Clinical trial NCT03405818
Conditions: Onychomycosis Tinea Unguium
Keywords: Fungal infection of the nail
Sponsor: Pfizer
Start date: 2015-10-22; Completion date: 2017-07-27
Enrollment: 55 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This was an open-label study to evaluate the safety and pharmacokinetics of tavaborole 5% topical solution in treating distal subungual onychomycosis (a fungal infection) of the toenail in children and adolescents (ages 6 to 16 years).

Following confirmation of eligibility, including laboratory evidence of a fungal organism in the toenail, tavaborole topical solution was applied once daily to all affected toenails for a 48-week treatment period.

Clinical assessment of the extent of infection and safety assessments were performed periodically throughout the 48-week treatment period, and again at 52 weeks (4 weeks after stopping the treatment).

A subgroup of enrolled subjects applied the topical solution to all 10 toenails and a small area of surrounding skin during the first 28 days. These subjects had blood samples analyzed to evaluate the pharmacokinetics (how the drug moves in the body) of tavaborole topical solution in children and adolescents.

Detailed description:
This was an open-label study to evaluate the safety, tolerability, and pharmacokinetics of tavaborole 5% topical solution in treating distal subungual onychomycosis (DSO) of the toenail in pediatric subjects aged 6 to 16 years and 11 months. An eligible subject had a target great toenail (TGT) with at least 20% involvement, with a positive potassium hydroxide (KOH) wet mount and positive fungal culture for T. rubrum or T. mentagrophytes.

Eligible subjects applied tavaborole 5% topical solution, once daily to all affected toenails (the TGT as well as all other toenails having the clinical characteristics of onychomycosis) throughout the 48 week treatment period.

Subjects were evaluated at Screening, Baseline (Day 1), and at Weeks 2, 4, 8, 16, 24, 32, 40, 48, and 52. Each evaluation included a clinical assessment of the AEs and local tolerability evaluation.

Additional procedures were performed as follows:

* Mycology sampling at Screening, Week 24, and Week 52/early termination (ET);
* Clinical disease severity of the TGT at Screening, Week 24, and Week 52/ET;
* Safety laboratory testing at Baseline, Week 24, and Week 52/ET;

In this study, there was a PK subgroup of evaluable subjects aged 12 to 16 years and 11 months studied under maximal use conditions. Subjects in this maximal use subgroup applied the study drug on all 10 toenails, including up to 2 mm of the surrounding skin, for 28 days. On Day 15, a predose PK sample was collected to assess steady state trough level. On Day 29, the study drug application was done at the study site, and PK samples were collected prior to dosing, as well as 4, 6, 8, and 24 hours postdose on Days 29 to 30.

Arms: arm 1: All study participants apply study drug
Interventions: intervention 1: Tavaborole 5% Topical Solution
Intervention descriptions: intervention 1: topical solution for application to toenails

Protocol documents:
Prot_000.pdf: 
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TAV-ONYC-401 Protocol Amendment 3 
 28 March 2016 
Page 4 of 62 
Anacor Pharmaceuticals, Inc. 
CONFIDENTIAL 
INVESTIGATOR SIGNATURE PAGE 
I have read the protocol and agree that it contains all necessary details for carrying out the 
study as described. I will conduct this protocol as outlined herein according to the 
principles of Good Clinical Practices (GCP), applicable laws and regulations, and the 
ethical principles that have their origin in the Declaration of Helsinki, and will make a 
reasonable effort to complete the study within the time designated. 
I agree to personally conduct or supervise the described study. 
I agree to inform any subject that the study drug is being used for investigational 
purposes and I will ensure that the requirements related to obtaining informed consent in 
accordance with International Conference on Harmonization (ICH) guidelines for GCP 
and local regulatory requirements. 
I agree to report adverse events that occur during the course of the study to the Sponsor in 
accordance with ICH guidelines for GCP and local regulatory requirements. 
I have read and understand the information in the Investigator’s Brochure, including the 
potential risks and side effects of the study drug. 
I agree to promptly report to the Ethics Committee (EC)/Institutional Review Board 
(IRB) all changes in the research activity and all unanticipated problems involving risks 
to subjects. I will not make any changes to the conduct of the study without EC/IRB and 
Sponsor approval, except when necessary to eliminate apparent immediate harm to 
subjects. 
I agree to maintain adequate and accurate records and make those records available for 
inspection in accordance with ICH guidelines for GCP and local regulatory requirements. 
I agree to ensure that all associates, colleagues, and employees assisting in the conduct of 
the study are qualified and informed of their obligations in meeting the above 
commitments. 
I understand that the study may be terminated or enrollment suspended at any time by 
Anacor Pharmaceuticals, with or without cause, or by me if it becomes necessary to 
protect the best interest of the subjects. 
 
 
Signature: __________________________________________ Date: __________ 
Investigator’s Name (Printed):  
 
 
 
 
 
 
 


TAV-ONYC-401 Protocol Amendment 3 
 28 March 2016 
Page 5 of 62 
Anacor Pharmaceuticals, Inc. 
CONFIDENTIAL 
1.0 
SYNOPSIS 
Title: 
An Open-label Study to Evaluate the Safety, Tolerability, and 
Pharmacokinetics of KERYDIN® (tavaborole) topical solution, 5% 
in the Treatment of Onychomycosis of the Toenail in Pediatric 
Subjects Ages 6 to 16 Years and 11 Months 
Protocol Number: TAV-ONYC-401 
Phase: 
4 
Number of Sites: 
Up to 20 study centers 
Study Population: 
Male or female pediatric subjects ages 6 to 16 years and 11 months with distal subungual 
onychomycosis (DSO) involving at least 20% of the total area of the target great toenail 
(TGT), accompanied by a positive potassium hydroxide (KOH) wet mount and a positive 
fungal culture for the dermatophytes Trichophyton rubrum (T. rubrum) or Trichophyton 
mentagrophytes (T. mentagrophytes) during the Screening period.  
Sample Size: 
The study will enroll subjects ages 6 to 16 years and 11 months with at least 40 subjects 
ages 12 to 16 years and 11 months. All subjects will be assigned to receive active 
treatment with KERYDIN® (tavaborole) topical solution, 5%. At least 16 evaluable 
subjects ages 12 to 16 years and 11 months will be studied under maximal use conditions 
(PK subgroup). 
Study Objective: 
The primary objective of this study is to assess the safety and tolerability of KERYDIN 
(tavaborole) topical solution, 5% applied once daily for 48 weeks in pediatric subjects 
ages 6 to 16 years and 11 months with onychomycosis of the toenails.  
The secondary objective is to perform pharmacokinetic (PK) assessments in a subgroup 
of at least 16 evaluable subjects ages 12 to 16 years and 11 months following topical 
administration under maximal use conditions. 
Duration of Subject Participation: 
• Screening period: up to 10 weeks (maximum duration of 70 days) 
• Treatment period: 48 weeks 
• Post-treatment follow-up period: 4 weeks 
Study Treatment: 
KERYDIN (tavaborole) topical solution, 5% will be applied topically once daily for 
48 weeks. 


TAV-ONYC-401 Protocol Amendment 3 
 28 March 2016 
Page 6 of 62 
Anacor Pharmaceuticals, Inc. 
CONFIDENTIAL 
Study Design: 
This is an open-label study to evaluate the safety, tolerability, and pharmacokinetics of 
KERYDIN (tavaborole) topical solution, 5% in treating distal subungual onychomycosis 
(DSO) of the toenails in pediatric subjects ages 6 to 16 years and 11 months. An eligible 
subject will have a TGT with at least 20% involvement with a positive KOH wet mount 
and positive fungal culture for T. rubrum or T. mentagrophytes from a sample obtained 
during the Screening period for one of the great toenails with DSO. KOH and fungal 
culture will be sent to a central mycology laboratory for eligibility determination. Both 
great toenails can be sampled at Screening.  
Eligible subjects will apply KERYDIN (tavaborole) topical solution, 5% once daily to all 
affected toenails (the TGT as well as all other toenails identified by the Investigator at the 
Baseline visit as having the clinical characteristics of onychomycosis) throughout the 
48-week treatment period.  
Subjects will be evaluated at Screening, Baseline (Day 1), and at Weeks 2, 4, 8, 16, 24, 
32, 40, 48, and 52. Each evaluation will include vital signs and a clinical assessment of 
adverse events (AEs) and a local tolerability evaluation.  
Additional procedures are performed as follows: 
• Mycology sampling at Screening, Week 24, and Week 52/early termination (ET) 
• Clinical involvement of the TGT at Screening, Week 24, and Week 52/ET 
• Safety laboratory testing at Baseline, Week 24, and Week 52/ET  
• Digital photography at Screening, Week 24, and Week 52/ET 
• Urine pregnancy tests (UPTs) will be performed on all postmenarchal females at 
all scheduled visits starting at Baseline. 
Subjects will start a diary at Baseline (Day 1) and will complete the diary as instructed. 
In this study, there will be at least 16 evaluable subjects ages 12 to 16 years and 
11 months studied under maximal use conditions (PK subgroup). Subjects in this 
maximal use subgroup will apply the study drug on all 10 toenails, including up to 2 mm 
of the surrounding skin. On Day 15, a pre-dose PK sample will be collected to assess 
steady state trough level. On Day 29, the study drug application will be done at the study 
site, and PK samples will be collected prior to dosing, as well as 4, 6, 8, and 24 hours 
post-dose on Days 29-30. After PK sampling is complete, study drug will be applied only 
to the affected toenails. 
Inclusion Criteria: 
Subjects must meet all of the following criteria to be eligible for this study: 
1. Male or female subjects, ages ≥6 years and ≤16 years and 11 months at the time 
of enrollment 
2. Have a parent or guardian able to understand, to agree to, and to sign the study 
informed consent form; subject has the ability to give assent based on their age, 
maturity, and psychological state at the time of parental/guardian consent 
3. A clinical diagnosis of DSO affecting either great toenail with positive KOH and 
T. rubrum or T. mentagrophytes culture from the TGT confirmed by a central 


TAV-ONYC-401 Protocol Amendment 3 
 28 March 2016 
Page 7 of 62 
Anacor Pharmaceuticals, Inc. 
CONFIDENTIAL 
mycology laboratory during the Screening period 
4. DSO involving at least 20% of the TGT 
5. TGT capable of growing, as assessed by the Investigator or qualified designee 
6. Subject and parent/guardian (if applicable) are willing and able to comply with 
study drug instructions, comply with study instructions, and commit to attending 
all visits 
7. Postmenarchal females must agree to use a medically accepted method of 
contraception for the entire study period 
Exclusion Criteria: 
Subjects with the following characteristics will be excluded from entering this study: 
1. One or more of the following conditions affecting the TGT: 
• Proximal subungual onychomycosis 
• Onychomycosis involving the lunula 
• Superficial white onychomycosis, dermatophytoma, exclusively lateral 
disease, or yellow/brown spikes 
• Screening culture results that demonstrate co-infection with Scopulariopsis 
spp., Scytalidium spp. or other nondermatophyte molds (exception: Candida 
spp. and Epidermophyton floccosum are permitted) 
2. Anatomic abnormalities of the toe(s) or toenail(s) to be treated including, but not 
limited to: genetic nail disorders, pigmentary disorders, onychogryphosis, trauma 
to the toenail(s) to be treated, or other abnormality that in the Investigator’s 
opinion may interfere with clinical evaluation of the toenail(s) or would indicate 
that the subject is unlikely to respond to a topical treatment for DSO 
3. Current or past history of chronic moccasin-type tinea pedis (involving the sides 
or dorsum of the foot) 
4. Current or past history of psoriasis or lichen planus involving the skin, nails or 
mucous membranes 
5. History of any significant chronic fungal disease other than onychomycosis (eg, 
chronic mucocutaneous candidiasis) 
6. Known diagnosis of type I or type II diabetes  
7. Concurrent use of or have used any of the following topical or systemic 
medications within the indicated timeframe prior to Screening: 
• Topical antifungals applied to the toenails: 2 weeks 
• Systemic corticosteroids (including intramuscular injections): 4 weeks 
• Systemic immunosuppressive agents: 4 weeks 
• Systemic antifungals for treatment of onychomycosis or with known activity 
against dermatophytes: 24 weeks 
8. Any significant active or past medical condition which, in the Investigator’s 
opinion, may expose the subject to unacceptable risk by study participation, 
confound the evaluation of treatment response or AEs, or interfere with the 


TAV-ONYC-401 Protocol Amendment 3 
 28 March 2016 
Page 8 of 62 
Anacor Pharmaceuticals, Inc. 
CONFIDENTIAL 
subject’s ability to complete the study 
9. History of any known immunodeficiency 
10. Known to be allergic to the study drug or excipients in the study drug 
11. History of drug or alcohol abuse (current or within the past 6 months) 
12. Participated in any other trial of an investigational drug or device within 30 days 
prior to Screening or participation in a research study concurrent with this study 
Criteria for Evaluation: 
Safety:  
• Frequency and severity of local tolerability reactions (LTRs), including 
burning/stinging, induration/edema, oozing and crusting, pruritus, erythema, and 
scaling  
• Frequency and severity of treatment-emergent adverse events (TEAEs) other than 
LTRs 
• Incidence of serious adverse events (SAEs) 
• Observed values and changes in vital signs and safety laboratory test parameters 
Pharmacokinetics:  
• Blood samples will be collected according to schedule, and descriptive statistical 
analysis of steady state systemic concentrations of tavaborole performed in a 
subgroup of 16 evaluable subjects ages 12 to 16 years and 11 months on Day 15 
and Day 29  
Efficacy: 
• Clinical assessment of disease severity of TGT 
• Mycology (KOH wet mount and fungal culture) 
Efficacy Endpoints: 
The following definitions will be applied to the clinical and mycological response to 
treatment in the TGT:  
Clinical and mycological characteristics: 
• Completely Clear Nail (CN): no clinical evidence of onychomycosis as 
evidenced by normal toenail plate, no onycholysis, and no subungual 
hyperkeratosis 
• Almost CN: no more than minimal evidence of onychomycosis as evidenced by 
toenail plate dystrophic or discolored ≤ 5% of the distal aspect, with minimally 
evident onycholysis and subungual hyperkeratosis  
• Mild onychomycosis: onychomycosis as evidenced by toenail plate dystrophic or 
discolored > 5% to ≤ 20% of the distal aspect, with clearly evident onycholysis 
and subungual hyperkeratosis  
• Moderate onychomycosis: onychomycosis as evidenced by toenail plate 


TAV-ONYC-401 Protocol Amendment 3 
 28 March 2016 
Page 9 of 62 
Anacor Pharmaceuticals, Inc. 
CONFIDENTIAL 
dystrophic or discolored > 20% to ≤ 50% of the distal aspect, with clearly evident 
onycholysis and subungual hyperkeratosis 
• Severe onychomycosis: onychomycosis as evidenced by a toenail plate 
dystrophic or discolored > 50% of the distal aspect, with pronounced onycholysis 
and subungual hyperkeratosis 
• Negative mycology: negative KOH wet mount and negative fungal culture 
Treatment Outcomes: 
• Complete cure: completely CN and negative mycology 
• Almost complete cure: almost CN and negative mycology 
• Treatment success: completely CN or almost CN 
Primary Efficacy Endpoint: 
The primary efficacy endpoint for this study is the complete cure rate of the TGT at 
Week 52 
Secondary Efficacy Endpoints: 
• Complete or Almost complete cure of the TGT at Weeks 24 and 52 
• Treatment success (Clinical Efficacy rate) of the TGT at Weeks 24 and 52 defined 
as completely CN or almost CN  
• 
Negative mycology (Mycological Cure rate) of the TGT at Weeks 24 and 52 
defined as negative KOH wet mount and negative fungal culture  
• 
Negative fungal culture of the TGT at Weeks 24 and 52 
Statistical Methods: 
All subjects who receive at least one confirmed dose of study drug and have at least 
one post-baseline safety assessment will be included in the Safety population. The PK 
population will include evaluable subjects from the maximal use subgroup with available 
PK data. 
The efficacy assessments are intended to assess compliance with treatment for the 
purposes of the safety assessment. Efficacy endpoints will be summarized descriptively 
for the safety population.  
Background and Demographic Characteristics: 
Subject demographic and Baseline characteristics will be summarized for the safety and 
PK populations.  
Efficacy: 
The primary and secondary efficacy endpoints will be summarized with descriptive 
statistics including sample size, frequency count, and percentage. 


TAV-ONYC-401 Protocol Amendment 3 
 28 March 2016 
Page 10 of 62 
Anacor Pharmaceuticals, Inc. 
CONFIDENTIAL 
Safety: 
All AEs occurring during the study will be recorded and classified on the basis of 
Medical Dictionary for Regulatory Activities terminology. TEAEs are those with an onset 
on or after the time of the first study drug administration. For the safety population, all 
reported TEAEs will be summarized by system organ class (SOC), preferred term, 
severity, relationship to study drug, and seriousness. When summarizing TEAEs by 
causality and severity, each subject will be counted only once within an SOC or a 
preferred term using the event with the closest relationship to study drug and the greatest 
severity within each classification. 
SAEs will be summarized by severity and relationship to study drug, and individual 
SAEs will be listed by subject. A list of subjects who prematurely discontinued from the 
study due to an AE will also be provided. 
LTRs will be evaluated with frequency tables for each visit. Additionally, LTRs will be 
summarized by descriptive statistics (mean, standard deviation, median, and minimum 
and maximum). 
Pharmacokinetics: 
Pharmacokinetics of tavaborole will be summarized by collection day.  
The following PK parameters will be calculated for Day 15 and Day 29 (± specified 
window): 
• Cmax:  
maximum observed plasma concentration 
• Tmax:  
time to maximum observed plasma concentration 
• AUC0-24:  area under the plasma concentration-time curve from Hour 0 to 
 
Hour 24, calculated using the linear trapezoidal rule 
• AUC0-∞:  
area under the plasma concentration-time curve extrapolated to 
 
infinity 
• λZ:  
elimination rate constant  
• t1/2:  
elimination half-life 
 


TAV-ONYC-401 Protocol Amendment 3 
 28 March 2016 
Page 11 of 62 
Anacor Pharmaceuticals, Inc. 
CONFIDENTIAL 
TABLE OF CONTENTS 
CLINICAL PROTOCOL ..............................................................................................................1 
CONTACT INFORMATION .......................................................................................................2 
1.0 
SYNOPSIS ..........................................................................................................................5 
Pharmacokinetics:............................................................................................................10 
TABLE OF CONTENTS ............................................................................................................11 
LIST OF IN-TEXT TABLES .....................................................................................................15 
2.0 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ..............................16 
3.0 
BACKGROUND AND RATIONALE ...........................................................................17 
3.1 
Disease Information ...............................................................................................17 
3.2 
Investigational Drug...............................................................................................18 
3.3 
Nonclinical Data ....................................................................................................18 
3.4 
Clinical Experience ................................................................................................19 
3.5 
Summary of Known and Potential Risk and Benefits ...........................................19 
3.6 
Dose Rationale .......................................................................................................19 
3.7 
Statement of Compliance .......................................................................................20 
3.8 
Population ..............................................................................................................20 
3.9 
Number of Sites .....................................................................................................20 
4.0 
STUDY OBJECTIVES ....................................................................................................20 
5.0 
STUDY DESIGN ..............................................................................................................20 
5.1 
Study Endpoints .....................................................................................................22 
5.1.1 
Safety Endpoints ...................................................................................22 
5.1.2 
Pharmacokinetic Endpoint ....................................................................22 
5.1.3 
Efficacy Endpoints ................................................................................22 
5.2 
Blinding and Maintenance of the Blind .................................................................22 
5.3 
Study Treatment .....................................................................................................22 
5.3.1 
Treatment Administration .....................................................................23 
5.3.2 
Labeling.................................................................................................23 
5.3.3 
Packaging and Storage ..........................................................................23 
5.3.4 
Duration of Study ..................................................................................24 
5.4 
Discontinuation of Study by Sponsor ....................................................................24 
5.5 
Discontinuation of Study Site by Sponsor .............................................................24 
5.6 
Product Accountability ..........................................................................................25 
5.7 
Data Identification .................................................................................................25 
5.8 
Prior and Concomitant Medications ......................................................................26 


TAV-ONYC-401 Protocol Amendment 3 
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Page 12 of 62 
Anacor Pharmaceuticals, Inc. 
CONFIDENTIAL 
5.8.1 
Medications Prohibited Prior to Screening/Baseline (Day 1) 
and During the Study ............................................................................26 
5.8.2 
Prohibited Procedures ...........................................................................27 
5.8.3 
Medications Allowed During the Study ................................................27 
5.9 
Females of Non-childbearing Potential .................................................................27 
5.10 
Females of Childbearing Potential .........................................................................27 
6.0 
STUDY POPULATION ..................................................................................................28 
6.1 
Sample Size ............................................................................................................28 
6.2 
Inclusion Criteria ...................................................................................................28 
6.3 
Exclusion Criteria ..................................................................................................29 
6.4 
Subject Withdrawal ................................................................................................30 
7.0 
STUDY PROCEDURES .................................................................................................31 
7.1 
Study Visits ............................................................................................................31 
7.2 
Study Procedures and Evaluations Schema ...........................................................31 
7.2.1 
Study Schema ........................................................................................31 
7.2.2 
Visit 1: Screening Visit (up to 70 Days Prior to Day 1) .......................33 
7.2.3 
Treatment Period (Visit 2 through Visit 10) .........................................34 
7.2.4 
Visit 11 (Week 52) or Early Termination .............................................36 
7.3 
Explain Study and Obtain Signed Informed Consent Form ..................................37 
7.4 
Demographics ........................................................................................................37 
7.5 
Review Inclusion/Exclusion Criteria .....................................................................37 
7.6 
Medical History and Medication History ..............................................................37 
7.7 
Concomitant Medications ......................................................................................37 
7.8 
Physical Examinations ...........................................................................................37 
7.9 
Identify Target Great Toenail (TGT) and Other Toenails .....................................37 
7.10 
Toenail Trimming Procedure .................................................................................38 
7.11 
KOH Mount and Central Fungal Culture...............................................................38 
7.12 
Study Drug Dispensing ..........................................................................................38 
7.13 
Study Drug Self-Administration ............................................................................39 
7.14 
Dosing Modifications.............................................................................................39 
7.15 
Study Drug Collection ...........................................................................................39 
7.16 
Dosing Diary ..........................................................................................................39 
7.17 
Digital Photography ...............................................................................................40 
8.0 
PHARMACOKINETIC ASSESSMENT .......................................................................40 
8.1 
Collection of Blood Samples for Pharmacokinetic Assessment ............................40 
8.2 
Specimen Assays ...................................................................................................40 


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9.0 
EFFICACY ASSESSMENT ...........................................................................................41 
9.1 
Clinical Assessment of the Target Toenail Involvement .......................................41 
9.2 
Primary Efficacy Endpoint ....................................................................................41 
9.3 
Secondary Efficacy Endpoints ...............................................................................42 
10.0 
SAFETY ASSESSMENT ................................................................................................42 
10.1 
Local Tolerability Reactions (LTRs) .....................................................................42 
10.2 
Vital Signs ..............................................................................................................43 
10.3 
Clinical Safety Laboratory Parameters and Pregnancy Tests ................................44 
11.0 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS ......................................44 
11.1 
Definition of Adverse Event ..................................................................................44 
11.2 
Relationship to Study Drug ....................................................................................46 
11.3 
Severity ..................................................................................................................46 
11.4 
Outcome .................................................................................................................47 
11.5 
Serious Adverse Event ...........................................................................................47 
11.6 
Safety Reporting Procedures..................................................................................48 
11.7 
Laboratory Test Abnormalities ..............................................................................49 
11.8 
Pregnancy ...............................................................................................................49 
12.0 
STATISTICAL PLAN .....................................................................................................49 
12.1 
Sample Size ............................................................................................................49 
12.2 
Statistical Analysis .................................................................................................50 
12.2.1 
Study Populations .................................................................................50 
12.2.2 
Background and Demographic Characteristics .....................................50 
12.2.3 
Efficacy .................................................................................................50 
12.2.4 
Pharmacokinetics ..................................................................................50 
12.2.5 
Safety.....................................................................................................51 
13.0 
ETHICAL CONSIDERATIONS ....................................................................................52 
13.1 
Ethical Conduct of the Study .................................................................................52 
13.2 
Subject Information, Informed Consent, and Assent .............................................52 
13.2.1 
Child Assent Considerations .................................................................53 
13.3 
IRB/EC Approval...................................................................................................54 
13.4 
Subject Confidentiality ..........................................................................................54 
14.0 
DOCUMENTATION AND STUDY MONITORING ..................................................55 
14.1 
Changes to Protocol ...............................................................................................55 
14.2 
Case Report Forms .................................................................................................56 
14.3 
Study Monitoring and Auditing .............................................................................56 
14.4 
Direct Access to Source Data/Documents .............................................................57 


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14.5 
Data Collection ......................................................................................................57 
14.6 
Document Retention ..............................................................................................57 
14.7 
Termination of Study .............................................................................................58 
14.8 
Investigator Agreement ..........................................................................................58 
15.0 
FINANCE AND INSURANCE .......................................................................................59 
16.0 
PUBLICATION POLICY ...............................................................................................59 
17.0 
REFERENCES .................................................................................................................60 
APPENDIX A: SUMMARY OF CHANGES ............................................................................61 
 


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LIST OF IN-TEXT TABLES 
Table 1: 
Medications Prohibited Prior to the Study .......................................................26 
Table 2: 
Concomitant Medications Prohibited During the Study ..................................27 
Table 3: 
Schedule of Events ...........................................................................................32 
Table 4: 
Grading of Local Tolerability Reactions (LTRs).............................................43 
Table 5: 
Safety Laboratory Parameters ..........................................................................44 
 
 
 


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2.0 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
AE 
Adverse Event 
AUC0-24 
Area Under the plasma Concentration-time curve from Hour 0 to 
Hour 24 
AUC0-∞ 
Area Under the plasma Concentration-time curve from Hour 0 
extrapolated to infinity 
CN 
Clear Nail 
Cmax 
maximum observed plasma concentration 
CRF 
Case Report Form  
DSO 
Distal Subungual Onychomycosis 
 
 
EC 
Ethics Committee 
ET 
FDA 
Early Termination 
Food and Drug Administration 
GCP 
Good Clinical Practice 
hERG 
human ether-à-go-go-related gene 
HIPAA 
Health Insurance Portability and Accountability Act 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form  
ICH 
International Conference on Harmonization 
IRB 
Institutional Review Board 
KOH 
potassium hydroxide  
λZ 
elimination rate constant 
LTR 
Local Tolerability Reactions 
 
 
PK 
Pharmacokinetic 
SAE 
Serious Adverse Event 
SOC 
System Organ Class 
SOP 
Standard Operating Procedures  
 
 
t½ 
elimination half-life 
TEAE 
Treatment-Emergent Adverse Event  
TGT 
Target Great Toenail 
Tmax 
time to maximum observed plasma concentration 
UPT 
Urine Pregnancy Test 
w/w 
weight for weight 
 


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3.0 
BACKGROUND AND RATIONALE 
KERYDIN® (tavaborole) topical solution, 5%, the first oxaborole antifungal agent, was 
approved by the Food and Drug Administration (FDA) for the topical treatment of 
onychomycosis of the toenails on 07 July 2014 (NDA 204427). This present study is 
being conducted to fulfill the postmarketing requirement for a pharmacokinetic 
(PK)/safety trial of KERYDIN (tavaborole) topical solution, 5% in pediatric subjects with 
onychomycosis of the toenails. 
3.1 
Disease Information 
Dermatophytes are a group of fungi that can infect the keratinous layers of the skin, hair, 
and nails. Very superficial infections with the dermatophytes are found only in the top 
layer, the stratum corneum, or scaly part of the skin. Dermatophytes are ubiquitous in the 
environment, commonly found in the soil. While all humans come into contact with 
dermatophytes in their environment, only a small percentage of the population develops 
symptomatic disease, leading some to conclude that dermatophytosis is an infectious 
disease but not a contagious disease. 
Dermatophyte infections of the skin are seen as tinea pedis (skin infection of the toes, 
more commonly known as athlete’s foot), tinea manuum (infection of the skin of the 
hand), tinea faciei (infection of facial skin), tinea cruris (infection of the groin area, more 
commonly known as jock itch), and tinea corporis (ringworm).  
When dermatophytes infect the nail unit, the resulting condition is referred to as 
onychomycosis. The characteristics of onychomycosis include onycholysis (separation of 
the nail plate from the nail bed), subungual hyperkeratosis (thickening of the nail bed), as 
well as changes in the nail plate which include thickening, changes in color, and 
brittleness.  
The clinical manifestations of onychomycosis can vary depending on what part of the 
nail unit is infected: the nail plate, the nail bed, and/or the paronychia (skin that surrounds 
the nail plate). Recognized clinical types of onychomycosis include superficial white 
onychomycosis in which only the surface of the nail plate is infected, proximal subungual 
onychomycosis in which the proximal portion of the nail is infected, and the most 
common distal subungual onychomycosis (DSO) in which the distal nail plate and nail 
bed are infected. 
Onychomycosis is the most common nail disorder in adults, affecting 2% to 13% of the 
adult population.1 It is more prevalent in older adults, with 28% to 40% of adults over the 
age of 60 years having some nail involvement with dermatophytes.1  
Onychomycosis in the pediatric population has been described as uncommon, unusual, 
and rare.5, 6 The low frequency of pediatric onychomycosis has been attributed to factors 


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such as a faster nail growth compared to the adult population, a smaller contact surface 
that offers less chance for trauma and fungal colonization, infrequent exposure to fungi in 
public places, and a lower prevalence of tinea pedis (all of which are risk factors for 
onychomycosis). Reports in the literature confirm a low prevalence of onychomycosis in 
the pediatric population, ranging between 0.2% and 2.6%, and indicate that 
onychomycosis is mainly reported after puberty.7 
Several approved oral and topical treatments are available for onychomycosis, including 
KERYDIN (tavaborole) topical solution, 5%.2,3 Oral medications, the most effective 
current treatment for onychomycosis, are associated with potential hepatotoxicity or 
cardiotoxicity.2  
3.2 
Investigational Drug 
KERYDIN (tavaborole) topical solution, 5% contains 5% tavaborole (w/w) in a clear, 
colorless alcohol-based solution for topical use. The active ingredient, tavaborole, is an 
oxaborole antifungal with the chemical name of 5-fluoro-1,3-dihydro-1-hydroxy-2,1-
benzoxaborole. KERYDIN (tavaborole) topical solution, 5% is approved by the FDA for 
the topical treatment of onychomycosis. The drug vehicle consists of alcohol, propylene 
glycol, and edetate calcium disodium. Refer to the Investigator’s Brochure4 (IB) or 
package insert for further information on the characteristics of KERYDIN (tavaborole) 
topical solution, 5%.8 
Tavaborole shows broad spectrum activity against the major dermatophytes that cause 
onychomycosis, Trichophyton rubrum (T. rubrum) and Trichophyton mentagrophytes 
(T. mentagrophytes), as well as against yeasts and molds. The drug’s novel mechanism of 
action is the inhibition of an aminoacyl-tRNA synthetase. Tavaborole forms an adduct 
with tRNALeu in the editing site of leucyl-tRNA synthetase. Data from both ex vivo 
human cadaver nails and human PK studies demonstrate good penetration of tavaborole 
into and through the nail plate with low systemic exposure. 
3.3 
Nonclinical Data 
Tavaborole has been tested in an extensive battery of toxicology studies with systemic 
administration in rats, rabbits, and dogs and with topical administration in mice, guinea 
pigs, rabbits, and minipigs. Tavaborole is not genotoxic, is not a sensitizer, and has a low 
potential of causing toxicity after single or repeated administration. The major finding 
after repeated oral administration was irritation of the nonglandular stomach in rats, and 
the major finding after repeated topical administration was local dermal irritation in 
minipigs. Tavaborole has been found to be non-carcinogenic in 2-year studies in rats 
(oral) and mice (topical). Based on its human ether-à-go-go-related gene (hERG) tail 
current inhibition (1 µM), tavaborole can be classified as a low-potency hERG-channel 
blocker. Fetal skeletal malformations were observed following very high oral doses of 
tavaborole in a rat embryo-fetal developmental toxicity study. Tavaborole did not affect 


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fertility or reproductive performance and did not affect prenatal and postnatal 
development or maternal function when dosed orally to rats. 
Tavaborole has a relatively short half-life in rats following oral administration. 
Radiolabeled studies with 14C-tavaborole showed extensive metabolism, including a 
major biotransformation pathway involving oxidative oxaborole ring cleavage, followed 
by further oxidation, glucuronidation, or sulfation. 
3.4 
Clinical Experience 
Refer to the IB4 or package insert,8 for further information on the clinical experience with 
KERYDIN (tavaborole) topical solution, 5%. 
3.5 
Summary of Known and Potential Risk and Benefits 
Details about specific benefits and risks for subjects participating in this clinical trial can 
be found in the IB4, package insert8, and in the sample informed consent form (ICF) 
document. KERYDIN (tavaborole) topical solution, 5% has not been studied in pediatric 
patients; thus, the safety of the drug has not been established in the patient population that 
will be enrolled in this trial. 
3.6 
Dose Rationale 
The NDA for KERYDIN (tavaborole) topical solution, 5% was approved by FDA in 
July 2014 for the treatment of onychomycosis of the toenails due to T. rubrum or 
T. mentagrophytes. KERYDIN (tavaborole) topical solution, 5% applied daily for 
48 weeks was studied in two Phase 3 registration studies. Data from the studies showed a 
statistically significant therapeutic effect compared with vehicle with no safety concerns. 
This 48-week long, open-label PK/safety trial will enable the study of the safety profile 
of KERYDIN (tavaborole) topical solution, 5% in subjects ages 6 to 16 years and 
11 months with onychomycosis of the toenails. 
The dosing regimen for the pharmacokinetic analysis is based on a Phase 1 maximal use 
absorption study in adults 9. In this Phase 1 study, elevated plasma concentrations of 
tavaborole in adult subjects with onychomycosis were achieved through once daily 
application to all 10 toenails and up to 2 mm of surrounding skin.  
While the Phase 1 maximal use study in adults required onychomycosis of at least 4 
involved toenails, including at least 1 great toenail with 50-75% nail involvement, this 
degree of disease severity in the pediatric population is exceedingly rare, and will 
therefore not be a study requirement. The maximal dosing regimen of once daily 
application to all 10 toenails and up to 2 mm of surrounding skin is expected to produce 
elevated plasma concentrations in this pediatric population. 
 


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3.7 
Statement of Compliance 
This study will be conducted in compliance with the protocol approved by the 
appropriate Institutional Review Boards (IRB) and Ethics Committees (EC), according to 
International Committee on Harmonization (ICH) and local Good Clinical Practice 
(GCP) standards, and in accordance with the ethical principles that have their origin in 
the Declaration of Helsinki.  
3.8 
Population 
Male or female subjects ages 6 to 16 years and 11 months with DSO involving at least 
20% of the total area of the target great toenail (TGT), accompanied by a positive 
potassium hydroxide (KOH) wet mount and a positive fungal culture for the 
dermatophytes T. rubrum or T. mentagrophytes during the Screening period. A PK 
subgroup of at least 16 evaluable subjects ages 12 to 16 years and 11 months will be 
studied under maximal use conditions. 
3.9 
Number of Sites 
Up to 20 study centers are planned. 
 
4.0 
STUDY OBJECTIVES 
The primary objective of this study is to assess the safety and tolerability of KERYDIN 
(tavaborole) topical solution, 5% applied once daily for 48 weeks in pediatric subjects 
ages 6 to 16 years and 11 months with onychomycosis of the toenails.  
The secondary objective is to perform PK assessments in at least 16 evaluable subjects 
ages 12 to 16 years and 11 months following topical administration under maximal use 
conditions. 
 
5.0 
STUDY DESIGN 
This is an open-label study to evaluate the safety, tolerability, and pharmacokinetics of 
KERYDIN (tavaborole) topical solution, 5% in treating DSO of the toenail in pediatric 
subjects ages 6 to 16 years and 11 months. An eligible subject will have a TGT with at 
least 20% involvement with a positive KOH wet mount and positive fungal culture for 
T. rubrum or T. mentagrophytes from a sample obtained during the Screening period for 
one of the great toenails. KOH and fungal culture will be sent to a central mycology 
laboratory for eligibility determination. Both great toenails can be sampled at Screening.  
The mycological confirmation of eligibility will be performed as follows: 


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1. Initial sample is KOH (+) and culture (+) for  T. rubrum or T. mentagrophytes, with 
or without co-infection with Candida spp. or E. floccosum, subject is eligible for 
enrollment within the maximum period of 10 weeks (i.e., within 70 days) from the 
Screening visit. 
2. Initial sample is KOH (−) or initial sample is KOH (+) and culture (−): The sample 
may be repeated and will be assessed as follows: 
• 
If a repeat sample is KOH (+) and culture (+) for T. rubrum or 
T. mentagrophytes with or without co-infection with Candida spp. or E. 
floccosum, for enrollment as long as the subject is enrolled within the 
maximum period of 10 weeks (i.e., within 70 days) from the Screening visit. 
Eligible subjects will apply KERYDIN (tavaborole) topical solution, 5% once daily to all 
affected toenails (the TGT as well as all other toenails identified by the Investigator at the 
Baseline visit as having the clinical characteristics of onychomycosis) throughout the 
48-week treatment period.  
Subjects will be evaluated at Screening, Baseline (Day 1), and at Weeks 2, 4, 8, 16, 24, 
32, 40, 48, and 52. Each evaluation will include a clinical assessment of the adverse 
events (AEs) and local tolerability evaluation.  
Additional procedures are performed as follows: 
• Mycology sampling at Screening, Week 24, and Week 52/early termination (ET) 
• Clinical disease severity of the TGT at Screening, Week 24, and Week 52/ET 
• Safety laboratory testing at Baseline, Week 24, and Week 52/ET  
• Digital photography at Screening, Week 24, and Week 52/ET 
• Urine pregnancy tests (UPTs) will be performed on all postmenarchal females at all 
scheduled visits starting at the Baseline visit. 
Subjects will start diaries at Baseline (Day 1) and will complete the diary as instructed. 
In this study, there will be a PK subgroup of at least 16 evaluable subjects ages 12 to 16 
years and 11 months studied under maximal use conditions. Subjects in this maximal use 
subgroup will apply the study drug on all 10 toenails, including up to 2 mm of the 
surrounding skin, for 28 days (±7 days). On Day 15, a pre-dose PK sample will be 
collected to assess steady state trough level. On Day 29, the study drug application will 
be done at the study site, and PK samples will be collected prior to dosing, as well as 4, 6, 
8, and 24 hours post-dose on Days 29-30. After PK sampling is complete, study drug will 
be applied only to the affected toenails. 


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5.1 
Study Endpoints 
5.1.1 
Safety Endpoints 
• Frequency and severity of local tolerability reactions (LTRs), including 
burning/stinging, induration/edema, oozing and crusting, pruritus, erythema, and 
scaling  
• Frequency and severity of treatment-emergent adverse events (TEAEs) other than 
LTRs 
• Incidence of serious adverse events (SAEs) 
• Observed values and changes in vital signs and safety laboratory test parameters 
5.1.2 
Pharmacokinetic Endpoint 
Blood samples will be collected according to schedule and descriptive statistical analysis 
of steady state systemic concentrations of tavaborole performed in a subgroup of subjects 
under maximal use conditions.  
5.1.3 
Efficacy Endpoints 
The primary efficacy endpoint for this study is the complete cure rate of the TGT at 
Week 52. Complete cure is defined as 0% clinical involvement of the TGT and negative 
mycology (negative KOH wet mount and negative fungal culture) at Week 52. 
The secondary efficacy endpoints include the following: 
• Complete or Almost complete cure of the TGT at Weeks 24 and 52 
• Treatment success (Clinical Efficacy rate) of the TGT at Weeks 24 and 52 defined as 
defined as completely Clear Nail (CN) or almost CN  
• Negative mycology (Mycological Cure rate) of the TGT at Weeks 24 and 52 defined 
as negative KOH wet mount and negative fungal culture 
• Negative fungal culture of the TGT at Weeks 24 and 52 
5.2 
Blinding and Maintenance of the Blind  
Not applicable to this study. 
5.3 
Study Treatment 
All subjects will receive KERYDIN (tavaborole) topical solution, 5%. Study drug will be 
applied topically once daily for 48 weeks by the subject and/or parent/guardian. 


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5.3.1 
Treatment Administration 
Study drug will be applied on all affected toenails daily with a supplied dropper, 
preferably at bed time, except for the clinic visit days during which the study drug will be 
applied at the visit. On Day 1, subjects and/or parent/guardian will be given instructions 
on how to apply the study drug and will apply the study drug at the study site, under the 
supervision of the Investigator or a qualified designee. 
Additionally, subjects in the maximal use PK subgroup will receive a minimum dose of 
each treatment to all 10 toenails, including up to 2 mm of surrounding skin defined as 
follows: 
• Great toenails: two (2) drops each 
• All other toenails: one (1) drop each 
KERYDIN (tavaborole) topical solution, 5% is for topical use on toenail(s) only. Contact 
with mucous membranes (i.e., inside of nostrils, mouth, vagina, urethra, and rectum) and 
the eyes should be avoided. 
5.3.2 
Labeling 
Each bottle and kit will be labeled in accordance with Good Manufacturing Practice and 
will include the following information: 
• Protocol number 
• Kit number 
• Unique alpha-numeric identifier (batch/lot number) 
• Storage requirement 
• Investigational use and appropriate caution statements 
• Sponsor identification 
5.3.3 
Packaging and Storage 
Each treatment kit will contain 2 bottles of KERYDIN (tavaborole) topical solution, 5% 
and applicators (droppers).  
KERYDIN (tavaborole) topical solution, 5% will be supplied in amber glass bottles each 
containing 10 mL of product. The Sponsor will provide all test preparations/supplies for 
KERYDIN (tavaborole) topical solution, 5%. 


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Study drug must be stored at the study site according to label conditions in a secure, 
limited-access location. 
Subjects and/or parents/guardians will be instructed to store the study drug at room 
temperature (not to refrigerate or freeze), in an upright position. 
5.3.4 
Duration of Study 
Each subject will participate in the study for up to 62 weeks from the time of signing the 
ICF through the final contact. After the Screening period of up to 10 weeks (maximum of 
70 days), each subject will receive open-label KERYDIN (tavaborole) topical solution, 
5% for up to 48 weeks followed by a 4 week post-treatment follow-up visit. The study is 
expected to have an overall duration of approximately 28 months, including an 
enrollment period of approximately 12 months. 
5.4 
Discontinuation of Study by Sponsor 
The Sponsor reserves the right to terminate the study at any time. If the Sponsor elects to 
discontinue the study because of a safety concern, the Sponsor will immediately notify 
the sites to discontinue treatment of all subjects currently enrolled in the study and will 
promptly notify the FDA. If the Sponsor elects to discontinue the study for any other 
reason, the Sponsor will notify the sites and the sites will notify subjects at their next 
scheduled visit. The IRB/EC will also be notified. 
Reasons for study discontinuation by the Sponsor may include, but are not limited to, the 
following: 
• The incidence or severity of AEs in this or other studies indicates a potential health 
hazard to subjects 
• Sponsor’s decision to discontinue investigation in a specific therapeutic area 
• Subject enrollment is unsatisfactory 
5.5 
Discontinuation of Study Site by Sponsor 
The Sponsor reserves the right to terminate a clinical study site from the study at any 
time. If the Sponsor elects to discontinue a clinical study site from the study because of a 
safety concern, the Sponsor will immediately notify the site to discontinue treatment of 
all subjects currently enrolled in the study and will promptly notify the FDA. If the 
Sponsor elects to discontinue a clinical study site from the study for any other reason, the 
Sponsor will notify the site, and the site will notify subjects at their next scheduled visit. 
In all cases, the Investigator must notify the IRB/EC in writing of the site’s 
discontinuation and send a copy of the notification to the Sponsor. 


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Reasons for study site discontinuation by the Sponsor may include, but are not limited to, 
the following: 
• Subject enrollment at the site is unsatisfactory 
• Investigator request to withdraw from participation 
• Serious and/or persistent noncompliance by the Investigator with the protocol, the 
clinical research agreement, or applicable regulatory guidelines in conducting the 
study 
• IRB/EC decision to terminate or suspend approval for the investigation 
5.6 
Product Accountability 
Subjects and/or parents/guardians will be instructed to return all used, unused, and empty 
study drug bottles at all protocol-specified visits for assessment of study drug 
accountability.  
An accurate and current accounting of the dispensing and return of study drug for each 
subject will be maintained on an ongoing basis by a member of the study site staff. The 
bottles contained in each medication kit will be weighed using a calibrated scale. The 
number of bottles dispensed and returned will be counted and the weight of the bottles 
(with cap on) after return will be measured and documented in the subject study drug log 
and/or site study drug log or an equivalent document and will be verified by the Sponsor's 
study monitor. The study drug log or equivalent document shall be retained at the study 
site and a copy supplied to the Sponsor when the study is complete.  
All study drug supplies, including all containers of study drug, whether empty or 
containing unused study drug, must be returned to the Sponsor’s designee, unless 
Investigators are instructed otherwise by the Sponsor or its designee. The Sponsor’s study 
monitor will provide instructions on the return of all study drug supplies.  
A final inventory of the total amount of study drug received at each study site against the 
amount dispensed and returned must be recorded in the site study drug log or an 
equivalent document. 
Inventory records must be readily available for inspection by the study monitor and/or 
auditor, and open to inspection by the regulatory authorities at any time. 
5.7 
Data Identification 
Electronic case report forms (CRF) will be used to record subject data during the course 
of the study.  


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All study data must be verifiable to the source data, which necessitates access to all 
original recordings, laboratory reports, and subjects’ records. The Investigator must 
therefore agree to allow access to subjects’ records, and source data must be made 
available for all study data. The subjects (or their legal representatives) must also allow 
access to the subjects’ medical records, and they will be informed of this and will be 
signing their agreement when giving informed consent. 
All aspects of the study will be carefully monitored by the Sponsor or authorized 
representatives of the Sponsor, with respect to current GCP and standard operating 
procedures (SOPs) for compliance with applicable government regulations. These 
individuals will have access, both during the trial and after trial completion, to review and 
audit all records necessary to ensure integrity of the data, and they will periodically 
review progress of the study with the Investigator. 
Every attempt must be made to follow the protocol and to obtain and record all data 
requested for each subject at the specified times. However, ethical reasons may warrant 
the failure to obtain and record certain data or to record data at the times specified. If this 
becomes necessary, the reasons must be clearly documented in the source chart. 
5.8 
Prior and Concomitant Medications 
Any prior use of systemic antifungal medication within 24 weeks prior to Screening, all 
medication taken within 30 days before Screening, and all concomitant medication taken 
during the study are to be recorded on the source documents and CRF. The identity of the 
medication and the reason for use must be recorded. The use of any concomitant 
medication must relate to an AE or the subject's medical history. 
5.8.1 
Medications Prohibited Prior to Screening/Baseline (Day 1) and During 
the Study 
The medications prohibited prior to Screening are listed in the exclusion criteria 
(Section 6.3) and summarized in Table 1 below.  
Table 1: 
Medications Prohibited Prior to the Study 
Class of Medication 
Washout Period 
Topical antifungal agents applied to the toenails  
2 weeks prior to and during Screening 
Systemic corticosteroids (including intramuscular injections) or 
immunosuppressive agents, except inhaled corticosteroids, 
which are allowed throughout the study 
4 weeks prior to and during Screening 
Systemic antifungal agents for treatment of onychomycosis or 
with known activity against dermatophytes 
24 weeks prior to and during 
Screening 
Any investigational drug  
30 days prior to and during Screening 
 


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Subjects must not take any of the medications listed in Table 2 during the study. 
Table 2: 
Concomitant Medications Prohibited During the Study 
Class of Medication 
Prohibited During Study, From: 
Topical antifungal agents applied to the toenails 
Screening 
Systemic antifungal treatments 
Screening 
Any investigational drug other than the study drug 
Screening 
 
5.8.2 
Prohibited Procedures 
Over-the-counter treatments, such as tea tree oil or holistic products, applied to the 
toenails are prohibited. Toenail polish is not allowed during the study. On the day of a 
study visit, subjects and/or parents/guardians should not apply the study drug or any other 
products to their feet or toenails until they have either been instructed to apply study drug 
during the visit or until they have completed the study visit. These restrictions will 
remain in effect, as applicable, throughout the study.  
5.8.3 
Medications Allowed During the Study 
Subjects with tinea pedis may be treated with topical antifungal agents  if treatment is 
indicated. Subjects should apply the topical antifungal to all affected areas as directed by 
the Investigator, avoiding all toenails. These restrictions will remain in effect, as 
applicable, throughout the study. 
5.9 
Females of Non-childbearing Potential 
Premenarchal female subjects will be considered to be of non-childbearing potential. 
5.10 
Females of Childbearing Potential 
Acceptable contraceptive methods for female subjects include one of the following: 
• Abstinence 
• Oral, transdermal, intrauterine, injected, or implanted hormonal methods of 
contraception 
• Tubal ligation 
• Placement of a copper-containing intrauterine device 
• Condom with spermicidal foam/gel/film/cream/suppository 


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• Male partner who has had a vasectomy for at least 4 months 
• Sterile (eg, total hysterectomy)  
An acceptable method of contraception must be used starting from the Screening visit 
and continue through the end of the study. 
 
6.0 
STUDY POPULATION 
Male or female subjects ages 6 to 16 years and 11 months with DSO involving at least 
20% of the total area of the TGT, accompanied by a positive KOH wet mount and a 
positive fungal culture for the dermatophytes T. rubrum or T. mentagrophytes, with or 
without co-infection with Candida spp. or E. floccosum, during the Screening period. A 
PK subgroup of at least 16 evaluable subjects ages 12 to 16 years and 11 months will be 
studied under maximal use conditions. 
6.1 
Sample Size 
The study will enroll subjects ages 6 to 16 years and 11 months with at least 40 subjects 
ages 12 to 16 years and 11 months. All subjects will be assigned to receive active 
treatment with KERYDIN (tavaborole) topical solution, 5%. A PK subgroup of at least 
16 evaluable subjects ages 12 to 16 years and 11 months will be studied under maximal 
use conditions. 
6.2 
Inclusion Criteria 
Subjects must meet all of the following inclusion criteria to be eligible for this study: 
1. Male or female subjects, ages ≥ 6 years and ≤ 16 years and 11 months at the time of 
enrollment 
2. Have a parent or guardian able to understand, to agree to, and to sign the study ICF; 
subject has the ability to give assent based on their age, maturity, and psychological 
state at the time of parental/guardian consent 
3. A clinical diagnosis of DSO affecting either great toenail with positive KOH and 
T. rubrum or T. mentagrophytes culture from the TGT confirmed by a central 
mycology laboratory during the Screening period 
4. DSO involving at least 20% of the TGT 
5. TGT capable of growing, as assessed by the Investigator or qualified designee 
6. Subject and parent/guardian (if applicable) are willing and able to comply with study 
drug instructions, comply with study instructions, and commit to attending all visits 


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7. Postmenarchal females must agree to use a medically accepted method of 
contraception for the entire study period 
6.3 
Exclusion Criteria 
Subjects who meet any of the following exclusion criteria will be excluded from entering 
this study: 
1. One or more of the following conditions affecting the TGT: 
• 
Proximal subungual onychomycosis 
• 
Onychomycosis involving the lunula 
• 
Superficial white onychomycosis, dermatophytoma, exclusively lateral 
disease, or yellow/brown spikes 
• Screening culture results that demonstrate co-infection with 
Scopulariopsis spp., Scytalidium spp. or other nondermatophyte molds 
(exception: Candida spp. and E. floccosum are permitted) 
2. Anatomic abnormalities of the toe(s) or toenail(s) to be treated including, but not 
limited to: genetic nail disorders, pigmentary disorders, onychogryphosis, trauma to 
the toenail(s) to be treated, or other abnormality that in the Investigator’s opinion may 
interfere with clinical evaluation of the toenail(s) or would indicate that the subject is 
unlikely to respond to a topical treatment for DSO 
3. Current or past history of chronic moccasin-type tinea pedis (involving the sides or 
dorsum of the foot) 
4. Current or past history of psoriasis or lichen planus involving the skin, nails or 
mucous membranes 
5. History of any significant chronic fungal disease other than onychomycosis (eg, 
chronic mucocutaneous candidiasis) 
6. Known diagnosis of type I or type II diabetes  
7. Concurrent use of or have used any of the following topical or systemic medications 
within the indicated timeframe prior to Screening: 
• 
Topical antifungals applied to the toenails: 2 weeks 
• 
Systemic corticosteroids (including intramuscular injections): 4 weeks 
• 
Systemic immunosuppressive agents: 4 weeks 


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• 
Systemic antifungals for treatment of onychomycosis or with known activity 
against dermatophytes: 24 weeks 
8. Any significant active or past medical condition which, in the Investigator’s opinion, 
may expose the subject to unacceptable risk by study participation, confound the 
evaluation of treatment response or AEs, or interfere with the subject’s ability to 
complete the study 
9. History of any known immunodeficiency 
10. Known to be allergic to the study drug or excipients in the study drug 
11. History of drug or alcohol abuse (current or within the past 6 months) 
12. Participated in any other trial of an investigational drug or device within 30 days prior 
to Screening or participation in a research study concurrent with this study 
6.4 
Subject Withdrawal 
Subjects may be withdrawn from the study (eg, from further study treatment) for the 
following reasons as well as other specified reasons: 
• AE (including LTR) 
• Lost to follow-up 
• Subject did not wish to continue for reasons related or unrelated to study treatment 
• Noncompliance with protocol 
• Administrative reasons (eg, study terminated, study on hold) 
• Pregnancy 
In all cases, the reason for and date of withdrawal must be recorded in the CRF and in the 
subject's source documents. The subject must be followed up to establish whether the 
reason was an AE, and if so, this must be reported in accordance with the procedures in 
Section 11.0. If a subject is withdrawn due to pregnancy, refer to Section 11.8 for 
follow-up procedures. 
As far as possible, all examinations scheduled for the final study visit must be performed 
on all subjects who receive the study drug but do not complete the study according to 
protocol.  
The Investigator must make every effort to contact subjects lost to follow-up. Attempts to 
contact such subjects must be documented in the subject’s records (eg, times and dates of 


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attempted telephone contact, receipt for sending a registered letter). 
 
7.0 
STUDY PROCEDURES 
7.1 
Study Visits 
Subjects will be required to visit the clinic for all scheduled visits (Screening, Baseline, 
and at Weeks 2, 4, 8, 16, 24, 32, 40, 48, and 52). The PK subgroup will have one extra 
visit (Visit 4a). The timing of each study visit is relative to Baseline (Day 1). Both the PK 
and non-PK visits will have a window of ± 7 days with the exception of PK Visit 3 which 
will have a +7 day window and PK Visit 4a which must immediately follow the 
proceeding day to allow for 24-hour PK draw). Additional unscheduled visits may be 
requested by the subject or Investigator to address any safety concerns. 
7.2 
Study Procedures and Evaluations Schema 
7.2.1 
Study Schema 
Table 3 displays the study procedures throughout the study. 
 


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Table 3: 
Schedule of Events 
Study Visit No. 
1 
(Screening) 
2 
(Baseline) 
3 
4 
4a  
(PK) 
5 
6 
7 
8 
9 
10 
11 
(or ET) 
Study Day (±7 days V4-11, +7 days V3) 
Up to -70 days 
1 
15 
29 
30 
 
 
 
 
 
 
 
Study Week 
 
 
2 
4 
 
8 
16 
24 
32 
40 
48 
52 
Informed consent 
x 
 
 
 
 
 
 
 
 
 
 
 
Obtain subject number  
x 
 
 
 
 
 
 
 
 
 
 
 
Demographics  
x 
 
 
 
 
 
 
 
 
 
 
 
Medical and medication history 
x 
x 
 
 
 
 
 
 
 
 
 
 
Abbreviated physical examination 
 
x 
 
 
 
 
 
 
 
 
 
 
KOH mount and fungal culturec 
x 
 
 
 
 
 
 
x 
 
 
 
x 
Review inclusion/exclusion criteria 
x 
x 
 
 
 
 
 
 
 
 
 
 
Identify target great toenail (TGT) 
x 
x 
 
 
 
 
 
 
 
 
 
 
Identify ‘other toes’ to be treated 
 
x 
 
 
 
 
 
 
 
 
 
 
Clinical assessment (% TGT disease severity) 
x 
 
 
 
 
 
 
x 
 
 
 
x 
Concomitant medications 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Adverse events (AEs) 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Safety laboratory tests 
 
x 
 
 
 
 
 
x 
 
 
 
x 
Urine pregnancy test (UPT) for 
postmenarchal females 
 
x 
x 
x 
 
x 
x 
x 
x 
x 
x 
x 
Vital signs (blood pressure, pulse rate, 
respiratory rate)a 
x 
x 
x 
x 
 
x 
x 
x 
x 
x 
x 
x 
LTR assessment 
 
x 
x 
x 
 
x 
x 
x 
x 
x 
x 
x 
PK subgroup sampling b 
 
 
x 
x 
xb 
 
 
 
 
 
 
 
Photography of the TGTc 
x 
 
 
 
 
 
 
x 
 
 
 
x 
Weigh and dispense new study drug kit 
 
x 
x 
x 
 
x 
x 
x 
x 
x 
 
 
Study drug collection/weighing/accountability 
 
 
x 
x 
 
x 
x 
x 
x 
x 
x 
 
Supervise study drug self-administrationd 
 
x 
x 
x 
 
x 
x 
x 
x 
x 
 
 
Diary review and training/re-training 
 
x 
x 
x 
 
x 
x 
x 
x 
x 
x 
 
Schedule next visit 
x 
x 
x 
x 
 
x 
x 
x 
x 
x 
x 
 
ET, early termination; KOH, potassium hydroxide; PK, pharmacokinetic; LTR, local tolerability reaction 
a Vital signs conducted after subject is sitting or supine for at least 5 minutes. 
b For subjects in the PK subgroup, at Visit 3 (Day 15) a pre-dose sample will be collected and Visit 4 (Day 29), PK samples will be collected prior 
to dosing, as well as 4, 6, and 8 hours post-dose. At Visit 4a (Day 30), the 24-hour post-dose sample is collected prior to dosing. 
c Perform photography procedures before mycology procedures. 
d Application occurs at the site on visit days. For PK subgroup participants, the application for Visit 3 (Day 15) and Visit 4a (Day 30) is to occur 
after the subject has had their PK specimen drawn. 


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7.2.2 
Visit 1: Screening Visit (up to 70 Days Prior to Day 1) 
Subjects who have taken prohibited medication(s) within the eligibility criteria exclusionary 
timeframe will fail Screening, but they may rescreen after the required timeframe has been 
met. If necessary, the Screening procedures may be completed over 70 days. The following 
procedures will be performed at the Screening visit (Visit 1): 
• Obtain informed consent prior to any study-specific evaluations or procedures 
• Obtain subject number  
• Collect demographic information 
• Verify subject eligibility (inclusion/exclusion criteria) 
• Identify the TGT (to be confirmed at Baseline) 
• Clinical assessment of the TGT 
• Collect medical and medication history including all medication taken within 30 days 
prior to Screening and any prior use of systemic antifungal agents for treatment of 
onychomycosis or with known activity against dermatophytes within 24 weeks prior to 
Screening 
• Review and record new AEs occurring after signed ICF  
• Obtain vital signs (blood pressure, pulse rate, respiratory rate) after subject is in sitting or 
supine position for at least 5 minutes 
• Take digital photographs (photography procedure is to occur before mycology procedure); 
o Take the first set of photographs after trimming the TGT to within 1 mm distal 
of the hyponychium or distal groove 
o Mark the TGT with indelible ink pen (distal groove and the proximal mycotic 
border) 
o  Take the second set of photographs after marking the TGT 
• Obtain sample for KOH wet mount and fungal culture (Do not perform mycology 
sampling until after photography procedure is completed) 
o A local KOH wet mount is an optional procedure, and only the central 
mycology laboratory reading will be used for analysis and eligibility 
determination. 


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o Trim toenails as needed: the unattached nail plate of the subject’s TGT can be 
trimmed as far as needed to obtain an adequate sample of subungual debris.  
• Schedule next visit 
7.2.3 
Treatment Period (Visit 2 through Visit 10) 
The treatment period consists of Visit 2 (Baseline visit) through Visit 10 (Week 48). An 
unscheduled visit may occur for follow-up of an AE, LTR, abnormal laboratory evaluation, 
replacement of lost study drug, or for any reason that, in the judgment of the Investigator, is 
required to ensure patient safety or study integrity. Procedures relevant to the reason for the 
unscheduled visit (i.e., repeat laboratory test) should be performed. At treatment period visits, 
the following assessments will be performed as indicated below. 
7.2.3.1 
Visit 2: Baseline Visit (Day 1) 
• Verify subject eligibility  
• Confirm medical and medication history 
• Collect concomitant medication information 
• Review and record AEs 
• Assess for LTR and grade the severity using the scales provided in Table 4 
• Perform an abbreviated physical examination (prior to enrolling and drug dispense)  
• Assess and confirm the identity of the TGT; if both great toenails are eligible, select the 
one with the greatest involvement 
• Assess other toenails (includes assessment of the presence of and visual estimate of the 
extent of the total toenail area that shows onycholysis and subungual hyperkeratosis) to 
determine which toenails (other than the TGT) will be treated during the study. For all 
subjects, assess and document other toenail involvement. However, ALL 10 toenails, 
affected and unaffected, including up to 2 mm of the surrounding skin, will receive study 
drug application for 28 days (± specified window) for the subjects in the PK subgroup. 
• Obtain vital signs (blood pressure, pulse rate, respiratory rate) after subject is in sitting or 
supine position for at least 5 minutes 
• Draw blood for safety laboratory tests  
• Conduct UPT (postmenarchal females only) 
• Dispense study drug after weighing and recording the weight of the bottles with caps  


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• Instruct the subject on drug storage and administration. Supervise self-administration of 
study drug and re-instruct as needed. Application occurs at the site on visit days.  
• Perform diary training 
• Schedule next visit. Instruct subject to save all study drug bottles and caps and bring all 
used and unused study drug bottles and caps to each visit. Remind the subject not to apply 
study drug or use products on the feet or nails on the day of clinic visits. 
7.2.3.2 
Visit 3 (Week 2) Through Visit 10 (Week 48)  
• Collect concomitant medication information 
• Review and record AEs 
• Obtain vital signs (blood pressure, pulse rate, respiratory rate) after subject is in sitting or 
supine position for at least 5 minutes 
• Week 24 only: draw blood for safety laboratory tests 
• Week 24 only: Clinical assessment of the TGT 
• Week 24 only: take digital photographs (photography procedure is to occur before 
mycology procedure); 
o Take the first set of photographs after trimming the TGT to within 1 mm distal 
of the hyponychium or distal groove 
o Mark the TGT with indelible ink pen (distal groove and the proximal mycotic 
border)  
o Take the second set of photographs after marking the TGT 
• Week 24 only: obtain sample for KOH wet mount and fungal culture (Do not perform 
mycology sampling until after photography procedure is completed) 
• Conduct UPT (postmenarchal females only) 
• Assess for LTR and grade the severity using the scales provided in Table 4 
• Trim toenails as needed 
• Collect study drug, perform accountability, and record the weight of the returned bottles 
with caps 


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• Dispense new study drug kit after weighing and recording the weight of the bottles with 
caps 
• Only for subjects in the maximal use subgroup at Visit 3, collect a pre-dose PK sample. At 
Visit 4 (Day 29) and Visit 4a (Day 30): collect PK samples prior to dosing, as well as 4, 6, 
8, and 24 hours post-dose. NOTE: 24 hours post-dose occurs at Visit 4a (Day 30) and 
occurs prior to application that day. 
• Supervise self-administration of study drug and re-instruct as needed. Application occurs 
at the site on visit days. For PK subgroup participants, the application for Visit 4a (Day 
30) occurs after the subject has had their 24-hour PK specimen drawn. 
• Review diary and re-train as needed  
• Schedule next visit. Instruct subject to save all study drug bottles and caps and bring all 
used and unused study drug bottles and caps to each visit. Remind the subject not to apply 
study drug or use products on the feet or nails on the day of clinic visits. 
7.2.4 
Visit 11 (Week 52) or Early Termination 
• Collect concomitant medication information 
• Review and record AEs 
• Clinical assessment of the TGT 
• Take digital photographs (photography procedure is to occur before mycology procedure); 
o Take the first set of photographs after trimming the TGT to within 1 mm distal 
of the hyponychium or distal groove 
o Mark the TGT with indelible ink pen (distal groove and the proximal mycotic 
border)  
o Take the second set of photographs after marking the TGT 
• Obtain sample for KOH wet mount and fungal culture (Do not perform mycology 
sampling until after photography procedure is completed)  
• Obtain vital signs (blood pressure, pulse rate, respiratory rate) after subject is in sitting or 
supine position for at least 5 minutes 
• Draw blood for safety laboratory tests 
• Conduct UPT (postmenarchal females only) 


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• Assess for LTR and grade the severity using the scales provided in Table 4 
• Collect study drug, perform accountability, and weigh the bottles and caps returned, if 
applicable 
7.3 
Explain Study and Obtain Signed Informed Consent Form 
At the Screening Visit, the Investigator or qualified designee will explain the study to the 
subject and/or parents/guardians, answer all of his/her/their questions, and obtain a signed 
ICF/assent before performing any study-related procedure. A copy of the signed ICF/assent 
will be given to the subject and/or parents/guardians. 
7.4 
Demographics 
The subjects' demographics collected at Screening on the CRF will include date of birth (age), 
sex, ethnicity, and race. 
7.5 
Review Inclusion/Exclusion Criteria 
The inclusion and exclusion criteria will be reviewed at Screening by the Investigator or 
qualified designee to ensure that the subject qualifies for the study. The inclusion and 
exclusion criteria will be reviewed again at Baseline to confirm that the subject still meets the 
criteria to participate in the study. 
7.6 
Medical History and Medication History 
A medical history and medication history will be obtained by the Investigator or qualified 
designee at Screening and confirmed at the Baseline visit. Subject history should include 
significant medical information, as well as history of and prior treatment for onychomycosis 
and any symptoms attributed to onychomycosis. Review of all appropriate medication 
washout times will be discussed with the subject.  
7.7 
Concomitant Medications 
At all visits, concomitant medication information will be collected. 
7.8 
Physical Examinations 
An abbreviated physical examination will be performed by the Investigator or a qualified 
designee at Baseline prior to enrollment (and drug dispensing). Abnormal physical 
examination findings at Baseline will be recorded on the medical history module of the CRF. 
7.9 
Identify Target Great Toenail (TGT) and Other Toenails 
At Screening, the Investigator will perform a visual assessment of the severity of nail 
involvement of the subject's great toenails to determine if Screening should proceed.  


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The TGT is defined as the most involved great toenail that meets eligibility criteria. The 
chosen great toenail (left or right) will be recorded on the CRF.  
At Baseline (Day 1) the Investigator will assess all other toenails for the presence of 
onychomycosis to determine what other toenails will be treated throughout the study. 
7.10 
Toenail Trimming Procedure 
At Screening, Week 24, and Week 52: 
Trimming procedure for photography: trim the TGT to within 1 mm distal of the 
hyponychium or distal groove. The photography procedure is to be completed prior to 
mycology trimming and sampling procedure. 
Trimming procedure for mycology sampling: after the photography procedure is complete, the 
TGT may be further trimmed for the purposes of mycology sampling. The unattached nail 
plate of the subject’s TGT can be trimmed as far as needed to obtain an adequate sample of 
subungual debris.  
At all other visits, the subject's toenails can be trimmed, as needed, by the Investigator or a 
qualified designee.   
7.11 
KOH Mount and Central Fungal Culture  
Mycology sampling is to occur after all photography procedures for that visit have been 
completed. At Screening, the Investigator may perform a KOH wet mount at the study site to 
confirm the clinical diagnosis of onychomycosis prior to obtaining a sample for the central 
mycology laboratory; however, care must be taken to obtain sufficient subungual debris for 
the analysis at the central laboratory. The local KOH wet mount is an optional procedure and 
only the central mycology laboratory reading will be used for analysis and eligibility 
determination. If both great toenails are potentially eligible by clinical criteria, then both great 
toenails can be sampled at Screening. A subject that fails mycology criteria may be resampled 
(see resample criteria in Section 5.0).  
A sample of subungual debris will be obtained again at Week 24 and Week 52/ET. 
Specimen collection and sample shipment instructions will be provided in the laboratory 
manual. 
7.12 
Study Drug Dispensing 
Dispensing occurs at Visits 2-9. Upon opening the study drug kit (carton), study site personnel 
should verify that each bottle in a given kit is tightly capped and contains study medication. 
Any information required on the bottle label (i.e., subject identifier) should be completed 


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before dispensing. The number of bottles contained in each medication kit will be verified and 
the bottles weighed with cap on before a kit is dispensed to a subject. 
7.13 
Study Drug Self-Administration 
During the Baseline visit (Day 1), subjects will be instructed on how to apply the study 
medication and will self-administer study drug application at each dispense visit under the 
supervision of site personnel. The subject will be retrained as needed. The subject will be 
instructed to self-administer study drug topically, once daily, on all affected toenails (TGT 
and other toenails identified by the Investigator). Application occurs at the site on visit days. 
For PK subgroup participants, the application for Visit 4a (Day 30) is to occur after the 
subject has had their 24-hour PK specimen drawn. Subjects should continue dosing all 
toenails that were identified as affected at Baseline throughout the study even if some of the 
affected toenails become clear. 
Subjects participating in the PK maximal use subgroup will initially be instructed to apply 
study medication to all 10 toenails, including up to 2 mm of the surrounding skin, once daily 
for 28 days (±7 days). Additionally, these subjects will receive a minimum dose of each 
treatment defined as follows: 
• Great toenails: two (2) drops each 
• All other toenails: one (1) drop each 
After PK assessments are complete, the subject will be instructed to apply study medication to 
all affected toenails once daily for the remainder of the study. 
7.14 
Dosing Modifications 
If dosing modification is needed due to local irritation, or any other reasons, the Investigator 
may implement a temporary interruption of study drug to one or more toes as applicable.   
7.15 
Study Drug Collection  
Subjects will be instructed to save all used, unused, and empty study drug bottles and caps and 
return them at each return visit. The subject will be reminded of these instructions at each 
visit. The Investigator or a qualified designee will collect study drug and perform 
accountability (bottle count and weighing the bottles with cap on). 
7.16 
Dosing Diary 
Subjects will start a diary at Baseline (Day 1) and will complete the diary as instructed. The 
diary will be reviewed at each study visit in order to assess compliance with treatment.  


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7.17 
Digital Photography 
At the Screening Visit, Week 24, and Week 52/ET, digital photographs of the TGT will be 
obtained before performing mycology sampling procedures: 
o Take the first set of photographs after trimming the TGT to within 1 mm distal 
of the hyponychium or distal groove 
o Mark the TGT with indelible ink pen (outline the distal groove and the 
proximal mycotic border)  
o Take the second set of photographs after marking the TGT 
Photography will occur at selected sites. Photographs will be utilized for purposes of 
publications. All photos will be sent to the central photography laboratory and photographic 
equipment will be provided to all sites by the central photography laboratory for use 
throughout the trial. The Investigator and qualified designees will be trained on the use of the 
camera and the appropriate lighting and positioning of the toe. Details on the digital 
photography procedure will be provided in a separate manual. 
 
8.0 
PHARMACOKINETIC ASSESSMENT  
8.1 
Collection of Blood Samples for Pharmacokinetic Assessment 
Blood samples for the determination of plasma levels of tavaborole and PK parameters will be 
obtained under maximal use conditions (once daily application to all 10 toenails, including up 
to 2 mm of the surrounding skin) from the subgroup of subjects ages 12 to 16 years and 11 
months to achieve at least 16 evaluable subjects. Subjects in the maximal use subgroup will 
apply the study drug on all 10 toenails, including up to 2 mm of the surrounding skin, for 
28 days ±7 days. At Visit 3 (Day 15) a pre-dose PK sample will be collected to assess steady 
state trough level. At Visit 4 (Day 29), the study drug application will be done at the study 
site, and PK samples will be collected prior to dosing, as well as 4, 6, and 8 hours post-dose. 
At Visit 4a (Day 30) the sample will be collected 24 hours post-dose and prior to the 
application for that day. 
Approximately 24 mL of blood (6 samples, 4 mL each) will be taken from each of the 
16 subjects for the PK determination. 
8.2 
Specimen Assays 
Each blood sample will be labeled appropriately and the actual time and date of each sample 
collection will be entered in the CRF. Procedures for PK sample collection, processing, 
handling, storage, and shipping will be provided in a separate PK laboratory manual.  
 


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9.0 
EFFICACY ASSESSMENT 
The efficacy assessments are intended to assess compliance with treatment for the purposes of 
the safety assessment. 
9.1 
Clinical Assessment of the Target Toenail Involvement 
Clinical involvement of the TGT will be assessed at Screening and Weeks 24 and 52/ET using 
the following definitions of disease severity: 
• Completely CN: no clinical evidence of onychomycosis as evidenced by normal toenail 
plate, no onycholysis, and no subungual hyperkeratosis 
• Almost CN: no more than minimal evidence of onychomycosis as evidenced by toenail 
plate dystrophic or discolored ≤ 5% of the distal aspect, with minimally evident 
onycholysis and subungual hyperkeratosis  
• Mild onychomycosis: onychomycosis as evidenced by toenail plate dystrophic or 
discolored > 5% to ≤ 20% of the distal aspect, with clearly evident onycholysis and 
subungual hyperkeratosis  
• Moderate onychomycosis: onychomycosis as evidenced by toenail plate dystrophic or 
discolored > 20% to ≤ 50% of the distal aspect, with clearly evident onycholysis and 
subungual hyperkeratosis 
• Severe onychomycosis: onychomycosis as evidenced by a toenail plate dystrophic or 
discolored > 50% of the distal aspect, with pronounced onycholysis and subungual 
hyperkeratosis 
9.2 
Primary Efficacy Endpoint 
The primary efficacy endpoint for this study is complete cure rate (no clinical evidence of 
onychomycosis as evidenced by a normal toenail plate, no onycholysis, and no subungual 
hyperkeratosis and negative KOH wet mount and fungal culture) of the TGT at Week 52.  
Treatment Outcomes are defined as follows: 
• Negative mycology: negative KOH wet mount and negative fungal culture 
• Complete cure: completely CN and negative mycology 
• Almost complete cure: almost CN and negative mycology 
• Treatment success: completely CN or almost CN 


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The efficacy assessments are intended to assess compliance with treatment for the purposes of 
the safety assessment. 
9.3 
Secondary Efficacy Endpoints 
The secondary efficacy endpoints include the following: 
• Complete or Almost complete cure of the TGT at Weeks 24 and 52 defined as (no clinical 
evidence of onychomycosis as evidenced by a normal toenail plate, no onycholysis, and 
no subungual hyperkeratosis) or almost CN (no more than minimal evidence of 
onychomycosis as evidenced by a toenail plate dystrophic or discolored over ≤ 5% of the 
distal aspect, with minimally evident onycholysis and subungual hyperkeratosis) of the 
TGT with negative mycology at Week 52;  
• Treatment success (Clinical Efficacy rate) of the TGT at Weeks 24 and 52 defined as 
completely CN or almost CN ; 
• Negative mycology (Mycological Cure rate) of the TGT at Weeks 24 and 52 defined as 
negative KOH wet mount and negative fungal culture  
• Negative fungal culture of the TGT at Weeks 24 and 52 
 
10.0 SAFETY ASSESSMENT 
Safety assessments will be performed according to the schedule of events shown in  
Table 3. Safety variables for this study include the frequency and severity of LTRs, frequency 
and severity of treatment-emergent adverse events (TEAEs) and SAEs (see Section 11.0), and 
abnormalities in clinical laboratory parameters and vital signs. Adverse events occurring from 
the informed consent signature up to the completion of the study or the early termination visit, 
as applicable, will be recorded. 
10.1 
Local Tolerability Reactions (LTRs) 
Safety evaluations will include LTRs (burning/stinging, induration/edema, oozing and 
crusting, pruritus, erythema, and scaling), as reported by the subject and/or evaluated by the 
Investigator at Baseline and each study visit thereafter. LTRs will be documented on the CRF 
specifically designed to capture LTR information (local tolerability signs CRF) and not on the 
AE CRF. LTRs that require treatment (eg, with a concomitant medication or drug interruption 
or drug discontinuation) are an exception to this guideline; these LTRs should be documented 
on both the local tolerability signs CRF and on the AE CRF. 
The grading of LTRs is presented in Table 4. 


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Table 4: 
Grading of Local Tolerability Reactions (LTRs) 
Grade  
Guideline 
Burning/Stinging 
0 - None  
No stinging/burning 
1 - Mild  
Slight warm, tingling sensation; not really bothersome 
2 - Moderate  
Definite warm; tingling/stinging sensation that is somewhat bothersome 
3 - Severe  
Hot, tingling/stinging sensation that has caused definite discomfort 
Induration/Edema 
0 - None  
No elevation 
1 - Mild  
Barely perceptible elevation 
2 - Moderate  
Clearly perceptible elevation but not extensive  
3 - Severe  
Marked and extensive elevation 
Oozing and Crusting 
0 - None  
Absent  
1 - Mild  
Faint signs of oozing 
2 - Moderate  
Definite oozing or crust but with 5 or fewer sites per area 
3 - Severe  
Marked and extensive oozing and crusting 
Pruritus  
0 - None  
No pruritus 
1 - Mild  
Occasional, slight itching/scratching 
2 - Moderate  
Constant or intermittent itching/scratching which is not disturbing sleep 
3 - Severe  
Severe bothersome itching/scratching which is disturbing sleep 
Erythema 
0 - None  
No redness present 
1 - Mild  
Faintly detectable erythema; very light pink 
2 - Moderate  
Dull red, clearly distinguishable 
3 - Severe  
Deep/dark red 
Scaling 
0 - None  
No scaling  
1 - Mild  
Barely perceptible shedding, noticeable only on light scratching or rubbing 
2 - Moderate  
Obvious but not profuse scaling 
3 - Severe  
Heavy scale production 
 
10.2 
Vital Signs 
Vital signs will be measured at each study visit after the subject has been sitting or supine for 
at least 5 minutes. Vital sign measurements taken will be blood pressure, pulse rate, and 
respiratory rate.  


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10.3 
Clinical Safety Laboratory Parameters and Pregnancy Tests 
Clinical safety laboratory parameters will be assessed at Baseline, Week 24, and Week 52/ET, 
if applicable. Laboratory tests may be repeated more often if clinically indicated. Blood 
samples may be taken with the subject in a non-fasting state.  
All out-of-normal range laboratory values must be evaluated by the Investigator or 
subinvestigator as to whether they are clinically significant (i.e., require medical intervention 
or have clinical signs and/or symptoms). Abnormal clinical laboratory parameters that are 
considered clinically significant by the Investigator will be recorded on the AE CRF except 
Baseline visit. Clinically significant laboratory abnormalities noted from the Baseline visit 
will be recorded as medical history. The AE should be reported as a clinical diagnosis when 
possible. Laboratory tests will be performed by the central laboratory and are presented in 
Table 5.  
UPTs will be performed at each scheduled visit on postmenarchal females starting at Baseline. 
If a UPT result is positive, the subject must be discontinued (see Section 11.8 for details).  
The Sponsor will designate a central laboratory for safety laboratory tests. All samples for 
clinical laboratory tests must be managed through the central laboratory designated by the 
Sponsor. Sample management (collection, storage, shipping, etc.) will be done according to 
the central laboratory instructions. 
Table 5: 
Safety Laboratory Parameters 
Hematology 
Chemistry 
Hemoglobin 
Hematocrit 
Red blood cell count 
Platelet count 
White blood cell count 
Neutrophils  
Eosinophils  
Monocytes  
Basophils  
Lymphocytes  
Blood urea nitrogen 
Creatinine 
Glucose (nonfasting) 
Sodium, Potassium 
Aspartate aminotransferase, alanine aminotransferase 
Total bilirubin 
Alkaline phosphatase 
Albumin 
Total protein 
Urine pregnancy test (all scheduled visits starting at Baseline) 
 
11.0 ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
11.1 
Definition of Adverse Event 
An AE is any untoward medical occurrence or unintended change from the subject’s Baseline 
(pretreatment) condition, including intercurrent illness, that occurs during a clinical trial after 
treatment has started, whether or not it is considered related to study treatment. An AE can 


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therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease temporally associated with the use of an investigational product. 
An AE is meant to include events that are either new or represent detectable exacerbations of 
preexisting conditions, and does not imply any judgment about causality.  
AEs will be assessed at each visit. Any AE occurring on or after the date of the dose of study 
drug administration on Day 1 and up to and including the completion/termination date will be 
counted as treatment-emergent. 
Adverse experiences may include but are not limited to subjective or objective symptoms 
spontaneously reported by the subject and/or observed by the Investigator or medical staff, 
including laboratory abnormalities of clinical significance. Preexisting conditions noted as 
part of the medical history at Screening must be reported on the appropriate medical history 
CRF page. Stable, ongoing conditions present at Screening should not be recorded as AEs if 
the severity at Screening remains unchanged during the study. However, preexisting 
conditions for which an increase in severity is observed after Screening must be recorded as 
AEs.  
Any AE a subject experiences from signing the ICF up to the completion of final study 
procedures will be reported as described and recorded on the CRF as follows:  
• LTRs: LTRs assessed at each visit are to be documented on the CRF specifically designed 
to capture LTR information (local tolerability symptoms CRF) and not on the AE CRF. 
An exception to this is that LTRs requiring treatment (eg, with a concomitant medication 
or drug interruption or drug discontinuation) should be documented on both the local 
tolerability symptoms CRF and on the AE CRF. 
• Life-threatening experience: An AE is considered "life-threatening" if, in the view of 
either the Investigator or Sponsor, its occurrence places the patient or subject at immediate 
risk of death. It does not include an AE or suspected adverse reaction that, had it occurred 
in a more severe form, might have caused death. 
• Persistent or significant disability/incapacity: Any adverse experience that, in the 
Investigator’s opinion, results in a substantial disruption of a person’s ability to conduct 
normal life functions. 


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• Unexpected AE: An AE is considered “unexpected” if it is not listed in the IB or is not 
listed at the specificity or severity that has been observed. For example, under this 
definition, hepatic necrosis would be unexpected (by virtue of greater severity) if the IB 
referred only to elevated hepatic enzymes or hepatitis. Similarly, cerebral 
thromboembolism and cerebral vasculitis would be unexpected (by virtue of greater 
specificity) if the IB listed only cerebral vascular accidents. "Unexpected," as used in this 
definition, also refers to AEs or suspected adverse reactions that are mentioned in the IB 
as occurring with a class of drugs or as anticipated from the pharmacological properties of 
the drug, but are not specifically mentioned as occurring with the particular drug under 
investigation. 
• Associated with the use of the drug: A reasonable possibility exists that the experience 
may have been caused by the drug. 
11.2 
Relationship to Study Drug 
The Investigator will assess the causal relation, if any, between the AE and the study drug 
using the following definitions: 
• Definite: A reaction or event that follows a reasonable temporal sequence from 
administration of study drug or in which the drug level has been established in body fluids 
or tissues, that follows a known or expected response pattern to the suspected study drug, 
and that is confirmed by improvement on stopping or reducing the dosage of study drug 
and reappearance of the reaction on rechallenge. 
• Probable: A reaction that follows a reasonable temporal sequence from administration of 
study drug, that follows a known or expected response pattern to the suspected study drug, 
and that could not be reasonably explained by the known characteristics of that subject’s 
clinical state. 
• Possible: A reaction that follows a reasonable temporal sequence from administration of 
study drug, that follows a known or expected response pattern to the suspected study drug, 
but that could readily have been produced by a number of other factors. 
• Unlikely: A reaction that does not follow a reasonable temporal sequence from 
administration of study drug. However, causality from the study drug cannot be ruled out. 
• Not related: A reaction for which sufficient data exist to indicate that the etiology is 
unrelated to the study drug. 
11.3 
Severity 
The assessment of severity is subjective, and the Investigator should use medical judgment to 
compare the reported adverse experience to similar type events observed in clinical practice. 
The guidelines for severity assessment are as follows: 


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• Mild: Symptom(s) barely noticeable to the subject or does not make the subject 
uncomfortable. The adverse experience does not influence performance or functioning. 
Prescription drugs are not ordinarily needed for relief of symptom(s). 
• Moderate: Symptom(s) of a sufficient severity to make the subject uncomfortable. 
Performance of daily activities is affected. Severity may lead to temporary cessation of 
treatment with the study drug. Treatment of symptom(s) may be needed. 
• Severe: Symptom(s) of a sufficient severity to cause the subject severe discomfort. 
Severity may lead to cessation of treatment with the study drug. Treatment for symptom(s) 
may be given.  
Grading for LTRs is defined in Table 4. 
11.4 
Outcome 
The outcome of an AE will be assessed as follows: 
• Recovered / Resolved 
• Not Recovered / Not Resolved 
• Recovered / Resolved with sequelae 
• Fatal 
• Unknown 
11.5 
Serious Adverse Event 
An SAE is defined as any untoward medical occurrence that at any dose: 
• Results in death 
• Is life-threatening 
• Requires or prolongs in-patient hospitalization 
• Results in persistent or significant disability/incapacity, or 
• Results in a congenital anomaly 
Medical and scientific judgment should be exercised in determining whether an event that 
does not meet any of the above criteria is an important medical event. Important medical 
events that may not result in death, be life threatening, or require hospitalization may be 
considered serious when, based upon appropriate medical judgment, they may jeopardize the 


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All AEs will be followed through the end of the study and will be noted as “ongoing” if not 
resolved at the last study visit. All SAEs will be followed to resolution or stabilization, as 
determined by the Investigator. 
The Investigator must document his/her efforts to obtain all follow-up information regarding 
the SAE requested by the Anacor Pharmacovigilance Group. 
11.7 
Laboratory Test Abnormalities 
The Investigator will review all safety laboratory results. All out-of-normal range laboratory 
values must be evaluated for clinical significance, and clinically significant abnormalities 
must be reported as AEs except from Baseline visit abnormalities which will be recorded as 
medical history. Clinically significant laboratory abnormalities are defined as laboratory 
abnormalities that have clinical manifestations or require medical intervention. Investigators 
should report clinical diagnoses as AEs rather than list individual laboratory test results when 
possible. 
11.8 
Pregnancy 
In the event that a subject becomes pregnant during study treatment or follow-up, the Anacor 
Pharmacovigilance Group and medical monitor must be notified immediately upon the 
Investigator becoming aware of the pregnancy. The subject will be discontinued from study 
drug. The outcome of the pregnancy will be collected by the safety group. 
 
12.0 STATISTICAL PLAN  
All statistical processing will be performed using SAS® unless otherwise stated.  
Descriptive statistics will include sample size, mean, median, standard deviation, minimum, and 
maximum continuous variables. Categorical variables will be tabulated with frequency counts 
and percentages. 
12.1 
Sample Size 
The study will enroll subjects ages 6 to 16 years and 11 months with at least 40 subjects ages 
12 to 16 years and 11 months. All subjects will be assigned to receive active treatment with 
KERYDIN (tavaborole) topical solution, 5%. A PK subgroup of at least 16 evaluable subjects 
ages 12 to 16 years and 11 months will be studied under maximal use conditions. 


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12.2 
Statistical Analysis 
12.2.1 
Study Populations 
The following populations will be used: 
• Safety population: all subjects who receive at least one confirmed dose of study drug and 
have at least one post-baseline safety assessment. 
• PK population: all subjects from the maximal use subgroup with available PK data. 
12.2.2 
Background and Demographic Characteristics 
Subject demographic (age, sex, race, and ethnicity) and Baseline characteristics will be 
summarized for the Safety and PK populations. Age will be represented as both a continuous 
and as a categorical variable.  
12.2.3 
Efficacy 
The primary and secondary efficacy endpoints including Complete cure rate, Complete or 
Almost complete cure rate, Treatment success (Clinical Efficacy), Mycological Cure rate, and 
negative fungal culture of the TGT at Week 24 and Week 52 will be summarized for the 
safety population with descriptive statistics including sample size, frequency count, and 
percentage. 
The efficacy assessments are intended to assess compliance with treatment for the purposes of 
the safety assessment.  
12.2.4 
Pharmacokinetics 
Pharmacokinetics will be tabulated for each collection day using descriptive statistics. Mean 
plasma concentrations will be plotted through time using both linear and semi-logarithmic 
scales. Plasma concentrations will also be plotted through time for each subject, using both 
linear and semi-logarithmic scales. Concentrations below the limit of quantitation will be set 
to zero for descriptive statistics.  
The following PK parameters will be calculated for Day 15 (steady state trough level only) 
and Day 29 [steady state (±specified window)]: 
• Cmax:  
maximum observed plasma concentration 
• Tmax:  
time to maximum observed plasma concentration 
• AUC0-24:  area under the plasma concentration-time curve from Hour 0 to Hour 24, 
calculated using the linear trapezoidal rule 


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• AUC0-∞:  area under the plasma concentration-time curve extrapolated to infinity 
• λZ:  
elimination rate constant  
• t1/2:  
elimination half-life 
PK parameters will be calculated using actual sampling times. 
12.2.5 
Safety 
No imputation will be made for missing safety data. 
12.2.5.1 
Extent of Exposure 
The extent of exposure to study drug will be summarized by the total number of days of 
dosing, total number of applications, and total amount of study drug applied. 
12.2.5.2 
Local Tolerability and Adverse Events 
LTRs (burning/stinging, induration/edema, oozing and crusting, pruritus, erythema, and 
scaling) will be evaluated by frequency tables for each visit. Additionally, LTRs will be 
summarized by descriptive statistics (mean, standard deviation, median, and minimum and 
maximum). 
All AEs occurring during the study will be recorded and classified on the basis of Medical 
Dictionary for Regulatory Activities terminology. TEAEs are those with an onset on or after 
the time of the first study drug administration. For the safety population, all reported TEAEs 
will be summarized by system organ class (SOC), preferred term, severity, relationship to 
study drug, and seriousness. When summarizing TEAEs by causality and severity, each 
subject will be counted only once within an SOC or a preferred term using the event with the 
closest relationship to study drug and the greatest severity within each classification. 
SAEs will be summarized by severity and relationship to study drug, and individual SAEs will 
be listed by subject. A list of subjects who prematurely discontinued from the study due to an 
AE will also be provided. 
All information pertaining to AEs noted during the study will be listed by subject, detailing 
the verbatim term reported by the Investigator, preferred term, SOC, onset date, resolution 
date, maximum severity, seriousness, action taken regarding study drug, corrective treatment, 
outcome, and drug relationship. The event onset will also be shown relative (in number of 
days) to date of first administration of study drug.  
12.2.5.3 
Laboratory Values and Vital Signs 
Changes from Baseline in vital signs and safety laboratory values will be summarized at each 
follow-up evaluation using descriptive statistics or frequency tables as applicable. 


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Additionally, changes from Baseline in safety laboratory values will be summarized using 
shift tables according to normal ranges. The last laboratory evaluation before the first dose of 
study drug will be used as Baseline for all laboratory analyses. 
12.2.5.4 
Concomitant Medications 
Concomitant medications will be coded using the World Health Organization Drug Dictionary 
Enhanced. All medications will be presented in the data listings. A table of concomitant 
medications by percentage of subjects who used them will also be provided. No statistical 
tests will be performed. 
 
13.0 ETHICAL CONSIDERATIONS 
13.1 
Ethical Conduct of the Study 
This protocol was designed and will be conducted, recorded, and reported in compliance with 
the principles of GCP (as defined in the ICH E6 Guideline for GCP). The Investigator and the 
site personnel are responsible for conducting this study in accordance with US Code of 
Federal Regulations, GCP, the ethical principles that have their origin in the Declaration of 
Helsinki, and all other applicable laws and regulations. 
13.2 
Subject Information, Informed Consent, and Assent 
The Investigator and designated site staff who will perform the consent/assent process are 
responsible for knowing country-specific regulations and other local requirements with regard 
to child assent and to ensure that the assent process is conducted in accordance with those 
requirements. 
An initial informed consent (for parent/guardian of adolescent subjects) and assent form (for 
adolescent subjects, as applicable) will be provided to the Investigator to prepare the ICF and 
assent documents to be used at the Investigator’s site. Updates to the informed consent 
template must be communicated to the Sponsor or designee prior to IRB/EC approval. Written 
informed consent and assent, in accordance with local clinical investigation regulations and 
approved by the IRB/EC, must be obtained prior to participation in the study. The Investigator 
will not undertake any measures specifically required for the clinical study unless and until 
valid consent and assent have been obtained. 
Information must be given both in oral and written form. For adolescent subjects, written 
informed consent and assent documents will be given to the parent/guardian and each 
applicable subject, respectively. Informed consent documents will contain all the elements 
required by the ICH E6 Guideline for GCP and any additional elements required by local 
regulations. The information provided in the informed consent will be in a language 
understandable to the adult subjects or parent/guardian of adolescent subjects and may not 
include any language that appears to waive any of the parent/guardian’s or subject’s legal 


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rights or appears to release the Investigator, the Sponsor, or the institution from liability or 
negligence. 
The Investigator will provide the parent/guardian and/or prospective subject sufficient time to 
consider whether to participate. The Investigator will explain to the subject and 
parent/guardian, as applicable, that withdrawal from the study is possible at any time without 
detriment to care. The ICF and assent must include acknowledgement that medical records 
and medical data derived from the study may be forwarded to the Sponsor or to the 
responsible authorities or federal authorities. 
At the first visit, and prior to initiation of any study-related procedures, the parent/guardian 
(or the subject’s legally authorized representative) of adolescent subjects will be asked to give 
written informed consent, and adolescent subjects will be asked to give assent (and written 
informed consent at the time they turn 18 years of age during the study), after having been 
informed about the nature and purpose of the study, participation/discontinuation conditions, 
and risks and benefits. If the parent/guardian is unable to provide written informed consent, 
the subject’s legally authorized representative may provide written consent as allowed by 
institution-specific guidelines. The informed consent and assent documents, as applicable, 
must be signed and dated by the parent/guardian (or the subject’s legally authorized 
representative) and the subject, prior to study participation. Copies of the signed informed 
consent and assent documents must be provided to the parent/guardian (or the subject’s 
legally authorized representative) and/or the subject.  
If the parent/guardian and/or the subject is unable to read, oral presentation and explanation of 
the ICF and/or assent must be provided to the parent/guardian and/or subject in the presence 
of an impartial witness or legally authorized representative. After the parent/guardian and/or 
subject provide oral and if capable written/dated informed consent and/or assent, the witness 
should sign and date the ICF and/or assent in accordance with the instructions of the relevant 
IRB/EC. By signing the ICF and/or assent, the witness attests that the written information was 
accurately explained to, and apparently understood by, the parent/guardian and/or subject, and 
that informed consent and/or assent was freely given by the parent/guardian and/or subject. 
Original signed/dated consent and assent forms (if applicable) must remain in the subject’s 
study file and be available for verification by the Sponsor or their designees at any time. 
13.2.1 
Child Assent Considerations 
The IRB/EC approval letter must clearly document the IRB/EC’s assessment of risk in 
accordance with 21 CFR 50.51–50.54, Subpart D. The ICF should reflect the correct number 
of signature lines for the parent(s)/guardian(s) in accordance with the IRB/EC’s risk 
assessment of the proposed research (see 21 CFR 50.55). 
The IRBs/ECs are required to determine if child assents are appropriate for all studies that 
include pediatric subjects. The IRB/ECs may opt to waive assent if the subjects are not 


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capable of understanding (i.e., based on level of intellectual development or maturity) or if the 
study is in the best interest of the subject (i.e., strong possibility of benefit and no other 
alternatives are available). If an IRB/EC chooses to waive assent, this must be documented in 
the IRB/EC approval letter or be documented in the meeting minutes. 
The contents of an assent are not mandated by the US FDA; however, assents must be 
factually correct, written at an age appropriate level, and not include any coercive language. 
The assent must have a date and signature line for the child. State laws differ in their 
requirements for subjects who have not reached the legal age of majority and IRB/ECs are 
responsible for following their local regulations. Use of an assent is not a substitute for 
parental permission. Parents/guardians must receive a full informed consent to review and 
sign.  
13.3 
IRB/EC Approval 
This protocol, the informed consent document, and all relevant supporting data, including any 
advertisement used to recruit study subjects, must be submitted to the IRB/EC for approval, 
which must be obtained before the study begins. At least once a year, the Investigator is 
responsible for informing the IRB/EC of the progress of the study and of any changes made to 
the protocol. The Investigator is also responsible for notifying the IRB/EC of any significant 
AEs that occur during the study. 
13.4 
Subject Confidentiality 
The Investigator must assure that subject anonymity will be maintained and that subject 
identity is protected from unauthorized parties. On CRFs and other documents that are 
submitted to the Sponsor, subjects should be identified by an identification code and not by 
their names. Electronic data will be stored in accordance with local data protection laws. The 
subjects will be informed that representatives of the Sponsor, independent IRB/EC, or 
regulatory authorities may inspect their medical records to verify the information collected 
and that all personal information made available for inspection will be handled in strictest 
confidence and in accordance with local data protection laws. 
The Investigator should keep a subject enrollment log showing codes, names, and addresses. 
All data obtained during the course of this study will be transferred, stored, managed, and 
analyzed in compliance with applicable privacy policy. 
The Sponsor or designee will ensure that the use and disclosure of protected health 
information obtained during a research study complies with the Health Insurance Portability 
and Accountability Act (HIPAA) Privacy Rule, if applicable. The HIPAA rule provides 
federal protection for the privacy of protected health information by implementing standards 
to protect and guard against the misuse of individually identifiable health information of 
subjects participating in the clinical trials. Authorization is required from each research 
subject (i.e., specific permission granted by an individual to a covered entity) for the use or 


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CONFIDENTIAL 
disclosure of his or her protected health information. A valid authorization must meet the 
implementation specifications under the HIPAA Privacy Rule. Authorization may be 
combined in the informed consent document (approved by the IRB/IEC) or it may be a 
separate document (approved by the IRB/IEC) or provided by the Investigator or Sponsor 
(without IRB/IEC). It is the responsibility of the Investigator and institution to obtain such 
waiver/authorization in writing from the appropriate individual. 
 
14.0 DOCUMENTATION AND STUDY MONITORING 
14.1 
Changes to Protocol 
Any changes or additions to this protocol requiring a protocol amendment must be approved 
by the Sponsor and the Investigator before implementation. Once the study has started, 
amendments should be made only in exceptional cases. The changes then become part of the 
clinical study protocol. Amendments must be evaluated to determine whether formal approval 
must be sought and whether the informed consent document should also be revised. 
Amendments affecting the safety of subjects, the scope of the investigation, or the scientific 
quality of the study require additional approval by the IRB/EC and by the regulatory 
authority. Examples of amendments requiring such approval are as follows: 
• An increase in study drug dosage or duration of exposure of subjects 
• A significant change in the study design (eg, addition or deletion of a control group) 
• An increase in the number of invasive procedures to which subjects are exposed 
• Addition or deletion of a test procedure for safety monitoring 
These requirements for approval should not prevent any immediate action from being taken 
by the Investigator or by the Sponsor in the interests of preserving the safety of all subjects 
included in the study. If the Investigator believes an immediate change to the protocol is 
necessary and he or she implements this change for safety reasons, the Medical Monitor and 
the IRB/EC should be notified accordingly. 
Amendments affecting only administrative aspects of the study do not require formal protocol 
amendments or IRB/EC approval, but the IRB/EC must be informed of such administrative 
changes. Examples of administrative changes not requiring formal protocol amendments and 
IRB/EC approval that can be treated as administrative amendments include: 
• Changes in analytical methods 
• Changes in the staff used to monitor studies (eg, Sponsor or contract research organization 
staff) 


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• Minor changes to the inclusion or exclusion criteria used to select study subjects 
• Minor changes in the packaging or labeling of study drug 
The Investigator must keep a record of all communication with the IRB/EC and, if applicable, 
between a coordinating Investigator and the IRB/EC. This also applies to any communication 
between the Investigator (or coordinating Investigator, if applicable) and the authorities. 
14.2 
Case Report Forms 
Information collected for this study will be entered onto the CRFs at the site. Site personnel 
will be trained on CRF guidelines prior to initiation of the study. The completed CRF 
casebook must be reviewed and signed by the Investigator named in the clinical study 
protocol or by a designated subinvestigator.  
14.3 
Study Monitoring and Auditing 
All aspects of the study will be carefully monitored by the Sponsor or authorized 
representatives of the Sponsor at regular intervals, and with respect to current GCP and SOPs 
for compliance with applicable government regulations. These individuals will have access, 
both during the study and after study completion, to review and audit all records necessary to 
ensure integrity of the data and verify the entries on the CRF. They will periodically review 
progress of the study with the Investigator.  
Training sessions, regular monitoring of Investigators by designated personnel, data 
verification, cross-checking, and data audits will be performed and instruction manuals 
provided to ensure quality of all study data.  
The Sponsor’s monitor or designee is responsible for inspecting the CRF as defined in the 
monitoring plan throughout the study to verify adherence to the protocol; completeness, 
accuracy, and consistency of data; and, adherence to local regulations on the conduct of 
clinical research. The Investigator will ensure that subjects’ medical records and other study-
related records needed to verify entries on the CRF are available at the Investigator site during 
monitoring visits. In addition to the monitoring visits, communications (letter, telephone, and 
fax), by the study monitor will also be used to determine whether the investigation is being 
conducted according to protocol design and regulatory requirements. The Investigator agrees 
to cooperate with the monitor to ensure that any problems detected in the course of these 
monitoring visits are resolved. 
In accordance with ICH guidelines and GCP, this study may be selected for audit by the 
Sponsor or designees. Inspection of the site facilities (eg, subject areas, drug storage areas, 
record storage areas) and review of study-related records will occur to evaluate the study 
conduct and compliance with the protocol, ICH, GCP, and applicable regulatory requirements. 
The study monitor will perform study close-out procedures. 


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14.4 
Direct Access to Source Data/Documents 
All study data must be verifiable to the source data, which necessitates access to all source 
documents. Source documents are defined as the results of original observations and activities 
of a clinical investigation. Source documents may include, but are not limited to, study 
progress notes, e-mail correspondence, computer printouts, laboratory data, and recorded data 
from automated instruments. All source documents produced in this study will be maintained 
by the Investigator and be made available for inspection by the Sponsor, or representatives of 
the Sponsor and/or regulatory authorities. The Investigator and study staff are responsible for 
maintaining a comprehensive and centralized filing system for all study-related (essential) 
documentation, suitable for inspection at any time by the Sponsor or Sponsor’s 
representatives, or applicable regulatory authorities. 
The subjects (or their legal representatives) must also allow access to the subjects’ medical 
records, and subjects will be informed of this and will indicate their agreement when giving 
informed consent.  
Data generated in this study must be available for inspection by any regulatory authorities, the 
Sponsor or designated representatives, and the IRB/EC as appropriate. At a subject’s request, 
medical information may be given to his or her personal physician or other appropriate 
medical personnel responsible for his or her welfare. Subject medical information obtained 
during the course of this study is confidential and disclosure to third parties other than those 
noted above is prohibited. 
14.5 
Data Collection 
To ensure the quality of clinical data across all subjects and sites, a clinical data management 
review will be performed on subject data. During this review, subject data will be checked for 
consistency, omissions, and any apparent discrepancies. In addition, the data will be reviewed 
for adherence to the protocol and GCP. To resolve any questions arising from the clinical data 
management review process, data queries and/or site notification will be sent to the site for 
completion and return to data management.  
All clinical information required by the protocol must be entered on the CRF from source 
documentation by study site personnel as information is available. If edits to entries in the 
source document or CRF are required, the change must be recorded in a manner that does not 
obscure the original entry. Additionally, the initials of the person making the change and the 
date that the change is made must be recorded.  
14.6 
Document Retention 
Government agency regulations and directives require that all study documentation pertaining 
to the conduct of a clinical trial must be retained by the Investigator for a specified time. 
Study-related records should be retained by the Investigator until notified by the Sponsor in 
writing that retention is no longer necessary. Should the Investigator wish to assign the study 


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records to another party or move them to another location, written notification must be given 
to the Sponsor or designee. 
The Investigator agrees to adhere to the document retention procedures by signing the 
protocol. Essential documents include but are not limited to: 
• Signed informed consent/assent documents for all subjects, as applicable 
• Subject identification code list, Screening log (if applicable), and enrollment log 
• Record of all communications between the Investigator and the IRB/EC 
• Composition of the IRB/EC 
• Record of all communications between the Investigator and Sponsor (or contract research 
organization) 
• List of subinvestigators and other appropriately qualified persons to whom the Investigator 
has delegated significant study-related duties, together with their roles in the study and 
their signatures 
• Copies of CRF and of documentation of corrections for all subjects 
• Investigational product accountability records 
• Record of any body fluids or tissue samples retained 
• All other source documents (subject medical records, hospital records, laboratory records, 
etc.) 
• All other documents as listed in Section 8 of the ICH E6 Guideline for GCP (Essential 
Documents for the Conduct of a Clinical Trial) 
14.7 
Termination of Study 
The Sponsor may discontinue the study at any time. The Investigator should notify the 
IRB/EC in writing of the study’s completion or early termination and send a copy of the 
notification to Sponsor. 
14.8 
Investigator Agreement 
An Investigator agreement will be included with the protocol. The Investigator will be 
responsible for signing and dating the Investigator agreement to officially note that he or she 
has read, understands, and agrees to conduct this study in accordance with all stipulations of 
the protocol and in accordance with applicable law, regulations, and guidelines. 
 


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15.0 FINANCE AND INSURANCE 
Before the start of the study, the Investigator will disclose to the Sponsor any proprietary or 
financial interests he or she might hold in the investigational products or the Sponsor 
company as outlined in the financial disclosure form provided by the Sponsor. The 
Investigator agrees to update this information in case of significant changes during the study 
or within 1 year of its completion. The Investigator also agrees that, where required by law or 
regulation, the Sponsor may submit this financial information to domestic or foreign 
regulatory authorities in applications for marketing authorizations. Similar information will be 
provided by each subinvestigator to whom the Investigator delegates significant study-related 
responsibilities. 
The financing and insurance for this study are outlined in the Clinical Trial Agreement. 
 
16.0 PUBLICATION POLICY 
The publication policy is outlined in the Clinical Trial Agreement. The data generated in this 
clinical trial are the exclusive property of the Sponsor and are confidential. Written approval 
from Sponsor is required prior to disclosing any information related to this clinical trial. 
Submission to the Sponsor for review and comment before submission to the publisher will be 
required. This requirement should not be construed as a means of restricting publication, but 
is intended solely to assure concurrence regarding data, evaluations, and conclusions and to 
provide an opportunity to share with the Investigator any new and/or unpublished information 
of which he/she may be unaware. 
The Investigator agrees by his/her participation that the results of this study may be used for 
submission to national and/or international registration and supervising authorities. If 
required, these authorities will be provided with the names of Investigators, their addresses, 
qualifications, and extent of involvement. The Investigator is required to provide the Sponsor 
with all study data, complete reports, and access to all study records. 


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CONFIDENTIAL 
17.0 REFERENCES 
1. 
Elewski BE, Charif MA. Prevalence of onychomycosis in patients attending a 
dermatology clinic in northeastern Ohio for other conditions. Arch Dermatol 
1997; 133(9):1172-1173. 
2. 
Lamisil® [package insert]. East Hanover, NJ: Novartis Pharmaceuticals 
Corporation; 2013. 
3. 
Sporanox® [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2014. 
4. 
Tavaborole Topical Solution, 5% (formerly AN2690) Investigator’s Brochure, 
version 13 edition. Palo Alto, CA: Anacor Pharmaceuticals; 2013. 
5. 
Gupta A P, Chang P, Del Rosso JQ, et al. Onychomycosis in children: prevalence 
and management. Pediatr Dermatol 1998:15(6):464–71. 
6. 
Huang P-H and Paller A. Itraconazole pulse therapy for dermatophyte 
onychomycosis in children. Arch Pediatr Adolesc Med 2000;154(6):614–8. 
7. 
Lateur N, Mortaki V, and André J. Two hundred ninety-six cases of 
onychomycosis in children and teenagers: a 10-year laboratory survey. Pediatr 
Dermatol 2003;20(5):385–8. 
8. 
KERYDIN (tavaborole) topical solution, 5% [Package Insert]. Palo Alto, CA: 
Anacor Pharmaceuticals, Inc.; March 2015. 
9. 
Protocol No. P06118. Evaluation of the pharmacokinetics of SCH 900340 in 
subjects with onychomycosis of the toenails. Schering-Plough Research Institute. 
Study Report No. 002-CLN PK-003-01. 
 
 


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CONFIDENTIAL 
APPENDIX A: SUMMARY OF CHANGES 
Summary of changes needed for clarification and consistency from Amendment 2 
(dated 15 July 2015) to Amendment 3 (dated 28 March 2016) 
The entire document was updated to clarify that subjects studied under ‘maximal use 
conditions’ are the PK subgroup and to reflect the changes detailed below: 
Study Objective 
Screening period of 4-10 weeks was clarified to read: Screening period: up to 10 weeks 
(maximum duration of 70 days) 
Study Design 
Local tolerability evaluation was modified to remove ‘of the TGT’ to clarify local 
tolerability evaluation is of all toes: Subjects will be evaluated at Screening, Baseline 
(Day 1), and at Weeks 2, 4, 8, 16, 24, 32, 40, 48, and 52. Each evaluation will include 
vital signs and a clinical assessment of adverse events (AEs) and a local tolerability 
evaluation.  
Treatment Outcomes 
The following missing definition was added:  
• Almost complete cure: almost CN and negative mycology 
Secondary Efficacy Endpoints 
The following text was corrected to remove ‘and negative mycology’ from the definition:  
• Treatment success (Clinical Efficacy rate) of the TGT at Weeks 24 and 52 defined 
as completely CN or almost CN 
A secondary end point was added:  
• Negative fungal culture of the TGT at Weeks 24 and 52 
Treatment Administration 
The following text was modified to clarify that study drug would be applied during the 
visit: Study drug will be applied on all affected toenails daily with a supplied dropper, 
preferably at bed time, except for the clinic visit days during which the study drug will be 
applied at the visit. 
Table 3:  
Schedule of Events 
‘Abbreviated’ was added to physical examination for clarification and consistency with 
Section 7.2.3.1 and Section 7.8. 


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CONFIDENTIAL 
 
Visit 2: Baseline Visit (Day 1) 
‘Abbreviated’ was added and ‘complete’ was deleted in the following bullet in Section 
7.2.3.1 to be consistent with the text in Section 7.8: 
• Perform an abbreviated complete physical examination (prior to enrolling and drug 
dispense)  
KOH Mount and Central Fungal Culture  
Typo was corrected to remove the word ‘once’ to clarify resampling can occur more than 
once: A subject that fails mycology criteria may be resampled (see resample criteria in 
Section 5.0). 
Dosing Diary 
The following text was deleted: The dosing diary will only be utilized to determine the 
total number of applications. All other dosing data; application date and time relevant for 
PK analysis and date of first and last application to determine total number of days of 
dosing will be based on data reported in the site paper source and recorded on the CRF. 
Digital Photography 
The following text was added: Photographs will be utilized for purposes of publications. 
Clinical Safety Laboratory Parameters and Pregnancy Tests 
The following text was modified to clarify that Baseline is recorded as medical history: 
Abnormal clinical laboratory parameters that are considered clinically significant by the 
Investigator will be recorded on the AE CRF except Baseline visit. Clinically significant 
laboratory abnormalities noted from the Baseline will be recorded as medical history. 
Safety Reporting Procedures 
The email address was removed and fax/efax number was added. 
Laboratory Test Abnormalities 
The following text was modified to clarify that Baseline is recorded as medical history: 
All out-of-normal range laboratory values must be evaluated for clinical significance, and 
clinically significant abnormalities must be reported as AEs except from Baseline visit 
abnormalities which will be recorded as medical history. 

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CONFIDENTIAL 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 3 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Change History: 
Table numbers were updated.  
Table 14.4.2 Summary of Concomitant Medications was added. 
No other changes were made to the statistical methods. 


CONFIDENTIAL 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 4 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
1.
TABLE OF CONTENTS
1.
TABLE OF CONTENTS ......................................................................................................4
2.
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ....................................6
3.
INTRODUCTION .................................................................................................................7
4.
STUDY OBJECTIVES .........................................................................................................7
5.
INVESTIGATIONAL PLAN ...............................................................................................7
5.1 Overall Study Design ......................................................................................................7 
5.1.1 
Schedule of Visits and Assessments .................................................................9 
5.2 Selection of Study Population .......................................................................................10 
5.2.1 
Inclusion Criteria .............................................................................................10 
5.2.2 
Exclusion Criteria ............................................................................................10 
5.3 Treatments ....................................................................................................................11 
5.4 Efficacy and Safety Variables .......................................................................................12 
5.4.1 
Efficacy Variables ...........................................................................................12 
5.4.1.1 
Clinical Assessment of the Target Toenail Involvement .............12 
5.4.1.2 
KOH Mount and Central Fungal Culture.....................................12 
5.4.2 
Pharmacokinetic Assessments .........................................................................13 
5.4.3 
Safety Variables ..............................................................................................13 
5.4.3.1 
Local Tolerability Reactions ........................................................13 
5.4.3.2 
Vital Signs ....................................................................................15 
5.4.3.3 
Clinical Safety Laboratory Parameters and Pregnancy Tests ......15 
5.4.3.4 
Adverse Events ............................................................................16 
5.5 Statistical Methods ........................................................................................................16 
5.5.1 
Disposition of Patients .....................................................................................16 
5.5.2 
Data Sets Analyzed .........................................................................................16 
5.5.3 
Demographic and Other Baseline Characteristics ...........................................17 
5.5.3.1 
Concomitant Medications ............................................................17 
5.5.4 
Measurements of Treatment Compliance ........................................................17 
5.5.5 
Analysis of Efficacy ........................................................................................17 
5.5.6 
Statistical/Analytical Issues .............................................................................18 
5.5.6.1 
Adjustments for Covariates..........................................................18 
5.5.6.2 
Handling of Dropouts or Missing Data ........................................18 
5.5.6.3 
Interim Analyses and Data Monitoring........................................18 
5.5.6.4 
Multicenter Studies ......................................................................18 
5.5.6.5 
Multiple Comparisons/Multiplicity .............................................18 


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Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 5 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
5.5.6.6 
Use of an “Efficacy Subset” of Patients ......................................18 
5.5.6.7 
Active-Control Studies Intended to Show Equivalence ...............18 
5.5.6.8 
Examination of Subgroups ...........................................................18 
5.5.7 
Pharmacokinetics .............................................................................................18 
5.5.8 
Safety Analyses ...............................................................................................19 
5.5.8.1 
Extent of Exposure .......................................................................19 
5.5.8.2 
Adverse Events ............................................................................19 
5.5.8.3 
Local Skin Reactions ...................................................................20 
5.5.8.4 
Safety Laboratory Values ............................................................20 
5.5.8.5 
Vital Sign Measurements .............................................................20 
5.5.9 
Determination of Sample Size .........................................................................20 
5.6 Changes in the Planned Analyses .................................................................................20 
6. 
INDEX OF PLANNED END-OF-TEXT TABLES ..........................................................21 
7. 
INDEX OF PLANNED LISTINGS ...................................................................................68 
 
 


CONFIDENTIAL 
 
 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 6 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
2. LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
AE 
Adverse event 
AUC0-24 
Area Under the plasma Concentration-time curve from Hour 0 to Hour 24 
AUC0-∞ 
Area Under the plasma Concentration-time curve from Hour 0 extrapolated 
to infinity 
CN 
Clear Nail 
Cmax 
maximum observed plasma concentration 
CRF 
Case report form 
DSO 
Distal subungal onychomycosis 
MedDRA 
Medical Dictionary for Regulatory Affairs 
λZ 
elimination rate constant 
LTR 
Local Tolerability Reactions 
N 
Sample size 
PK 
Pharamacokinetic 
SAE 
Serious adverse event 
SD 
Standard deviation 
t½ 
elimination half-life 
TEAE 
Treatment-emergent adverse event 
TGT 
Target great toenail 
Tmax 
time to maximum observed plasma concentration 
UPT 
Urine Pregnancy Test 
WHO 
World Health Organization 
 
 
 


CONFIDENTIAL 
 
 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 7 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
3. INTRODUCTION 
KERYDIN® (tavaborole) topical solution, 5%, the first oxaborole antifungal agent, was 
approved by the Food and Drug Administration for the topical treatment of onychomycosis of 
the toenails on 07 July 2014 (NDA 204427). This protocol is intended to satisfy the post-
marketing study requirements (PMR-2154-1) and the Written Request of KERYDIN 
(tavaborole) topical solution, 5% in pediatric subjects with onychomycosis of the toenails. 
4. STUDY OBJECTIVES 
The primary objective of this study is to assess the safety and tolerability of KERYDIN 
(tavaborole) topical solution, 5% applied once daily for 48 weeks in pediatric subjects ages 6 to 
16 years and 11 months with onychomycosis of the toenails.  
The secondary objective is to perform PK assessments in a subgroup of at least 16 evaluable 
subjects ages 12 to 16 years and 11 months following topical administration under maximal use 
conditions. 
5. INVESTIGATIONAL PLAN 
5.1 
Overall Study Design 
This is an open-label study to evaluate the safety, tolerability, and pharmacokinetics of 
KERYDIN (tavaborole) topical solution, 5% in treating distal subungal onycomychosis (DSO) of 
the toenail in pediatric subjects ages 6 to 16 years and 11 months. An eligible subject will have a 
target great toenail (TGT) with at least 20% involvement with a positive potassium hydroxide 
(KOH) wet mount and positive fungal culture for T. rubrum or T. mentagrophytes from a sample 
obtained from an affected great toenail during the Screening period. KOH and fungal culture will 
be sent to a central mycology laboratory for eligibility determination. Both great toenails can be 
sampled at Screening.  
The mycological confirmation of eligibility will be performed as follows: 
 
1. Initial sample is KOH (+) and culture (+) for  T. rubrum or T. mentagrophytes, with or 
without co-infection with Candida spp. or E. floccosum, subject is eligible for enrollment 
within the maximum period of 10 weeks (i.e., within 70 days) from the Screening visit. 
2. Initial sample is KOH (−) or initial sample is KOH (+) and culture (−): The sample may be 
repeated and will be assessed as follows: 
• 
If a repeat sample is KOH (+) and culture (+) for T. rubrum or T. mentagrophytes 
with or without co-infection with Candida spp. or E. floccosum, for enrollment as 
long as the subject is enrolled within the maximum period of 10 weeks (i.e., within 
70 days) from the Screening visit. 


CONFIDENTIAL 
 
 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 8 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Eligible subjects will apply KERYDIN (tavaborole) topical solution, 5% once daily to all 
affected toenails (the TGT as well as all other toenails identified by the Investigator at the 
Baseline visit as having the clinical characteristics of onychomycosis) throughout the 48-week 
treatment period.  
Subjects will be evaluated at Screening, Baseline (Day 1), and at Weeks 2, 4, 8, 16, 24, 32, 40, 
48, and 52. Each evaluation will include a clinical assessment of the adverse events (AEs) and 
local tolerability evaluation.  
Additional procedures are performed as follows: 
• Mycology sampling at Screening, Week 24, and Week 52/early termination (ET) 
• Clinical disease severity of the TGT at Screening, Week 24, and Week 52/ET 
• Safety laboratory testing at Baseline, Week 24, and Week 52/ET  
• Digital photography at Screening, Week 24, and Week 52/ET 
• Urine pregnancy tests (UPTs) will be performed on all postmenarchal females at all 
scheduled visits starting at the Baseline visit. 
Subjects will start diaries at Baseline (Day 1) and will complete the diary as instructed. 
In this study, there will be a PK subgroup of at least 16 evaluable subjects ages 12 to 16 years 
and 11 months studied under maximal use conditions. Subjects in this maximal use subgroup 
will apply the study drug on all 10 toenails, including up to 2 mm of the surrounding skin, for 
28 days (±7 days). On Day 15, a pre-dose PK sample will be collected to assess steady state 
trough level. On Day 29, the study drug application will be done at the study site, and PK 
samples will be collected prior to dosing, as well as 4, 6, 8, and 24 hours post-dose on Days 29-
30. After PK sampling is complete, study drug will be applied only to the affected toenails. 
 
 
 


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Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
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Protocol Number: TAV-ONYC-401 
June 2, 2017 
5.1.1 
Schedule of Visits and Assessments 
Study Visit No. 
1 
(Screenin
g) 
2 
(Baseli
ne) 
3 
4 4a  
(P
K) 
5 
6 
7 
8 
9 
10 
11 
(or 
ET) 
Study Day (±7 days V4-11, +7 
days V3) 
Up to -70 
days 
1 
15 29 
30 
 
 
 
 
 
 
 
Study Week 
 
 
2 
4 
 
8 16 
24 
32 
40 
48 
52 
Informed consent 
x 
 
 
 
 
 
 
 
 
 
 
 
Obtain subject number  
x 
 
 
 
 
 
 
 
 
 
 
 
Demographics  
x 
 
 
 
 
 
 
 
 
 
 
 
Medical and medication history 
x 
x 
 
 
 
 
 
 
 
 
 
 
Abbreviated physical 
examination 
 
x 
 
 
 
 
 
 
 
 
 
 
KOH mount and fungal culturec 
x 
 
 
 
 
 
 
x 
 
 
 
x 
Review inclusion/exclusion 
criteria 
x 
x 
 
 
 
 
 
 
 
 
 
 
Identify target great toenail 
(TGT) 
x 
x 
 
 
 
 
 
 
 
 
 
 
Identify ‘other toes’ to be treated 
 
x 
 
 
 
 
 
 
 
 
 
 
Clinical assessment (% TGT 
disease severity) 
x 
 
 
 
 
 
 
x 
 
 
 
x 
Concomitant medications 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Adverse events (AEs) 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Safety laboratory tests 
 
x 
 
 
 
 
 
x 
 
 
 
x 
Urine pregnancy test (UPT) for 
postmenarchal females 
 
x 
x 
x 
 
x 
x 
x 
x 
x 
x 
x 
Vital signs (blood pressure, 
pulse rate, respiratory rate)a 
x 
x 
x 
x 
 
x 
x 
x 
x 
x 
x 
x 
LTR assessment 
 
x 
x 
x 
 
x 
x 
x 
x 
x 
x 
x 
PK subgroup sampling b 
 
 
x 
x 
xb 
 
 
 
 
 
 
 
Photography of the TGTc 
x 
 
 
 
 
 
 
x 
 
 
 
x 
Weigh and dispense new study 
drug kit 
 
x 
x 
x 
 
x 
x 
x 
x 
x 
 
 
Study drug 
collection/weighing/accountabili
ty 
 
 
x 
x 
 
x 
x 
x 
x 
x 
x 
 
Supervise study drug self-
administrationd 
 
x 
x 
x 
 
x 
x 
x 
x 
x 
 
 
Diary review and training/re-
training 
 
x 
x 
x 
 
x 
x 
x 
x 
x 
x 
 
Schedule next visit 
x 
x 
x 
x 
 
x 
x 
x 
x 
x 
x 
 
ET, early termination; KOH, potassium hydroxide; PK, pharmacokinetic; LTR, local tolerability 
reaction 
a Vital signs conducted after subject is sitting or supine for at least 5 minutes. 
b For subjects in the PK subgroup, at Visit 3 (Day 15) a pre-dose sample will be collected and Visit 4 
(Day 29), PK samples will be collected prior to dosing, as well as 4, 6, and 8 hours post-dose. At 
Visit 4a (Day 30), the 24-hour post-dose sample is collected prior to dosing. 
c Perform photography procedures before mycology procedures. 
d Application occurs at the site on visit days. For PK subgroup participants, the application for Visit 3 
(Day 15) and Visit 4a (Day 30) is to occur after the subject has had their PK specimen drawn. 
 
 


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Statistical Analysis Anacor Pharmaceuticals, Inc. 
Page 10 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
5.2 
Selection of Study Population 
5.2.1 
Inclusion Criteria 
Subjects must meet all of the following inclusion criteria to be eligible for this study: 
 
1. Male or female subjects, ages ≥ 6 years and ≤ 16 years and 11 months at the time of 
enrollment 
2. Have a parent or guardian able to understand, to agree to, and to sign the study ICF; subject 
has the ability to give assent based on their age, maturity, and psychological state at the time 
of parental/guardian consent 
3. A clinical diagnosis of DSO affecting either great toenail with positive KOH and T. rubrum 
or T. mentagrophytes culture from the TGT confirmed by a central mycology laboratory 
during the Screening period 
4. DSO involving at least 20% of the TGT 
5. TGT capable of growing, as assessed by the Investigator or qualified designee 
6. Subject and parent/guardian (if applicable) are willing and able to comply with study drug 
instructions, comply with study instructions, and commit to attending all visits 
7. Postmenarchal females must agree to use a medically accepted method of contraception for 
the entire study period 
5.2.2 
Exclusion Criteria  
Subjects who meet any of the following exclusion criteria will be excluded from entering the 
study: 
 
1. One or more of the following conditions affecting the TGT: 
• 
Proximal subungual onychomycosis 
• 
Onychomycosis involving the lunula 
• 
Superficial white onychomycosis, dermatophytoma, exclusively lateral disease, or 
yellow/brown spikes 
• Screening culture results that demonstrate co-infection with Scopulariopsis spp., 
Scytalidium spp. or other nondermatophyte molds (exception: Candida spp. and E. 
floccosum are permitted) 


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Protocol Number: TAV-ONYC-401 
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2. Anatomic abnormalities of the toe(s) or toenail(s) to be treated including, but not limited to: 
genetic nail disorders, pigmentary disorders, onychogryphosis, trauma to the toenail(s) to be 
treated, or other abnormality that in the Investigator’s opinion may interfere with clinical 
evaluation of the toenail(s) or would indicate that the subject is unlikely to respond to a 
topical treatment for DSO 
3. Current or past history of chronic moccasin-type tinea pedis (involving the sides or dorsum 
of the foot) 
4. Current or past history of psoriasis or lichen planus involving the skin, nails or mucous 
membranes 
5. History of any significant chronic fungal disease other than onychomycosis (eg, chronic 
mucocutaneous candidiasis) 
6. Known diagnosis of type I or type II diabetes  
7. Concurrent use of or have used any of the following topical or systemic medications within 
the indicated timeframe prior to Screening: 
• 
Topical antifungals applied to the toenails: 2 weeks 
• 
Systemic corticosteroids (including intramuscular injections): 4 weeks 
• 
Systemic immunosuppressive agents: 4 weeks 
• 
Systemic antifungals for treatment of onychomycosis or with known activity against 
dermatophytes: 24 weeks 
8. Any significant active or past medical condition which, in the Investigator’s opinion, may 
expose the subject to unacceptable risk by study participation, confound the evaluation of 
treatment response or AEs, or interfere with the subject’s ability to complete the study 
9. History of any known immunodeficiency 
10. Known to be allergic to the study drug or excipients in the study drug 
11. History of drug or alcohol abuse (current or within the past 6 months) 
12. Participated in any other trial of an investigational drug or device within 30 days prior to 
Screening or participation in a research study concurrent with this study 
5.3 
Treatments 
KERYDIN (tavaborole) topical solution, 5% will be applied topically once daily for 48 weeks. 


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Statistical Analysis Anacor Pharmaceuticals, Inc. 
Page 12 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
5.4 
Efficacy and Safety Variables 
5.4.1 
Efficacy Variables 
The efficacy assessments are intended to assess compliance with treatment for the purposes of 
the safety assessment. 
5.4.1.1 
Clinical Assessment of the Target Toenail Involvement 
Clinical involvement of the TGT will be assessed at Screening and Weeks 24 and 52/ET using 
the following definitions of disease severity: 
• Completely CN: no clinical evidence of onychomycosis as evidenced by normal toenail 
plate, no onycholysis, and no subungual hyperkeratosis 
• Almost CN: no more than minimal evidence of onychomycosis as evidenced by toenail plate 
dystrophic or discolored ≤ 5% of the distal aspect, with minimally evident onycholysis and 
subungual hyperkeratosis  
• Mild onychomycosis: onychomycosis as evidenced by toenail plate dystrophic or discolored 
> 5% to ≤ 20% of the distal aspect, with clearly evident onycholysis and subungual 
hyperkeratosis  
• Moderate onychomycosis: onychomycosis as evidenced by toenail plate dystrophic or 
discolored > 20% to ≤ 50% of the distal aspect, with clearly evident onycholysis and 
subungual hyperkeratosis 
• Severe onychomycosis: onychomycosis as evidenced by a toenail plate dystrophic or 
discolored > 50% of the distal aspect, with pronounced onycholysis and subungual 
hyperkeratosis 
5.4.1.2 
KOH Mount and Central Fungal Culture 
Mycology sampling is to occur after all photography procedures for that visit have been 
completed. At Screening, the Investigator may perform a KOH wet mount at the study site to 
confirm the clinical diagnosis of onychomycosis prior to obtaining a sample for the central 
mycology laboratory; however, care must be taken to obtain sufficient subungual debris for the 
analysis at the central laboratory. The local KOH wet mount is an optional procedure and only 
the central mycology laboratory reading will be used for analysis and eligibility determination. If 
both great toenails are potentially eligible by clinical criteria, then both great toenails can be 
sampled at Screening. A subject that fails mycology criteria may be resampled.  
A sample of subungual debris will be obtained again at Week 24 and Week 52/ET. 


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Statistical Analysis Anacor Pharmaceuticals, Inc. 
Page 13 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
5.4.2 
Pharmacokinetic Assessments 
Blood samples for the determination of plasma levels of tavaborole and PK parameters will be 
obtained under maximal use conditions (once daily application to all 10 toenails, including up to 
2 mm of the surrounding skin) from the subgroup of subjects ages 12 to 16 years and 11 months 
to achieve at least 16 evaluable subjects. Subjects in the maximal use subgroup will apply the 
study drug on all 10 toenails, including up to 2 mm of the surrounding skin, for 28 days ±7 days. 
At Visit 3 (Day 15) a pre-dose PK sample will be collected to assess steady state trough level. At 
Visit 4 (Day 29), the study drug application will be done at the study site, and PK samples will 
be collected prior to dosing, as well as 4, 6, and 8 hours post-dose. At Visit 4a (Day 30) the 
sample will be collected 24 hours post-dose and prior to the application for that day. 
Approximately 24 mL of blood (6 samples, 4 mL each) will be taken from each of the 16 
subjects for the PK determination. 
5.4.3 
Safety Variables 
5.4.3.1 
Local Tolerability Reactions 
Safety evaluations will include local tolerability reactions (LTRs) (burning/stinging, 
induration/edema, oozing and crusting, pruritus, erythema, and scaling), as reported by the 
subject and/or evaluated by the Investigator at Baseline and each study visit thereafter. LTRs will 
be documented on the case report form (CRF) specifically designed to capture LTR information 
(local tolerability signs CRF) and not on the AE CRF. LTRs that require treatment (eg, with a 
concomitant medication or drug interruption or drug discontinuation) are an exception to this 
guideline; these LTRs should be documented on both the local tolerability signs CRF and on the 
AE CRF. 


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Statistical Analysis Anacor Pharmaceuticals, Inc. 
Page 14 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Grade  
Guideline 
Burning/Stinging 
0 - None  
No stinging/burning 
1 - Mild  
Slight warm, tingling sensation; not really bothersome 
2 - Moderate  
Definite warm; tingling/stinging sensation that is somewhat bothersome 
3 - Severe  
Hot, tingling/stinging sensation that has caused definite discomfort 
Induration/Edema 
0 - None  
No elevation 
1 - Mild  
Barely perceptible elevation 
2 - Moderate  
Clearly perceptible elevation but not extensive  
3 - Severe  
Marked and extensive elevation 
Oozing and Crusting 
0 - None  
Absent  
1 - Mild  
Faint signs of oozing 
2 - Moderate  
Definite oozing or crust but with 5 or fewer sites per area 
3 - Severe  
Marked and extensive oozing and crusting 
Pruritus  
0 - None  
No pruritus 
1 - Mild  
Occasional, slight itching/scratching 
2 - Moderate  
Constant or intermittent itching/scratching which is not disturbing sleep 
3 - Severe  
Severe bothersome itching/scratching which is disturbing sleep 
Erythema 
0 - None  
No redness present 
1 - Mild  
Faintly detectable erythema; very light pink 
2 - Moderate  
Dull red, clearly distinguishable 
3 - Severe  
Deep/dark red 
Scaling 
0 - None  
No scaling  
1 - Mild  
Barely perceptible shedding, noticeable only on light scratching or rubbing 
2 - Moderate  
Obvious but not profuse scaling 
3 - Severe  
Heavy scale production 
 
 


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Statistical Analysis Anacor Pharmaceuticals, Inc. 
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Protocol Number: TAV-ONYC-401 
June 2, 2017 
5.4.3.2 
Vital Signs 
Vital signs will be measured at each study visit after the subject has been sitting or supine for at 
least 5 minutes. Vital sign measurements taken will be blood pressure, pulse rate, and respiratory 
rate. 
5.4.3.3 
Clinical Safety Laboratory Parameters and Pregnancy Tests 
Clinical safety laboratory parameters will be assessed at Baseline, Week 24, and Week 52/ET, if 
applicable. Laboratory tests may be repeated more often if clinically indicated. Blood samples 
may be taken with the subject in a non-fasting state.  
All out-of-normal range laboratory values must be evaluated by the Investigator or 
subinvestigator as to whether they are clinically significant (i.e., require medical intervention or 
have clinical signs and/or symptoms). Abnormal clinical laboratory parameters that are 
considered clinically significant by the Investigator will be recorded on the AE CRF except 
Baseline visit. Clinically significant laboratory abnormalities noted from the Baseline visit will 
be recorded as medical history. The AE should be reported as a clinical diagnosis when possible. 
Laboratory tests will be performed by the central laboratory and are presented in Table 5.  
UPTs will be performed at each scheduled visit on postmenarchal females starting at Baseline. If 
a UPT result is positive, the subject must be discontinued.  
The Sponsor will designate a central laboratory for safety laboratory tests. All samples for 
clinical laboratory tests must be managed through the central laboratory designated by the 
Sponsor. Sample management (collection, storage, shipping, etc.) will be done according to the 
central laboratory instructions. 
Safety Laboratory Parameters 
Hematology 
Chemistry 
Hemoglobin 
Hematocrit 
Red blood cell count 
Platelet count 
White blood cell count 
Neutrophils  
Eosinophils  
Monocytes  
Basophils  
Lymphocytes  
Blood urea nitrogen 
Creatinine 
Glucose (nonfasting) 
Sodium, Potassium 
Aspartate aminotransferase, alanine aminotransferase 
Total bilirubin 
Alkaline phosphatase 
Albumin 
Total protein 
Urine pregnancy test (all scheduled visits starting at Baseline) 
 


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Statistical Analysis Anacor Pharmaceuticals, Inc. 
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Protocol Number: TAV-ONYC-401 
June 2, 2017 
5.4.3.4 
Adverse Events 
An AE is any untoward medical occurrence or unintended change from the subject’s Baseline 
(pretreatment) condition, including intercurrent illness, that occurs during a clinical trial after 
treatment has started, whether or not it is considered related to study treatment. An AE can 
therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease temporally associated with the use of an investigational product. 
An AE is meant to include events that are either new or represent detectable exacerbations of 
preexisting conditions, and does not imply any judgment about causality.  
AEs will be assessed at each visit. Any AE occurring on or after the date of the dose of study 
drug administration on Day 1 and up to and including the completion/termination date will be 
counted as treatment-emergent. 
Adverse experiences may include but are not limited to subjective or objective symptoms 
spontaneously reported by the subject and/or observed by the Investigator or medical staff, 
including laboratory abnormalities of clinical significance. Preexisting conditions noted as part 
of the medical history at Screening must be reported on the appropriate medical history CRF 
page. Stable, ongoing conditions present at Screening should not be recorded as AEs if the 
severity at Screening remains unchanged during the study. However, preexisting conditions for 
which an increase in severity is observed after Screening must be recorded as AEs. 
5.5 
Statistical Methods 
All statistical processing will be performed using SAS® unless otherwise stated.  
Descriptive statistics will include sample size, mean, median, standard deviation, minimum, and 
maximum continuous variables. Categorical variables will be tabulated with frequency counts 
and percentages. 
5.5.1 
Disposition of Patients 
A tabulation of subject disposition will be provided. The tabulation will include the numbers of 
subjects who enter the study, complete the study, and discontinue the study. The reasons for 
discontinuation will be included. 
5.5.2 
Data Sets Analyzed 
The following populations will be used: 
• Safety population: all subjects who receive at least one confirmed dose of study drug and 
have at least one post-baseline safety assessment. 


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Statistical Analysis Anacor Pharmaceuticals, Inc. 
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Protocol Number: TAV-ONYC-401 
June 2, 2017 
• PK population: all subjects from the maximal use subgroup with available PK data at Day 
15 and at least one collection on Day 29. 
5.5.3 
Demographic and Other Baseline Characteristics 
Subject demographic (age, sex, race, and ethnicity) and Baseline characteristics will be 
summarized for the Safety and PK populations. Age will be represented as both a continuous and 
as a categorical variable. 
5.5.3.1 
Concomitant Medications 
Concomitant medications will be coded using the World Health Organization Drug Dictionary 
Enhanced. All medications will be presented in the data listings. A table of concomitant 
medications by percentage of subjects who used them will also be provided. No statistical tests 
will be performed. 
5.5.4 
Measurements of Treatment Compliance 
No formal evaluations of compliance are planned. 
5.5.5 
Analysis of Efficacy 
Efficacy assessments will be summarized at Baseline, Week 24 and Week 52. 
The primary efficacy endpoint for this study is the complete cure rate of the TGT at Week 52. 
Complete cure is defined as 0% clinical involvement of the TGT and negative mycology 
(negative KOH wet mount and negative fungal culture) at Week 52. 
The secondary efficacy endpoints include the following: 
• Complete or almost complete cure of the TGT at Weeks 24 and 52 
• Treatment success (Clinical Efficacy rate) of the TGT at Weeks 24 and 52 defined as 
completely Clear Nail (CN) or almost CN  
• Negative mycology (Mycological Cure rate) of the TGT at Weeks 24 and 52 defined as 
negative KOH wet mount and negative fungal culture 
• Negative fungal culture of the TGT at Weeks 24 and 52 
The primary and secondary efficacy endpoints will be summarized for the safety population with 
descriptive statistics including sample size, frequency count, and percentage. 
 


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Statistical Analysis Anacor Pharmaceuticals, Inc. 
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Protocol Number: TAV-ONYC-401 
June 2, 2017 
5.5.6 
Statistical/Analytical Issues 
5.5.6.1 
Adjustments for Covariates 
No planned analyses include covariates. 
5.5.6.2 
Handling of Dropouts or Missing Data 
No imputations will be made for missing data. 
5.5.6.3 
Interim Analyses and Data Monitoring 
No interim analyses are planned. 
5.5.6.4 
Multicenter Studies 
The study will be conducted at multiple investigational centers with the intention of pooling the 
results for analysis. 
5.5.6.5 
Multiple Comparisons/Multiplicity 
Not applicable. 
5.5.6.6 
Use of an “Efficacy Subset” of Patients 
Not applicable. 
5.5.6.7 
Active-Control Studies Intended to Show Equivalence 
Not applicable. 
5.5.6.8 
Examination of Subgroups 
No subgroup summaries are planned. 
5.5.7 
Pharmacokinetics 
Pharmacokinetics will be tabulated for each collection day using descriptive statistics. Mean 
plasma concentrations will be plotted through time using both linear and semi-logarithmic scales. 
Plasma concentrations will also be plotted through time for each subject, using both linear and 
semi-logarithmic scales. Concentrations below the limit of quantitation will be set to zero for 
descriptive statistics.  
The following PK parameters will be calculated for Day 15 (steady state trough level only) and 
Day 29 [steady state (±specified window)]: 


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Statistical Analysis Anacor Pharmaceuticals, Inc. 
Page 19 
Protocol Number: TAV-ONYC-401 
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• Cmax:  
maximum observed plasma concentration 
• Tmax:  
time to maximum observed plasma concentration 
• AUC0-24:  area under the plasma concentration-time curve from Hour 0 to Hour 24, 
calculated using the linear trapezoidal rule 
• AUC0-∞:  area under the plasma concentration-time curve extrapolated to infinity 
• λZ:  
elimination rate constant  
• t1/2:  
elimination half-life 
PK parameters will be calculated using actual sampling times. 
5.5.8 
Safety Analyses 
No imputation will be made for missing safety data. 
5.5.8.1 
Extent of Exposure 
The extent of exposure to study drug will be summarized by the total number of days of dosing, 
total number of applications, and total amount of study drug applied. 
5.5.8.2 
 Adverse Events 
All AEs occurring during the study will be recorded and classified on the basis of Medical 
Dictionary for Regulatory Activities terminology. TEAEs are those with an onset on or after the 
time of the first study drug administration. For the safety population, all reported TEAEs will be 
summarized by system organ class (SOC), preferred term, severity, relationship to study drug, 
and seriousness. When summarizing TEAEs by causality and severity, each subject will be 
counted only once within an SOC or a preferred term using the event with the closest 
relationship to study drug and the greatest severity within each classification. 
SAEs will be summarized by severity and relationship to study drug, and individual SAEs will 
be listed by subject. A list of subjects who prematurely discontinued from the study due to an AE 
will also be provided. 
All information pertaining to AEs noted during the study will be listed by subject, detailing the 
verbatim term reported by the Investigator, preferred term, SOC, onset date, resolution date, 
maximum severity, seriousness, action taken regarding study drug, corrective treatment, 
outcome, and drug relationship. The event onset will also be shown relative (in number of days) 
to date of first administration of study drug. 


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Statistical Analysis Anacor Pharmaceuticals, Inc. 
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Protocol Number: TAV-ONYC-401 
June 2, 2017 
5.5.8.3 
Local Skin Reactions 
LTRs (burning/stinging, induration/edema, oozing and crusting, pruritus, erythema, and scaling) 
will be evaluated by frequency tables for Baseline and Weeks 2, 4, 8, 16, 24, 32, 40, 48, and 52. 
Additionally, LTRs as well as change from baseline in LTRs will be summarized by descriptive 
statistics (mean, standard deviation, median, and minimum and maximum). 
5.5.8.4 
Safety Laboratory Values 
Laboratory values as well as changes from Baseline in laboratory values will be summarized 
with descriptive statistics at Baseline, Week 24 and Week 52.  In addition, shift tables will be 
created according to normal ranges. The last laboratory evaluation before the first dose of study 
drug will be used as Baseline for all laboratory analyses. 
5.5.8.5 
Vital Sign Measurements 
Vital signs will be summarized with descriptive statistics at Baseline and Weeks 2, 4, 8, 16, 24, 
32, 40, 48, and 52. Change from Baseline in vital signs will be summarized at Weeks 2, 4, 8, 16, 
24, 32, 40, 48, and 52 
5.5.9 
Determination of Sample Size 
The study will enroll subjects ages 6 to 16 years and 11 months with at least 40 subjects ages 12 
to 16 years and 11 months. All subjects will be assigned to receive active treatment with 
KERYDIN (tavaborole) topical solution, 5%. A PK subgroup of at least 16 evaluable subjects 
ages 12 to 16 years and 11 months will be studied under maximal use conditions.  
The sample size is considered adequate to achieve the study objectives.  No formal power 
calculations were performed. 
5.6 
Changes in the Planned Analyses 
There are no changes to planned analyses. The PK population definition was clarified to include 
available PK data. 
 
 


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6. INDEX OF PLANNED END-OF-TEXT TABLES 
Table 14.1.1.1: Summary of Subject Completion/Discontinuation ...............................................23 
Table 14.1.1.1.1: Summary of Subject Enrollment and Evaluability ............................................24 
Table 14.1.2.1: Summary of Subject Demographic Characteristics (Safety Population) ..............25 
Table 14.1.2.2: Summary of Subject Demographic Characteristics (PK Population) ...................26 
Table 14.1.2.3: Summary of Subject Baseline Characteristics (Safety Population) ......................27 
Table 14.1.2.4: Summary of Subject Baseline Characteristics (PK Population) ...........................28 
Table 14.2.1: Summary of  Clinical and Mycological Characteristics by Visit (Safety Population)29 
Table 14.2.2: Summary of the Primary Efficacy Endpoint: Complete Cure at Week 52 
(Safety Population)................................................................................30 
Table 14.2.3: Summary of  Secondary Efficacy Endpoints (Safety Population) ...........................31 
Table 14.3.1.1.1: Summary of  Local Tolerability Reactions by Visit (Safety Population) ..........33 
Table 14.3.1.1.2: Means Summary of Local Tolerabilty Reactions by Visit (Safety Population) 36 
Table 14.3.1.2.1: Summary of Treatment-Emergent Adverse Event Characteristics  
(Safety Population)................................................................................42 
Table 14.3.1.2.2: Summary of Treatment-Emergent Adverse Events Leading to Permanent 
Withdrawal of Study Drug and/or  Early Discontinuation From the 
Study  (Safety Population) ....................................................................44 
Table 14.3.1.2.3: Summary of Treatment-Emergent Adverse Events by MedDRA System Organ 
Class and Preferred Term  (Safety Population).....................................45 
Table 14.3.1.2.4: Summary of Treatment-Emergent Adverse Events by Severity 
(Safety Population)................................................................................46 
Table 14.3.1.2.4: Summary of Treatment-Emergent Adverse Events by Relationship 
(Safety Population)................................................................................47 
Table 14.3.2.2.1: Summary of Treatment-Emergent Serious Adverse Event Characteristics  
(Safety Population)................................................................................48 
Table 14.3.2.2.2: Summary of Treatment-Emergent Serious Adverse Events by MedDRA 
System Organ Class and Preferred Term  (Safety Population) .............50 
Table 14.3.2.2.3: Summary of Treatment-Emergent Serious Adverse Events by Severity 
(Safety Population)................................................................................51 
Table 14.3.2.2.4: Summary of Treatment-Emergent Serious Adverse Events by Relationship 
(Safety Population)................................................................................52 
Table 14.3.4.1.1: Summary of Hematology Results (Safety Population) ......................................53 
Table 14.3.4.1.2: Summary of Chemistry Results (Safety Population) .........................................54 
Table 14.3.5.1: Summary of  Vital Signs by Visit (Safety Population) .........................................55 


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Table 14.4.1: Extent of Exposure (Safety Population) ..................................................................59 
Table 14.4.2: Summary of Concomitant Medications (Safety Population) ...................................60 
Table 14.4.4.1: Summary of Tavaborole Plasma Concentrations (PK Population) ......................61 
Figure 14.4.4.1.1: Linear Plot of Mean Plasma Concentrations of Tavaborole by Time (PK 
Population) ............................................................................................62 
Figure 14.4.4.1.2:  Semi-logarithmic Plot of Mean Plasma Concentrations of Tavaborole by 
Time (PK Population) ...........................................................................63 
Figure 14.4.4.1.3: By-Subject Linear Plots of Plasma Concentrations of Tavaborole by Time (PK 
Population) ............................................................................................64 
Figure 14.4.4.1.4: By-Subject Semi-logarithmic Plots of Plasma Concentrations of Tavaborole 
by Time (PK Population) ......................................................................65 
Table 14.4.5.1: Summary of Pharmacokinetic Parameters of Tavaborole at Day 29 (PK 
Population) ............................................................................................66 
 
 


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Protocol Number: TAV-ONYC-401 
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Table 14.1.1.1: Summary of Subject Completion/Discontinuation 
 
  
KERYDIN®  
 
(N=xx)  
 
Completed Study 
Yes 
xx ( xx.x%) 
No 
xx ( xx.x%) 
Reason for Discontinuation 
Adverse Event 
xx ( xx.x%) 
Lost to Follow-Up  
xx ( xx.x%) 
Pregnancy  
xx ( xx.x%) 
Protocol Deviation  
xx ( xx.x%) 
Withdrawal by Subject  
xx ( xx.x%) 
Other  
xx ( xx.x%) 
 
 
Listing 16.2.1.1  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 24 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.1.1.1.1: Summary of Subject Enrollment and Evaluability 
 
  
KERYDIN® 
 
Number of Subjects Included in the Safety Population 
xx 
Number of Subjects Excluded from the Safety Population 
xx 
Reason for Exclusion from the Safety Population 
No Confirmed Dose of Study Drug 
xx 
No Post-Baseline Safety Assessment 
xx 
Number of Subjects Included in the Maximal Use Subgroup 
xx 
Number of Subjects Included in the PK Population 
xx 
Number of Subjects Excluded from the PK Population 
xx 
Reason for Exclusion from the PK Population 
Not Included in Maximal Use Subgroup  
xx 
No Available PK Data  
xx 
 
 
Listing 16.2.3  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 
 
 
 
 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 25 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.1.2.1: Summary of Subject Demographic Characteristics 
(Safety Population) 
 
  
KERYDIN®  
 
(N=xx)  
 
Age (years) 
N 
xx 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min. to Max. 
xx to xx 
6 to less than 12 years 
xx ( xx.x%) 
12 years to 16 years, 11 months 
xx ( xx.x%) 
Sex 
N 
xx  
Male 
xx ( xx.x%) 
Female 
xx ( xx.x%) 
Ethnicity 
N 
xx  
Hispanic or Latino 
xx ( xx.x%) 
Not Hispanic or Latino 
xx ( xx.x%) 
Race 
N 
xx  
American Indian or Alaska Native 
xx ( xx.x%) 
Asian 
xx ( xx.x%) 
Black or African American 
xx ( xx.x%) 
Native Hawaiian or Other Pacific Islander 
xx ( xx.x%) 
White 
xx ( xx.x%) 
 
 
Listing 16.2.4.1  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 26 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.1.2.2: Summary of Subject Demographic Characteristics 
(PK Population) 
 
  
KERYDIN®  
 
(N=xx)  
 
Age (years) 
N 
xx 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min. to Max. 
xx to xx 
6 to less than 12 years 
xx ( xx.x%) 
12 years to 16 years, 11 months 
xx ( xx.x%) 
Sex 
N 
xx  
Male 
xx ( xx.x%) 
Female 
xx ( xx.x%) 
Ethnicity 
N 
xx  
Hispanic or Latino 
xx ( xx.x%) 
Not Hispanic or Latino 
xx ( xx.x%) 
Race 
N 
xx  
American Indian or Alaska Native 
xx ( xx.x%) 
Asian 
xx ( xx.x%) 
Black or African American 
xx ( xx.x%) 
Native Hawaiian or Other Pacific Islander 
xx ( xx.x%) 
White 
xx ( xx.x%) 
 
 
Listing 16.2.4.1  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 27 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.1.2.3: Summary of Subject Baseline Characteristics 
(Safety Population) 
 
  
KERYDIN®  
 
(N=xx)  
 
Clinical Assessment of Disease Severity of Target Great Toenail 
N 
xx  
Completely Clear Nail 
xx ( xx.x%) 
Almost Clear Nail 
xx ( xx.x%) 
Mild Onychomycosis  
xx ( xx.x%) 
Moderate Onychomycosis  
xx ( xx.x%) 
Severe Onychomycosis 
xx ( xx.x%) 
% Involvement of Target Great Toenail 
N 
xx 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min. to Max. 
xx to xx 
Number of Other Affected Toenails 
N 
xx 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min. to Max. 
xx to xx 
 
 
Listings 16.2.6.1, 16.2.6.2 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 28 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.1.2.4: Summary of Subject Baseline Characteristics 
(PK Population) 
 
  
KERYDIN®  
 
(N=xx)  
 
Clinical Assessment of Disease Severity of Target Great Toenail 
N 
xx  
Completely Clear Nail 
xx ( xx.x%) 
Almost Clear Nail 
xx ( xx.x%) 
Mild Onychomycosis  
xx ( xx.x%) 
Moderate Onychomycosis  
xx ( xx.x%) 
Severe Onychomycosis 
xx ( xx.x%) 
% Involvement of Target Great Toenail 
N 
xx 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min. to Max. 
xx to xx 
Number of Other Affected Toenails 
N 
xx 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min. to Max. 
xx to xx 
 
 
Listings 16.2.6.1, 16.2.6.2 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 29 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
 
Table 14.2.1: Summary of  Clinical and Mycological Characteristics by Visit 
(Safety Population) 
  
KERYDIN® (N=xx) 
 
Baseline 
 
 
Week 24 
 
 
Week 52 
 
Clinical Assessment of Disease Severity of Target Great 
Toenail 
N 
xx  
xx  
xx  
Completely Clear Nail 
xx  ( xx.x%) 
xx  ( xx.x%) 
xx  ( xx.x%) 
Almost Clear Nail 
xx  ( xx.x%) 
xx  ( xx.x%) 
xx  ( xx.x%) 
Mild Onychomycosis  
xx  ( xx.x%) 
xx  ( xx.x%) 
xx  ( xx.x%) 
Moderate Onychomycosis  
xx  ( xx.x%) 
xx  ( xx.x%) 
xx  ( xx.x%) 
Severe Onychomycosis 
xx  ( xx.x%) 
xx  ( xx.x%) 
xx  ( xx.x%) 
Fungal Culture Result (T. rubrum and T. mentagrophytes) 
N 
xx  
xx  
xx  
Positive  
xx  ( xx.x%) 
xx  ( xx.x%) 
xx  ( xx.x%) 
Negative 
xx  ( xx.x%) 
xx  ( xx.x%) 
xx  ( xx.x%) 
KOH Result 
N 
xx  
xx  
xx  
Positive  
xx  ( xx.x%) 
xx  ( xx.x%) 
xx  ( xx.x%) 
Negative 
xx  ( xx.x%) 
xx  ( xx.x%) 
xx  ( xx.x%) 
 
 
Note: No imputation of missing data. 
Listing 16.2.6.1 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 30 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.2.2: Summary of the Primary Efficacy Endpoint: Complete Cure at Week 52 
(Safety Population) 
 
  
KERYDIN®  
 
(N=xx)  
 
Complete Curea at Week 52 
N 
xx  
Yes 
xx ( xx.x%) 
No 
xx ( xx.x%) 
 
 
a Complete Cure defined as Completely Clear Nail, Negative Fungal Culture and Negative KOH. 
Note: No imputation of missing data. 
Listing 16.2.6.1 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 31 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.2.3: Summary of  Secondary Efficacy Endpoints 
(Safety Population) 
(Page 1 of 2) 
 
  
KERYDIN®  
 
(N=xx)  
 
Complete or Almost Complete Curea at Week 24 
N 
xx  
Yes 
xx ( xx.x%) 
No 
xx ( xx.x%) 
Complete or Almost Complete Curea at Week 52 
N 
xx  
Yes 
xx ( xx.x%) 
No 
xx ( xx.x%) 
Treatment Successb at Week 24 
N 
xx  
Yes 
xx ( xx.x%) 
No 
xx ( xx.x%) 
Treatment Successb at Week 52 
N 
xx  
Yes 
xx ( xx.x%) 
No 
xx ( xx.x%) 
 
 
a Complete or Almost Complete Cure defined as Completely Clear or Almost Clear Nail, Negative Fungal Culture and Negative KOH. 
b Treatment Success defined as Completely Clear or Almost Clear Nail. 
c Negative Mycology defined as Negative Fungal Culture and Negative KOH. 
Note: No imputation of missing data. 
Listing 16.2.6.1 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 32 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.2.3: Summary of  Secondary Efficacy Endpoints 
(Safety Population) 
(Page 2 of 2) 
 
  
KERYDIN®  
 
(N=xx)  
 
Negative Mycologyc at Week 24 
N 
xx  
Yes 
xx ( xx.x%) 
No 
xx ( xx.x%) 
Negative Mycologyc at Week 52 
N 
xx  
Yes 
xx ( xx.x%) 
No 
xx ( xx.x%) 
Fungal Culture at Week 24 (T. rubrum and T. mentagrophytes) 
N 
xx  
Negative 
xx ( xx.x%) 
Positive 
xx ( xx.x%) 
Fungal Culture at Week 52 (T. rubrum and T. mentagrophytes) 
N 
xx  
Negative 
xx ( xx.x%) 
Positive 
xx ( xx.x%) 
 
 
a Complete or Almost Complete Cure defined as Completely Clear or Almost Clear Nail, Negative Fungal Culture and Negative KOH. 
b Treatment Success defined as Completely Clear or Almost Clear Nail. 
c Negative Mycology defined as Negative Fungal Culture and Negative KOH. 
Note: No imputation of missing data. 
Listing 16.2.6.1 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 33 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.3.1.1.1: Summary of  Local Tolerability Reactions by Visit 
(Safety Population) 
(Page 1 of 3) 
  
KERYDIN® (N=xx) 
Burning/Stinging 
 
Baseline  
  
Week 2  
  
Week 4 
  
Week 8  
  
Week 16  
 
N 
xx 
xx 
xx 
xx 
xx 
0 – None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
Week 24  
  
Week 32 
  
Week 40  
  
Week 48  
  
Week 52  
 
N 
xx 
xx 
xx 
xx 
xx 
0 – None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Induration/Edema 
 
Baseline  
  
Week 2  
  
Week 4 
  
Week 8  
  
Week 16  
 
N 
xx 
xx 
xx 
xx 
xx 
0 – None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
Week 24  
  
Week 32 
  
Week 40  
  
Week 48  
  
Week 52  
 
N 
xx 
xx 
xx 
xx 
xx 
0 – None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: No imputation of missing data. 
Listing 16.2.7.1 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 34 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.3.1.1.1: Summary of  Local Tolerability Reactions by Visit 
(Safety Population) 
(Page 2 of 3) 
  
KERYDIN® (N=xx) 
Oozing and Crusting 
 
Baseline  
  
Week 2  
  
Week 4 
  
Week 8  
  
Week 16  
 
N 
xx 
xx 
xx 
xx 
xx 
0 – None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
Week 24  
  
Week 32 
  
Week 40  
  
Week 48  
  
Week 52  
 
N 
xx 
xx 
xx 
xx 
xx 
0 – None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Pruritus 
 
Baseline  
  
Week 2  
  
Week 4 
  
Week 8  
  
Week 16  
 
N 
xx 
xx 
xx 
xx 
xx 
0 – None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
Week 24  
  
Week 32 
  
Week 40  
  
Week 48  
  
Week 52  
 
N 
xx 
xx 
xx 
xx 
xx 
0 – None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: No imputation of missing data. 
Listing 16.2.7.1 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 35 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.3.1.1.1: Summary of  Local Tolerability Reactions by Visit 
(Safety Population) 
(Page 3 of 3) 
  
KERYDIN® (N=xx) 
Erythema 
 
Baseline  
  
Week 2  
  
Week 4 
  
Week 8  
  
Week 16  
 
N 
xx 
xx 
xx 
xx 
xx 
0 – None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
Week 24  
  
Week 32 
  
Week 40  
  
Week 48  
  
Week 52  
 
N 
xx 
xx 
xx 
xx 
xx 
0 – None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Scaling 
 
Baseline  
  
Week 2  
  
Week 4 
  
Week 8  
  
Week 16  
 
N 
xx 
xx 
xx 
xx 
xx 
0 – None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
Week 24  
  
Week 32 
  
Week 40  
  
Week 48  
  
Week 52  
 
N 
xx 
xx 
xx 
xx 
xx 
0 – None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: No imputation of missing data. 
Listing 16.2.7.1 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 36 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.3.1.1.2: Means Summary of Local Tolerabilty Reactions by Visit 
(Safety Population) 
(Page 1 of 6) 
  
KERYDIN® (N=xx) 
Burning/Stinging 
 
Baseline  
  
Week 2  
  
Week 4 
  
Week 8  
  
Week 16  
  
Week 24  
 
N 
xx 
xx 
xx 
xx 
xx 
xx 
Mean 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
SD 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
x to x 
x to x 
x to x 
x to x 
x to x 
x to x 
Change from Baseline 
N 
xx 
xx 
xx 
xx 
xx 
Mean 
x.x 
x.x 
x.x 
x.x 
x.x 
SD 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
x to x 
x to x 
x to x 
x to x 
x to x 
Burning/Stinging 
 
Week 32  
  
Week 40 
  
Week 48  
  
Week 52  
 
N 
xx 
xx 
xx 
xx 
Mean 
x.x 
x.x 
x.x 
x.x 
SD 
x.xx 
x.xx 
x.xx 
x.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
x to x 
x to x 
x to x 
x to x 
Change from Baseline 
N 
xx 
xx 
xx 
xx 
Mean 
x.x 
x.x 
x.x 
x.x 
SD 
x.xx 
x.xx 
x.xx 
x.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
x to x 
x to x 
x to x 
x to x 
 
 
Note: No imputation of missing data. 
Listing 16.2.7.1 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 37 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.3.1.1.2: Means Summary of Local Tolerabilty Reactions by Visit 
(Safety Population) 
(Page 2 of 6) 
  
KERYDIN® (N=xx) 
Induration/Edema 
 
Baseline  
  
Week 2  
  
Week 4 
  
Week 8  
  
Week 16  
  
Week 24  
 
N 
xx 
xx 
xx 
xx 
xx 
xx 
Mean 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
SD 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
x to x 
x to x 
x to x 
x to x 
x to x 
x to x 
Change from Baseline 
N 
xx 
xx 
xx 
xx 
xx 
Mean 
x.x 
x.x 
x.x 
x.x 
x.x 
SD 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
x to x 
x to x 
x to x 
x to x 
x to x 
Induration/Edema 
 
Week 32  
  
Week 40 
  
Week 48  
  
Week 52  
 
N 
xx 
xx 
xx 
xx 
Mean 
x.x 
x.x 
x.x 
x.x 
SD 
x.xx 
x.xx 
x.xx 
x.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
x to x 
x to x 
x to x 
x to x 
Change from Baseline 
N 
xx 
xx 
xx 
xx 
Mean 
x.x 
x.x 
x.x 
x.x 
SD 
x.xx 
x.xx 
x.xx 
x.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
x to x 
x to x 
x to x 
x to x 
 
 
Note: No imputation of missing data. 
Listing 16.2.7.1 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 38 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.3.1.1.2: Means Summary of Local Tolerabilty Reactions by Visit 
(Safety Population) 
(Page 3 of 6) 
  
KERYDIN® (N=xx) 
Oozing and Crusting 
 
Baseline  
  
Week 2  
  
Week 4 
  
Week 8  
  
Week 16  
  
Week 24  
 
N 
xx 
xx 
xx 
xx 
xx 
xx 
Mean 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
SD 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
x to x 
x to x 
x to x 
x to x 
x to x 
x to x 
Change from Baseline 
N 
xx 
xx 
xx 
xx 
xx 
Mean 
x.x 
x.x 
x.x 
x.x 
x.x 
SD 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
x to x 
x to x 
x to x 
x to x 
x to x 
Oozing and Crusting 
 
Week 32  
  
Week 40 
  
Week 48  
  
Week 52  
 
N 
xx 
xx 
xx 
xx 
Mean 
x.x 
x.x 
x.x 
x.x 
SD 
x.xx 
x.xx 
x.xx 
x.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
x to x 
x to x 
x to x 
x to x 
Change from Baseline 
N 
xx 
xx 
xx 
xx 
Mean 
x.x 
x.x 
x.x 
x.x 
SD 
x.xx 
x.xx 
x.xx 
x.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
x to x 
x to x 
x to x 
x to x 
 
 
Note: No imputation of missing data. 
Listing 16.2.7.1 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 39 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.3.1.1.2: Means Summary of Local Tolerabilty Reactions by Visit 
(Safety Population) 
(Page 4 of 6) 
  
KERYDIN® (N=xx) 
Pruritus 
 
Baseline  
  
Week 2  
  
Week 4 
  
Week 8  
  
Week 16  
  
Week 24  
 
N 
xx 
xx 
xx 
xx 
xx 
xx 
Mean 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
SD 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
x to x 
x to x 
x to x 
x to x 
x to x 
x to x 
Change from Baseline 
N 
xx 
xx 
xx 
xx 
xx 
Mean 
x.x 
x.x 
x.x 
x.x 
x.x 
SD 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
x to x 
x to x 
x to x 
x to x 
x to x 
Pruritus 
 
Week 32  
  
Week 40 
  
Week 48  
  
Week 52  
 
N 
xx 
xx 
xx 
xx 
Mean 
x.x 
x.x 
x.x 
x.x 
SD 
x.xx 
x.xx 
x.xx 
x.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
x to x 
x to x 
x to x 
x to x 
Change from Baseline 
N 
xx 
xx 
xx 
xx 
Mean 
x.x 
x.x 
x.x 
x.x 
SD 
x.xx 
x.xx 
x.xx 
x.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
x to x 
x to x 
x to x 
x to x 
 
 
Note: No imputation of missing data. 
Listing 16.2.7.1 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 40 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.3.1.1.2: Means Summary of Local Tolerabilty Reactions by Visit 
(Safety Population) 
(Page 5 of 6) 
  
KERYDIN® (N=xx) 
Erythema 
 
Baseline  
  
Week 2  
  
Week 4 
  
Week 8  
  
Week 16  
  
Week 24  
 
N 
xx 
xx 
xx 
xx 
xx 
xx 
Mean 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
SD 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
x to x 
x to x 
x to x 
x to x 
x to x 
x to x 
Change from Baseline 
N 
xx 
xx 
xx 
xx 
xx 
Mean 
x.x 
x.x 
x.x 
x.x 
x.x 
SD 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
x to x 
x to x 
x to x 
x to x 
x to x 
Erythema 
 
Week 32  
  
Week 40 
  
Week 48  
  
Week 52  
 
N 
xx 
xx 
xx 
xx 
Mean 
x.x 
x.x 
x.x 
x.x 
SD 
x.xx 
x.xx 
x.xx 
x.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
x to x 
x to x 
x to x 
x to x 
Change from Baseline 
N 
xx 
xx 
xx 
xx 
Mean 
x.x 
x.x 
x.x 
x.x 
SD 
x.xx 
x.xx 
x.xx 
x.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
x to x 
x to x 
x to x 
x to x 
 
 
Note: No imputation of missing data. 
Listing 16.2.7.1 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 41 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.3.1.1.2: Means Summary of Local Tolerabilty Reactions by Visit 
(Safety Population) 
(Page 6 of 6) 
  
KERYDIN® (N=xx) 
Scaling 
 
Baseline  
  
Week 2  
  
Week 4 
  
Week 8  
  
Week 16  
  
Week 24  
 
N 
xx 
xx 
xx 
xx 
xx 
xx 
Mean 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
SD 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
x to x 
x to x 
x to x 
x to x 
x to x 
x to x 
Change from Baseline 
N 
xx 
xx 
xx 
xx 
xx 
Mean 
x.x 
x.x 
x.x 
x.x 
x.x 
SD 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
x to x 
x to x 
x to x 
x to x 
x to x 
Scaling 
 
Week 32  
  
Week 40 
  
Week 48  
  
Week 52  
 
N 
xx 
xx 
xx 
xx 
Mean 
x.x 
x.x 
x.x 
x.x 
SD 
x.xx 
x.xx 
x.xx 
x.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
x to x 
x to x 
x to x 
x to x 
Change from Baseline 
N 
xx 
xx 
xx 
xx 
Mean 
x.x 
x.x 
x.x 
x.x 
SD 
x.xx 
x.xx 
x.xx 
x.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
x to x 
x to x 
x to x 
x to x 
 
 
Note: No imputation of missing data. 
Listing 16.2.7.1 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 42 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
 
Table 14.3.1.2.1: Summary of Treatment-Emergent Adverse Event Characteristics  
(Safety Population) 
(Page 1 of 2) 
 
  
KERYDIN®  
 
(N=xx)  
 
Subjects Reporting Any Adverse Event 
xx ( xx.x%) 
Subjects Reporting Any Serious Adverse Event 
xx ( xx.x%) 
Subjects Who Died 
xx ( xx.x%) 
Subjects Who Discontinued Study Drug Due to Adverse Event 
xx ( xx.x%) 
Total Number of Adverse Events Reported 
xx  
By Subject 
By Maximum Severity 
Mild 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
By Strongest Relationship to Study Drug 
xx ( xx.x%) 
Definite 
xx ( xx.x%) 
Probable  
xx ( xx.x%) 
Possible  
xx ( xx.x%) 
Unlikely  
xx ( xx.x%) 
Not Related  
xx ( xx.x%) 
 
 
Note: Treatment-emergent adverse events are those with an onset on or after the first application of study drug. 
Listing 16.2.7.2.3 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 43 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.3.1.2.1: Summary of Treatment-Emergent Adverse Event Characteristics  
(Safety Population) 
(Page 2 of 2) 
 
  
KERYDIN®  
 
(N=xx)  
 
By Subject 
Maximum Severity within Relationship 
to Study Drug 
Definite 
 Mild 
xx ( xx.x%) 
 Moderate 
xx ( xx.x%) 
 Severe 
xx ( xx.x%) 
Probable  
 
 Mild 
xx ( xx.x%) 
 Moderate 
xx ( xx.x%) 
 Severe 
xx ( xx.x%) 
Possible  
 
 Mild 
xx ( xx.x%) 
 Moderate 
xx ( xx.x%) 
 Severe 
xx ( xx.x%) 
Unlikely  
 
 Mild 
xx ( xx.x%) 
 Moderate 
xx ( xx.x%) 
 Severe 
xx ( xx.x%) 
Not Related  
 
 Mild 
xx ( xx.x%) 
 Moderate 
xx ( xx.x%) 
 Severe 
xx ( xx.x%) 
 
 
Note: Treatment-emergent adverse events are those with an onset on or after the first application of study drug. 
Listing 16.2.7.2.3 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 44 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.3.1.2.2: Summary of Treatment-Emergent Adverse Events Leading to Permanent Withdrawal of Study Drug and/or  
Early Discontinuation From the Study  
(Safety Population) 
(Page xx of yy) 
 
System Organ Classa 
Preferred Term  
 
  
KERYDIN®  
 
(N=xx)  
 
 
System Organ Class 
xx ( xx.x%) 
Preferred Term 
xx ( xx.x%) 
 
a Counts reflect numbers of subjects reporting one or more adverse events that map to MedDRA. At each level of summarization (System Organ Class or  
Preferred Term) subjects are counted once. 
Note: MedDRA Version 18.0. 
Note: Treatment-emergent adverse events are those with an onset on or after the first application of study drug. 
Listing 16.2.7.2.3 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 45 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.3.1.2.3: Summary of Treatment-Emergent Adverse Events by MedDRA System Organ Class and Preferred Term  
(Safety Population) 
(Page xx of yy) 
 
System Organ Classa 
Preferred Term  
 
  
KERYDIN®  
 
(N=xx)  
 
 
System Organ Class 
xx ( xx.x%) 
Preferred Term 
xx ( xx.x%) 
 
a Counts reflect numbers of subjects reporting one or more adverse events that map to MedDRA. At each level of summarization (System Organ Class or  
Preferred Term) subjects are counted once. 
Note: MedDRA Version 18.0. 
Note: Treatment-emergent adverse events are those with an onset on or after the first application of study drug. 
Listing 16.2.7.2.3 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 
 
 
 
 
 
{NOTE TO PROGRAMMER: Order table by decreasing incidence of Total column.  All subsequent tables including summaries by  MedDRA SOC 
and PT should display the SOC and PT in the same order.} 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 46 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.3.1.2.4: Summary of Treatment-Emergent Adverse Events by Severity 
(Safety Population) 
(Page xx of yy) 
 
System Organ Classa 
Preferred Term  
 Severity 
  
KERYDIN®  
 
(N=xx)  
 
 
System Organ Class 
Mild 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
Preferred Term 
Mild 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
 
a Counts reflect numbers of subjects reporting one or more adverse events that map to MedDRA. At each level of summarization (System Organ Class or  
Preferred Term) subjects are counted once under the greatest reported severity. 
Note: MedDRA Version 18.0. 
Note: Treatment-emergent adverse events are those with an onset on or after the first application of study drug. 
Listing 16.2.7.2.3 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 47 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.3.1.2.4: Summary of Treatment-Emergent Adverse Events by Relationship 
(Safety Population) 
(Page xx of yy) 
 
System Organ Classa 
Preferred Term  
 Relationship 
  
KERYDIN®  
 
(N=xx)  
 
 
System Organ Class 
Definite 
xx ( xx.x%) 
Probable 
xx ( xx.x%) 
Possible 
xx ( xx.x%) 
Unlikely 
xx ( xx.x%) 
Not Related 
xx ( xx.x%) 
Preferred Term 
Definite 
xx ( xx.x%) 
Probable 
xx ( xx.x%) 
Possible 
xx ( xx.x%) 
Unlikely 
xx ( xx.x%) 
Not Related 
xx ( xx.x%) 
 
a Counts reflect numbers of subjects reporting one or more adverse events that map to MedDRA. At each level of summarization (System Organ Class or  
Preferred Term) subjects are counted once under the greatest reported relationship. 
Note: MedDRA Version 18.0. 
Note: Treatment-emergent adverse events are those with an onset on or after the first application of study drug. 
Listing 16.2.7.2.3 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 48 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.3.2.2.1: Summary of Treatment-Emergent Serious Adverse Event Characteristics  
(Safety Population) 
(Page 1 of 2) 
 
  
KERYDIN®  
 
(N=xx)  
 
Subjects Reporting Any Serious Adverse Event 
xx ( xx.x%) 
Subjects Who Died 
xx ( xx.x%) 
Subjects Who Discontinued Study Drug Due to Adverse Event 
xx ( xx.x%) 
Total Number of Adverse Events Reported 
xx  
By Subject 
By Maximum Severity 
Mild 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
By Strongest Relationship to Study Drug 
xx ( xx.x%) 
Definite 
xx ( xx.x%) 
Probable  
xx ( xx.x%) 
Possible  
xx ( xx.x%) 
Unlikely  
xx ( xx.x%) 
Not Related  
xx ( xx.x%) 
 
 
Note: Treatment-emergent serious adverse events are those with an onset on or after the first application of study drug. 
Listing 16.2.7.2.4 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 49 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.3.2.2.1: Summary of Treatment-Emergent Serious Adverse Event Characteristics  
(Safety Population) 
(Page 2 of 2) 
 
  
KERYDIN®  
 
(N=xx)  
 
By Subject 
Maximum Severity within Relationship 
to Study Drug 
Definite 
 Mild 
xx ( xx.x%) 
 Moderate 
xx ( xx.x%) 
 Severe 
xx ( xx.x%) 
Probable  
 
 Mild 
xx ( xx.x%) 
 Moderate 
xx ( xx.x%) 
 Severe 
xx ( xx.x%) 
Possible  
 
 Mild 
xx ( xx.x%) 
 Moderate 
xx ( xx.x%) 
 Severe 
xx ( xx.x%) 
Unlikely  
 
 Mild 
xx ( xx.x%) 
 Moderate 
xx ( xx.x%) 
 Severe 
xx ( xx.x%) 
Not Related  
 
 Mild 
xx ( xx.x%) 
 Moderate 
xx ( xx.x%) 
 Severe 
xx ( xx.x%) 
 
 
Note: Treatment-emergent serious adverse events are those with an onset on or after the first application of study drug. 
Listing 16.2.7.2.4 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 50 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.3.2.2.2: Summary of Treatment-Emergent Serious Adverse Events by MedDRA System Organ Class and Preferred Term  
(Safety Population) 
(Page xx of yy) 
 
System Organ Classa 
Preferred Term  
 
  
KERYDIN®  
 
(N=xx)  
 
 
System Organ Class 
xx ( xx.x%) 
Preferred Term 
xx ( xx.x%) 
 
a Counts reflect numbers of subjects reporting one or more serious adverse events that map to MedDRA. At each level of summarization (System Organ  
Class or Preferred Term) subjects are counted once. 
Note: MedDRA Version 18.0. 
Note: Treatment-emergent serious adverse events are those with an onset on or after the first application of study drug. 
Listing 16.2.7.2.4 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 
 
 
 
 
 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 51 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.3.2.2.3: Summary of Treatment-Emergent Serious Adverse Events by Severity 
(Safety Population) 
(Page xx of yy) 
 
System Organ Classa 
Preferred Term  
 Severity 
  
KERYDIN®  
 
(N=xx)  
 
 
System Organ Class 
Mild 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
Preferred Term 
Mild 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
 
a Counts reflect numbers of subjects reporting one or more serious adverse events that map to MedDRA. At each level of summarization (System Organ  
Class or Preferred Term) subjects are counted once under the greatest reported severity. 
Note: MedDRA Version 18.0. 
Note: Treatment-emergent serious adverse events are those with an onset on or after the first application of study drug. 
Listing 16.2.7.2.4 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 52 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.3.2.2.4: Summary of Treatment-Emergent Serious Adverse Events by Relationship 
(Safety Population) 
(Page xx of yy) 
 
System Organ Classa 
Preferred Term  
 Relationship 
  
KERYDIN®  
 
(N=xx)  
 
 
System Organ Class 
Definite 
xx ( xx.x%) 
Probable 
xx ( xx.x%) 
Possible 
xx ( xx.x%) 
Unlikely 
xx ( xx.x%) 
Not Related 
xx ( xx.x%) 
Preferred Term 
Definite 
xx ( xx.x%) 
Probable 
xx ( xx.x%) 
Possible 
xx ( xx.x%) 
Unlikely 
xx ( xx.x%) 
Not Related 
xx ( xx.x%) 
 
a Counts reflect numbers of subjects reporting one or more serious adverse events that map to MedDRA. At each level of summarization (System Organ  
Class or Preferred Term) subjects are counted once under the greatest reported relationship. 
Note: MedDRA Version 18.0. 
Note: Treatment-emergent serious adverse events are those with an onset on or after the first application of study drug. 
Listing 16.2.7.2.4 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 
 
 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 53 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.3.4.1.1: Summary of Hematology Results 
(Safety Population) 
(Page 1 of x) 
  
Test name (units) 
 
 KERYDIN® 
 
 (N=xxx) 
 
 
 
Baseline 
 
 
Week 24 
 
 Change from  
 
Baseline 
 
 
Baseline 
 
 
Week 52 
 
 Change from  
 
Baseline 
 
N 
xxx 
Xxx 
xxx 
xxx 
xxx 
xxx 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
 
Week 24 
 
 
Week 52 
 
Baseline 
 
BNL 
 
 
WNL 
 
 
ANL 
 
 
BNL 
 
 
WNL 
 
 
ANL 
 
BNL 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
WNL 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
ANL 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: BNL=Below Normal Limit, WNL=Within Normal Limits, ANL=Above Normal Limit. 
Note: No imputation of missing values.  
 
Listing 16.2.8.2.1 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 54 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.3.4.1.2: Summary of Chemistry Results 
(Safety Population) 
(Page 1 of x) 
  
Test name (units) 
 
 KERYDIN® 
 
 (N=xxx) 
 
 
 
Baseline 
 
 
Week 24 
 
 Change from  
 
Baseline 
 
 
Baseline 
 
 
Week 52 
 
 Change from  
 
Baseline 
 
N 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
 
Week 24 
 
 
Week 52 
 
Baseline 
 
BNL 
 
 
WNL 
 
 
ANL 
 
 
BNL 
 
 
WNL 
 
 
ANL 
 
BNL 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
WNL 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
ANL 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: BNL=Below Normal Limit, WNL=Within Normal Limits, ANL=Above Normal Limit. 
Listing 16.2.8.2.1 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 55 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.3.5.1: Summary of  Vital Signs by Visit 
(Safety Population) 
(Page 1 of 4) 
  
KERYDIN® (N=xx) 
Systolic Blood Pressure (mmHg) 
 
Baseline  
  
Week 2  
  
Week 4 
  
Week 8  
  
Week 16  
  
Week 24  
 
N 
xx 
xx 
xx 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
Change from Baseline 
N 
xx 
xx 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
Systolic Blood Pressure (mmHg) 
 
Week 32  
  
Week 40 
  
Week 48  
  
Week 52  
 
N 
xx 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
Change from Baseline 
N 
xx 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
 
 
Note: No imputation of missing data. 
Listing16.2.8.3 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 56 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.3.5.1: Summary of  Vital Signs by Visit 
(Safety Population) 
(Page 2 of 4) 
  
KERYDIN® (N=xx) 
Diastolic Blood Pressure (mmHg) 
 
Baseline  
  
Week 2  
  
Week 4 
  
Week 8  
  
Week 16  
  
Week 24  
 
N 
xx 
xx 
xx 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
Change from Baseline 
N 
xx 
xx 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
Diastolic Blood Pressure (mmHg) 
 
Week 32  
  
Week 40 
  
Week 48  
  
Week 52  
 
N 
xx 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
Change from Baseline 
N 
xx 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
 
 
Note: No imputation of missing data. 
Listing16.2.8.3 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 57 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.3.5.1: Summary of  Vital Signs by Visit 
(Safety Population) 
(Page 3 of 4) 
  
KERYDIN® (N=xx) 
Pulse Rate (beats/min) 
 
Baseline  
  
Week 2  
  
Week 4 
  
Week 8  
  
Week 16  
  
Week 24  
 
N 
xx 
xx 
xx 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
Change from Baseline 
N 
xx 
xx 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
Pulse Rate (beats/min) 
 
Week 32  
  
Week 40 
  
Week 48  
  
Week 52  
 
N 
xx 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
Change from Baseline 
N 
xx 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
 
 
Note: No imputation of missing data. 
Listing16.2.8.3 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 58 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.3.5.1: Summary of  Vital Signs by Visit 
(Safety Population) 
(Page 4 of 4) 
  
KERYDIN® (N=xx) 
Respiratory Rate (breaths/min) 
 
Baseline  
  
Week 2  
  
Week 4 
  
Week 8  
  
Week 16  
  
Week 24  
 
N 
xx 
xx 
xx 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
Change from Baseline 
N 
xx 
xx 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
Respiratory Rate (breaths/min) 
 
Week 32  
  
Week 40 
  
Week 48  
  
Week 52  
 
N 
xx 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
Change from Baseline 
N 
xx 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
 
 
Note: No imputation of missing data. 
Listing16.2.8.3 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 59 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.4.1: Extent of Exposure 
(Safety Population) 
 
  
KERYDIN®  
 
(N=xx)  
 
Total Number of Dosing Days 
N 
xx 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min. to Max. 
xx to xx 
Total Number of Applications 
N 
xx 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min. to Max. 
xx to xx 
Total Amount of Study Drug Applied (g) 
N 
xx 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min. to Max. 
xx to xx 
 
 
Listings 16.2.5.2, 16.2.5.3 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 60 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.4.2: Summary of Concomitant Medications 
(Safety Population) 
(Page xx of yy) 
 
ATC Level 2 Terma 
Preferred Name 
 
  
KERYDIN®  
 
(N=xx)  
 
 
ATC Level 2 Term 
xx ( xx.x%) 
Preferred Name  
xx ( xx.x%) 
 
a Counts reflect numbers of subjects with concomitant medications that map to WHO-DDE. At each level of summarization (ATC Level 2 Term or  
Preferred Name) subjects are counted once. 
Note: WHO-DDE Format B2, Version March 1, 2015. 
Listing 16.2.4.3.2 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 61 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.4.4.1: Summary of Tavaborole Plasma Concentrations 
(PK Population) 
 
 
KERYDIN® (N=xx) 
 
Day 15 
 
  
Pre-Dose  
 
Plasma Concentration 
Below the Lower Limit of Quantification 
xxx ( 
xx.x%) 
Detectable Concentrations 
N 
xxx 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min. to Max. 
xx to xx 
 
Day 29 
 
  
Pre-Dose  
 
 4 Hour Post-Dose   6 Hours Post-Dose    8 Hours Post-Dose  24 Hours Post-Dose   
Plasma Concentration 
Below the Lower Limit of Quantification 
xxx ( 
xx.x%) 
xxx ( 
xx.x%) 
xxx ( 
xx.x%) 
xxx ( 
xx.x%) 
xxx ( 
xx.x%) 
Detectable Concentrations 
N 
xxx 
xxx 
xxx 
xxx 
xxx 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
 
 
Note: Lower Limit of Quantification = x ng/mL 
Note: No imputation of missing data. 
Listing 16.2.6.3 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 62 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Figure 14.4.4.1.1: Linear Plot of Mean Plasma Concentrations of Tavaborole by Time 
(PK Population) 
(Page xx of yy) 
 
 
 
Note: Figure represents mean concentrations +/- standard errors. 
Note: No imputation of missing data. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 63 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Figure 14.4.4.1.2:  Semi-logarithmic Plot of Mean Plasma Concentrations of Tavaborole by Time 
(PK Population) 
(Page xx of yy) 
 
 
 
Note: Figure represents mean concentrations +/- standard errors. 
Note: No imputation of missing data. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 64 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Figure 14.4.4.1.3: By-Subject Linear Plots of Plasma Concentrations of Tavaborole by Time 
(PK Population) 
(Page xx of yy) 
 
Subject xxxxx 
 
 
Note: No imputation of missing data. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 65 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Figure 14.4.4.1.4: By-Subject Semi-logarithmic Plots of Plasma Concentrations of Tavaborole by Time 
(PK Population) 
(Page xx of yy) 
 
Subject xxxxx 
 
 
Note: No imputation of missing data. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 66 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
 
Table 14.4.5.1: Summary of Pharmacokinetic Parameters of Tavaborole at Day 29 
(PK Population) 
(Page 1 of 2) 
 
Day 29 
  
KERYDIN®  
 
(N=xx)  
 
Cmax 
N 
xx 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min. to Max. 
xx to xx 
Tmax 
N 
xx 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min. to Max. 
xx to xx 
AUC0-24 
N 
xx 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min. to Max. 
xx to xx 
 
 
Note: Lower Limit of Quantification = x ng/mL 
Note: No imputation of missing data. 
Listing 16.2.6.4 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 67 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
Table 14.4.5.1: Summary of Pharmacokinetic Parameters at Day 29 
(PK Population) 
(Page 2 of 2) 
 
Day 29 
  
KERYDIN®  
 
(N=xx)  
 
AUC0-∞ 
N 
xx 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min. to Max. 
xx to xx 
Constant of Elimination (λZ) 
N 
xx 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min. to Max. 
xx to xx 
Elimination half-life (t1/2) 
N 
xx 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min. to Max. 
xx to xx 
 
 
Note: Lower Limit of Quantification = x ng/mL 
Note: No imputation of missing data. 
Listing 16.2.6.4 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


CONFIDENTIAL 
 
 
 
 
Statistical Analysis Plan for Anacor Pharmaceuticals, Inc. 
Page 68 
Protocol Number: TAV-ONYC-401 
June 2, 2017 
7. INDEX OF PLANNED LISTINGS 
Listing 16.2.1.1: End of Study Information ................................................................................  
Listing 16.2.1.2.1: Discontinued Subjects ..................................................................................  
Listing 16.2.2: Inclusion/Exclusion Criteria Violations .............................................................  
Listing 16.2.3: Analysis Populations ..........................................................................................  
Listing 16.2.4.1: Subject Demographic Information ..................................................................  
Listing 16.2.4.2: Medical History ...............................................................................................  
Listing 16.2.4.3.1: Unique Medication Names Coded to WHO-DD ATC Level 2 Terms and 
Preferred Names........................................................................................................  
Listing 16.2.4.3.2: Prior and Concomitant Medications .............................................................  
Listing 16.2.4.4: Prior and Concomitant Therapies and Procedures ..........................................  
Listing 16.2.5.1: Study Visit Compliance ...................................................................................  
Listing 16.2.5.2: Study Medication Accountability Log ............................................................  
Listing 16.2.5.3: Dosing Diary Information ...............................................................................  
Listing 16.2.6.1: Target Great Toenail Assessments ..................................................................  
Listing 16.2.6.2: Non-Target Great Toenail Assessments ..........................................................  
Listing 16.2.6.3: Pharmacokinetic Blood Draw Information .....................................................  
Listing 16.2.6.4: Pharmacokinetic Parameters ...........................................................................  
Listing 16.2.7.1: Local Tolerability Reactions ...........................................................................  
Listing 16.2.7.2.1: Unique Adverse Events Coded to MedDRA System Organ Classes and 
Preferred Terms ........................................................................................................  
Listing 16.2.7.2.2: Pre-Treatment Adverse Events .....................................................................  
Listing 16.2.7.2.3: Treatment-Emergent Adverse Events ...........................................................  
Listing 16.2.7.2.4: Serious Adverse Events ................................................................................  
Listing 16.2.7.2.5: Subjects Who Permanently Discontinued Study Drug and/or Discontinued 
from the Study Due to Adverse Events.....................................................................  
Listing 16.2.8.1: Pregnancy Tests ...............................................................................................  
Listing 16.2.8.2.1: Laboratory Results........................................................................................  
Listing 16.2.8.2.2: Abnormal Laboratory Results ......................................................................  
Listing 16.2.8.3: Vital Signs .......................................................................................................