Clinical trial NCT03337490
Conditions: Head Lice
Sponsor: Mayne Pharma International Pty Ltd
Start date: 2017-10-02; Completion date: 2017-12-18
Enrollment: 296 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a phase 3 randomized, multi-center, double-blind, placebo controlled, parallel group design study.

Detailed description:
This study is comprised of two phases: screening and treatment. The screening period is 24 hours, followed by the treatment phase of 15 ± 3 days. During the treatment phase, subjects will be randomized to either test, reference of placebo treatments (3:3:1) in a double-blind manner in an outpatient setting. Once eligibility is confirmed, randomization will occur at visit 2 (baseline, Day 1) i.e. initiation of treatment phase. The treatment phase will be 15 ± 3 days in duration wherein subject will receive treatment with investigational product (either test, reference or placebo) on Day 1 or baseline (visit 2). Efficacy will be evaluated at Day 15. Safety and tolerability will be evaluated based upon AEs and patient self-assessments and self-assessments collected during follow-up visits.

Arms: arm 1: Ivermectin 0.5% lotion, topical, 117g, single dose arm 2: Sklice 0.5% Lotion, topical, 117g, single dose arm 3: 0% lotion, 117g, single dose
Interventions: intervention 1: Ivermectin 0.5% Topical Application Lotion intervention 2: Ivermectin 0.5% Topical Application Lotion [SKLICE] intervention 3: Placebo 0% Lotion
Intervention descriptions: intervention 1: Subjects on Test Product will receive a single dose, 117g, during the study to be applied at baseline. intervention 2: Subjects on Reference Product will receive a single dose, 117g, during the study to be applied at baseline. intervention 3: Subjects on Placebo will receive a single dose, 117g, during the study to be applied at baseline.

Protocol documents:
Prot_001.pdf: 
Protocol Number: MAP-7189                                                                                                                                                       
 
Version 1.3;   28 December 2017 
 
CLINICAL STUDY PROTOCOL 
A Randomized, Multi-Center, Double-blind, Placebo Controlled, Parallel Group Trial to Evaluate Efficacy and Safety 
of Mayne Pharma’s Ivermectin 0.5% Lotion Compared to Sklice® Ivermectin 0.5% Lotion in the Treatment of Head 
Lice 
Protocol Identifying Number:  MAP-7189 
Sponsor: Mayne Pharma, LLC 
1240 Sugg Parkway, 
Greenville, NC 27834 USA 
Phone: +1 (252) 717-1382 
Fax: +1 (252) 758-8522 
Funded by: Mayne Pharma, LLC 
Protocol Version 1.3; 28 December2017 
 
 
 
 
 
 
 
 
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Protocol Number: MAP-7189                                                                                                                                                       
 
Version 1.3;   28 December 2017 
Table of Contents 
SIGNATURE PAGE.............................................................................................................................................. 2 
Table of Contents ................................................................................................................................................. 3 
Protocol Amendment 2 Summary of Changes....................................................................................................... 6 
Protocol Amendment 1 Summary of Changes....................................................................................................... 7 
List of Abbreviations ............................................................................................................................................. 8 
INVESTIGATOR SIGNATURE PAGE ................................................................................................................... 9 
Synopsis ............................................................................................................................................................ 10 
1 
Key Roles .............................................................................................................................................. 16 
2 Study Introduction ........................................................................................................................................... 17 
2.1 Background Information .............................................................................................................................. 17 
2.2 Rationale .................................................................................................................................................... 17 
2.3 Potential Risks and Benefits ........................................................................................................................ 18 
2.3.1 Known Potential Risks ............................................................................................................................ 18 
2.3.2 Known Potential Benefits ........................................................................................................................ 18 
3 Objectives and Purpose ................................................................................................................................... 19 
4 Study Design and Endpoints ............................................................................................................................ 19 
4.1 Description of the Study Design .................................................................................................................. 19 
4.2 Study Endpoint ........................................................................................................................................... 20 
4.2.1 Primary Endpoint .................................................................................................................................... 20 
4.2.2. Secondary Endpoint .............................................................................................................................. 20 
5 Study Enrollment and Withdrawal .................................................................................................................... 20 
5.1 Inclusion Criteria ......................................................................................................................................... 20 
5.2 Exclusion Criteria ........................................................................................................................................ 21 
5.3 Criteria for Inclusion of Minor Subjects ........................................................................................................ 22 
5.4 Strategies for Recruitment and Retention .................................................................................................... 22 
5.5 Subject Withdrawal and Termination ........................................................................................................... 22 
5.5.1 Potential Reasons for Withdrawal ........................................................................................................... 22 
5.5.2 Handling of Subject Withdrawals or Termination ..................................................................................... 23 
5.6 Premature Suspension or Termination of Study .......................................................................................... 23 
6 Study Drug ...................................................................................................................................................... 24 
6.1 Study Agent (s) and Control Description ...................................................................................................... 24 
6.1.1 Acquisition .............................................................................................................................................. 24 
6.1.2 Formulation, Appearance, Packaging and Labeling ................................................................................. 24 
6.1.3 Product Storage and Stability .................................................................................................................. 24 
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6.1.4 Preparation ............................................................................................................................................. 24 
6.1.5 Dosing and Administration ...................................................................................................................... 25 
6.1.6 Route of Administration ........................................................................................................................... 25 
6.1.7 Blinding .................................................................................................................................................. 25 
6.1.8 Duration of Therapy ................................................................................................................................ 25 
6.1.9 Tracking of Dose and Treatment Compliance .......................................................................................... 26 
6.2 Study Drug Accountability ........................................................................................................................... 26 
7 Study Procedures and Schedule of Events ...................................................................................................... 26 
7.1 Study Procedures/Evaluations .................................................................................................................... 26 
7.1.1 Study Specific Procedures ...................................................................................................................... 27 
7.2 Laboratory Procedures/Evaluations ............................................................................................................. 27 
7.2.1 Clinical Laboratory Evaluations ............................................................................................................... 27 
7.3 Study Schedule........................................................................................................................................... 27 
7.3.1 Screening ............................................................................................................................................... 27 
7.3.2 
Enrollment/Baseline ..................................................................................................................... 28 
7.3.3 Follow-up ................................................................................................................................................ 28 
7.3.4 Final Study Visit ...................................................................................................................................... 29 
7.3.5 Unscheduled Visit ................................................................................................................................... 29 
7.3.6 Rescreening ........................................................................................................................................... 29 
7.4 Concomitant Medications, Treatments, and Procedures .............................................................................. 29 
7.4.1 Precautionary Medications, Treatments, and Procedures ........................................................................ 30 
7.5 Prohibited Medications, Treatments, and Procedures .................................................................................. 30 
7.6 
Rescue Medications, Treatments, and Procedures................................................................................. 30 
7.7 
Participant Access to Study Drug at Study Center .................................................................................. 30 
8 
Assessment of Safety ............................................................................................................................ 30 
8.1 Specification of Study Parameters............................................................................................................... 30 
8.1.1 Definition of Adverse Events (AE) ........................................................................................................... 30 
8.1.2 Definition of Serious Adverse Events (SAE) ............................................................................................ 31 
8.1.3 Definition of Unanticipated Problems....................................................................................................... 32 
8.2 Classification of an Adverse Event .............................................................................................................. 32 
8.2.1 Severity of Event .................................................................................................................................... 32 
8.2.2 Relationship to Study Drug ..................................................................................................................... 32 
8.2.3 Expectedness ......................................................................................................................................... 32 
8.3 Time Period and Frequency for Event Assessment and Follow-Up .............................................................. 33 
8.4 Reporting Procedures ................................................................................................................................. 33 
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8.4.1 Adverse Event Reporting ........................................................................................................................ 33 
8.4.2 Serious Adverse Event Reporting ........................................................................................................... 33 
8.4.3 Unanticipated Problem Reporting............................................................................................................ 33 
8.4.4 Reporting of Pregnancy .......................................................................................................................... 33 
8.5 Safety Oversight ......................................................................................................................................... 34 
9 
Clinical Monitoring ................................................................................................................................. 34 
10 Statistical Considerations............................................................................................................................... 34 
10.1 Statistical and Analytical Plans .................................................................................................................. 35 
10.2 Data Sets to Be Evaluated ........................................................................................................................ 35 
10.3 Statistical Hypotheses ............................................................................................................................... 35 
10.4 
Description of Statistical Methods .......................................................................................................... 35 
10.4.1 
Subject Disposition and Demography ........................................................................................... 35 
10.4.2 
Assessment of Bioequivalence and Superiority for Primary and Secondary Endpoints .................. 36 
10.4.3 
Safety Analyses ........................................................................................................................... 36 
10.5 
Sample Size .......................................................................................................................................... 37 
11 Source Documents and Access to Source Data/Documents .......................................................................... 37 
12 Ethics/Subject Protection ............................................................................................................................... 37 
12.1 Ethical Standard ....................................................................................................................................... 37 
12.2 Institutional Review Board ......................................................................................................................... 37 
12.3 Informed Consent Process ........................................................................................................................ 38 
12.3.1 Other Informational Documents Provided to Participants ....................................................................... 38 
12.3.2 Consent Procedures and Documentation .............................................................................................. 38 
12.4 Participant and Data Confidentiality ........................................................................................................... 38 
13 
Data Handling and Record Keeping ....................................................................................................... 39 
13.1 Study Records Retention .......................................................................................................................... 39 
13.2 
Protocol Deviations ................................................................................................................................ 39 
13.3 
Publication and Data Sharing Policy....................................................................................................... 40 
14 Conflict of Interest Policy ............................................................................................................................... 40 
15 Literature References .................................................................................................................................... 41 
16 Appendices ................................................................................................................................................... 42 
16.1 Schedule of Events ................................................................................................................................... 42 
16.2 Subject Diary ............................................................................................................................................ 43 
16.3 Subject Self-Assessment .......................................................................................................................... 47 
16.4 Site Assessment ....................................................................................................................................... 48 
 
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Protocol Amendment 2 Summary of Changes 
 
Section 
Description of Change 
Synopsis, Inclusion Criteria #1 
The index subject must be the youngest family 
member, under the age of 18, changed to index 
subject must be the youngest family member, 
through 18 years of age. 
Synopsis, Inclusion Criteria #4 
Index subject 6 months of age and a maximum 18 
years of age changed to Index subject is at least 6 
months through 18 years of age. 
Synopsis, Inclusion Criteria #6 
Assent form administration age for children changed 
from 6-18 years to 6-17 years. 
Section 4.1, Description of Study Design 
Subject population changed from 6 months to 18 
years changed to 6 months through 18 years. 
Section 5.1, Inclusion Criteria #1 
The index subject must be the youngest family 
member, under the age of 18, changed to index 
subject must be the youngest family member, 
through 18 years of age. 
Section 5.1, Inclusion Criteria #4 
Index subject 6 months of age and a maximum 18 
years of age changed to Index subject is at least 6 
months through 18 years of age. 
Section 5.1, Inclusion Criteria #6 
Assent form administration age for children changed 
from 6-18 years to 6-17 years. 
Section 5.3, Criteria for Inclusion of 
Minor Subjects 
Subjects under the age of 18 must sign assent form 
changed to subjects aged 6 years through 17 years of 
age must sign assent form. 
 
Change made to Sponsor representative when transfer of oversight took place at Mayne Pharma, LLC 
 
 
 
 
 
 
 
 
 
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Protocol Amendment 1 Summary of Changes 
 
Affected Section(s) 
Summary of Revisions Made 
Rationale 
Protocol Synopsis, 
Inclusion Criteria # 6 
Assent form administration age for 
children changed from 12-18 years to 6-
18 years. 
Assent Age Range approved by IRB directly 
contradicts Assent Age Range listed in 
Protocol Inclusion Criteria # 6 (12-18 years). 
Section 5.1, 
Inclusion Criteria # 6 
Assent form administration age for 
children changed from 12-18 years to 6-
18 years. 
Assent Age Range approved by IRB directly 
contradicts Assent Age Range listed in 
Protocol Inclusion Criteria # 6 (12-18 years). 
Section 6.1.7, 
Blinding 
Replaced the word ‘IWRS’ with 
‘Unblinded Treatment List’ to unblind the 
treatment for the individual subject, if 
situation arises. 
A decision was made to perform 
Randomization and Unblinding the 
treatment of an individual subject manually 
instead of using IWRS. 
 
 
 
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List of Abbreviations 
AE 
Adverse Event 
CFR 
Code of Federal Regulations 
CMP 
Clinical Monitoring Plan 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
eCRF 
Electronic Case Report Forms 
EOS 
End of Study 
ET 
Early Termination 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IMV 
Interim Monitoring Visit 
IRB 
Investigational Review Board 
ITT 
Intent to Treat 
LOCF 
Last Observation Carried Forward 
Mayne 
Mayne Pharma, LLC/ Mayne Pharma International Pty Ltd 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
Modified Intent-to-Treat 
MRT 
Mean Residence Time 
OTC 
Over the Counter 
PI 
Principal Investigator 
PMH 
Past Medical History 
PP 
Per-Protocol 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SAS 
Statistical Analysis System 
SD 
Standard deviation 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
SUSAR 
Suspected Unexpected Serious Adverse Event 
TEAE 
Treatment Emergent Adverse Event 
US 
 United States 
WHO 
World Health Organization 
 
 
 
 
 
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INVESTIGATOR SIGNATURE PAGE 
 
The signature below constitutes approval of this protocol and provides the necessary assurance that this study will be conducted at 
his/her investigational site according to all stipulations of the protocol including all statements of confidentiality and in accordance 
with International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) and local regulatory requirements. 
 
Print Name 
 
Title 
 
Address of Institution / Site 
 
 
 
 
Telephone Number: 
 
INVESTIGATOR SIGNATURE: ___________________________   DATE: _____________ 
 
 
 
 
 
 
 
 
 
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Synopsis 
 
Study Title 
A Randomized, Multi-Center, Double-blind, Placebo Controlled, Parallel Group Trial to 
Evaluate Efficacy and Safety of Mayne Pharma’s Ivermectin 0.5% Lotion Compared to 
Sklice® 0.5% Lotion in the Treatment of Head Lice 
Protocol Number 
MAP-7189 
Development Phase 
3 
Type of Study 
Clinical Endpoint Bioequivalence 
Test Product 
Ivermectin 0.5% Lotion 
Sklice® 0.5% Lotion 
Placebo Lotion 
Name of Active 
Ingredient 
Ivermectin 
Route, Dose and 
Dosage Regimen 
Route: Topical application 
Dose:  Apply full tube amount (4 oz.) to dry hair to completely cover scalp and hair.  
Apply closest to the scalp first, and then apply outwards towards the ends of the hair. 
Regimen: One 10-minute application then thoroughly rinse with warm water 
Sponsor 
Mayne Pharma, LLC 
Greenville, NC, USA 
Study Objectives 
The primary objective of the study is to establish the efficacy of a single application of 
Ivermectin 0.5% lotion in the treatment of head lice (Pediculus humanus capitis) 
under at-home conditions compared with Sklice® 0.5% lotion, and to demonstrate 
that both active lotions have superior efficacy compared to Placebo. 
The secondary objective of the study is to demonstrate the safety and local 
tolerability of Ivermectin 0.5% lotion compared with Sklice® 0.5% lotion.  
 
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Study Endpoints 
The primary efficacy endpoint is the proportion of index subjects who are lice free 
(defined as no live lice, adults or nymphs) 14 days (Day 15) after treatment.   
The secondary efficacy endpoint is the number and percentage of all index subjects 
who are lice-free at Day 2. 
Number of Subjects 
and Sites 
The planned overall sample size for this clinical trial is approximately 280 index 
subjects, who will be randomized at approximately 6 geographically diverse clinical 
research centers in the United States 
Eligibility Criteria 
Subjects who satisfy ALL the following inclusion and have NONE of the following 
exclusion criteria may be enrolled in the study: 
INCLUSION CRITERIA: 
1. Subjects must have an active head lice infestation defined as: At least 3 
live lice (adults and/or nymphs) present on the scalp and/or hair, as 
determined by a trained evaluator. The index subject must be the 
youngest family member, through the age of 18, presenting with an active 
head lice infestation.  
2. Household members that have an active head lice infestation defined as: 
At least 1 live louse (adult and/or nymph) present on the scalp and/or hair, 
as determined by a trained evaluator (with the exception of the male head 
of household who may self-assess as being lice free) will receive the 
Standard of Care with an over-the-counter head lice treatment product. 
Up to 3 infested household members may receive treatment, if more than 
3 household members are infested, the entire household will be excluded 
from the study. 
3. Subject is male or female. 
4. Index subject is at least 6 months through 18 years of age at time of 
enrollment. 
5. Subject is in good general health based on medical history. 
6. Each subject must have an appropriately signed Informed Consent 
agreement. A caregiver must sign an Informed Consent agreement for 
children not old enough to do so. Children ages 6-17 years of age will be 
administered a child's Assent Form. 
7. The caregiver of a subject must be willing to allow all household members 
to be screened for head lice. If other household members are found to 
have an active head lice infestation, they must be willing and able to 
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participate in receiving the Standard of Care. No more than one working 
male per household may be excluded from evaluation if he is assessed as 
being lice free by himself or the caregiver and cannot come in due to his 
work schedule. If this individual may have lice, he must come to the test 
facility; otherwise the entire household will be excluded from study 
participation. 
8. Subject and/or their caregiver must be physically able and willing to apply 
the test product according to established treatment methods. 
9. Subject agrees not to use any other form of lice treatments (commercial, 
community-anecdotal, or mechanical/manual) while participating in the 
study. 
10. Following application and rinsing of the test product, subject agrees not to 
shampoo, wash, or rinse their hair or scalp until the 24-hour post-
treatment evaluation has been completed. 
11. Subject agrees to not cut or chemically treat their hair while participating 
in the study. 
12. Subject agrees to follow all study instructions, including attending all 
follow-up appointments. 
13. Female index subjects of childbearing potential must be willing to have a 
urine pregnancy test prior to inclusion in this study. 
14. In the event of a subject judged to be incapable of self-treating, the 
household must have a caregiver willing to apply the treatment at home. 
 
EXCLUSION CRITERIA: 
1. Index subjects with greater than 3 household members with at least 1 live 
louse (adult and/or nymph) present on the scalp and/or hair, as 
determined by a trained evaluator will be automatically excluded from the 
trial. 
2. Youngest household member is over 18 years of age. 
3. History of irritation or sensitivity to ivermectin or the lotion components, 
pediculicides or hair care products. 
4. Presentation at the treatment site with visible skin/scalp condition(s) that 
are not attributable to head lice infestation, such as an erythema score 
that is >2, blisters, vesicles which, in the opinion of the investigative 
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personnel or medical monitor, will interfere with safety and/or efficacy 
evaluations. 
5. Presentation at the treatment site with eczema or atopic dermatitis. 
6. Treatment for head lice (Over the counter [OTC], home remedy and/or 
Prescription) in the last 15 days. 
7. Any condition or illness that, in the opinion of the investigator, may 
compromise the objective of the protocol. 
8. Is receiving any other treatment which, in the opinion of the investigator 
or medical monitor, may interfere with the study results. 
9. Females (including caregivers who come in contact with the investigational 
product) who are pregnant, nursing or planning a pregnancy which could 
include index subjects. If a household has a pregnant female who has an 
active case of lice, the entire household is excluded from participation. If 
this pregnant household member does not have an active infestation, this 
individual must NOT be the caregiver (one who provides treatment to 
other household members). 
10. Index subject of child-bearing potential, and unwilling to use an adequate 
method of contraception for the duration of the study. Adequate methods 
of contraception include: abstinence, vasectomized partner, oral birth 
control pills, birth control injections or patches, Intra uterine devices, 
condoms with a spermicidal jelly or a diaphragm with spermicidal jelly, 
surgical sterilization. Index subjects and/or their caregivers will be 
considered non-child-bearing if the following has occurred: full 
hysterectomy or bilateral oophorectomy is considered surgically sterile. 
Tubal ligation is not considered equivalent to female sterilization. 
11. Participation in a previous investigational drug study within the past 30 
days. 
12. Does not understand the requirements for study participation and/or may 
likely exhibit poor compliance, in the opinion of the investigator. 
13. Does not have a known household affiliation with their household 
members (i.e., do not stay in one household consistently, sleeping at one 
place several nights and then at another place or location). Household is 
defined as living in a shared area or space (for example the same house or 
apartment unit). 
 
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Withdrawal and Early 
Discontinuation 
A subject will be discontinued from this study if any of the following criteria are 
met: 
• 
Withdrawal of consent by the subject is received. 
• 
In the opinion of the Investigator or Medical Monitor it is not in the subject’s 
best interests to continue in the study. 
• 
Occurrence of an Adverse Event (AE) or Serious Adverse Event (SAE), which, 
in the opinion of the Investigator, warrants discontinuation of the subject 
from the study. 
• 
Pregnancy as informed by the subject or as determined by a positive urine 
pregnancy test.  If found to be positive, subject will be discontinued from the 
study.  
• 
Significant non-compliance with study procedures that would interfere with 
the study results or increase the subject’s risks in the study, as determined by 
the Investigator.  
• 
Subject is deemed to be a treatment failure if upon revisit it is determined 
that they are still infested. They will be terminated from the study and 
provided the standard of care at that point in the study.  
• 
Any clinical adverse event (AE), laboratory abnormality, or other medical 
condition or situation occurs such that continued participation in the study 
would not be in the best interest of the participant 
• 
The participant meets an exclusion criterion (either newly developed or not 
previously recognized) that precludes further study participation. 
Prohibited 
Concomitant 
Medication/Products 
and Treatments 
• 
Head lice treatment product (over the counter [OTC], home remedy and/or 
Prescription) may include:  
• 
Nix 
• 
Rid 
• 
Kwell 
• 
LiceMD 
• 
No medications are contraindicated for use with topical ivermectin lotion 
Study Agents 
• 
Ivermectin 0.5% Lotion 
• 
Sklice® 0.5% Lotion 
• 
Placebo Lotion 
Study Duration 
15 Days +/- 3 Day window 
Statistical Analysis 
ANALYSIS POPULATIONS 
Safety Population includes all subjects who were randomized and dispensed 
treatment.  This is the population that will be used for the safety assessments. 
Modified Intent-to-Treat (mITT) population includes all Index subjects who met all 
inclusion/exclusion criteria, were randomized, dispensed treatment, and had at least 
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one post-treatment efficacy evaluation.  This is the primary population for 
determination of the superiority of the active treatments over placebo. 
Per-Protocol (PP) population includes all mITT subjects who applied their dispensed 
treatment, had no protocol deviations which could have interfered with the accurate 
assessment of treatment efficacy, and returned for the Day 15 visit within the allowed 
window. This is the primary population for the efficacy comparisons between the two 
active treatment groups.  
EFFICACY ANALYSIS 
Primary Efficacy Endpoint 
The primary efficacy endpoint is the proportion of index subjects who are lice free 
(defined as no live lice, adults or nymphs) 14 days (Day 15) after treatment.  The 
superiority of Test and Reference treatment’s cure proportions over that of the 
placebo will be evaluated using continuity-corrected Z-tests (α = 0.05, 2-sided). The 
comparability of the Test and Reference treatments will be evaluated using a 90% 
continuity-corrected confidence interval on the difference between their cure 
proportions and a bioequivalence margin = 0.20 (20%).  
Secondary Efficacy Endpoint  
The secondary efficacy endpoint is the number and percentage of all index subjects 
who are lice free at Day 2.  
SAFETY ANALYSIS 
Descriptive statistics on the severity and duration of adverse events (AEs) from all 
subjects will be determined for each treatment group for any AE that occurs in at least 
5% of the subjects. 
Analysis of tolerability will be based on scores of Stinging/Burning and Itching 
sensations collected during Subject Self-Assessment and Site Assessment at all follow-
up visits between the test and reference treatment groups. 
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1 Key Roles 
 
PRINCIPAL CONTACTS 
 
 
 
CLINICAL PROTOCOL AND CONDUCT INQUIRIES 
Chandra Vattikonda, M.Pharm., Ph.D. 
Senior Director, Clinical Pharmacology 
Mayne Pharma Inc. 
email: Chandra.Vattikonda@maynepharma.com 
1240 Sugg Parkway, 
Greenville, NC 27834 USA 
Phone: +1 (252) 707-6266 
Fax: +1 (252) 758-8522 
 
Phoevos Hughes, J.D. 
Project Director 
Biorasi LLC 
email:  phughes@biorasi.com 
19495 Biscayne Blvd., Suite #900 
Aventura, FL 33180 
Phone: +1 (786) 888-2245 
 
CLINICAL SAFETY INQUIRIES 
Sergey Pavlenko, MD 
Medical Monitor 
Biorasi Safety and Pharmacovigilance 
email: spavlenko@biorasi.com 
19495 Biscayne Blvd., Suite #900 
Aventura, FL 33180 
Fax: +1 (786) 221-3531 
 
REPORTING OF SERIOUS ADVERSE EVENTS (SAES), 
PROTOCOL DEVIATIONS  
Biorasi Safety and Pharmacovigilance 
email: MAP7189_safety@biorasi.com 
19495 Biscayne Blvd., Suite #900 
Aventura, FL 33180 
Fax: +1 (786) 221-3531 
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2 Study Introduction 
2.1 Background Information 
 
The head louse, or Pediculus humanus capitis, is a wingless, parasitic insect that can be found on the head, eyebrows, and 
eyelashes of people. Head lice feed on human blood several times a day and live close to the human scalp.  
Head lice are found worldwide. In the United States, infestation with head lice is most common among pre-school children 
attending child care, elementary schoolchildren, and the household members of infested children. Although reliable data 
on how many people in the United States get head lice each year are not available, an estimated 6 million to 12 million 
infestations occur each year in the United States among children 3 to 11 years of age.  [1] 
Ivermectin is a member of the avermectin class of broad-spectrum antiparasitic agents which have a unique mode of 
action. Compounds of the class cause death primarily through binding selectively and with high affinity to glutamate-gated 
chloride channels, which occur in invertebrate nerve and muscle cells. This leads to an increase in the permeability of the 
cell membrane to chloride ions with hyperpolarization of the nerve or muscle cell, resulting in paralysis and death of the 
parasite. Compounds of this class may also interact with other ligand-gated chloride channels, such as those gated by the 
neurotransmitter gamma-aminobutyric acid (GABA). The selective activity of compounds of this class is attributable to the 
fact that some mammals do not have glutamate-gated chloride channels and that the avermectins have a low affinity for 
mammalian ligand-gated chloride channels. In addition, ivermectin does not readily cross the blood-brain barrier in 
humans. [2] 
 
Safety of Ivermectin was evaluated in two pivotal trials. Supportive safety data is also available from five other sponsor-
conducted Phase 1 and 2 trials.  Adverse events which occurred in less than 1% of subjects included conjunctivitis, ocular 
hyperemia, eye irritation, dandruff, dry skin, and skin burning sensation. Evaluation of cutaneous safety, scalp irritation 
(Phases 1, 2, 3) and ocular irritation (Phase 3), did not reveal clinically notable signals. [3] 
Long-term studies in animals have not been performed to evaluate the carcinogenic potential of Ivermectin, yet it was 
found not to be genotoxic in vitro in the Ames test, the mouse lymphoma assay, or the unscheduled DNA synthesis assay 
in human fibroblasts. [4]  
2.2 Rationale 
 
There are many FDA-approved drugs (including prescription and nonprescription drugs) for the treatment of head lice 
infestation, but genetic resistance of lice to lindane and to the most commonly used treatments, pyrethroids, is not 
uncommon in the United States, thus development of additional drugs for this indication is encouraged.  [5] 
Because the infestation is communicable, children diagnosed with head lice infestation may be precluded from attending 
school until they have received effective treatment, indicating the need for a safe and bioequivalent alternative. [7] There 
is a public health need for products for the treatment of head lice with a favorable side effect profile and approval for use 
in children less than 4 years of age. [3] 
The proposed study is aimed to evaluate the safety and efficacy of Ivermectin 0.5% lotion.  A randomized, multi-center, 
double-blind, placebo controlled, parallel group trial has been selected in order to evaluate the efficacy and safety of 
Mayne Pharma’s Ivermectin 0.5% lotion compared to Sklice® 0.5% lotion in the treatment of head lice. [3]  
The index subjects will be selected according to predefined inclusion and exclusion criteria.  The study treatment duration 
of 15 days is expected to be sufficient to show a treatment effect.  
 
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2.3 Potential Risks and Benefits 
2.3.1 Known Potential Risks               
 
Safety and efficacy has been established for pediatric patients 6 months of age or older. Ivermectin 0.5% lotion is not 
recommended for patients under 6 months of age due to the increased risk of systemic absorption, given a high ratio of 
skin surface area to body mass.   
 
The following reactions, reported in less than 1% of subjects treated with Ivermectin 0.5% lotion include:  
 
• 
Conjunctivitis 
• 
Ocular hyperemia 
• 
Eye irritation 
• 
Dandruff 
• 
Dry skin 
• 
Skin burning sensation 
In the case of accidental or significant exposure, the following adverse effects have been reported most frequently:  
• 
Rash 
• 
Edema 
• 
Headache 
• 
Dizziness 
• 
Asthenia 
• 
Nausea 
• 
Vomiting 
• 
Diarrhea 
Other adverse effects that have been reported include: 
• 
Seizure  
• 
Ataxia 
• 
Dyspnea  
• 
Abdominal pain 
• 
Paresthesia 
• 
Urticaria  
• 
Contact dermatitis  
A theoretical concern exists about medication errors that might result in the ingestion of the ivermectin product 
(particularly in young children), therefore it should only be administered under the direct supervision of an adult.     
 
2.3.2 Known Potential Benefits 
 
The adverse event profile observed reveals a product safe for use in children as young as 6 months. The demonstration of 
efficacy with a single 10-minute treatment is unique amongst anti-lice products and will likely improve compliance.  
Ivermectin 0.5% lotion represents a significant addition to the current armamentarium for the treatment of head lice. 
This medication is widely used and prescribed because the benefits associated with the use of it is greater than the risk of 
the side effects.  Ivermectin 0.5% lotion has demonstrated robust efficacy in comparison to placebo with a single 10-
minute treatment for head lice in subjects 6 months of age and older. 
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3 Objectives and Purpose 
 
The primary objective of the study is to establish the efficacy of a single application of Ivermectin 0.5% lotion in the 
treatment of head lice under at-home use conditions compared with Sklice® 0.5% lotion, and to demonstrate that both 
active lotions have superior efficacy compared to Placebo. 
The secondary objective of the study is to demonstrate the safety and local tolerability of Ivermectin 0.5% lotion compared 
with Sklice® 0.5% lotion. 
4 Study Design and Endpoints 
4.1 Description of the Study Design 
 
This is a Phase 3 Randomized, Multi-Center, Double-blind, Placebo Controlled, Parallel Group Trial to Evaluate Efficacy and 
Safety of Mayne Pharma’s Ivermectin 0.5% Lotion Compared to Sklice® 0.5% Lotion in the Treatment of Head Lice.  The 
subject population includes healthy male and female subjects aged 6 months through 18 years who are infested with 
Pediculus humanus capitis. The youngest infested household member will be considered the index subject.  Household 
members, up to a maximum of 3 members, infested with an active head lice infestation defined as at least 1 live louse 
(adult and/or nymph) present on the scalp and/or hair, as determined by a trained evaluator will receive treatment with 
an over-the-counter head lice treatment product at baseline. 
The planned overall sample size for this clinical trial is approximately 280 index subjects, who will be randomized at 
different geographical clinical research centers in the United States. 
Potential subjects will be screened and the index subject will be eligible for enrollment into the study. During the baseline 
visit (Day 1), which can occur on the same day as screening (Day 0), the Investigator will record subject’s demographics, 
medical history, review concomitant medication, identifying any prohibited therapies the subject may receive, perform 
physical examination, collect vital signs and perform urine pregnancy test.  Eligible subjects will be randomized in a ratio 
of 3:3:1 to receive either the Mayne Pharma’s Ivermectin 0.5% lotion, Sklice® 0.5% lotion, or placebo lotion treatment and 
will be trained on the application of the study drug and subject’s diary completion. Infested household members, up to 3 
members per household, will be treated with an over-the-counter head lice treatment product on-site. 
The study drug will be applied as a single, at-home dose.  Subjects will be instructed to apply a full tube amount (4 oz.) of 
Ivermectin 0.5% lotion to fully coat dry hair and scalp, avoiding the eyes and mucus membranes. The lotion will be left on 
the hair and scalp for 10 minutes, then rinsed off with warm water.  The tube is intended for a single use; all used tubes 
should be returned at the second visit (first follow-up visit) to the clinical site for product accountability.  In addition to 
receiving the study drug, the index subjects and household members will be instructed on an overall lice management 
program, which includes: 
• 
Wash (in hot water) or dry-clean all recently worn clothing, hats, used bedding and towels.  
• 
Wash (in hot water) personal care items such as combs, brushes and hair clips. 
• 
A fine-tooth comb or special nit comb may be used to remove dead lice and nits after treatment. 
Index subjects will return for post-baseline visits assessments at Days 2, 8, and 15, returning used tubes of the study drug 
at Day 2, which will be accounted for along with diary cards, which will be reviewed by the site personnel for completeness. 
The Investigator will perform a visual assessment for the presence or absence of head lice, record local application site 
reactions, and perform an ocular irritation assessment. The site will provide a Subject Self-Assessment worksheet to record 
tolerability of treatment. Urine pregnancy testing will be performed at the Screening Visit and the Final Study Visit, with 
interim visits confirming pregnancy has not occurred through questioning of the index subject. 
 
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4.2 Study Endpoint 
4.2.1 Primary Endpoint 
 
The primary efficacy endpoint is the proportion of index subjects who are lice free (defined as no live lice, adults or 
nymphs) 14 days (Day 15) after treatment.   
4.2.2. Secondary Endpoint 
 
The secondary efficacy endpoint is the number and percentage of all index subjects who are lice-free at Day 2. 
5 Study Enrollment and Withdrawal 
5.1 Inclusion Criteria 
 
In order to be eligible to participate in this study, an individual must meet ALL of the following criteria: 
1. Subjects must have an active head lice infestation defined as: At least 3 live lice (adults and/or nymphs) 
present on the scalp and/or hair, as determined by a trained evaluator. The index subject must be the 
youngest family member, through the age of 18, presenting with an active head lice infestation.  
2. Household members that have an active head lice infestation defined as: At least 1 live louse (adult and/or 
nymph) present on the scalp and/or hair, as determined by a trained evaluator (with the exception of the 
male head of household who may self-assess as being lice free) will receive the Standard of Care with an over-
the-counter head lice treatment product. Up to 3 infested household members may receive treatment, if 
more than 3 household members are infested, the entire household will be excluded from the study. 
3. Subject is male or female. 
4. Index subject is at least 6 months through 18 years of age at time of enrollment. 
5. Subject is in good general health based on medical history. 
6. Each subject must have an appropriately signed Informed Consent agreement. A caregiver must sign an 
Informed Consent agreement for children not old enough to do so. Children 6-17 years of age will be 
administered a child's Assent Form. 
7. The caregiver of a subject must be willing to allow all household members to be screened for head lice. If 
other household members are found to have an active head lice infestation, they must be willing and able to 
participate in receiving the Standard of Care. No more than one working male per household may be excluded 
from evaluation if he is assessed as being lice free by himself or the caregiver and cannot come in due to his 
work schedule. If this individual may have lice, he must come to the test facility; otherwise the entire 
household will be excluded from study participation. 
8. Subject and/or their caregiver must be physically able and willing to apply the test product according to 
established treatment methods. 
9. Subject agrees not to use any other form of lice treatments (commercial, community-anecdotal, or 
mechanical/manual) while participating in the study. 
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10. Following application and rinsing of the test product, subject agrees not to shampoo, wash, or rinse their hair 
or scalp until the 24-hour post-treatment evaluation has been completed. 
11. Subject agrees to not cut or chemically treat their hair while participating in the study. 
12. Subject agrees to follow all study instructions, including attending all follow-up appointments. 
13. Female index subjects of childbearing potential must be willing to have a urine pregnancy test prior to 
inclusion in this study. 
14. In the event of a subject judged to be incapable of self-treating, the household must have a caregiver willing 
to apply the treatment at home. 
 
5.2 Exclusion Criteria 
 
An individual who meets any of the following criteria will be excluded from participation in this study: 
1. Index subjects with greater than 3 household members with at least 1 live louse (adult and/or nymph) present 
on the scalp and/or hair, as determined by a trained evaluator will be automatically excluded from the trial. 
2. Youngest household member is over 18 years of age. 
3. History of irritation or sensitivity to ivermectin or the lotion components, pediculicides or hair care products. 
4. Presentation at the treatment site with visible skin/scalp condition(s) that are not attributable to head lice 
infestation, such as an erythema score that is >2, blisters, vesicles which, in the opinion of the investigative 
personnel or medical monitor, will interfere with safety and/or efficacy evaluations. 
5. Presentation at the treatment site with eczema or atopic dermatitis. 
6. Treatment for head lice (Over the counter [OTC], home remedy and/or Prescription) in the last 15 days. 
7. Any condition or illness that, in the opinion of the investigator, may compromise the objective of the protocol. 
8. Is receiving any other treatment which, in the opinion of the investigator or medical monitor, may interfere 
with the study results. 
9. Females (including caregivers who come in contact with the investigational product) who are pregnant, 
nursing or planning a pregnancy which could include index subjects.  If a household has a pregnant female 
who has an active case of lice, the entire household is excluded from participation. If this pregnant household 
member does not have an active infestation, this individual must NOT be the caregiver (one who provides 
treatment to other household members). 
10. Is of child-bearing potential, including index subjects, and unwilling to use an adequate method of 
contraception for the duration of the study. Adequate methods of contraception include: abstinence, 
vasectomized partner, oral birth control pills, birth control injections or patches, Intra uterine devices, 
condoms with a spermicidal jelly or a diaphragm with spermicidal jelly, surgical sterilization. Index subjects 
and/or caregivers will be considered non-child-bearing if the following has occurred: full hysterectomy or 
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bilateral oophorectomy is considered surgically sterile. Tubal ligation is not considered equivalent to female 
sterilization. 
11. Participation in a previous investigational drug study within the past 30 days. 
12. Does not understand the requirements for study participation and/or may likely exhibit poor compliance, in 
the opinion of the investigator. 
13. Does not have a known household affiliation with their household members (i.e., do not stay in one household 
consistently, sleeping at one place several nights and then at another place or location). Household is defined 
as living in a shared area or space (for example the same house or apartment unit). [6] 
 
5.3 Criteria for Inclusion of Minor Subjects 
 
Subjects aged 6 years through 17 years of age must sign the Assent Form that will be written in such a way as to be 
understandable to a child and to obtain parental or legal guardian consent prior to enrollment in this study.  
 
5.4 Strategies for Recruitment and Retention 
 
• 
Expected total number of screened subjects will be 311. 
• 
Given a 10% screen failure rate, an anticipated number of enrolled subjects will be 280. 
• 
Assumed dropout rate is 10%, therefore an expected number of 252 subjects will complete the study. 
• 
Source of subjects will be primarily from area schools, along with referrals by local pediatricians to these 
participating, dedicated clinical lice centers. 
• 
Retention of subjects will be supported by thorough visit reminders and proper education on the study 
itself, including study duration, activities and responsibilities. 
• 
Approximately 6 geographically diverse clinical research centers in the US will be participating. 
 
5.5 Subject Withdrawal and Termination 
5.5.1 Potential Reasons for Withdrawal 
 
In accordance with the Declaration of Helsinki and other applicable regulations, a subject has the right to withdraw from 
the study at any time and for any reason without prejudice to his or her future medical care. The Investigator or Medical 
Monitor may also withdraw the subject at any time if it is medically necessary or in the interest of subject safety. 
A subject will be discontinued from this study if any of the following criteria are met: 
• 
Withdrawal of consent by the subject is received. 
• 
In the opinion of the Investigator or Medical Monitor it is not in the subject’s best interests to continue in the 
study. 
• 
Occurrence of an Adverse Event (AE) or Serious Adverse Event (SAE), which, in the opinion of the Investigator, 
warrants discontinuation of the subject from the study. 
• 
Pregnancy as informed by the subject or as determined by a positive urine pregnancy test. 
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• 
Significant non-compliance with study procedures that would interfere with the study results or increase the 
subject’s risks in the study, as determined by the Investigator.  
• 
Subject is deemed to be a treatment failure if upon revisit it is determined that they are still infested. They will 
be terminated from the study and provided the standard of care at that point in the study.  
• 
Any clinical adverse event (AE), laboratory abnormality, or other medical condition or situation occurs such 
that continued participation in the study would not be in the best interest of the participant 
• 
The participant meets an exclusion criterion (either newly developed or not previously recognized) that 
precludes further study participation. 
 
5.5.2 Handling of Subject Withdrawals or Termination 
 
The Sponsor reserves the right to discontinue the trial prior to inclusion of the intended number of subjects. After such a 
decision, the Investigator must contact all participating subjects within a time period specified by the Sponsor to inform 
them of the decision to discontinue the trial. 
5.6 Premature Suspension or Termination of Study 
 
The following criteria may result in either temporary suspension or early termination of the study: 
• 
New information regarding the safety or efficacy of the investigational product that indicates a change in the 
known risk/benefit profile for the compound, such that the risk/benefit is no longer acceptable for subjects 
participating in the study. 
• 
Significant violation of GCP that compromises the ability to achieve the primary study objectives or 
compromises subject safety. 
 
The Sponsor reserves the right to discontinue the trial for other valid administrative reasons. 
Criteria for Premature Termination or Suspension of Investigational Sites: 
 
• 
A study site may be terminated prematurely or suspended if the site (including the Investigator) is found to 
be in significant violation of GCP, protocol, contractual agreement, or is unable to ensure adequate 
performance of the study. 
 
Procedures for Premature Termination or Suspension of the Study or Investigational Site(s): 
 
• 
In the event that the Sponsor elects to terminate or suspend the study or the participation of an investigational 
site, a study-specific procedure for early termination or suspension will be provided by the Sponsor; the 
procedure will be followed by applicable investigational sites during the course of termination or study 
suspension.  
• 
Appropriate therapy and follow-up should be ensured for any study subject by the sponsor. 
• 
Ensure where required by applicable regulatory requirements that the regulatory authority is properly 
informed. 
• 
If the sponsor terminates the study or the subject withdraws, the end of treatment visit and/or 
discontinuation visit should be conducted. 
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6 Study Drug 
6.1 Study Agent (s) and Control Description 
6.1.1 Acquisition 
 
The drug depot will receive study agents and perform IP accountability and monitoring, including assurance of adequate 
contents and quantities, based upon the IP packing list. For acquisition of study agents at the clinical sites, study agents 
will be shipped to each individual clinical site through the designated drug depot. The drug depot will provide initial study 
agents for study initiation and resupply thereafter, as needed. 
 
 
6.1.2 Formulation, Appearance, Packaging and Labeling 
6.1.2.1. Reference Product 
 
The reference product Sklice®, marketed by Arbor Pharmaceuticals, is supplied in 4 oz. tubes. It is an off-white/tan lotion.  
The formulation composition Sklice® consists of the following ingredients according to the FDA-approved labelling: 
Study agent lotion: 0.5%; each gram of lotion contains 5 mg of ivermectin active ingredient. 
Inactive ingredients: water, olive oil, oleyl alcohol, Crodalan AWS, lanolin alcohol, cyclomethicone, shea butter, sodium 
citrate, sorbitan tristearate, methylparaben, propylparaben, and citric acid. 
 
6.1.2.2. Test  
 
The test product is Ivermectin Lotion 0.5% manufactured by Mayne Pharma International Pty Ltd., supplied in 4 oz. tubes.  
It is a white to off-white lotion.  The formulation composition of the test product consists of the following ingredients: 
Study agent Lotion: 0.5%; each gram of lotion contains 5 mg of ivermectin active ingredient. 
Inactive ingredients:  Medium Chain Triglycerides, Carbomer Homopolymer, Polyoxyl 50 Stearate, Glyceryl Monostearate, 
Propylene Glycol, Paraffin Liquid, Methyl Hydroxybenzoate, Propyl Hydroxybenzoate, Citric Acid Anhydrous, Sodium 
Citrate, Triethanolamine, Sodium hydroxide, Purified water. 
 
6.1.3 Product Storage and Stability 
 
Store at room temperature 20°C to 25°C (68°F to 77°F); excursions permitted to 15° to 30°C (59°F to 86°F).  Do not freeze.  
All study drug supplies will be kept in a secure cabinet or room with controlled access. Only the designated study personnel 
will have access to study drug supplies. 
The Investigator will maintain temperature monitoring of the study drug with daily temperature readings. All temperature 
excursions must be reported to the Sponsor using the Temperature Excursion Form. If the study drug was exposed to the 
temperature excursion outside the range 15-30oC, or within this range, but for the period greater than 24 hours, the study 
drug must be quarantined until the Medical Monitor / Sponsor’s approval on future use. Please refer to the Pharmacy 
Manual for additional detail on the Temperature Excursions and temperature monitoring during the shipment and storage 
at the site pharmacy.  
6.1.4 Preparation 
 
Ivermectin 0.5% lotion requires no preparation prior to use.   
 
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6.1.5 Dosing and Administration 
 
Apply full tube amount (4 oz.) to dry hair to completely cover the scalp and hair for index subjects ages 5 and older.  For 
babies, please apply 1 oz. of product, equivalent to ¼ of the study tube amount. For toddlers, please apply 2 oz., equivalent 
to ½ of the study tube amount. Apply closest to the scalp first, and then apply outwards towards the ends of the hair.  
Leave on the hair and scalp for 10 minutes, and then rinse off with water.  
The tube is intended for single use, do not retreat.   
Keep out of reach of children. Use on children should be under the direct supervision of an adult. 
Avoid contact with eyes.  Do not swallow. Thoroughly wash hands after applying lotion. 
Ivermectin lotion should be used in the context of an overall lice management program: 
 
• 
Wash (in hot water) or dry-clean all recently worn clothing, hats, used bedding and towels.  
• 
Wash (in hot water) personal care items such as combs, brushes and hair clips. 
• 
A fine-tooth comb or special nit comb may be used to remove dead lice and nits, as recommended per the FDA 
Guidance on the treatment of Head Lice. 
 
6.1.6 Route of Administration 
 
Ivermectin 0.5% lotion, is for topical use only.  It is not for oral, ophthalmic, or intravaginal use.   
6.1.7 Blinding 
 
This is a double-blind study, thus Sponsor, CRO, assessor site staff, study monitors, and subjects will be blinded to the 
randomization scheme. The packaging of the study drug products will be similar in appearance to make difference in 
treatment less obvious to the subjects. Blank, opaque diaper labels will be applied to each study tube for maintenance of 
study blinding. Each tube will be packaged in individualized cartons. Neither the Investigator nor the subject should be 
able to identify the received treatment. The dispensed investigational product will NOT be opened by the index subject 
and their family members at the study center. 
The blinding code must not be broken except in emergency situations for which the identification of the study treatment 
of a subject is required by the Investigator to complete a serious adverse event report. In such situations, the Medical 
Monitor or the Investigator will use the Unblinded Treatment List in order to unblind the treatment for the individual 
subject. Unblinded information will be held by designated individual(s), and the date and reason for breaking the blind 
must be recorded.  
The Medical Monitor must be contacted by telephone prior to unblinding but no later than 24 hours after unblinding. As 
the study is blinded, the Investigator should promptly document and explain to the Sponsor any premature unblinding 
(e.g., accidental unblinding, unblinding due to a serious adverse event) of the investigational product(s). 
 
6.1.8 Duration of Therapy 
 
The study is comprised of three phases:  Screening, Treatment, and Follow-Up.  The duration of this study is 15 days (+/- 
3). The Screening Phase is Day -1-0.  The Treatment Phase is Day 1.  Preferably, screening and treatment will occur on the 
same day. The Final Study Visit is on day 15 (+/- 3 days) following administration of the study product.   
 
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6.1.9 Tracking of Dose and Treatment Compliance 
 
Subject diaries will be distributed and accounted for, along with return of used test tubes.  Subjects will fill out their diaries 
upon treatment application noting the following: 
• 
Time and date of application 
• 
Time and date of removal (washing off the study drug) 
• 
Confirmation that subject disinfected personal clothes, towels, linens and all potentially infected household items 
• 
Confirmation that the entire scalp and hair has been covered by the application 
 
Subjects will return their diaries to the clinical site for compliance review at Follow-up Day 2. The Investigator will verify 
that the subject complied with the application requirements and disinfection regimen. Both the subject and the study 
staff will sign off on completed diary. If the subject has missed the treatment application notation, this is considered a 
protocol deviation and must be reported. 
6.2 Study Drug Accountability 
 
The Sponsor will supply sufficient quantities of the study drug for the completion of this study.   
 
The study pharmacist or designated study personnel will maintain a Drug Receipt Log and a Subject Study Drug 
Accountability Log itemizing all study drug received, dispensed to and returned from each subject during the study. All 
dispensed tubes must be accounted for, and any discrepancies explained. Study site should contact site Clinical Research 
Associate (CRA) in case of any dispensing errors or if discrepancies are discovered. 
 
Prior to site closure and at appropriate intervals during the study, site CRA will perform study drug accountability and 
reconciliation. At the end of the study, the Investigator will retain all the original documentation regarding study drug 
accountability, return, and copies will be sent to the Sponsor. 
All unused and used Study Drug tubes will be returned to the Sponsor or its designee for destruction at the end of the 
study. 
7 Study Procedures and Schedule of Events 
7.1 Study Procedures/Evaluations 
 
Basic demographic information, including date of birth, sex, ethnicity, and race will be recorded at the Screening Visit. 
Medical history will be collected at the Screening and Baseline Visits. Relevant medical history, alcohol and tobacco history, 
and past history of head lice will be documented.  
All medications (both prescription and nonprescription, including vitamins, herbals, topical, inhaled, and intranasal) taken 
within 30 days prior to the start of the Study Drug and through the final study visit will be recorded on the appropriate eCRF 
(using their generic and brand names, if known) with the corresponding indication, start and stop dates. At each study visit, 
subjects will be asked whether they have started or discontinued any medication since their previous study visit. This 
includes single use or PRN (as needed) medication use. 
Vital signs will be collected at Baseline Visit 1 and Final Study Visit 5. Vital signs will include body temperature, heart rate 
and blood pressure (systolic and diastolic). Blood pressure and pulse rate will be measured after the subject has been sitting 
restfully for at least 5 minutes. Any abnormal characteristics of vital signs will be evaluated by the Investigator based on 
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their significance. Any abnormal vital signs will be considered AEs if they require therapeutic medical intervention, and/or 
if the Investigator considers them to be AEs based on his/her clinical judgement. 
Physical examination, including height, weight, and evaluation of organs and systems (General Appearance, 
Heart/Cardiovascular, Lungs, Gastrointestinal, Ears / Nose / Throat, Extremities, and Skin) will be assessed at the Screening 
Visit. 
 
7.1.1 Study Specific Procedures 
 
In addition to the regular standard of clinical care, the following study specific procedures will be included as part of the 
study.  
 
Past medical history of and previous treatment of head lice must be recorded irrespective of the term it was given.  
Corresponding condition shall be captured in the subject’s Medical History. 
 
Visual Assessment of Head Lice: 
Subjects and their household members will be thoroughly assessed for a minimum of 15 minutes for the presence or 
absence of live head lice, including adult lice, nymphs, and nits. Results will be recorded on the Site Assessment form. 
 
Skin/Scalp Irritation Assessment: 
Subjects will be assessed for skin and scalp pruritus, erythema, excoriation, and pyoderma. Results will be recorded on the 
Site Assessment form. 
 
Ocular Irritation: 
Subjects will be assessed for eye irritation, conjunctivitis, and ocular hyperemia. Results will be recorded on the Site 
Assessment form. 
 
Subject Diary: 
Administration of a checklist for laundry disinfection measures, application and removal of the study drug for index subject. 
Subject Assessments: 
Administration of questionnaires for subject-reported outcomes. The site will provide a Subject Self-Assessment 
Worksheet to record the grading of Itching and Stinging/Burning sensations. Analysis of tolerability will be based on scoring 
scales of Stinging/Burning and Itching sensations collected during Subject Self-Assessment at all follow-up visits between 
the test and reference treatment groups.   
   
 
7.2 Laboratory Procedures/Evaluations 
7.2.1 Clinical Laboratory Evaluations 
 
A urine pregnancy test will be performed for females of childbearing potential, this includes index subjects.  The baseline 
result must be available and must be negative before the index subject can apply the study drug. A positive pregnancy 
test will disqualify the entire household from participation in the study.  
7.3 Study Schedule 
7.3.1 Screening 
 
Screening Visit Day -1 to 0 (Visit 1) 
• 
Obtain informed consent of potential participant verified by signature on written informed consent for screening 
form. 
• 
Record demographic information, obtain medical history, alcohol and tobacco use, and history of head lice.   
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• 
Review medications history and concomitant/prohibited medications to determine eligibility based on 
inclusion/exclusion criteria. 
• 
Verify inclusion/exclusion criteria. 
• 
Perform medical examinations needed to determine eligibility based on inclusion/exclusion criteria. 
• 
Collect urine sample for pregnancy testing for all index subjects of child bearing potential. 
• 
Perform assessment for living head lice on index subjects and household members for a minimum of 15 minutes.  
The index subject must be the youngest family member presenting with at least 3 live lice.  After the index subject 
has been identified, additional infested household members will also be assessed for infestation (up to 3 per 
household). 
• 
Household members must have an active head lice infestation defined as: At least 1 live louse (adult and/or 
nymph) present on the scalp and/or hair, as determined by a trained evaluator (with the exception of the male 
head of household who may self-assess as being lice free). 
• 
Schedule study visits for participants who are eligible and available for the duration of the study.  
 
 
7.3.2 Enrollment/Baseline 
 
Enrollment/Baseline Visit Day 1 (Visit 1/ Visit 2)  
• 
Review concomitant and prohibited medications. 
• 
Record vital signs, results of examinations, other assessments. 
• 
Perform assessment for living head lice on index subject and household members (up to 3 per household) for 
visual confirmation of infestation for a minimum of 15 minutes. 
• 
Provide Standard of Care treatment on-site to infested household members (up to 3 per household).  
• 
Randomize the index subject. 
• 
Provide the study treatment for index subject. 
• 
Provide index subject with subject diary and homecare instructions. 
• 
Record Subject Self-Assessment for index subjects. 
• 
Inform index subject when to come back for their first follow-up visit. 
 
7.3.3 Follow-up 
 
Follow-up Visit Day 2 (Visit 3) (+/- 1 Day) 
• 
Record adverse events as reported by participant or observed by investigator. 
• 
Collect used test tube product from index subject. 
• 
Concomitant and prohibited medication review. 
• 
Perform assessment for living head lice on index subject for visual confirmation of infestation for a minimum 
of 15 minutes. 
• 
If active lice are present on index subject, provide Standard of Care and withdraw the subject from the study.  
• 
Record Subject Self-Assessment for index subjects. 
• 
Perform skin/scalp irritation and ocular irritation for index subjects and record results on Site Assessment 
form. 
• 
Record index subject’s adherence to treatment program through collection of subject diary. 
• 
Inform index subject when to come back for their follow-up visit. 
 
 
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Follow-up Visit Day 8 (Visit 4) (+/- 2 day) 
• 
Record adverse events as reported by participant or observed by investigator. 
• 
Concomitant and prohibited medication review. 
• 
Perform assessment for living head lice on index subject for visual confirmation of infestation for a minimum 
of 15 minutes. 
• 
If active lice are present, provide Standard of Care and withdraw the subject from the study.  
• 
Record Subject Self-Assessment for index subjects. 
• 
Perform skin/scalp irritation and ocular irritation for index subjects and record results on Site Assessment 
form. 
• 
Inform index subject when to come back for their final study visit. 
 
7.3.4 Final Study Visit 
 
Final Study Visit Day 15 (Visit 5) (+/- 3 days) 
• 
Record adverse events as reported by participant or observed by investigator. 
• 
Perform vital signs, results of examinations, and other assessments. 
• 
Concomitant and prohibited medication review. 
• 
Collect urine sample for pregnancy testing for any index subject of child bearing potential. 
• 
Perform assessment for living head lice on index subject for visual confirmation of infestation for a minimum of 
15 minutes. 
• 
Record Subject Self-Assessment for index subjects. 
• 
Perform skin/scalp irritation and ocular irritation for index subjects and record results on Site Assessment form. 
• 
Provide rescue standard of care treatment for any index subjects requiring additional treatment. 
 
7.3.5 Unscheduled Visit 
 
Subjects will be encouraged to report any complications or adverse effects during their participation. Investigator may 
evaluate the subject at an unscheduled visit, if subject’s condition is considered to be worsening. 
 
7.3.6 Rescreening 
 
If for some reason a subject is approved to participate in the study, but cannot return to the clinical site within 24 hours 
of their screening visit, they may be rescreened within 1 week.  This rescreening may also occur if all household members 
cannot be assessed at the clinical site within 24 hours of the index subject’s approval to participate in the study.  
Rescreening will be considered on an individual subject basis and must first be approved by the Investigator or Medical 
Monitor.   
 
7.4 Concomitant Medications, Treatments, and Procedures 
 
All medications (both prescription and nonprescription, and including vitamins, herbals, topical, inhaled, and intranasal) 
taken within 30 days prior to the start of the Study Drug and through the final study visit will be recorded on the 
appropriate eCRF (using their generic and brand names, if known) with the corresponding indication, start and stop dates. 
At each study visit, subjects will be asked whether they have started or discontinued any medication since their previous 
study visit. This includes single use or PRN (as needed) medication use. 
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Previous treatment of head lice must be recorded irrespective of the term it was given. Corresponding condition shall be 
captured in the subject’s Medical History. 
 
7.4.1 Precautionary Medications, Treatments, and Procedures 
 
In previous studies for topical Ivermectin, no exploration of drug-drug interactions was performed. 
 
7.5 Prohibited Medications, Treatments, and Procedures 
 
Head lice treatment products (over the counter [OTC], home remedy and/or Prescription) are prohibited 15 days prior to 
and during the study.  These include, but are not limited to: 
• 
Nix 
• 
Rid 
• 
Kwell 
• 
LiceMD 
 
7.6 Rescue Medications, Treatments, and Procedures 
 
If live lice are present on Day 2, Day 8 or Day 15, the subject will receive an over-the-counter (OTC) rescue treatment for 
head lice and their study participation will be considered complete and will be considered a treatment failure, with 
subjects to be considered in both the mITT and PP population. 
 
7.7  Participant Access to Study Drug at Study Center 
 
Participants will receive the study medication at their Enrollment/Baseline Visit. 
8  Assessment of Safety 
8.1 Specification of Study Parameters 
 
The Investigator will monitor each subject for clinical evidence of adverse events on a routine basis throughout the study. 
The Investigator will assess and record any AE in detail including the date of onset, description, severity, time course, 
duration and outcome, relationship of the adverse event to study drug, an alternate etiology for events not considered 
“related” or “probably related” to study drug, final diagnosis, if known, and any action(s) taken. For AEs to be considered 
intermittent, the events must be of similar nature and severity and each intermittent AE will be reported separately. AEs 
and SAEs, whether in response to a query, observed by site personnel, or reported spontaneously by the subject will be 
recorded, monitored and followed-up until the resolution (or until the Investigator deems the event to be stable/chronic). 
 
8.1.1 Definition of Adverse Events (AE) 
 
An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a 
pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can 
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therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of a medicinal (investigational) product, whether or not the event is considered 
causally related to the use of the investigational product. Treatment-emergent AEs (TEAE) will include any AEs reported 
beginning with the first application of study drug on Day 1. 
 
Such an event can result from use of the drug as stipulated in the protocol or labeling, as well as from accidental or 
intentional overdose, drug abuse, or drug withdrawal. Any worsening of a pre-existing condition or illness is considered 
an AE. I.e., if a new signs or symptom or worsening of a sign or symptom was believed by the investigator to be related to 
the study drug and not the disease, then it was recorded as an AE. Clinically significant abnormalities are to be followed 
to resolution (i.e. become stable, return to normal, return to baseline, or become explainable). Changes in vital signs are 
considered to be AEs only if they necessitate therapeutic medical intervention, and/or if the Investigator considers them 
to be AEs. 
 
8.1.2 Definition of Serious Adverse Events (SAE) 
 
If an AE meets any of the following criteria, it is to be reported to the Sponsor’s Safety department and Pharmacovigilance 
as a serious adverse event (SAE) using SAE report form within 24 hours of occurrence or notification to the study site: 
 
Death of Subject 
An event that results in the death of a subject. 
Life-Threatening 
An event that, in the opinion of the Investigator, would have resulted in immediate 
fatality if medical intervention had not been taken. This does not include an event that 
would have been fatal if it had occurred in a more severe form. 
Hospitalization 
An event that results in an admission to the hospital for any length of time. This does not 
include an emergency room visit or admission to an out-patient facility. 
Prolongation of 
Hospitalization 
An event that occurs while the study subject is hospitalized and prolongs the subject's 
hospital stay. 
Congenital Anomaly/birth 
defect 
An anomaly detected at or after birth or any anomaly that result in fetal loss. 
Persistent or Significant 
Disability/Incapacity 
An event that results in a condition that substantially interferes with the activities of daily 
living of a study subject. Disability is not intended to include experiences of relatively 
minor medical significance such as headache, nausea, vomiting, diarrhea, influenza, and 
accidental trauma (e.g., sprained ankle). 
Other Important Medical 
Event 
An important medical event that may not be immediately life-threatening or result in 
death or hospitalization, but based on medical judgment may jeopardize the subject and 
may require medical or surgical intervention to prevent any of the outcomes listed above 
(i.e., death of subject, life- threatening, hospitalization, prolongation of hospitalization, 
congenital anomaly, or persistent or significant disability/incapacity). Examples of such 
events include allergic bronchospasm requiring intensive treatment in an emergency 
room or at home, blood dyscrasias or convulsions that do not result in inpatient 
hospitalization, or the development of drug dependency or drug abuse. 
 
 
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8.1.3 Definition of Unanticipated Problems 
 
An Unexpected Adverse Event is any AE that is not identified in nature, severity, or frequency in the current Investigator’s 
Brochure or product information. 
A Serious and Unexpected Suspected Adverse Reaction (SUSAR) is any suspected adverse reaction to the study product 
that is both serious and unexpected.  
 
8.2 Classification of an Adverse Event 
8.2.1 Severity of Event 
 
The Investigator will use the following definitions to rate the severity of each AE and SAE: 
Mild 
The event is transient and easily tolerated by the subject. 
Moderate 
The event causes the subject discomfort and interrupts the subject's usual activities. 
Severe 
The event causes considerable interference with the subject's usual activities and may be 
incapacitating or life-threatening. 
 
8.2.2 Relationship to Study Drug 
 
The Investigator will use the following definitions to assess the relationship of the AE/SAE to the use of investigational 
product: 
Definitely Related 
The event occurred within a reasonable time after drug administration or drug 
concentration and body fluids demonstrated that the study drug was present: the event 
could not be reasonably explained by known characteristics including concomitant 
therapies; the adverse event abated after discontinuing the study drug. 
Probably Related 
The event has a strong temporal relationship to study drug or recurs on re-challenge and 
another etiology is unlikely or significantly less likely. 
Possibly Related 
The event has a strong temporal relationship to the study drug and an alternative etiology 
is equally or less likely compared to the potential relationship to study drug. 
Probably Not Related 
The event has little or no temporal relationship to the study drug and/or a more likely 
alternative etiology exists. 
Not Related 
The event is due to an underlying or concurrent illness or effect of another drug and is not 
related to the study drug (e.g., has no temporal relationship to study drug or has a much 
more likely alternative etiology). 
 
If an Investigator's opinion of not related to study drug is given, an alternate etiology must be provided by the Investigator 
for the AE. 
 
8.2.3 Expectedness 
 
The Principal Investigator will be responsible for determining whether an AE is expected or unexpected. An AE will be 
considered unexpected if the nature, severity, or frequency of the event is not consistent with the risk information 
previously described for the study agent. 
 
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8.3 Time Period and Frequency for Event Assessment and Follow-Up 
 
The Investigator will monitor each subject for clinical evidence of adverse events on a routine basis throughout the study. 
Any AE/SAE prior to the Baseline visit will be considered past medical history (PMH). The AE reporting period for this study 
begins upon receiving the first application of investigational product and ends at the final protocol required visit. SAE(s) 
that are observed or spontaneously reported during the subject’s participation in the trial will be captured and monitored 
until the Investigator deems the event to be chronic or not clinically significant or the subject to be stable. 
8.4 Reporting Procedures 
 
8.4.1 Adverse Event Reporting 
8.4.2 Serious Adverse Event Reporting 
 
In the event of a SAE, whether related to study drug or not, the Investigator or representative must make an accurate and 
adequate report consisting of at least the minimum criteria (Site and Subject ID, Date site became aware of the event, SAE 
Term, Seriousness criteria, Study Drug information, Investigator/Reporter and site address) within 24 hours by email, fax, 
or telephone to Biorasi Safety and Pharmacovigilance team. Biorasi Safety and Pharmacovigilance team will complete the 
SAE report onto a MedWatch 3500A form for evaluation and convey for review by the Medical Monitor and Sponsor 
contact. Accurate Completion of the MedWatch 3500A form will consist of all data supplied such as Subject’s demography, 
SAE narrative, concomitant medication, laboratory parameters and relevant medical history. 
In addition, if required by the applicable IRB/IEC, the Investigator will submit the SAE reports to the IRB/IEC within 15 
calendar days of discovering the SAE, or alternatively, within accordance of applicable regulations or IRB/IEC requirements. 
Copies of each report with the associated documentation (i.e., queries, medical records, lab records, IRB/IEC 
communications and all source documents) will be kept in the site’s study file. 
A subject experiencing one or more SAEs will receive treatment and follow-up evaluations by the Investigator or may be 
referred to another appropriate physician for treatment and follow-up. The Investigational Site will be responsible for 
collection and forwarding follow-up SAE information to the Biorasi Safety and Pharmacovigilance. 
 
MEDICAL MONITOR 
Sergey Pavlenko, MD 
Biorasi Safety and Pharmacovigilance 
E-mail: spavlenko@biorasi.com 
19495 Biscayne Blvd., Suite #900, Aventura, FL 33180 
Fax: +1 (786) 221-3531 
 
8.4.3 Unanticipated Problem Reporting 
 
All Serious and Unexpected Suspected Adverse Reactions (SUSAR) will be submitted as expedited reports to the applicable 
regulatory authorities/federal agencies. 
8.4.4 Reporting of Pregnancy 
 
If a subject, or female partner of male subject becomes pregnant during the participation in the study, the Investigator 
will immediately discontinue the subject from the study and contact the Medical Monitor and the Sponsor. Diligent efforts 
will be made to determine the outcome for all pregnancy exposures in the clinical trial. Information on the status of the 
mother and the child will be forwarded to the Sponsor’s Safety Team using the Pregnancy Data Collection Form. Generally, 
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follow-up will occur within 6 to 8 weeks following the estimated delivery date. Any premature termination of the 
pregnancy will be reported. Detailed guidance on the reporting of Pregnancies will be provided in SAE and Pregnancy 
Reporting Guidance. 
 
8.5 Safety Oversight 
 
Safety oversight will be under the direction of a medical monitor, working with the Biorasi Safety team.  The medical 
monitor is an expert that advises the study investigators and monitors participant safety.  The role of the medical monitor 
is to: 
• 
Review all adverse events on a regular basis throughout the trial 
• 
Be available to advise the investigators on trial-related medical questions or problems 
• 
Evaluate cumulative participant safety data and make recommendations regarding the safe continuation of 
the study 
 
The medical monitor remains blinded throughout the conduct of the clinical trial unless unblinding is warranted to 
optimize management of an adverse event or for other safety reasons. 
9 Clinical Monitoring 
 
Conducting Interim Monitoring Visits (IMV) helps verify that the rights, safety and well-being of Study participants are 
being protected, the Study data is accurate, complete, and verifiable from Source Documents and the Study is being 
conducted in compliance with the currently approved Protocol/amendment(s), Good Clinical Practice (GCP), Biorasi SOPs 
and site SOPs (if any) and other Regulatory requirement(s). 
Clinical site monitoring is conducted to ensure that the rights and well-being of human subjects are protected, that the 
reported trial data are accurate, complete, and verifiable, and that the conduct of the trial is in compliance with the 
currently approved protocol/amendment(s), with GCP, and with applicable regulatory requirement(s).   
A separate Clinical Monitoring Plan (CMP) will be used in this study. The CMP will outline in detail the parameters for 
clinical site monitoring, including who will conduct the monitoring, the frequency of monitoring, at what level of detail 
monitoring will be performed, and the distribution of reports.   
10 Statistical Considerations 
 
The sections below summarize the intended statistical methods and analyses of data for the study. 
Descriptive statistical methods will be used to summarize the data from this study, with confidence intervals calculated 
for the primary and secondary efficacy endpoints. Unless stated otherwise, the term “descriptive statistics” refers to 
number of subjects (n), mean, median, standard deviation (SD), minimum, and maximum for continuous data and 
frequencies and proportions for categorical data. The term “treatment group” refers to randomized treatment 
assignment: active-test, active-reference, and placebo. All data collected during the study will be included in data listings. 
Unless otherwise noted, the data will be sorted first by treatment assignment, subject number, and then by date within 
each subject number. 
Unless specified otherwise, all statistical testing will be two-sided and will be performed using a significance (alpha) level 
of 0.05. 
All statistical analyses will be conducted with the SAS® System, version 9.4. or higher. 
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10.1 Statistical and Analytical Plans 
 
A more detailed statistical analysis plan will be written prior to finalization of the clinical trial database. Any changes to 
the planned methods and analyses will be described and justified in the protocol and/or in the final clinical study report, 
as appropriate. 
 
10.2 Data Sets to Be Evaluated 
 
The subject populations are defined as follows: 
Safety Population includes all subjects who were randomized and dispensed treatment.  This is the population that will 
be used for the safety assessments. 
Modified Intent-to-Treat (mITT) population includes all Index subjects who met all inclusion/exclusion criteria, were 
randomized, dispensed treatment, and had at least one post-treatment efficacy evaluation.  This is the primary population 
for determination of the superiority of the active treatments over placebo. 
Per-Protocol (PP) population includes all mITT subjects who applied their dispensed treatment, had no protocol deviations 
which could have interfered with the accurate assessment of treatment efficacy, and returned for the Day 15 visit within 
the allowed window. This is the primary population for the efficacy comparisons between the two active treatment 
groups.  
Subjects whose condition worsens and require alternate or supplemental therapy for the treatment of head lice during 
the study will be discontinued, included in both the mITT and PP population analyses as treatment failures. Subjects who 
discontinue early for reasons other than treatment failure will be excluded from the PP population, but included in the 
mITT population, using Last Observation Carried Forward (LOCF). 
Efficacy analyses will be performed on both the per-protocol population and the mITT population. Safety analyses will be 
performed using the Safety population as defined. 
 
10.3 Statistical Hypotheses 
 
Primary Efficacy Endpoint: 
The primary efficacy endpoint is the proportion of index subjects who are lice free (defined as no live lice, adults or 
nymphs) 14 days (Day 15) after treatment.   
 
Secondary Efficacy Endpoint: 
 
The secondary efficacy endpoint is the number and percentage of all index subjects who are lice-free at Day 2. 
 
10.4 Description of Statistical Methods 
10.4.1 Subject Disposition and Demography 
 
Descriptive statistics will be generated by treatment group for selected continuous variables. The number and percentage 
of subjects in each class of categorical demographic and Baseline variables (e.g., gender, ethnicity, and race) will be 
tabulated by treatment group. Individual subject demographic and Baseline characteristic data will be listed. 
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10.4.2 Assessment of Bioequivalence and Superiority for Primary and Secondary Endpoints 
 
Bioequivalence assessment will be evaluated by comparing proportions of index subjects cured in the test and the 
reference treatment groups. Bioequivalence between the test and the reference product will be established if the 90% 
continuity-corrected confidence interval for the difference in proportions cured between test and reference treatment is 
contained within the equivalence limits [-0.20, +0.20]. 
The 90% confidence interval criteria are the same as rejecting the null hypotheses for the following two, one-sided t-tests, 
each at the α = 0.05 significance level: 
 
Ho: πT – πR < -0.20 
Ho: πT – πR > 0.20 
 
Ha: πT – πR ≥ -0.20 
Ha: πT – πR ≤ 0.20 
 
 
Combined Ha: -0.20 ≤ πT – πR ≤ 0.20 
 
 
where,  
 
πT and πR = the true cure proportions for Test and Reference treatments, respectively. 
 
 
 
The Bioequivalence results in the PP population will be considered definitive, with those in the mITT population 
considered supportive. 
The superiority assessments for each active treatment vs. the Placebo will be conducted using two-sided, continuity 
corrected Z-tests based on the following hypotheses: 
 
Ho: πT = πP 
Ho: πR = πP 
 
Ha: πT ≠ πP 
Ha: πR ≠ πP 
 
where,  
 
πT, πR, and πP = the true cure proportions for Test, Reference, and Placebo treatments, respectively. 
If both null hypotheses are rejected (p<0.05) and the observed cure proportions for the Test and Reference treatments 
are greater than that for the Placebo, then Superiority will be considered to have been demonstrated.   
The Superiority results in the mITT population will be considered definitive, with those in the PP population considered 
supportive. 
 
10.4.3 Safety Analyses 
 
The reporting of safety data is descriptive, and will include all subjects in the Safety population. The variables for safety 
endpoints are AEs. AEs will be summarized based on their frequency and their severity. All AEs will be coded using Medical 
Dictionary for Regulatory Activities (MedDRA) and summarized by treatment group. Data will be summarized using 
preferred term and primary system organ class. 
If a subject experiences multiple events that map to a single preferred term, the greatest severity and strongest 
Investigator assessment of relation to study drug will be assigned to the preferred term for the appropriate summaries. 
Should an event have a missing severity or relationship, it will be classified as having the highest severity and/or strongest 
relationship to study drug. 
Summaries of treatment-emergent AEs will include any AEs reported beginning with the first dose of study drug on Day 1. 
The occurrence of treatment-emergent adverse events will be summarized by treatment group using preferred terms, 
system organ classifications, and severity. Separate summaries of treatment-emergent serious adverse events, treatment-
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emergent adverse events related to study drug, and events leading to the discontinuation of study drug will be generated. 
All adverse events reported will be listed for individual subjects showing both verbatim and preferred terms. 
Concomitant medications will be coded using the World Health Organization (WHO) drug dictionary. These data will be 
summarized by treatment group. Previous and concomitant medications will be presented in a data listing. 
 
10.5 Sample Size 
 
Under the assumption that the Test and Reference treatments are equally efficacious with a true cure rate of at least 67%, 
and that the placebo has a true cure rate no greater than 27%, computer simulations were performed to determine the 
probability (power) of study success for different sample sizes. Study success in a simulated trial was defined as having 
the 90% continuity-corrected confidence interval in the PP population for the Test-to-Reference difference in cure 
proportions be contained in the bioequivalence interval [-0.20, +0.20] at the same time that both active treatments were 
demonstrated in the mITT population to have cure rates that were greater than, and statistically different (p<0.05) from, 
that of the placebo.  It was assumed that approximately 90% of the mITT subjects would qualify as PP ones. 
It was determined that for at least an 80% probability of study success, 280 mITT index subjects would be needed 
(120:120:40; Test: Reference: Placebo) to obtain 252 PP ones (108:108:36; Test: Reference: Placebo).   
11 Source Documents and Access to Source Data/Documents 
 
The Investigator/institution will permit study-related monitoring, audits/inspections, IRB/IEC review and regulatory 
inspection providing direct access to source documents, including all medical records or pertinent data relevant to the 
audit/inspection. Source documents will represent a record of the raw data.  Source document templates may be provided 
by either the clinical site, Sponsor representative, or the Sponsor. If provided by the clinical site, the source document 
template must be provided to the Sponsor prior to subject recruitment.  The source documents will become part of the 
subject's permanent medical record maintained by the clinical site. If computerized systems are used to create, modify, 
maintain, archive, retrieve or transmit source data, they must comply with the applicable regulatory regulations and/or 
guidance (ex. 21 CFR Part 11 and 312). 
12 Ethics/Subject Protection 
12.1 Ethical Standard 
 
The study will be conducted according to the protocol, GCP, as outlined in the ICH Guidelines and Code of Federal 
Regulations. Written informed consent for the study must be obtained from all subjects before protocol specific 
procedures are performed. Subjects must be informed of their right to withdraw from the study at any time and for any 
reason.  
12.2 Institutional Review Board 
 
It is the responsibility of the Investigator to have prospective approval of the study protocol, protocol amendments, 
informed consent forms, and other relevant documents, (e.g., recruitment advertisements, subject’s diaries, if applicable) 
from the IRB/IEC. All correspondence with the IRB/IEC will be retained in the Investigator File. Copies of IRB/IEC approvals 
should be forwarded to the Sponsor or its designee. 
The only circumstance in which an amendment may be initiated prior to IRB/IEC approval is where the change is necessary 
to eliminate apparent immediate hazards to the subjects. In case of such an event, the Investigator must notify the IRB/IEC 
and the Sponsor in writing immediately after the implementation. 
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12.3 Informed Consent Process 
12.3.1 Other Informational Documents Provided to Participants 
 
In addition to IRB/IEC approval, all other required approvals (e.g. approval from local Research and Development Board 
or Scientific Committee) required by the individual site for participating in this study will be obtained by the Investigator 
prior to recruitment of subjects into the study and shipment of the investigational product(s). It is the responsibility of the 
Investigator to notify the Sponsor and the CRO of the requirement of such approvals prior to participating tin the study. 
 
12.3.2 Consent Procedures and Documentation 
 
It is the responsibility of the Investigator to give each subject (or the subject’s acceptable representative), prior to inclusion 
in the trial, full and adequate verbal and written information regarding the objective and procedures of the trial and the 
possible risks involved. The subjects must be informed about their right to withdraw from the trial at any time. 
Furthermore, it is the responsibility of the Investigator, or a person designated by the Investigator, to obtain signed 
informed consent forms from each subject or the subject’s legally acceptable representative prior to inclusion in the trial. 
The Investigator will retain the original of each subject's signed consent form. 
The informed consent form will be in compliance with ICH GCP, local regulatory, and legal requirements. The informed 
consent form used in this study, and any changes made during the course of the study, must be prospectively approved 
by both the IRB/IEC and the Sponsor before use, and shared with the subject and/or their representative for continued 
inclusion in the study.  
   
12.4 Participant and Data Confidentiality 
 
All parties will ensure protection of subject personal data and will not include subject names on any Sponsor forms, 
reports, publications, or in any other disclosures, except where required by law. In case of data transfer, the Sponsor will 
maintain high standards of confidentiality and protection of subject personal data. 
The Sponsor and designees affirm and uphold the principle of the subject’s right to protection against invasion of privacy. 
Throughout this study, a subject’s source data will only be linked to the Sponsor’s clinical study database or documentation 
via a unique identification number. As permitted by all applicable laws and regulations, limited subject attributes, such as 
sex, age, or date of birth, and subject initials may be used to verify the subject and accuracy of the subject’s unique 
identification number. 
To comply with ICH Guidelines for GCP and to verify compliance with this protocol, the Sponsor requires the Investigator 
to permit its monitor or designee’s monitor, representatives from any regulatory authority (e.g., FDA), the Sponsor’s 
designated auditors, and the appropriate IRBs and IECs to review the subject’s original medical records (source data or 
documents), including, but not limited to, laboratory test result reports, ECG reports, admission and discharge summaries 
for hospital admissions occurring during a subject’s study participation, and autopsy reports. Access to a subject’s original 
medical records requires the specific authorization of the subject as part of the informed consent process. 
Copies of any subject source documents that are provided to the Sponsor must have certain personally identifiable 
information removed (i.e., subject name, address, and other identifier fields not collected on the subject’s CRF). 
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13 Data Handling and Record Keeping 
13.1 Study Records Retention 
 
To enable evaluations and/or audits from regulatory authorities or the Sponsor, the Investigator agrees to keep records, 
including the identity of all participating subjects (sufficient information to link records, e.g., CRFs and hospital records), 
all original signed Informed Consent Forms, copies of all CRFs, SAE forms, source documents, detailed records of drug 
disposition, and adequate documentation of relevant correspondence (e.g., letters, meeting minutes, telephone calls 
reports).  
The records will be retained by the Investigator according to the International Conference on Harmonization (ICH), local 
regulations, or as specified in the Clinical Study Agreement. 
If the Investigator becomes unable for any reason to continue to retain study records for the required period (e.g., 
retirement, relocation), the Sponsor will be prospectively notified. The study records must be transferred to a designee 
acceptable to the Sponsor, such as another Investigator, another institution, or to the Sponsor. The Investigator must 
obtain Sponsor’s written permission before disposing of any records, even if retention requirements have been met. 
13.2 Protocol Deviations 
 
The Investigator should not deviate from the protocol, except where necessary to eliminate an immediate hazard to study 
subjects. The site should document all protocol deviations in the subject’s source documents. In the event of a significant 
deviation, the site will notify the Sponsor or its designee (and IRB or IEC, as required). Significant deviations include, but 
are not limited to, those that involve fraud or misconduct, increase the health risk to the subject, or confound 
interpretation of primary study assessments. Deviations from the inclusion/exclusion criteria will not be permitted unless 
written approval by the Sponsor has been obtained. Should other unexpected circumstances arise that will require 
deviation from protocol-specified procedures, the Investigator will contact the Sponsor or designee at the below 
mentioned address in order to determine the appropriate course of action.  
Site will be responsible for proper maintaining and filing of all Protocol Deviation related documentation in the site files. 
Protocol Compliance review: 
• 
Verify that the Investigator and lnvestigational Site personnel are adhering to the IRB/IEC approved Protocol 
and all amendments. In addition to the Protocol, the Monitoring Plan may include (or reference) verification 
strategies which define a percentage of data points to be reviewed or other methodologies for verification of 
lnvestigational Site compliance. The Monitoring Plan should be followed regarding verification and study 
specific problem escalation, however the below are items that are often reviewed to verify Protocol 
compliance:  
o 
Checking that the correct randomization and Protocol-defined procedures, assessments and sampling 
requirements (if applicable) are being followed.  
o 
If unblinding has occurred (accidental or intentional), determine if the unblinding was done by 
authorized personnel, after consultation with the relevant Study team member(s) (e.g. Medical 
Monitor or Sponsor) and that the occurrence and reporting was appropriately documented in Source 
Documents, the regulatory binder and CRF, as required.  
• 
Verify that the Investigator is enrolling only eligible Study participants and all entry criteria are satisfied for 
each Study participant verified, as per the current approved Protocol. Documentation and verification of 
participant status in the study. 
• 
Verify that no prohibited medications or changes in dose for indication-related medications are being used 
without prior approval from Medical Monitor or Sponsor Designee.  
39 
 


Protocol Number: MAP-7189                                                                                                                                                       
 
Version 1.3;   28 December 2017 
  
 
• 
Address any protocol deviations with site personnel during the IMV and identify ways to prevent the 
recurrence of similar issues e.g. training the site team on that particular issue.  
 
13.3 Publication and Data Sharing Policy 
 
No publication or disclosure of study results will be permitted, except under the terms and conditions of a separate, 
written agreement between Sponsor and the Investigator and/or the Investigator’s institution. 
 
The Sponsor must have the opportunity to review and approve all proposed abstracts, manuscripts, or presentations 
regarding this study prior to submission for publication/presentation. Any information identified by the Sponsor as 
confidential must be deleted prior to submission. 
14 Conflict of Interest Policy 
 
The independence of this study from any actual or perceived influence, such as by the pharmaceutical industry, is critical.  
Therefore, any actual conflict of interest of persons who have a role in the design, conduct, analysis, publication, or any 
aspect of this trial will be disclosed and managed.  Furthermore, persons who have a perceived conflict of interest will be 
required to have such conflicts managed in a way that is appropriate to their participation in the trial.  
40 
 


Protocol Number: MAP-7189                                                                                                                                                       
 
Version 1.3;   28 December 2017 
  
 
15 Literature References 
 
1. Frequently Asked Questions.  Parasites, Lice, Head Lice.  Centers for Disease Control. C2015 [cited 2017 May 
17].  Available from:  https://www.cdc.gov/parasites/lice/head/gen_info/faqs.html 
 
2. Center for Drug Evaluation and Research, Application number 202736Orig1s000, Medical Review(s).  Available 
from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202736Orig1s000MedR.pdf 
3. Ivermectin Clinical Review.  Food and Drug Administration. c 2009. [cited 2017 May 17].  Available from: 
https://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DevelopmentResources/UCM331169.p
df 
 
4. Sklice® Lotion Prescribing Information, Center for Drug Evaluation and Research, February 2012.  Available 
from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202736Orig1s000LBL.pdf 
 
5. Head Lice Infestation: Developing Drugs for Topical Treatment Guidance for Industry, U.S. Department of 
Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER), 
October 2016.  Available from: 
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm 
 
6. Study Comparing the Safety and Efficacy of 0.5% Ivermectin Cream to Placebo in Lice Infested Subjects.  
ClinicalTrials.gov Identifier NCT00994422.  c2017 [cited 2017 May 17].  Available from: 
https://clinicaltrials.gov/ct2/show/NCT00994422?term=NCT00994422&rank=1 
 
7. Center for Drug Evaluation and Research, Application number 202736Orig1s000, Summary Review(s).  Available 
from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202736Orig1s000SumR.pdf 
 
 
41 
 


Protocol Number: MAP-7189                                                                                                                                                       
 
Version 1.3;   28 December 2017 
  
 
16 Appendices 
16.1 Schedule of Events 
Visit Number 
Visit 1 
Screening1 
Visit 2 
Baseline2 
Visit 3  
Follow-up 
Visit 4 
Follow-up 
Visit 5 
EOS/ET3 
Visit Day 
Day 
-1 to 0 
Day 1 
Day 24  
Day 8 
(±2) 
Day 15 
(±3) 
Informed Consent 
X 
 
 
 
 
Eligibility Criteria 
X 
 
 
 
 
Subject Demographics 
X 
 
 
 
 
Medical History 
X 
 
 
 
 
Physical Examination 
X5 
 
 
 
 
Investigational Product 
Dispensation/Randomization 
 
X6 
 
 
 
Vital Signs7 
 
X 
 
 
X 
Urine Pregnancy Test8 
X 
 
 
 
X 
Head Lice Visual Assessment 
X9 
X9 
X 
X 
X 
Household Members Standard of 
Care Treatment 
 
X 
 
 
 
Local Skin/Scalp Irritation 
Assessment 
 
 
X 
X 
X 
Ocular Irritation Assessment 
 
 
X 
X 
X 
Subject Self-Assessment 
 
X 
X 
X 
X 
Investigational Product 
Accountability 
 
 
X 
 
 
Subject Diary Dispensation 
 
X 
 
 
 
Subject Diary Collection and 
Compliance Review 
 
 
X 
 
 
Concomitant and Prohibited 
Medication Review 
X 
X 
X 
X 
X 
Adverse Events Assessment 
 
 
X10 
X 
X 
 
 
 
1 Rescreening will be permitted for out of window index subjects and those subjects whose household members cannot accompany them at their initial screening visit. 
2 Visit 2 (Baseline) may be completed on the same day as visit 1 (Screening). If Screening and Baseline are completed on the same day, assessments performed on both 
Screening and Baseline need only be performed once. Refer to Section 7. Study Procedures and Schedule of Events for details and restrictions. 
3 Index subjects identified as treatment failures will be terminate early from the study and be provided the standard of care rescue treatment. 
4 Must be within 24 hours of treatment. 
5 Physical examinations are to be performed if Inclusion/Exclusion Criteria are satisfied at Screening. 
6 Prior to Randomization, the Investigator must confirm the subject still meets all Inclusion/Exclusion Criteria. 
7 Vital signs will include body temperature, heart rate and blood pressure (systolic and diastolic). Blood pressure and heart rate will be measured after the subject has been 
sitting restfully for at least 5 minutes. 
8 For female index subjects of child-bearing potential.  
9 For both index subjects and infested household members. 
10 AE reporting period for this study begins upon receiving the first application of investigational product and ends at the final protocol required visit. 
42 
 
                                                             


Protocol Number: MAP-7189                                                                                                                                                       
 
Version 1.3;   28 December 2017 
  
 
16.2 Subject Diary 
 
 
 
SUBJECT 
NUMBER: 
 
 
 
 
 
 
SUBJECT 
INITIALS:   
 
BASELINE VISIT 
DATE: 
 
 
 
 
 
 
 
 
 
 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 
 
To be completed by the study team member & cover page to remain at the site 
SUBJECT TREATMENT INFORMATION 
Study Visit 
Visit 2 
    
HOUSEHOLD MEMBERS TREATMENT INFORMATION 
Number of Infested Household Members 
 
Number of Non-Infested Household Members 
 
Total Number of Household Members 
 
Infested Household Member # 1 Standard of Care Treatment 
 Yes     
No 
Infested Household Member # 2 Standard of Care Treatment 
 Yes     
No 
Infested Household Member # 3 Standard of Care Treatment  
 Yes     
No 
 
 
 
 
 
Protocol Number:  MAP-7189 
Study Title:  
A Randomized, Multi-Center, Double-blind, Placebo Controlled, Parallel Group 
Trial to Evaluate Efficacy and Safety of Mayne Pharma’s Ivermectin 0.5% Lotion 
Compared to Sklice® Ivermectin 0.5% Lotion in the Treatment of Head Lice 
Subject Diary  
43 
 


Protocol Number: MAP-7189                                                                                                                                                       
 
Version 1.3;   28 December 2017 
  
 
SUBJECT 
NUMBER: 
 
 
 
 
 
 
SUBJECT 
INITIALS:   
 
VISIT DATE: 
 
 
 
 
 
 
 
 
 
 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 
APPLICATION OF THE STUDY DRUG 
Activity 
Instructions for Application of study drug 
Status check (Tick) 
Application of 
Lotion 
• 
Apply full tube amount (4 oz.) to fully coat dry 
hair and scalp for children ages 5 and older 
• 
For babies, apply 1 oz. (1/4 of a tube) and for 
toddlers apply 2 oz. (1/2 of a tube). 
• 
Avoid contact with eyes and mucus membranes 
• 
Record the date and time the lotion was applied 
• 
Leave on for 10 minutes  
 
 
 
 Yes     
No 
Date of Application 
 
Time of Application
 
AFTER 
• 
After 10 minutes fully rinse lotion off with warm 
water 
• 
Record the date and time the lotion was washed 
off  
• 
Caregivers to properly wash hands after 
treatment. 
 
 
Yes     
No 
Date of Removal 
Time of Removal  
 
AFTER  
(cont.)  
• 
Do not shampoo, wash, or rinse hair or scalp 
until the 24-hour post-treatment evaluation 
has been completed. 
 
 
Yes     
No 
Date to Shampoo Hair 
Time to Shampoo Hair 
 
ASSOCIATED STEPS WITH STUDY TREATMENT 
Activity  
Status check (Tick) 
LAUNDRY DISINFECTION:  
• 
Wash (in hot water) or dry-clean all recently worn clothing, hats, used bedding & 
towels.  
 Yes     
No 
44 
 


Protocol Number: MAP-7189                                                                                                                                                       
 
Version 1.3;   28 December 2017 
  
 
• 
Wash (in hot water) personal care items such as combs, brushes, & hair clips 
45 
 


Protocol Number: MAP-7189                                                                                                                                                       
 
Version 1.3;   28 December 2017 
  
 
SUBJECT 
NUMBER: 
 
 
 
 
 
 
SUBJECT 
INITIALS:   
 
VISIT DATE: 
 
 
 
 
 
 
 
 
 
 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 
 
Please answer the following questions by ticking the correct box: 
1. Have you had any health problems since your last visit to clinic?                             
    Yes 
 
No 
      If yes, please discuss with Principal Investigator at your next visit.:  
 
2. Have you had any local skin reactions since your last visit to clinic?                
                                
   Yes 
                No 
      If yes, please discuss with Principal Investigator at your next visit: 
 
3. Have you taken any new medications since your last visit to clinic?             
                                         
     Yes 
              No 
          If yes, please discuss with Principal Investigator at your next visit 
 
In case of medical emergency call 911 immediately. 
Remember the next study visit date is on (Next Day): _________________ 
 
Subject’s Signature: ____________________________________  
Date: ___ ___ - ___ ___ ___ - ___ ___ ___ ___  
AND/OR 
Caregiver’s Signature: ____________________________________  
Date: ___ ___ - ___ ___ ___ - ___ ___ ___ ___  
 
Initials of Site Staff verifying the completeness of the Subject Diary: ___- ___ - ___ 
Date of Verification: ___ ___ - ___ ___ ___ - ___ ___ ___ ___ 
 
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Protocol Number: MAP-7189                                                                                                                                                       
 
Version 1.3;   28 December 2017 
  
 
16.3 Subject Self-Assessment 
SUBJECT SELF ASSESSMENT 
SITE PERSONELL TO COMPLETE: 
SUBJECT 
NUMBER: 
 
 
 
 
 
 
SUBJECT 
INITIALS:   
 
VISIT DATE: 
 
 
 
 
 
 
 
 
 
 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 
 
Visit Number 
Visit 2 [Baseline] 
Visit 3 [Follow Up] 
Visit 4 [Follow Up] 
Visit 5 [Final Study Visit] 
Visit Day 
Day 1 
 
Day 2 
 
Day 8 
 
Day 15 
 
  
TO BE COMPLETED BY SUBJECT AND/OR CAREGIVER: 
This assessment is aimed to rate the itching and stinging/burning sensations you may have experienced after the 
application of the lotion. Please rate the experience in the tables below.  
ITCHING 
(Intense, distracting irritation or tickling sensation in the last 24 hours) 
Score 
Grade 
Definition 
Check one 
0 
None 
The scalp does not itch. 
 
1 
Mild 
Occasional episodes of itching, not bothersome.  
 
2 
Moderate 
Frequent, several times a day, bothersome. 
 
3 
Severe 
Nearly constant, frequent, very bothersome. 
 
STINGING/BURNING 
(Sensation of the skin is painfully hot or noticeable tingling sensation in the last 24 hours) 
Score 
Grade 
Definition 
Check one 
0 
None 
Absent 
 
1 
Mild 
Slight, barely present 
 
2 
Moderate 
Distinct presence 
 
3 
Severe 
Marked, intense 
 
Subject and/or Caregiver (Initials): _____________________  
 
Date__________________ 
 
Completed & Reviewed By (Initials): ______________       
 
Date__________________  
 
 
47 
 


Protocol Number: MAP-7189                                                                                                                                                       
 
Version 1.3;   28 December 2017 
  
 
16.4 Site Assessment 
SITE ASSESSMENT 
SUBJECT 
NUMBER: 
 
 
 
 
 
 
SUBJECT 
INITIALS:   
 
VISIT DATE: 
 
 
 
 
 
 
 
 
 
 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 
SITE PERSONNEL TO COMPLETE: 
1. Head Lice Evaluation minimum of 15 minutes: 
 
 
Live Adult Lice Present:     
 Yes     
 No 
Number of: __________________ 
Live Nymphs Present:        
 Yes     
 No 
Number of: __________________ 
2. Skin/Scalp Irritation Assessment (include forehead, neck and ears):  
 
Rating 
Type of Irritation 
Pruritus= Itching 
Erythema= Redness of 
the scalp 
Excoriation= Breaking of the 
skin, usually caused by 
scratching 
Pyoderma= Sores filled with 
clear fluid, pus or crusting 
None = 0 
The scalp does not 
itch. 
No redness of the 
scalp. 
No broken skin on the scalp. 
No lesions visible on the 
scalp. 
Mild = 1 
Occasional episodes 
of itching, not 
bothersome.  
Faint, barely 
perceptible erythema 
with limited 
distribution. 
One or two areas on the 
scalp on which skin is 
broken. 
One or two lesions visible 
with crusting or other 
evidence of infection. 
Moderate = 2 
Frequent, several 
times a day, 
bothersome. 
Diffuse pink areas of 
scalp are readily 
visible. 
More than two separate 
areas of the scalp with 
broken skin but not 
generalized across the scalp. 
Presence of more than two 
lesions with crusting or 
other evidence of infection, 
but not generalized across 
the scalp. 
Severe = 3 
Nearly constant, 
frequent scratching, 
very bothersome. 
Large areas of the 
scalp are red. 
Widespread breaking of the 
skin involving most of the 
scalp. 
Lesions with crusting or 
other evidence of infection, 
involving most of the scalp. 
Pruritus Score= 
______ 
Erythema Score= ______ 
Excoriation Score= ______ 
Pyoderma Score= ______ 
3. Ocular Irritation Assessment: 
 
Eye irritation present:            
 Yes     
 No 
 
Conjunctivitis present:           
 Yes     
 No 
 
Ocular Hyperemia present:   
 Yes     
 No 
Completed By (Initials): _________           Date___________ 
48 
 

SAP_000.pdf: 
Mayne Pharma, LLC 
MAP-7189 
  
Statistical Analysis Plan 
Version 1 
 
 
 
 
Statistical Analysis Plan 
 
Study Title: 
A Randomized, Multi-Center, Double-blind, Placebo 
Controlled, Parallel Group Trial to Evaluate Efficacy and 
Safety of Mayne Pharma’s Ivermectin 0.5% Lotion 
Compared to Sklice® Ivermectin 0.5% Lotion in the 
Treatment of Head Lice 
 
 
Phase: 
Phase 3 
 
 
Protocol No.: 
MAP-7189  
 
 
Original Protocol Version 1.0 
17 August 2017 
Protocol Amendment Version 1.3 
28 December 2017 
 
 
Analysis Plan Version and Date 
Version 1.0: 30 November 2017 
 
 
Prepared By: 
Jon Roth 
VP Data Sciences and Biometrics 
Biorasi, LLC 
 
 
 
 
Prepared For: 
MAYNE PHARMA, LLC. 
1240 Sugg Parkway, 
Greenville, NC 27858 USA 
Phone:  +1 (252) 717-1382 
Fax:  +1 (252) 758-8522 
 
 
CONFIDENTIAL AND PROPRIETARY INFORMATION 
 
 
CONFIDENTIAL 
Page 1 
30 November 2017 




Mayne Pharma, LLC 
MAP-7189 
  
Statistical Analysis Plan 
Version 1 
Contents 
STATISTICAL ANALYSIS PLAN REVIEW AND APPROVAL ..............................................2 
1 
INTRODUCTION ........................................................................................................5 
1.1 
Study Overview ............................................................................................................5 
1.2 
Time and Events Schedule ............................................................................................7 
1.3 
Glossary of Terms .........................................................................................................8 
2 
OBJECTIVES ..............................................................................................................9 
3 
GENERAL STATISTICAL CONSIDERATIONS .......................................................9 
3.1 
Sample Size Estimation .................................................................................................9 
3.2 
Randomization ..............................................................................................................9 
3.3 
Blinding and Procedures for Unblinding the Study ...................................................... 10 
3.4 
Handling of Data ......................................................................................................... 11 
3.4.1 
Examination of Subject Subsets ............................................................................... 11 
3.4.2 
Missing Data ........................................................................................................... 11 
3.4.3 
Definitions and Terminology ................................................................................... 11 
3.5 
Planned Analyses ........................................................................................................ 12 
4 
ANALYSIS POPULATIONS ..................................................................................... 12 
5 
STATISTICAL METHODS ....................................................................................... 12 
5.1 
Subject Disposition, Demographic and Baseline Characteristics .................................. 13 
5.2 
Efficacy Analyses ....................................................................................................... 13 
5.2.1 
Primary Efficacy Endpoint ...................................................................................... 13 
5.2.2 
Primary Efficacy Analyses ...................................................................................... 14 
5.2.3 
Secondary Efficacy Endpoints ................................................................................. 15 
5.2.4 
Secondary Efficacy Analyses................................................................................... 15 
5.3 
Retreatment Assessment ............................................................................................. 15 
5.4 
Tolerability Assessment .............................................................................................. 15 
5.5 
Safety Assessment ...................................................................................................... 16 
5.5.1 
Adverse Events ........................................................................................................ 16 
5.5.2 
Vital Signs ............................................................................................................... 17 
5.5.3 
Previous and Concomitant Medications ................................................................... 17 
6 CHANGES IN THE PLANNED ANALYSES .................................................................... 17 
7 PROGRAMMING CONVENTIONS .................................................................................. 17 
8 TABLES, LISTINGS AND FIGURES ................................................................................ 20 
 
 
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Mayne Pharma, LLC 
MAP-7189 
  
Statistical Analysis Plan 
Version 1 
Tables ....................................................................................................................................... 20 
Data Listings ............................................................................................................................. 22 
APPENDIX A:  ITCHING SENSATION SCALE .................................................................... 24 
APPENDIX B: STINGING/ BURNING SENSATION SCALE ................................................ 24 
APPENDIX C:  SKIN/SCALP IRRITATION ASSESSMENT 
APPENDIX D: OCULAR IRRITATION ASSESSMENT 
 
 
 
 
 
 
 
 
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Mayne Pharma, LLC 
MAP-7189 
  
Statistical Analysis Plan 
Version 1 
1.   INTRODUCTION 
This document describes the statistical methods and data presentations to be used in the summary 
and analysis of data from Protocol MAP-7189.  Background information is provided for the overall 
study design and objectives.  The reader is referred to the study protocol and electronic case report 
forms (eCRFs) for details of study conduct and data collection. 
1.1.   Study Overview 
Clinical protocol MAP-7189 is a Randomized, Multi-Center, Double-blind, Placebo Controlled, 
Parallel Group Trial to Evaluate Efficacy and Safety of Mayne Pharma’s Ivermectin 0.5% Lotion 
Compared to Sklice® Ivermectin 0.5% Lotion in the Treatment of Head Lice.  The primary 
objective of the study is to establish the efficacy of a single application of Ivermectin 0.5% lotion 
in the treatment of head lice under at-home use conditions compared with Sklice® 0.5% lotion, 
and to demonstrate that both active lotions have superior efficacy compared to Placebo. 
The study also assesses comparative safety of Ivermectin 0.5% Lotion (Mayne Pharma, LLC) and 
Sklice® Ivermectin 0.5% Lotion and local tolerability of Ivermectin 0.5% Lotion. 
The subject population includes healthy male and female subjects aged 6 months to 18 years who 
are infested with Pediculus humanus capitis. The youngest infested household member will be 
considered the index subject.  Household members, up to a maximum of 3 members, infested with 
an active head lice infestation defined as at least 1 live louse (adult and/or nymph) present on the 
scalp and/or hair, as determined by a trained evaluator will receive treatment with an over-the-
counter head lice treatment product at baseline. 
The study is comprised of three phases:  Screening, Treatment, and Follow-Up.  The duration of 
this study is 15 days (+/- 3). The Screening Phase is Day -1-0.  The Treatment Phase is Day 1.  
Preferably, screening and treatment will occur on the same day. The Final Study Visit is on day 
15 (+/- 3 days) following administration of the study product.   
Potential subjects will be screened and the index subject will be eligible for enrollment into the 
study. During the baseline visit (Day 1), which can occur on the same day as screening (Day 0), 
the Investigator will record subject’s demographics, medical history, review concomitant 
medication, identifying any prohibited therapies the subject may receive, perform physical 
examination, collect vital signs and perform urine pregnancy test.   
Eligible subjects will be randomized in a ratio of 3:3:1 to receive either the Mayne Pharma’s 
Ivermectin 0.5% lotion, Sklice® 0.5% lotion, or placebo lotion treatment and will be trained on 
the application of the study drug and subject’s diary completion. Infested household members, up 
to 3 members per household, will be treated with an over-the-counter head lice treatment product 
on-site. 
The study drug will be applied as a single, at-home dose.  Subjects will be instructed to apply a 
full tube amount (4 oz.) of Ivermectin 0.5% lotion to fully coat dry hair and scalp, avoiding the 
 
 
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Mayne Pharma, LLC 
MAP-7189 
  
Statistical Analysis Plan 
Version 1 
eyes and mucus membranes. The lotion will be left on the hair and scalp for 10 minutes, then 
rinsed off with warm water.  The tube is intended for a single use; all used tubes should be returned 
at the second visit (first follow-up visit) to the clinical site for product accountability.  In addition 
to receiving the study drug, the index subjects and household members will be instructed on an 
overall lice management program, which includes: 
• Wash (in hot water) or dry-clean all recently worn clothing, hats, used bedding and 
towels.  
• Wash (in hot water) personal care items such as combs, brushes and hair clips. 
• A fine-tooth comb or special nit comb may be used to remove dead lice and nits after 
treatment. 
Index subjects will return for post-baseline visits assessments at Days 2, 8, and 15, returning used 
tubes of the study drug at Day 2, which will be accounted for along with diary cards, which will 
be reviewed by the site personnel for completeness. The Investigator will perform a visual 
assessment for the presence or absence of head lice, record local application site reactions, and 
perform an ocular irritation assessment. The site will provide a Subject Self-Assessment worksheet 
to record tolerability of treatment. Urine pregnancy testing will be performed at the Screening Visit 
and the Final Study Visit, with interim visits confirming pregnancy has not occurred through 
questioning of the index subject. 
Final efficacy, safety and tolerability assessments will occur at visit 5 (Day 15±3). Subjects will 
be encouraged to report any complications or adverse effects during their participation.   
 
 
 
 
 
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Mayne Pharma, LLC 
MAP-7189 
  
Statistical Analysis Plan 
Version 1 
1.2.   Time and Events Schedule 
TABLE 1.2 Study Procedures and Assessments. 
Visit Number 
Visit 1 
Screening1 
Visit 2 
Baseline2 
Visit 3  
Follow-up 
Visit 4 
Follow-up 
Visit 5 
EOS/ET3 
Visit Day 
Day 
-1 to 0 
Day 1 
Day 24  
Day 8 
(±2) 
Day 15 
(±3) 
Informed Consent 
X 
 
 
 
 
Eligibility Criteria 
X 
 
 
 
 
Subject Demographics 
X 
 
 
 
 
Medical History 
X 
 
 
 
 
Physical Examination 
X5 
 
 
 
 
Investigational Product 
Dispensation/Randomization 
 
X6 
 
 
 
Vital Signs7 
 
X 
 
 
X 
Urine Pregnancy Test8 
X 
 
 
 
X 
Head Lice Visual Assessment 
X9 
X9 
X 
X 
X 
Household Members Standard 
of Care Treatment 
 
X 
 
 
 
Local Skin/Scalp Irritation 
Assessment 
 
 
X 
X 
X 
Ocular Irritation Assessment 
 
 
X 
X 
X 
Subject Self-Assessment 
 
X 
X 
X 
X 
Investigational Product 
Accountability 
 
 
X 
 
 
Subject Diary Dispensation 
 
X 
 
 
 
Subject Diary Collection and 
Compliance Review 
 
 
X 
 
 
Concomitant and Prohibited 
Medication Review 
X 
X 
X 
X 
X 
Adverse Events Assessment 
 
 
X10 
X 
X 
1 Rescreening will be permitted for out of window index subjects and those subjects whose household members cannot accompany them at their initial screening visit. 
2 visit 2 (baseline) may be completed on the same day as visit 1 (screening). If screening and baseline are completed on the same day, assessments performed on both 
screening and baseline need only be performed once. Refer to section 7. Study procedures and schedule of events for details and restrictions. 
3 index subjects identified as treatment failures will be terminate early from the study and be provided the standard of care rescue treatment. 
4 must be within 24 hours of treatment. 
5 physical examinations are to be performed if inclusion/exclusion criteria are satisfied at screening. 
6 prior to randomization, the investigator must confirm the subject still meets all inclusion/exclusion criteria. 
7 vital signs will include body temperature, heart rate and blood pressure (systolic and diastolic). Blood pressure and heart rate will be measured after the subject has 
been sitting restfully for at least 5 minutes. 
8 for female index subjects of child-bearing potential.  
9 for both index subjects and infested household members. 
10AE reporting period for this study begins upon receiving the first application of investigational product and ends at the final protocol required visit. 
 
 
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Mayne Pharma, LLC 
MAP-7189 
  
Statistical Analysis Plan 
Version 1 
1.3.   Glossary of Terms 
AE 
Adverse Event 
CFR 
Code of Federal Regulations 
CMP 
Clinical Monitoring Plan 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
eCRF 
Electronic Case Report Forms 
EOS 
End of Study 
ET 
Early Termination 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IMV 
Interim Monitoring Visit 
IRB 
Investigational Review Board 
ITT 
Intent to Treat 
LOCF 
Last Observation Carried Forward 
Mayne 
Mayne Pharma, LLC/ Mayne Pharma International Pty Ltd 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
Modified Intent-to-Treat 
MRT 
Mean Residence Time 
OTC 
Over the Counter 
PI 
Principal Investigator 
PMH 
Past Medical History 
PP 
Per-Protocol 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SAS 
Statistical Analysis System 
SD 
Standard deviation 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
SUSAR 
Suspected Unexpected Serious Adverse Event 
TEAE 
Treatment Emergent Adverse Event 
US 
United States 
 
 
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Mayne Pharma, LLC 
MAP-7189 
  
Statistical Analysis Plan 
Version 1 
2.  OBJECTIVES 
The primary objective of this study is: 
• To establish the efficacy of a single application of Ivermectin 0.5% lotion in the treatment 
of head lice (Pediculus humanus capitis) under at-home conditions compared with Sklice® 
0.5% lotion 
• To demonstrate that both active lotions have superior efficacy compared to Placebo 
The secondary objective of this study is: 
• To demonstrate comparative safety and local tolerability of Ivermectin 0.5% lotion (Mayne 
Pharma, LLC) vs Sklice® 0.5% lotion. 
3.   GENERAL STATISTICAL CONSIDERATIONS 
3.1.   Sample Size Estimation 
Under the assumption that the Test and Reference treatments are equally efficacious with a true 
cure rate of at least 67%, and that the placebo has a true cure rate no greater than 27%, computer 
simulations were performed to determine the probability (power) of study success for different 
sample sizes.  Study success in a simulated trial was defined as having the 90% continuity-
corrected confidence interval in the PP population for the Test-to-Reference difference in cure 
proportions be contained in the bioequivalence interval [-0.20, +0.20] at the same time that both 
active treatments were demonstrated in the mITT population to have cure rates that were greater 
than, and statistically different (p<0.05) from, that of the placebo.  It was assumed that 
approximately 90% of the mITT subjects would qualify as PP ones. 
It was determined that for at least an 80% probability of study success, 280 mITT index subjects 
would be needed (120:120:40; Test: Reference: Placebo) to obtain 252 PP ones (108:108:36; Test: 
Reference: Placebo).   
3.2.   Randomization 
This is a double-blind study, thus all site staff, study monitor, and subjects will be blinded to the 
randomization scheme except for the Unblinded Site Personnel/ designee and Unblinded 
Monitor. Furthermore, the randomization scheme will be retained by the Drug Depot and will 
only be shared with Unblinded Site Personnel or designee.  
The actual treatment given to individual subjects is determined by a computerized block 
randomization scheme prepared by an independent third party.  The independent third party will 
prepare the randomization list and hold it throughout the conduct of the study.  Subjects are 
randomized on a 3:3:1 basis (test drug: active comparator: placebo) and stratified by clinical site. 
 
 
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After signing the Informed Consent, each subject will be assigned a unique subject number.  Subjects 
are identified using subject initials, subject number, and date of birth. The subject numbers will be 
generated by the EDC and assigned sequentially in the order in which subjects are consented at 
each center.  
If a subject discontinues from the study, the subject number and randomization number are not to 
be reused, and the subject is not allowed to re-enter the study. 
The randomization scheme for treatment allocation will be used for statistical and reporting 
purposes. A copy of the randomization assignment will be retained at each clinical site by 
unblinded personnel and will be available to FDA or other regulatory agency investigators at the 
time of site inspection to allow for verification of the treatment identity of each subject. 
3.3.   Blinding and Procedures for Unblinding the Study 
This is a double-blind study, thus Sponsor, CRO, assessor site staff, study monitors, and subjects 
will be blinded to the randomization scheme. The packaging of the study drug products will be 
similar in appearance to make difference in treatment less obvious to the subjects. Blank, opaque 
diaper labels will be applied to each study tube for maintenance of study blinding. Each tube will 
be packaged in individualized cartons. Neither the Investigator nor the subject should be able to 
identify the received treatment. The dispensed investigational product will NOT be opened by the 
index subject and their family members at the study center. 
The blinding code must not be broken except in emergency situations for which the identification 
of the study treatment of a subject is required by the Investigator to complete a serious adverse 
event report. In such situations, the Medical Monitor or the Investigator will use the Unblinded 
Treatment List in order to unblind the treatment for the individual subject. Unblinded information 
will be held by designated individual(s), and the date and reason for breaking the blind must be 
recorded.  
The Medical Monitor must be contacted by telephone prior to unblinding but no later than 24 hours 
after unblinding. As the study is blinded, the Investigator should promptly document and explain 
to the Sponsor any premature unblinding (e.g., accidental unblinding, unblinding due to a serious 
adverse event) of the investigational product(s). Every effort should be made to avoid unblinding 
extra study personnel. 
 
 
 
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3.4.   Handling of Data 
3.4.1.   Examination of Subject Subsets 
The primary and secondary efficacy endpoints will be summarized separately using descriptive 
statistics by treatment group and study day, where appropriate. No formal statistical testing will 
be utilized.  
3.4.2.   Missing Data  
Every effort will be made to obtain required data at each scheduled evaluation from all subjects 
who have been randomized. In situations where it is not possible to obtain all safety data, 
imputation of missing data will not be conducted.  A Last-Observation-Carried-Forward 
imputation method for missing efficacy data will be used for the mITT population.  
3.4.3.   Definitions and Terminology 
Treatment Day 1 (Baseline) 
Treatment Day 1 is the day that study treatment is first initiated. 
Study Day  
Study Day is defined relative to study treatment initiation (Study Day 1). Thus, the study day of 
an event is calculated as: 
Study Day = event date – date of Study Day 1 +1. 
Days on Study 
Days on Study is the number of days from Study Day 1 to the date of study completion or early 
termination as recorded on the study termination eCRF. 
End of Treatment 
For efficacy assessments, end of treatment is defined as the last non-missing assessment taken 
prior to discontinuation of study treatment. 
Concomitant Medications 
Concomitant medications are those medications taken on or after the initiation of study treatment.  
This definition includes prescription and all over-the-counter (OTC) medications and all dietary 
supplements. 
 
 
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Previous Medications 
Previous medications are those medications taken within the 30 days and stopped prior to the 
initiation of study therapy. 
Treatment-Emergent Adverse Event  
A treatment-emergent adverse event is defined as any adverse event occurring on or after the 
initiation of study treatment.  For the purpose of defining treatment-emergent adverse events, it is 
assumed that an adverse event which was reported to have started on Treatment Day 1 without an 
associated onset time may have occurred after the initiation of study treatment.  Hence, adverse 
events occurring on Treatment Day 1 are assumed to be treatment-emergent. 
3.5.  Planned Analyses 
A final analysis is planned after the last subject completes or discontinues the study, and the 
resulting clinical database has been cleaned, quality checked, and locked. 
4.   ANALYSIS POPULATIONS 
The populations defined for analysis will include the modified intent-to-treat (mITT), per-protocol 
(PP), and the safety population.  
Safety Population includes all subjects who were randomized and dispensed treatment.  This is the 
population that will be used for the safety assessments. 
Modified Intent-to-Treat (mITT) Population includes all Index subjects who met all 
inclusion/exclusion criteria, were randomized, dispensed treatment, and had at least one post-
treatment efficacy evaluation.  This is the primary population for determination of the superiority 
of the active treatments over placebo. 
Per-Protocol (PP) Population includes all mITT subjects who applied their dispensed treatment, 
had no protocol deviations which could have interfered with the accurate assessment of treatment 
efficacy, and returned for the Day 15 visit within the allowed window. This is the primary 
population for the efficacy comparisons between the two active treatment groups.  
Subjects whose condition worsens and require alternate or supplemental therapy for the treatment 
of head lice during the study will be discontinued, included in both the mITT and PP population 
analyses as treatment failures. Subjects who discontinue early for reasons other than treatment 
failure will be excluded from the PP population, but included in the mITT population. Last 
Observation Carried Forward (LOCF) will be used to impute any missing endpoints. 
Efficacy analyses will be performed on both the per-protocol population and the mITT population. 
Safety analyses will be performed using the Safety population as defined. 
 
 
 
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5.   STATISTICAL METHODS 
Descriptive statistical methods will be used to summarize the data from this study, with confidence 
intervals calculated for the primary and secondary efficacy endpoints.  The term “descriptive 
statistics” refers to number of subjects (n), mean, median, standard deviation (SD), minimum, and 
maximum for continuous data and frequencies and percentages for categorical data.  The term 
“treatment group” refers to randomized treatment assignment: active-test, active-reference, and 
placebo.  All data collected during the study will be included in data listings.  The data will be 
sorted first by subject number, and then by date within each subject number. Unless specified 
otherwise, all statistical testing will be two-sided and will be performed using a significance 
(alpha) level of 0.05. 
All statistical analyses will be conducted with the SAS® System, version 9.4 or higher within a 
validated statistical computing environment.  
5.1.  Subject Disposition, Demographic and Baseline Characteristics 
Subject disposition, including the number of subjects who completed the study, discontinued from 
the study, reasons for early discontinuation, and the number of days on study will also be provided 
and presented for all subjects randomized. Subject disposition will be summarized by treatment 
group. 
 
Demographic data and baseline characteristics including age, ethnicity, race, gender, severity of 
itching and stinging/burning sensations, and skin/scalp irritation assessment will be summarized 
using appropriate descriptive statistics by treatment group for the mITT and PP populations. 
Descriptive statistics will be generated for continuous variables (e.g. age).  The number and 
percentage of subjects in each class of categorical demographic and Baseline variables (e.g. 
gender, ethnicity, race, severity of itching and stinging/burning sensation; skin/scalp irritation 
assessment) will be tabulated by treatment group and population (mITT and PP) for Baseline (Visit 
1).  Individual subject demographic and Baseline characteristics data will be listed. No inferential 
testing will be performed.   
5.2.  Efficacy Analyses 
5.2.1.  Primary Efficacy Endpoint 
The primary efficacy endpoint is the proportion of index subjects who are lice free (defined as no 
live lice, adults or nymphs) 14 days (Day 15) after treatment.   
Descriptive statistics (number of subjects, number of subjects cured, and proportion of cured) for 
the primary efficacy variable will be tabulated by treatment group and population (mITT and PP).   
 
 
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5.2.2.  Primary Efficacy Analyses 
Bioequivalence assessment will be evaluated by comparing proportions of patients successfully 
cured in the test and the reference treatment groups. Bioequivalence between the test and the 
reference product will be established if the continuity-corrected 90% confidence interval for the 
difference in cure proportions between test and reference treatment is contained between the 
equivalence limits [-0.20, +0.20].  The hypothesis testing for the two, one-sided tests will be 
conducted using a 5% level of significance. 
In this case, the compound two, one-sided tests hypothesis is: 
H0: pT – pR < -0.20 or pT – pR > 0.20  (meaning test product is not bioequivalent to the 
reference); 
HA: -0.20 ≤ pT –pR ≤ 0.20 (supporting bioequivalence); 
where pT = cure rate of test treatment,  pR = cure rate of reference treatment.  
Let nT = sample size of test treatment group, nR = sample size of reference treatment group and 
se = (𝑝𝑝𝑇𝑇 
ෞ(1 −𝑝𝑝𝑇𝑇 
ෞ) 𝑛𝑛𝑇𝑇+ 
⁄
𝑝𝑝𝑅𝑅 
ෞ(1 −𝑝𝑝𝑅𝑅 
ෞ) 𝑛𝑛𝑅𝑅) 
⁄
1
2. 
The 90% confidence interval will be estimated as follows, using Yates correction: 
L = (𝑝𝑝̂𝑇𝑇−𝑝𝑝̂𝑅𝑅) −1.645 ×  𝑠𝑠𝑠𝑠−(
1
𝑛𝑛𝑇𝑇+ 
1
𝑛𝑛𝑅𝑅) 2
⁄  
U = (𝑝𝑝̂𝑇𝑇−𝑝𝑝̂𝑅𝑅) + 1.645 ×  𝑠𝑠𝑠𝑠+ (
1
𝑛𝑛𝑇𝑇+ 
1
𝑛𝑛𝑅𝑅) 2
⁄  
H0 is rejected if L ≥ -0.20 and U ≤ 0.20 resulting in accepting HA and concluding bioequivalence 
of the two products. 
The primary endpoint is the evaluation at Day 15. The bioequivalence results in the PP population 
will be considered definitive, with those in the mITT population as supportive.   
The following SAS code will be used for testing bioequivalence: 
proc freq data = dataset; 
weight count; 
tables treat*outcome/ riskdiffc (equiv); 
run; 
 
The efficacy assessments for each active treatment vs. the Placebo will be conducted using two-
sided, continuity corrected Z-tests based on the following hypotheses: 
 
Ho: πT = πP 
 
 
Ha: πT ≠ πP 
 
 
 
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where,  
 
πT, πR, and πP = the true cure proportions for Test, Reference, and Placebo treatments, 
respectively. 
If both null hypotheses are rejected (p<0.05) and the observed cure proportions for the Test and 
Reference treatments are greater than that for the Placebo, then Superiority will be considered to 
have been demonstrated.   
The superiority results in the mITT population will be considered definitive, with those in the PP 
population considered supportive. 
 
5.2.3.   Secondary Efficacy Endpoints 
The secondary efficacy endpoint is the number and percentage of all index subjects who are lice-
free at Day 2.  Descriptive statistics (number of subjects, number of subjects cured, and proportion 
cured) for the secondary efficacy variable will be tabulated by treatment group and population 
(mITT and PP).   
 
5.2.4.   Secondary Efficacy Analyses 
As a secondary endpoint evaluation, patients’ clinical progress at Visit 4 (Day 14) will be assessed 
and proportion of cured patients in treatment arms will be compared using the procedures 
described in the analysis of the primary efficacy endpoint. 
 
5.3.  Tolerability Assessment 
Subjects’ self-assessment of itching and stinging/ burning sensations during screening and 
treatment periods (Visits 2 through 5), skin/scalp irritation assessment by clinical site personnel 
(Visits 2 through 5), and ocular irritation assessment (Visits 3 through 5) by clinical site personnel 
will used to assess tolerability to the study treatments.  Itching is defined as intense, distracting 
irritation or tickling sensation in the last 24 hours and is evaluated on a scale from 0 (No Itching) 
to 3 (Severe Itch).  Stinging/ burning is defined as sensation of the skin is painfully hot or 
noticeable tingling sensation in the last 24 hours and is evaluated on a scale from 0 (Absent) to 3 
(Severe).  Skin/Scalp irritation is evaluated on a scale from 0 (None) to 3 (Severe) for four types 
of irritation including Pruritus= Itching, Erythema= Redness of the scalp, Excoriation= Breaking 
of the skin, usually caused by scratching, Pyoderma= Sores filled with clear fluid, pus or crusting.  
Each type of irritation is evaluated separately and its total score is recorded.  Ocular irritation is 
evaluated for the presence of eye irritation, Conjunctivitis, and Ocular Hyperemia on a scale from 
0 (No) to 1 (Yes). 
 
 
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Descriptive statistics using categorical methods will be used to compare tolerability measures 
between the test and reference treatment groups and various study days (e.g. Baseline (Visit 2), 
Visit 3, Visit 4, and Visit 5).  Tolerability analyses will be presented for mITT and PP populations.   
5.4.   Safety Assessment 
The reporting of safety data is descriptive, and will include all subjects in the Safety population. 
The variables for safety endpoints are AEs. AEs will be summarized based on their frequency and 
their severity. All AEs will be coded using Medical Dictionary for Regulatory Activities 
(MedDRA) and summarized by treatment group. Data will be summarized using preferred term 
and primary system organ class. 
If a subject experiences multiple events that map to a single preferred term, the greatest severity 
and strongest Investigator assessment of relation to study drug will be assigned to the preferred 
term for the appropriate summaries. Should an event have a missing severity or relationship, it will 
be classified as having the highest severity and/or strongest relationship to study drug. 
Summaries of treatment-emergent AEs will include any AEs reported beginning with the first dose 
of study drug on Day 1. The occurrence of treatment-emergent adverse events will be summarized 
by treatment group using preferred terms, system organ classifications, and severity. Separate 
summaries of treatment-emergent serious adverse events, treatment-emergent adverse events 
related to study drug, and events leading to the discontinuation of study drug will be generated. 
All adverse events reported will be listed for individual subjects showing both verbatim and 
preferred terms. 
Concomitant medications will be coded using the World Health Organization (WHO) drug 
dictionary. These data will be summarized by treatment group. Previous and concomitant 
medications will be presented in a data listing. 
5.4.1.  Adverse Events 
Analysis of adverse events as safety variables will be based on all adverse event (AE) capture 
measuring severity and frequency utilizing MedDRA terminology for consistency. AEs will be 
mapped to a MedDRA-preferred term and system organ classification.  If a subject experiences 
multiple events that map to a single preferred term, the greatest severity and strongest Investigator 
assessment of relation to study drug will be assigned to the preferred term for the appropriate 
summaries. Should an event have a missing severity or relationship, it will be classified as having 
the highest severity and/or strongest relationship to study drug.  
Summaries of treatment-emergent AEs will include any AEs reported beginning with the first dose 
of study drug on Day 1. The occurrence of treatment-emergent adverse events will be summarized 
by treatment group using preferred terms, system organ classifications, and severity.  Separate 
summaries of treatment-emergent serious adverse events (SAEs), treatment-emergent adverse 
events related to study drug, and events leading to the discontinuation of study drug will be 
generated.   
 
 
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All AEs will be listed for individual subjects showing both verbatim and preferred terms.   
5.4.2.  Vital Signs 
Vital signs will be collected at the Screening visit; on the Baseline, and at Visit 5 (or upon 
subject discontinuation). Vital signs will include body temperature (oral), heart rate and blood 
pressure (systolic and diastolic). Any abnormal characteristics will be evaluated by the 
Investigator based on their clinical significance. Abnormal vital signs will be considered AEs if 
they require therapeutic medical intervention, and/or if the Investigator considers them to be AEs 
due to the clinical judgement. 
5.4.3.  Previous and Concomitant Medications 
All medications (both prescription and nonprescription, and including vitamins, herbals, topical, 
inhaled, and intranasal) taken within 30 days prior to the start of the Study Drug and through the 
final study visit will be recorded on the appropriate eCRF (using their generic and brand names, if 
known) with the corresponding indication, start and stop dates. At each study visit, subjects will 
be asked whether they have started or discontinued any medication since their previous study visit. 
This includes single use or PRN (as needed) medication use. 
Previous treatment of head lice must be recorded irrespective of the term it was given. 
Corresponding condition shall be captured in the subject’s Medical History. 
 
6.   CHANGES IN THE PLANNED ANALYSES 
No deviations in the conduct of the study or the planned analysis are anticipated.  Should any 
deviations from the analyses specified in the authorized statistical analysis plan arise, such 
deviations will be documented in the final clinical study report. 
7.  PROGRAMMING CONVENTIONS 
Statistical programs will be developed using SAS® version 9.4 or higher.  Programs will be 
documented, produced, and validated.  Additionally, the following conventions should be 
incorporated: 
• Page orientation, margins, and fonts: Summary tables, listings, and figures will appear in 
landscape orientation.  There should be a minimum of a 1.25” boundary on the upper (bound) 
edge, and a minimum of a 1.0” boundary on the remaining three edges.  Output should be 
printed in Courier New with a point size of at least 8.  Titles may be printed using a larger font 
(e.g., Arial point size 10). 
 
 
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• Identification of analysis population: Every summary table and figure should clearly specify 
the analysis population being summarized.  Listings will be prepared for all subjects. 
• Group headers: In the summary tables, the group headers will identify the treatment group and 
the within-group sample size for the indicated analysis population.  Of note, the header’s 
sample size does not necessarily equal the number of subjects summarized within any given 
summary module; some subjects in the analysis population may have missing values and, thus, 
may not be summarized. 
• Suppression of percentages corresponding to null categories: When count data are presented 
as category frequencies and corresponding percentages, the percent should be suppressed when 
the count is zero in order to draw attention to the non-zero counts. 
• Presentation of sample sizes: Summary modules should indicate, in one way or another, the 
number of subjects contributing to the summary statistics presented in any given summary 
module.  As mentioned above, this may be less than the number of subjects in the analysis 
population. 
♦ In the quantitative modules describing continuous variables (and thus presenting sample 
size, means, and standard deviations), the sample size should be the number of non-missing 
observations. 
♦ For categorical variables that are presented in frequency tables, the module should present 
the total count in addition to the count in each category.  Percentages should be calculated 
using this total as the denominator, and the percentage corresponding to the sum itself (that 
is, 100%) should be presented to indicate clearly to a reviewer the method of calculation. 
Missing data will not contribute to the calculation of percentages. 
• Sorting: Listings will be sorted by treatment group, subject identification number and date, if 
applicable.  If a listing is sorted in a different manner, a footnote will indicate as such.  
• General formatting rules: Rounding for all variables will occur only as the last step, 
immediately prior to presentation in listings, tables, and figures.  No intermediate rounding 
will be performed on derived variables.  The standard rounding practice of rounding numbers 
ending in 0-4 down and numbers ending in 5-9 up will be employed.   
• The presentation of numerical values will adhere to the following guidelines:  
♦ Raw measurements will be reported to the number of significant digits as captured 
electronically on the eCRFs.   
♦ Standard deviations will be reported to one decimal place beyond the number of decimal 
places the original parameter is presented. 
♦ Means will be reported to the same number of significant digits as the parameter, unless 
the parameter is an integer, then 1 decimal place will be reported.  
♦ Calculated percentages will be reported with no decimals. 
 
 
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• Dates will be formatted as DDMMMYYYY.  Partial dates will be presented on data listings 
as recorded on CRFs. 
• Time will be presented according to the 24-hour clock (HHMM). 
 
 
 
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8.   TABLES, LISTINGS AND FIGURES 
Tables 
 
1.  Summary of Subject Enrollment and Disposition. 
2.  Summary of Subject Demographics at Screening (mITT population). 
3. Summary of Subject Demographics at Screening (PP Population). 
4. Summary of Medical History/Other Concomitant Illness at Screening. 
5. Summary of Physical Exam Abnormalities. 
6. The Difference in proportion of patients that are identified as cured on Study Day 15 (Visit 5) 
Treated with Ivermectin and Sklice (mITT population). 
7. The Difference in proportion of patients that are identified as cured on Study Day 15 (Visit 5) 
Treated with Ivermectin and Sklice visit (PP population). 
8. The Difference in proportion of patients that are identified as cured on Study Day 15 (Visit 5) 
Treated with Ivermectin Vs Placebo and Sklice Vs Placebo (mITT population). 
9. The Difference in proportion of patients that are identified as cured on Study Day 15 (Visit 5) 
Treated with Ivermectin Vs Placebo and Sklice Vs Placebo (PP population). 
10. Summary of Head Lice visual examination at each visit (mITT population). 
11. Summary of Head Lice visual examination at each visit (PP Population). 
12. The Difference in proportion of patients that are identified as cured on Study Day 2 (Visit 3) 
Treated with Ivermectin and Sklice (mITT population). 
13. The Difference in proportion of patients that are identified as cured on Study Day 2 (Visit 3) 
Treated with Ivermectin and Sklice (PP population). 
14. The Difference in proportion of patients that are identified as cured on Study Day 2 (Visit 3) 
Treated with Ivermectin Vs Placebo and Sklice Vs Placebo (mITT population). 
15. The Difference in proportion of patients that are identified as cured on Study Day 2 (Visit 3) 
Treated with Ivermectin Vs Placebo and Sklice Vs Placebo (PP population). 
16. Summary of self-assessment of itching and stinging/ burning sensations at each visit (mITT 
population). 
17. Summary of self-assessment of itching and stinging/ burning sensations at each visit (PP 
population). 
18. Summary of change of self-assessment of itching and stinging/ burning sensations from 
baseline at each visit (mITT population). 
19. Summary of change of self-assessment of itching and stinging/ burning sensations from 
baseline at each visit (PP population). 
20. Summary of local skin/scalp irritation assessment at each visit (mITT population). 
21. Summary of local skin/scalp irritation assessment at each visit (PP population). 
22. Summary of ocular irritation assessment at each visit (mITT population). 
23. Summary of ocular irritation assessment at each visit (PP population). 
24. Summary of change of local skin/scalp irritation assessment from baseline at each visit 
(mITT population). 
25. Summary of change of local skin/scalp irritation assessment from baseline at each visit (PP 
population). 
26. Adverse Events by System Organ Class and Preferred Term. 
27. Adverse Events with incidence >5 % by System Organ Class and Preferred Term. 
 
 
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28. Treatment Emergent Adverse Events by System Organ Class and Preferred Term. 
29. Treatment Emergent Adverse Events by maximum Severity. 
30. Summary of Treatment Emergent Adverse Events possible or probably related to the study 
drug. 
31. Summary of Serious Adverse Events by System Organ Class and Preferred Term. 
32. Summary of Concomitant Medications. 
 
 
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Data Listings 
 
1. Listing of Analysis Population and Study Completion. 
2. Listing of Subjects Who Discontinued. 
3. Listing of Patients Excluded from Per Protocol Efficacy Analysis. 
4. Listing of Protocol Deviation. 
5. Listing of Subject Demographics. 
6. Listing of Drug Accountability. 
7. Listing of Head Lice visual examination of index subjects. 
8. Listing of Head Lice visual examination of house hold members. 
9. Listing of Subject Diary data. 
10. Listing of Patient Self-assessment. 
11. Listing of local skin/scalp irritation assessment. 
12. Listing of ocular irritation assessment. 
13. Listing of Adverse Events. 
14. Listing of Treatment Emergent Adverse Events. 
15. Listing of Non-Treatment Emergent Adverse Events. 
16. Listing of Adverse drug reaction. 
17. Listing of Treatment Emergent Adverse Events which lead to discontinuation of study 
treatment. 
18. Listing of Non-Treatment Emergent Adverse Events which lead to discontinuation of 
study treatment. 
19. Listing of Treatment Emergent Adverse Events which lead to Withdrawal from the study. 
20. Listing of Non-Treatment Emergent Adverse Events which lead to Withdrawal from the 
study. 
21. Listing of Concomitant Medication. 
22. Listing of Serious Adverse Events. 
23. Listing of Serious Adverse Events with fatal outcome. 
24. Listing of Medical History. 
25. Listing of Physical Examination. 
26. Listing of Pregnancy test. 
27. Listing of Subject Vital Signs for Randomized Population. 
28. Listing of Inclusion/Exclusion Criteria (Randomized Population). 
 
 
 
 
 
 
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Figures 
 
1. The proportion of patients that are identified as cured at the Study Day 2 and 15. (mITT 
population). 
2. The proportion of patients that are identified as cured at the Study Day 2 and 15. (PP 
population). 
3. The summary of self-assessment of itching. (mITT population). 
4. The summary of self-assessment of itching.  (PP population). 
5. The summary of self-assessment of stinging/burning sensations at each visit. (mITT 
population). 
6. The summary of self-assessment of stinging/burning sensations at each visit. (PP 
population). 
7. The summary of local skin/scalp irritation assessment each visit. (mITT population). 
8. The summary of local skin/scalp irritation assessment at each visit. (PP population). 
9. The summary of ocular irritation assessment each visit. (mITT population). 
10. The summary of ocular irritation assessment at each visit. (PP population). 
 
 
 
 
 
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APPENDIX A:  ITCHING SENSATION SCALE 
 
Itching – Intense, distracting irritation or tickling sensation in the last 24 hours 
Score Grade 
Definition 
0 
None 
The scalp does not itch. 
1 
Mild 
Occasional episodes of itching, not bothersome.  
2 
Moderate 
Frequent, several times a day, bothersome. 
3 
Severe 
Nearly constant, frequent, very bothersome. 
 
 
APPENDIX B: STINGING/ BURNING SENSATION SCALE 
 
Stinging/Burning – Sensation of the skin is painfully hot or noticeable tingling sensation in the 
last 24 hours 
Score 
Grade 
Definition 
0 
None 
Absent 
1 
Mild 
Slight, barely present 
2 
Moderate 
Distinct presence 
3 
Severe 
Marked, intense 
 
APPENDIX C:  Skin/Scalp Irritation Assessment (include forehead, neck and ears):  
 
Rating 
Type of Irritation 
Pruritus= Itching 
Erythema= 
Redness of the 
scalp 
Excoriation= Breaking 
of the skin, usually 
caused by scratching 
Pyoderma= Sores 
filled with clear fluid, 
pus or crusting 
None = 0 
The scalp does 
not itch. 
No redness of the 
scalp. 
No broken skin on the 
scalp. 
No lesions visible on 
the scalp. 
Mild = 1 
Occasional 
episodes of 
itching, not 
bothersome.  
Faint, barely 
perceptible 
erythema with 
limited 
distribution. 
One or two areas on 
the scalp on which 
skin is broken. 
One or two lesions 
visible with crusting 
or other evidence of 
infection. 
 
 
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Moderate = 
2 
Frequent, several 
times a day, 
bothersome. 
Diffuse pink areas 
of scalp are 
readily visible. 
More than two 
separate areas of the 
scalp with broken skin 
but not generalized 
across the scalp. 
Presence of more than 
two lesions with 
crusting or other 
evidence of infection, 
but not generalized 
across the scalp. 
Severe = 3 
Nearly constant, 
frequent 
scratching, very 
bothersome. 
Large areas of the 
scalp are red. 
Widespread breaking 
of the skin involving 
most of the scalp. 
Lesions with crusting 
or other evidence of 
infection, involving 
most of the scalp. 
 
APPENDIX D.  Ocular Irritation Assessment: 
 
 
Eye irritation present:            
 Yes     
 No 
 
Conjunctivitis present:           
 Yes     
 No 
 
Ocular Hyperemia present:   
 Yes     
 No 
 
 
 
CONFIDENTIAL 
Page 25 
30 November 2017