Conditions: Head Lice
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 905
Healthy volunteers: yes

Brief summary:
This clinical study is designed to evaluate the clinical (therapeutic) effect of a generic ivermectin lotion 0.5% (Actavis Laboratories UT, Inc.) relative to that of the Food and Drug Administration (FDA) Reference Listed Drug (RLD) SKLICE® (ivermectin) lotion, 0.5% (Arbor Pharmaceuticals, LLC) in participants with active head lice infestation. Additionally, both the test and reference (that is; the RLD) treatments were tested for superiority to a placebo.

Detailed description:
Participants will be randomized by household in a 3:3:1 ratio to receive generic ivermectin lotion 0.5%, Sklice (ivermectin) lotion 0.5%, or vehicle lotion.

Arms:
arm 1: Infested household participants will administer a single application of up to 117 grams (1 tube) of generic ivermectin 0.5% topical lotion to the dry hair (avoiding contact with eyes) at home on Day 1, leave the lotion on the hair and scalp for 10 minutes, and then rinse off with warm water. Participants will be instructed to wash their hands after application of the study drug, allow hair to dry naturally (pat drying with decontaminated towel is permitted), and to leave hair uncovered after application of the study drug. Following application and rinsing of the study drug, participants are not to shampoo, wash, or rinse their hair or scalp until the Day 2 visit has been completed. arm 2: Infested household participants will administer a single application of up to 117 grams (1 tube) of Sklice ivermectin 0.5% topical lotion to the dry hair (avoiding contact with eyes) at home on Day 1, leave the lotion on the hair and scalp for 10 minutes, and then rinse off with warm water. Participants will be instructed to wash their hands after application of the study drug, allow hair to dry naturally (pat drying with decontaminated towel is permitted), and to leave hair uncovered after application of the study drug. Following application and rinsing of the study drug, participants are not to shampoo, wash, or rinse their hair or scalp until the Day 2 visit has been completed. arm 3: Infested household participants will administer a single application of up to 117 grams (1 tube) of vehicle topical lotion to the dry hair (avoiding contact with eyes) at home on Day 1, leave the lotion on the hair and scalp for 10 minutes, and then rinse off with warm water. Participants will be instructed to wash their hands after application of the study drug, allow hair to dry naturally (pat drying with decontaminated towel is permitted), and to leave hair uncovered after application of the study drug. Following application and rinsing of the study drug, participants are not to shampoo, wash, or rinse their hair or scalp until the Day 2 visit has been completed.

Interventions: intervention 1: Generic Ivermectin Lotion 0.5% intervention 2: Sklice® (Ivermectin) Lotion 0.5% intervention 3: Vehicle Lotion
Intervention descriptions: intervention 1: Topical lotion, generic formulation of the brand product. intervention 2: Topical lotion, brand product. intervention 3: Topical lotion, placebo. Has no active ingredient.

Protocol document:
Prot_000.pdf: 
Clinical Study Protocol 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical 
Study to Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% 
(Actavis Laboratories UT, Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor 
Pharmaceuticals, LLC) in the Treatment of Human Head Lice Infestation 
Study Number 71691702 
NCT03301649 
Protocol Approval Date:  1 February 2018 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
71691702  Rev. 1  Actavis Laboratories LLC  Page 1 of 54 
1.0 TITLE PAGE 
Drug Product: 
Ivermectin Lotion 0.5% 
Population: 
Male and female patients, 6 months of age and older, with an active Pediculus 
humanus capitis (human head lice) infestation, of which approximately 378 
are expected to be index patients. 
Study Design: 
Randomized, double-blind, placebo-controlled, parallel-design, multiple-site 
bioequivalence study with clinical endpoints. 
Sponsor: 
Actavis LLC 
Study/Protocol Number: 
71691702 
Protocol Date: 
02/01/2018 
This document is a confidential communication of 
 and Actavis 
LLC Receipt of this document constitutes an agreement by the recipient that no unpublished information 
contained herein will be disclosed without written approval from 
 and Actavis. 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 2 of 54 
 
2.0 KEY STUDY PERSONNEL AND FACILITIES 
Sponsor: 
Actavis LLC 
400 Interpace Parkway 
Morris Corporate Center III 
Parsippany, NJ 07054 
CRO: 
 
 
Sponsor’s Representative: 
 
 
Actavis LLC 
 
  
CRO Representative: 
 
 
 
 
 
 
Medical Monitor: 
 
 
 
 
 
Biostatistician: 
 
 
 
 
 
IWRS Vendor: 
 
 
 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 3 of 54 
 
3.0 SIGNATURE PAGE 
We, the undersigned, have carefully read this protocol and agree that it contains all the necessary 
information required to conduct the study. The study will be performed according to this protocol, all 
applicable FDA regulations, ICH guidelines and Good Clinical Practice standards. 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date 
 
 
 
 
 
 
 
 
  
 
 
 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date 
 
Actavis LLC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date 
 
Actavis LLC 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 4 of 54 
 
PRINCIPAL INVESTIGATOR’S SIGNATURE 
 
 
I _______________________________________, agree to conduct protocol 71691702 Rev 1 in accordance 
with FDA regulations, ICH guidelines and Good Clinical Practice. I understand that no deviations from the 
protocol may be made without the prior permission of the Sponsor (Actavis LLC) or 
 
, the company managing the study. 
 
 
 
 
 
___________________________________ 
 
 
 __________ 
Principal Investigator 
 
 
 
 
 
 
Date 
 
 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 5 of 54 
 
4.0 TABLE OF CONTENTS 
 
1.0 TITLE PAGE .......................................................................................................................................... 1 
2.0 KEY STUDY PERSONNEL AND FACILITIES .................................................................................. 2 
3.0 SIGNATURE PAGE .............................................................................................................................. 3 
4.0 TABLE OF CONTENTS ........................................................................................................................ 5 
5.0 SYNOPSIS .............................................................................................................................................. 9 
6.0 STUDY SCHEMATIC ......................................................................................................................... 16 
7.0 LIST OF ABBREVIATIONS AND TERMS ....................................................................................... 17 
8.0 INTRODUCTION ................................................................................................................................ 18 
8.1 Disease Being Treated ...................................................................................................................... 18 
8.2 Availability and Efficacy of Already Approved Therapies .............................................................. 18 
8.3 Scientific and Statistical Considerations ........................................................................................... 19 
8.4 Justification for use of Placebo ......................................................................................................... 19 
8.5 Risks and Benefits ............................................................................................................................. 19 
9.0 STUDY OBJECTIVES ......................................................................................................................... 20 
10.0 INVESTIGATIONAL PLAN ............................................................................................................. 20 
10.1 Study Design and Plan Description ................................................................................................ 20 
10.2 Selection of Study Design ............................................................................................................... 22 
10.3 Selection of Study Population ......................................................................................................... 22 
10.3.1 Inclusion Criteria...................................................................................................................... 22 
10.3.2 Exclusion Criteria .................................................................................................................... 22 
10.3.3 Restrictions During the Study .................................................................................................. 24 
10.3.4 Removal of Patients From the Study ....................................................................................... 24 
10.4 Treatments....................................................................................................................................... 25 
10.4.1 Treatments Administration ...................................................................................................... 25 
10.4.2 Identity of Investigational Product ........................................................................................... 25 
10.4.3 Study Product Shipment, Storage, and Retention .................................................................... 25 
10.4.4 Method of Assigning Patients to Treatment Groups ................................................................ 26 
10.4.5 Study Blind .............................................................................................................................. 27 
10.4.6 Compliance .............................................................................................................................. 27 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 6 of 54 
 
10.5 Study Conduct ................................................................................................................................. 28 
10.5.1 Visit 1 (Day -1 to 1): Screening/Baseline ................................................................................ 28 
10.5.2 Visit 2 (Day 2): Interim Visit ................................................................................................... 29 
10.5.3 Visit 3 (Day 8 ± 2 days): Interim Visit .................................................................................... 29 
10.5.4 Visit 4 (Day 15 ± 2 days): End of Study .................................................................................. 30 
10.6 Study Procedures ............................................................................................................................ 31 
10.6.1 Informed Consent ..................................................................................................................... 31 
10.6.2 Medical History and Demographics ........................................................................................ 31 
10.6.3 Concomitant Medication .......................................................................................................... 31 
10.6.4 Adverse Events ........................................................................................................................ 31 
10.6.5 Vital Signs ................................................................................................................................ 31 
10.6.6 Pregnancy Test ......................................................................................................................... 31 
10.6.7 Louse Examination .................................................................................................................. 32 
10.6.8 Inclusion/Exclusion Criteria Review ....................................................................................... 32 
10.6.9 Application Site Reactions ....................................................................................................... 32 
10.6.10 Ocular Irritation Assessment .................................................................................................. 32 
10.6.11 Dispense Study Product ......................................................................................................... 32 
10.6.12 Collect Study Product ............................................................................................................ 32 
10.6.13 Provide Patient Diary ............................................................................................................. 32 
10.6.14 Collect and Review Patient Diary .......................................................................................... 32 
10.7 Adverse Events ............................................................................................................................... 33 
10.7.1 Adverse Event Definition ......................................................................................................... 33 
10.7.2 Serious Adverse Events ........................................................................................................... 33 
10.7.3 Other Significant Adverse Events ............................................................................................ 34 
10.7.4 Severity .................................................................................................................................... 34 
10.7.5 Relationship of an Adverse Event to the Study Drug .............................................................. 34 
10.7.6 Expectedness ............................................................................................................................ 35 
10.7.7 Recording and Reporting of Adverse Events ........................................................................... 36 
10.7.8 Reporting of Serious Adverse Events ...................................................................................... 36 
10.7.9 Submission of SAEs................................................................................................................. 39 
10.8 Early Termination (Patient, Study) ................................................................................................. 39 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 7 of 54 
 
10.9 Pregnancy ........................................................................................................................................ 40 
10.10 Medication Error and Special Situations....................................................................................... 40 
10.11 Follow-up of Subjects After AE ................................................................................................... 41 
11.0 STATISTICAL METHODS ............................................................................................................... 42 
11.1 Statistical Plan ................................................................................................................................. 42 
11.2 Sample Size Determination ............................................................................................................. 42 
11.3 Study Populations ........................................................................................................................... 43 
11.3.1 Per-Protocol Population ........................................................................................................... 43 
11.3.2 Modified Intent-to-Treat (mITT) Population ........................................................................... 43 
11.3.3 Safety Populations.................................................................................................................... 43 
11.4 Baseline Comparability ................................................................................................................... 43 
11.5 Efficacy Endpoints .......................................................................................................................... 44 
11.6 Primary and Secondary Endpoint Analyses .................................................................................... 44 
11.7 Treatment-by-Site Interaction and Pooling of Clinical Sites .......................................................... 45 
11.8 Safety Analysis ............................................................................................................................... 45 
12.0 REGULATORY OBLIGATIONS ...................................................................................................... 45 
12.1 Institutional Review Board ............................................................................................................. 45 
12.2 Study Documentation ...................................................................................................................... 46 
12.2.1 Protocol .................................................................................................................................... 46 
12.2.2 Informed Consent ..................................................................................................................... 46 
12.2.3 Protocol and Informed Consent Changes ................................................................................. 46 
12.2.4 Source Documents and Case Report Forms ............................................................................. 47 
12.2.5 Drug Accountability ................................................................................................................. 47 
12.2.6 Drug Storage ............................................................................................................................ 47 
12.2.7 Retention of Reserve Samples ................................................................................................. 47 
12.2.8 Return of Clinical Supplies ...................................................................................................... 48 
12.2.9 Reporting Safety Information to the IRB ................................................................................. 48 
12.2.10 Record Retention.................................................................................................................... 48 
12.2.11 Study Monitoring and Auditing ............................................................................................. 48 
12.2.12 End of the Trial ...................................................................................................................... 48 
12.2.13 Clinical Study Report ............................................................................................................. 49 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 8 of 54 
 
12.2.14 Termination of the Study ....................................................................................................... 49 
13.0 REFERENCES ................................................................................................................................... 50 
14.0 APPENDICES .................................................................................................................................... 51 
14.1 Appendix A: Application Site Reactions ........................................................................................ 51 
14.2 Appendix B: SKLICE® (ivermectin) Lotion, 0.5% Product Insert ................................................. 52 
14.3 Appendix C: Patient Status ............................................................................................................. 53 
14.4 Appendix E: Amendments to the Protocol...................................................................................... 54 
 
 
 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 9 of 54 
 
5.0 SYNOPSIS 
Protocol Number 
71691702 
Title 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, 
Multiple-Site Clinical Study to Evaluate the Therapeutic Equivalence and 
Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, Inc.) to 
SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the 
Treatment of Human Head Lice Infestation 
Objectives 
The objectives of this study are to: 
1. Evaluate the therapeutic equivalence of the Test formulation, 
Ivermectin Lotion 0.5% (Actavis Laboratories UT, Inc.) to the 
Reference product, SKLICE® (ivermectin) Lotion, 0.5% (Arbor 
Pharmaceuticals, LLC) in the treatment of active head lice infestation. 
2. Demonstrate the superiority of the Test and Reference (active) 
treatments over Placebo treatment in patients with active head lice 
infestation. 
3. Compare the safety of Test, Reference and Placebo treatments in 
patients with active head lice infestation. 
Sponsor 
Actavis LLC 
Study Products 
• 
Test: Ivermectin Lotion, 0.5% (Actavis Laboratories UT, Inc.) 
• 
Reference: SKLICE® (ivermectin) Lotion, 0.5% (Arbor 
Pharmaceuticals, LLC) 
• 
Placebo: Placebo (vehicle) lotion (Actavis Laboratories UT, Inc.) 
Study products will be supplied in 4 oz (117 g) tubes. 
Dosage Regimen 
Patients will be instructed to administer a single application of study 
product to the hair on Day 1. 
Route of 
Administration 
Topical 
Treatment 
Randomization 
 
Patient Population 
Male and female patients, 6 months of age and older, with active Pediculus 
humanus capitis (human head lice) infestation, of which approximately 378 
are expected to be index patients. 
Study Design 
Randomized, double-blind, placebo-controlled, parallel-design, multiple-
site bioequivalence study with clinical endpoints 
Study Conduct 
Eligible patients will be randomized 
 to one of three 
treatments (Test, Reference or Placebo) at Visit 1. All members of the 
household will be examined for lice, 
 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 10 of 54 
 
 
 
 
 
 
 
 Patients 
 will 
be instructed to administer a single application of the study product to the 
hair on the day of or day after enrollment into the study, leave the study 
product on the hair and scalp for 10 minutes, and then rinse off with warm 
water. Patients 
 will be instructed to apply 
the study product at home. The day of dosing will be considered Day 1. 
Patients will attend the following four scheduled clinics visits: 
• 
Visit 1 (Day -1 to 1): Screening/Baseline 
• 
Visit 2 (Day 2): Interim Visit 
• 
Visit 3 (Day 8 ± 2): Interim Visit 
• 
Visit 4 (Day 15 ± 2): End of Study 
At Visit 2 (Day 2), 
enrolled 
 will return the study product to the clinic. Visit 2 must occur the 
day after dosing. 
 
. At Visits 2, 3, 
and 4, patients will be examined for the presence of live head lice (i.e., live 
adults and/or nymphs). Louse examination should be conducted for 15 
minutes or longer, unless any live lice are detected in less time. Duration of 
examination should be recorded. 
 
 Patients who have 
live lice present at Visits 2 or 3 should be dropped from the study and 
provided with alternative treatment. Unscheduled visits will be allowed as 
deemed necessary by the Investigator or Sponsor to ensure patient safety or 
to perform other study-related procedures. 
Definitions 
• 
 
 
• 
 
 
 
 
• 
Non-index patient: Any household member who has agreed to 
participate in the study but is not the youngest member of the 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 11 of 54 
 
household. 
• 
Index patient: The youngest household member who is randomized 
into the study. 
Inclusion Criteria 
1. Signed Institutional Review Board (IRB)-approved informed consent 
form that meets all criteria of current Food and Drug Administration 
regulations. For patients who are considered minors in the state the 
study is being conducted (< 18 years in most states), the parent or legal 
guardian should sign the consent form and the child will be required to 
sign a patient “assent” form, as appropriate. Patients 11-17 years of age 
will read and sign an IRB-approved assent form and patients 6-10 years 
of age will provide verbal assent. Patients 6 months-5 years of age will 
be exempt from providing assent based on the child’s comprehension 
and cognitive skills. 
2. The patient and/or the patient’s parent (legal guardian) is willing to 
apply the study product as directed, comply with study instructions and 
commit to all follow-up visits for the duration of the study. 
3. Male or non-pregnant, non-lactating female, 6 months of age or older. 
4. Females of childbearing potential must not be pregnant or lactating at 
Visit 1 (as confirmed by a negative urine pregnancy test with a 
sensitivity of less than 50 mIU/mL or equivalent units of human 
chorionic gonadotropin). Women of childbearing potential must agree 
to the use of a reliable method of contraception. (e.g., total abstinence, 
intrauterine device, a double-barrier method, oral, transdermal, 
injected, or implanted non-hormonal or hormonal contraceptive) 
throughout the study. Female patients using hormonal contraceptives 
should have been on the same product/dosing regimen for at least 28 
days before Visit 1 and should not change this regimen during the 
study. A sterile sexual partner is not considered an adequate form of 
birth control. 
5. Index patients (i.e., the youngest household member) must have an 
active head lice infestation, defined as ≥ 3 live lice (i.e., live adults 
and/or nymphs), at Visit 1. 
6. Household members participating in the study must have at least one 
live louse (i.e., live adults and/or nymphs) at Visit 1. 
7. All members of the household must be present for examination. Any 
male head of household who is unable to attend Visit 1 may be 
assessed by a second member of the household as being lice free. 
Exclusion Criteria 
1. Females who are pregnant, lactating or planning to become pregnant 
during the study period. 
2. Patients who do not have a known household affiliation with their 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 12 of 54 
 
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). 
3. Any infested member of the household is unable or unwilling to be 
treated with the study product. This includes male heads of household 
who do not attend Visit 1 but report infestation with lice. 
4. More than three members of the household infested with lice. 
5. Presence of visible skin/scalp condition(s) or open wounds at the 
application site that are not attributable to head lice infestation and that 
in the opinion of the Investigator will interfere with safety and/or 
efficacy evaluations. 
6. Presence of eczema or atopic dermatitis at the application site. 
7. Use of any prescription, over-the-counter, or home remedies for the 
treatment of head lice within 7 days before Visit 1. 
8. Use of pediculicides within four weeks before Visit 1. 
9. Use of systemic anti-parasitic agents within four weeks before Visit 1. 
10. Patients with very short (shaved) hair or who are planning to shave 
head during the study. 
11. Use of any hair dye, bleaches, hair straightening or permanent wave 
solution on the hair within 14 days before Visit 1. 
12. History of allergy or sensitivity to pediculicides or hair care products. 
13. History of any drug hypersensitivity or intolerance that, in the opinion 
of the Investigator, would compromise the safety of the patient or 
results of the study. 
14. Significant history or current acute or chronic infectious disease, 
system disorder, Netherton’s Syndrome, organ disorder (e.g., hepatic or 
renal impairment) or insufficiency, immunosuppression (from medical 
treatment or disease), organ transplant, uncontrolled diabetes, 
uncontrolled hypertension, current ocular condition, or other medical 
condition that, in the Investigator’s opinion, would place the study 
patient at undue risk by participating in the study. 
15. Patients or non-infested household members who would act as the 
primary caregiver who are of intellectually competent age but unable to 
understand the protocol requirements, instructions, and study-related 
restrictions, the nature, scope, and possible consequences of the clinical 
study. 
16. Receipt of any drug as part of a research study within 30 days before 
Visit 1. 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 13 of 54 
 
17. The patient is a member of the investigational study staff or a member 
of the family of the investigational study staff. 
18. Previous participation in this study. 
Efficacy Endpoints 
Primary Efficacy Endpoint 
The primary efficacy endpoint is the proportion of index patients in each 
treatment group who are considered a Treatment Success on Day 15 ± 2. 
Treatment Success is defined as the absence of live lice. 
Secondary Efficacy Endpoint 
The secondary efficacy endpoint is the proportion of all randomized 
patients (i.e., index + non-index) who are considered a Treatment Success 
on Day 15 ± 2. Treatment Success is defined as the absence of live lice. 
Evaluation of 
Therapeutic 
Equivalence and 
Superiority 
Therapeutic Equivalence Analysis 
Therapeutic equivalence will be evaluated for both primary and secondary 
endpoints using the per-protocol (PP) population. If the 90% confidence 
interval for the absolute difference between the proportion of patients who 
are considered a Treatment Success in the Test and Reference groups is 
contained within the range [-20%, +20%] then therapeutic equivalence of 
the Test product to the Reference product will be considered to have been 
demonstrated. 
The same statistical approach will be conducted for analysis of the 
secondary endpoint in the PP population. 
To declare therapeutic equivalence of the Test product to the Reference 
product, therapeutic equivalence must be demonstrated for only the 
primary endpoint in the PP population. 
Superiority Analysis 
Superiority of the Test and Reference products against the Placebo for the 
primary endpoint will be tested at the 5% significance level (p < 0.05; two-
sided, Cochran-Mantel-Haenszel (CMH) test, stratified by clinical site) in 
the mITT population using last observation carried forward. If the 
proportions of patients who are considered a Treatment Success in the Test 
and Reference groups are numerically and statistically superior to that of 
the Placebo (p < 0.05; using two-sided, CMH test stratified by clinical site), 
then superiority of the Test and Reference products over Placebo will be 
concluded. 
The same statistical approach will be conducted for analysis of the 
secondary endpoint in the mITT population. 
To declare superiority of the Test and Reference products over Placebo, 
their superiority must be demonstrated for only the primary endpoint in the 
mITT population. The superiority testing will treat all patients who have no 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 14 of 54 
 
data on Day 15 as treatment failure. 
Treatment-by-Site Interaction and Pooling of Clinical Sites 
As this is a multiple-site study, the interaction of treatment-by-site may be 
evaluated for the primary efficacy endpoint in the PP population (for 
equivalence testing). The treatment-by-site interaction will be evaluated by 
the Breslow-Day test for homogeneity of the odds ratio at the 5% 
significance level (p < 0.05). A site(s) with a low enrollment rate(s) may be 
pooled with its geographically closest site, so as to avoid bias in the 
estimation of a treatment-by-site interaction effect. The pooling will be 
done for low enrolling sites that account for less than 4-7% of the total 
number of patients in the PP population at the site with the highest 
enrolling rate in the PP population. If the treatment-by-site interaction term 
is found to be statistically significant (p < 0.05) then the interaction term 
will also be assessed for clinical relevance before pooling the data across 
sites. This will include examination of Treatment Success rates at each site 
where sample sizes per treatment may be influential in the assessment of 
the interaction. 
Safety Analysis 
Adverse events (AEs) will be classified using standard Medical Dictionary 
for Regulatory Activities (MedDRA) terminology Version 20.0 or higher 
and summarized by treatment group. Summary tables comparing the type, 
date of onset, date of resolution, incidence, severity, relationship to the 
study product, action taken, and outcome will be prepared by treatment 
group. If sufficient data exist, then AE frequencies will be compared 
among treatments using Fisher’s exact test or a similar test. Application site 
reactions and ocular discomfort will be compared descriptively among 
treatment groups. 
Concomitant medication use during the randomized treatment period will 
be tabulated by patient. 
Signs and symptoms of head lice will not be considered AEs, unless in the 
Investigator’s opinion, they have increased in frequency and/or severity to 
such an extent that the Investigator/patient considers to be clinically 
significant. 
All patients who are randomized and received study product will be 
included in the comparative safety analysis. 
Sample Size 
Determination 
For the primary endpoint analysis (proportion of index patients in the PP 
population who are considered to be a Treatment Success on Day 15 ± 2), 
sample size is estimated for therapeutic equivalence of the Test to the 
Reference product and superiority of each of the active treatments groups 
over Placebo. The sample size estimations are based on data reported in the 
product label for SKLICE® (ivermectin) Lotion, 0.5%. 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 15 of 54 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 16 of 54 
 
6.0 STUDY SCHEMATIC 
 
PROCEDURE 
VISIT 1 
(Day -1 to 1)* 
Screening/Baseline 
VISIT 2 
(Day 2)† 
Interim Visit 
VISIT 3 
(Day 8 ± 2 Days) 
Interim Visit 
VISIT 4 
(Day 15 ± 2 Days) 
End of Study 
Informed 
Consent/Assent 
X 
 
 
 
Medical History and 
Demographics 
X 
 
 
 
Concomitant Medication 
X 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
Vital Signs 
X 
X 
X 
X 
Pregnancy Test‡ 
X 
X 
X 
X 
Louse Examination 
X 
X 
X 
X 
Inclusion/Exclusion  
X 
 
 
 
Application Site 
Reactions 
X 
X 
X 
X 
Ocular Irritation 
Assessment 
 
X 
 
 
Dispense Study Product 
X 
 
 
 
Collect Study Product 
 
X 
 
 
Provide Patient Diary  
X 
X 
X 
 
Collect and Review 
Patient Diary 
 
X 
X 
X 
*Study product will be administered on Day 1. 
†Visit 2 must occur the day after patient dosing. 
‡For females of childbearing potential 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 17 of 54 
 
7.0 LIST OF ABBREVIATIONS AND TERMS 
ADaM 
Analysis Dataset Model 
AE 
Adverse Event 
C 
Celsius 
CDISC 
Clinical Data Interchange Consortium 
CFR 
Code of Federal Regulations 
CMH 
Cochran-Mantel-Haenszel 
CRO  
Clinical Research Organization 
eCRF  
electronic Case Report Form 
F 
Fahrenheit 
FDA 
Food and Drug Administration 
g 
Gram 
ICF  
Informed Consent Form 
ICH 
International Council on Harmonisation 
IRB 
Institutional Review Board 
IWRS 
Interactive Web Response System 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
Milligram 
mITT 
modified Intent-to-Treat 
mL 
milliliter 
NDA  
New Drug Application 
OTC 
Over-The-Counter 
PP 
Per-Protocol 
RLD 
Reference Listed Drug 
SAE  
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SAS 
Statistical Analysis Software 
SDTM 
Study Data Tabulation Model 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 18 of 54 
 
8.0 INTRODUCTION 
8.1 Disease Being Treated 
Pediculus humanus capitis, the head louse, is an ectoparasite whose only host are humans. The louse 
feeds on blood several times daily and resides close to the scalp to maintain its body temperature.1 
Head lice infestation is widespread, affecting both children and adults. In the United States it is 
estimated that between 6 and 12 million infestations occur each year among children 3 to 11 years of 
age.2 Head lice infestations can be asymptomatic, particularly with an initial infestation or when the 
infestation is mild. Itching is the most common symptom associated with head lice infestation and is 
caused by an allergic reaction to louse bites. Although head lice are not known to transmit any 
disease, untreated infections can lead to poor sleep and sores on the head caused by scratching. These 
sores can become infected with bacteria commonly found on a person’s hands.3,4 
8.2 Availability and Efficacy of Already Approved Therapies 
There are a number of prescription and over-the-counter (OTC) therapies currently available for the 
treatment of head lice. Over-the-counter medications contain either pyrethrins or permethrin. 
Pyrethrins (e.g., A-200®, Rid®) are naturally occurring pyrethroid extracts from the chrysanthemum 
flower. Pyrethrins can only kill live lice, not unhatched eggs. A second treatment is recommended to 
kill any newly hatched lice. 
Permethrin (e.g., Nix®) is a synthetic pyrethroid similar to naturally occurring pyrethrins. Like 
pyrethrins, this product only kills live lice. Although it may continue to kill newly hatched lice for 
several days after treatment, a second treatment is often required.5 
Prescription treatment options include benzyl alcohol, malathion, spinosad, and ivermectin. Benzyl 
alcohol (e.g., ULESFIA®) is an aromatic alcohol approved for the treatment of head lice in patients 6 
months of age and older. The safety of this product in patients over 60 years of age has not been 
established. Benzyl alcohol is thought to work by preventing lice from closing their respiratory 
spiracles, allowing the vehicle to obstruct these spiracles and causing the lice to suffocate. Similar to 
approved OTC treatments, benzyl alcohol only kills live lice and a second treatment is required.6 
Malathion (e.g., OVIDE®) is an organophosphate approved in the United States for the treatment of 
head lice. Malathion acts as a pediculicide by inhibiting cholinesterase activity in vivo. This product 
kills live lice as well as some lice eggs. Retreatment is recommended if live lice are still present 7-9 
days after treatment. Inadvertent transdermal absorption of malathion has occurred from its 
agricultural use. In such cases, acute toxicity was manifested by excessive cholinergic activity, i.e., 
increased sweating, salivary and gastric secretion, gastrointestinal and uterine motility, and 
bradycardia. The potential for transdermal absorption of malathion is unknown, therefore use of this 
product is limited to children 6 years of age and older. Chemical burns, including second-degree 
burns, have been reported with use of this product.7 
Spinosad (e.g., NATROBA) topical suspension is approved for the treatment of head lice in patients 
6 months of age and older. Spinosad, which is derived from soil bacteria, causes neuronal excitation 
in insects. After periods of hyperexcitation, lice become paralyzed and die. Unlike other treatments, 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 19 of 54 
 
spinosad kills both live lice and unhatched eggs. Most patients require only one treatment with this 
product.8,9 
Ivermectin (e.g., SKLICE®) topical lotion is approved for the treatment of head lice in patients 6 
months of age and older. Like spinosad, ivermectin is derived from soil bacteria. Ivermectin causes 
death of parasites by increasing the permeability of the cell membrane to chloride ions with 
hyperpolarization of the nerve or muscle cell. This results in paralysis and death of the parasite.10 
Although ivermectin is not ovicidal, it appears to prevent newly hatched lice from surviving. 
Ivermectin is effective in most patients with a single treatment.5 
Supplemental measures, including nit combing and decontamination of linens and personal items, are 
recommended along with drug therapy to avoid re-infestation of lice.5 
8.3 Scientific and Statistical Considerations 
Statistical analyses of the clinical data will be based on recommendations in the FDA guidances on 
malathion lotion, 0.5% and spinosad topical suspension, 0.9%.11,12 
8.4 Justification for use of Placebo 
A placebo group is included to confirm the sensitivity of the study and minimize the possibility of a 
false positive result of therapeutic equivalence. Therefore, in addition to demonstrating 
bioequivalence between Test and Reference products, both active products must show statistical 
superiority to the Placebo.13,14 
 
 
 
 
8.5 Risks and Benefits 
The risks and benefits to patients enrolled in clinical research studies that include a placebo treatment 
group must be carefully considered based on three main criteria, namely: the disease being treated, 
the availability, efficacy and safety of approved therapies, and the scientific and statistical 
requirements of the desired outcome of the research study. 
Randomized patients will be enrolled in the study for 15 ± 2 days. Although the potential for any 
drug-related side effects of significance occurring during the study is low, the risk is higher in the two 
active treatment groups than in the Placebo group. 
All patients who do not respond to treatment will be provided with alternative therapy, in some cases 
within 24 hours. 
All patients enrolled in this study will receive the benefit of free specialized medical care beyond 
standard medical treatment that would be expected through most health insurance plans. 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 20 of 54 
 
9.0 STUDY OBJECTIVES 
The objectives of this study are to: 
1. Evaluate the therapeutic equivalence of the Test formulation, Ivermectin Lotion 0.5% (Actavis 
Laboratories UT, Inc.) to the Reference product, SKLICE® (ivermectin) Lotion, 0.5% (Arbor 
Pharmaceuticals, LLC) in the treatment of active head lice infestation. 
2. Demonstrate the superiority of the Test and Reference (active) treatments over Placebo treatment in 
patients with active head lice infestation. 
3. Compare the safety of Test, Reference and Placebo treatments in patients with active head lice 
infestation. 
10.0 INVESTIGATIONAL PLAN 
10.1 Study Design and Plan Description 
This randomized, double-blind, placebo-controlled, parallel-design, multiple-site clinical study has 
been designed to evaluate the efficacy and safety of a generic Ivermectin Lotion 0.5% (Actavis 
Laboratories UT, Inc.) compared to the Food and Drug Administration (FDA) Reference Listed Drug 
(RLD) SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in patients with active 
head lice infestation. Additionally, both the Test and Reference (i.e., the RLD) treatments will be 
tested for superiority to a Placebo. 
Before any study-specific procedures are performed, all patients will read and sign the IRB-approved 
informed consent form (ICF). In addition, patients who are considered minors in the state the study is 
being conducted (< 18 years of age in most states), must have a signed parental/guardian ICF, 
indicating approval to participate, as well as a signed assent to participate form, as appropriate. 
Patients 11-17 years of age will read and sign an IRB-approved assent form and patients 6-10 years of 
age will provide verbal assent. Patients 6 months-5 years of age will be exempt from providing assent 
based on the child’s comprehension and cognitive skills. 
Males and females, 6 months of age and older with an active head lice infestation will be randomized 
 to one of the three study products as follows: 
• 
Test: Ivermectin Lotion, 0.5% (Actavis Laboratories UT, Inc.) 
• 
Reference: SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) 
• 
Placebo: Placebo (vehicle) lotion (Actavis Laboratories UT, Inc.) 
 
 
 
 
 
 
Patients, infested household members, and/or caregivers will be instructed to administer a single 
application of the study product to the hair on the day of or the day after enrollment into the study, 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 21 of 54 
 
leave the study product on the hair and scalp for 10 minutes, and then rinse off with warm water. 
Patients and infested household members will be instructed to apply the study product at home. The 
day of dosing will be considered Day 1. 
Patients will attend the following four scheduled clinics visits: 
• 
Visit 1 (Day -1 to 1): Screening/Baseline 
• 
Visit 2 (Day 2): Interim Visit 
• 
Visit 3 (Day 8 ± 2): Interim Visit 
• 
Visit 4 (Day 15 ± 2): End of Study 
At Visit 2 (Day 2), 
enrolled 
 will return the study 
product to the clinic. Visit 2 must occur the day after dosing.
 
. At Visits 2, 3, and 4, 
patients will be examined for the presence of live head lice (i.e., live adults and/or nymphs). Louse 
examination should be conducted for 15 minutes or longer, unless any live lice are detected in less 
time. Duration of examination should be recorded. 
 
 
 Unscheduled visits will be 
allowed as deemed necessary by the Investigator or Sponsor to ensure patient safety or to perform 
other study-related procedures. 
At Visit 2, patients will be questioned about any ocular discomfort associated with the study product. 
Also at Visits 2, 3, and 4, patients will be questioned about any adverse events (AEs), application site 
reactions (Appendix A), and any new concomitant medication use. 
Definitions 
• 
 
 
 
 
 
• 
Non-index patient: Any household member who has agreed to participate in the study but is not 
the youngest member of the household. 
• 
Index patient: The youngest household member who is randomized into the study. 
Therapeutic equivalence will be assessed by evaluating the proportion of index patients in each 
treatment group who are considered a Treatment Success on Day 15 ± 2. Treatment Success is 
defined as the absence of live lice. The proportion of all patients (i.e., index + non-index) who are 
considered a Treatment Success on Day 15 ± 2 will be evaluated as a secondary endpoint. The 
analysis of superiority will compare both active treatment groups to the Placebo group for the same 
primary and secondary endpoints. 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 22 of 54 
 
10.2 Selection of Study Design 
This protocol is based on procedures and results from studies conducted as part of the New Drug 
Application (NDA) # 202-736 for SKLICE® (ivermectin) Lotion, 0.5%, recommendations from the 
FDA industry guidance for the development of topical head lice drugs, and recommendations from 
the FDA guidances on malathion lotion, 0.5% and spinosad topical suspension, 0.9%, which are 
products that have a similar indication and usage for treatment of head lice infestation.11,12,15,16 
10.3 Selection of Study Population 
10.3.1 Inclusion Criteria 
1. Signed Institutional Review Board (IRB)-approved ICF that meets all criteria of current FDA 
regulations. For patients who are considered minors in the state the study is being conducted 
(< 18 years in most states), the parent or legal guardian should sign the consent form and the 
child will be required to sign a patient “assent” form, as appropriate. Patient 11-17 years of 
age will read and sign an IRB-approved assent form and patients 6-10 years of age will 
provide verbal assent. Patients 6 months-5 years of age will be exempt from providing assent 
based on the child’s comprehension and cognitive skills. 
2. The patient and/or the patient’s parent (legal guardian) is willing to apply the study product as 
directed, comply with study instructions and commit to all follow-up visits for the duration of 
the study. 
3. Male or non-pregnant, non-lactating female, 6 months of age or older. 
4. Females of childbearing potential must not be pregnant or lactating at Visit 1 (as confirmed 
by a negative urine pregnancy test with a sensitivity of less than 50 mIU/mL or equivalent 
units of human chorionic gonadotropin). Women of childbearing potential must agree to the 
use of a reliable method of contraception (e.g., total abstinence, intrauterine device, a double-
barrier method, oral, transdermal, injected, or implanted non-hormonal or hormonal 
contraceptive) throughout the study. Female patients using hormonal contraceptives should 
have been on the same product/dosing regimen for at least 28 days before Visit 1 and should 
not change this regimen during the study. A sterile sexual partner is not considered an 
adequate form of birth control. 
5. Index patients (i.e., the youngest household member) must have an active head lice 
infestation, defined as ≥ 3 live lice (i.e., live adults and/or nymphs), at Visit 1. 
6. Household members participating in the study must have at least one live louse (i.e., live 
adults and/or nymphs) at Visit 1. 
7. All members of the household must be present for examination. Any male head of household 
who is unable to attend Visit 1 may be assessed by a second household member as being lice 
free. 
10.3.2 Exclusion Criteria 
1. Females who are pregnant, lactating or planning to become pregnant during the study period. 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 23 of 54 
 
2. Patients who do 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). 
3. Any infested member of the household is unable or unwilling to be treated with the study 
product. This includes male heads of household who do not attend Visit 1 but report 
infestation with lice. 
4. More than three members of the household infested with lice. 
5. Presence of visible skin/scalp condition(s) or open wounds at the application site that are not 
attributable to head lice infestation and that in the opinion of the Investigator will interfere 
with safety and/or efficacy evaluations. 
6. Presence of eczema or atopic dermatitis at the application site. 
7. Use of any prescription, OTC, or home remedies for the treatment of head lice within 7 days 
before Visit 1. 
8. Use of pediculicides within 4 weeks before Visit 1. 
9. Use of systemic anti-parasitic agents within 4 weeks before Visit 1. 
10. Patients with very short (shaved) hair or who are planning to shave head during the study. 
11. Use of any hair dye, bleaches, hair straightening or permanent wave solution on the hair 
within 14 days before Visit 1. 
12. History of allergy or sensitivity to pediculicides or hair care products. 
13. History of any drug hypersensitivity or intolerance that, in the opinion of the Investigator, 
would compromise the safety of the patient or results of the study. 
14. Significant history or current acute or chronic infectious disease, system disorder, Netherton’s 
Syndrome, organ disorder (e.g., hepatic or renal impairment) or insufficiency, 
immunosuppression (from medical treatment or disease), organ transplant, uncontrolled 
diabetes, uncontrolled hypertension, current ocular condition, or other medical condition that, 
in the Investigator’s opinion, would place the study patient at undue risk by participating in 
the study. 
15. Patients or non-infested household members who would act as the primary caregiver who are 
of intellectually competent age but unable to understand the protocol requirements, 
instructions, and study-related restrictions, the nature, scope, and possible consequences of 
the clinical study. 
16. Receipt of any drug as part of a research study within 30 days before Visit 1. 
17. The patient is a member of the investigational study staff or a member of the family of the 
investigational study staff. 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 24 of 54 
 
18. Previous participation in this study. 
10.3.3 Restrictions During the Study 
The following concomitant medications, products or procedures will not be allowed while 
enrolled in the study: 
• 
Any prescription, OTC, home remedy, or mechanical/manual methods (e.g., nit combing) 
for the treatment of head lice. This includes any medicated shampoos specifically used in 
the treatment of head lice. 
• 
Pediculicides. 
• 
Hair dye, bleaches, hair straightening or permanent wave solution on the hair. 
• 
Topical or systemic anti-parasitic agents. 
Patients will be instructed to avoid occlusion of the scalp with any agent (e.g., petroleum) and 
sleeping at different locations. Patients should not shave their head until after study completion. 
Patients will be questioned about all prescription and OTC concomitant medication use (including 
vitamins or nutritional supplements) at each study visit. All concomitant medications will be 
recorded in the patient’s source documents. Any patient who violates any of the listed restrictions 
may be dropped from continued participation in the study by the Investigators. 
10.3.4 Removal of Patients From the Study 
Patients will be advised that they are free to withdraw from the study at any time. If necessary, 
the Investigator may withdraw a patient from the study to protect the health of that patient. In 
case of early termination the Investigator will fully document the reason for early termination. 
The clinical report will include all reasons for early withdrawals. Reasons for removal may 
include the following: 
• 
Patient withdrew consent. 
• 
Significant AE that led the Investigator or patient to withdraw for safety reasons. 
• 
Non-compliance with protocol requirements (e.g., use of restricted medication, not 
following dosing procedures, failure to make scheduled study visits in a timely fashion). 
• 
Presence of live lice at any post-treatment visit. 
• 
Participant enrolls in another clinical trial during the study, or is found to have previously 
enrolled in this clinical trial. 
If a randomized patient terminates from the study early, all efforts will be made to complete the 
End of Study procedures. Patients who withdraw or are removed from the study will not be 
replaced. 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 25 of 54 
 
10.4 Treatments 
10.4.1 Treatments Administration 
Patients will be provided with verbal and written instructions on how to administer the study 
product at home. At Visit 1, eligible patients will receive a 4 oz (117 g) tube of randomized study 
product (i.e., Test, Reference or Placebo). Study product should be applied on the day of or the 
day after enrollment into the study. The day of dosing will be considered Day 1. Patients, infested 
household members, and/or caregivers will be instructed to apply the study product to dry hair in 
an amount sufficient (up to 1 tube) to thoroughly coat the hair and scalp, avoiding contact with 
the eyes. Study product should be left on the scalp for 10 minutes before rinsing with water only. 
Patients should wash their hands after application of the study product. Hair should be allowed to 
dry naturally (pat drying with decontaminated towel is permitted) and left uncovered after 
application of the study product. Following application and rinsing of the study product, patients 
may not shampoo, wash, or rinse their hair or scalp until the Day 2 visit has been completed. 
If any non-infested household member is pregnant or lactating at the time of the study, this person 
may not be involved with application of the study product to any household members. 
The study product should be applied as a single dose. Patients should not use the product more 
than once. Tubes of study product will be collected at Visit 2 and the site will verify the product 
was used and rinsed. If a patient inadvertently does not return a tube of study product at its 
respective return visit, the patient should be instructed to return it as soon as possible or at the 
next visit. 
On Day 1, before applying treatment, all bedding, hats, clothing, and towels used by infested 
persons or their household, sexual, and close contacts in the two days before treatment should be 
decontaminated by machine washing in high temperatures (at least 150°F) and drying in a hot 
dryer for at least 20 minutes (additional time should be added if large loads are dried). Clothing or 
items that are not washable can be dry-cleaned or sealed in a plastic bag and stored for two 
weeks. Personal care items such as combs, brushes, and hair clips should be washed in hot water 
(at least 135°F) for 10 minutes. Instructions on good hygiene and proper methods of 
decontamination will be provided to the patient and caregivers. 
10.4.2 Identity of Investigational Product 
The following products will be used in the study: 
• 
Test: Ivermectin Lotion, 0.5% (Actavis Laboratories UT, Inc.) 
• 
Reference: SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) 
• 
Placebo: Placebo (vehicle) lotion (Actavis Laboratories UT, Inc.) 
10.4.3 Study Product Shipment, Storage, and Retention 
An individual tube of study product (i.e., Test, Reference or Placebo) will be packaged, as a 
patient kit. Each patient will be assigned to one patient kit. 
 
 The study product will be blinded, packaged and delivered to the site in bulk. The study 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 26 of 54 
 
products will be shipped to each Investigator’s site from a centralized location. The Principal 
Investigator at each site is responsible for ensuring that all study products are stored in a locked, 
secure location, with access limited to the Investigator and his/her designee(s). An accurate 
inventory of the study product will be maintained in accordance with federal regulations. 
Study product is to be stored in a secure, locked location, at room temperature between 20-25°C 
(68°F to 77°F) with excursions permitted to 15º–30ºC (59º–86ºF). Any excursions from the 
permitted excursion range of 15º–30ºC (59º–86ºF) will require prompt notification to 
, and 
thereafter 
 will notify the Sponsor. 
For every study product shipment received at the investigative site, the Investigator (or designee) 
will randomly select study product kits for retention, unless otherwise instructed by the Sponsor 
and/or 
. The selection process will ensure a sufficient amount of retention samples are 
retained as per Sponsor requirement. These kits will be affixed with a label provided by 
 
to be clearly marked as retention samples and are not to be used for dispensing to study patients. 
The selected retention samples will be retained at a third party storage facility 
 
 under FDA regulations as study retention samples.17 
Once the site has been notified that they may do so, all unused study product and empty or 
partially used tubes of study product, other than that randomly selected for retention samples will 
be returned to the Sponsor (Actavis) or designee. It is important that retention samples not be 
returned to 
, the Sponsor or the packaging company during or at the end of the study. 
Sufficient study product tubes must be retained among the sites participating in the study to meet 
the sample retention requirements as outlined by the FDA.17 
10.4.4 Method of Assigning Patients to Treatment Groups 
The study product will be randomized, packaged and blinded by an independent packaging 
company 
. The randomization will be pre-planned according to a computer-
generated randomization schedule. 
 
. 
Using 
 (IWRS), all eligible and non-
eligible patients who are consented and screened into the study will be assigned a patient number. 
The patient number is assigned after a patient is consented. It is the only identifier for screened 
patients.
 
 
 
 
The system will also assign 
a study product kit number (based on the randomization schedule created by an independent 
biostatistician). The study product kit number is the identifying number listed on the study 
product dispensed to eligible patients. 
. This 
will be the identifier used for randomized patients (i.e., randomization number). Both the patient 
number and randomization number will be entered into the patient's eCRF. At the end of the 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 27 of 54 
 
study, after all the clinical data have been entered and the study database has been locked, a copy 
of the randomization schedule will be sent to the statistician. 
10.4.5 Study Blind 
The Investigator, staff at the study site, study monitors, and data analysis/management personnel 
will be blinded to the patient assignment. Each study site will have at least one Independent 
Dispenser. The role of the Independent Dispenser is to dispense and collect study product to/from 
the patients, maintain dispensing records, and ensure the study product logs are complete and 
accurate. The patient will be requested not to discuss the appearance of the study product with the 
Investigator or study staff outside of the Independent Dispenser. 
 
 
 
 
 
. The Test, Reference and 
Placebo products will be blinded with identical outer cartons and labels. This will allow the study 
to be conducted under double-blind conditions (i.e., such that neither the patient nor the 
Investigator nor study staff members will know the identity of the patient’s treatment). 
To ensure that information that could potentially bias handling of data is not disclosed, the 
packaging company will hold the randomization scheme until after database lock. During the 
clinical phase of the study, 
 IWRS includes a form for Investigators to 
complete to determine treatment assignment (i.e., to unblind individual patient) to be completed 
for a medical emergency only. 
 
 
 
 Whenever possible, the 
 Medical Monitor should 
be contacted before breaking the blind for any patient. If the Medical Monitor cannot be reached, 
then the Vice President Clinical Trials and Data Management or designee will be contacted 
before unblinding. Investigative sites can use either one of the above methods to unblind a 
patient, when unblinding is deemed necessary by the Principal Investigator. 
In the event the blind is broken for any reason, Sponsor and 
 will be notified as soon as 
possible in writing of the details of the occurrence. 
At the conclusion of the study, after the database has been locked, each site will be sent a sealed 
envelope containing the full study randomization scheme that should be retained with the study 
documents in the event of an FDA inspection. 
10.4.6 Compliance 
Patients will be provided with a diary to record the time and date of dosing, other concomitant 
medications, and AEs. Patients who do not dose as instructed on Day 1 will be considered non-


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 28 of 54 
 
compliant with dosing, and excluded from the per-protocol (PP) population. Dosing compliance 
will be checked based on the dosing diary entry and verbal discussion with the patient at Visit 2. 
10.5 Study Conduct 
Unscheduled visits will be allowed as deemed necessary by the Investigator or Sponsor to ensure 
patient safety or to perform other study-related procedures. 
10.5.1 Visit 1 (Day -1 to 1): Screening/Baseline 
1. Informed Consent: Patients who are willing to comply with study procedures will read and 
sign the ICF, as appropriate. Patients who are considered minors will read and sign the assent 
to participate form, as appropriate, and their parent or legal guardian must sign the ICF. 
Patient’s 11-17 years of age will read and sign an IRB-approved assent form and patients 6-
10 years of age will provide verbal assent. Patients 6 months-5 years of age will be exempt 
from providing assent based on the child’s comprehension and cognitive skills. All infested 
members of a household must agree to receive treatment for anyone in the household to be 
enrolled. 
2. Medical History and Baseline Demographics: Review the patient’s demographic and 
medical history. 
3. Concomitant Medication: Review the patient’s use of any medications in the last four 
weeks. 
4. Vital Signs: The patient’s vital signs will be recorded (pulse, blood pressure, temperature and 
respiration rate). 
5. Pregnancy Test: A urine pregnancy test will be required of all female patients of 
childbearing potential before enrollment. 
6. Louse Examination: An Investigator or staff member, who is experienced and trained in 
detection and evaluation of head lice, will perform a visual inspection for the presence of live 
lice (i.e., live adults and/or nymphs). Louse examination should be conducted for 15 minutes 
or longer, unless any live lice are detected in less time. Duration of examination and number 
of live lice should be recorded in the patient’s eCRF. 
7. Inclusion/Exclusion Criteria Review: Study staff will confirm that the patient meets all 
inclusion/exclusion criteria. 
8. Application Site Reactions: The Investigator will grade the individual signs and symptoms 
presented in Appendix A. This will serve as a baseline for subsequent assessments of 
application site reactions. 
9. Dispense Study Product: Eligible patients will receive one tube of study product with 
instructions for dosing at home. Tubes will be dispensed for all members of a patient’s 
household. 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 29 of 54 
 
10. Provide Patient Diary: A diary will be provided to record date and time of dosing, AEs, 
including any ocular discomfort, and concomitant medications. 
11. Adverse Events: Patients will be questioned about any AEs that occurred during the visit. 
10.5.2 Visit 2 (Day 2): Interim Visit 
Visit 2 must occur the day after patient dosing. All treated household members will return for 
follow-up at Visit 2 only. 
1. Concomitant Medication: Review the patient’s use of any new or ongoing concomitant 
medications since the last visit. 
2. Adverse Events: Patients will be questioned about any health status changes/AEs since last 
visit. All AEs will be recorded. 
3. Vital Signs: The patient’s vital signs will be recorded (pulse, blood pressure, temperature and 
respiration rate). 
4. Pregnancy Test: A urine pregnancy test will be required of all female patients of 
childbearing potential. 
5. Louse Examination: An Investigator or staff member, who is experienced and trained in 
detection and evaluation of head lice, will perform a visual inspection for the presence of live 
lice (i.e., live adults and/or nymphs). Louse examination should be conducted for 15 minutes 
or longer, unless any live lice are detected in less time. If any live lice are found during the 
exam, the patient should be discontinued and provided with alternative therapy. Duration of 
examination and number of live lice should be recorded in the patient’s eCRF. 
6. Application Site Reactions: Patients will be asked about any application site reactions since 
last visit (see Appendix A). Any reactions will be recorded. 
7. Ocular Irritation Assessment: Patients will be questioned about any ocular discomfort 
resulting from contact with the study product. Any discomfort will be documented as an AE. 
8. Return Study Product: Patients will return the used study product tube. 
9. Collect and Review Patient Diary: Study staff will collect previously provided diary and 
review for compliance with the protocol. 
10. Provide Patient Diary: A diary will be provided to record AEs and concomitant 
medications. 
10.5.3 Visit 3 (Day 8 ± 2 days): Interim Visit 
1. Concomitant Medication: Review the patient’s use of any new or ongoing concomitant 
medications since the last visit. 
2. Adverse Events: Patients will be questioned about any health status changes/AEs since the 
last visit. All AEs will be recorded. 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 30 of 54 
 
3. Vital Signs: The patient’s vital signs will be recorded (pulse, blood pressure, temperature and 
respiration rate). 
4. Pregnancy Test: A urine pregnancy test will be required of all female patients of 
childbearing potential. 
5. Louse Examination: An Investigator or staff member, who is experienced and trained in 
detection and evaluation of head lice, will perform a visual inspection for the presence of live 
lice (i.e., live adults and/or nymphs). Louse examination should be conducted for 15 minutes 
or longer, unless any live lice are detected in less time. If any live lice are found during the 
exam, the patient should be discontinued and provided with alternative therapy. Duration of 
examination and number of live lice should be recorded in the patient’s eCRF. 
6. Application Site Reactions: Patients will be asked about any application site reactions since 
last visit (see Appendix A). Any reactions will be recorded. 
7. Collect and Review Patient Diary: Study staff will collect previously provided diary and 
review for compliance with the protocol. 
8. Provide Patient Diary: A diary will be provided to record AEs and concomitant 
medications. 
10.5.4 Visit 4 (Day 15 ± 2 days): End of Study 
1. Concomitant Medication: Review the patient’s use of any new or ongoing concomitant 
medications since the last visit. 
2. Adverse Events: Patients will be questioned about any health status changes/AEs since the 
last visit. All AEs will be recorded. 
3. Vital Signs: The patient’s vital signs will be recorded (pulse, blood pressure, temperature and 
respiration rate). 
4. Pregnancy Test: A urine pregnancy test will be required of all female patients of 
childbearing potential. 
5. Louse Examination: An Investigator or staff member, who is experienced and trained in 
detection and evaluation of head lice, will perform a visual inspection for the presence of live 
lice (i.e., live adults and/or nymphs). Louse examination should be conducted for 15 minutes 
or longer, unless any live lice are detected in less time. Duration of examination and number 
of live lice should be recorded in the patient’s eCRF. 
6. Application Site Reactions: Patients will be asked about any application site reactions since 
last visit (see Appendix A). Any reactions will be recorded. 
7. Collect and Review Patient Diary: Study staff will collect previously provided diary and 
review for compliance with the protocol. 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 31 of 54 
 
10.6 Study Procedures 
10.6.1 Informed Consent 
At Visit 1, before performing any study-related procedures all patients will read and sign an IRB-
approved ICF. In addition, patients who are considered minors in the state the study is being 
conducted (< 18 years of age in most states) must have a signed parental/guardian ICF, indicating 
approval to participate, as well as a signed assent to participate form, as appropriate. Patient’s 11-
17 years of age will read and sign an IRB-approved assent form and patients 6-10 years of age 
will provide verbal assent. Patients 6 months-5 years of age will be exempt from providing assent 
based on the child’s comprehension and cognitive skills. If any other language is required, 
translation will be performed by a certified translator. 
10.6.2 Medical History and Demographics 
At Visit 1, each patient will be required to provide basic demographic information: date of birth, 
gender, ethnicity and race. Patients will also be questioned about medical history, including acute 
and chronic medical history and medical history relevant to their head lice. 
10.6.3 Concomitant Medication 
At Visit 1, patients will be questioned about current and previous medication use over the last 
four weeks. At all subsequent visits, patients will be questioned about ongoing or new 
concomitant medication use. 
10.6.4 Adverse Events 
At the end of Visit 1, patients will be questioned about any AEs that occurred during the visit. At 
Visits 2, 3, and 4 patients will be questioned regarding any changes in their medical status since 
their previous visit. Any significant changes observed after ICF/assent signing will be reported as 
AEs. 
10.6.5 Vital Signs 
The patient’s vital signs will be recorded (pulse, blood pressure, temperature and respiration rate) 
at Visits 1, 2, 3, and 4. 
10.6.6 Pregnancy Test 
Urine pregnancy tests on females of childbearing potential will be performed at each visit. The 
test must be negative for the patient to be eligible for inclusion in the study. If the patient is of 
non-childbearing potential, the source document must list the reason why she is of non-
childbearing potential (e.g., postmenopausal). 
Any patient who becomes pregnant during the study must be discontinued and End of Study 
procedures completed. The outcome of the pregnancy will be followed by the Investigator to birth 
or early termination as appropriate. The pregnancy will be reported as an AE. 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 32 of 54 
 
10.6.7 Louse Examination 
The Investigator or other qualified staff will perform a visual inspection for the presence of live 
lice (i.e., live adults and/or nymphs) at each visit. Louse examination should be conducted for 15 
minutes or longer, unless any live lice are detected in less time. Duration of examination and 
number of live lice should be recorded in the patient’s eCRF. Patients with live lice present at 
Visits 2 or 3 should be discontinued from the study and provided with alternative therapy. 
Determination of live lice can be aided by the use of a mild magnification (e.g., 5x). 
10.6.8 Inclusion/Exclusion Criteria Review 
At Visit 1, inclusion/exclusion criteria will be reviewed to ensure patients’ eligibility for 
participation in the study. 
10.6.9 Application Site Reactions 
At Visit 1, the Investigator will grade the individual signs and symptoms (erythema, pyoderma, 
excoriation, pain, pruritus, edema) per Appendix A. This will serve as a baseline for subsequent 
assessments of application site reactions. At Visits 2, 3, and 4, application site reactions will be 
assessed by clinic staff. Reactions will be scored and recorded. 
10.6.10 Ocular Irritation Assessment 
At Visit 2, patients will be asked if the study product came into contact with their eyes. If contact 
is reported, they will be asked to report any signs or symptoms experienced. Any reported signs 
or symptoms should be recorded as AEs. 
10.6.11 Dispense Study Product 
 
. 
10.6.12 Collect Study Product 
Tubes of study product will be collected from all patients at Visit 2 and checked for compliance 
or evidence of tampering with the blind. 
10.6.13 Provide Patient Diary 
At Visit 1, patients will be provided with a diary to record the time and date of dosing, other 
concomitant medications and AEs, including any ocular discomfort. 
At Visits 2 and 3, patients will be provided with a diary to record concomitant medications and 
AEs. 
An adult member of the household will complete the diary for younger patients who are unable to 
complete the diary on their own. 
10.6.14 Collect and Review Patient Diary 
At Visits 2, 3, and 4, patient diaries will be collected and reviewed for compliance with the 
protocol. 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 33 of 54 
 
10.7 Adverse Events 
Patients will be encouraged to report signs, symptoms and any changes in health to the clinic staff. 
Severity of each AE will be determined based on observation and questioning of the patient. The 
Investigator will judge the severity and relationship of the event to the study products. 
10.7.1 Adverse Event Definition 
An AE is any untoward medical occurrence in a patient, regardless of whether it has a causal 
relationship with this treatment. 
In this study, any AE occurring after the patient has signed the ICF/assent until the end of follow-up 
period should be recorded and reported as an AE. 
An AE can, therefore, be any unfavorable and unintended physical sign, symptom, or laboratory 
parameter that develops or worsens in severity during the course of this study, or significant 
worsening of the disease under study or of any concurrent disease, whether or not considered 
related to the study product. A new condition or the worsening of a pre-existing condition will be 
considered an AE. Stable chronic conditions (such as arthritis) that are present before study entry 
and do not worsen during this study will not be considered AEs. 
Accordingly, an AE can include any of the following: 
• 
intercurrent illnesses 
• 
physical injuries 
• 
events possibly related to concomitant medication 
• 
significant worsening (change in nature, severity, or frequency) of the disease under 
study or other pre-existing conditions drug interactions 
• 
events occurring during diagnostic procedures or during any washout phase of this study 
• 
laboratory or diagnostic test abnormalities that result in the withdrawal of the patient 
from the study, are associated with clinical signs and symptoms or a serious adverse 
event (SAE), or require medical treatment or further diagnostic work up, or are 
considered by the Investigator to be clinically significant (Note: Abnormal laboratory test 
results at the screening visit that preclude a patient from entering the study or receiving 
study treatment are not considered AEs.) 
A treatment-emergent AE is any AE that occurs after initiation of study product, or any event 
already present that worsens in either intensity or frequency following exposure to study product. 
10.7.2 Serious Adverse Events 
An SAE is an AE, regardless of the relationship to study product, that results in any of the 
following outcomes or actions: 
• 
Death 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 34 of 54 
 
• 
A life-threatening AE (i.e., the patient was at immediate risk of death from the event as it 
occurred; does not include an event that, had it occurred in a more severe form, might 
have caused death) 
• 
Inpatient hospitalization or prolongation of existing hospitalization means that hospital 
inpatient admission and/or prolongation of hospital stay were required for treatment of an 
AE, or that they occurred as a consequence of the event. Hospitalizations scheduled prior 
to study entry will not be considered SAEs, unless there was worsening of the pre-
existing condition during the patient’s participation in this study 
• 
Persistent or significant disability or incapacity (refers to a substantial disruption of one’s 
ability to conduct normal life functions) 
• 
A congenital anomaly/birth defect 
• 
An important medical event that may not result in death, be life-threatening, or require 
hospitalization, but may jeopardize the subject and may require medical intervention to 
prevent one of the outcomes listed in this definition. Examples of such events are 
intensive treatment in an emergency room or at home for allergic bronchospasm; blood 
dyscrasias or convulsions that do not result in hospitalization; or the development of drug 
dependency or drug abuse. Note: Any suspected transmission of an infectious agent via a 
medicinal product is considered an important medical event. 
An AE that does not meet any of the criteria for seriousness listed above will be regarded as a 
non-serious AE. 
10.7.3 Other Significant Adverse Events 
When tested, marked haematological and other laboratory abnormalities (other than those 
meeting the definition of serious) and any events that led to an intervention, including withdrawal 
of test drug/investigational product treatment, dose reduction, or significant additional 
concomitant therapy, other than those reported as SAEs should be collected in the eCRF and 
summarized in the clinical study report. 
10.7.4 Severity 
The severity of each AE must be recorded as one of the choices on the following scales: 
• 
Mild: No limitation of usual activities 
• 
Moderate: Some limitation of usual activities 
• 
Severe: Inability to carry out usual activities 
10.7.5 Relationship of an Adverse Event to the Study Drug 
Adverse events will be assessed for the relationship to the study product (causality) according to 
the following scale: 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 35 of 54 
 
TERM 
DEFINITION 
CLARIFICATION 
No Reasonable 
Possibility (not 
related) 
This category applies to those 
AEs which, after careful 
consideration, are clearly due to 
extraneous causes (disease, 
environment, etc.) or to those 
AEs, which after careful medical 
consideration at the time they are 
evaluated, are judged to be 
unrelated to the test drug. 
An adverse experience may be considered 
No Reasonable Possibility if it is clearly due to 
extraneous causes or when (must have two): 
It does not follow a reasonable temporal 
sequence from the administration of the test 
drug. 
It could readily have been produced by the 
patient's clinical state, environmental or 
toxic factors, or other modes of therapy 
administered to the patient. 
It does not follow a known pattern of 
response to the test drug. 
It does not reappear or worsen when the 
drug is re-administered.  
Reasonable 
Possibility 
(related) 
This category applies to those 
AE for which, after careful 
medical consideration at the time 
they are evaluated, a connection 
with the test drug administration 
cannot be ruled out with 
certainty or felt with a high 
degree of certainty to be related 
to the test drug. 
An adverse experience may be considered 
Reasonable Possibility related if or when (at least 
two of the following): 
It follows a reasonable temporal sequence 
from administration of the drug. 
It could not be reasonably explained by the 
known characteristics of the patient's 
clinical state, environmental or toxic factors, 
or other modes of therapy administered to 
the patient. 
It disappears or decreases on cessation or 
reduction in dose. There are important 
exceptions when an AE does not disappear 
upon discontinuation of the drug, yet drug-
relatedness clearly exists. 
It follows a known pattern of response to the 
test drug. 
10.7.6 Expectedness 
An AE that is not included in the AE section of the relevant Safety Information Reference by its 
specificity, severity, outcome or frequency is considered an unexpected AE. 
The reference safety information for this study, SKLICE® (ivermectin) Lotion, 0.5% Product 
Insert, to be used as reference for safety information can be found in Appendix B. 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 36 of 54 
 
The Sponsor’s Pharmacovigilance Department will determine the expectedness for all SAEs. 
Neither the contract research organization (CRO) nor the Investigators will determine the 
expectedness. 
10.7.7 Recording and Reporting of Adverse Events 
In this study, safety will be assessed by qualified study personnel by evaluating reported AEs, 
application site reactions, ocular safety assessment, vital signs measurements and use of 
concomitant medication. 
For AE recording, the study period is defined for each patient as that time period from signature 
of the ICF through the end of the study (including any follow-up period). 
All AEs that occur during the defined study period must be recorded on the source 
documentation, regardless of the severity of the event or judged relationship to the study product. 
For SAEs, the SAE form must also be completed and the SAE must be reported immediately (see 
section 10.7.8). The Investigator does not need to actively monitor subjects for AEs once the 
study has ended. However, SAEs occurring in a patient after the treatment of that patient has 
ended should be reported to the Sponsor if the Investigator becomes aware of them. 
At each contact with the patient, the Investigator or designee must question the patient about AEs 
by asking an open ended question such as, “Have you had any unusual symptoms or medical 
problems since the last visit? If yes, please describe.” All reported or observed signs and 
symptoms will be recorded individually, except when considered manifestations of a medical 
condition or disease state. A precise diagnosis will be recorded whenever possible. When such a 
diagnosis is made, all related signs, symptoms, and any test findings may be recorded collectively 
as a single diagnosis on the eCRF and, if it is an SAE, on the Serious Adverse Event Form. 
The onset and end dates and times, action taken regarding study product, treatment administered, 
and outcome for each AE must be recorded on the source documentation. 
The relationship of each AE to study product treatment and study procedures, and the severity 
and seriousness of each AE, as judged by the Investigator, must be recorded as described above. 
The clinical course of each AE will be monitored at suitable intervals until resolved or stabilized 
or returned to baseline, until the patient is referred for continued care to a health care professional 
or until a determination of a cause unrelated to the study product or study procedure is made. 
Adverse events will be coded according to Medical Dictionary for Regulatory Activities 
(MedDRA) Version 20.0 or higher and reported with respect to severity, duration, relationship to 
study product(s), seriousness and action taken. 
10.7.8 Reporting of Serious Adverse Events 
To satisfy regulatory requirements, all SAEs (as described in section 10.7.2) that occur during the 
study period (including any protocol-defined follow-up period), regardless of judged relationship 
to treatment with the study product, must be reported to the Sponsor or CRO by the Investigator. 
The event must be reported within 24 hours of when the Investigator learns about it. Completing 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 37 of 54 
 
the SAE form and reporting the event must not be delayed, even if not all the information is 
available. 
PLEASE NOTE THAT EMAIL IS THE PREFERRED MEANS OF COMMUNICATION. 
The CRO should inform the Sponsor's Pharmacovigilance Department if the whole study is 
discontinued early because of safety reasons. 
For studies conducted in USA: It is the responsibility of the CRO to report an SAE to the FDA 
within proper time constraints as per the Guidance for Industry and Investigators Safety 
Reporting Requirements for INDs and BA/BE Studies- December 2012. Confirmation of 
submission of this report must then be provided to Teva’s study representative as well as their 
Pharmacovigilance department (contact info below). 
Sites outside of the USA will be responsible for reporting the SAE to 
 and local regulatory 
authorities, as appropriate. 
The timeliness for submission of expedite reports should be 15 days or 7 days (death cases) or as 
otherwise specified in local regulations. 
Any serious or unexpected AEs should be reported to 
 within 24 hours. Following is the 
contact information: 
 
 
 
Or 
 
 
All SAEs, whether or not drug-related, will be immediately (within 1 business day) reported by 
 to the following Sponsor contact by email and followed by a written report within five (5) 
working days: 
USA Pharmacovigilance Unit 
 
 
Sponsor’s Contact person for this Biostudy (copy of the SAE details for information purposes 
only): 
 
 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 38 of 54 
 
Actavis LLC 
 
 
These SAE reports must contain the following information, preferably using the template 
provided by the Sponsor: 
A. Study name/number 
B. Study Product 
C. Investigator details (name, phone, fax, email) 
D. Subject Number 
E. Subject Initials when appropriate 
F. Subject Demographics 
G. Clinical Event 
1) Description 
2) Date of onset 
3) Treatment (drug, dose, dosage form) 
4) AE Relationship to study product 
5) Action taken regarding study product in direct relationship to the AE 
H. If the AE was Fatal: 
1) Cause of death (whether or not the death was related to study drug) 
2) Autopsy findings (if available) 
The SAE form and supportive documents should be filled/written in English. The SAE form 
completion and reporting must not be delayed even if all of the information is not available at the 
time of the initial contact. Additional information (follow-up) about any SAE unavailable at the 
initial reporting should be forwarded within 24 hours of the information becoming available to 
the same address as the initial report. Patients who have had an SAE during the treatment period 
must be followed clinically until all parameters (including laboratory) have either returned to 
normal or have stabilized or are otherwise explained. 
Each report of an SAE will be reviewed and evaluated by the Investigator and the Sponsor's 
Pharmacovigilance Department to assess the nature of the event and the relationship of the event 
to the study product, study procedures, and to underlying disease. 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 39 of 54 
 
10.7.9 Submission of SAEs 
Any SAE will be reported to competent authority and ethics committee according to the country 
specific requirements and the responsibilities defined in section 10.7.8. All AEs will be reported 
in the clinical study report with the complete information named above according to the 
requirements of the Note for Guidance on Structure and Content of Clinical Study Reports 
(CPMP/ICH/137/95). 
10.8 Early Termination (Patient, Study) 
A patient may terminate from the study early for any reason at any time without any disadvantages. In 
this case, the Investigator should make every effort to have the patient return to the next scheduled 
visit to perform all required End of Study / Study Completion / Early Termination visit activities and 
to collect and reconcile all test articles. If the patient does not return for the End of Study / Study 
Completion / Early Termination visit, the site should fully document the reason for early termination. 
All data, including the date and primary reason for termination, must be recorded on the End of Study 
/ Study Completion / Early Termination eCRF, and source document. 
Any patient who experiences an AE may be terminated from the study or from study treatment at any 
time at the discretion of the Investigator. In this case, the patient should be followed at the discretion 
of the Investigator until the resolution or stabilization of the AE. All applicable data should be 
recorded in the AE section of the eCRF. If a patient terminates from the study early for multiple 
reasons that include AEs, the End of Study / Study Completion / Early Termination eCRF should 
indicate that early termination was related to an AE. 
An exception to this requirement will be the occurrence of an AE that in the opinion of the 
Investigator is not severe enough to warrant early termination but that requires the use of a prohibited 
medication, thereby requiring discontinuation of the patient. In such a case, the reason for 
discontinuation would be need to take a prohibited medication, not the AE. 
The Investigator must inform the clinical project physician/clinical leader/Principal Investigator as 
soon as possible of all patients who are being considered for early termination due to AEs. Additional 
reports must be provided when requested. 
The Sponsor reserves the right to terminate the study at any time for administrative reasons. The 
study may also be terminated by regulatory authorities or by the Investigator for his/her site following 
consultation with the Sponsor. Following a decision to discontinue the trial, the Investigator will 
immediately inform both the study patients and the IRB responsible for this trial within 10 working 
days, stating the reasons for discontinuation of the study and, furthermore, advise them in writing of 
any potential risks to the health of study patients or other persons. It is Sponsor’s responsibility to 
report the premature termination of the study to the regulatory agencies within 15 days providing 
them with the reasons for the trial discontinuation and advising them in writing of any potential risks 
to the health of study patients or other persons. The CRO may notify the regulatory agency on behalf 
of the Sponsor. 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 40 of 54 
 
10.9 Pregnancy 
Non-infested household members who are pregnant at the time of the study may not be involved with 
the application of the study product to other household members. 
Female patients of childbearing potential must have been using and must agree to continue to use 
accepted methods of birth control, throughout the study. All female patients are considered to be of 
childbearing potential unless they are pre-menarchal, have been surgically sterilized or have been 
postmenopausal for at least 1 year. Abstinence is an accepted method of birth control. Alternatively, 
any of the following methods of birth control are acceptable: oral contraceptives, contraceptive 
patches/implants (e.g., Skyla® and Mirena®), Depo-Provera®, double-barrier methods (e.g., condom 
and spermicide) or intrauterine device. Before study enrollment women of childbearing potential must 
be advised of the importance of avoiding pregnancy during study participation. 
A negative result of a urine pregnancy test having a minimum sensitivity of at least 50 mIU/mL for 
hCG should be obtained, before study participation. Pregnancy testing will be performed at all clinic 
visits (i.e., 1-4) and the results of all pregnancy tests (positive or negative) will be documented. 
All pregnancies (of women participating in the study and partners of men participating in the study, if 
possible) that occur during the study, or within 30 days for unknown half-lives days of completion of 
the study, are to be reported immediately to the individual identified in the clinical study personnel 
contact information section of this protocol, and the Investigator must provide the Sponsor with the 
pregnancy form. The process for reporting a pregnancy is the same as that for reporting a SAE (as 
above). 
Any female patient becoming pregnant during the study will discontinue treatment. All patients who 
become pregnant will be monitored for the outcome of the pregnancy (including spontaneous or 
voluntary termination). If the pregnancy continues to term, the outcome (health of the infant up to 8 
weeks of age), including details of birth and presence or absence of any birth defect, congenital 
abnormalities, or maternal and newborn complications, will be reported to the Sponsor. Any 
complication of pregnancy during the study and any complication of pregnancy that the Investigator 
becomes aware of after termination from the study will be reported as an AE or SAE, as appropriate. 
If the pregnancy does not continue to term, one of the following actions will be taken: 
• 
For a spontaneous abortion, report as an SAE. 
• 
For an elective abortion due to developmental anomalies, report as an SAE. 
• 
For an elective abortion not due to developmental anomalies, report on the pregnancy 
form; do not report as an AE. 
10.10 Medication Error and Special Situations 
Any administration of medication that is not in accordance with the study protocol should be reported 
on the eCRF, regardless of whether an AE occurs as a result. 
Types of medication errors and special situations: 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 41 of 54 
 
1. Breastfeeding - Suspected adverse reactions which occur in infants following exposure to a 
medicinal product from breast milk. 
2. Unexpected Benefits of Drug. 
3. Medication error: Any unintentional error in the prescribing, dispensing, or administration of 
a medicinal product while in the control of the healthcare professional, patient, or consumer. 
4. Overdose: Administration of a quantity of a medicinal product given per administration or 
cumulatively which is above the maximum recommended dose according to the authorized 
product information. Clinical judgment should always be applied. 
5. Misuse: Situations where the medicinal product is intentionally and inappropriately used not 
in accordance with the authorized product information. 
6. Abuse: Persistent or sporadic, intentional excessive use of medicinal products which is 
accompanied by harmful physical or psychological effects. 
7. Off-label use: Situations where a medicinal product is intentionally used for a medical 
purpose not in accordance with the authorized product information. 
8. Occupational exposure: Exposure to a medicinal product, as a result of one’s professional or 
non-professional occupation. 
9. Lack of efficacy. 
10.11 Follow-up of Subjects After AE 
The staff of the clinical facility has to monitor the clinical trial patient's safety from the occurrence of 
an AE until satisfactory recovery. 
Any AE which remains unresolved at the time point of patient’s last visit requires detailed evaluation 
and follow-up until the AE has been resolved or a reasonable explanation for its persistence is found; 
in case of AEs related to the study product every effort has to be made to follow-up clinical trial 
patients in order to determine the final outcome. If follow-up cannot be completed until release of 
eCRF by the Investigator, follow-up information will be documented separately in the patient’s 
record and outcome, including a short description on follow-up procedures performed, must be sent to 
the Sponsor. 
It is the Investigator’s responsibility to assure that patients experiencing adverse reactions will receive 
definitive treatment for any adverse reaction, if required. Details of follow-up care are to be provided 
(i.e., if treatment or hospitalization is required). The responsibility to provide adequate follow-up for 
AEs includes periodically repeating laboratory tests yielding clinically abnormal results at the End of 
Study evaluation. 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 42 of 54 
 
11.0 STATISTICAL METHODS 
11.1 Statistical Plan 
A Statistical Analysis Plan (SAP), including study data report format, detailing the intended statistical 
analysis of the study data, will be prepared as a separate document and finalized before database lock. 
Any deviation from the original statistical plan will be described and justified in the final report, as 
appropriate. The procedure for accounting for missing, unused and spurious data will be included in 
the SAP. 
If not otherwise specified, statistical significance is defined as p < 0.05, two-sided. Data will be 
summarized with respect to demographic and baseline characteristics, efficacy variables and safety 
variables. For categorical variables, the number and percent of each category within a parameter will 
be calculated for non-missing data. For continuous variables, statistics will include number of 
observations, mean, standard deviation, median, minimum and maximum values. 
All statistical analysis will be conducted using Statistical Analysis Software (SAS®), Version 9.4 or 
higher. Datasets will be prepared using headings from Clinical Data Interchange Consortium 
(CDISC), Study Data Tabulation Model (SDTM) implementation for human clinical trials, and 
Analysis Dataset Model (ADaM). 
11.2 Sample Size Determination 
For the primary endpoint analysis (proportion of index patients in the PP population who are 
considered to be a Treatment Success on Day 15 ± 2), sample size is estimated for therapeutic 
equivalence of the Test to the Reference product and superiority of each of the active treatments 
groups over Placebo. The sample size estimations are based on data reported in the product label for 
SKLICE® (ivermectin) Lotion, 0.5%. 
 
 
 
 
to demonstrate therapeutic equivalence (i.e., the 90% confidence interval (Yates’ 
continuity-corrected) of the absolute difference between the Test and Reference cure rates is within a 
defined equivalence range [-20% to +20%]). 
 
 
 
 
 
 
 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 43 of 54 
 
 
 
 
 
 
11.3 Study Populations 
11.3.1 Per-Protocol Population 
The PP population will include all randomized patients who: 
• 
Meet all inclusion and exclusion criteria. 
• 
 
 
 
 
• 
 
 
 
• 
Have no significant protocol deviations. 
• 
Apply the study product as instructed on Day 1. 
 
 
 
11.3.2 Modified Intent-to-Treat (mITT) Population 
The mITT population will include all randomized patients who meet all inclusion/exclusion 
criteria, apply the study product as instructed, and return for at least one post-baseline evaluation 
visit. 
11.3.3 Safety Populations 
The Safety population will include all patients who are randomized and received study product. 
11.4 Baseline Comparability 
Baseline characteristics will be evaluated separately for the PP, mITT and Safety populations. 
The following baseline demographics (determined from their initial study visit) will be evaluated: 
• 
Age (years) 
• 
Gender (Male/Female) 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 44 of 54 
 
• 
Ethnicity (Hispanic/non-Hispanic) 
• 
Race (White, Black/African American, Native Hawaiian or Other Pacific Islander, Asian, 
American Indian or Alaska Native, Other) 
• 
Number of live lice 
Summary tables by treatment group will be presented. Continuous variables will be summarized 
using descriptive statistics (number of observations, median, minimum, maximum, mean and standard 
deviation). Categorical variables will be summarized using frequencies and percentage. Baseline 
treatment comparisons will be presented using Chi-Square or Cochran-Mantel-Haenszel (CMH) tests 
for the categorical variables, and Analysis of Variance (ANOVA) for the continuous variables. 
All data will be listed by treatment and patient. 
11.5 Efficacy Endpoints 
Primary Efficacy Endpoint 
The primary efficacy endpoint is the proportion of index patients in each treatment group who are 
considered a Treatment Success on Day 15 ± 2. Treatment Success is defined as the absence of live 
lice. 
Secondary Efficacy Endpoint 
The secondary efficacy endpoint is the proportion of all randomized patients (i.e., index + non-index) 
who are considered a Treatment Success on Day 15 ± 2. Treatment Success is defined as the absence 
of live lice. 
11.6 Primary and Secondary Endpoint Analyses 
Therapeutic Equivalence Analysis 
Therapeutic equivalence will be evaluated for both primary and secondary endpoints using the PP 
population. If the 90% confidence interval for the absolute difference between the proportion of 
patients who are considered a Treatment Success in the Test and Reference groups is contained within 
the range [-20%, +20%] then therapeutic equivalence of the Test product to the Reference product 
will be considered to have been demonstrated. 
The same statistical approach will be conducted for analysis of the secondary endpoint in the PP 
population. 
To declare therapeutic equivalence of the Test product to the Reference product, therapeutic 
equivalence must be demonstrated for only the primary endpoint in the PP population. 
Superiority Analysis 
Superiority of the Test and Reference products against the Placebo for the primary endpoint will be 
tested at the 5% significance level (p < 0.05; two-sided, CMH test, stratified by clinical site) in the 
mITT population using last observation carried forward. If the proportions of patients who are 
considered a Treatment Success in the Test and Reference groups are numerically and statistically 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 45 of 54 
 
superior to that of the Placebo (p < 0.05; using two-sided, CMH test stratified by clinical site), then 
superiority of the Test and Reference products over Placebo will be concluded. 
The same statistical approach will be conducted for analysis of the secondary endpoint in the mITT 
population. 
To declare superiority of the Test and Reference products over Placebo, their superiority must be 
demonstrated for only the primary endpoint in the mITT population. 
11.7 Treatment-by-Site Interaction and Pooling of Clinical Sites 
As this is a multiple-site study, the interaction of treatment-by-site may be evaluated for the primary 
efficacy endpoint in the PP population (for equivalence testing). The treatment-by-site interaction will 
be evaluated by the Breslow-Day test for homogeneity of the odds ratio at the 5% significance level 
(p < 0.05). A site(s) with a low enrollment rate(s) may be pooled with its geographically closest site, 
so as to avoid bias in the estimation of a treatment-by-site interaction effect. The pooling will be done 
for low enrolling sites that account for less than 4-7% of the total number of patients in the PP 
population at the site with the highest enrolling rate in the PP population. If the treatment-by-site 
interaction term is found to be statistically significant (p < 0.05) then the interaction term will also be 
assessed for clinical relevance before pooling the data across sites. This will include examination of 
Treatment Success rates at each site where sample sizes per treatment may be influential in the 
assessment of the interaction. 
11.8 Safety Analysis 
Adverse events will be classified using standard Medical Dictionary for Regulatory Activities 
(MedDRA) terminology Version 20.0 or higher and summarized by treatment group. Summary tables 
comparing the type, date of onset, date of resolution, incidence, severity, relationship to the study 
product, action taken, and outcome will be prepared by treatment group. If sufficient data exist, then 
AE frequencies will be compared among treatments using Fisher’s exact test or a similar test. 
Application site reactions and ocular discomfort will be compared descriptively among treatment 
groups. 
Concomitant medication use during the randomized treatment period will be tabulated by patient. 
Signs and symptoms of head lice will not be considered AEs, unless in the Investigator’s opinion, 
they have increased in frequency and/or severity to such an extent that the Investigator/patient 
considers to be clinically significant. 
All patients who received randomized treatment and received study product will be included in the 
comparative safety analysis. 
12.0 REGULATORY OBLIGATIONS 
12.1 Institutional Review Board 
The study protocol, ICF/assent form, Investigator's Brochure, or package insert (as applicable), and 
any specific advertising will be submitted to, and approved by, an IRB before the start of the study. A 
form must be signed by the chairman or designee of the IRB noting the approvals. This notification of 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 46 of 54 
 
the board's approval along with a description by profession and gender of the board's composition 
will be provided to the Sponsor. 
12.2 Study Documentation 
This study will be conducted in compliance with the protocol; Good Clinical Practices and all 
applicable regulations, including the Federal Food, Drug and Cosmetics Act, US applicable Code of 
Federal Regulations (title 21), parts 50, 56, 312, 320, and any IRB requirements relative to clinical 
studies; and the Declaration of Helsinki, June 1964, as modified by the 64th World Medical 
Association General Assembly, October 2013.18-21 The Investigator will permit trial-related 
monitoring, audits, IRB review and regulatory inspections providing direct access to source 
data/documents. 
12.2.1 Protocol 
The Investigator indicated on FDA Form 1572 will act as the Principal Investigator at each study 
site. Protocols will be noted as approved by placement of the 
 Representative’s signature 
on the cover page. The Sponsor of the study will also approve the protocol by having a study-
responsible individual sign the protocol cover page. 
12.2.2 Informed Consent 
An ICF that includes all of the relevant elements currently required by FDA and local state 
regulations will be provided to each prospective study patient before enrollment into the study. In 
addition, patients 11-17 years of age will read and sign an IRB-approved assent form and patients 
under the age 6-10 years old will provide verbal assent. Patients 6 months-5 years of age will be 
exempt from providing assent based on the child’s comprehension and cognitive skills. The type 
and method of study, tests to be administered, any potential or possible hazards, and the patient’s 
right to withdraw from the study at any time will be explained to the patients by the Investigator 
or designee. Once the Investigator or designee is assured that an individual candidate understands 
the implications of participating in this study, the patient will be asked to give consent by signing 
and dating in the appropriate areas of the ICF or assent, as appropriate. The Investigator or 
designee will also sign and date the form, along with a staff member who will sign the ICF as a 
witness to verify that the patient has indeed received information. If any other language is 
required, translation will be performed by a certified translator. A copy of the ICF and/or assent 
will be provided to the patient. 
12.2.3 Protocol and Informed Consent Changes 
Sponsor approved changes to the protocol or the ICFs will be implemented as revisions to the 
original documents and will require additional review and approval by the IRB. Revisions to the 
original protocol will be documented in amendments, incorporated as a preface to the new 
version. Any revision that substantially alters the study design or increases potential risk to the 
patient requires the patient’s consent to continue in the study. The approvals will be processed in 
accordance with the established IRB procedures. Copies of all protocol and ICF 
amendments/revisions, along with letters noting IRB approval, will be submitted to the Sponsor. 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 47 of 54 
 
12.2.4 Source Documents and Case Report Forms 
All patients will be identified by initials, date of birth, and a unique patient number. Source 
documents will be used to record all study-related data. Source document entries will be used to 
complete eCRFs. A set of eCRFs will be completed for each patient enrolled in the study. All 
data and eCRFs will be reviewed, evaluated and signed by the Investigator. 
The original source documents and a copy of the corresponding eCRFs will be retained by the 
Investigator. Patients who terminate early from the study will have the Visit 4 (End of Study) 
Source/eCRF completed. 
12.2.5 Drug Accountability 
All study product receipt, inventory, dispensing, dosing and reconciliation records will be 
maintained in compliance with federal regulations. The study product will be dispensed to 
qualified study patients according to established procedures. At the end of the study (i.e., at the 
site’s close-out visit) all used and unused study product will be returned to Sponsor or designee. 
12.2.6 Drug Storage 
All study product will be stored at controlled room temperature 20°C to 25°C (68°F to 77ºF) with 
excursions permitted to 15º–30ºC (59º–86ºF), in a secure place with access by authorized 
individuals only. Any excursions from the above temperature range, including those within the 
permitted excursion range of 15º–30ºC (59º–86ºF), will require prompt notification to 
, 
and thereafter 
 will notify the Sponsor. The Investigator will be responsible for 
maintaining accurate records of study product receipt, dispensing, and return. At the end of the 
study (i.e., at the site’s close-out visit), all partially used and unused study product will be 
returned to Sponsor or designee. 
12.2.7 Retention of Reserve Samples 
For every study product shipment received at the Investigator site, the Investigator (or designee) 
will randomly select study product kits for retention, unless otherwise instructed by the Sponsor 
and/or 
. The selection process will ensure a sufficient amount of retention samples are 
retained as per Sponsor requirement. The number of each patient kit kept for retention will be 
noted on the drug accountability form as a retention sample, in addition to the retention sample 
log. These retention samples should be stored under the appropriate storage conditions for a 
minimum of 5 years following the application approval or, if not approved, at least 5 years after 
the 
completion 
of 
the 
study. 
Retention 
samples 
should 
not 
be 
returned 
to 
Sponsor/CRO/packaging group at any time. The retention samples will be shipped to a third party 
storage facility: 
 
 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 48 of 54 
 
12.2.8 Return of Clinical Supplies 
With the exception of the retention samples, all unused kits of study product will be returned to 
Actavis’s Drug Labeling, Packaging and Shipping Facility: 
 
Actavis Laboratories UT, Inc. 
 
 
 
12.2.9 Reporting Safety Information to the IRB 
The Investigator must promptly report to the Investigator’s IRB all unanticipated problems 
involving risks to patients. This includes death from any cause and all SAEs occurring during the 
study, regardless of the assessed causality.22 
12.2.10 Record Retention 
All drug accountability records, eCRFs, source data and related regulatory documents must be 
retained according to 21 CFR 312.62(c) for a period of 2 years following the date the marketing 
application is approved for the drug for the indication for which it is being investigated; or, if no 
application is to be filed or if the application is not approved for such indication, until 2 years 
after the investigation is discontinued and FDA is notified. 
12.2.11 Study Monitoring and Auditing 
 will be responsible for monitoring the study according to Good Clinical Practice and 
applicable regulations. Monitoring visits are for the purpose of confirming adherence to the 
protocol and to verify complete and accurate data collection. The clinical site will make all 
records associated with the study available to 
 representative during such visits and 
audits. 
The study may be subject to audit by the Sponsor, Sponsor Representative or by regulatory 
authorities. If such an audit occurs the Investigator must agree to allow access to required patient 
records. By signing this protocol, the Investigator grants permission to personnel from the 
Sponsor, its representatives and appropriate regulatory authorities for on-site monitoring of all 
appropriate study documentation, as well as on-site review of study procedures. 
12.2.12 End of the Trial 
The end of the trial is defined as the time at which the last patient has completed his/her last visit 
in the study. Upon completion of the study, the study product will no longer be available to the 
patient but the Investigator can, at his/her discretion, discuss alternative treatments with the 
patient. 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 49 of 54 
 
12.2.13 Clinical Study Report 
At the end of the study a full report per requirements of Sponsor and regulatory authorities will be 
prepared which will include a narrative of the clinical conduct and results of the study, a 
statistical report including a description of the analysis performed, and other documentation as 
may be appropriate. The report will be in electronic format according to eCTD and International 
Council on Harmonisation (ICH) formatting standards and guidelines.23 ANDA summary tables 
will also be generated. Data sets will be provided in SAS® transport (.xpt) format with 
appropriate description (Read Me) files as required by FDA. 
12.2.14 Termination of the Study 
The Sponsor reserves the right to terminate the study at any time for administrative reasons.


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 50 of 54 
 
 
13.0 REFERENCES 
1 
CDC. Head Lice - Biology. (2015). 
2 
CDC. Head Lice - Epidemiology & Risk Factors, 
<https://www.cdc.gov/parasites/lice/head/epi.html> (2013). 
3 
CDC. Head Lice - Disease. (2013). 
4 
Lebwohl, M., Clark, L. & Levitt, J. Therapy for head lice based on life cycle, resistance, and 
safety considerations. Pediatrics 119, 965-974, doi:10.1542/peds.2006-3087 (2007). 
5 
CDC. Head Lice - Treatment, <https://www.cdc.gov/parasites/lice/head/treatment.html> (2016). 
6 
Prescribing Information for ULESFIA® Lotion. (2012). 
7 
Package Insert for OVIDE® (malathion) Lotion, 0.5%. (2011). 
8 
Prescribing Information for NATROBA Topical Suspension. (2014). 
9 
Stough, D., Shellabarger, S., Quiring, J. & Gabrielsen, A. A., Jr. Efficacy and safety of spinosad 
and permethrin creme rinses for pediculosis capitis (head lice). Pediatrics 124, e389-395, 
doi:10.1542/peds.2008-3762 (2009). 
10 
Arbor Pharmaceuticals, LLC. Package Insert for SKLICE® (ivermectin) Lotion, 0.5%. (2012). 
11 
FDA. Draft Guidance on Malathion. (2012). 
12 
FDA. Draft Guidance on Spinosad. (2016). 
13 
ICH. Choice of Control Group and Related Issues in Clinical Trials E10. 20 July (2000). 
14 
Penslar. IRB Guidebook, Office for Human Rights Protection. US Department of Health and 
Human Services (1993). 
15 
FDA. Summary Basis of Approval for SKLICE® (ivermectin) Lotion, 0.5% (2012). 
16 
FDA. Head Lice Infestation: Developing Drugs for Topical Treatment - Guidance for Industry. 
(2016). 
17 
FDA. Guidance for Industry. Handling and Retention of BA and BE Testing Samples U.S. 
Department of Health and Human Services, Food and Drug Administration, Center for Drug 
Evaluation and Research (CDER). May (2004). 
18 
FDA. 21CFR 320 Procedures for Determining the Bioavailability or Bioequivalence of Drug 
Products. Department of Health and Human Services, Subchapter D-Drugs for Human Use 5 
(2014). 
19 
FDA. 21CFR Part 50 Protection of Human Subjects. Department of Health and Human Services, 
Subchapter A-General 1 (2014). 
20 
FDA. 21CFR Part 56 Institutional Review Boards. Department of Health and Human Services, 
Subchapter A-General 1 (2014). 
21 
World Medical Association Declaration of Helsinki: ethical principles for medical research 
involving human subjects. Jama 310, 2191-2194, doi:10.1001/jama.2013.281053 (2013). 
22 
FDA. 21CFR 312.32: IND Safety Reporting. (2010). 
23 
ICH. Structure and Content of Clinical Study Reports E3. Step 4 version (1996). 
 
 
 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 51 of 54 
 
14.0 APPENDICES 
14.1 Appendix A: Application Site Reactions 
The following application site reactions will be evaluated at each visit based on the scale provided 
below: 
 
Signs and Symptoms: 
Erythema 
Pyoderma 
Excoriation 
Pain 
Pruritus 
Edema 
 
Grading Scale: 
Absent   
0 
 
Mild  
 
1  
(slight, barely perceptible) 
Moderate 
2 
(distinct presence) 
Severe  
3 
(marked, intense) 
 
 
 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 52 of 54 
 
14.2 Appendix B: SKLICE® (ivermectin) Lotion, 0.5% Product Insert 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to Evaluate the Therapeutic Equivalence and 
Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the 
Treatment of Human Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 53 of 54 
 
14.3 Appendix C: Patient Status 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis Laboratories UT, 
Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in the Treatment of Human 
Head Lice Infestation 
 
71691702  Rev. 1  Actavis Laboratories LLC  Page 54 of 54 
 
14.4 Appendix E: Amendments to the Protocol 
Amendment 
Date 
 
1 
02/01/2018 
 
The following revisions were made to the protocol dated 06/21/2017. 
• 
Increased enrollment to approximately 378 index patients. 
• 
Criteria for the PP population were updated. 
• 
Yates’ correction removed from analysis methods. 
 

SAP_001.pdf: 
 
 
 
 
Statistical Analysis Plan with Amendment 02 
 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical 
Study to Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% 
(Actavis Laboratories UT, Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor 
Pharmaceuticals, LLC) in the Treatment of Human Head Lice Infestation 
 
 
Study Number 71691702 
 
NCT03301649 
 
Statistical Analysis Plan with Amendment 02 Approval Date: 12 January 2018  
 


  
 
STATISTICAL ANALYSIS PLAN 
 
Ivermectin Lotion 0.5%                                                              Protocol / Study No. 71691702 
 
 
01/12/2017                               
 Actavis LLC             
            Page 1 of 52                                             
                      
STATISTICAL ANALYSIS PLAN 
           
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study 
to Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% (Actavis 
Laboratories UT, Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) in 
the Treatment of Human Head Lice Infestation 
 
 
Protocol Number:  71691702 
 71691702 
 
 
Sponsor: 
Actavis LLC 
400 Interpace Parkway 
Morris Corporate Center III 
Parsippany, NJ 07054    
 
 
Contract Research Organization: 
 
 
 
 
January 12, 2018 
Draft Version 2.0 
 


  
 
STATISTICAL ANALYSIS PLAN 
 
Ivermectin Lotion 0.5%                                                              Protocol / Study No. 71691702 
 
 
01/12/2017                               
 Actavis LLC             
            Page 2 of 52                                             
 
 
 
SAP FINAL VERSION APPROVALS 
 
 
 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical 
Study to Evaluate the Therapeutic Equivalence and Safety of Ivermectin Lotion 0.5% 
(Actavis Laboratories UT, Inc.) to SKLICE® (ivermectin) Lotion, 0.5% (Arbor 
Pharmaceuticals, LLC) in the Treatment of Human Head Lice Infestation 
         
 
 
Written By: 
 
Signature: _____________________________  
 
 
 
 
 
 
Date:___________________ 
Reviewed By: 
 
Signature: ____________________________ 
 
 
 
 
 
 
 
Date:___________________ 
Approved By: 
 
Signature: ____________________________  
 
 
 
Actavis LLC 
 
 
 
Date:___________________ 
 
 
 
 


  
 
STATISTICAL ANALYSIS PLAN 
 
Ivermectin Lotion 0.5%                                                              Protocol / Study No. 71691702 
 
 
01/12/2017                               
 Actavis LLC             
            Page 3 of 52                                             
 
Revision History 
VERSION 
DATE 
DESCRIPTION OF REVISIONS 
REVISED BY 
Draft 1.0 
December 06, 2017 
New Document 
 
Draft 2.0 
January 12, 2018 
Incorporate client comments 
 
 
 
 
 
 


  
 
STATISTICAL ANALYSIS PLAN 
 
Ivermectin Lotion 0.5%                                                              Protocol / Study No. 71691702 
 
 
01/12/2017                               
 Actavis LLC             
            Page 4 of 52                                             
 
List of Abbreviations and Definition of Terms 
ADaM  
 
Analysis Data Model  
AE 
 
 
Adverse Event 
ANOVA 
 
Analysis of Variance 
C 
 
 
Celsius 
CDISC 
 
Clinical Data Interchange Standards Consortium 
CMH  
 
Cochran-Mantel-Haenszel 
CRF 
 
 
Case Report Form 
CRO  
 
Contract Research Organization 
EOS   
 
End of Study 
F 
 
 
Fahrenheit 
FDA  
 
Food and Drug Administration 
GLM  
 
Generalized Linear Model 
Hg 
 
 
Mercury 
ICF 
 
 
Informed Consent Form 
ICH 
 
 
International Conference on Harmonisation 
IWRS  
 
Interactive Web Response System 
LOCF  
 
Last Observation Carried Forward 
MedDRA 
 
Medical Dictionary for Regulatory Activities  
mITT  
 
modified Intent-to-Treat Population 
OGD  
 
Office of Generic Drugs 
PP 
 
 
Per-Protocol Population 
RLD  
 
Reference Listed Drug 
SAE 
 
 
Serious Adverse Event 
SAP 
 
 
Statistical Analysis Plan 
SAS 
 
 
Statistical Analysis System 
SD 
  
 
Standard Deviation 
SDTM  
 
Study Data Tabulation Model 
 
 
 
 


  
 
STATISTICAL ANALYSIS PLAN 
 
Ivermectin Lotion 0.5%                                                              Protocol / Study No. 71691702 
 
 
01/12/2017                               
 Actavis LLC             
            Page 5 of 52                                             
TABLE OF CONTENTS 
1. INTRODUCTION ............................................................................................................. 7 
2. OBJECTIVES .................................................................................................................... 7 
3. OVERALL STUDY DESIGN ........................................................................................... 7 
4. RANDOMIZATION AND BLINDING.......................................................................... 11 
5. SAMPLE SIZE ................................................................................................................ 11 
6. ANALYSIS POPULATION ............................................................................................ 12 
7. EFFICACY ENDPOINTS ............................................................................................... 13 
8. STATISTICAL ANALYSIS METHODS ....................................................................... 13 
8.1 Baseline Characteristics ................................................................................................. 14 
8.1.1 Baseline Comparability ............................................................................................... 14 
8.1.2 Medical History .......................................................................................................... 14 
8.1.3 Concomitant Medications ........................................................................................... 14 
8.1.4 Pregnancy Test ............................................................................................................ 15 
8.2 Efficacy Analyses .......................................................................................................... 15 
8.2.1 Primary and Secondary Endpoint Analysis ................................................................ 15 
8.2.2 Treatment-by-Site Interaction and Pooling of Clinical Sites ...................................... 16 
8.3 Safety Analysis .............................................................................................................. 17 
8.3.1 Adverse Events ........................................................................................................... 17 
8.3.2 Application Site Reactions .......................................................................................... 17 
8.3.3 Vital Signs ................................................................................................................... 18 
8.4 Multiple Comparisons .................................................................................................... 18 
8.5 Methods for Handling Missing Data.............................................................................. 18 
8.6 Interim Analyses ............................................................................................................ 18 
9. TABLE, LISTING AND FIGURE SHELLS .................................................................. 19 
T16.1.9.1 Summary of Discontinued Patients ..................................................................... 21 
T16.1.9.2 Summary of Protocol Deviations ........................................................................ 22 
T16.1.9.3.1 Summary of Patients Excluded from Efficacy Analysis .................................. 23 
T16.1.9.3.2 Summary of Patients Included in Analysis Population by Study Center ......... 25 
T16.1.9.4 Summary of Demographic Data and Baseline Characteristics  (Safety Population)
 ................................................................................................................................ 26 
T16.1.9.5 Summary of Demographic Data and Baseline Characteristics (modified Intent-to-Treat 
Population).............................................................................................................. 28 
T16.1.9.6 Summary of Demographic Data and Baseline Characteristics (Per-Protocol 
Population).............................................................................................................. 28 
T16.1.9.7.1 Summary of Analysis Results of Primary Efficacy Endpoint .......................... 29 
T16.1.9.7.2 Sensitivity Analysis Results of Primary Efficacy EndpointError! Bookmark not 
defined. 
T16.1.9.7.3 Sensitivity Analysis Results of Primary Efficacy EndpointError! Bookmark not 
defined. 


  
 
STATISTICAL ANALYSIS PLAN 
 
Ivermectin Lotion 0.5%                                                              Protocol / Study No. 71691702 
 
 
01/12/2017                               
 Actavis LLC             
            Page 6 of 52                                             
T16.1.9.8 Summary of Analysis Results of Secondary Efficacy Endpoint ......................... 30 
T16.1.9.9 Overall Summary of Adverse Events  (Safety Population) ................................. 31 
T16.1.9.10 Summary of Frequency of All Adverse Events by Body System  (Safety Population)
 ................................................................................................................................ 32 
T16.1.9.11 Summary of Frequency of All Adverse Events by Severity (Safety Population)33 
T16.1.9.12 Summary of Frequency of All Adverse Events by Relationship  (Safety Population)
 ................................................................................................................................ 34 
T16.1.9.13 Summary of Frequency of Serious Adverse Events  (Safety Population)......... 35 
T16.1.9.14 Summary of Frequency of Application Site Reaction  (Safety Population) ..... 36 
T16.1.9.15 Summary of Vital Signs  (Safety Population) ................................................... 37 
T16.1.9.16 Summary of Frequence of Patients who are Treatment Failures at Visit 2 and Visit 3 
(Safety Population) ................................................................................................. 38 
T16.1.9.17 Summary of Fequency of Patients with Re-Infestation (Safety Population) .... 39 
L16.2.1 Listing of Discontinued Patients ............................................................................ 40 
L16.2.2 Listing of Protocol Deviations................................................................................ 41 
L16.2.3.1 Listing of Patients Excluded from the Per-Protocol Population ......................... 42 
L16.2.3.2 Lisitng of Patients Excluded from the Modified Intent-to-Treat Population ...... 43 
L16.2.4.1 Listing of Demographic Data .............................................................................. 44 
L16.2.4.2 Listing of Medical History .................................................................................. 45 
L16.2.4.3 Listing of Concomitant Medications ................................................................... 46 
L16.2.5 Listing of Visit Date Information ........................................................................... 47 
L16.2.6 Listing of Louse Examination Results ................................................................... 48 
L16.2.7.1 Listing of Adverse Events by Treatment Group.................................................. 49 
L16.2.7.2 Listing of Application Site Reactions.................................................................. 50 
L16.2.8.1 Listing of Pregnancy Test Results ....................................................................... 51 
L16.2.8.2 Listing of Vital Signs........................................................................................... 52 


  
 
STATISTICAL ANALYSIS PLAN 
 
Ivermectin Lotion 0.5%                                                              Protocol / Study No. 71691702 
 
 
01/12/2017                               
 Actavis LLC             
            Page 7 of 52                                             
1. INTRODUCTION 
This Statistical Analysis Plan (SAP) is based on the final Clinical Study Protocol 71691702 Rev. 
0 dated 06/21/2017. The SAP provides details on the planned statistical methodology for the 
analysis of the study data. The SAP also outlines the statistical programming specifications for 
the tables, listings and figures. 
 
This SAP describes the study endpoints, derived variables, anticipated data transformations and 
manipulations, and other details of the analyses not provided in the study protocol. This SAP 
therefore outlines in detail all other aspects pertaining to the planned analyses and presentations 
for this study. 
 
The following documents were reviewed in preparation of this SAP: 
 
• Final Clinical Study Protocol 71691702 Rev.0  dated 06/21/2017 
• Final eCRF Version 1.0 for Study No. 71691702 
 
The reader of this SAP is encouraged to also read the clinical protocol for details on the 
conduct of this study, and the operational aspects of clinical assessments and timing for 
completing a patient in this study. 
 
2. OBJECTIVES 
The objectives of this study are to: 
1. Evaluate the therapeutic equivalence of the Test formulation, Ivermectin Lotion 0.5% 
(Actavis Laboratories UT, Inc.) to the Reference product, SKLICE® (ivermectin) Lotion, 
0.5% (Arbor Pharmaceuticals, LLC) in the treatment of active head lice infestation. 
2. Demonstrate the superiority of the Test and Reference (active) treatments over Placebo 
treatment in patients with active head lice infestation. 
3. Compare the safety of Test, Reference and Placebo treatments in patients with active head 
lice infestation. 
 
3. OVERALL STUDY DESIGN 
This randomized, double-blind, placebo-controlled, parallel-design, multiple-site clinical study 
has been designed to evaluate the efficacy and safety of a generic Ivermectin Lotion 0.5% 
(Actavis Laboratories UT, Inc.) compared to the Food and Drug Administration (FDA) 
Reference Listed Drug (RLD) SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, 


  
 
STATISTICAL ANALYSIS PLAN 
 
Ivermectin Lotion 0.5%                                                              Protocol / Study No. 71691702 
 
 
01/12/2017                               
 Actavis LLC             
            Page 8 of 52                                             
LLC) in patients with active head lice infestation. Additionally, both the Test and Reference (i.e., 
the RLD) treatments will be tested for superiority to a Placebo. 
Before any study-specific procedures are performed, all patients will read and sign the IRB-
approved informed consent form (ICF). In addition, patients who are considered minors in the 
state the study is being conducted (< 18 years of age in most states), must have a signed 
parental/guardian ICF, indicating approval to participate, as well as a signed assent to participate 
form, as appropriate. Patients 11-17 years of age will read and sign an IRB-approved assent form 
and patients 6-10 years of age will provide verbal assent. Patients 6 months-5 years of age will 
be exempt from providing assent based on the child’s comprehension and cognitive skills. 
Males and females, 6 months of age and older with an active head lice infestation will be 
randomized 
 to one of the three study products as 
follows: 
• Test: Ivermectin Lotion, 0.5% (Actavis Laboratories UT, Inc.) 
• Reference: SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) 
• Placebo: Placebo (vehicle) lotion (Actavis Laboratories UT, Inc.) 
 
 
 
 
 
 
 
Patients, 
 will be instructed to administer a single 
application of the study product to the hair on the day of or the day after enrollment into the 
study, leave the study product on the hair and scalp for 10 minutes, and then rinse off with warm 
water. Patients and infested household members will be instructed to apply the study product at 
home. The day of dosing will be considered Day 1. 
Patients will attend the following four scheduled clinics visits: 
• Visit 1 (Day -1 to 1): Screening/Baseline 
• Visit 2 (Day 2): Interim Visit 
• Visit 3 (Day 8 ± 2): Interim Visit 
• Visit 4 (Day 15 ± 2): End of Study 
At Visit 2 (Day 2), 
enrolled 
 will return the 
study product to the clinic. Visit 2 must occur the day after dosing.
 
 At 
Visits 2, 3, and 4, patients will be examined for the presence of live head lice (i.e., live adults 


  
 
STATISTICAL ANALYSIS PLAN 
 
Ivermectin Lotion 0.5%                                                              Protocol / Study No. 71691702 
 
 
01/12/2017                               
 Actavis LLC             
            Page 9 of 52                                             
and/or nymphs). Louse examination should be conducted for 15 minutes or longer, unless any 
live lice are detected in less time. Duration of examination should be recorded. 
 
 
 
Unscheduled visits will be allowed as deemed necessary by the 
Investigator or Sponsor to ensure patient safety or to perform other study-related procedures. 
At Visit 2, patients will be questioned about any ocular discomfort associated with the study 
product. Also at Visits 2, 3, and 4, patients will be questioned about any adverse events (AEs), 
application site reactions (Appendix A), and any new concomitant medication use. 
Definitions 
• 
 
 
 
 
 
 
• Non-index patient: Any household member who has agreed to participate in the study 
but is not the youngest member of the household. 
• Index patient: The youngest household member who is randomized into the study. 
Therapeutic equivalence will be assessed by evaluating the proportion of index patients in each 
treatment group who are considered a Treatment Success on Day 15 ± 2. Treatment Success is 
defined as the absence of live lice. The proportion of all patients (i.e., index + non-index) who 
are considered a Treatment Success on Day 15 ± 2 will be evaluated as a secondary endpoint. 
The analysis of superiority will compare both active treatment groups to the Placebo group for 
the same primary and secondary endpoints. 
 


  
 
STATISTICAL ANALYSIS PLAN 
 
Ivermectin Lotion 0.5%                                                              Protocol / Study No. 71691702 
 
 
01/12/2017                               
 Actavis LLC             
            Page 10 of 52                                          
Study Schematic 
 
 
PROCEDURE 
VISIT 1 
(Day -1 to 1)* 
Screening/Baseline 
VISIT 2 
(Day 2)† 
Interim 
Visit 
VISIT 3 
(Day 8 ± 2 
Days) 
Interim Visit 
VISIT 4 
(Day 15 ± 2 
Days) 
End of Study 
Informed 
Consent/Assent 
X 
 
 
 
Medical History and 
Demographics 
X 
 
 
 
Concomitant 
Medication 
X 
X 
X 
X 
Adverse Events 
X
X 
X 
X 
Vital Signs 
X 
X 
X 
X 
Pregnancy Test‡ 
X 
X 
X 
X 
Louse Examination 
X 
X 
X 
X 
Inclusion/Exclusion  
X 
 
 
 
Application Site 
Reactions 
X 
X 
X 
X 
Ocular Irritation 
Assessment 
 
X 
 
 
Dispense Study 
Product 
X 
 
 
 
Collect Study Product 
 
X 
 
 
Provide Patient Diary  
X 
X 
X 
 
Collect and Review 
Patient Diary 
 
X 
X 
X 
*Study product will be administered on Day 1. 
†Visit 2 must occur the day after patient dosing. 
‡For females of childbearing potential 
 
 
 
 
 


  
 
STATISTICAL ANALYSIS PLAN 
 
Ivermectin Lotion 0.5%                                                              Protocol / Study No. 71691702 
 
 
01/12/2017                               
 Actavis LLC             
            Page 11 of 52                                          
 
4. RANDOMIZATION AND BLINDING 
The study product will be randomized, packaged and blinded by an independent packaging 
company (Actavis, SLC site). The randomization will be pre-planned according to a computer-
generated randomization schedule. All enrolled members of a household will be randomized to 
the same treatment arm. 
Using 
 Interactive Web Response Technology System (IWRS), all eligible and non-
eligible patients who are consented and screened into the study will be assigned a patient 
number. The patient number is assigned after a patient is consented. It is the only identifier for 
screened patients.
 
 
 
 
The system will 
also assign a study product kit number (based on the randomization schedule created by an 
independent biostatistician). The study product kit number is the identifying number listed on the 
study product dispensed to eligible patients. The study product kit number is a five-digit number. 
This will be the identifier used for randomized patients (i.e., randomization number). Both the 
patient number and randomization number will be entered into the patient's eCRF. At the end of 
the study, after all the clinical data have been entered and the study database has been locked, a 
copy of the randomization schedule will be sent to the statistician. 
The Investigator, staff at the study site, study monitors, and data analysis/management personnel 
will be blinded to the patient assignment.   
5. SAMPLE SIZE 
For the primary endpoint analysis (proportion of index patients in the PP population who are 
considered to be a Treatment Success on Day 15 ± 2), sample size is estimated for therapeutic 
equivalence of the Test to the Reference product and superiority of each of the active treatments 
groups over Placebo. The sample size estimations are based on data reported in the product label 
for SKLICE® (ivermectin) Lotion, 0.5%. 
 
 
 
 
 
 


  
 
STATISTICAL ANALYSIS PLAN 
 
Ivermectin Lotion 0.5%                                                              Protocol / Study No. 71691702 
 
 
01/12/2017                               
 Actavis LLC             
            Page 12 of 52                                          
 
 
 
 
 
 
 
 
Under the above assumptions,
 
 
 
approximately 364 index patients 
may be randomized
 
 
6. ANALYSIS POPULATION  
Per-Protocol Population (PPP) 
 
The PP population will include all randomized patients who: 
• Meet all inclusion and exclusion criteria. 
• 
 
 
 
 
• 
 
 
• Have no significant protocol deviations. 
• Apply the study product as instructed on Day 1. 
 
 
 


  
 
STATISTICAL ANALYSIS PLAN 
 
Ivermectin Lotion 0.5%                                                              Protocol / Study No. 71691702 
 
 
01/12/2017                               
 Actavis LLC             
            Page 13 of 52                                          
Modified Intent-to-Treat Population (mITT) 
 
 
The mITT population will include all randomized patients who meet all inclusion/exclusion 
criteria, apply the study product as instructed, and return for at least one post-baseline evaluation 
visit. 
 
Safety Population 
 
The Safety population will include all patients who are randomized and received study product. 
 
7. EFFICACY ENDPOINTS  
Primary Efficacy Endpoint 
The primary efficacy endpoint is the proportion of index patients in each treatment group who 
are considered a Treatment Success on Day 15 ± 2. Treatment Success is defined as the absence 
of live lice. 
Secondary Efficacy Variable 
The secondary efficacy endpoint is the proportion of all randomized patients (i.e., index + non-
index) who are considered a Treatment Success on Day 15 ± 2. Treatment Success is defined as 
the absence of live lice. 
 
8. STATISTICAL ANALYSIS METHODS 
If not otherwise specified, statistical significance is defined as p < 0.05 and is two-tailed. Data 
will be summarized with respect to demographic and baseline characteristics, efficacy variables 
and safety variables. 
 
For categorical variables, the number and percent of each category within a parameter will be 
calculated for non-missing data.  For continuous variables, statistics will include number of 
observations, mean, standard deviation, median, minimum and maximum values.  
All statistical analyses will be conducted using SAS®, Version 9.4 or higher. Datasets will be prepared 
using headings from Clinical Data Interchange Consortium (CDISC) Study Data Tabulation Model 
(SDTM) implementation for human clinical trials and ADaM (Analysis Dataset Model). ADaM 
datasets will include but not limited to ADSL, ADEFF, ADAE, ADVS, ADCM and ADMH. 


  
 
STATISTICAL ANALYSIS PLAN 
 
Ivermectin Lotion 0.5%                                                              Protocol / Study No. 71691702 
 
 
01/12/2017                               
 Actavis LLC             
            Page 14 of 52                                          
8.1 Baseline Characteristics 
8.1.1 Baseline Comparability 
Baseline characteristics will be evaluated separately for the PP, mITT and Safety populations. 
Demographic information collected at baseline includes the following:   
• Age (years) 
• Gender (Male/Female) 
• Ethnicity (Hispanic/non Hispanic) 
• Race (White, Black/African American, Native Hawaiian or Other Pacific Islander, 
Asian, American Indian or Alaska Native, Other) 
• Number of live lice 
 
Summary tables by treatment group will be presented. Continuous variables will be summarized 
using descriptive statistics (number of observations, median, minimum, maximum, mean and  
standard  deviation).  Categorical variables will be summarized using frequencies and 
percentage. Baseline treatment comparisons will be presented using Chi-Square test for the 
categorical variables, and Analysis of Variance (ANOVA) for the continuous variables. 
 
All data will be listed by treatment and patient. 
8.1.2 Medical History 
At Visit 1, each patient will be required to provide basic demographic information: date of birth, 
gender, ethnicity and race. Patients will also be questioned about medical history, including acute 
and chronic medical history and medical history relevant to their head lice. 
Medical history data will be listed by treatment and patient. 
8.1.3 Concomitant Medications 
At Visit 1, patients will be questioned about current and previous medication use over the last 
four weeks. At all subsequent visits, patients will be questioned about ongoing or new 
concomitant medication use. 
All prior and concomitant medications taken since screening until the end of the study will be 
listed by treatment and patient.  


  
 
STATISTICAL ANALYSIS PLAN 
 
Ivermectin Lotion 0.5%                                                              Protocol / Study No. 71691702 
 
 
01/12/2017                               
 Actavis LLC             
            Page 15 of 52                                          
8.1.4 Pregnancy Test 
All females of childbearing potential will have a urine pregnancy test performed at each visit. 
 
Pregnancy test results will be listed by treatment and patient. 
8.2 Efficacy Analyses 
8.2.1 Primary and Secondary Endpoint Analysis 
Therapeutic Bioequivalence Analysis 
The primary measure of therapeutic equivalence will be evaluated using the Per-Protocol 
population.  
Based on the usual method used in OGD for binary outcomes, the 90% confidence interval for 
the difference in success proportions between test and reference treatment should be contained 
within [-0.20, +0.20] in order to establish equivalence.  
 
The compound hypothesis to be tested is:  
 
 
     versus   
 
 
 
 
where   
  =  success rate of test treatment  
             
 =  success rate of reference treatment.  
Let  
  =  sample size of test treatment group  
=  number of subjects considered as Treatment Success in test treatment group  
  =  sample size of reference treatment group  
=  number of subjects considered as Treatment Success in reference treatment group  
  
 
 ,       and 
 
           
  
 
 
The 90% confidence interval for the difference in proportions between test and reference will be 
calculated as follows: 


  
 
STATISTICAL ANALYSIS PLAN 
 
Ivermectin Lotion 0.5%                                                              Protocol / Study No. 71691702 
 
 
01/12/2017                               
 Actavis LLC             
            Page 16 of 52                                          
           
  
 
           
 
If the 90% confidence interval for the absolute difference between the proportion of patients who 
are considered a Treatment Success in the Test and Reference groups is contained within the 
range [-20%, +20%] then therapeutic equivalence of the Test product to the Reference product 
will be considered to have been demonstrated. 
The same statistical approach will be conducted for analysis of the secondary endpoint in the PP 
population. 
To declare therapeutic equivalence of the Test product to the Reference product, therapeutic 
equivalence must be demonstrated for only the primary endpoint in the PP population. 
Superiority to Placebo Analysis 
Superiority of the Test and Reference products against the Placebo for the primary endpoint will 
be tested at the 5% significance level (p < 0.05; two-sided, CMH test, stratified by clinical site) 
in the mITT population using last observation carried forward (LOCF). If the proportions of 
patients who are considered a Treatment Success in the Test and Reference groups are 
numerically and statistically superior to that of the Placebo (p < 0.05; using two-sided, CMH test 
stratified by clinical site), then superiority of the Test and Reference products over Placebo will 
be concluded. 
The same statistical approach will be conducted for analysis of the secondary endpoint in the 
mITT population. 
To declare superiority of the Test and Reference products over Placebo, their superiority must be 
demonstrated for only the primary endpoint in the mITT population.  
8.2.2 Treatment-by-Site Interaction and Pooling of Clinical Sites 
As this is a multiple-site study, the interaction of treatment-by-site may be evaluated for the 
primary efficacy endpoint in the PP population (for equivalence testing). The treatment-by-site 
interaction will be evaluated by the Breslow-Day test for homogeneity of the odds ratio at the 5% 
significance level (p < 0.05). A site(s) with a low enrollment rate(s) may be pooled with its 
geographically closest site, so as to avoid bias in the estimation of a treatment-by-site interaction 
effect. The pooling will be done for low enrolling sites that account for less than 4-7% of the 
total number of patients in the PP population at the site with the highest enrolling rate in the PP 
population. If the treatment-by-site interaction term is found to be statistically significant (p < 
0.05) then the interaction term will also be assessed for clinical relevance before pooling the data 


  
 
STATISTICAL ANALYSIS PLAN 
 
Ivermectin Lotion 0.5%                                                              Protocol / Study No. 71691702 
 
 
01/12/2017                               
 Actavis LLC             
            Page 17 of 52                                          
across sites. This will include examination of Treatment Success rates at each site where sample 
sizes per treatment may be influential in the assessment of the interaction. 
 
8.3 Safety Analysis 
All safety analyses will be based on the Safety Population. 
8.3.1 Adverse Events 
All the adverse events (AEs) reported throughout the study will be coded and classified 
according to the MedDRA (Medical Dictionary for Regulatory Activities) coding dictionary 
(Version 20.0 or higher). Each adverse event is to be evaluated for date of start and end, 
seriousness, severity, causal relationship with the study drugs, action taken and outcome.   
The total number and percentage of patients with at least one AEs, discontinued study drug due 
to AEs, AE severity and AEs related to investigational product, serious AEs and death will be 
summarized by treatment groups.  
A summary table of the number and percent of patients with AEs by system organ class, 
preferred term, and treatment group will be presented.  Each patient will be counted only once 
within each preferred term.   
A frequency summary table of the number of AEs by system organ class, preferred term, 
severity, and treatment group will be presented. Severity will be classified as “Mild”, 
“Moderate”, or “Severe”.  
Similarly, a frequency summary table of the number of AEs by system organ class, preferred 
term, and relationship to a study drug, and treatment group will be presented. Relationship to a 
study drug will be classified as “Related” or “Not Related”. 
Adverse event frequencies will be compared between treatments using Fisher’s exact test. If the 
overall Fisher’s test is statistically significant, a pairwise test will be conducted for Test and 
Reference to determine if the difference in AEs is related to the active product. 
8.3.2 Application Site Reactions 
The following application site reactions will be evaluated at each visit based on the scale 
provided below: 
Signs and Symptoms: 
Erythema 
Pyoderma 


  
 
STATISTICAL ANALYSIS PLAN 
 
Ivermectin Lotion 0.5%                                                              Protocol / Study No. 71691702 
 
 
01/12/2017                               
 Actavis LLC             
            Page 18 of 52                                          
Excoriation 
Pain 
Pruritus 
Edema 
 
Grading Scale: 
Absent   
0 
 
Mild   
1  
(slight, barely perceptible) 
Moderate 
2 
(distinct presence) 
Severe  
3 
(marked, intense) 
 
Application site reactions and ocular discomfort will be compared descriptively among treatment 
groups. A frequency summary table comparing the application site reactions for each treatment 
group will be presented by visit. 
 
8.3.3 Vital Signs 
Vital signs will be recorded (pulse, blood pressure, temperature and respiration rate) at each 
visit. 
 
Descriptive summaries (number of observations, mean, standard deviation, minimum, median 
and maximum) will be provided by treatment and visit.  
 
All data will be listed by treatment and patient. 
8.4 Multiple Comparisons 
No multiple comparison adjustment will be made in this study. 
8.5 Methods for Handling Missing Data 
For demographic and baseline characteristics, each variable will be analyzed using all available 
data. Patients with missing data will be excluded only from analyses for which data are not 
available. 
8.6 Interim Analyses 
There is no interim analysis planned in this study. 


  
 
STATISTICAL ANALYSIS PLAN 
 
Ivermectin Lotion 0.5%                                                              Protocol / Study No. 71691702 
 
 
01/12/2017                               
 Actavis LLC             
            Page 19 of 52                                          
9. TABLE, LISTING AND FIGURE SHELLS 
The following shells are provided in order to provide a framework for the display of data from 
this study. These shells may not be reflective of every aspect of this study but are intended to 
show the general layout of the Tables, Listings and Figures that will be included in the final 
clinical study report. Tables, Listings and Figures are numbered following the ICH structure. 
Table headers, variables names and footnotes will be modified as needed following data 
analyses. All descriptive and inferential statistical analyses will be performed using SAS® 
statistical software Version 9.4 or higher, unless otherwise noted.   


 
STATISTICAL ANALYSIS PLAN 
Ivermectin Cream 0.5%                                                                                                                Protocol / Study No.  71691702 
 
01/12/2017                   
                Actavis LLC             
                   Page 20 of 52                                                                                                   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TABLE, LISTING AND FIGURE SHELLS 
 
 
 


 
STATISTICAL ANALYSIS PLAN 
Ivermectin Cream 0.5%                                                                                                                Protocol / Study No.  71691702 
 
01/12/2017                   
                Actavis LLC             
                   Page 21 of 52                                                                                                   
 
 
 
T16.1.9.1 Summary of Discontinued Patients 
 
 
Patients 
 
Test 
Reference 
Placebo 
Total 
Randomized 
xxx 
xxx 
xxx 
xxx 
Completed Study 
xxx 
xxx 
xxx 
xxx 
Terminated Early 
xxx 
xxx 
xxx 
xxx 
     Lost to Follow-Up 
xxx 
xxx 
xxx 
xxx 
    Withdrew Consent 
xxx 
xxx 
xxx 
xxx 
    Randomized in Error 
xxx 
xxx 
xxx 
xxx 
    etc. 
 
 
 
 
 
 
 
 
 
Test: Ivermectin Lotion, 0.5% (Actavis Laboratories UT, Inc.) 
Reference: SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) 
Placebo: Placebo (vehicle) lotion (Actavis Laboratories UT, Inc.) 
 
OUTPUT: L:\DEV\917\71691702\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm                                                                                                                                                                      Page 1 of N 
 


 
STATISTICAL ANALYSIS PLAN 
Ivermectin Cream 0.5%                                                                                                                Protocol / Study No.  71691702 
 
01/12/2017                   
                Actavis LLC             
                   Page 22 of 52                                                                                                   
 
 
 
T16.1.9.2 Summary of Protocol Deviations 
 
 
 
 
Test 
Reference 
Placebo 
 
Total 
Total Patients with Protocol Deviations 
xxx 
xxx 
xxx 
xxx 
Total Deviations 
xxx 
xxx 
xxx 
xxx 
     Outside Visit Window 
xxx 
xxx 
xxx 
xxx 
     Randomized in Error 
xxx 
xxx 
xxx 
xxx 
     Missed Visit 
xxx 
xxx 
xxx 
xxx 
     Restricted Medication 
xxx 
xxx 
xxx 
xxx 
     etc 
xxx 
xxx 
xxx 
xxx 
     Other 
xxx 
xxx 
xxx 
xxx 
                    Test: Ivermectin Lotion, 0.5% (Actavis Laboratories UT, Inc.) 
     Reference: SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) 
     Placebo: Placebo (vehicle) lotion (Actavis Laboratories UT, Inc.) 
 
OUTPUT: L:\DEV\917\71691702\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm                                                                                                                                                                      Page 1 of N 


 
STATISTICAL ANALYSIS PLAN 
Ivermectin Cream 0.5%                                                                                                                Protocol / Study No.  71691702 
 
01/12/2017                   
                Actavis LLC             
                   Page 23 of 52                                                                                                   
 
 
T16.1.9.3.1 Summary of Patients Excluded from Efficacy Analysis  


 
STATISTICAL ANALYSIS PLAN 
Ivermectin Cream 0.5%                                                                                                                Protocol / Study No.  71691702 
 
01/12/2017                   
                Actavis LLC             
                   Page 24 of 52                                                                                                   
 
 
 
 
 
 
 
Test 
Reference 
Placebo 
 
Total 
Randomized 
Total 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
 
Safety Population 
Total 
xxx 
xxx 
xxx 
xxx 
Excluded from Safety  
Total 
xxx 
xxx 
xxx 
xxx 
 
Not randomized or did not 
received study product 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
 
mITT Population 
Total 
xxx 
xxx 
xxx 
xxx 
Excluded from mITT  
Total 
xxx 
xxx 
xxx 
xxx 
 
Did not dose 
xxx 
xxx 
xxx 
xxx 
 
etc. 
 
 
 
 
 
 
 
 
 
 
PP Population 
Total 
xxx 
xxx 
xxx 
xxx 
Excluded from Excluded from PPP  
Total 
xxx 
xxx 
xxx 
xxx 
 
Restricted Medication 
xxx 
xxx 
xxx 
xxx 
 
etc. 
 
 
 
 
Test: Ivermectin Lotion, 0.5% (Actavis Laboratories UT, Inc.) 
Reference: SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) 
Placebo: Placebo (vehicle) lotion (Actavis Laboratories UT, Inc.) 
 
OUTPUT: L:\DEV\917\71691702\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm                                                                                                                                                                      Page 1 of N 
 


 
STATISTICAL ANALYSIS PLAN 
Ivermectin Cream 0.5%                                                                                                                Protocol / Study No.  71691702 
 
01/12/2017                   
                Actavis LLC             
                   Page 25 of 52                                                                                                   
 
 
T16.1.9.3.2 Summary of Patients Included in Analysis Population by Study Center 
 
 
PP 
 
mITT 
 
Safety 
Site 
No. 
Name 
Total 
Randomized 
Test 
Reference Placebo Total  Test Reference Placebo Total  
Test 
Reference Placebo Total 
xxx 
xxxx 
xxx 
xxx 
xxx 
xxx 
xxx  xxx 
xxx 
xxx 
xxx  
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
      Test: Ivermectin Lotion, 0.5% (Actavis Laboratories UT, Inc.) 
     Reference: SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) 
     Placebo: Placebo (vehicle) lotion (Actavis Laboratories UT, Inc.) 
 
OUTPUT: L:\DEV\917\71691702\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm                                                                                                                                                                      Page 1 of N 


 
STATISTICAL ANALYSIS PLAN 
Ivermectin Cream 0.5%                                                                                                                Protocol / Study No.  71691702 
 
01/12/2017                   
                Actavis LLC             
                   Page 26 of 52                                                                                                   
 
 
T16.1.9.4 Summary of Demographic Data and Baseline Characteristics  
(Safety Population) 
 
 
 
 
 
Test 
(N = xxx) 
Reference 
(N = xxx) 
Placebo 
(N = xxx) 
 
P-value 
Age (years) 
n 
xxx 
xxx 
xxx 
x.xxxx 
 
Mean ± SD 
xx.x ± xx.x 
xx.x ± xx.x 
xx.x ± xx.x 
 
 
Median 
xx.x 
xx.x 
xx.x 
 
 
Range 
xx.x – xx.x 
xx.x – xx.x 
xx.x – xx.x 
 
Race 
White 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
     x.xxxx 
 
Black/African American 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
Native Hawaiian or other Pacific Islander 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
Asian 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
American Indian or Alaska Native 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
Other 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
Gender 
Female 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
x.xxxx 
 
Male 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
 
 
 
 
 
 
            N= number of patients in the specific treatment group;     n= number of patient with data available;      % is based on N 
            Test: Ivermectin Lotion, 0.5% (Actavis Laboratories UT, Inc.) 
          Reference: SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) 
          Placebo: Placebo (vehicle) lotion (Actavis Laboratories UT, Inc.) 
 
OUTPUT: L:\DEV\917\71691702\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm                                                                                                                                                                      Page 1 of N 


 
STATISTICAL ANALYSIS PLAN 
Ivermectin Cream 0.5%                                                                                                                Protocol / Study No.  71691702 
 
01/12/2017                   
                Actavis LLC             
                   Page 27 of 52                                                                                                   
 
 
T16.1.9.4 Summary of Demographic Data and Baseline Characteristics 
(Safety Population) 
 
 
 
 
Test 
(N = xxx) 
Reference 
(N = xxx) 
Placebo 
(N = xxx) 
 
 
P-value 
Ethnicity 
Hispanic or Latino 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
x.xxxx 
 
Not Hispanic or Latino 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
 
Number of live lice 
n 
xxx 
xxx 
xxx 
x.xxxx 
 
Mean ± SD 
xx.x ± x.x 
xx.x ± xx.x 
xx.x ± xx.x 
 
 
Median 
xx.x 
xx.x 
xx.x 
 
 
Range 
xx.x – xx.x 
xx.x – xx.x 
xx.x – xx.x 
 
           Note:  N= number of patients in the specific treatment group;     n= number of patient with data available;      % is based on N 
           Test: Ivermectin Lotion, 0.5% (Actavis Laboratories UT, Inc.) 
         Reference: SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) 
         Placebo: Placebo (vehicle) lotion (Actavis Laboratories UT, Inc.) 
 
OUTPUT: L:\DEV\917\71691702\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm                                                                                                                                                                      Page 1 of N 


 
STATISTICAL ANALYSIS PLAN 
Ivermectin Cream 0.5%                                                                                                                Protocol / Study No.  71691702 
 
01/12/2017                   
                Actavis LLC             
                   Page 28 of 52                                                                                                   
 
 
 
 
 
Similar tables will be created for T16.1.9.5 and T16.1.9.6 
 
 
 
 
T16.1.9.5 Summary of Demographic Data and Baseline Characteristics 
(modified Intent-to-Treat Population) 
 
 
T16.1.9.6 Summary of Demographic Data and Baseline Characteristics 
(Per-Protocol Population) 


 
STATISTICAL ANALYSIS PLAN 
Ivermectin Cream 0.5%                                                                                                                Protocol / Study No.  71691702 
 
01/12/2017                   
                Actavis LLC             
                   Page 29 of 52                                                                                                   
 
 
T16.1.9.7 Summary of Analysis Results of Primary Efficacy Endpoint  
(Proportion of Index Patients with Treatment Successes between Treatment Groups) 
Equivalence: Per-Protocol Population 
Number of 
Patients (N) 
 
Number of 
Treatment  
Successes (n) 
Proportion of 
Treatment  
Successes (%) 
Difference Between Treatments 
Treatment  
Group 
Difference (%) 
90% CI Evaluation 
Test 
xxx 
xxx 
xx.x 
 
 
Reference 
xxx 
xxx 
xx.x 
xx.x 
xx.x – xx.x 
 
Superiority: modified Intent-to-Treat Population 
Treatment  
Group 
 
Number of 
Patients (N) 
Number of 
Treatment  
Successes (n) 
Proportion of 
Treatment  
Successes (%) 
 
 
P-value 
Placebo 
xxx 
xxx 
xx.x 
 
Test 
xxx 
xxx 
xx.x 
x.xxxx 
Reference 
xxx 
xxx 
xx.x 
x.xxxx 
      Superiority of Active treatments over Placebo were tested using a two-sided Cochran-Mantel-Haenszel (CMH) test, stratified by   
       clinical site, at the 5% significance level. 
       The superiority testing include patients in the mITT population using last observation carried forward (LOCF). 
                    Test: Ivermectin Lotion, 0.5% (Actavis Laboratories UT, Inc.) 
     Reference: SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) 
     Placebo: Placebo (vehicle) lotion (Actavis Laboratories UT, Inc.) 
 
OUTPUT: L:\DEV\917\71691702\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm                                                                                                                                                                      Page 1 of N 


 
STATISTICAL ANALYSIS PLAN 
Ivermectin Cream 0.5%                                                                                                                Protocol / Study No.  71691702 
 
01/12/2017                   
                Actavis LLC             
                   Page 30 of 52                                                                                                   
 
 
T16.1.9.8 Summary of Analysis Results of Secondary Efficacy Endpoint  
(Proportion of All Randomized Patients with Treatment Successes between Treatment Groups) 
Equivalence: Per-Protocol Population 
Number of 
Patients (N) 
 
Number of 
Treatment  
Successes (n) 
Proportion of 
Treatment  
Successes (%) 
Difference Between Treatments 
Treatment  
Group 
Difference (%) 
90% CI Evaluation 
Test 
xxx 
xxx 
xx.x 
 
 
Reference 
xxx 
xxx 
xx.x 
xx.x 
xx.x – xx.x 
 
Superiority: modified Intent-to-Treat Population 
Treatment  
Group 
 
Number of 
Patients (N) 
Number of 
Treatment  
Successes (n) 
Proportion of 
Treatment  
Successes (%) 
 
 
P-value 
Placebo 
xxx 
xxx 
xx.x 
 
Test 
xxx 
xxx 
xx.x 
x.xxxx 
Reference 
xxx 
xxx 
xx.x 
x.xxxx 
                      
      Superiority of Active treatments over Placebo were tested using a two-sided Cochran-Mantel-Haenszel(CMH) test, stratified by   
       clinical site, at the 5% significance level. 
                    Test: Ivermectin Lotion, 0.5% (Actavis Laboratories UT, Inc.) 
     Reference: SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) 
     Placebo: Placebo (vehicle) lotion (Actavis Laboratories UT, Inc.) 
 
OUTPUT: L:\DEV\917\71691702\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm                                                                                                                                                                      Page 1 of N 


 
STATISTICAL ANALYSIS PLAN 
Ivermectin Cream 0.5%                                                                                                                Protocol / Study No.  71691702 
 
01/12/2017                   
                Actavis LLC             
                   Page 31 of 52                                                                                                   
 
 
T16.1.9.9 Overall Summary of Adverse Events  
(Safety Population) 
 
 
Description 
 
 
Test 
 
 
Reference 
 
 
Placebo 
 
 
Total 
 
Patients Randomized 
xxx 
xxx 
xxx 
xxx 
     Patients with at least one AE 
xx (xx.x%) 
xx (xx.x%)  
xx (xx.x%) 
xx (xx.x%) 
     Discontinued study drug due to above AE 
xx (xx.x%) 
xx (xx.x%)  
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
AEs reported 
xxx 
xxx 
xxx 
xxx 
      Mild 
xx (xx.x%) 
xx (xx.x%)  
xx (xx.x%) 
xx (xx.x%) 
      Moderate 
xx (xx.x%) 
xx (xx.x%)  
xx (xx.x%) 
xx (xx.x%) 
      Severe 
xx (xx.x%) 
xx (xx.x%)  
xx (xx.x%) 
xx (xx.x%) 
      Not Related 
xx (xx.x%) 
xx (xx.x%)  
xx (xx.x%) 
xx (xx.x%) 
      Related 
xx (xx.x%) 
xx (xx.x%)  
xx (xx.x%) 
xx (xx.x%) 
      Death 
xx (xx.x%) 
xx (xx.x%)  
xx (xx.x%) 
xx (xx.x%) 
      Serious AE 
xx (xx.x%) 
xx (xx.x%)  
xx (xx.x%) 
xx (xx.x%) 
                    Test: Ivermectin Lotion, 0.5% (Actavis Laboratories UT, Inc.) 
     Reference: SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) 
     Placebo: Placebo (vehicle) lotion (Actavis Laboratories UT, Inc.) 
 
OUTPUT: L:\DEV\917\71691702\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm                                                                                                                                                                      Page 1 of N 


 
STATISTICAL ANALYSIS PLAN 
Ivermectin Cream 0.5%                                                                                                                Protocol / Study No.  71691702 
 
01/12/2017                   
                Actavis LLC             
                   Page 32 of 52                                                                                                   
 
 
T16.1.9.10 Summary of Frequency of All Adverse Events by Body System  
(Safety Population) 
 
Body System 
MedDRA Term  
Test  
(N = xxx) 
 
Reference 
(N = xxx) 
   
Placebo 
(N = xxx) 
 
Fisher’s 
P-value 
Events 
Patients 
Events 
Patients 
Events 
Patients 
Patient with at least 
one AE 
Total 
xx 
xx (xx.x%)  
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
x.xxxx 
Ear and labyrinth 
disorders 
Ear pain 
xx 
xx (xx.x%)  
xx 
xx (xx.x%) 
xx 
xx (xx.x%) 
x.xxxx 
 
etc. 
 
 
 
 
 
 
 
 
 
 
etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Comparison of treatment groups is with respect to the number of patients with at least one occurrence of the AE. 
Test: Ivermectin Lotion, 0.5% (Actavis Laboratories UT, Inc.) 
 Reference: SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) 
 Placebo: Placebo (vehicle) lotion (Actavis Laboratories UT, Inc.) 
 
OUTPUT: L:\DEV\917\71691702\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm                                                                                                                                                                      Page 1 of N 
 
 


 
STATISTICAL ANALYSIS PLAN 
Ivermectin Cream 0.5%                                                                                                                Protocol / Study No.  71691702 
 
01/12/2017                   
                Actavis LLC             
                   Page 33 of 52                                                                                                   
 
 
T16.1.9.11 Summary of Frequency of All Adverse Events by Severity 
(Safety Population) 
 
 
 
 
Test 
# Events 
(N=xx) 
 
 
Reference 
# Events 
(N=xx) 
  
 
Placebo 
# Events 
(N=xx) 
 
Body System 
MedDRA Term 
Mild 
Moderate 
Severe 
Mild 
Moderate Severe 
Mild 
Moderate 
Severe 
 
Total AEs  
Total AEs 
 xx(xx.x%) xx(xx.x%) xx (xx.x%)  xx(xx.x%) xx(xx.x%) xx (xx.x%) xx (xx.x%) xx (xx.x%) xx (xx.x%)  
 
 
 
 
 
 
 
 
 
 
 
 
Ear and labyrinth 
disorders 
Ear pain 
 xx(xx.x%) xx(xx.x%) xx (xx.x%)  xx(xx.x%) xx(xx.x%) xx (xx.x%) xx (xx.x%) xx (xx.x%) xx (xx.x%)  
 
Hypoacusis 
 xx(xx.x%) xx(xx.x%) xx (xx.x%)  xx(xx.x%) xx(xx.x%) xx (xx.x%) xx (xx.x%) xx (xx.x%) xx (xx.x%)  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
          N = Total number of events in each treatment group;       Percentage is based on total number of events. 
          Test: Ivermectin Lotion, 0.5% (Actavis Laboratories UT, Inc.) 
         Reference: SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) 
         Placebo: Placebo (vehicle) lotion (Actavis Laboratories UT, Inc.) 
 
OUTPUT: L:\DEV\917\71691702\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm                                                                                                                                                                      Page 1 of N 


 
STATISTICAL ANALYSIS PLAN 
Ivermectin Cream 0.5%                                                                                                                Protocol / Study No.  71691702 
 
01/12/2017                   
                Actavis LLC             
                   Page 34 of 52                                                                                                   
 
 
T16.1.9.12 Summary of Frequency of All Adverse Events by Relationship  
(Safety Population) 
 
 
 
 
Test 
# Events 
(N=xx) 
 
 
Reference 
# Events 
(N=xx) 
  
 
 
Placebo 
# Events 
(N=xx) 
 
Body System 
MedDRA Term 
Related 
Not Related 
Related 
Not Related 
Related 
Not Related 
 
Total AEs 
Total AEs 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
 
 
Ear and labyrinth 
disorders 
Ear pain 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Hypoacusis 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
            N = Total number of events in each treatment group;       Percentage is based on total number of events. 
            Test: Ivermectin Lotion, 0.5% (Actavis Laboratories UT, Inc.) 
          Reference: SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) 
          Placebo: Placebo (vehicle) lotion (Actavis Laboratories UT, Inc.) 
 
OUTPUT: L:\DEV\917\71691702\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm                                                                                                                                                                      Page 1 of N 


 
STATISTICAL ANALYSIS PLAN 
Ivermectin Cream 0.5%                                                                                                                Protocol / Study No.  71691702 
 
01/12/2017                   
                Actavis LLC             
                   Page 35 of 52                                                                                                   
 
 
T16.1.9.13 Summary of Frequency of Serious Adverse Events  
(Safety Population) 
 
Body System 
MedDRA Term 
 
Test 
# Events 
Reference 
# Events 
Placebo 
# Events 
Injury, poisoning and procedural complications 
Alcohol poisoning 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
                    Test: Ivermectin Lotion, 0.5% (Actavis Laboratories UT, Inc.) 
     Reference: SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) 
     Placebo: Placebo (vehicle) lotion (Actavis Laboratories UT, Inc.) 
 
OUTPUT: L:\DEV\917\71691702\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm                                                                                                                                                                      Page 1 of N 


 
STATISTICAL ANALYSIS PLAN 
Ivermectin Cream 0.5%                                                                                                                Protocol / Study No.  71691702 
 
01/12/2017                   
                Actavis LLC             
                   Page 36 of 52                                                                                                   
 
 
 
T16.1.9.14 Summary of Frequency of Application Site Reaction  
(Safety Population) 
 
Signs and  
Symptoms 
Visit 
 
Statistic 
 
Placebo 
(N = xxx) 
 
Test 
(N = xxx) 
 
Reference 
(N = xx) 
Edema 
Visit 1 
Absent 
xxx (x.x%) 
xxx (x.x%) 
xxx (x.x%) 
 
 
Mild 
xxx (x.x%) 
xxx (x.x%) 
xxx (x.x%) 
 
 
Moderate 
xxx (x.x%) 
xxx (x.x%) 
xxx (x.x%) 
 
 
Severe 
xxx (x.x%) 
xxx (x.x%) 
xxx (x.x%) 
 
Visit 2 
 
 
 
 
 
Visit 3 
 
 
 
 
 
Visit 4 
 
 
 
 
Erythema 
 
 
 
 
 
Excoriation 
 
 
 
 
 
Pain  
 
 
 
 
 
Pruritus 
 
 
 
 
 
Pyoderma 
 
 
 
 
 
 
 
 
 
 
 
          Test: Ivermectin Lotion, 0.5% (Actavis Laboratories UT, Inc.) 
         Reference: SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) 
         Placebo: Placebo (vehicle) lotion (Actavis Laboratories UT, Inc.) 
 
OUTPUT: L:\DEV\917\71691702\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm                                                                                                                                                                      Page 1 of N 
 


 
STATISTICAL ANALYSIS PLAN 
Ivermectin Cream 0.5%                                                                                                                Protocol / Study No.  71691702 
 
01/12/2017                   
                Actavis LLC             
                   Page 37 of 52                                                                                                   
 
T16.1.9.15 Summary of Vital Signs  
(Safety Population) 
 
Vital Signs 
Visit 
 
Statistic 
 
Test 
(N = xxx) 
 
Reference 
(N = xxx) 
 
Placebo 
(N = xxx) 
Systolic Blood Pressure (mmHg) 
Visit 1 
n 
xxx 
xxx 
xxx 
 
 
Mean ± SD 
xxx.x ± xxx.x 
xxx.x ± xxx.x 
xxx.x ± xxx.x 
 
 
Median 
xxx.x 
xxx.x 
xxx.x 
 
 
Range 
xxx.x – xxx.x 
xxx.x – xxx.x 
xxx.x – xxx.x 
 
Visit 2 
 
 
 
 
 
Visit 3 
 
 
 
 
 
Visit 4 
 
 
 
 
Diastolic Blood Pressure (mmHg) 
 
 
 
 
 
Heart Rate (beats/min) 
 
 
 
 
 
Respiration Rate (breaths/min) 
 
 
 
 
 
Temperature (F) 
 
 
 
 
 
 
 
 
 
 
 
     Test: Ivermectin Lotion, 0.5% (Actavis Laboratories UT, Inc.) 
    Reference: SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) 
    Placebo: Placebo (vehicle) lotion (Actavis Laboratories UT, Inc.) 
 
OUTPUT: L:\DEV\917\71691702\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm                                                                                                                                                                      Page 1 of N 


 
STATISTICAL ANALYSIS PLAN 
Ivermectin Cream 0.5%                                                                                                                Protocol / Study No.  71691702 
 
01/12/2017                   
                Actavis LLC             
                   Page 38 of 52                                                                                                   
 
T16.1.9.16 
 
(Safety Population) 
 
Visit 
Test 
(N = xxx) 
Reference 
(N = xxx) 
Placebo 
(N = xxx) 
 
xxx (x.x%) 
xxx (x.x%) 
xxx (x.x%) 
 
xxx (x.x%) 
xxx (x.x%) 
xxx (x.x%) 
 
     Test: Ivermectin Lotion, 0.5% (Actavis Laboratories UT, Inc.) 
     Reference: SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) 
     Placebo: Placebo (vehicle) lotion (Actavis Laboratories UT, Inc.) 
 
OUTPUT: L:\DEV\917\71691702\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm                                                                                                                                                                      Page 1 of N 


 
STATISTICAL ANALYSIS PLAN 
Ivermectin Cream 0.5%                                                                                                                Protocol / Study No.  71691702 
 
01/12/2017                   
                Actavis LLC             
                   Page 39 of 52                                                                                                   
 
 
T16.1.9.17 
 
(Safety Population) 
 
Test 
(N = xxx) 
Reference 
(N = xxx) 
Placebo 
(N = xxx) 
xxx (x.x%) 
xxx (x.x%) 
xxx (x.x%) 
 
 
 
 
     Test: Ivermectin Lotion, 0.5% (Actavis Laboratories UT, Inc.) 
     Reference: SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) 
     Placebo: Placebo (vehicle) lotion (Actavis Laboratories UT, Inc.) 
     Re-infestation is defined as treatment success at Visit 2 and treatment failure at either Visit 3 or 4, or treatment success at Visits 2 and 3 and  
     treatment failure at Visit 4. 
 
OUTPUT: L:\DEV\917\71691702\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm                                                                                                                                                                      Page 1 of N 
 
 
 
 


 
STATISTICAL ANALYSIS PLAN 
Ivermectin Cream 0.5%                                                                                                                Protocol / Study No.  71691702 
 
01/12/2017                   
                Actavis LLC             
                   Page 40 of 52                                                                                                   
 
 
L16.2.1 Listing of Discontinued Patients 
 
 Treatment 
 Group 
Patient 
Number 
Discontinuation 
Reason 
Population 
 Test 
xxx-xxx-xx 
Withdrew Consent 
mITT  
 
xxx-xxx-xx 
Lost to Follow-up 
Safety 
 
 
 
 
 
 
 
 
 
 
 
 
 Reference 
 
 
 
 Placebo 
 
 
 
                    Test: Ivermectin Lotion, 0.5% (Actavis Laboratories UT, Inc.) 
     Reference: SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) 
     Placebo: Placebo (vehicle) lotion (Actavis Laboratories UT, Inc.) 
 
OUTPUT: L:\DEV\917\71691702\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm                                                                                                                                                                      Page 1 of N 
 


 
STATISTICAL ANALYSIS PLAN 
Ivermectin Cream 0.5%                                                                                                                Protocol / Study No.  71691702 
 
01/12/2017                   
                Actavis LLC             
                   Page 41 of 52                                                                                                   
 
 
 
L16.2.2 Listing of Protocol Deviations 
 
Treatment  
Group 
Patient 
Number 
Protocol Deviation Summary 
Population 
Test 
xxx-xxx-xx 
Outside Visit Window 
Safety 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference 
 
 
 
Placebo 
 
 
 
                    Test: Ivermectin Lotion, 0.5% (Actavis Laboratories UT, Inc.) 
     Reference: SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) 
     Placebo: Placebo (vehicle) lotion (Actavis Laboratories UT, Inc.) 
 
OUTPUT: L:\DEV\917\71691702\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm                                                                                                                                                                      Page 1 of N 
 
 


 
STATISTICAL ANALYSIS PLAN 
Ivermectin Cream 0.5%                                                                                                                Protocol / Study No.  71691702 
 
01/12/2017                   
                Actavis LLC             
                   Page 42 of 52                                                                                                   
 
 
 
L16.2.3.1 Listing of Patients Excluded from the Per-Protocol Population 
 
Treatment 
Group 
Patient 
Number 
Exclusion 
Reason 
Test 
xxx-xxx-xx 
Patient did not meet IE criterion. 
 
xxx-xxx-xx 
Patient took prohibited medications 
 
 
 
 
 
 
 
Reference 
 
 
Placebo 
 
 
 
 
 
                    Test: Ivermectin Lotion, 0.5% (Actavis Laboratories UT, Inc.) 
     Reference: SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) 
     Placebo: Placebo (vehicle) lotion (Actavis Laboratories UT, Inc.) 
 
OUTPUT: L:\DEV\917\71691702\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm                                                                                                                                                                      Page 1 of N 
 


 
STATISTICAL ANALYSIS PLAN 
Ivermectin Cream 0.5%                                                                                                                Protocol / Study No.  71691702 
 
01/12/2017                   
                Actavis LLC             
                   Page 43 of 52                                                                                                   
 
 
 
L16.2.3.2 Listing of Patients Excluded from the Modified Intent-to-Treat Population 
 
Treatment 
Group 
Patient 
Number 
Exclusion 
Reason 
Test 
xxx-xxx-xx 
Patient did not have at least one post-randomization evaluation 
 
xxx-xxx-xx 
Patient did not have at least one post-randomization evaluation 
 
 
 
 
 
 
Reference 
 
 
Placebo 
 
 
 
 
 
                     Test: Ivermectin Lotion, 0.5% (Actavis Laboratories UT, Inc.) 
     Reference: SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) 
     Placebo: Placebo (vehicle) lotion (Actavis Laboratories UT, Inc.) 
 
OUTPUT: L:\DEV\917\71691702\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm                                                                                                                                                                      Page 1 of N 
 


 
STATISTICAL ANALYSIS PLAN 
Ivermectin Cream 0.5%                                                                                                                Protocol / Study No.  71691702 
 
01/12/2017                   
                Actavis LLC             
                   Page 44 of 52                                                                                                   
 
 
L16.2.4.1 Listing of Demographic Data  
 
Treatment 
Group 
Patient 
Number 
 
Age 
 
Gender 
 
Ethnicity 
Race 
  Test 
xxx-xxx-xx 
30 
Female 
Not Hispanic or Latino 
Black or African American 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference 
 
 
 
 
Placebo 
 
 
 
 
 
 
 
 
 
             Test: Ivermectin Lotion, 0.5% (Actavis Laboratories UT, Inc.) 
           Reference: SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) 
           Placebo: Placebo (vehicle) lotion (Actavis Laboratories UT, Inc.) 
 
OUTPUT: L:\DEV\917\71691702\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm                                                                                                                                                                      Page 1 of N 
 
 
 
 
 


 
STATISTICAL ANALYSIS PLAN 
Ivermectin Cream 0.5%                                                                                                                Protocol / Study No.  71691702 
 
01/12/2017                   
                Actavis LLC             
                   Page 45 of 52                                                                                                   
 
 
 
L16.2.4.2 Listing of Medical History 
 
Treatment 
Group 
Patient 
Number 
System 
Diagnosis or Surgical 
Procedure 
 
Start Date 
 
End Date 
 
Ongoing 
Test 
xxx-xxx-xx 
Gynecologic 
Menopause 
2003 
2003 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference 
 
 
 
 
 
Placebo 
 
 
 
 
 
 
 
 
 
 
 
                    Test: Ivermectin Lotion, 0.5% (Actavis Laboratories UT, Inc.) 
     Reference: SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) 
     Placebo: Placebo (vehicle) lotion (Actavis Laboratories UT, Inc.) 
 
OUTPUT: L:\DEV\917\71691702\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm                                                                                                                                                                      Page 1 of N 


 
STATISTICAL ANALYSIS PLAN 
Ivermectin Cream 0.5%                                                                                                                Protocol / Study No.  71691702 
 
01/12/2017                   
                Actavis LLC             
                   Page 46 of 52                                                                                                   
 
 
 
L16.2.4.3 Listing of Concomitant Medications 
 
Treatment 
Group 
Patient 
Number 
 
Medication 
TX 
Area 
Dosage 
Frequency 
 
Route 
Start/End 
Date 
 
Indication 
Test 
xxx-xxx-xx 
LISINOPRIL 
Yes 
20 MG 
QD 
PO 
yyyy-mm-dd/ 
yyyy-mm-dd 
HYPERTENSION 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference 
 
 
 
 
 
 
 
 
Placebo 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
                    Test: Ivermectin Lotion, 0.5% (Actavis Laboratories UT, Inc.) 
     Reference: SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) 
     Placebo: Placebo (vehicle) lotion (Actavis Laboratories UT, Inc.) 
 
OUTPUT: L:\DEV\917\71691702\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm                                                                                                                                                                      Page 1 of N 


 
STATISTICAL ANALYSIS PLAN 
Ivermectin Cream 0.5%                                                                                                                Protocol / Study No.  71691702 
 
01/12/2017                   
                Actavis LLC             
                   Page 47 of 52                                                                                                   
 
 
 
L16.2.5 Listing of Visit Date Information 
 
Treatment  
Group 
Patient 
Number 
Informed Consent 
Date 
Visit 1 
Visit 2 
Visit 3 
Visit 4 or  
Discontinuation 
Test 
xxx-xxx-xx 
yyyy-mm-dd 
yyyy-mm-dd 
yyyy-mm-dd 
yyyy-mm-dd 
yyyy-mm-dd 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
                    Test: Ivermectin Lotion, 0.5% (Actavis Laboratories UT, Inc.) 
     Reference: SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) 
     Placebo: Placebo (vehicle) lotion (Actavis Laboratories UT, Inc.) 
 
OUTPUT: L:\DEV\917\71691702\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm                                                                                                                                                                      Page 1 of N 


 
STATISTICAL ANALYSIS PLAN 
Ivermectin Cream 0.5%                                                                                                                Protocol / Study No.  71691702 
 
01/12/2017                   
                Actavis LLC             
                   Page 48 of 52                                                                                                   
 
 
 
L16.2.6 Listing of Louse Examination Results 
 
Treatment  
Group 
Patient 
Number 
Visit 
Were Live Head 
 Lice Present? 
 
Number of Live 
Head Lice 
Treatment  
Success 
Duration of Louse 
Examination 
(minutes) 
Test 
xxx-xxx-xx 
Visit 1 
Yes 
6 
 
xx 
 
 
Visit 2 
Yes 
5 
 
xx 
 
 
Visit 3 
Yes 
2 
 
xx 
 
 
Visit 4 
No 
0 
Yes 
xx 
 
xxx-xxx-xx 
Visit 1 
Yes 
6 
 
xx 
 
 
Visit 2 
Yes 
5 
 
xx 
 
 
Visit 3 
Yes 
2 
 
xx 
 
 
Visit 4 
Yes 
2 
No 
xx 
 
etc 
 
 
 
 
 
 
 
 
 
 
 
 
Reference 
 
 
 
 
 
 
Placebo 
 
 
 
 
 
 
 
 
 
 
 
 
 
                    Test: Ivermectin Lotion, 0.5% (Actavis Laboratories UT, Inc.) 
     Reference: SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) 
     Placebo: Placebo (vehicle) lotion (Actavis Laboratories UT, Inc.) 
 
OUTPUT: L:\DEV\917\71691702\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm                                                                                                                                                                      Page 1 of N 
 


 
STATISTICAL ANALYSIS PLAN 
Ivermectin Cream 0.5%                                                                                                                Protocol / Study No.  71691702 
 
01/12/2017                   
                Actavis LLC             
                   Page 49 of 52                                                                                                   
 
 
 
L16.2.7.1 Listing of Adverse Events by Treatment Group 
 
 
Treatment 
group 
 
Patient 
Number 
Body System/ 
MedDRA Term/ 
AE Term 
 
TX 
Area 
Start /End  
Date 
Severity 
Relationship  
to Study  
Drug 
 
Outcome 
Action Taken with 
Study Drug/ 
Other Action 
Taken 
 
 
SAE? 
Test 
xxx-xxx-xx 
Nervous system disorders/ headache/  
Headache 
No 
yyyy-mm-dd / 
yyyy-mm-dd 
Mild 
Not Related 
Recovered Drug withdrawn/ None 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference 
 
 
 
 
 
 
 
 
Placebo 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Test: Ivermectin Lotion, 0.5% (Actavis Laboratories UT, Inc.) 
Reference: SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) 
Placebo: Placebo (vehicle) lotion (Actavis Laboratories UT, Inc.) 
 
OUTPUT: L:\DEV\917\71691702\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm                                                                                                                                                                      Page 1 of N 


 
STATISTICAL ANALYSIS PLAN 
Ivermectin Cream 0.5%                                                                                                                Protocol / Study No.  71691702 
 
01/12/2017                   
                Actavis LLC             
                   Page 50 of 52                                                                                                   
 
 
 
L16.2.7.2 Listing of Application Site Reactions 
 
Treatment 
Group 
Patient 
Number 
 
Visit 
 
Edema 
 
 
Erythema 
 
 
Excoriation 
 
 
Pain 
 
 
Pruritus 
 
 
Pyoderma 
 
Test 
xxx-xxx-xx 
Visit 1 
0 
0 
0 
1 
0 
0 
 
 
Visit 2 
0 
1 
0 
0 
0 
0 
 
 
Visit 3 
0 
0 
0 
1 
0 
0 
 
 
Visit 4 
0 
0 
0 
1 
0 
0 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference 
 
 
 
 
 
 
 
 
Placebo 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
          Test: Ivermectin Lotion, 0.5% (Actavis Laboratories UT, Inc.) 
         Reference: SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) 
         Placebo: Placebo (vehicle) lotion (Actavis Laboratories UT, Inc.) 
 
OUTPUT: L:\DEV\917\71691702\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm                                                                                                                                                                      Page 1 of N 
 
 


 
STATISTICAL ANALYSIS PLAN 
Ivermectin Cream 0.5%                                                                                                                Protocol / Study No.  71691702 
 
01/12/2017                   
                Actavis LLC             
                   Page 51 of 52                                                                                                   
 
 
 
L16.2.8.1 Listing of Pregnancy Test Results 
 
Treatment  
Group 
Patient   
Number 
Visit 1 
Visit 2 
Visit 3 
Visit 4 or  
Discontinuation 
Test 
xxx-xxx-xx 
Negative 
Negative 
Negative 
Negative 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference 
 
 
 
 
Placebo 
 
 
 
 
 
 
 
 
 
                    Test: Ivermectin Lotion, 0.5% (Actavis Laboratories UT, Inc.) 
     Reference: SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) 
     Placebo: Placebo (vehicle) lotion (Actavis Laboratories UT, Inc.) 
 
OUTPUT: L:\DEV\917\71691702\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm                                                                                                                                                                      Page 1 of N 


 
STATISTICAL ANALYSIS PLAN 
Ivermectin Cream 0.5%                                                                                                                Protocol / Study No.  71691702 
 
01/12/2017                   
                Actavis LLC             
                   Page 52 of 52                                                                                                   
 
 
 
L16.2.8.2 Listing of Vital Signs 
 
Treatment 
Group 
Patient   
Number 
Visit 
Systolic BP 
(mmHg) 
Diastolic BP 
(mmHg) 
Pulse Rate 
(beats/min ) 
Respiration Rate 
(breaths/min) 
Temperature 
(F) 
 
Test 
xxx-xxx-xx 
Visit 1 
120 
70 
84 
18 
98.6 
 
 
 
Visit 2 
140 
80 
74 
18 
97 
 
 
 
Visit 3 
120 
70 
84 
18 
98.6 
 
 
 
Visit 4 
140 
80 
74 
18 
97 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference 
 
 
 
 
 
 
 
Placebo 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
                 Test: Ivermectin Lotion, 0.5% (Actavis Laboratories UT, Inc.) 
  Reference: SKLICE® (ivermectin) Lotion, 0.5% (Arbor Pharmaceuticals, LLC) 
  Placebo: Placebo (vehicle) lotion (Actavis Laboratories UT, Inc.) 
 
OUTPUT: L:\DEV\917\71691702\SAS\OUT\XXXX 
Created on: ddmmmyy hh:mm                                                                                                                                                                      Page 1 of N