Clinical trial NCT03178942
Conditions: Scabies
Sponsor: Encube Ethicals Pvt. Ltd.
Start date: 2017-06-01; Completion date: 2017-11-11
Enrollment: 254 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Study to Evaluate the Therapeutic Equivalence of Permethrin Cream 5%in the Treatment of Scabies.

Detailed description:
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic Equivalence of Permethrin Cream 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) in the Treatment of Scabies.

The objectives of this study are to:

1. Evaluate the therapeutic equivalence of the Test formulation, Permethrin Cream, 5% (Encube Ethicals) to the marketed product, Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) in patients with scabies.
2. Compare the safety of Test and Reference treatments in patients with scabies.

Arms: arm 1: Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) arm 2: Test: Permethrin Cream, 5% (Encube Ethicals)
Interventions: intervention 1: Permethrin Cream, 5% intervention 2: Elimite™ Cream (permethrin) 5%
Intervention descriptions: intervention 1: Permethrin Cream 5% intervention 2: Permethrin Cream 5%

Protocol documents:
Prot_000.pdf: 
COVER PAGE 
PROTOCOL 
November 3, 2017 
Rev. 1.0              
NCT03178942 
 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream 
(permethrin) 5% (Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Protocol Number: 71675502 
Novum Study Number: 71675502 
 
 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 1 of 42 
 
 
1.0 TITLE PAGE 
 
 
 
 
 
 
 
 
 
 
 
 
This document is a confidential communication of Novum Pharmaceutical Research Services. Receipt of 
this document constitutes an agreement by the recipient that no unpublished information contained herein 
will be disclosed without Novum Pharmaceutical Research Services’ written approval.
Study Title 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site 
Study to Evaluate the Therapeutic Equivalence of Permethrin 
Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream 
(permethrin) 5% (Prestium Pharma, Inc.) in the Treatment of 
Scabies 
Drug Product 
Permethrin Cream, 5%  
Population 
Approximately 250 patients, 2 years of age and older with 
clinically documented evidence of infestation with Sarcoptes 
scabiei (scabies) 
Study Design 
Randomized, double-blind, parallel-design,multiple-site 
bioequivalence study with clinical endpoints 
Sponsor 
Encube Ethicals 
Protocol/Study Number 
71675502 
Protocol Date 
11/03/2017 
NIIRB 
November 14, 2017 
APPROVED 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 2 of 42 
 
 
2.0 KEY STUDY PERSONNEL AND FACILITIES 
Sponsor: 
Encube Ethicals 
Unit No. 24, Steelmade Indl Estate, 
Opposite To Jalaram Store, 
Marol, Andheri East, Mumbai, 
Maharashtra 400059, India 
CRO: 
Novum Pharmaceutical Research Services (Novum) 
225 W. Station Square Drive, Suite 200 
Pittsburgh, PA 15219 
Sponsor’s Representative: 
Pratik Kamani 
GM- Strategy & Commercial  
Encube Ethicals Pvt Ltd 
Phone:+91-22-6228-8000, Ext 8003 
Fax: +91-22-6693-5230 
Email: pratik.k@encubeethicals.com 
CRO Representative: 
Gail Gongas 
Vice President, Clinical Trials and Data Management 
Novum Pharmaceutical Research Services 
Phone: 412-363-3300 x 522 
Fax: 412-291-3171 
Email: gdgongas@novumprs.com 
Novum Medical Monitor: 
Paolo Maria Fanzio, MD 
Medical Director, Novum Pharmaceutical Research Services 
Phone: 412-363-3300 x 597 
Fax: 412-924-0522 
Email: pmfanzio@novumprs.com 
Novum Biostatistician: 
Jianhua Liu, MSc 
Senior Biostatistician 
Novum Pharmaceutical Research Services 
Phone: 613-483-6836 
Fax: 412-924-0522 
Email: jliu@novumprs.com 
 
 




CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 4 of 42 
 
 
PRINCIPAL INVESTIGATOR’S SIGNATURE 
 
 
I _______________________________________, agree to conduct protocol 71675502 Rev 1 in 
accordance with FDA regulations, ICH guidelines and GCP. I understand that no deviations from the 
protocol may be made without the prior permission of the Sponsor (Encube Ethicals) or Novum 
Pharmaceutical Research Services, the company managing the study. 
 
 
 
 
 
 
___________________________________  
 
 __________ 
Principal Investigator 
 
 
 
 
 
 
 
 
 
Date 
 
 
 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 5 of 42 
 
 
4.0 TABLE OF CONTENTS 
1.0 TITLE PAGE .......................................................................................................................................... 1 
2.0 KEY STUDY PERSONNEL AND FACILITIES .................................................................................. 2 
3.0 SIGNATURE PAGE .............................................................................................................................. 3 
4.0 TABLE OF CONTENTS ........................................................................................................................ 5 
5.0 SYNOPSIS .............................................................................................................................................. 8 
6.0 STUDY SCHEMATIC ......................................................................................................................... 13 
7.0 LIST OF ABBREVIATIONS AND TERMS ....................................................................................... 14 
8.0 INTRODUCTION ................................................................................................................................ 15 
8.1 Disease Being Treated ...................................................................................................................... 15 
8.2 Availability and Efficacy of Already Approved Therapies .............................................................. 15 
8.3 Scientific and Statistical Considerations ........................................................................................... 15 
9.0 STUDY OBJECTIVES ......................................................................................................................... 17 
10.0 INVESTIGATIONAL PLAN ............................................................................................................. 17 
10.1 Study Design and Plan Description ................................................................................................ 17 
10.2 Selection of Study Design ............................................................................................................... 18 
10.3 Selection of Study Population ......................................................................................................... 19 
10.3.1 Inclusion Criteria...................................................................................................................... 19 
10.3.2 Exclusion Criteria .................................................................................................................... 19 
10.3.3 Restrictions During the Study .................................................................................................. 20 
10.3.4 Removal of Patients from the Study ........................................................................................ 20 
10.3.5 Early Terminations ................................................................................................................... 21 
10.4 Treatments....................................................................................................................................... 21 
10.4.1 Treatment Administration ........................................................................................................ 21 
10.4.2 Identity of Investigational Product ........................................................................................... 22 
10.4.3 Study Product Shipment, Storage, and Retention .................................................................... 22 
10.4.4 Method of Assigning Patients to Treatment Groups ................................................................ 23 
10.4.5 Study Blind .............................................................................................................................. 23 
10.4.6 Compliance .............................................................................................................................. 24 
10.5 Study Conduct ................................................................................................................................. 24 
10.5.1 Visit 1 (Day 1): Screening/Baseline ......................................................................................... 24 
10.5.2 Visit 2 (Day 14 ± 4): Interim Visit ........................................................................................... 25 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 6 of 42 
 
 
10.5.3 Visit 3 (Day 28 ± 4): End of Study or Early Termination........................................................ 25 
10.6 Study Procedures ............................................................................................................................ 26 
10.6.1 Informed Consent ..................................................................................................................... 26 
10.6.2 Medical History and Demographics ........................................................................................ 26 
10.6.3 Vital Signs ................................................................................................................................ 26 
10.6.4 Adverse Events ........................................................................................................................ 26 
10.6.5 Concomitant Medication .......................................................................................................... 26 
10.6.6 Microscopic Examination ........................................................................................................ 27 
10.6.7 Scabies Signs and Symptoms Rating ....................................................................................... 27 
10.6.8 Pregnancy Test ......................................................................................................................... 27 
10.6.9 Review Inclusion/Exclusion Criteria ....................................................................................... 27 
10.6.10 Collect and Review Patient Diary .......................................................................................... 27 
10.6.11 Provide Patient Diary ............................................................................................................. 27 
10.6.12 Dispense Study Product ......................................................................................................... 27 
10.6.13 Collect and Weigh Study Product .......................................................................................... 28 
10.7 Adverse Events ............................................................................................................................... 28 
10.7.1 Adverse Event Definitions ....................................................................................................... 28 
10.7.2 Severity of Adverse Event ....................................................................................................... 28 
10.7.3 Relationship of Adverse Event ................................................................................................ 28 
10.8 Serious Adverse Events .................................................................................................................. 29 
10.8.1 Definition of a Serious Adverse Event..................................................................................... 29 
10.8.2 Reporting Serious Adverse Events .......................................................................................... 29 
11.0 STATISTICAL METHODS ............................................................................................................... 30 
11.1 Statistical Plan ................................................................................................................................. 30 
11.2 Determination of Sample Size ........................................................................................................ 30 
11.3 Study Populations ........................................................................................................................... 31 
11.3.1 Per-Protocol Population ........................................................................................................... 31 
11.3.2 Safety Population ..................................................................................................................... 31 
11.4 Baseline Comparability ................................................................................................................... 31 
11.5 Efficacy Endpoint ........................................................................................................................... 32 
11.6 Efficacy Analyses ........................................................................................................................... 32 
11.7 Treatment-by-Site Interaction and Pooling of Clinical Sites .......................................................... 33 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 7 of 42 
 
 
11.8 Safety Analysis ............................................................................................................................... 33 
12.0 REGULATORY OBLIGATIONS ...................................................................................................... 33 
12.1 Institutional Review Board ............................................................................................................. 33 
12.2 Study Documentation ...................................................................................................................... 33 
12.2.1 Protocol .................................................................................................................................... 34 
12.2.2 Informed Consent ..................................................................................................................... 34 
12.2.3 Protocol and Informed Consent Changes ................................................................................. 34 
12.2.4 Source Documents and Electronic Case Report Forms (eCRF) .............................................. 34 
12.2.5 Drug Accountability ................................................................................................................. 35 
12.2.6 Drug Storage ............................................................................................................................ 35 
12.2.7 Retention of Reserve Samples ................................................................................................. 35 
12.2.8 Pregnancies .............................................................................................................................. 35 
12.2.9 Reporting Safety Information to the IRB ................................................................................. 36 
12.2.10 Record Retention.................................................................................................................... 36 
12.2.11 Study Monitoring and Auditing ............................................................................................. 36 
12.2.12 End of the Trial ...................................................................................................................... 36 
12.2.13 Clinical Study Report ............................................................................................................. 36 
13.0 REFERENCES ................................................................................................................................... 38 
14.0 APPENDICES .................................................................................................................................... 39 
14.1 APPENDIX A: RATING OF SCABIES SIGNS AND SYMPTOMS ........................................... 39 
14.2 APPENDIX B: DERMOSCOPY AND MICROSCOPY FOR SCABIES DIAGNOSIS ............... 40 
14.3 APPENDIX C: PRODUCT INSERT FOR ELIMITE™ .................................................................... 41 
14.4 APPENDIX D: AMENDMENTS TO THE PROTOCOL.............................................................. 42 
 
 
 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 8 of 42 
 
 
5.0 SYNOPSIS 
Protocol Number 
71675502 
Title 
A Randomized, Double-Blind,  Parallel-Design, Multiple-Site Study to 
Evaluate the Therapeutic Equivalence of Permethrin Cream 5% (Encube 
Ethicals) Compared to Elimite™ Cream (permethrin) 5% (Prestium Pharma, 
Inc.) in the Treatment of Scabies 
Objectives 
The objectives of this study are to: 
1. Evaluate the therapeutic equivalence of the Test formulation, Permethrin 
Cream, 5% (Encube Ethicals) to the marketed product, Elimite™ Cream 
(permethrin) 5% (Prestium Pharma, Inc.) in patients with scabies. 
2. Compare the safety of Test and Reference treatments in patients with 
scabies. 
Sponsor 
Encube Ethicals 
Study Products 
• 
Test: Permethrin Cream, 5% (Encube Ethicals) 
• 
 Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) 
Study products will be supplied in tubes (60 grams).  
Dosage Regimen 
Patients will administer a single dose of study product on the day of Visit 1 
(i.e., Day 1). A second application may be required if evidence of scabies 
infestation is microscopically demonstrated (i.e., living mites, viable mite 
eggs, or mite fecal matter) are present on Visit 2 (Day 14 ± 4). Each patient 
will receive up to two applications. 
Route of 
Administration 
Topical 
Treatment 
Randomization 
1:1 (Test: Reference) 
Patient Population 
Approximately 250 patients, 2 years of age and older with clinically 
documented evidence of active infestation with Sarcoptes scabiei (scabies). 
Study Design 
Randomized, double-blind, parallel-group, multiple-site bioequivalence  
study with clinical endpoints 
Study Conduct 
Eligible patients will be randomized in a 1:1 ratio to one of the two 
treatments (Test or Reference) at Visit 1. Patients will administer a single 
application of study product on the day of Visit 1 (i.e., Day 1). A second 
application may be required if presence of active scabies infestation is 
microscopically demonstrated (i.e., living mites, viable mite eggs, or mite 
fecal matter present) on Visit 2 (Day 14 ± 4). Patients will complete three 
clinic visits as follows: 
• 
Visit 1 (Day 1): Screening/Baseline 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 9 of 42 
 
 
• 
Visit 2 (Day 14 ± 4): Interim Visit 
• 
Visit 3 (Day 28 ± 4): End of Study Or Early Termination 
Final assessments will be carried out at Visit 3 (Day 28 ± 4), which is the 
test-of-cure visit. Therapeutic cure of scabies will be evaluated based on 
microscopic evidence of absence of scabies infestation (i.e., no living mites, 
no viable mite eggs, and no mite fecal matter), visual evidence of absence of 
new lesions and healing of original lesions, regardless of the presence of 
post-scabetic nodules (i.e., post-scabetic nodules need not be considered as 
new lesions or persistence of old lesions). 
Inclusion Criteria 
1. Male or non-pregnant, non-lactating female, 2 years of age or older. 
2. If female and of childbearing potential, prepared to abstain from sexual 
intercourse or use a reliable method of contraception during the study 
(e.g., double barrier methods, IUD, oral, transdermal or injected 
hormonal contraceptives). Female patients using hormonal contraceptives 
should have been on the same product/dosing regimen for at least 28 days 
before baseline and should not change this regimen during the study.  
3. Signed informed consent that meets all criteria of current FDA and ICH 
regulations. For patients who are considered minors in the state the study 
is being conducted (< 18 years in most states) the parent or legal guardian 
should sign the consent form and the child will be required to sign a 
patient “assent” form, as appropriate. Patients 11-17 years of age will 
read and sign an IRB-approved assent form and patients 6-10 years of 
age will provide verbal assent. Patients 2-5 years of age will be exempt 
from providing assent based on the child’s comprehension and cognitive 
skills. 
4. Clinical diagnosis of active scabies by presence of a burrow and/or 
typical scabietic lesions at the classic sites of infestation. 
5. Parasitological confirmation of clinical diagnosis with demonstration 
under light microscope of mites and/or their products (larvae, eggs or 
fecal material). 
6. Symptom score of 2 or 3 on a 4-point rating scale of 0-3 for nocturnal 
itching/pruritus. 
7. Ability to apply or have study product applied as directed. If patient is a 
child, then parent/guardian will apply study product to him/her. 
Exclusion Criteria 
1. Patients who are pregnant, lactating, or planning to become pregnant 
during the study. 
2. Any systemic or dermatologic disorder that, in the opinion of the 
Investigator, will interfere with the study results or increase the risk of 
adverse events (AEs). 
3. Known hypersensitivity to permethrin cream or any of its components, 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 10 of 42 
 
 
ragweed or chrysanthemums, synthetic pyrethroids or pyrethrin. 
4. Use of any systemic or topical acaricide or ectoparasiticide within one 
month before Screening. 
5. Patient has signs of a systemic infection or is receiving systemic therapy 
for an infectious disease. 
6. Patients with severe cutaneous bacterial or fungal infections requiring 
therapy (including systemic and topical antibiotics) or coexisting 
dermatological disorder that could interfere with the diagnosis and 
subsequent monitoring of scabies) or heavily crusted with lesions 
consistent with Norwegian scabies. 
7. Patients with an underlying immunodeficient state (including prolonged 
treatment with corticosteroids), immunosuppressive disorders requiring 
therapy, severe systemic disease and history of HIV infection. 
8. Any condition, medical, psychological, or social, that, in the 
Investigator’s opinion, would interfere with participation in the study. 
9. Family members of employees of the clinic or Investigator. 
10. Patients who, in the opinion of the Investigator, would be non-compliant 
with the requirements of the study protocol. 
11. Patients whose close personal contacts will not or are not willing to 
comply with standard of care for Scabies management. 
12. Receipt of any drug as part of a research study within 30 days before 
Screening. 
13. History of seizures. 
14. Use of systemic corticosteroids within two weeks before Screening. 
15. Use of topical corticosteroids within one week before Screening. 
16. Previous participation in this study. 
Efficacy Endpoint 
The primary efficacy endpoint is the proportion of patients in each treatment group 
with Therapeutic Cure (parasitological cure plus clinical cure) of scabies at the test-
of-cure visit conducted at Day 28 ± 4. A parasitological cure is defined as failure to 
demonstrate microscopically the presence of scabies infestation (i.e., no living mites, 
no viable mite eggs, and no mite fecal matter present). A clinical cure is defined as 
visual evidence of absence of new lesions and healing of original lesions, regardless 
the presence of post-scabietic nodules (i.e., post-scabietic nodules need not be 
considered as new lesions or persistence of old lesions). 
Evaluation of 
Therapeutic 
Equivalence  
Primary Analysis: 
Therapeutic equivalence of the Test product to the Reference product based 
on the primary endpoint will be evaluated in the per-protocol (PP) population. 
If the 90% confidence interval on the absolute difference between the 
proportion of patients who are considered a Therapeutic Cure (primary) in the 
Test and Reference groups is contained within the range [-20%, +20%] then 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 11 of 42 
 
 
therapeutic equivalence of the Test product to the Reference product will be 
considered to have been demonstrated. 
Supportive Analyses: 
The following supportive analyses will be performed for the primary 
endpoint: 
1. The primary analysis will be performed including patients who 
completed Visit 2 within 14 ± 2 days and Visit 3 within 28 ± 4 days. 
2. The primary analysis will be performed including patients who 
completed Visit 2 within 14 ± 2 days and Visit 3 between Day 26 and 
Day 32, inclusive. 
3. The primary analysis will be performed including patients who 
completed Visit 2 within 14 ± 2 days and Visit 3 within 28 ± 2 days. 
To declare therapeutic equivalence of the Test product to the Reference product, 
therapeutic equivalence must be demonstrated for only the primary analysis. 
Treatment-by-Site Interaction and Pooling of Clinical Sites 
As this is a multiple-site study, the interaction of treatment-by-site may be 
evaluated for the primary efficacy endpoint in the PP population (for 
equivalence testing). The treatment-by-site interaction will be evaluated by 
the Breslow-Day test for homogeneity of the odds ratio at the 5% significance 
level (p < 0.05). A site(s) with a low enrollment rate(s) may be pooled with 
its geographically closest site, so as to avoid bias in the estimation of a 
treatment-by-site interaction effect. The pooling will be done for low 
enrolling sites that account for less than 4-7% of the total number of patients 
in the PP population at the site with the highest enrolling rate in the PP 
population. If the treatment-by-site interaction term is found to be statistically 
significant (p < 0.05) for the primary endpoint, then the interaction term will 
also be assessed for clinical relevance before pooling the data across sites. 
This will include examination of Therapeutic Cure rates at each site where 
sample sizes per treatment may be influential in the assessment of the 
interaction. 
Safety Analysis 
Adverse events will be classified using standard Medical Dictionary for 
Regulatory Activities (MedDRA) terminology Version 20.0 or higher and 
summarized by treatment group. Summary tables comparing the type, 
incidence, date of onset, date of resolution, severity, action taken, outcome 
and Investigator’s opinion of relationship to the study product will be 
prepared by treatment group. If sufficient data exist, AE frequencies will be 
compared between treatments using Fisher’s exact test or a similar test. 
Signs and symptoms of scabies will not be considered AEs, unless in the 
Investigator’s opinion, they have increased in frequency and/or severity to 
such an extent that the Investigator/patient considers that it is in the patient’s 
best interest to be dropped from continued participation in the study and 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 12 of 42 
 
 
given alternative therapy for their condition. 
Concomitant medication use during the study will be tabulated by patient and 
by treatment. 
All patients who are randomized to the active treatment period of the study 
who received study product will be included in the comparative safety 
analysis. 
Sample Size 
Determination 
For the primary endpoint analysis (proportion of patients in the PP population 
who are considered to be a Therapeutic Cure on Day 28 ± 4), sample size is 
estimated for therapeutic equivalence of the Test to the Reference product. 
Based on data from a previous bioequivalence study conducted to support 
approval of the first generic product of permethrin cream, 5%, the 
Therapeutic Cure rate (pR) of the Reference product (Elimite™ permethrin 
cream 5%) is expected to be about 88% in the PP population. Assuming that 
the Therapeutic Cure rate for the Test group (pT) is an absolute difference of 
5% lower than the Therapeutic Cure rate for the Reference group (i.e., pT-
pR = -5%), a sample size of 107 patients in each active group in PP 
population will provide at least 90% power to demonstrate therapeutic 
equivalence (i.e., the 90% confidence interval [Yates’ continuity-corrected] 
on pT-pR  is within a defined equivalence range [-20% to +20%]). 
To allow for approximately 14% of patients who may drop out from the study 
or are otherwise non-evaluable, approximately 250 patients (125 in each 
treatment group) will be randomized, such that there will be an estimated 214 
patients (107 per group) in the PP population for statistical evaluation of 
therapeutic equivalence. 
 
 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 13 of 42 
 
 
6.0 STUDY SCHEMATIC 
 
Visit 1 
Screening/Baseline 
(Day 1) 
Visit 2 
Interim Visit 
(Day 14 ± 4) 
Visit 3 
(Day 28 ± 4) 
End of Study 
or Early 
Termination 
Informed Consent 
X 
 
 
Medical history and 
Baseline Demographics 
X 
 
 
Vital Signs 
X 
 
X 
Adverse Events 
X 
X 
X 
Concomitant Medications 
X 
X 
X 
Microscopic Examination 
X 
X 
X 
Scabies Signs and 
Symptoms Rating (pruritus, 
lesion count)  
X 
X 
X 
Urine Pregnancy Test 
X 
 
X 
Review Inclusion/Exclusion 
Criteria 
X 
 
 
Collect and Review Diary 
 
X 
X 
Provide Diary 
X 
X 
 
Dispense Study Product 
X 
X* 
 
Collect and Weigh Study 
Product 
 
X 
X* 
*If retreatment is necessary, the originally dispensed (i.e., at Visit 1) study product will be 
dispensed at Visit 2 and collected at Visit 3.


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 14 of 42 
 
 
7.0 LIST OF ABBREVIATIONS AND TERMS 
ADaM 
Analysis Dataset Model 
AE 
Adverse Event 
ANDA 
Abbreviated New Drug Application 
ANOVA 
Analysis of variance 
C 
Celsius 
CDISC 
Clinical Data Interchange Consortium 
CMH 
Cochran-Mantel-Haenszel 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
eCTD 
Electronic Common Technical Document 
F 
Fahrenheit 
FDA 
Food & Drug Administration 
GCP 
Good Clinical Practices 
hCG 
Human Chorionic Gonadotropin  
HIV 
Human Immunodeficiency Virus 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IRB 
Institutional Review Board 
IUD 
Intrauterine Device 
LOCF 
Last Observation Carried Forward 
MedDRA 
Medical Dictionary for Regulatory Activities  
OGD 
Office of Generic Drugs 
OTC 
Over-the-Counter 
PP 
Per-Protocol 
RLD 
Reference Listed Drug 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SAS 
Statistical Analysis Software 
USA 
United States of America 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 15 of 42 
 
 
8.0 INTRODUCTION 
8.1 Disease Being Treated 
Scabies is an infestation of the skin by the human itch mite (Sarcoptes scabiei). The microscopic 
scabies mite burrows into the upper layer of the skin where it lives and lays its eggs. The most 
common signs and symptoms of scabies are intense itching, skin rash and the presence of tiny 
burrows caused by the female mites tunneling through the superficial surface of the skin. The scabies 
mite is spread by direct, prolonged, skin-to-skin contact with infected persons.1,2 
As of 2010, scabies affects approximately 100 million people (1.5% of the world population) and is 
equally common in both sexes. Scabies is found worldwide and affects people of all races and social 
classes. Scabies outbreaks are common in crowded public places, nursing homes, extended-care 
facilities, prisons and child care facilities.1,2 
Initial infections require 4-6 weeks to become symptomatic. Re-infection, however, may manifest 
symptoms within as few as 24 hours. Scabies symptoms are allergic, exhibiting a delay in onset as 
well as relief after the parasites have been eradicated. A more severe form of infection is crusted 
scabies, formerly known as Norwegian scabies, which is often associated with immunosuppression.1,2 
Diagnosis of scabies is made based on clinical symptoms, such as nocturnal itching and appearance 
and distribution of the rash. Definitive diagnosis includes the microscopic identification of the mite, 
mite eggs, or mite fecal matter in the skin. This can be done by carefully removing a mite or skin 
scraping from the end of its burrow (or near a lesion) using the tip of a needle and observing under a 
microscope.1,2 
8.2 Availability and Efficacy of Already Approved Therapies 
Food & Drug Administration (FDA)-approved scabies therapies, called scabicides are available only 
by prescription. Such treatments include topical medications such as permethrin cream 5% 
(Elimite™), crotamiton lotion/cream 10% (Eurax®, Crotan®) and lindane lotion 1%. Oral anti-
parasitic therapy includes ivermectin (Stromectol®), which is considered effective in combination 
with topical therapy.1,2 
Permethrin, a pyrethroid, is active against a broad range of pests including lice, ticks, fleas, mites, and 
other arthropods. It acts on the nerve cell membrane to disrupt the sodium channel current by which 
the polarization of the membrane is regulated. Delayed repolarization and paralysis of the pests are 
the consequences of this disturbance.  
Permethrin is considered the drug of choice for the treatment of scabies. It is safe for use in adults and 
children 2 months and older. One or two applications, about a week apart may be necessary to 
eliminate all mites and eggs on the patient’s body. 1,2 
8.3 Scientific and Statistical Considerations 
Permethrin is rapidly metabolized by ester hydrolysis to inactive metabolites which are excreted 
primarily in the urine. Although the amount of permethrin absorbed after a single application of the 
5% cream has not been determined precisely, data from studies with 14C-labeled permethrin and 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 16 of 42 
 
 
absorption studies of the cream applied to patients with moderate to severe scabies indicate it is 2% or 
less of the amount applied. As the systemic absorption of the Reference product, Elimite™ cream 
(permethrin) 5% is extremely low , its relevance to clinical activity is not significant.3 A therapeutic 
efficacy evaluation based on relief from scabies symptoms and eradication of living mites     in the 
skin after using study products is considered the most appropriate methodology for this study.4,5 
A previous bioequivalence study conducted for the FDA marketing approval for the first generic 
product of permethrin cream, 5% indicated that the rate of clinical cure for this product and that for 
the Reference product, Elimite™ cream (permethrin) 5%, was about 88%; there was no placebo 
treatment arm in that study.6 
The design and sample size estimation for the study described in this protocol are based on a previous 
bioequivalence study. 
The FDA published a Draft Guidance on Permethrin Cream in October 2017,7 which was after the 
start of the conduct of study 71675502 (last patient, last visit occurred on October 30, 2017). 
Therefore, this protocol was revised to accommodate recommendations in that Guidance, as 
appropriate. Key revisions are the following: 
1. Revised definition of the per-protocol (PP) population to include those patients that are 
treatment failures on Day 14 as Therapeutic Failures in the final analysis (see section 11.3.1). 
2. Revised definition of the Safety population (see section 11.3.2). 
3. Removed the secondary efficacy endpoint (see section 11.5). 
4. Removed the Yates’ continuity correction for calculation of 90% confidence intervals on the 
absolute difference between the proportion of patients who are considered a Therapeutic Cure 
in the Test and Reference groups (see section 11.6). 
5. Added three supportive analyses to evaluate different evaluation windows for Visit 2 
(Day 14) and Visit 3 (Day 28) (see section 11.6). 
6. Added descriptive statistics for the number and frequency of re-infestations from Day 14 
(Therapeutic Cure) to Day 28 (Therapeutic Failure) in the PP population. 
The Guidance recommends a ± 2-day window for both the Day 14 and Day 28 visits. This protocol 
incorporates a ± 4-day window for both visits. The justification for the wider visit window is that 
permethrin cream 5% is expected to cure scabies infestation after a single treatment. That is, if it 
works by Day 14 it should still work by Day 28, and thus the re-infestation rate from Day 14 to 
Day 28 is expected to be low. Therefore, a wider visit window on Day 28 should be acceptable. The 
effect of different visit window durations at Day 14 and Day 28 will be explored in the three 
supportive analyses. 
The Guidance also recommends that the youngest patient (with scabies infestation who meets the 
inclusion criteria) from each household is considered to be the index or primary patient of the 
household for evaluation of the primary endpoint, that other members of the household and close 
contacts are enrolled as secondary patients (not included in primary endpoint analysis) and evaluated 
for all safety parameters, and that secondary patients should receive the same study treatment as the 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 17 of 42 
 
 
index patient. This protocol did not define an index patient and secondary patients from each 
household. Instead all eligible household members that qualified for the study were separately 
randomized to receive study product (Test or Reference) and included in the primary endpoint 
analysis. The justification for this design is that there is no placebo treatment arm in this study; 
therefore, there is minimal chance that household members would exchange or share treatments, 
given that each enrolled member would receive active treatment. Because the risk of treatment 
exchange or sharing within a household is higher when some members receive active treatment and 
others receive placebo treatment, the Guidance-recommendation that primary and secondary subjects 
within a household all receive the same study treatment is necessary for a placebo-controlled study 
but is not necessary for an active-treatment-only study. 
9.0 STUDY OBJECTIVES 
The objectives of this study are to: 
1. Evaluate the therapeutic equivalence of the Test formulation, Permethrin Cream, 5% (Encube 
Ethicals) to the marketed product, Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) in 
patients with scabies. 
2. Compare the safety of Test and Reference treatments in patients with scabies. 
10.0 INVESTIGATIONAL PLAN 
10.1 Study Design and Plan Description 
This randomized, double-blind, parallel-design, multiple-site study is designed to evaluate the 
therapeutic efficacy and safety of a generic Permethrin Cream, 5% (Encube Ethicals) compared to the 
FDA Reference Listed Drug (RLD), Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) in 
patients with scabies. 
Before any study-specific procedures are performed, all patients will read and sign the IRB-approved   
informed consent that meets all criteria of current FDA and International Conference of 
Harmonisation (ICH) regulations. For patients who are considered minors in the state the study is 
being conducted (< 18 years in most states) the parent or legal guardian should sign the consent form 
and the child will be required to sign a patient “assent” form, as appropriate. Patients 11-17 years of 
age will read and sign an IRB-approved assent form and patients 6-10 years of age will provide verbal 
assent. Patients 2-5 years of age will be exempt from providing assent based on the child’s 
comprehension and cognitive skills.  
Approximately 250 eligible patients, 2 years of age and older with a clinical diagnosis of active 
scabies based on signs and symptoms and confirmation of microscopic evidence of scabies mites in 
the skin will be randomized in a 1:1 ratio (Test: Reference) to one of the two study products as 
follows: 
• 
Test: Permethrin Cream, 5%, (Encube Ethicals) 
• 
Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.*) 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 18 of 42 
 
 
(*Note: The RLD used to conduct the bioequivalence studies is Elimite™ (permethrin) 
topical cream (5%) (NDC Code 40076-230-60) manufactured by DPT Laboratories 
LTD., San Antonio TX 78215 and Manufactured for Prestium Pharma Inc. Although the 
RLD labeling indicates that the product is manufactured for Prestium Pharma Inc., please 
note that Prestium Pharma Inc., Newtown PA 18940 was acquired by Mylan 
Pharmaceuticals Inc., which is also the NDA holder of the RLD. This is consistent with 
the information verified in the Orange Book: Approved Drug Products with Therapeutic 
Equivalence Evaluations.) 
Patients will be instructed to self-administer a single dose of study product or, if patient is a child, 
then parent/guardian will apply study product to him/her on Day 1 according to the dosing 
instructions provided. A second application may be required if presence of scabies infestation is 
microscopically demonstrated (i.e., living mites, viable mite eggs, or mite fecal matter present) at 
Visit 2. The second dose will be self-administered by the patient or if patient is a child, then 
parent/guardian will apply study product to him/her on the evening of Visit 2. Eligible household 
members and close contacts of the patient who were in need of treatment will be offered generic 
permethrin cream as a method to reduce cross-contamination within a household. Additionally, 
household members will be requested to follow the standard hygiene practices. Patients whose 
household members are not willing to comply with the standard of care for Scabies management (i.e., 
use of generic permethrin cream and standard hygiene practices) will not be enrolled in the study.  
During the study, patients will visit the clinical center for a total of three scheduled visits: 
• 
Visit 1 (Day 1): Screening/Baseline 
• 
Visit 2 (Day 14 ± 4): Interim Visit 
• 
Visit 3 (Day 28 ± 4): End of Study or Early Termination 
Final assessments will be carried out at Visit 3 (Day 28 ± 4), which is the test-of-cure visit. The test-
of-cure visit will occur 4 weeks (± 4 days) after the end of the single application treatment on study 
Day 1 or 2 weeks (± 4 days) after the end of a second application, if necessary, on Day 14 ± 4. 
Therapeutic cure of scabies will be evaluated based on microscopic evidence of absence of scabies 
infestation (i.e., no living mites, no viable mite eggs, and no mite fecal matter), visual evidence of 
absence of new lesions, and healing of original lesions, regardless of the presence of post-scabetic 
nodules (i.e., post-scabetic nodules need not be considered as new lesions or persistence of old 
lesions). The primary statistical analysis of interest is the proportion of patients in each treatment 
group with Therapeutic Cure (parasitological cure plus clinical cure) of scabies 
10.2 Selection of Study Design 
This study has been designed based on information provided in the Summary Basis for Approval of 
permethrin cream, 5% (Alpharma, U.S. Pharmaceuticals Division) and prescription information for 
the Reference product, Elimite™ cream (permethrin) 5%.6 
Statistical analyses of the clinical data will be based on recommendations in FDA Guidances.5,7-10 
Details of the analyses will be outlined within the Statistical Analysis Plan (SAP).  


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 19 of 42 
 
 
10.3 Selection of Study Population 
10.3.1 Inclusion Criteria   
1. Male or non-pregnant, non-lactating female, 2 years of age or older. 
2. If female and of childbearing potential, prepared to abstain from sexual intercourse or use a 
reliable method of contraception during the study (e.g., double barrier method, IUD, oral, 
transdermal or injected hormonal contraceptives). Female patients using hormonal 
contraceptives should have been on the same product/dosing regimen for at least 28 days 
before baseline and should not change this regimen during the study. 
3. Signed informed consent that meets all criteria of current FDA and ICH regulations. For 
patients who are considered minors in the state the study is being conducted (< 18 years in 
most states) the parent or legal guardian should sign the consent form and the child will be 
required to sign a patient “assent” form, as appropriate. Patients 11-17 years of age will read 
and sign an IRB-approved assent form and patients 6-10 years of age will provide verbal 
assent. Patients 2-5 years of age will be exempt from providing assent based on the child’s 
comprehension and cognitive skills. 
4. Clinical diagnosis of active scabies by presence of a burrow and/or typical scabietic lesions at 
the classic sites of infestation. 
5. Parasitological confirmation of clinical diagnosis with demonstration under light microscope 
of mites and/or their products (larvae, eggs or fecal material). 
6. Symptom score of 2 or 3 on a 4-point rating scale of 0-3 for nocturnal itching/pruritus. 
7. Ability to apply or have study product applied as directed. If patient is a child, then 
parent/guardian will apply study product to him/her 
10.3.2 Exclusion Criteria 
1. Patients who are pregnant, lactating, or planning to become pregnant during the study. 
2. Any systemic or dermatologic disorder that, in the opinion of the Investigator, will interfere 
with the study results or increase the risk of adverse events (AEs). 
3. Known hypersensitivity to permethrin cream or any of its components, ragweed or 
chrysanthemums, synthetic pyrethroids or pyrethrin. 
4. Use of any systemic or topical acaricide or ectoparasiticide within one month before 
Screening. 
5. Patient has signs of a systemic infection or is receiving systemic therapy for an infectious 
disease. 
6. Patients with severe cutaneous bacterial or fungal infections requiring therapy (including 
systemic and topical antibiotics) or coexisting dermatological disorder that could interfere 
with the diagnosis and subsequent monitoring of scabies) or heavily crusted with lesions 
consistent with Norwegian scabies. 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 20 of 42 
 
 
7. Patients with an underlying immunodeficient state (including prolonged treatment with 
corticosteroids), immunosuppressive disorders requiring therapy, severe systemic disease and 
history of HIV infection. 
8. Any condition, medical, psychological, or social, that, in the Investigator’s opinion, would 
interfere with participation in the study. 
9. Family members of employees of the clinic or Investigator. 
10. Patients who, in the opinion of the Investigator, would be non-compliant with the 
requirements of the study protocol. 
11. Patients whose close personal contacts will not or are not willing to comply with standard of 
care for Scabies management. 
12. Receipt of any drug as part of a research study within 30 days before Screening. 
13. History of seizures. 
14. Use of systemic corticosteroids within two weeks before Screening. 
15. Use of topical corticosteroids within one week before Screening. 
16. Previous participation in this study. 
10.3.3 Restrictions During the Study 
Patients will be instructed to refrain from the following treatments throughout the study: 
• 
Any other prescription/over-the-counter (OTC)/natural/herbal scabicides. 
• 
Systemic and topical corticosteroids or immunosuppressants (e.g., high dose of systemic 
corticosteroids, systemic calcineurin inhibitors, Azathioprine). 
• 
Prolonged exposure to sunlight/UV, use of tanning beds, chemical treatments/peels, 
dermabrasion or any dermatological procedures that will potentially influence or hinder 
the evaluation of scabies signs and symptoms. 
Note: Use of antibiotics (systemic and topical) for cutaneous bacterial infections during the 
conduct of the study will be allowed after the Screening/Baseline visit, but the usage should be 
restricted to the Principal Investigator’s discretion in cases of secondary infections of scabietic 
lesions. The usage of the antibiotic should be included on the concomitant medication page. 
10.3.4 Removal of Patients from the Study 
Patients will be advised that they are free to withdraw from the study at any time for any reason 
or, if necessary, the Investigator may withdraw a patient from the study to protect the health of 
that patient. A patient may also be withdrawn for not complying with study procedures. The 
clinical report will include all reasons for early withdrawals. 
Reasons for removal may include, but are not limited to the following: 
• 
Patient withdrew consent 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 21 of 42 
 
 
• 
Significant AE that led the Investigator or patient to withdraw for safety reasons 
• 
Non-compliance with protocol including the use of restricted medication 
• 
Pregnancy 
• 
Significant worsening of scabies such that the Investigator and/or patient believes it is in 
the best interest of the patient to withdraw from the study and be provided alternative 
treatment 
• 
Participant enrolls in another clinical trial, or is found to have previously enrolled in this 
study 
10.3.5 Early Terminations 
If a randomized patient terminates from the study early, all efforts will be made to complete the 
End of Study procedures. For early termination the Investigator will fully document the reason 
for early termination. 
10.4 Treatments 
10.4.1 Treatment Administration 
Patients will be provided with verbal and written instructions on how to administer the study 
product. Eligible household members and close contacts of the patient will be offered permethrin 
cream (if they are in need of treatment) and will follow the appropriate application and 
decontamination instructions as follows. Patients whose household members are not willing to 
comply with the standard of care for Scabies management (i.e., use of generic permethrin cream 
and standard hygiene practices) will not be enrolled in the study. 
Patients will be instructed to thoroughly massage study product into (clean) skin from the head to 
the soles of the feet, including all folds, interdigital space, groin, navel, and external genitalia, as 
well as the skin under nails and jewelry (i.e., rings, watches). Scabies rarely infests the scalp of 
adults, although the hairline, neck, temple, and forehead may be infested in infants and geriatric 
patients. Usually 30 grams is sufficient for an average adult. Patients must NOT wash their hands 
from the time the product is applied until the time the product is removed. Study product should 
be reapplied if hands are washed after application. Scabies rarely infests the scalp of adults, 
although the hairline, neck, temple, and forehead may be infested in toddlers and geriatric 
patients. For toddlers, only the following areas on the head should be treated: the scalp, temple, 
and forehead, avoiding the eyes, because transmission of mites may potentially occur during 
breastfeeding.  Clean clothing should be worn after product application. The cream should be 
removed by washing (shower or bath) after 8 to 14 hours. Contact with eyes during application 
must be avoided. Eyes should be flushed with water immediately if the study product gets in the 
eyes.  
On Day 1, before applying treatment, all bedding, clothing, and towels used by infested persons 
or their household, sexual, and close contacts 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. 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 22 of 42 
 
 
Instructions on good hygiene and proper methods of decontamination will be provided to the 
patient. 
Patients may experience persistent pruritus after treatment. This is not to be considered a sign of 
treatment failure and is not an indication for retreatment. Demonstrable living mites (i.e., living 
mites, viable mite eggs, or mite fecal matter) on at Visit 2 indicate that re-treatment is necessary. 
Retreatment should occur the evening of Visit 2. 
 Standard anti-itch medication (oral hydroxyzine capsule or oral solution) will be provided by the 
Investigator, as deemed necessary based on his/her judgment, for the relief of intolerable itching, 
or to facilitate nighttime sleep during the treatment period (when the itching severely affects 
sleep). Frequent use of the anti-itch medication is not encouraged. Suggested dosing for patients 
> 12 years old is 25 mg per os every 6-8 hours as needed or at hora somni; the maximum dosage 
allowed is 100 mg/24 h. For patients ≥ 2 years old is 2 mg/kg/day per os divided every 6-8 hours 
as needed; the maximum dosage allowed is 50 mg/24 h. Patients will be required to record the use 
(date, time and dose) of rescue medication in the patient diary. 
Skin sores that become infected may be treated with an appropriate antibiotic provided by the 
Investigator if such decision is made based on the clinical picture and at the discretion of the 
Investigator. 
10.4.2 Identity of Investigational Product 
The following products will be used in the study: 
• 
Test: Permethrin Cream, 5% (Encube Ethicals) 
• 
Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.*) 
10.4.3 Study Product Shipment, Storage, and Retention 
The study product will be shipped to each Investigator’s Site from a centralized pharmacy. The 
Principal Investigator at each site is responsible for ensuring that all study products are stored in a 
locked, secure location, with access limited to the Investigator and his/her designee(s). An 
accurate inventory of the study product will be maintained in accordance with federal regulations. 
Study product will be stored at controlled room temperature 20-25°C (68-77°F) [USP Controlled 
Room Temperature]. Any excursions from the permitted range of 15–30ºC (59º–86ºF) will 
require prompt notification to Novum, and thereafter Novum will notify the Sponsor. 
For every study product shipment received at the site, the Investigator (or designee) will 
randomly select at least one block of study product for retention. The selection process will 
ensure a sufficient amount of retention samples are retained as per Sponsor requirement (i.e., 
amount needed for 5x release testing). Each kit in the block selected for retention will be labeled 
as a retention sample and should not be dispensed to study patients. The selected retention 
samples will be retained by each site under FDA regulations as study retention samples.11 
Once the site has been notified that they may do so, all unused study product and empty or 
partially used tubes of study product, other than that randomly selected for retention samples will 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 23 of 42 
 
 
be returned to the Sponsor or designee. It is important that retention samples not be returned to 
Novum, the Sponsor or the packaging company during or at the end of the study. 
10.4.4 Method of Assigning Patients to Treatment Groups 
The study product will be randomized, packaged and blinded by an independent packaging 
company. Randomization will be pre-planned according to a computer-generated randomization 
schedule. All randomized study products will be blinded and packaged in sealed boxes. Each 
block will contain two patients’ worth of product (1 Test and 1 Reference). Each patient kit will 
include 1 x 60 gram tube of study product, which should be sufficient for full treatment. 
The randomization number will be a unique four-digit number. Patient numbers will be assigned 
immediately before dispensing of study product and in ascending sequential order, beginning 
with the lowest available number at the study site. Each patient kit and each dispensed study tube 
should include the four-digit patient number on the label. 
At the end of the study, after all the clinical data have been entered and the study database has 
been locked, a copy of the randomization schedule will be sent to the statistician. 
10.4.5 Study Blind 
The Investigator, staff at the study site, study monitors, and data analysis/management personnel 
will be blinded to the patient assignment. Each study site will have at least one Independent 
Dispenser. The role of the Independent Dispenser is to dispense and collect study product to/from 
the patients, maintain dispensing records, and ensure the study product logs are complete and 
accurate. The patient will be requested not to discuss the appearance of the study product with the 
Investigator or study staff. 
A perforated or two-part label will be attached to the study product supplies for each patient. One 
part of the label will remain attached to the box. This part should include the following 
information: 
• 
Protocol number 
• 
Randomization number 
• 
Space for patient’s initials 
• 
Caution New Drug limited by federal law to investigational use 
• 
Space for dispensing date, storage information, general directions and the Sponsor’s 
name 
The other part will be removed before dispensing and attached to patient’s source documentation. 
To ensure information that could potentially bias handling of data is not disclosed, the clinical 
packaging company will hold the randomization scheme until database lock.  For each patient  the 
tear off portion of the label will have a concealed scratch off area describing the assigned 
treatment, to be unblinded only in the case of medical emergency and should be kept at the site 
with the study documents when the study is completed. 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 24 of 42 
 
 
Whenever possible, the Novum Medical Monitor must be contacted before breaking the blind for 
any patient. 
At the end of the study, after the database has been locked, each site will be sent a sealed 
envelope containing the full study randomization that should be retained with the study 
documents in the event of an FDA inspection.   
10.4.6 Compliance 
Patients will be provided with a diary to record the time and date of dosing, concomitant 
medications and AEs. Use of restricted medications will be reviewed based on patient diary 
entry(s) and verbal discussion with the patient. Dosing compliance will be checked based on the 
dosing diary entry and verbal discussion with the patient at Visits 2 and 3 (when applicable). 
Patients will be considered compliant with dosing if they administer 100% of the required number 
of doses (i.e., one or, if necessary, two doses). 
10.5 Study Conduct 
10.5.1 Visit 1 (Day 1): Screening/Baseline 
1. Informed Consent: Patients should sign informed consent that meets all criteria of current 
FDA regulations. For patients who are considered minors in the state the study is being 
conducted (< 18 years in most states) the parent or legal guardian should sign the consent 
form and the child will be required to sign a patient “assent” form, as appropriate. Patients 
11-17 years of age will read and sign an IRB-approved assent form and patients 6-10 years of 
age will provide verbal assent. Patients 2-5 years of age will be exempt from providing assent 
based on the child’s comprehension and cognitive skills. 
2. Medical History and Baseline Demographics: Review the patient’s demographic and 
medical history within the last six months. 
3. Vital Signs: Record Patient’s blood pressure, pulse, temperature and respiration rate. 
4. Adverse Events: Patients will be questioned about any changes in patient’s health status, 
including occurrence of AEs since signing the ICF or Assent or AEs that may have occurred 
during the visit. All AEs will be recorded. 
5. Concomitant Medications: Review the patient’s use of current and prior medication use 
over the previous 6 months. 
6. Microscopic Examination: Skin scrapings will be taken to assess microscopic evidence of 
scabies mites/eggs/feces in the skin. Refer to Appendix B. 
7. Scabies Signs and Symptoms Rating (pruritus, lesion count): Patients will be asked to 
complete a rating scale to record symptom severity of nocturnal itching/pruritus. Investigators 
will be asked to complete a rating scale to record severity of lesion count infestation. Refer to 
Appendix A 
8. Pregnancy Test: Women of childbearing potential will take a urine pregnancy test. 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 25 of 42 
 
 
9. Review Inclusion/Exclusion Criteria: Confirm the patient meets all inclusion/exclusion 
criteria. 
10. Provide Dosing Diary: Patients will receive a diary to record date and time of dosing and 
duration of application, AEs and concomitant medications. 
11. Dispense Study Product: Eligible patients will receive randomized study product with 
instructions for dosing at home. 
10.5.2 Visit 2 (Day 14 ± 4): Interim Visit 
1. Adverse Events: Patients will be questioned about any health status changes/AEs since last 
visit. All AEs will be recorded. 
2. Concomitant Medication: Review the patient’s use of any new or ongoing concomitant 
medications since the last visit. 
3. Microscopic Examination: Skin scrapings will be taken to record microscopic evidence of 
scabies mites/eggs/feces in the skin. Refer to Appendix B. 
4. Scabies Signs and Symptoms Rating (pruritus, lesion count): Patients will be asked to 
complete a rating scale to record symptom severity of nocturnal itching. Investigators will be 
asked to complete a rating scale to record severity of lesion count infestation. Refer to 
Appendix A 
5. Collect and Review Patient Diary: Collect previously dispensed diary and review for 
compliance with the protocol. 
6. Provide Patient Diary: Patients will receive a diary to record any changes in health status 
(AEs), and concomitant medication.   
7. Collect and Weigh Study Product: Collect and weigh used study product tubes. The weight 
of the used study will be recorded in the drug accountability log. Patients who do not require 
a second application will return the used study product tube. Patients deemed eligible by the 
Investigator for a second application (based on presence of living mites by microscopic 
examination at Visit 2) will keep study product, and apply a second dose at home. 
10.5.3 Visit 3 (Day 28 ± 4): End of Study or Early Termination 
1. Vital Signs: Record Patient’s blood pressure, pulse, temperature and respiration rate. 
2. Adverse Events: Patients will be questioned about any health status changes/AEs since last 
visit. All AEs will be recorded. 
3. Concomitant Medication: Review the patient’s use of any new or ongoing concomitant 
medications since the last visit. 
4. Microscopic Examination: Skin scrapings will be taken to record microscopic evidence of 
scabies mites/eggs/feces in the skin. Refer to Appendix B. 
5. Scabies Signs and Symptoms Rating (pruritus, lesion count): Patients will be asked to 
complete a rating scale to record symptom severity of nocturnal itching. Investigators will be 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 26 of 42 
 
 
asked to complete a rating scale to record severity of lesion count infestation. Refer to 
Appendix A 
6. Pregnancy Test: A pregnancy test will be required of all female patients of childbearing 
potential. 
7. Collect and Review Patient Diary: Collect previously dispensed diary and review for 
compliance with the protocol. 
8. Collect and Weigh Study Product: Collect and weigh used study product tubes (in cases 
when re-treatment was required or if the patient inadvertently did not return the study product 
at Visit 2). The weight of the used study tube will be recorded in the drug accountability log. 
9. Review completeness of all source documents and discharge from the study. 
10.6 Study Procedures 
10.6.1 Informed Consent 
At Visit 1, before performing any study-related procedures, patients should sign informed consent 
that meets all criteria of current FDA regulations. For patients who are considered minors in the 
state the study is being conducted (< 18 years in most states) the parent or legal guardian should 
sign the consent form and the child will be required to sign a patient “assent” form, as 
appropriate. Patients 11-17 years of age will read and sign an IRB-approved assent form and 
patients 6-10 years of age will provide verbal assent. Patients 2-5 years of age will be exempt 
from providing assent based on the child’s comprehension and cognitive skills.  
10.6.2 Medical History and Demographics 
At Visit 1, each patient will be required to provide basic demographic information: date of birth, 
gender, ethnicity and race. Patients will also be questioned about medical history, including acute 
and chronic medical history and medical history relevant to their scabies. 
10.6.3 Vital Signs 
At Visit 1 and at the end of the study (Visit 3 or early study termination as appropriate), sitting 
blood pressure, pulse, respiration rate and temperature will be recorded. 
10.6.4 Adverse Events 
At Visit 1, patients will be questioned about any changes in patient’s health status, including 
occurrence of AEs since signing the ICF or Assent or AEs that may have occurred during the 
visit. All AEs will be recorded. At Visits 2 and 3 patients will be questioned regarding any 
changes in their medical status since their previous visit. Any changes will be reported as AEs. 
10.6.5 Concomitant Medication 
At Visit 1, patients will be questioned about current and prior medication use over the previous 6 
months. At Visits 2 and 3 patients will be questioned about ongoing or any new concomitant 
medication use.  


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 27 of 42 
 
 
10.6.6 Microscopic Examination 
At each clinic visit, the Investigator will conduct a dermatological examination to identify living 
mites in the skin. A dermoscope can be used (but is not required) to observe 
lesions/papules/blisters/burrows on the skin. Once determined that the lesions are characteristic of 
scabies, the Investigator will collect a skin scraping sample for identification of living 
mites/eggs/feces by light microscopy. See Appendix B for details. 12-14 
10.6.7 Scabies Signs and Symptoms Rating 
At each clinic visit, patients will be asked to rate the severity of nocturnal pruritus using a 4-point 
scale for pruritus severity. Investigators will be asked to complete a rating scale to record severity 
of lesion count infestation (Appendix A).15 
10.6.8 Pregnancy Test 
All females of childbearing potential will have a urine pregnancy test performed at Visits 1 and 3. 
The test must be negative at Visit 1 for the patient to be eligible for inclusion in the study. If the 
patient is of non-childbearing potential, the source document must list the reason why she is of 
non-childbearing potential (e.g., postmenopausal). 
Any patient who becomes pregnant during the study must be discontinued and End of Study 
procedures completed. The outcome of the pregnancy will be followed by the Investigator to birth 
or early termination as appropriate. The pregnancy will be reported as an AE. 
10.6.9 Review Inclusion/Exclusion Criteria 
At Visit 1, inclusion/exclusion criteria will be reviewed to ensure patients’ eligibility for 
participation in the study. 
10.6.10 Collect and Review Patient Diary 
At Visits 2 and 3, patient diaries will be collected and reviewed for compliance with the protocol. 
10.6.11 Provide Patient Diary 
Patients will be given a diary with instructions on dosage administration and diary completion. 
The diary will be reviewed by the study staff at Visits 2 and 3 (when applicable). 
10.6.12 Dispense Study Product 
After the Investigator has determined that the study participant meets the inclusion/exclusion 
criteria for the study the “Independent Dispenser” will dispense one 60 gram tube of study 
product to the patient using the lowest patient randomization number available at that 
investigative site, and if necessary, at Visit 2 (re-dispense the same tube to the patient, i.e., no 
new tube will be provided) with dosing instructions. The Independent Dispenser will ensure the 
study product logs are reported correctly. Eligible household members and close contacts of the 
patient will be administered generic Permethrin cream and will follow the appropriate application 
and decontamination instructions. 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 28 of 42 
 
 
10.6.13 Collect and Weigh Study Product 
Study product tubes will be collected and weighed at Visit 2 or Visit 3 (in cases when re-
treatment is required or if the patient inadvertently did not return the study product at Visit 2) by 
the Independent Dispenser and checked for compliance or evidence of tampering with the blind. 
The weight will be recorded in the drug accountability log. 
10.7 Adverse Events 
The patients will be monitored throughout the study for any AEs. Adverse events will be collected 
through both solicited and unsolicited means and subsequently coded in tabular form using the 
Medical Dictionary for Regulatory Activities (MedDRA) (Version 20.0 or higher) AE Dictionary. 
The patients will be encouraged to report signs, symptoms, and any changes in health to the clinic 
staff. Severity of each AE will be determined by the staff based on observation and questioning of the 
patients. The Investigator will judge the relationship of the event to the study treatments. AEs should 
be followed up until they have resolved or stabilized. 
10.7.1 Adverse Event Definitions 
Adverse Event: Any untoward medical occurrence in a patient or clinical investigation patient 
administered a pharmaceutical product and which does not necessarily have a causal relationship 
with treatment. An AE can therefore be any unfavorable and unintended sign, symptom or 
disease, temporally associated with the use of a medicinal (investigational) product, whether or 
not related to this product. This includes events not seen at baseline, or worsened even if present 
at baseline. 
Unexpected Adverse Event: An AE where the nature or severity of is not consistent with the 
applicable product information (e.g., Investigator’s Brochure for an unapproved investigational 
product or package insert/summary of product characteristics for an approved product). 
Adverse Drug Reaction: All noxious and unintended responses to a medical product related to 
any dose should be considered adverse drug reactions. The response to a ‘medical product’ means 
that a causal relationship between a medicinal product and an AE is at least a reasonable 
possibility, i.e., the relationship cannot be ruled out. 
10.7.2 Severity of Adverse Event 
The severity of the AE will be graded by the Investigator using the following criteria as 
guidelines: 
• 
MILD: Awareness of symptom but does not interfere with routine activities. 
• 
MODERATE: Discomfort sufficient to interfere with routine activities. 
• 
SEVERE: Impossible to perform routine activities. 
10.7.3 Relationship of Adverse Event 
Relationship to the study product will be evaluated by the Investigator as follows: 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 29 of 42 
 
 
• 
Not Related: A causal relationship between the study treatment and the AE is not a 
reasonable possibility 
• 
Related: A causal relationship between the study treatment and the AE is a reasonable 
possibility. 
10.8 Serious Adverse Events 
10.8.1 Definition of a Serious Adverse Event 
A serious adverse event (SAE) is any untoward medical occurrence that at any dose suggests a 
medically significant hazard, including any event that: 
• 
Results in death: includes all deaths, even those that appear to be completely unrelated to 
study treatment (e.g., car accident where patient is a passenger). 
• 
Is life-threatening: in the view of the Investigator, the patient is at immediate risk of death 
at the time of the event. 
• 
Results in persistent or significant disability or incapacity (substantial disruption of one’s 
ability to conduct normal life). 
• 
Requires inpatient hospitalization or prolongation of existing hospitalization. 
• 
Causes congenital anomaly or birth defect. 
• 
Is an important medical event that may not be immediately life-threatening or result in 
death or hospitalization, but may jeopardize the patient or may require medical or 
surgical intervention to prevent one of the serious outcomes listed above (e.g., intensive 
treatment in an emergency room, convulsions that do not result in hospitalizations). 
Emergency Room visits that require medical or surgical intervention to prevent one of the 
other serious outcomes listed above are considered an SAE. 
10.8.2 Reporting Serious Adverse Events 
Investigator Reporting of SAEs 
Adverse events that meet the above criteria for "Serious" will be reported to the Sponsor and IRB 
within 24 hours of notice whether or not they are considered expected or drug-related. All SAEs 
will be reported as per applicable regulations. All SAEs encountered during the study will be 
reported on the appropriate form and summarized in the final report. 
Any serious or unexpected AEs should be reported to Novum within 24 hours. Following is 
the contact information: 
Gail Gongas 
Vice President, Clinical Trials and Data Management 
Cell Phone 412-606-1603 
Phone: 412-363-3300 x 522 
Fax: 412-291-3171 
Or 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 30 of 42 
 
 
Paolo Fanzio, MD 
Medical Director 
Phone: 412-363-3300 x 597 
Fax: 412-291-3171 
Novum will report any SAE to Sponsor: 
Documentation of serious or unexpected AEs and follow-up information should be sent to the 
Sponsor within 24 hours from Novum being made aware of the SAE. Following is the contact 
information: 
Pratik Kamini 
GM- Strategy & Commercial  
Encube Ethicals Pvt ltd 
Phone: +91-22-6228-8000 Ext 8003 
Mobile: +91-98-2047-9316 
Email: Pratik.K@EncubeEthicals.com  
Novum will be responsible for notifying the FDA of any SAEs. Novum must notify FDA of fatal 
or life-threatening SAE as soon as possible, but no later than seven calendar days from reporting 
the event by the Investigator. 
Novum will inform all the participating investigators of any SAEs reported at other study sites 
within 15 days from the initial report. Sites outside of the US will be responsible for reporting to 
their local regulatory authorities as appropriate. 
11.0 STATISTICAL METHODS 
11.1 Statistical Plan 
A Statistical Analysis Plan (SAP), detailing the intended statistical analyses of the study data, will be 
prepared as a separate document and finalized before database lock. Any deviation from the original 
SAP will be described and justified in the final report, as appropriate. The procedure for accounting 
for missing, unused and spurious data will be included in the SAP. 
All statistical analyses will be performed by Novum Pharmaceutical Research Services and conducted 
using the Statistical Analysis System (SAS®), Version 9.4 or higher. Datasets will be prepared using 
headings from Clinical Data Interchange Standards Consortium (CDISC) Study Data Tabulation 
Model (SDTM) implementation for human clinical trials and Analysis Dataset Model (ADaM). 
11.2 Determination of Sample Size 
For the primary endpoint analysis (proportion of patients in the PP population who are considered to 
be a Therapeutic Cure on Day 28 ± 4), sample size is estimated for therapeutic equivalence of the 
Test to the Reference product. 
Based on data from a previous bioequivalence study conducted to support approval of the first generic 
product of permethrin cream, 5%, the therapeutic cure rate (pR) of the Reference product (Elimite™ 
permethrin cream 5%) is expected to be about 88% in the PP population. Assuming that the 
Therapeutic Cure rate for the Test group (pT) is an absolute difference of 5% lower than the Reference 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 31 of 42 
 
 
group (i.e., pT-pR = -5%), a sample size of 107 patients in each active group in PP population will 
provide at least 90% power to demonstrate therapeutic equivalence (i.e., the 90% confidence interval 
[Yates’ continuity corrected] on pT-pR is within a defined equivalence range [-20%, +20%]). 
To allow for approximately 14% of patients who may drop out from the study or are otherwise non-
evaluable, approximately 250 patients (125 in each treatment group) will be randomized, such that 
there will be an estimated 214 patients (107 per group) in the PP population for statistical evaluation 
of therapeutic equivalence.  
11.3 Study Populations 
11.3.1 Per-Protocol Population 
The PP population will include: 
• 
Met the inclusion/exclusion criteria as defined in this protocol at Visit 1. 
• 
Did not take any prohibited medications throughout the study. 
• 
Did not have any significant deviations from the protocol. 
• 
Did not develop any concurrent dermatological condition or illness exhibiting symptoms 
similar to scabies, or symptoms that in the Investigator’s opinion would interfere with 
endpoint assessments. 
• 
Completed the last study visit (Visit 3) Day 28 ± 4. 
Patients will be included in the PP population as treatment failures in the final analysis on Day 28 
(provided they had no significant protocol deviations) if they 1) withdrew from the study because 
of lack of efficacy, 2) show therapeutic cure at Day 14 ± 4 but re-infestation at Day 28 ± 4, or 3) 
do not respond to the initial treatment and have new lesions or microscopic confirmation of mites, 
ova, or fecal matter on Day 14 ± 4. 
11.3.2 Safety Population 
The safety population will include all patients who are randomized who applied at least one dose 
of the assigned study product. 
11.4 Baseline Comparability 
Baseline comparability of all treatment groups will be evaluated separately in the PP and Safety 
populations. The following baseline demographics (determined from their initial study visit) will be 
evaluated: 
• 
Age (years) 
• 
Gender (male/female) 
• 
Ethnicity (Hispanic/non-Hispanic) 
• 
Race (White, Black/African American, Native Hawaiian or Other Pacific Islander, Asian, 
American Indian or Alaska Native, Other) 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 32 of 42 
 
 
• 
Baseline severity score of nocturnal itching 
• 
Severity of lesion count infestation pretreatment (mild, moderate, severe) 
Summary tables by treatment group will be presented. Continuous variables will be summarized 
using descriptive statistics (number of observations, median, minimum, maximum, mean and standard 
deviation). Categorical variables will be summarized using frequencies and percentage. Baseline 
treatment comparisons will be presented using Chi-Square or Cochran-Mantel-Haenszel (CMH) tests 
for the categorical variables, and Analysis of Variance (ANOVA) for the continuous variables. 
All data will be listed by treatment and patient. 
11.5 Efficacy Endpoint 
The primary efficacy endpoint is the proportion of patients in each treatment group with Therapeutic 
Cure (parasitological cure plus clinical cure) of scabies at the test-of-cure visit conducted at 
Day 28 ± 4. A parasitological cure is defined as failure to demonstrate microscopically the presence 
of scabies infestation (i.e., no living mites, no viable mite eggs, and no mite fecal matter present). A 
clinical cure is defined as visual evidence of absence of new lesions and healing of original lesions, 
regardless the presence of post-scabietic nodules (i.e., post-scabietic nodules need not be considered 
as new lesions or persistence of old lesions). 
Patients who do not respond to the initial treatment and have new lesions or microscopic confirmation 
of mites, ova, or fecal matter on Day 14 ± 4 will be treated as treatment failure in the final analysis on 
Day 28.  
11.6 Efficacy Analyses 
Primary Analysis: 
Therapeutic equivalence of the Test product to the Reference product based on the primary endpoint 
will be evaluated in the PP population. If the 90% confidence interval on the absolute difference 
between the proportion of patients who are considered a Therapeutic Cure (primary) in the Test and 
Reference groups is contained within the range [-20%, +20%] then therapeutic equivalence of the 
Test product to the Reference product will be considered to have been demonstrated. 
Supportive Analyses: 
The following supportive analyses will be performed for the primary endpoint: 
1. The primary analysis will be performed including patients who completed Visit 2 within 
14 ± 2 days and Visit 3 within 28 ± 4 days. 
2. The primary analysis will be performed including patients who completed Visit 2 within 
14 ± 2 days and Visit 3 between Day 26 and Day 32, inclusive. 
3. The primary analysis will be performed including patients who completed Visit 2 within 
14 ± 2 days and Visit 3 within 28 ± 2 days. 
To declare therapeutic equivalence of the Test product to the Reference product, therapeutic 
equivalence must be demonstrated for only the primary analysis. 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 33 of 42 
 
 
11.7 Treatment-by-Site Interaction and Pooling of Clinical Sites 
As this is a multiple-site study, the interaction of treatment-by-site may be evaluated for the primary 
efficacy endpoint in the PP population (for equivalence testing). The treatment-by-site interaction will 
be evaluated by the Breslow-Day test for homogeneity of the odds ratio at the 5% significance level 
(p < 0.05). A site(s) with a low enrollment rate(s) may be pooled with its geographically closest site, 
so as to avoid bias in the estimation of a treatment-by-site interaction effect. The pooling will be done 
for low enrolling sites that account for less than 4-7% of the total number of patients in the PP 
population at the site with the highest enrolling rate in the PP population. If the treatment-by-site 
interaction term is found to be statistically significant (p < 0.05) for the primary endpoint, then the 
interaction term will also be assessed for clinical relevance before pooling the data across sites. This 
will include examination of Therapeutic Cure rates at each site where sample sizes per treatment may 
be influential in the assessment of the interaction. 
11.8 Safety Analysis 
Adverse events will be classified using standard MedDRA terminology Version 20.0 or higher and 
summarized by treatment group. Summary tables comparing the type, incidence, date of onset, date of 
resolution, severity, action taken, outcome and Investigator’s opinion of relationship to the study 
product will be prepared by treatment group. If sufficient data exist, AE frequencies will be compared 
between treatments using Fisher’s exact test or a similar test in the Safety population. 
Signs and symptoms of scabies will not be considered AEs, unless in the Investigator’s opinion, they 
have increased in frequency and/or severity to such an extent that the Investigator/patient considers 
that it is in the patient’s best interest to be dropped from continued participation in the study and 
given alternative therapy for their condition. 
Concomitant medication use during the study will be tabulated by patient. 
12.0 REGULATORY OBLIGATIONS 
12.1 Institutional Review Board 
The study protocol, ICF, Investigator's Brochure, or package insert (as applicable), and any specific 
advertising will be submitted to, and approved by, an IRB before the start of the study. A form must 
be signed by the chairman or designee of the IRB noting the approvals. This notification of the 
board's approval along with a description by profession and gender of the board's composition will be 
provided to the Sponsor. 
12.2 Study Documentation 
This study will be conducted in compliance with the protocol; GCP and all applicable regulations, 
including the Federal Food, Drug and Cosmetics Act, US applicable Code of Federal Regulations 
(title 21), parts 50, 56, 312, 320, and any IRB requirements relative to clinical studies; and the 
Declaration of Helsinki, June 1964, as modified by the 64th World Medical Association General 
Assembly, October 2013.16-19 The Investigator will permit trial-related monitoring, audits, IRB review 
and regulatory inspections providing direct access to source data/documents. 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 34 of 42 
 
 
12.2.1 Protocol 
The Investigator indicated on FDA Form 1572 will act as the Principal Investigator at each study 
site. Protocols will be noted as approved by placement of the Novum Representative’s signature 
on the cover page. The Sponsor of the study will also approve the protocol by having a study-
responsible individual sign the protocol cover page. The Principal Investigator will sign the 
protocol signature page indicating their agreement to conduct the study according to the protocol. 
12.2.2 Informed Consent 
An ICF that includes all of the relevant elements currently required by FDA, ICH, and local state 
regulations will be provided to each prospective study patient before enrollment into the study. 
The type and method of study, tests to be administered, any potential or possible hazards, and the 
patient's right to withdraw from the study at any time will be explained to the patients by the 
Investigator or designee. Once the Investigator or designee is assured that an individual candidate 
understands the implications of participating in this study, the patient will be asked to give 
consent by signing and dating in the appropriate areas of the ICF. The Investigator or designee 
will also sign and date the form, along with a staff member who will sign the ICF as a witness to 
verify that the patient has indeed received information. If any other language is required, 
translation will be performed by a certified translator. A copy of the ICF will be provided to the 
patient. For patients who are considered minors in the state the study is being conducted (< 18 
years in most states) the parent or legal guardian should sign the consent form and the child will 
be required to sign a patient “assent” form, as appropriate. Patients 11-17 years of age will read 
and sign an IRB-approved assent form and patients 6-10 years of age will provide verbal assent. 
Patients 2-5 years of age will be exempt from providing assent based on the child’s 
comprehension and cognitive skills. 
12.2.3 Protocol and Informed Consent Changes 
Sponsor approved changes to the protocol or the ICF will be implemented as revisions to the 
original documents and will require additional review and approval by the IRB. Revisions to the 
original protocol will be documented in amendments, incorporated as a preface to the new 
version. Any revision that substantially alters the study design or increases potential risk to the 
patient requires the patient’s consent to continue in the study. The approvals will be processed in 
accordance with the established IRB procedures. Copies of all protocol and ICF 
amendments/revisions, along with letters noting IRB approval, will be submitted to the Sponsor. 
12.2.4 Source Documents and Electronic Case Report Forms (eCRF) 
All patients will be identified by initials, date of birth and a unique patient number. Source 
documents will be used to record all study-related data. Source document entries will be used to 
complete eCRFs. A set of eCRFs will be completed for each patient randomized in the study. All 
data and eCRFs will be reviewed, evaluated and signed by the Investigator. 
The original source documents and a copy of the corresponding eCRFs will be retained by the 
Investigator. Patients who terminate early from the study will have the Visit 3 (End of Study) 
source/eCRF completed. 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 35 of 42 
 
 
12.2.5 Drug Accountability 
All study product receipt, inventory, dispensing, dosing and reconciliation records will be 
maintained in compliance with federal regulations. The study product will be dispensed to 
qualified study patients according to established procedures. At the end of the study (after the 
database has been locked) all used and unused study product will be returned to Sponsor or 
designee. 
12.2.6 Drug Storage 
Study product will be stored at controlled room temperature 20-25°C (68-77°F) [USP Controlled 
Room Temperature] in a secure place with access by authorized individuals only. The 
Investigator will be responsible for maintaining accurate records of drug receipt, dispensing, and 
return. After finalizing the study report, all partially used and unused study product will be 
returned to Sponsor or designee. 
12.2.7 Retention of Reserve Samples 
For every study product shipment received at the Investigator site, the Investigator (or designee) 
will randomly select at least one block of study product for retention, unless otherwise instructed 
by the Sponsor and/or Novum. These retention samples should be stored under the appropriate 
storage conditions for a minimum of 5 years following the application approval or, if not 
approved, at least 5 years after the completion of the study. Retention samples should not be 
returned to Sponsor/CRO/packaging group at any time. 
12.2.8 Pregnancies 
Patients with a positive pregnancy test during screening will not be enrolled in the study. Patients 
who report that they have become pregnant during the study or have a positive pregnancy test at 
Visit 3 will be followed to completion of the pregnancy. The pregnancy will be reported as an 
AE. 
Female patients of childbearing potential must have been using and must agree to continue to use 
accepted methods of birth control, throughout the study. Acceptable methods of birth control 
include total abstinence, intrauterine device, a double-barrier method (such as condom with 
spermicide or diaphragm with spermicide), oral, transdermal, injected, or implanted non-
hormonal or hormonal contraceptive throughout the study. Female patients using hormonal 
contraceptives should have been on the same product/dosing regimen for at least 28 days before 
Visit 1 and should not change this regimen during the study. A sterile sexual partner is not 
considered an adequate form of birth control. Before study enrollment women of childbearing 
potential must be advised of the importance of avoiding pregnancy during study participation. 
A negative result of a urine pregnancy test having a minimum sensitivity of at least 50 mIU/mL 
for human chorionic gonadotropin (hCG) should be obtained, before study participation. 
Pregnancy testing will be performed at Visits 1 and 3 and the results of all pregnancy tests 
(positive or negative) will be documented. 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 36 of 42 
 
 
If following initiation of study treatment, it is subsequently discovered that a study patient is 
pregnant or may have been pregnant at the time of study product exposure, the study product will 
be permanently discontinued. The Principal Investigator or designee must immediately notify the 
Medical Monitor of this event. Reporting timelines and Novum/Sponsor contact will be 
consistent with SAE reporting guidelines (i.e., pregnancies will be reported to the 
Sponsor/Novum within 24 hours to the contacts listed in section 10.8.2). 
Protocol-required procedures for study discontinuation and follow-up must be performed on the 
patient. Other appropriate pregnancy follow-up procedures should be considered if indicated. All 
follow-up information regarding the course of the pregnancy, including perinatal and neonatal 
outcome will be communicated as per the above guidelines. Infants should be followed for a 
minimum of eight weeks after birth. 
12.2.9 Reporting Safety Information to the IRB 
The Investigator must promptly report to the Investigator’s IRB all unanticipated problems 
involving risks to patients. This includes death from any cause and all SAEs occurring during the 
study, regardless of the assessed causality.20 
12.2.10 Record Retention 
All drug accountability records, eCRFs, source data and related regulatory documents must be 
retained for at least two years following completion of the study or Test product approval for 
marketing by the FDA. 
12.2.11 Study Monitoring and Auditing 
Novum will be responsible for monitoring the study according to GCP and applicable regulations. 
Monitoring visits are for the purpose of confirming adherence to the protocol and to verify 
complete and accurate data collection. The clinical site will make all records associated with the 
study available to Novum’s representative during such visits and audits. 
The study may be subject to audit by the Sponsor, Sponsor Representative or by regulatory 
authorities. If such an audit occurs the Investigator must agree to allow access to required patient 
records. By signing this protocol, the Investigator grants permission to personnel from the 
Sponsor, its representatives and appropriate regulatory authorities for on-site monitoring of all 
appropriate study documentation, as well as on-site review of study procedures. 
12.2.12 End of the Trial 
The end of the trial is defined as the time at which the last patient has completed their last visit in 
the study. Upon completion of the study, the study product will no longer be available to the 
patient but the Investigator can, at their discretion, discuss alternative treatments with the patient. 
12.2.13 Clinical Study Report 
At the end of the study a full report per requirements of Sponsor and regulatory authorities will be 
prepared which will include a narrative of the clinical conduct and results of the study, a 
statistical report including a description of the analysis performed, and other documentation as 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 37 of 42 
 
 
may be appropriate. The report will be in electronic format according to eCTD and ICH 
formatting standards and guidelines.21 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 38 of 42 
 
 
13.0 REFERENCES 
1 
CDC. http://www.cdc.gov/parasites/scabies/. Centers for Disease Control and Prevention. 
2 
AAD. https://www.aad.org/dermatology. American Acedemy of Dermatology. 
3 
Inc, P. P. Prescribing Information for Elimite™ Cream (permethrin) 5%.  (2012). 
4 
ICH. Choice of Control Group and Related Issues in Clinical Trials E10.  20 July (2000). 
5 
FDA. Draft Guidance for Industry: Topical Dermatological Drug Product NDAs and ANDAs ---
In Vivo Bioavailability, Bioequivalence, In Vitro Release, and Associated Studies. U.S. 
Department of Health and Human Services, Center for Drug Evaluation and Research (CDER) 
(1998). 
6 
Alpharma. FDA Approval Package for Permethrin Cream 5% (Application # 074806).  (1998). 
7 
FDA. Draft Guidance on Permethrin Cream.  (2017). 
8 
Westlake, W. J. Statistical aspects of comparative bioavailability trials. Biometrics 35, 273-280 
(1979). 
9 
FDA. 21CFR 320 Procedures for Determining the Bioavailability or Bioequivalence of Drug 
Products. Department of Health and Human Services, Subchapter D-Drugs for Human Use 5 
(2014). 
10 
FDA. Guidance for Industry: Statistical Approaches to Establishing Bioequivalence. US 
Department of Health and Human Services, CDER (2001). 
11 
FDA. Guidance for Industry. Handling and Retention of BA and BE Testing Samples U.S. 
Department of Health and Human Services, Food and Drug Administration, Center for Drug 
Evaluation and Research (CDER). May (2004). 
12 
Walter, B. et al. Comparison of dermoscopy, skin scraping, and the adhesive tape test for the 
diagnosis of scabies in a resource-poor setting. Archives of dermatology 147, 468-473, 
doi:10.1001/archdermatol.2011.51 (2011). 
13 
Park, J. H., Kim, C. W. & Kim, S. S. The diagnostic accuracy of dermoscopy for scabies. Annals 
of dermatology 24, 194-199, doi:10.5021/ad.2012.24.2.194 (2012). 
14 
Leung, V. & Miller, M. Detection of scabies: A systematic review of diagnostic methods. The 
Canadian journal of infectious diseases & medical microbiology = Journal canadien des 
maladies infectieuses et de la microbiologie medicale / AMMI Canada 22, 143-146 (2011). 
15 
Furue, M. et al. Verbalizing extremes of the visual analogue scale for pruritus: a consensus 
statement. Acta dermato-venereologica 93, 214-215, doi:10.2340/00015555-1446 (2013). 
16 
FDA. 21CFR 320 Procedures for Determining the Bioavailability or Bioequivalence of Drug 
Products. Department of Health and Human Services, Subchapter D-Drugs for Human Use 5 
(2017). 
17 
FDA. 21CFR Part 50 Protection of Human Subjects. Department of Health and Human Services, 
Subchapter A-General 1 (2017). 
18 
FDA. 21CFR Part 56 Institutional Review Boards. Department of Health and Human Services, 
Subchapter A-General 1 (2017). 
19 
World Medical Association Declaration of Helsinki: ethical principles for medical research 
involving human subjects. Jama 310, 2191-2194, doi:10.1001/jama.2013.281053 (2013). 
20 
FDA. 21CFR 312.32: IND Safety Reporting.  (2010). 
21 
ICH. Structure and Content of Clinical Study Reports E3.  Step 4 version (1996). 
 
 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 39 of 42 
 
 
14.0 APPENDICES 
14.1 APPENDIX A: RATING OF SCABIES SIGNS AND SYMPTOMS 
PRURITUS 
At each clinic visit, patients will be asked to rate the severity of pruritus (overall itch intensity and 
effect of itching on nighttime sleep) on the following 4-point scale. 
  
0 = none (complete absence of itching) 
 
1 = mild (slight itching, no sleep loss) 
 
2 = moderate (definitely present, interrupts sleep) 
 
3 = severe (marked, intense, cannot sleep) 
LESION COUNT 
At each clinic visit, the lesion count will be evaluated and rated as follows: 
 
< 50 = mild 
 
50-100 = moderate 
> 100 = severe 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 40 of 42 
 
 
14.2 APPENDIX B: DERMOSCOPY AND MICROSCOPY FOR SCABIES DIAGNOSIS 
SKIN SCRAPING/MICROSCOPY 
Skin scrapings will be obtained with a sterile scalpel after the application of 1 drop of mineral oil onto 
the lesion. The scraped material will be transferred to a slide and covered with a cover slip. Reading 
is to be performed immediately under a microscope, or within 3 hours, at 40 X magnification. The 
number of scraped sites until the examination is declared negative will be left to the recognition of the 
attending Investigator in relation to the clinical picture. 
A single scraping is not considered sufficient to adequately define parasitological cure. 
 
The best efforts should be made to attempt valid skin scrapings for microscopic examinations, even in 
case of virtually healed lesions as appropriate.  
 
 
 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 41 of 42 
 
 
14.3 APPENDIX C: PRODUCT INSERT FOR ELIMITE™ 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream (permethrin) 5% 
(Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Confidential Protocol 71675502  Rev 1  November 3rd, 2017  Encube Ethicals   Page 42 of 42 
 
 
14.4 APPENDIX D: AMENDMENTS TO THE PROTOCOL 
Amendment 
Date 
 
1 
10/31/2017 
 
The following revisions were made to the protocol dated 05/02/2017. 
• 
Removed Yates’ correction in the primary analysis. 
• 
Removed the secondary endpoint and related analysis language. 
• 
Added supportive analyses. 
• 
Revised the PP population and Safety population inclusion criteria. 
• 
Added justification for the change in statistics and deviation from the FDA guidance. 
• 
Made minor typographical corrections throughout the document. 
 
 





SAP_001.pdf: 
COVER PAGE 
STATISTICAL ANALYSIS PLAN    
November 2, 2017 
Final Version 1.0              
NCT03178942 
 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream 
(permethrin) 5% (Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Protocol Number: 71675502 
Novum Study Number: 71675502 
 
 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
 
Permethrin Cream, 5% 
 
       
 
 
        Protocol / Study No. 71675502 
 
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                              Encube Ethicals 
                                    Page 1 of 55 
            
STATISTICAL ANALYSIS PLAN                 
 
 
A Randomized, Double-Blind, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic 
Equivalence of Permethrin Cream, 5% (Encube Ethicals) Compared to Elimite™ Cream 
(permethrin) 5% (Prestium Pharma, Inc.) in the Treatment of Scabies 
 
 
Protocol Number: 71675502 
Novum Study Number: 71675502 
 
 
Sponsor: 
Encube Ethicals 
Unit No. 24, Steelmade Indl Estate, 
Opposite To Jalaram Store, 
Marol, Andheri East, Mumbai, 
Maharashtra 400059, India 
 
 
Contract Research Organization: 
Novum Pharmaceutical Research Services 
225 W. Station Square Drive, Suite 200 
Pittsburgh, PA 15219 
 
November 2, 2017 
Final Version 1.0 
 
 




NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
 
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Revision History 
 
VERSION 
DATE 
DESCRIPTION OF REVISIONS 
REVISED 
BY 
Draft 1.0 
July 26, 2017 
New Document 
Jianhua Liu 
Final 1.0 
November 2, 2017 
Incorporate client comments and finalize SAP 
Jianhua Liu 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
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List of Abbreviations and Definition of Terms 
ADaM  
 
Analysis Data Model 
AE 
 
 
Adverse Event 
BP 
 
 
Blood Pressure 
C 
 
 
Celsius 
CRF 
 
 
Case Report Form 
CDISC 
 
Clinical Data Interchange Standards Consortium 
CRO  
 
Contract Research Organization 
F 
 
 
Fahrenheit 
FDA  
 
Food and Drug Administration 
HR 
 
 
Heart Rate 
Hg 
 
 
Mercury 
HIV 
 
 
Human Immunodeficiency Virus 
ICF 
 
 
Informed Consent Form 
ICH 
 
 
International Conference on Harmonization 
IND 
 
 
Investigational New Drug 
IWRS  
 
Interactive Web Response System 
LOCF  
 
Last Observation Carried Forward 
MedDRA 
 
Medical Dictionary for Regulatory Activities 
mITT  
 
Modified Intent-to-Treat 
LOCF  
 
Last Observation Carried Forward 
OGD  
 
The Office of Generic Drugs 
PP 
 
 
Per-Protocol 
SAE 
 
 
Serious Adverse Event 
SAP 
 
 
Statistical Analysis Plan 
SAS 
 
 
Statistical Analysis System 
SDTM  
 
Study Data Tabulation Model 
USA  
 
United States of America 
 
 


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TABLE OF CONTENTS 
1. INTRODUCTION .......................................................................................................................8 
2. OBJECTIVES ..............................................................................................................................8 
3. OVERALL STUDY DESIGN .....................................................................................................8 
4. RANDOMIZATION AND BLINDING....................................................................................11 
5. SAMPLE SIZE ..........................................................................................................................11 
6. STUDY ENDPOINT .................................................................................................................11 
7. STUDY POPULATIONS ..........................................................................................................12 
8. STATISTICAL ANALYSIS METHODS .................................................................................12 
8.1 Baseline Characteristics ......................................................................................................13 
8.1.1 Patient Disposition ......................................................................................................13 
8.1.2 Demographic and Other Baseline Characteristics .......................................................13 
8.1.3 Medical History ...........................................................................................................14 
8.1.4 Concomitant Medications ...........................................................................................14 
8.1.5 Pregnancy Test ............................................................................................................14 
8.2 Efficacy Analyses................................................................................................................14 
8.2.1 Primary Efficacy Analysis ..........................................................................................14 
8.2.2 Supportive Analyses ....................................................................................................15 
8.2.3 Treatment-by-Site Interaction and Pooling of Clinical Sites ......................................16 
8.3 Safety Analysis ...................................................................................................................16 
8.3.1 Adverse Events ............................................................................................................16 
8.3.2 Vital Signs ...................................................................................................................17 
8.4 Multiple Comparisons .........................................................................................................17 
8.5 Methods for Handling Missing Data ...................................................................................17 
8.6 Interim Analyses .................................................................................................................17 
9. TABLE, LISTING AND FIGURE SHELLS ............................................................................17 
T14.1.1 Summary of  Patient's Disposition ...............................................................................19 
T14.1.2 Summary of Protocol Deviations ................................................................................20 
T14.1.3.1 Summary of Patients Excluded from Efficacy Analysis  (Population 
Determination) ...................................................................................................................21 
T14.1.3.2 Summary of Patients Included in Analysis Population by Study Center .................22 
T14.1.4 Summary of Demographic Data and Baseline Characteristics (Safety 
Population) .........................................................................................................................24 
T14.1.5 Summary of Demographic Data (Per-Protocol Population) ........................................25 
T14.1.6 Summary of Microscopic Evaluation of Scabies  (Per-Protocol Population) .............26 
T14.1.7 Summary of Frequency of Scabies Signs and Symptoms Rating  (Per-Protocol 
Population) .........................................................................................................................27 
T14.1.8.1 Summary of Equivalence Analysis Results of Primary Efficacy Endpoint  
(Proportion of Patients in each Treatment Group with Therapeutic Cure 
(Parasitological Cure plus Clinical Cure)  of Scabies at Day 28 ± 4) (Per-Protocol 
Population) .........................................................................................................................28 


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T14.1.8.2 Sensitivity Analysis Summary of Equivalence Analysis Results of Primary 
Efficacy Endpoint  (Proportion of Patients in each Treatment Group with 
Therapeutic Cure (Parasitological Cure plus Clinical Cure)  of Scabies at Day 28 
± 4) (Safety Population) .....................................................................................................28 
T14.1.9.1 Supportive Analysis #1: Summary of Equivalence Analysis Results of 
Primary Efficacy Endpoint  (Per-Protocol Population) .....................................................29 
T14.1.9.2 Supportive Analysis #2: Summary of Equivalence Analysis Results of 
Primary Efficacy Endpoint  (Per-Protocol Population) .....................................................29 
T14.1.9.3 Supportive Analysis #3: Summary of Equivalence Analysis Results of 
Primary Efficacy Endpoint  (Per-Protocol Population) .....................................................29 
T14.1.10 Summary of Frequency of Patient Pruritus Assessment  (Per-Protocol 
Population) .........................................................................................................................30 
T14.1.11 Overall Summary of Adverse Events ........................................................................31 
T14.1.12 Summary of Frequency of Adverse Events by Body System  (Safety 
Population) .........................................................................................................................32 
T14.1.13 Summary of Frequency of Adverse Events by Relationship  (Safety 
Population) .........................................................................................................................33 
T14.1.14 Summary of Frequency of Adverse Events by Severity  (Safety Population) ..........34 
T14.1.15 Summary of Frequency of Serious Adverse Events  (Safety Population) .................35 
T14.1.16 Summary of Vital Signs  (Safety Population) ...........................................................36 
T14.1.17 Summary of Frequency of Patients with Re-Infestation from Day 14 
(treatment success) to Day 28 (treatment failure) (Per-Protocol Population)....................37 
T14.1.18 Summary of Frequency of Patients who are Therapeutic Failures on Day 14 
± 4  (Per-Protocol Population) ...........................................................................................38 
L16.2.1 Listing of Discontinued Patients ..................................................................................39 
L16.2.2 Listing of Protocol Deviations .....................................................................................40 
L16.2.3 Patients Excluded from the Per-Protocol Population ..................................................41 
L16.2.4.1 Listing of Demographic Data ...................................................................................42 
L16.2.4.2 Listing of Medical History .......................................................................................43 
L16.2.4.3 Listing of Concomitant Medication ..........................................................................44 
L16.2.4.4 Listing of Treatment for Family Members/Close Contacts ......................................45 
L16.2.5.1 Listing of Visit Date Information .............................................................................46 
L16.2.5.2 Listing of Drug Administration ................................................................................47 
L16.2.6.1 Listing of Scabies Signs and Symptoms Rating and Microscopic Evaluation 
of Scabies ...........................................................................................................................48 
L16.2.6.2 Listing of Patient Pruritus Assessment .....................................................................49 
L16.2.6.3 Listing of Investigator Evaluator Initials On Scabies Signs & Symptoms 
Rating .................................................................................................................................50 
L16.2.7 Listing of Adverse Events by Treatment .....................................................................51 
L16.2.8.1 Listing of Pregnancy Test Results ............................................................................52 
L16.2.8.2 Listing of Vital Signs ................................................................................................53 
F15.1.1 Histogram of Proportion of Patients with Therapeutic Cure on Day 28 ±4 ................54 
Reference: ......................................................................................................................................55 


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1. INTRODUCTION 
This Statistical Analysis Plan (SAP) is based on the final Clinical Study Protocol 71675502 [Rev 
1] dated 10/31/2017. The SAP provides details on the planned statistical methodology for the 
analysis of the study data. The SAP also outlines the statistical programming specifications for 
the tables, listings and figures. 
This SAP describes the study endpoints, derived variables, anticipated data transformations and 
manipulations, and other details of the analyses not provided in the study protocol. This SAP 
therefore outlines in detail all other aspects pertaining to the planned analyses and 
presentations for this study. 
The following documents were reviewed in preparation of this SAP: 
 Final Clinical Study Protocol 71675502 [Rev 1] dated 10/31/2017.  
 Case Report Form Booklet Version 1.0 for Novum Study No. 71675502 
The reader of this SAP is encouraged to also read the clinical protocol for details on the 
conduct of this study, and the operational aspects of clinical assessments and timing for 
completing a patient in this study. 
2. OBJECTIVES 
The objectives of this study are to: 
1. 
Evaluate the therapeutic equivalence of the Test formulation, Permethrin Cream, 5% 
(Encube Ethicals) to the marketed product, Elimite™ Cream (permethrin) 5% (Prestium 
Pharma, Inc.) in patients with scabies. 
2. 
Compare the safety of Test and Reference treatments in patients with scabies. 
3. OVERALL STUDY DESIGN 
This randomized, double-blind, parallel-design, multiple-site study is designed to evaluate the 
therapeutic efficacy and safety of a generic Permethrin Cream, 5% (Encube Ethicals) compared 
to the FDA Reference Listed Drug (RLD), Elimite™ Cream (permethrin) 5% (Prestium Pharma, 
Inc.) in patients with scabies. 
Before any study-specific procedures are performed, all patients will read and sign the IRB-
approved informed consent that meets all criteria of current FDA and International Conference 
of Harmonisation (ICH) regulations. For patients who are considered minors in the state the 
study is being conducted (< 18 years in most states) the parent or legal guardian should sign the 
consent form and the child will be required to sign a patient “assent” form, as appropriate. 
Patients 11-17 years of age will read and sign an IRB-approved assent form and patients 6-10 


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years of age will provide verbal assent. Patients 2-5 years of age will be exempt from providing 
assent based on the child’s comprehension and cognitive skills.  
Approximately 250 eligible patients, 2 years of age and older with a clinical diagnosis of active 
scabies based on signs and symptoms and confirmation of microscopic evidence of scabies mites 
in the skin will be randomized in a 1:1 ratio (Test: Reference) to one of the two study products as 
follows: 
 Test: Permethrin Cream, 5%, (Encube Ethicals) 
 Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) 
Patients will be instructed to self-administer a single dose of study product or, if patient is a 
child, then parent/guardian will apply study product to him/her on Day 1 according to the dosing 
instructions provided. A second application may be required if presence of scabies infestation is 
microscopically demonstrated (i.e., living mites, viable mite eggs, or mite fecal matter present) at 
Visit 2. The second dose will be self-administered by the patient or if patient is a child, then 
parent/guardian will apply study product to him/her at Visit 2. Eligible household members and 
close contacts of the patient will be offered permethrin cream (if they are in need of treatment) as 
a method to reduce cross-contamination within a household. Additionally, household members 
will be requested to follow the standard hygiene practices. Patients whose household members 
are not willing to comply with the standard of care for Scabies management (i.e., use of generic 
permethrin cream and standard hygiene practices) will not be enrolled in the study.  
During the study, patients will visit the clinical center for a total of three scheduled visits: 
 Visit 1 (Day 1): Screening/Baseline 
 Visit 2 (Day 14 ± 4): Interim Visit 
 Visit 3 (Day 28 ± 4): End of Study or Early Termination 
Final assessments will be carried out at Visit 3 (Day 28 ± 4), which is the test-of-cure visit. The 
test-of-cure visit will occur 4 weeks (± 4 days) after the end of the single application treatment 
on study Day 1 or 2 weeks (± 4 days) after the end of a second application, if necessary, on study 
Visit 2. Therapeutic cure of scabies will be evaluated based on microscopic evidence of absence 
of scabies infestation (i.e., no living mites, no viable mite eggs, and no mite fecal matter), visual 
evidence of absence of new lesions and healing of original lesions, regardless of the presence of 
post-scabetic nodules (i.e., post-scabetic nodules need not be considered as new lesions or 
persistence of old lesions). The primary statistical analysis of interest is the proportion of patients 
in each treatment group with therapeutic cure (parasitological cure plus clinical cure) of scabies. 


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      Figure 1 Study Schematic 
 
     
Visit 1 
Screening/Baseline 
(Day 1) 
Visit 2 
Interim Visit 
(Day 14 ± 4) 
Visit 3 
(Day 28 ± 4) 
End of Study 
or Early Termination 
Informed Consent 
X 
 
 
Medical history and 
Baseline Demographics 
X 
 
 
Vital Signs 
X 
 
X 
Adverse Events 
X 
X 
X 
Concomitant Medications 
X 
X 
X 
Microscopic Examination 
X 
X 
X 
Scabies Signs and 
Symptoms Rating 
(pruritus, lesion count)  
X 
X 
X 
Urine Pregnancy Test 
X 
 
X 
Review 
Inclusion/Exclusion 
Criteria 
X 
 
 
Collect and Review Diary 
 
X 
X 
Provide Diary 
X 
X 
 
Dispense Study Product 
X 
X* 
 
Collect and Weigh Study 
Product 
 
X 
X* 
*If retreatment is necessary, the originally dispensed (i.e., at Visit 1) study product will be 
dispensed at Visit 2 and collected at Visit 3. 
 


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4. RANDOMIZATION AND BLINDING 
The study product will be randomized, packaged and blinded by an independent packaging 
company. Randomization will be pre-planned according to a computer-generated randomization 
schedule. All randomized study products will be blinded and packaged in sealed boxes. Each 
block will contain two patients’ worth of product (1 Test and 1 Reference). Each patient kit will 
include 1 x 60 gram tube of study product, which should be sufficient for full treatment. 
The randomization number will be a unique four-digit number. Patient numbers will be assigned 
immediately before dispensing of study product and in ascending sequential order, beginning 
with the lowest available number at the study site. Each patient kit and each dispensed study tube 
should include the four-digit patient number on the label. 
At the end of the study, after all the clinical data have been entered and the study database has 
been locked, a copy of the randomization schedule will be sent to the statistician. 
The Investigator, staff at the study site, study monitors, and data analysis/management personnel 
will be blinded to the patient assignment.  
5. SAMPLE SIZE 
For the primary endpoint analysis (proportion of patients in the PP population who are 
considered to be a Therapeutic Cure on Day 28 ± 4), sample size is estimated for therapeutic 
equivalence of the Test to the Reference product. 
Based on data from a previous bioequivalence study conducted to support approval of the first 
generic product of permethrin cream, 5%, the therapeutic cure rate (pR) of the Reference product 
(Elimite™ permethrin cream 5%) is expected to be about 88% in the PP population. Assuming 
that the Therapeutic Cure rate for the Test group (pT) is an absolute difference of 5% lower than 
the Reference group (i.e., pT-pR = -5%), a sample size of 107 patients in each active group in PP 
population will provide at least 90% power to demonstrate therapeutic equivalence (i.e., the 90% 
confidence interval [Yates’ continuity corrected] on pT-pR is within a defined equivalence range 
[-20%, +20%]). 
To allow for approximately 14 % of patients who may drop out from the study or are otherwise 
non-evaluable, approximately 250 patients (125 in each treatment group) will be randomized, 
such that there will be an estimated 214 patients (107 per group) in the PP population for 
statistical evaluation of therapeutic equivalence.  
6. STUDY ENDPOINT 
The primary efficacy endpoint is the proportion of patients in each treatment group with 
Therapeutic Cure (parasitological cure plus clinical cure) of scabies at the test-of-cure visit 


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conducted at Day 28 ± 4. A parasitological cure is defined as failure to demonstrate 
microscopically the presence of scabies infestation (i.e., no living mites, no viable mite eggs, and 
no mite fecal matter present). A clinical cure is defined as visual evidence of absence of new 
lesions and healing of original lesions, regardless the presence of post-scabietic nodules (i.e., 
post-scabietic nodules need not be considered as new lesions or persistence of old lesions). 
Patients who do not respond to the initial treatment and have new lesions or microscopic 
confirmation of mites, ova, or fecal matter on Day 14 ± 4 will be treated as treatment failure in 
the final analysis on Day 28. 
7. STUDY POPULATIONS 
Per-Protocol (PP) Population 
The PP population will include: 
 Met the inclusion/exclusion criteria as defined in this protocol at Visit 1. 
 Did not take any prohibited medications throughout the study. 
 Did not have any significant deviations from the protocol. Did not develop any 
concurrent dermatological condition or illness exhibiting symptoms similar to 
scabies, or symptoms that in the Investigator’s opinion would interfere with 
endpoint assessments. 
 Completed the last study visit (Visit 3) Day 28 ± 4. 
Patients will be included in the PP population as treatment failures in the final analysis on 
Day 28 (provided they had no significant protocol deviations) if they 1) withdrew from the study 
because of lack of efficacy, 2) show therapeutic cure at Day 14 ± 4 but re-infestation at 
Day 28 ± 4, or 3) do not respond to the initial treatment and have new lesions or microscopic 
confirmation of mites, ova, or fecal matter on Day 14 ± 4. 
Safety Population 
The safety population will include all patients who are randomized who applied at least one dose 
of the assigned study product. 
8. STATISTICAL ANALYSIS METHODS 
If not otherwise specified, statistical significance is defined as p < 0.05 and is two-tailed. Data 
will be summarized with respect to demographic and baseline characteristics and safety 
variables. 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
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        Protocol / Study No. 71675502 
 
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For categorical variables, the number and percentage of each category within a parameter will be 
calculated for non-missing data. For continuous variables, statistics will include n, mean, standard 
deviation, median, minimum and maximum values. 
All statistical analyses will be conducted using SAS®, Version 9.4 or higher. Datasets will be prepared 
using headings from Clinical Data Interchange Consortium (CDISC), Study Data Tabulation Model 
(SDTM) implementation for human clinical trials, and ADaM (Analysis Dataset Model). 
8.1 Baseline Characteristics 
8.1.1 Patient Disposition 
The patient disposition information will be summarized by treatment. The number of patients 
randomized, treated with study medication will be tabulated by treatment. In addition, completion 
status and primary reason for withdrawal will be summarized by treatment. 
8.1.2 Demographic and Other Baseline Characteristics 
Baseline comparability of all treatment groups will be evaluated separately in the PP and Safety 
populations.  
The following baseline demographics (determined from their initial study visit) will be 
evaluated: 
 Age (years) 
 Sex (male/female) 
 Ethnicity (Hispanic/non Hispanic) 
 Race (White, Black/African American, Native Hawaiian or Other Pacific Islander, 
Asian, American Indian or Alaska Native, Other) 
 Baseline severity score of nocturnal itching 
 Severity of lesion count infestation pretreatment (mild, moderate, severe) 
Summary tables by treatment will be presented. Continuous variables will be summarized using 
descriptive statistics (n, mean, standard deviation, median, minimum, maximum). Categorical 
variables will be summarized using frequencies and percentage.  
Baseline comparability of the treatments will be presented using Chi-square test for the 
categorical variables, and Analysis of Variance for the continuous variables. 
All data will be listed by treatment and patient. 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
 
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                              Encube Ethicals 
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8.1.3 Medical History 
At Visit 1 patients will be questioned about medical history, including acute and chronic medical 
history and medical history relevant to their scabies.  
Medical history data will be listed by treatment and patient. 
8.1.4 Concomitant Medications 
All concomitant medication use within 6 months of Visit 1 and throughout the study will be 
recorded. 
All prior and concomitant medications taken since screening until the end of the study will be 
listed by treatment and patient. 
8.1.5 Pregnancy Test 
All females of childbearing potential will have a urine pregnancy test performed at Visit 1 and 
Visit 3.  
Pregnancy test results will be listed by treatment and patient. 
8.2 Efficacy Analyses 
8.2.1 Primary Efficacy Analysis 
Bioequivalence with Clinical Endpoints Analysis 
The proportion of patients in each treatment group with Therapeutic Cure is the primary efficacy 
endpoint of the study.  
The Per Protocol (PP) Population will be used for the analysis of equivalence. 
Based on the usual method used in OGD for binary outcomes, the 90% confidence interval for 
the difference in success proportions between test and reference treatment should be contained 
within [-0.20, +0.20]  (or [-20%, +20%] in percent) in order to establish equivalence.  
 
The compound hypothesis to be tested is:  
 
                                         versus   
 
                       


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
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                              Encube Ethicals 
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where       =   percent cure rate of test treatment  
                 =   percent cure rate of reference treatment.  
 
Let  
    =  sample size of test treatment group  
   =  number of cured patients in test treatment group  
    =  sample size of reference treatment group  
   =  number of cured patients in reference treatment group  
 
                      ,       and 
 
                                                    
  
  
 
where      =   estimated cure rate (%) of test treatment  
               =  estimated cure rate (%) of reference treatment.  
 
The 90% confidence interval for the absolute difference between the proportions of patients in 
test and reference who are considered a therapeutic cure (primary) will be calculated as follows: 
                                  
                                
If the 90% confidence interval0 for the absolute difference between the proportion of patients 
who are considered a therapeutic cure (primary) in the Test and Reference groups is contained 
within the range [-20% + 20%] then bioequivalence of the Test product to the Reference product 
will be considered to have been demonstrated for the primary endpoint. 
Sensitivity Analysis for Primary Efficacy Endpoint 
As a sensitivity analysis, the primary efficacy analysis will be performed on the safety 
population using LOCF. This analysis will use LOCF such that subjects with no post-dose data 
will be considered as non-responders. 
8.2.2 Supportive Analyses 
The following supportive analyses will be performed for the primary endpoint: 
1. The primary analysis will be performed including patients who completed Visit 2 
within 14 ± 2 days and Visit 3 within 28 ± 4 days. 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
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2. The primary analysis will be performed including patients who completed Visit 2 
within 14 ± 2 days and Visit 3 between Day 26 and Day 32, inclusive. 
3. The primary analysis will be performed including patients who completed Visit 2 
within 14 ± 2 days and Visit 3 within 28 ± 2 days. 
To declare therapeutic equivalence of the Test product to the Reference product, therapeutic 
equivalence must be demonstrated for only the primary analysis. 
8.2.3 Treatment-by-Site Interaction and Pooling of Clinical Sites 
As this is a multiple-site study, the interaction of treatment-by-site may be evaluated for the 
primary efficacy endpoint in the PP population (for equivalence testing). The treatment-by-site 
interaction will be evaluated by the Breslow-Day test for homogeneity of the odds ratio at the 5% 
significance level (p < 0.05). A site(s) with a low enrollment rate(s) may be pooled with its 
geographically closest site, so as to avoid bias in the estimation of a treatment-by-site interaction 
effect. The pooling will be done for low enrolling sites that account for less than 4-7% of the 
total number of patients in the PP population at the site with the highest enrolling rate in the PP 
population. If the treatment-by-site interaction term is found to be statistically significant 
(p < 0.05) for the primary endpoint, then the interaction term will also be assessed for clinical 
relevance before pooling the data across sites. This will include examination of Therapeutic Cure 
rates at each site where sample sizes per treatment may be influential in the assessment of the 
interaction. 
8.3 Safety Analysis 
Safety analysis will be conducted on safety population.   
8.3.1 Adverse Events 
All the adverse events (AEs) reported throughout the study will be coded and classified 
according to the MedDRA (Medical Dictionary for Regulatory Activities) coding dictionary 
(Version 20.0 or higher). Each adverse event is to be evaluated for date of start and end, 
seriousness, severity, causal relationship with the study drugs, action taken and outcome. 
All AEs will be listed by treatment and patient. 
A summary table of the number and percent of patients with AEs by system organ class, 
preferred term, and treatment will be presented. Each patient will be counted only once within 
each preferred term. 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
 
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                              Encube Ethicals 
                                    Page 17 of 55 
A frequency summary table of the number of AEs by system organ class, preferred term, 
severity, and treatment will be presented. Severity will be classified as “Mild”, “Moderate”, or 
“Severe”. 
Similarly, a frequency summary table of the number of AEs by system organ class, preferred 
term, and relationship to a study drug, and treatment will be presented. Relationship to a study 
drug will be classified as “Not Related” or “Related”.  
Adverse event frequencies will be compared between treatments using Fisher’s exact test. 
8.3.2 Vital Signs 
The patient’s vital signs will be recorded (heart rate, blood pressure, temperature and respiration 
rate) at Visit 1 and Visit 3. 
Descriptive summaries (number of observations, mean, standard deviation, minimum, median 
and maximum) will be provided by treatment and visit. 
All data will be listed by treatment and patient. 
8.4 Multiple Comparisons 
No multiple comparison adjustment will be made in this study. 
8.5 Methods for Handling Missing Data 
For demographic and baseline characteristics, each variable will be analyzed using all available 
data. Patients with missing data will be excluded only from analyses for which data are not 
available. 
8.6 Interim Analyses 
There is no interim analysis planned in this study. 
9. TABLE, LISTING AND FIGURE SHELLS 
The following shells are provided in order to provide a framework for the display of data from 
this study. These shells may not be reflective of every aspect of this study but are intended to 
show the general layout of the Tables, Listings and Figures that will be included in the final 
clinical study report. Tables, Listings and Figures are numbered following the ICH structure. 
Table headers, variables names and footnotes will be modified as needed following data 
analyses. All descriptive and inferential statistical analyses will be performed using SAS® 
statistical software Version 9.4 or higher, unless otherwise noted. 


Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 18 of 55 
 
 
 
 
 
TABLE, LISTING AND FIGURE SHELLS 
 
 
Programming note:  
Put Program Name in the footnote where it is stored, Location of Output stored, and Date and time when the output is 
generated. 
 
 


Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 19 of 55 
 
T14.1.1 Summary of  Patient's Disposition  
Patients Randomized 
Test  
N = xxx 
n (%) 
Reference  
N = xxx 
n (%) 
Total 
N = xxx 
n (%) 
 
 
 
 
Completed Study 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
Terminated Early 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
Adverse Event 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
Lack of efficacy 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
Protocol Deviation 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
Pregnancy 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
etc. 
 
 
 
 
 
 
 
Other 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
Test: Permethrin Cream, 5%, (Encube Ethicals) 
Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) 
                             N= number of patients randomized in that particular  group; n= number of patient with data available for that particular group;   
                             total % is based on N 
 
 
 
 
PROGRAM: L:\DEV\755\71675502\SAS\PGM\XXXX 
OUTPUT: L:\DEV\755\71675502\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm 
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Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 20 of 55 
 
T14.1.2 Summary of Protocol Deviations 
 
 
Test  
N = xxx 
n (%) 
Reference  
N = xxx 
n (%) 
Total 
N = xxx 
n (%) 
Total Patients with Protocol Deviations 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
Total Deviations 
xxx 
xxx 
xxx 
 
 
 
 
Lost to Follow-up 
xxx 
xxx 
xxx 
Missed Visit 
xxx 
xxx 
xxx 
Non-compliance with dosing requirements 
xxx 
xxx 
xxx 
Outside Visit Window 
xxx 
xxx 
xxx 
Restricted Medication Use 
xxx 
xxx 
xxx 
Randomized in Error 
xxx 
xxx 
xxx 
Other 
xxx 
xxx 
xxx 
Test: Permethrin Cream, 5%, (Encube Ethicals) 
Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) 
                             N= number of patients randomized in that particular group; n= number of patient with data available for that particular group;  
                             total % is based on N 
 
 
PROGRAM: L:\DEV\755\71675502\SAS\PGM\XXXX 
OUTPUT: L:\DEV\755\71675502\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm 
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Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 21 of 55 
 
T14.1.3.1 Summary of Patients Excluded from Efficacy Analysis  
(Population Determination) 
 
Test  
N = xxx 
n (%) 
Reference  
N = xxx 
n (%) 
Total 
N = xxx 
n (%) 
Safety Population 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
      Excluded from Safety population 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
PP Population 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
      Excluded from PP population  
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
      Inclusion/Exclusion criteria not met 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
      Non-compliant with dosing requirement 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
      Major protocol deviations 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
      etc. 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
    
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
Test: Permethrin Cream, 5%, (Encube Ethicals) 
Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.)                  
                             N= number of patients randomized in that particular group; n= number of patient with data available for that particular group;  
                             total % is based on N 
 
 
 
PROGRAM: L:\DEV\755\71675502\SAS\PGM\XXXX 
OUTPUT: L:\DEV\755\71675502\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm 
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Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 22 of 55 
 
T14.1.3.2 Summary of Patients Included in Analysis Population by Study Center 
 
PP 
 
Safety 
 
Site 
No. 
Name 
Total 
Randomized 
Test  
Reference  Total 
 
Test  
Reference  
Total 
 
xx 
xxxx 
xxx 
xxx 
xxx 
xxx 
 
xxx 
xxx 
xxx 
 
xx 
xxxx 
xxx 
xxx 
xxx 
xxx 
 
xxx 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Test: Permethrin Cream, 5%, (Encube Ethicals) 
Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) 
 
 
PROGRAM: L:\DEV\755\71675502\SAS\PGM\XXXX 
OUTPUT: L:\DEV\755\71675502\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm 
Page 1 of N 
 
 


Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 23 of 55 
 
T14.1.3.3 Study Timelines ( Screened subjects) 
 
 
Trial Timelines 
Date 
First Patient First Visit (FPFV) 
mm-DDD-YYYY 
Last Patient Last Visit (LPLV) 
mm-DDD-YYYY 
Trial Duration (Days) 
xxx 
__________________________________________________________________________________________________________________ 
Note: Trial Duration (Days) = (Date of LPLV - Date of FPFV) + 1 
 
__________________________________________________________________________________________________________________ 
 
 
PROGRAM: L:\DEV\755\71675502\SAS\PGM\XXXX 
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Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 24 of 55 
T14.1.4 Summary of Demographic Data and Baseline Characteristics 
(Safety Population) 
 
 
Test  
n = xxx 
n (%) 
Reference  
n = xxx 
n (%) 
Total 
N = xxx 
n (%) 
P-value 
Age (years) 
n 
xxx 
xxx 
xxx 
x.xxxx 
 
Mean ± SD 
xx.x ± xx.x 
xx.x ± xx.x 
xx.x ± xx.x 
 
 
Median 
xx.x 
xx.x 
xx.x 
 
 
Range 
xx.x - xx.x 
xx.x - xx.x 
xx.x - xx.x 
 
Age Groups 
< 18 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
x.xxxx 
 
18 – 40 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
 
41 – 64 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
 
65 – 75 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
 
> 75 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
Race 
American Indian or Alaska Native 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
x.xxxx 
 
Asian 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
 
Black/African American 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
 
Native Hawaiian or other Pacific 
Islander 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
 
White 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
 
Other 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
Ethnicity 
Hispanic or Latino 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
x.xxxx 
 
Not Hispanic or Latino 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
 
 
 
 
 
 
Test: Permethrin Cream, 5%, (Encube Ethicals) 
Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) 
N= number of patients randomized in that particular group; n= number of patient with data available for that particular group; total % is based on N 
 
PROGRAM: L:\DEV\755\71675502\SAS\PGM\XXXX 
OUTPUT: L:\DEV\755\71675502\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm 
Page 1 of N 
 
 


Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 25 of 55 
T14.1.4 Summary of Demographic Data 
(Safety Population) 
 
 
 
Test  
N = xxx 
n (%) 
Reference  
N = xxx 
n (%) 
Total 
N = xxx 
n (%) 
P-value 
Sex 
Female 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
x.xxxx 
 
Male 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
Baseline Severity Score of Nocturnal 
Itching  Pretreatment 
None 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
x.xxxx 
 
Mild 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
 
Moderate 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
 
Severe 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
Baseline Severity of Lesion Count 
Infestation Pretreatment 
Mild 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
x.xxxx 
 
Moderate 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
 
Severe 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
 
 
 
 
 
 
   Test: Permethrin Cream, 5%, (Encube Ethicals) 
   Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) 
    N= number of patients randomized in that particular group; n= number of patient with data available for that particular group; total % is based on N 
 
PROGRAM: L:\DEV\755\71675502\SAS\PGM\XXXX 
OUTPUT: L:\DEV\755\71675502\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm 
Page 1 of N 
 
Similar tables will be created for T14.1.5. 
T14.1.5 Summary of Demographic Data (Per-Protocol Population) 
 
 
 


Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 26 of 55 
T14.1.6 Summary of Microscopic Evaluation of Scabies  
(Per-Protocol Population) 
Visit 
 
Microscopic 
 Evaluation 
Statistic 
Test  
N = xxx 
n (%) 
Reference  
N = xxx 
n (%) 
1 (Baseline) 
Microscopic examination result 
Positive 
xxx (xx.x) 
xxx (xx.x) 
 
 
Negative 
xxx (xx.x) 
xxx (xx.x) 
 
Number of scraped sites  
n 
xxx 
xxx 
 
 
Mean ± SD 
xx.x ± xx.x 
xx.x ± xx.x 
 
 
Median 
xx.x 
xx.x 
 
 
Range 
xx.x - xx.x 
xx.x - xx.x 
 
 
 
 
 
2 
Microscopic examination result 
Positive 
xxx (xx.x) 
xxx (xx.x) 
 
 
Negative 
xxx (xx.x) 
xxx (xx.x) 
 
Number of scraped sites  
n 
xxx 
xxx 
 
 
Mean ± SD 
xx.x ± xx.x 
xx.x ± xx.x 
 
 
Median 
xx.x 
xx.x 
 
 
Range 
xx.x - xx.x 
xx.x - xx.x 
 
 
 
 
 
3 (EOS) 
Microscopic examination result 
Positive 
xxx (xx.x) 
xxx (xx.x) 
 
 
Negative 
xxx (xx.x) 
xxx (xx.x) 
 
Number of scraped sites  
n 
xx 
xx 
 
 
Mean ± SD 
xx.x ± xx.x 
xx.x ± xx.x 
 
 
Median 
xx.x 
xx.x 
 
 
Range 
xx.x - xx.x 
xx.x - xx.x 
 
 
 
 
 
Test: Permethrin Cream, 5%, (Encube Ethicals) 
Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) 
N= number of patients randomized in that particular group; n= number of patient with data available for that particular group; total % is based on N 
 
 
PROGRAM: L:\DEV\755\71675502\SAS\PGM\XXXX 
OUTPUT: L:\DEV\755\71675502\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm 
Page 1 of N 
 
 
 


Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 27 of 55 
 
T14.1.7 Summary of Frequency of Scabies Signs and Symptoms Rating  
(Per-Protocol Population) 
Visit 
Grade (Lesion Count) 
Test  
N = xxx 
n (%) 
Reference  
N = xxx 
n (%) 
1 
Mild (<50) 
xxx (xx.x) 
xxx (xx.x) 
 
Moderate (50 – 100 ) 
xxx (xx.x) 
xxx (xx.x) 
 
Severe (>100) 
xxx (xx.x) 
xxx (xx.x) 
 
 
 
 
2 
Mild (<50) 
xxx (xx.x) 
xxx (xx.x) 
 
Moderate (50 – 100 ) 
xxx (xx.x) 
xxx (xx.x) 
 
Severe (>100) 
xxx (xx.x) 
xxx (xx.x) 
 
 
 
 
3 
Mild (<50) 
xxx (xx.x) 
xxx (xx.x) 
 
Moderate (50 – 100 ) 
xxx (xx.x) 
xxx (xx.x) 
 
Severe (>100) 
xxx (xx.x) 
xxx (xx.x) 
Test: Permethrin Cream, 5%, (Encube Ethicals) 
Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) 
N= number of patients randomized in that particular group; n= number of patient with data available for that particular group; total % is based on N 
 
 
PROGRAM: L:\DEV\755\71675502\SAS\PGM\XXXX 
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Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 28 of 55 
 
T14.1.8.1 Summary of Equivalence Analysis Results of Primary Efficacy Endpoint  
(Proportion of Patients in each Treatment Group with Therapeutic Cure (Parasitological Cure plus Clinical Cure)  
of Scabies at Day 28 ± 4) 
(Per-Protocol Population) 
Number of 
Patients (N) 
 
Number of Patients with 
Therapeutic Cure (n)  
Proportion of 
Therapeutic Cure (%) 
Difference Between Treatments 
Treatment  
Group 
Difference (%) 
90% CI Evaluation 
Test 
Xxx 
xxx 
xx.x 
 
 
Reference 
Xxx 
xxx 
xx.x 
xx.x 
xx.x – xx.x 
            Test: Permethrin Cream, 5%, (Encube Ethicals) 
            Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) 
               
           
PROGRAM: L:\DEV\755\71675502\SAS\PGM\XXXX 
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T14.1.8.2 Sensitivity Analysis Summary of Equivalence Analysis Results of Primary Efficacy Endpoint  
(Proportion of Patients in each Treatment Group with Therapeutic Cure (Parasitological Cure plus Clinical Cure)  
of Scabies at Day 28 ± 4) 
(Safety Population) 


Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 29 of 55 
T14.1.9.1 Supportive Analysis #1: Summary of Equivalence Analysis Results of Primary Efficacy Endpoint  
(Per-Protocol Population) 
Number of 
Patients (N) 
 
Number of Patients with 
Therapeutic Cure (n)  
Proportion of 
Therapeutic Cure (%) 
Difference Between Treatments 
Treatment  
Group 
Difference (%) 
90% CI Evaluation 
Test 
Xxx 
xxx 
xx.x 
 
 
Reference 
Xxx 
xxx 
xx.x 
xx.x 
xx.x – xx.x 
            Test: Permethrin Cream, 5%, (Encube Ethicals) 
            Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) 
      The primary analysis will be performed including patients who completed Visit 2 within 14 ± 2 days and Visit 3 within 28 ± 4 days. 
 
           
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T14.1.9.2 Supportive Analysis #2: Summary of Equivalence Analysis Results of Primary Efficacy Endpoint  
(Per-Protocol Population) 
Note: The primary analysis will be performed including patients who completed Visit 2 within 14 ± 2 days and Visit 3 between 
Day 26 and Day 32, inclusive. 
 
T14.1.9.3 Supportive Analysis #3: Summary of Equivalence Analysis Results of Primary Efficacy Endpoint  
(Per-Protocol Population) 
Note: The primary analysis will be performed including patients who completed Visit 2 within 14 ± 2 days and Visit 3 within 
28 ± 2 days. 


Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 30 of 55 
T14.1.10 Summary of Frequency of Patient Pruritus Assessment 
 (Per-Protocol Population) 
Visit 
Grade (Score) 
Test  
N = xxx 
n (%) 
Reference  
N = xxx 
n (%) 
1 
NONE: Complete absence of itching  ( 0 ) 
xxx (xx.x) 
xxx (xx.x) 
 
MILD: Slight itching, no sleep loss  ( 1 ) 
xxx (xx.x) 
xxx (xx.x) 
 
MODERATE: Definitely present, interrupts sleep  ( 2 ) 
xxx (xx.x) 
xxx (xx.x) 
 
SEVERE: Marked, intense, cannot sleep ( 3 ) 
xxx (xx.x) 
xxx (xx.x) 
 
 
 
 
2 
NONE: Complete absence of itching  ( 0 ) 
xxx (xx.x) 
xxx (xx.x) 
 
MILD: Slight itching, no sleep loss  ( 1 ) 
xxx (xx.x) 
xxx (xx.x) 
 
MODERATE: Definitely present, interrupts sleep  ( 2 ) 
xxx (xx.x) 
xxx (xx.x) 
 
SEVERE: Marked, intense, cannot sleep ( 3 ) 
xxx (xx.x) 
xxx (xx.x) 
 
 
 
 
3 
NONE: Complete absence of itching  ( 0 ) 
xxx (xx.x) 
xxx (xx.x) 
 
MILD: Slight itching, no sleep loss  ( 1 ) 
xxx (xx.x) 
xxx (xx.x) 
 
MODERATE: Definitely present, interrupts sleep  ( 2 ) 
xxx (xx.x) 
xxx (xx.x) 
 
SEVERE: Marked, intense, cannot sleep ( 3 ) 
xxx (xx.x) 
xxx (xx.x) 
Test: Permethrin Cream, 5%, (Encube Ethicals) 
Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) 
N= number of patients randomized in that particular group; n= number of patient with data available for that particular group; total % is based on N 
 
PROGRAM: L:\DEV\755\71675502\SAS\PGM\XXXX 
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Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 31 of 55 
T14.1.11 Overall Summary of Adverse Events  
(Safety Population) 
 
Description 
 
Test  
 
 
Reference  
 
 
Total 
 
Subjects in Safety Analysis Set  
xxx 
xxx 
xxx 
    Subjects with at least one AE  
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
    Discontinued study drug due to above AE  
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
 
 
 
AEs reported  
xxx 
xxx 
xxx 
  Mild  
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
  Moderate  
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
  Severe  
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
  Not Related  
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
  Related  
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
  Death  
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
  Serious AE  
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
Test: Permethrin Cream, 5%, (Encube Ethicals) 
Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) 
 
Note: subjects having multiple AEs within same system organ class were counted only once in respective system organ class.  
Under any event subjects having multiple AEs with same Preferred Term were counted only once within the respective preferred term. 
 
 
 
 
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Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 32 of 55 
T14.1.12 Summary of Frequency of Adverse Events by Body System  
(Safety Population) 
 
Test  
N = xxx 
 
Reference  
N = xxx 
 
 
Body System 
Preferred Term 
Events 
Patients 
n (%) 
 
Events 
Patients 
n (%) 
 
Fisher's 
p-value 
Patients with at least one AE 
Total 
xx 
xxx (xx.x) 
 
xx 
xxx (xx.x) 
 
x.xxxx 
Ear and labyrinth disorders 
Ear pain 
xx 
xxx (xx.x) 
 
xx 
xxx (xx.x) 
 
x.xxxx 
 
etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Test: Permethrin Cream, 5%, (Encube Ethicals) 
Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) 
                             N= number of patients in safety population in that particular group; n= number of patient with data available for that particular group;    
                             total % is based on N 
 
 
 
 
PROGRAM: L:\DEV\755\71675502\SAS\PGM\XXXX 
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Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 33 of 55 
T14.1.13 Summary of Frequency of Adverse Events by Relationship  
(Safety Population) 
             
 
 
Test  
# of Events 
(N = xxx) 
 
Reference  
# of Events 
(N = xxx) 
 
Body System 
Preferred Term 
Related 
n (%) 
Not Related 
n (%) 
 
 
Related 
n (%) 
Not Related 
n (%) 
 
 
Total AEs 
Total 
xxx (xx.x) 
xxx (xx.x) 
 
 
xxx (xx.x) 
xxx (xx.x) 
 
 
Ear and labyrinth disorders 
Ear pain 
xxx (xx.x) 
xxx (xx.x) 
 
 
xxx (xx.x) 
xxx (xx.x) 
 
 
 
Hypoacusis 
xxx (xx.x) 
xxx (xx.x) 
 
 
xxx (xx.x) 
xxx (xx.x) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
                  Test: Permethrin Cream, 5%, (Encube Ethicals) 
                  Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) 
                  N = Total number of events in that particular group group; Percentage is based on total number of events. 
                 
 
 
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Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 34 of 55 
T14.1.14 Summary of Frequency of Adverse Events by Severity  
(Safety Population) 
 
 
Test  
# of Events 
(N = xxx) 
 
Reference  
# of Events 
(N = xxx) 
 
Body System 
Preferred Term 
Mild 
n (%) 
Moderate 
n (%) 
Severe 
n (%) 
 
Mild 
n (%) 
Moderate 
n (%) 
Severe 
n (%) 
 
Total AEs 
Total 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x)  xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x)  
Ear and labyrinth disorders 
Ear pain 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x)  xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x)  
 
Hypoacusis 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x)  xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x)  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
                 Test: Permethrin Cream, 5%, (Encube Ethicals) 
                  Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) 
      N = Total number of events in that particular group group; Percentage is based on total number of events. 
 
 
 
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Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 35 of 55 
T14.1.15 Summary of Frequency of Serious Adverse Events  
(Safety Population) 
Body System 
Preferred Term 
Test  
# Events 
Reference  
# Events 
Injury, poisoning and procedural complications 
Alcohol poisoning 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Test: Permethrin Cream, 5%, (Encube Ethicals) 
Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) 
 
 
PROGRAM: L:\DEV\755\71675502\SAS\PGM\XXXX 
OUTPUT: L:\DEV\755\71675502\SAS\OUT\XXXX 
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Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 36 of 55 
T14.1.16 Summary of Vital Signs  
(Safety Population) 
Vital Signs 
Visit 
Statistic 
Test  
N = xxx 
Reference  
N = xxx 
Systolic Blood Pressure (mmHg) 
1 
n 
xxx 
xxx 
 
 
Mean ± SD 
xxx.x ± xx.x 
xxx.x ± xx.x 
 
 
Median 
xxx.x 
xxx.x 
 
 
Range 
xxx.x – xxx.x 
xxx.x – xxx.x 
 
 
 
 
 
 
3 
 
 
 
 
 
 
 
 
Diastolic Blood Pressure (mmHg) 
 
 
 
 
Pulse Rate (beats/min) 
 
 
 
 
Respiration Rate (breaths/min) 
 
 
 
 
Temperature (F) 
 
 
 
 
 
 
 
 
 
Test: Permethrin Cream, 5%, (Encube Ethicals) 
Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) 
 
 
PROGRAM: L:\DEV\755\71675502\SAS\PGM\XXXX 
OUTPUT: L:\DEV\755\71675502\SAS\OUT\XXXX 
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Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 37 of 55 
 
T14.1.17 Summary of Frequency of Patients with Re-Infestation from Day 14 (treatment success) to Day 28 (treatment failure) 
(Per-Protocol Population) 
Test 
(N = xxx) 
n (%) 
Reference 
(N = xxx) 
n (%) 
xxx (xx.x) 
xxx (xx.x) 
 
 
Test: Permethrin Cream, 5%, (Encube Ethicals) 
Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) 
 
              N= number of patients randomized in that particular analysis group; n= number of patient with data available for that particular group;  
                                  total % is based on N 
 
PROGRAM: L:\DEV\755\71675502\SAS\PGM\XXXX 
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Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 38 of 55 
T14.1.18 Summary of Frequency of Patients who are Therapeutic Failures on Day 14 ± 4  
(Per-Protocol Population) 
Test 
(N = xxx) 
n (%) 
Reference 
(N = xxx) 
n (%) 
xxx (xx.x) 
xxx (xx.x) 
 
 
Test: Permethrin Cream, 5%, (Encube Ethicals) 
Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) 
 
              N= number of patients randomized in that particular analysis group; n= number of patient with data available for that particular group;  
                                  total % is based on N 
 
PROGRAM: L:\DEV\755\71675502\SAS\PGM\XXXX 
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Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 39 of 55 
L16.2.1 Listing of Discontinued Patients 
Treatment 
Group 
Patient 
Randomization 
Number 
Discontinuation 
Reason 
Population 
Test  
xxxx 
Withdrawal by Patient 
Per-Protocol 
 
xxxx 
Lost to Follow-up 
Safety 
 
 
 
 
 
 
 
 
 
 
 
 
Reference  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Test: Permethrin Cream, 5%, (Encube Ethicals) 
Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) 
 
PROGRAM: L:\DEV\755\71675502\SAS\PGM\XXXX 
OUTPUT: L:\DEV\755\71675502\SAS\OUT\XXXX 
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Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 40 of 55 
L16.2.2 Listing of Protocol Deviations 
Treatment 
Group 
Patient 
Randomization 
Number 
Event Description 
Population    
 
Test  
xxxx 
Outside Visit Window (Visit 3) Safety 
 
 
 
 
 
 
Reference  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Test: Permethrin Cream, 5%, (Encube Ethicals) 
Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) 
 
PROGRAM: L:\DEV\755\71675502\SAS\PGM\XXXX 
OUTPUT: L:\DEV\755\71675502\SAS\OUT\XXXX 
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Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 41 of 55 
L16.2.3 Patients Excluded from the Per-Protocol Population 
Treatment 
Group 
Patient 
Randomization 
Number 
Exclusion Reason 
Test  
xxxx 
Major protocol deviation 
 
 
 
 
 
 
Reference  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Test: Permethrin Cream, 5%, (Encube Ethicals) 
Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) 
 
PROGRAM: L:\DEV\755\71675502\SAS\PGM\XXXX 
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Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 42 of 55 
L16.2.4.1 Listing of Demographic Data 
Treatment 
Group 
Patient 
Randomization 
Number 
Age 
Sex 
Ethnicity 
Race 
Test  
xxxx 
30 
Female 
Not Hispanic or Latino 
Black or African American 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Test: Permethrin Cream, 5%, (Encube Ethicals) 
Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) 
 
PROGRAM: L:\DEV\755\71675502\SAS\PGM\XXXX 
OUTPUT: L:\DEV\755\71675502\SAS\OUT\XXXX 
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Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 43 of 55 
L16.2.4.2 Listing of Medical History 
Treatment 
Group 
Patient 
Randomization 
Number 
System 
Diagnosis or 
Surgical 
Procedure 
Start Date 
End Date 
Ongoing 
Test  
xxxx 
Gynecologic 
Menopause 
yyyy-mm-dd 
yyyy-mm-dd 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Test: Permethrin Cream, 5%, (Encube Ethicals) 
Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) 
 
PROGRAM: L:\DEV\755\71675502\SAS\PGM\XXXX 
OUTPUT: L:\DEV\755\71675502\SAS\OUT\XXXX 
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Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 44 of 55 
L16.2.4.3 Listing of Concomitant Medication 
Treatment 
Group 
Patient 
Randomization 
Number 
Treatment 
Area 
Medication 
Dosage 
Frequency Route 
Start/End 
Date/ Ongoing Indication 
Test  
xxxx 
No 
Lisinopril 
20 MG 
QD 
PO 
yyyy-mm-dd / 
yyyy-mm-dd 
Hypertension 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Test: Permethrin Cream, 5%, (Encube Ethicals) 
Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) 
 
PROGRAM: L:\DEV\755\71675502\SAS\PGM\XXXX 
OUTPUT: L:\DEV\755\71675502\SAS\OUT\XXXX 
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Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 45 of 55 
L16.2.4.4 Listing of Treatment for Family Members/Close Contacts 
Treatment 
Group 
Patient 
Randomization 
Number 
 
 
 
Visit 
Date 
 
How many members in the 
patient’s house-hold (e.g., 
close personal contacts, 
and/or family member(s)) 
are affected with scabies? 
 
Has the patient come into 
contact with the affected 
family member(s) and/or 
close personal contacts? 
 
Have affected family 
member(s)/close personal 
contacts of the patient been 
given prescription generic 
permethin? 
Test  
xxxx 
yyyy-mm-dd 
xxx 
Yes 
Yes 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Test: Permethrin Cream, 5%, (Encube Ethicals) 
Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) 
 
PROGRAM: L:\DEV\755\71675502\SAS\PGM\XXXX 
OUTPUT: L:\DEV\755\71675502\SAS\OUT\XXXX 
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Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 46 of 55 
L16.2.5.1 Listing of Visit Date Information 
Treatment 
Group 
Patient 
Randomization 
Number 
Informed 
Consent Signed 
Date Assent 
Signed 
Visit 1 
Visit 2 
Visit 3 /  
Early 
Termination  
Safety 
Population 
Per-Protocol 
Population 
Test  
xxxx 
yyyy-mm-dd 
yyyy-mm-dd 
yyyy-mm-dd 
yyyy-mm-dd 
yyyy-mm-dd 
Yes 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Test: Permethrin Cream, 5%, (Encube Ethicals) 
Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) 
 
PROGRAM: L:\DEV\755\71675502\SAS\PGM\XXXX 
OUTPUT: L:\DEV\755\71675502\SAS\OUT\XXXX 
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Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 47 of 55 
L16.2.5.2 Listing of Drug Administration 
Treatment 
Group 
Patient 
Randomization 
Number 
Date of 
First Dose 
Date of 
Last Dose 
Total 
Doses Applied 
 
Treatment 
Compliance* 
Test  
xxxx 
yyyy-mm-dd 
yyyy-mm-dd 
xx 
Yes 
 
 
 
 
 
 
 
 
 
 
 
 
Reference  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Test: Permethrin Cream, 5%, (Encube Ethicals) 
Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) 
 
*Treatment compliance will be calculated based off the following criteria: 1.) all patients randomized will have at least 1 dose, confirmed from 
the study drug administration form via the eCRF. Date of first and last dose and total confirmed doses applied will confirm treatment use. 2.) A 
patient who is required to dose a second time, compliance will be calculated using criteria 1 and the following data points (via the eCRF) 
positive microscopic result at Visit 2 and selection of “yes” regarding the question “based on your assessment and microscopic results, is 
continued treatment required?” 
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Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 48 of 55 
L16.2.6.1 Listing of Scabies Signs and Symptoms Rating and Microscopic Evaluation of Scabies 
Treatment 
Group 
Patient 
Randomization 
Number 
Visit 
Scabies 
Lesion 
Count 
Are there any 
new lesions 
present? 
Have all 
original lesions 
healed? 
Number  
of scraped 
sites 
Microscopic 
Examination 
Result 
 
Clinical 
Cure 
Parasito-
logical  
Cure 
 
Therapeutic 
Cure 
Test  
xxxx 
1 
Moderate 
NA 
NA 
3 
Positive 
(mites, eggs) 
 
 
 
 
 
2 
Mild 
No 
No 
3 
Positive 
(eggs) 
 
 
 
 
 
3 
Mild 
No 
Yes 
0 
Negative 
Yes 
Yes 
Yes 
 
xxxx 
1 
Moderate 
NA 
NA 
3 
Positive 
(eggs) 
 
 
 
 
 
2 
Mild 
No 
No 
3 
Positive 
(eggs) 
 
 
 
 
 
3 
Mild 
Yes 
Yes 
0 
Negative 
No 
Yes 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Test: Permethrin Cream, 5%, (Encube Ethicals) 
Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) 
 
 
PROGRAM: L:\DEV\755\71675502\SAS\PGM\XXXX 
OUTPUT: L:\DEV\755\71675502\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm 
Page 1 of N 
 
 


Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 49 of 55 
L16.2.6.2 Listing of Patient Pruritus Assessment 
Treatment 
Group 
Patient 
Randomization 
Number 
Visit 1 
Visit 2 
Visit 3 / Early 
Termination 
No Itch 
Persistence 
Test  
xxxx 
1 (Mild) 
1 (Mild) 
0 (None) 
Yes 
 
 
2 (Moderate) 
1 (Mild) 
1 (Mild) 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Test: Permethrin Cream, 5%, (Encube Ethicals) 
Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) 
 
 
 
PROGRAM: L:\DEV\755\71675502\SAS\PGM\XXXX 
OUTPUT: L:\DEV\755\71675502\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm 
Page 1 of N 
 
 


Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 50 of 55 
L16.2.6.3 Listing of Investigator Evaluator Initials On Scabies Signs & Symptoms Rating 
Treatment 
Group 
Patient 
Randomization 
Number 
Visit 1 
Visit 2 
Visit 3 / Early 
Termination 
Test  
xxxx 
XYZ 
D-G 
D-G 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Test: Permethrin Cream, 5%, (Encube Ethicals) 
Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) 
 
PROGRAM: L:\DEV\755\71675502\SAS\PGM\XXXX 
OUTPUT: L:\DEV\755\71675502\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm 
Page 1 of N 
 
 


Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 51 of 55 
L16.2.7 Listing of Adverse Events by Treatment 
Treatment 
Group 
Patient 
Randomization 
Number 
Body System / 
MedDRA Term / 
AE Term 
Treatment 
Area 
Start /End 
 Date/ 
Ongoing 
Severity 
Relationship 
to Study 
Drug 
Outcome 
Action Taken/ 
Other Action 
Taken 
SAE TEAE 
Test  
xxxx 
Nervous system disorders / 
Headache / 
Headache 
No 
yyyy-mm-dd / 
yyyy-mm-dd 
Mild 
Related  
 
Recovere
d 
Dose Not 
Changed/ 
None 
No 
Yes 
 
 
 
 
 
 
 
 
 
  
Reference  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
Test: Permethrin Cream, 5%, (Encube Ethicals) 
Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) 
 
 
PROGRAM: L:\DEV\755\71675502\SAS\PGM\XXXX 
OUTPUT: L:\DEV\755\71675502\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm 
Page 1 of N 
 
 


Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 52 of 55 
L16.2.8.1 Listing of Pregnancy Test Results 
Treatment 
Group 
Patient 
Randomization 
Number 
Visit 1 
Visit 3 / Early 
Termination 
Test  
xxxx 
Negative 
Negative 
 
 
 
 
 
 
 
 
 
 
 
 
Reference  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Test: Permethrin Cream, 5%, (Encube Ethicals) 
Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) 
 
 
PROGRAM: L:\DEV\755\71675502\SAS\PGM\XXXX 
OUTPUT: L:\DEV\755\71675502\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm 
Page 1 of N 
 
 


Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 53 of 55 
L16.2.8.2 Listing of Vital Signs 
Treatment 
Group 
Patient 
Randomization 
Number 
Visit 
Systolic BP 
(mmHg) 
Diastolic BP 
(mmHg) 
Pulse Rate 
(beats/min) 
Respiration 
Rate 
(breaths/min) 
Temperature 
(F) 
Test  
xxxx 
1 
120 
70 
84 
18 
98.6 
 
 
3 
140 
100 (NCS) 
74 
18 
97.0 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Test: Permethrin Cream, 5%, (Encube Ethicals) 
Reference: Elimite™ Cream (permethrin) 5% (Prestium Pharma, Inc.) 
 
PROGRAM: L:\DEV\755\71675502\SAS\PGM\XXXX 
OUTPUT: L:\DEV\755\71675502\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm 
Page 1 of N 
 
 


Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 54 of 55 
 
F15.1.1 Histogram of Proportion of Patients with Therapeutic Cure on Day 28 ±4 
 
 
 
 
 
0 
10 
20 
30 
40 
50 
60 
70 
80 
90 
100 
Permethrin Cream 
Elimite™ Cream  
Proportion of Patients with Therapeutic Cure on 
Day 28 ± 4 


Encube Ethicals                                                                                                                    Novum Pharmaceutical Research Services 
Permethrin Cream, 5%                                                                                                                           Protocol / Study No. 71675502 
11/2/2017                                                                        Encube Ethicals                                                                  Page 55 of 55 
 
Reference: 
 
1. 
FDA  Draft Guidance on Malathion, June 2012.