents to confirm that the data recorded on CRFs is accurate. The Investigator/institution will allow 
the Sponsor’s monitors or designees and appropriate regulatory authorities direct access to source 
documents to perform this verification. 
The study site may also be subject to quality assurance audits performed by the Sponsor or companies 
working with or on behalf of the Sponsor, and/or review by the IRB/IEC, and/or to inspection by 
appropriate regulatory authorities 
It is important that the Investigator(s) and their relevant personnel are available during the monitoring 
visits and possible audits or inspections, and that sufficient time is devoted to the process. 
10.3.2 Protocol Deviations 
The Investigator should not deviate from the protocol, except where necessary to eliminate an immediate 
hazard to study subjects. The site should document all protocol deviations (PDs) in the subject’s source 
documents. In the event of a significant deviation, the site will notify the Sponsor or its designee (and IRB 
or IEC, as required). Significant deviations include, but are not limited to, those that involve fraud or 
misconduct, increase the health risk to the subject, or confound interpretation of primary study 
assessments. Deviations from the inclusion/exclusion criteria will not be permitted unless written 
approval by the Mayne Pharma, Inc. has been obtained. Should other unexpected circumstances arise 
that will require deviation from protocol-specified procedures, the Investigator will contact Biorasi Safety 
and Pharmacovigilance at the below mentioned address in order to determine the appropriate course of 
action.  
BIORASI SAFETY AND PHARMACOVIGILANCE  
E-mail: safety@biorasi.com 
19495 Biscayne Blvd., Suite #900 
Aventura, FL 33180 
Fax: +1 (786) 221-3531 
Site will be responsible for proper maintaining and filing of all PD related documentation in the site files. 


 
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10.4 Trial Discontinuation/Investigative Site Termination 
The Sponsor reserves the right to discontinue the trial prior to inclusion of the intended number of 
subjects, but intends only to exercise this right for valid scientific or administrative reasons.  
After such a decision, the Investigator must contact all participating subjects within a time period specified 
by the Sponsor to inform them of the decision to discontinue the trial. 
10.4.1 Criteria for Premature Termination or Suspension of the Study 
The following criteria may result in either temporary suspension or early termination of the study: 
 
New information regarding the safety or efficacy of the investigational product that indicates a 
change in the known risk/benefit profile for the compound, such that the risk/benefit is no longer 
acceptable for subjects participating in the study. 
 
Significant violation of GCP that compromises the ability to achieve the primary study objectives 
or compromises subject safety. 
The Sponsor reserves the right to discontinue the trial for other valid administrative reasons. 
10.4.2 Criteria for Premature Termination or Suspension of Investigational Sites 
A study site may be terminated prematurely or suspended if the site (including the Investigator) is found 
to be in significant violation of GCP, protocol, contractual agreement, or is unable to ensure adequate 
performance of the study. 
10.4.3 Procedures for Premature Termination or Suspension of the Study or Investigational 
Site(s) 
In the event that the Sponsor elects to terminate or suspend the study or the participation of an 
investigational site, a study-specific procedure for early termination or suspension will be provided by the 
Sponsor; the procedure will be followed by applicable investigational sites during the course of 
termination or study suspension. 


 
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11. 
REFERENCES 
1. Chosidow, O. (2000). Scabies and pediculosis. The Lancet, 355(9206), 819-26. 
2. Currie, B. J., McCarthy, J. S. (2010). Permethrin and ivermectin for scabies. The New England 
Journal of Medicine, 362(8), 717-25. 
3. Permethrin 5% w/w Cream. SPC. Last Updated on eMC 27-Jun-2014. Available at URL: 
http://www.medicines.org.uk/emc/medicine/21718 
4. CDC - Scabies – Treatment. http://www.cdc.gov/parasites/scabies/treatment.html. September 6, 
2016. 
5. Goldust, M., Rezaee, E., Raghifar, R., Hemayat, S. (2013). Treatment of scabies: the topical 
ivermectin vs permethrin 2.5%. Annals of Parasitology, 59(2), 79-84. 
6. Ranjkesh, M.R., Naghili, B., Goldust, M., Rezaee, E. (2013). The efficacy of permethrin 5% vs. oral 
ivermectin for the treatment of scabies. Annals of Parasitology, 59(4), 189- 194. 
7. Bachewar, N.P., Thawani, V.R., Mali, S.N., Gharpure, K.J., Shingade, V.P., Dakhale, G.N. (2009). 
Comparison of safety, efficacy, and cost effectiveness of benzyl benzoate, permethrin, and 
ivermectin in patients of scabies. Indian J Pharmacol, 41(1), 9-14. 


 
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12. 
APPENDICES 
12.1 Appendix A. Study Flowchart 
 
 
Figure 1. Enrolling Subjects with Affected or High-Risk bedmates/Family Members 


 
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12.2 Appendix B. Schedule of Events 
Visit Number 
Visit 1 
Screening 
Visit 2 
Baseline1 
Visit 3  
Interim 
Visit 4 
Interim 
Visit 5 
EOS/ET2 
Visit Day 
Day 
-5 to 1 
Day 1 
Day 7 
(±1) 
Day 14 
(±2) 
Day 28 
(±4) 
Informed Consent 
X 
 
 
 
 
Eligibility Criteria 
X 
 
 
 
 
Subject Demographics 
X 
 
 
 
 
Medical History 
X 
 
 
 
 
Physical Examination 
X3 
 
 
 
 
Randomization 
 
X4 
 
 
 
Vital Signs 
X 
X 
 
 
X 
Urine Pregnancy Test5 
X 
 
 
 
X 
Visual Examination of Lesions 
X 
X 
X 
X 
X 
Microscopic Examination of Skin Scraping6 
X 
 
 
 
 
Patient Self-Assessment 
 
X 
X 
X 
X 
Investigational Product Dispensation 
 
X 
 
X7 
 
Treatment with Investigational Product 
 
X 
 
X8 
 
Investigational Product Accountability 
 
 
X 
 
X8 
Subject Diary Compliance Review 
 
 
X 
 
X8 
Concomitant and Prohibited Medication Review 
X 
X 
X 
X 
X 
Adverse Events Assessment 
 
 
X8 
X 
X 
                                                          
1 Visit 2 (Baseline) may be completed on the same day as visit 1 (Screening). If Screening and Baseline are completed on the same 
day, assessments performed on both Screening and Baseline need only be performed once. Refer to Section 6.3.2 for details and 
restrictions. 
2 End of Study/Early Termination. 
3 Physical examinations are to be performed if Inclusion/Exclusion Criteria are satisfied at Screening 
4 Prior to Randomization, the Investigator must confirm the subject still meets all Inclusion/Exclusion Criteria. 
5 For females of child-bearing potential. 
6 Any new lesions identified at visits 3, 4 or 5 will be confirmed by microscopic evaluation of skin scraping. 
7 Applicable for subjects requiring second application of the investigational product. 
8 AE reporting period for this study begins upon receiving the first application of investigational product and ends at the final 
protocol required visit. 


 
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12.3 Appendix C. Subject Diary 


 
 
 
 
MAP-8184: Subject Diary (Confidential)                                                                                                                     Page 1 of 7 
Version 2.0, Date: 29 Aug 2016 
 
 
 
 
 
To be completed by the study team member 
 
SUBJECT 
NUMBER : 
 
 
 
 
 
 
 
SUBJECT 
INITIALS:   
 
 
SUBJECT TREATMENT INFORMATION 
Study Visit  
Baseline 
Day 14 
Dose Application 
1st Application 
2nd Application 
Status  
  Required 
 
  Required 
  Not Required 
 
HOUSEHOLD MEMBERS TREATMENT INFORMATION 
No of Household Members with Active scabies 
 
Number of Standard of Care tubes provided 
 
 
 
 
Protocol 
Number  :  
MAP-8184 
Study Title    :  
A Multi-Center, Double-Blind, Randomized, Parallel-Group Study 
Comparing Permethrin Cream, 5% (Mayne Pharma, Inc.) with 
Elimite™ in patients with active scabies 
SUBJECT DIARY 


 
SUBJECT DIARY 
 
 
 
MAP-8184: Subject Diary (Confidential)                                                                                                                 Page 7 of 7 
Version 2.0, Date: 29 Aug 2016 
VISIT 2:  BASELINE (DAY 1) 
VISIT DATE AT CLINIC: 
 
 
 
 
 
 
 
 
 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
PRIOR TO APPLICATION OF THE STUDY DRUG 
Please follow the instructions given below and check the box for confirmation of the same. Provide supervision 
to children and those who require assistance. 
Activity  
Instructions 
Status check (Tick)  
LAUNDRY 
DISINFECTION 
 Machine-wash personal clothes, towels, linens and 
other items of all household members with scabies 
that have everyday physical contact for the last week 
with in a hot water (at least 50 oC or 120 oF) 
 Dry these items using a high heat cycle.  
 Non-washable items can be put into the dryer for at 
least 20 minutes on a high heat. Alternatively, they can 
be sealed in a plastic bags for a week. 
 Yes     
No 
NAILS HYGIENE 
 Clip fingernail and toenails with your scissors or clipper 
 Wash and scrub under-the-nails areas in hot soapy 
water 
 Yes     
No 
BODY HYGIENE 
 Take a warm shower (NOT a hot bath) using a non-
medicated soap 
 Dry thoroughly and cool-down before the next step 
 Yes     
No 
 
APPLICATION OF THE STUDY DRUG 
Activity  
Instructions for Application of study drug 
Status check (Tick) 
 
Application 
of Cream 
 Apply thin layer of the Study Drug to the entire 
body from the neck down to the bottom of the 
feet. 
 Pay special attention to the areas between fingers 
and toes, under nails, wrists, armpits, skin surface 
of around genitalia (but NOT internally), breasts 
and buttocks.  
 The cream rubs completely into the skin so you do 
not need to keep applying more cream until you 
can see it on the skin. 
 Avoid contact with eyes. Flush with water 
immediately if the cream gets into your eyes 
 Record the date and time of Application. 
 Leave the cream on your body for 8-14 hours 
before washing it out (for example, you can leave 
it overnight). Re-apply the Study Drug to hands if 
 Yes     
No 
 
Date of Application 
 
Time of Application 
 


 
SUBJECT DIARY 
 
 
 
MAP-8184: Subject Diary (Confidential)                                                                                                                 Page 7 of 7 
Version 2.0, Date: 29 Aug 2016 
APPLICATION OF THE STUDY DRUG 
Activity  
Instructions for Application of study drug 
Status check (Tick) 
they are washed with soap and water within 8 
hours of treatment.  
 
AFTER 
Application 
of Cream 
 
 Record the date and time when the cream was 
washed off. 
 Wear clean clothes after treatment is completed. 
Do not wear the same clothes that were worn 
while treating; likewise, change bedding and towels 
etc. 
 Yes     
No 
 
Date of Wash-off 
 
Time of Wash-off 
 
 
TREATMENT CHECK FOR AFFECTED HOUSEHOLD MEMBERS 
Household members are to follow the same instruction as detailed above for you (subject of the study). Please 
ensure you and your affected household members take treatment on the same day. 
Activity  
Status check (Tick) 
LAUNDRY DISINFECTION : Machine-wash personal clothes, towels, linens and 
other items 
 Yes     
No 
NAILS HYGIENE : Finger nails clipped and wash hands in hot soapy water 
 Yes     
No 
BODY HYGIENE : Warm shower using a non-medicated soup 
 Yes     
No 
CREAM APPLICATION: Apply cream and leave on for 8 hours 
 Yes     
No 
CREAM WASH-OFF: Wash-off cream after 8 hours and within 14 hours 
 Yes     
No 
 
 
 
 
Cream Applied
Wash-off with 
soap and 
water 
after 8 hours 
and 
within 14 
hours
Leave the 
cream on 
for at least 
8 hours


 
SUBJECT DIARY 
 
 
 
MAP-8184: Subject Diary (Confidential)                                                                                                                 Page 7 of 7 
Version 2.0, Date: 29 Aug 2016 
Please answer the following questions by ticking the correct box: 
1. Have you had any health problems since your last visit to clinic?                             
Yes
 
No
 
 
2. Have you had any local skin reactions since your last visit to clinic?                
                                
                                                            Yes
 
No
 
 
3. Have you taken any new medications since your last visit to clinic?             
                                         
                                                                                Yes
 
No
  
 
In case of medical emergency call 911 immediately. 
Remember the next study visit date is Day 7 i.e. 6 days from Visit 2 (Day 1): _________________ 
 
Subject’s Initials: ___- ___ - ___  
Date: ___ ___ - ___ ___ ___ - ___ ___ ___ ___  
 
Initials of Site Staff verifying the completeness of the Subject Diary: ___- ___ - ___ 
Date of Verification: ___ ___ - ___ ___ ___ - ___ ___ ___ ___ 
 
 


 
SUBJECT DIARY 
 
 
 
MAP-8184: Subject Diary (Confidential)                                                                                                                 Page 7 of 7 
Version 2.0, Date: 29 Aug 2016 
VISIT 4:  INTERIM (DAY 14) 
VISIT DATE AT CLINIC: 
 
 
 
 
 
 
 
 
 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
Does the subject require second Application of the Study Drug?    
 Yes     
 No 
Note for Site Staff:  
If YES: Dispense the study drug and provide this Subject Diary 
If NO: File this Subject Diary along with the Source Document Worksheet. 
 
PRIOR TO APPLICATION OF THE STUDY DRUG 
Please follow the instructions given below and check the box for confirmation of the same. Provide supervision 
to children and those who require assistance. 
Activity  
Instructions 
Status check (Tick)  
LAUNDRY 
DISINFECTION 
 Machine-wash personal clothes, towels, linens and other items 
of all household members with scabies that have everyday 
physical contact for the last week with in a hot water (at least 
50 oC or 120 oF) 
 Dry these items using a high heat cycle.  
 Non-washable items can be put into the dryer for at least 20 
minutes on a high heat. Alternatively, they can be sealed in a 
plastic bags for a week. 
 Yes     
No 
NAILS HYGIENE 
 Clip fingernail and toenails with your scissors or clipper 
 Wash and scrub under-the-nails areas in hot soapy water 
 Yes     
No 
BODY HYGIENE 
 Take a warm shower (NOT a hot bath) using a non-medicated 
soap 
 Dry thoroughly and cool-down before the next step 
 Yes     
No 
 
APPLICATION OF THE STUDY DRUG 
Activity  
Instructions for Application of study drug 
Status check (Tick) 
 
Application 
of Cream 
 Apply thin layer of the Study Drug to the entire body 
from the neck down to the bottom of the feet. 
 Pay special attention to the areas between fingers and 
toes, under nails, wrists, armpits, skin surface of around 
genitalia, breasts and buttocks.  
 The cream rubs completely into the skin so you do not 
need to keep applying more cream until you can see it on 
the skin. 
 Avoid contact with eyes. Flush with water immediately if 
the cream gets into your eyes 
 Record the date and time of Application  
 Leave the cream on your body for 8-14 hours before 
washing it out (for example, you can leave it 
 Yes     
No 
 
Date of Application 
 
Time of Application 
 


 
SUBJECT DIARY 
 
 
 
MAP-8184: Subject Diary (Confidential)                                                                                                                 Page 7 of 7 
Version 2.0, Date: 29 Aug 2016 
APPLICATION OF THE STUDY DRUG 
Activity  
Instructions for Application of study drug 
Status check (Tick) 
overnight). Re-apply the Study Drug to hands if they 
are washed with soap and water within 8 hours of 
treatment.  
 
AFTER 
Application 
of Cream 
 
 Record the date and time of the cream was washed 
off. 
 Wear clean clothes after treatment is completed. Do 
not wear the same clothes that were worn while 
treating; likewise, change bedding and towels etc. 
 Yes     
No 
 
Date of Wash-off 
Time of Wash-off 
 
 
 
TREATMENT CHECK FOR AFFECTED HOUSEHOLD MEMBERS 
Household members are to follow the same instruction as detailed above for you (subject of the study). Please 
ensure you and your affected household members take treatment on the same day. 
Activity  
Status check (Tick) 
LAUNDRY DISINFECTION : Machine-wash personal clothes, towels, linens and 
other items 
 Yes     
No 
NAILS HYGIENE : Finger nails clipped and wash hands in hot soapy water 
 Yes     
No 
BODY HYGIENE : Warm shower using a non-medicated soup 
 Yes     
No 
CREAM APPLICATION: Apply cream and leave on for 8 hours 
 Yes     
No 
CREAM WASH-OFF: Wash-off cream after 8 hours and within 14 hours 
 Yes     
No 
 
 
Please answer the following questions by ticking the correct box: 
Cream Applied
Wash-off with 
soap and 
water 
after 8 hours 
and 
within 14 
hours
Leave the 
cream on 
for at least 
8 hours


 
SUBJECT DIARY 
 
 
 
MAP-8184: Subject Diary (Confidential)                                                                                                                 Page 7 of 7 
Version 2.0, Date: 29 Aug 2016 
1. Have you had any health problems since your last visit to clinic?                             
Yes
 
No
 
 
2. Have you had any local skin reactions since your last visit to clinic?                
                                
                                                             Yes
 
No
 
 
3. Have you taken any new medications since your last visit to clinic?             
                                         
                                                                                Yes
 
No
  
 
In case of medical emergency call 911 immediately. 
Remember the next study visit date is Day 28 i.e. 14 days from Visit 4 (Day 14): _________________ 
 
Subject’s Initials: ___- ___ - ___  
Date: ___ ___ - ___ ___ ___ - ___ ___ ___ ___  
 
Initials of Site Staff verifying the completeness of the Subject Diary: ___- ___ - ___ 
Date of Verification: ___ ___ - ___ ___ ___ - ___ ___ ___ ___ 
 
 


 
Protocol Number: MAP-8184 
Original Protocol Version 1.0; 18 Mar 2016 
 
 
 
 
CONFIDENTIAL 
Page 65 of 66 
12.4 Appendix D. Patient Self-Assessment 


 
PATIENT SELF-ASSESSMENT 
 
 
MAP-8184: Patient Self-Assessment (Confidential) 
                                 Page 1 of 1  
Version 1.0 , Date: 21 April 2016                                                                                                 Staff Initials & Date: ______________ 
 
PROTOCOL NO:  
MAP-8184 
SUBJECT 
NUMBER : 
 
 
 
 
 
 
 
Subject 
Initials:   
 
 
Visit Number 
Visit 2 [Baseline] 
Visit 3 [Interim] 
Visit 4 [Interim] 
Visit 5 [EOS/ET] 
Visit Day 
Day 1 
Day 7 
Day 14 
Day 28 
Check one 
 
 
 
 
  
VISIT DATE : 
 
 
 
 
 
 
 
 
 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 
This self-assessment is aimed to see how bad are the itching and stinging/burning sensations that you 
may experience during the last 24 hours. Please rate these feelings by marking one most suitable 
option from each table below. 
ITCHING 
(Intense, distracting irritation or tickling sensation in the last 24 hours) 
Score 
Grade 
Definition 
Check one 
0 
None 
No Itching 
 
1 
Mild 
Barely perceptible, slightly present itch 
 
2 
Moderate 
Distinct presence of itch 
 
3 
Severe 
Marked, intense, yet tolerable itch 
 
4 
Very Severe 
Unbearable, intense itch 
 
 
STINGING/BURNING 
(Sensation of the skin is painfully hot or noticeable tingling sensation in the last 24 hours) 
Score 
Grade 
Definition 
Check one 
0 
None 
Absent 
 
1 
Mild 
Slight, barely present 
 
2 
Moderate 
Distinct presence 
 
3 
Severe 
Marked, intense 
 
 
 
Subject Initials: _____________________   
 
Date: __________________________  

SAP_001.pdf: 
Mayne Parma 
MAP-8184 
  
Statistical Analysis Plan 
Version 1 
 
 
CONFIDENTIAL 
Page 1 
14 March 2013 
 
 
 
 
Statistical Analysis Plan 
 
Study Title: 
A multi-center, double-blind, randomized, parallel-group 
study comparing Permethrin 5% cream (Mayne Pharma, Inc.) 
with ElimiteTM in patients with active scabies 
 
 
Phase: 
Phase 3 
 
 
Protocol No.: 
MAP-8184  
 
 
Original Protocol Version 1.0 
18 March 2016 
Protocol Amendment No. 1 
Version 2.0 
14 October 2016 
 
 
Analysis Plan Version and Date 
Version 1: 14 April 2017 
 
 
Prepared By: 
Jon Roth 
VP Data Sciences and Biometrics 
Biorasi, LLC 
 
 
 
 
Prepared For: 
MAYNE PHARMA, INC. 
1240 Sugg Parkway, 
Greenville, NC 27858 USA 
Phone:  +1 (252) 717-1382 
Fax:  +1 (252) 758-8522 
 
 
CONFIDENTIAL AND PROPRIETARY INFORMATION 


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STATISTICAL ANALYSIS PLAN REVIEW AND APPROVAL 
This Statistical Analysis Plan has been prepared in accordance with team reviewers’ 
specifications.   
 
Prepared by: 
 
Jon Roth, VP Data Sciences and Biometrics 
 
Date 
 
Statistical Review: 
 
Yuliya Yurova, PhD Statistics 
 
Date 
 
Sponsor Review:  
 
 
 
 
Mayne Pharma, Inc. 
 
 
Date 
 
 
 
 
Mayne Pharma, Inc.  
 
Date 




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Contents 
STATISTICAL ANALYSIS PLAN REVIEW AND APPROVAL ............................................... 2 
1 
INTRODUCTION ........................................................................................................... 5 
1.1 
Study Overview ................................................................................................................ 5 
1.2 
Time and Events Schedule ............................................................................................... 7 
1.3 
Glossary of Terms ............................................................................................................ 8 
2 
OBJECTIVES .................................................................................................................. 9 
3 
GENERAL STATISTICAL CONSIDERATIONS ......................................................... 9 
3.1 
Sample Size Estimation .................................................................................................... 9 
3.2 
Randomization ................................................................................................................. 9 
3.3 
Blinding and Procedures for Unblinding the Study ....................................................... 10 
3.4 
Handling of Data ............................................................................................................ 11 
3.4.1 
Examination of Subject Subsets ................................................................................. 11 
3.4.2 
Missing Data ............................................................................................................... 11 
3.4.3 
Definitions and Terminology...................................................................................... 12 
3.5 
Planned Analyses ........................................................................................................... 13 
4 
ANALYSIS POPULATIONS ....................................................................................... 13 
5 
STATISTICAL METHODS .......................................................................................... 13 
5.1 
Subject Disposition, Demographic and Baseline Characteristics .................................. 14 
5.2 
Efficacy Analyses ........................................................................................................... 14 
5.2.1 
Primary Efficacy Endpoint ......................................................................................... 14 
5.2.2 
Primary Efficacy Analyses ......................................................................................... 14 
5.2.3 
Secondary Efficacy Endpoints .................................................................................... 15 
5.2.4 
Secondary Efficacy Analyses ..................................................................................... 15 
5.3 
Retreatment Assessment ................................................................................................ 16 
5.4 
Tolerability Assessment ................................................................................................. 16 
5.5 
Safety Assessment .......................................................................................................... 16 
5.5.1 
Adverse Events ........................................................................................................... 16 
5.5.2 
Vital Signs .................................................................................................................. 17 
5.5.3 
Previous and Concomitant Medications ..................................................................... 17 
6 CHANGES IN THE PLANNED ANALYSES ...................................................................... 17 
7 PROGRAMMING CONVENTIONS ..................................................................................... 17 
8 TABLES, LISTINGS AND FIGURES .................................................................................. 19 


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Tables ............................................................................................................................................ 19 
Data Listings ................................................................................................................................. 20 
APPENDIX A:  ITCHING SENSATION SCALE ...................................................................... 22 
APPENDIX B: STINGING/ BURNING SENSATION SCALE ................................................. 22 
 
 
 
 
 
 


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1.   INTRODUCTION 
This document describes the statistical methods and data presentations to be used in the summary 
and analysis of data from Protocol MAP-8184.  Background information is provided for the overall 
study design and objectives.  The reader is referred to the study protocol and electronic case report 
forms (eCRFs) for details of study conduct and data collection. 
1.1.   Study Overview 
Clinical protocol MAP-8184 is a multicenter, randomized (1:1), double blind, two-arm parallel 
group study to compare the treatment success of the test product, Permethrin Cream, 5% (Mayne 
Pharma, Inc.), and the Reference product, ElimiteTM (marketed by Prestium Pharma, Inc.) on scabies 
infestations.   
This study assesses the comparative efficacy of Permethrin Cream, 5% (Mayne Pharma, Inc.) and 
ElimiteTM in patients with scabies infestation at the end of the treatment period (28±4 days). 
The study also assesses comparative safety of Permethrin Cream, 5% (Mayne Pharma, Inc.) and 
ElimiteTM and tolerability of Permethrin Cream, 5%. 
This study is comprised of two phases: screening and treatment. The screening period will be up 
to 5 days in duration and treatment will be 28±4 days in duration. Please refer Table 1.2 below for 
a more detailed presentation of the study visits and assessments.  After signing informed consent 
during screening (Visit 1), subjects, at least 12 years of age, male or female, of any race, will be 
evaluated to determine if they meet inclusion/exclusion criteria.  Any subject under the age of 18 
must sign the Assent Form and have the signature by a parent or legal guardian on informed 
consent form prior to enrollment in this study. Eligible patients will be enrolled and randomized 
in a 1:1 ratio for Test and Reference, and will be stratified by site.  Following the receipt of 
informed consent, the subject’s medical history will be recorded along with concomitant 
medications and prohibited treatments will be assessed as they should be discontinued.  A physical 
examination will be performed for all subjects and a urine pregnancy test will be performed for 
women of childbearing potential.  The subject’s scabies infestation will be evaluated for papules 
and burrows during the visual examination. Presence of acarids, feces, or ova will be assessed via 
microscopic exam of skin lesion scraping. Subjects who meet all inclusion/exclusion criteria will 
return to the office for visit 2 within 5 days. 
At Visit 2 (Baseline, Day 1), the subject’s concomitant medications will be updated and any 
changes to medical history will be recorded.  If subjects meet the randomization criteria, they will 
be assigned to one of the two treatment arms (Test or Reference) and the respective investigational 
product will be dispensed to subjects along with detailed instructions of drug application.  The 
subjects also will be instructed on completion of subject diaries.  Visits 1 and 2 can be combined, 
if subject’s eligibility can be confirmed at the Screening visit and conducted on the same day, 


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which then is Day 1.  All regular bedmates of the subject and individuals with prolonged physical 
contact with the subject will undergo an assessment by the Investigator and receive one 60 g tube 
of the standard of care generic Permethrin Cream, 5% at the Baseline visit, sufficient for two 
applications to prevent cross-infestation within the household.  
Subject will return at visit 3 (Day 7±1) with the used investigational product tube and subject 
diaries. Compliance with investigational product applications will be assessed. Safety and 
tolerability assessments will be conducted. 
At visit 4 (Day 14±2), subjects will return for efficacy, safety and tolerability assessments. If signs 
of active scabies infection are present at this visit, the subject will be treated with a second 
application of their assigned investigational product.  
Final efficacy, safety and tolerability assessments will occur at visit 5 (Day 28±4). If the subject 
was retreated, the used tube of the investigational product will be returned at this visit. The duration 
of each subject’s participation in the study will be a maximum of 37 days.  
Subjects will be encouraged to report any complications or adverse effects during their 
participation.  Investigator may evaluate the subject at an unscheduled visit, if subject’s condition 
will be considered as worsening.  If the Investigator assesses the subject’s condition at any time 
and determines that the subject’s condition has worsened to the degree that it is unsafe for the 
subject to continue in the study, the subject may be discontinued from the study as treatment 
failure. Visit 5 Early Termination procedures will be performed, and a standard of care treatment 
may be advised at the Investigator’s discretion. 
 


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1.2.   Time and Events Schedule 
TABLE 1.2 Study Procedures and Assessments. 
Visit Number 
Visit 1 
Screening 
Visit 2 
Baseline1 
Visit 3 
Interim 
Visit 4 
Interim 
Visit 5 
EOS/ET2 
Visit Day 
Day 
-5 to 1 
Day 1 
Day 7 
(±1) 
Day 14 
(±2) 
Day 28 
(±4) 
Informed Consent 
X 
 
 
 
 
Eligibility Criteria 
X 
 
 
 
 
Subject Demographics 
X 
 
 
 
 
Medical History 
X 
 
 
 
 
Physical Exam 
 X3 
 
 
 
 
Randomization 
 
X4 
 
 
 
Vital Signs 
X
 
X 
 
 
X 
Urine Pregnancy Test5 
X 
 
 
 
X 
Visual Examination of Lesions 
X 
X 
X 
X 
X 
Microscopic Examination of Skin Scraping6 
X 
 
 
 
 
Patient Self-Assessment 
 
X 
X 
X 
X 
Investigational Product Dispensation 
 
X 
 
X7 
 
Treatment with Investigational Product 
 
X 
 
X7 
 
Investigational Product Accountability 
 
 
X 
 
X8 
Subject Diary Compliance Review 
 
 
X 
 
X8 
Concomitant and Prohibited Medication Review 
X 
X 
X 
X 
X 
Adverse Events Assessment 
 
X8 
X 
X 
X 
1. 
Visit 2 (Baseline) may be completed on the same day as visit 1 (Screening). If Screening and Baseline are 
completed on the same day, assessments performed on both screening and baseline need only be performed once. 
2. 
End of Study/Early Termination 
3. 
Physical examinations are to be performed if Inclusion/Exclusion Criteria are satisfied at Screening 
4. 
Prior to Randomization, the Investigator must confirm the subject still meets all Inclusion/Exclusion Criteria. 
5. 
For females of child-bearing potential 
6. 
Any new lesions identified at Visits 3, 4, or 5 will be confirmed by microscopic evaluation of skin scraping 
7. 
Applicable for subjects requiring second application of the investigational product 
8. 
AE reporting period for this study begins from the time of application of the investigational product and ends at the final 
protocol required visit 
 


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1.3.   Glossary of Terms 
AE 
Adverse Event 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CTMF 
Clinical Trial Master File 
CTP 
Clinical Trial Protocol 
eCRF 
Electronic Case Report Form 
GCP 
Good Clinical Practice 
IB 
Investigator’s Brochure 
ICH 
International Conference On Harmonization 
IEC 
Independent Ethics Committee 
IGE 
Investigator’s Global Evaluation 
IP 
Investigation Product 
IRB 
Institutional Review Board 
ISF 
Investigator Site File 
LOCF 
Last Observation Carried Forward 
mITT 
Modified Intent-To-Treat 
PP 
Per-Protocol 
PD 
Protocol Deviation 
PDRR 
Protocol Deviation Review Request 
SAE 
Serious Adverse Event 
SOP 
Standard Operating Procedures 
SUSAR 
Suspected Unexpected Serious Adverse Reactions 
 


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2.  OBJECTIVES 
The primary objective of this study is: 
• To demonstrate bioequivalence between Permethrin Cream, 5% (Mayne Pharma, Inc.) and 
ElimiteTM in patients with active scabies. 
The secondary objective of this study is: 
• To demonstrate comparative safety of Permethrin Cream, 5% (Mayne Pharma, Inc.) vs 
ElimiteTM and tolerability of 5% Permethrin cream. 
3.   GENERAL STATISTICAL CONSIDERATIONS 
3.1.   Sample Size Estimation 
Under the assumption that the Reference product has a cure rate of at least 88%, sample size 
evaluations were conducted, via computer simulation, to determine the probability (power) of the 
calculated 90% continuity-corrected confidence interval on the Test-to-Reference difference in 
cure proportions to be contained in the bioequivalence interval [-0.20, +0.20]. When the Test 
product was assumed to have the same 88% cure rate, the required number of PP subjects in each 
treatment group was determined to be 56 (112 total) for a power ≥0.80. Assuming 20% of drop-
out rate, 70 subjects in each treatment group (140 total) would be needed.  
If it is assumed that the Test product cure rate might deviate from that of the Reference by as much 
as 2% (e.g. 86% instead of 88%) and if a higher power, ≥0.95, was desired, then 91 PP subjects in 
each treatment group (182 total) would be needed. Assuming 20% drop-out rate, 114 subjects in 
each treatment group (228 total) would need to be enrolled. 
3.2.   Randomization 
The actual treatment given to individual subjects is determined by a computerized block 
randomization scheme prepared by an independent third party.  The independent third party will 
prepare the randomization list and hold it throughout the conduct of the study.  The content of the 
randomization list will not be available to either clinical sites or sponsor up until the database is 
locked.  Subjects are randomized on a 1:1 basis (test drug: active comparator) in blocks of two and 
stratified by clinical site. The subject randomization number corresponds to either one of the active 
drugs treatment allocation. 
Clinical sites will contact the independent third party responsible for the randomization scheme at 
the time subject has met all inclusion criteria and is ready for enrollment.  Blocks of two (2) tubes 
will be supplied to the sites. Site’s dispensing pharmacist will randomly select a tube with an 


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investigational product from the block for the study subject. Next enrolled subject will receive the 
remaining investigational product from the same block until the block is entirely used. Subject 
eligibility is established before treatment randomization at Visit 2 (Screening and Visit 2 
Randomization can be combined into one visit). Subjects are randomized strictly sequentially, as 
subjects are eligible at the clinical sites. 
After signing the Informed Consent, each subject will be assigned a unique subject number.  Subjects 
are identified using subject initials, subject number, and date of birth. The subject numbers will be 
generated by the EDC and assigned sequentially in the order in which subjects are consented at 
each center.  
If a subject discontinues from the study, the subject number and randomization number are not to 
be reused, and the subject is not allowed to re-enter the study. 
Based on the clinical judgement and requirements described in the protocol, the Investigator may 
provide a retreatment to the study subject. Only one retreatment is allowed per subject. The 
retreatment assignment must belong to the same treatment arm. In order to dispense the correct 
treatment, the following process is to be followed:  
1. Study pharmacist will contact the Drug Depot, specifying subject’s identifying information.  
2. Drug Depot will specify which kit number shall be dispensed for retreatment.  
The randomization scheme for treatment allocation will be used for statistical and reporting 
purposes. A sealed copy of the randomization assignment will be retained at each clinical site and 
will be available to FDA or other regulatory agency investigators at the time of site inspection to 
allow for verification of the treatment identity of each subject. 
3.3.   Blinding and Procedures for Unblinding the Study 
This is a double-blind study in which the study subjects, the Investigator, the Study Coordinator, 
clinical staff, Sponsor (with the exception of the independent third party who generated the 
randomization code), and any personnel involved in the monitoring, evaluation, and analysis of 
study data will not be aware of treatment assignment for any subject until after the database for 
the study has been finalized. Members of the Data Monitoring Committee may, on occasion, use 
the treatment assignment codes provided by the unblinded statistician at the independent third 
party to determine the treatment assignment of a subject reviewed by the committee.  
The packaging of the test and the reference products will be similar in appearance to make 
difference in treatment less obvious to the subjects. To maintain adequate blinding of Investigators 
and subject evaluators, it is recommended that the investigational product dispensation and 
accountability be performed by the study pharmacist, or designated study personnel who will not 


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be involved in any other activities of this study. Neither the Investigator nor the patient should be 
able to identify the received treatment. The dispensed investigational product will NOT be opened 
by the subject at the study center except in front of the study pharmacist, or designated study 
personnel. The randomization scheme will not be available to the physician, the study pharmacist 
or designated study personnel for investigational product dispensation and accountability and 
nursing staff or study coordinators involved in the collection, monitoring, revision, or evaluation 
of adverse events or to clinical staff who could have an impact on the outcome of the study. 
 
A sealed copy of the randomization code will be supplied with each block of the investigational 
product and will be retained at each clinical site. Randomization codes must be available to the 
FDA or other regulatory agency investigators at the time of site inspection to allow for verification 
of the treatment identity of each subject. 
From Day 1 through the end of the study, the randomization code must not be broken except in 
emergency situations for which the identification of the study treatment of a subject is required by 
the Qualified Investigator for subject safety and medical care.  In the event of a medical emergency 
requiring identification of the study drug administered to an individual subject, Investigator will 
make every attempt to contact the Biorasi Project Manager by telephone, explaining the need for 
unblinding, before or no later than 24 hours of breaking the blinding.  The Investigator must 
document the time, date, and reason for the unblinding and the names of the personnel involved 
on the CRF, in the site file, and in the medical notes. The Investigator must notify the Sponsor in 
writing as soon as possible following the unblinding event explaining the necessity of unblinding 
of the investigational product(s).  Every effort should be made to avoid unblinding extra study 
personnel. 
3.4.   Handling of Data 
3.4.1.   Examination of Subject Subsets 
The primary and secondary efficacy endpoints will be summarized separately using descriptive 
statistics by treatment group and study day, where appropriate. No formal statistical testing will 
be utilized.  
3.4.2.   Missing Data  
Every effort will be made to obtain required data at each scheduled evaluation from all subjects 
who have been randomized. In situations where it is not possible to obtain all safety data, 
imputation of missing data will not be conducted.  A Last-Observation-Carried-Forward 
imputation method for missing efficacy data will be used for the mITT population.  


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3.4.3.   Definitions and Terminology 
Treatment Day 1 (Baseline) 
Treatment Day 1 is the day that study treatment is first initiated. 
Study Day  
Study Day is defined relative to study treatment initiation (Study Day 1). Thus, the study day of 
an event is calculated as: 
Study Day = event date – date of Study Day 1 +1. 
Days on Study 
Days on Study is the number of days from Study Day 1 to the date of study completion or early 
termination as recorded on the study termination eCRF. 
End of Treatment 
For efficacy assessments, end of treatment is defined as the last non-missing assessment taken 
prior to discontinuation of study treatment. 
Concomitant Medications 
Concomitant medications are those medications taken on or after the initiation of study treatment.  
This definition includes prescription and all over-the-counter (OTC) medications and all dietary 
supplements. 
Previous Medications 
Previous medications are those medications taken within the 30 days and stopped prior to the 
initiation of study therapy. 
Treatment-Emergent Adverse Event  
A treatment-emergent adverse event is defined as any adverse event occurring on or after the 
initiation of study treatment.  For the purpose of defining treatment-emergent adverse events, it is 
assumed that an adverse event which was reported to have started on Treatment Day 1 without an 
associated onset time may have occurred after the initiation of study treatment.  Hence, adverse 
events occurring on Treatment Day 1 are assumed to be treatment-emergent. 


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3.5.  Planned Analyses 
A final analysis is planned after the last subject completes or discontinues the study, and the 
resulting clinical database has been cleaned, quality checked, and locked. 
4.   ANALYSIS POPULATIONS 
The populations defined for analysis will include the modified intent-to-treat (mITT), per-protocol 
(PP), and the safety population.  
Safety population: The safety population is any randomized individual who: (a) was enrolled into 
the study, and (b) received at least one application of study treatment.  Subjects will be analyzed 
according to the treatment received.  This population will be used for safety assessment. 
Modified Intent-to-Treat (mITT): A modified intent-to-treat subject is any randomized individual 
who: (a) was enrolled into the study, (b) met inclusion/exclusion criteria, (c) received at least one 
application of study treatment, and (d) had at least one post-baseline visit. Subjects will be 
analyzed according to the randomized treatment.  This population will be used for secondary and 
primary efficacy analysis as supportive analysis. 
Per Protocol (PP): A per-protocol subject is any randomized individual who: (a) enrolled into the 
study and met inclusion/exclusion criteria, (b)received the assigned study treatment, (c) had not 
taken any concomitant medications prohibited by the protocol or experienced any major 
deviations that interfered with or may have interfered with the therapeutic administration of the 
treatment or the precise evaluation of treatment efficacy, and (d) completed the primary endpoint 
evaluation within the designated visit window (±4 days).  
Subjects whose condition worsens and require alternate or supplemental therapy for the treatment of 
scabies during the study will be discontinued, included in both the mITT and PP population analyses as 
treatment failures. Subjects who discontinue early for reasons other than treatment failure will be 
excluded from the PP population, but included in the mITT population, using Last Observation Carried 
Forward (LOCF). 
5.   STATISTICAL METHODS 
Descriptive statistical methods will be used to summarize the data from this study, with confidence 
intervals calculated for the primary and secondary efficacy endpoints.  The term “descriptive 
statistics” refers to number of subjects (n), mean, median, standard deviation (SD), minimum, and 
maximum for continuous data and frequencies and percentages for categorical data.  The term 
“treatment group” refers to randomized treatment assignment: Test and Reference.  All data 
collected during the study will be included in data listings.  The data will be sorted first by subject 


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number, and then by date within each subject number. Unless specified otherwise, all statistical 
testing will be two-sided and will be performed using a significance (alpha) level of 0.05. 
All statistical analyses will be conducted with the SAS® System, version 9.4 or higher within a 
validated statistical computing environment.  
5.1.  Subject Disposition, Demographic and Baseline Characteristics 
Subject disposition, including the number of subjects who completed the study, discontinued from 
the study, reasons for early discontinuation, and the number of days on study will also be provided 
and presented for all subjects randomized. Subject disposition will be summarized by treatment 
group.  Additionally, study therapy compliance will be summarized by treatment group. 
 
Demographic data and baseline characteristics including age, ethnicity, race, gender, and severity 
of itching and burning sensations will be summarized using appropriate descriptive statistics by 
treatment group for the mITT and PP populations. Descriptive statistics will be generated for 
continuous variables (e.g. age).  The number and percentage of subjects in each class of categorical 
demographic and Baseline variables (e.g. gender, ethnicity, race, and severity of itching and 
burning sensation) will be tabulated by treatment group and population (mITT and PP) for Baseline 
(Visit 2 or Visit 1 if applicable).  Individual subject demographic and Baseline characteristics data 
will be listed. No inferential testing will be performed.   
5.2.  Efficacy Analyses 
5.2.1.  Primary Efficacy Endpoint 
The primary endpoint will be the proportion of patients that are identified as cured at the end of 
the treatment period on Study Day 28 (Visit 5). Cure is defined as the absence of new lesions and 
the healing of all old lesions. Residual, dry, non-inflammatory papules are not counted as active. 
Descriptive statistics (number of subjects, number of subjects cured, and proportion of cured) for 
the primary efficacy variable will be tabulated by treatment group and population (mITT and PP).  
The results for the PP population will be considered definitive with those in the mITT population 
as supportive. 
5.2.2.  Primary Efficacy Analyses 
Bioequivalence assessment will be evaluated by comparing proportions of patients successfully 
cured in the test and the reference treatment groups. Bioequivalence between the test and the 
reference product will be established if the continuity-corrected 90% confidence interval for the 
difference in cure proportions between test and reference treatment is contained between the 
equivalence limits [-0.20, +0.20].  The hypothesis testing for the two, 1-sided tests will be 
conducted using a 5% level of significance. 


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In this case, the compound two, 1-sided tests hypothesis is: 
H0: pT – pR < -0.20 or pT – pR > 0.20  (meaning test product is not bioequivalent to the 
reference); 
HA: -0.20 ≤ pT –pR ≤ 0.20 (supporting bioequivalence); 
where pT = cure rate of test treatment,  pR = cure rate of reference treatment.  
Let nT = sample size of test treatment group, nR = sample size of reference treatment group and 
se = (𝑝𝑝𝑇𝑇 
ෞ(1 −𝑝𝑝𝑇𝑇 
ෞ) 𝑛𝑛𝑇𝑇+ 
⁄
𝑝𝑝𝑅𝑅 
ෞ(1 −𝑝𝑝𝑅𝑅 
ෞ) 𝑛𝑛𝑅𝑅) 
⁄
1
2. 
The 90% confidence interval will be estimated as follows, using Yates correction: 
L = (𝑝𝑝̂𝑇𝑇−𝑝𝑝̂𝑅𝑅) −1.645 ×  𝑠𝑠𝑠𝑠−(
1
𝑛𝑛𝑇𝑇+ 
1
𝑛𝑛𝑅𝑅) 2
⁄  
U = (𝑝𝑝̂𝑇𝑇−𝑝𝑝̂𝑅𝑅) + 1.645 ×  𝑠𝑠𝑠𝑠+ (
1
𝑛𝑛𝑇𝑇+ 
1
𝑛𝑛𝑅𝑅) 2
⁄  
H0 is rejected if L ≥ -0.20 and U ≤ 0.20 resulting in accepting HA and concluding bioequivalence 
of the two products. 
The primary endpoint is the evaluation at Day 28. The results in the PP population will be 
considered definitive, with those in the mITT population as supportive.   
The following SAS code will be used for testing bioequivalence: 
proc freq data = dataset; 
weight count; 
tables treat*outcome/ riskdiffc (equiv); 
run; 
 
5.2.3.   Secondary Efficacy Endpoints 
The secondary endpoint will be the proportion of patients that are identified as cured at the end of 
the treatment period on Study Day 14 (Visit 4). Descriptive statistics (number of subjects, number 
of subjects cured, and proportion of cured) for the secondary efficacy variable will be tabulated by 
treatment group and population (mITT and PP).  The results for the PP population will be 
considered definitive with those in the mITT population as supportive. 
 
5.2.4.   Secondary Efficacy Analyses 
As a secondary endpoint evaluation, patients’ clinical progress at Visit 4 (Day 14) will be assessed 
and proportion of cured patients in treatment arms will be compared using the procedure described 


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in the analysis of the primary efficacy endpoint. 
 
5.3.  Tolerability Assessment 
Subjects’ self-assessment of itching and stinging/ burning sensations during screening and 
treatment periods (Visits 2 through 5) will used to assess tolerability to the study treatments.  
Itching is defined as intense, distracting irritation or tickling sensation in the last 24 hours and is 
evaluated on a scale from 0 (No Itching) to 4 (Unbearable, Intense Itch).  Stinging/ burning is 
defined as sensation of the skin is painfully hot or noticeable tingling sensation in the last 24 hours 
and is evaluated on a scale from 0 (Absent) to 3 (Marked, Intense).   
Descriptive statistics using categorical methods will be used to compare tolerability measures 
between the test and reference treatment groups and various study days (e.g. Baseline (Visit 2), 
Visit 3, Visit 4, and Visit 5).  Tolerability analyses will be presented for mITT and PP populations.   
5.4.   Safety Assessment 
Safety analyses will be presented for the Safety Population, defined as all subjects who receive at 
least one dose of study medication.  Adverse events and vital signs measurements will be used as 
safety endpoints and summarized by treatment group.  The previous and concomitant medications 
will also be summarized.   
5.4.1.  Adverse Events 
Analysis of adverse events as safety variables will be based on all adverse event (AE) capture 
measuring severity and frequency utilizing MedDRA terminology for consistency. AEs will be 
mapped to a MedDRA-preferred term and system organ classification.  If a subject experiences 
multiple events that map to a single preferred term, the greatest severity and strongest Investigator 
assessment of relation to study drug will be assigned to the preferred term for the appropriate 
summaries. Should an event have a missing severity or relationship, it will be classified as having 
the highest severity and/or strongest relationship to study drug.  
Summaries of treatment-emergent AEs will include any AEs reported beginning with the first dose 
of study drug on Day 1. The occurrence of treatment-emergent adverse events will be summarized 
by treatment group using preferred terms, system organ classifications, and severity.  Separate 
summaries of treatment-emergent serious adverse events (SAEs), treatment-emergent adverse 
events related to study drug, and events leading to the discontinuation of study drug will be 
generated.   
All AEs will be listed for individual subjects showing both verbatim and preferred terms.   


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5.4.2.  Vital Signs 
Vital signs will be collected at the Screening visit; on the Baseline, and at visit 5 (or upon subject 
discontinuation). Vital signs will include body temperature (oral), heart rate and blood pressure 
(systolic and diastolic). Any abnormal characteristics will be evaluated by the Investigator based 
on their clinical significance. Abnormal vital signs will be considered AEs if they require 
therapeutic medical intervention, and/or if the Investigator considers them to be AEs due to the 
clinical judgement. 
5.4.3.  Previous and Concomitant Medications 
Concurrent medications and any medications taken in the 30 days prior to the start of the study 
will be recorded as prior/concomitant medications (using their generic and brand name, if known) 
with the corresponding indication.  Concomitant medications will be coded using the WHO 
dictionary.  These data will be summarized by treatment group.  Previous and concomitant 
medications will be presented in a data listing. 
6.   CHANGES IN THE PLANNED ANALYSES 
No deviations in the conduct of the study or the planned analysis are anticipated.  Should any 
deviations from the analyses specified in the authorized statistical analysis plan arise, such 
deviations will be documented in the final clinical study report. 
7.  PROGRAMMING CONVENTIONS 
Statistical programs will be developed using SAS® version 9.4 or higher.  Programs will be 
documented, produced, and validated.  Additionally, the following conventions should be 
incorporated: 
• Page orientation, margins, and fonts: Summary tables, listings, and figures will appear in 
landscape orientation.  There should be a minimum of a 1.25” boundary on the upper (bound) 
edge, and a minimum of a 1.0” boundary on the remaining three edges.  Output should be 
printed in Courier New with a point size of at least 8.  Titles may be printed using a larger font 
(e.g., Arial point size 10). 
• Identification of analysis population: Every summary table and figure should clearly specify 
the analysis population being summarized.  Listings will be prepared for all subjects. 
• Group headers: In the summary tables, the group headers will identify the treatment group and 
the within-group sample size for the indicated analysis population.  Of note, the header’s 
sample size does not necessarily equal the number of subjects summarized within any given 
summary module; some subjects in the analysis population may have missing values and, thus, 
may not be summarized. 


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• Suppression of percentages corresponding to null categories: When count data are presented 
as category frequencies and corresponding percentages, the percent should be suppressed when 
the count is zero in order to draw attention to the non-zero counts. 
• Presentation of sample sizes: Summary modules should indicate, in one way or another, the 
number of subjects contributing to the summary statistics presented in any given summary 
module.  As mentioned above, this may be less than the number of subjects in the analysis 
population. 
♦ In the quantitative modules describing continuous variables (and thus presenting sample 
size, means, and standard deviations), the sample size should be the number of non-missing 
observations. 
♦ For categorical variables that are presented in frequency tables, the module should present 
the total count in addition to the count in each category.  Percentages should be calculated 
using this total as the denominator, and the percentage corresponding to the sum itself (that 
is, 100%) should be presented to indicate clearly to a reviewer the method of calculation. 
Missing data will not contribute to the calculation of percentages. 
• Sorting: Listings will be sorted by treatment group, subject identification number and date, if 
applicable.  If a listing is sorted in a different manner, a footnote will indicate as such.  
• General formatting rules: Rounding for all variables will occur only as the last step, 
immediately prior to presentation in listings, tables, and figures.  No intermediate rounding 
will be performed on derived variables.  The standard rounding practice of rounding numbers 
ending in 0-4 down and numbers ending in 5-9 up will be employed.   
• The presentation of numerical values will adhere to the following guidelines:  
♦ Raw measurements will be reported to the number of significant digits as captured 
electronically on the eCRFs.   
♦ Standard deviations will be reported to one decimal place beyond the number of decimal 
places the original parameter is presented. 
♦ Means will be reported to the same number of significant digits as the parameter, unless 
the parameter is an integer, then 1 decimal place will be reported.  
♦ Calculated percentages will be reported with no decimals. 
• Dates will be formatted as DDMMMYYYY.  Partial dates will be presented on data listings 
as recorded on CRFs. 
• Time will be presented according to the 24-hour clock (HHMM). 
 


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8.   TABLES, LISTINGS AND FIGURES 
Tables 
 
1.  Summary of Subject Enrollment and Disposition. 
2.  Summary of Subject Demographics at Screening (mITT population). 
3. Summary of Subject Demographics at Screening (PP Population). 
4. Summary of Medical History/Other Concomitant Illness at Screening. 
5. Summary of Physical Exam Abnormalities. 
6. The proportion of patients that are identified as cured on Study Day 28 (Visit 5) (mITT 
population). 
7. The proportion of patients that are identified as cured on Study Day 28 (Visit 5) visit (PP 
population). 
8. Summary of Visual examination at each visit (mITT population). 
9. Summary of Visual examination at each visit (PP Population). 
10. The proportion of patients that are identified as cured on Study Day 14 (mITT population). 
11. The proportion of patients that are identified as cured on Study Day 14 (PP population). 
12. Summary of self-assessment of itching and stinging/ burning sensations at each visit (mITT 
population). 
13. Summary of self-assessment of itching and stinging/ burning sensations at each visit (PP 
population). 
14. Summary of change of self-assessment of itching and stinging/ burning sensations from 
baseline at each visit (mITT population). 
15. Summary of change of self-assessment of itching and stinging/ burning sensations from 
baseline at each visit (PP population). 
16. Adverse Events by System Organ Class and Preferred Term. 
17. Adverse Events with incidence >5 % by System Organ Class and Preferred Term. 
18. Treatment Emergent Adverse Events by System Organ Class and Preferred Term. 
19. Treatment Emergent Adverse Events by maximum Severity. 
20. Summary of Treatment Emergent Adverse Events possible or probably related to the study 
drug. 
21. Summary of Serious Adverse Events by System Organ Class and Preferred Term. 
22. Summary of Concomitant Medications. 


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Data Listings 
 
1. Listing of Analysis Population and Study Completion. 
2. Listing of Subjects Who Discontinued. 
3. Listing of Patients Excluded from Per Protocol Efficacy Analysis. 
4. Listing of Protocol Deviation. 
5. Listing of Subject Demographics. 
6. Listing of Drug Accountability. 
7. Listing of Visual Examination. 
8. Listing of Subject Diary data. 
9. Listing of Patient Self-assessment. 
10. Listing of Adverse Events. 
11. Listing of Treatment Emergent Adverse Events. 
12. Listing of Non-Treatment Emergent Adverse Events. 
13. Listing of Adverse drug reaction. 
14. Listing of Treatment Emergent Adverse Events which lead to discontinuation of study 
treatment. 
15. Listing of Non-Treatment Emergent Adverse Events which lead to discontinuation of 
study treatment. 
16. Listing of Treatment Emergent Adverse Events which lead to Withdrawal from the study. 
17. Listing of Non-Treatment Emergent Adverse Events which lead to Withdrawal from the 
study. 
18. Listing of Concomitant Medication. 
19. Listing of Serious Adverse Events. 
20. Listing of Serious Adverse Events with fatal outcome. 
21. Listing of Medical History. 
22. Listing of Physical Examination. 
23. Listing of Pregnancy test. 
24. Listing of Microscopic Examination for Skin Scraping 
25. Listing of Subject Vital Signs for Randomized Population. 
26. Listing of Inclusion/Exclusion Criteria (Randomized Population). 
 
 
 
 


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Figures 
 
1. The proportion of patients that are identified as cured at the Study Day 14 and 28. (mITT 
population). 
2. The proportion of patients that are identified as cured at the Study Day  14 and 28. (PP 
population). 
3. The summary of self-assessment of itching and stinging. (mITT population). 
4. The summary of self-assessment of itching and stinging.  (PP population). 
5. The summary of self-assessment of burning sensations at each visit. (mITT population). 
6. The summary of self-assessment of burning sensations at each visit. (PP population). 
 
 
 


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APPENDIX A:  ITCHING SENSATION SCALE 
 
Itching – Intense, distracting irritation or tickling sensation in the last 24 hours 
Score Grade 
Definition 
0 
None 
No Itching. 
1 
Mild 
Barely perceptible, slightly present itch 
2 
Moderate 
Distinct presence of itch 
3 
Severe 
Marked, intense, yet tolerable itch 
4 
Very Severe 
Unbearable, intense itch 
 
 
APPENDIX B: STINGING/ BURNING SENSATION SCALE 
 
Stinging/Burning – Sensation of the skin is painfully hot or noticeable tingling sensation in the 
last 24 hours 
Score 
Grade 
Definition 
0 
None 
Absent 
1 
Mild 
Slight, barely present 
2 
Moderate 
Distinct presence 
3 
Severe 
Marked, intense