Clinical trial NCT03130738
Conditions: Otomycosis
Sponsor: Hill Dermaceuticals, Inc.
Start date: 2017-04-20; Completion date: 2019-08-06
Enrollment: 65 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of the study is to evaluate the efficacy and safety of active treatment (miconazole oil) for 7 versus 14 days, and to compare 14 days of active treatment (miconazole oil) to inactive treatment (placebo) over a 14-day treatment duration, in subjects with fungal infection (otomycosis) of the external ear.

Detailed description:
Miconazole, an imidazole antifungal agent, is commonly used for different types of fungal skin infections, such as Candida, ringworm, jock itch, athlete's foot, nail fungus, vaginal yeast infections, and oropharyngeal candidiasis. The 2% formulation of miconazole is commonly used for dermatophytic infections. The mechanisms of action of miconazole against fungi in general appear to be applicable to fungi associated with otomycosis, in that miconazole has been demonstrated to have activity in vitro against some clinical isolates of fungi associated with human otomycosis in the US.

Miconazole targets the cytochrome P450-dependent enzyme 14-α-sterol demethylase, an enzyme that is also involved in mammalian cholesterol synthesis, resulting in inhibition of ergosterol biosynthesis in the cell membrane of the fungal organism. Because ergosterol is an important component of the cell membrane, inhibition of its synthesis inhibits fungal cell growth.

In addition to its activity toward the enzyme 14-α-sterol demethylase, miconazole also leads to increased reactive oxygen species in fungal organisms, which appears to result in fungicidal activity.

Arms: arm 1: 7 days of 2x per day of treatment with Miconazole Oil (Active Drug Product 2% Miconazole) arm 2: 14 days of 2x per day of treatment with Miconazole Oil (Active Drug Product 2% Miconazole) arm 3: 14 days of 2x per day of treatment with Placebo - Oil Vehicle, Study Drug base without active ingredient
Interventions: intervention 1: 7-Day Miconazole Oil (Miconazole 2%) intervention 2: 14-Day Miconazole Oil (Miconazole 2%) intervention 3: 14-Day Placebo - Oil Vehicle
Intervention descriptions: intervention 1: 7 days of 2x per day treatment with Miconazole Oil (Active Drug Product 2% Miconazole) intervention 2: 14 days of 2x per day treatment with Miconazole Oil (Active Drug Product 2% Miconazole) intervention 3: 14 days of 2x per day treatment with Placebo - Oil Vehicle, Study Drug base without active ingredient

Protocol documents:
Prot_000.pdf: 
Hill Dermaceuticals, Inc. 
 
Protocol HD-MCZ-PHII-DRF062016 
                                                                                                                   17 April 2019 / Version 6 
Page 1 of 64 
CLINICAL TRIAL PROTOCOL 
 
Study Title: 
Dose-Ranging Study of the Efficacy and Safety of Miconazole 
Oil Used for 7 or 14 Days Compared with Vehicle in the 
Treatment of Otomycosis 
Study Number: 
HD-MCZ-PHII-DRF062016 
Study Drug: 
Miconazole oil 
Sponsor: 
Hill Dermaceuticals, Inc. 
2650 S. Mellonville Ave 
Sanford, FL 32773 
Protocol Date/Version: 
17 April 2019 / Version 6 
Previous versions: 
10 August 2016 / Version 1 
14 February 2017 / Version 2 
14 June 2017 / Version 3 
11 October 2017 / Version 4 
11 May 2018 / Version 5 
The information contained in this document is confidential and proprietary property of Hill 
Dermaceuticals, Inc. 


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PROTOCOL APPROVAL 
The following individuals approve the 17 April 2019 version of the HD-MCZ-PHII-DRF062016 
protocol. All changes to this version of the protocol must have prior written approval and require 
an amendment or administrative letter. 
 
Company: 
Hill Dermaceuticals, Inc. 
Name: 
Rosario G. Ramirez, MD 
Title: 
Medical Director, Research & Development 
Address: 
2650 South Mellonville Avenue 
 
Sanford, FL 32773 
 
 
 
 
 
Signature                                                      Date 
 
Rosario Ramirez
Digitally signed by Rosario Ramirez 
DN: c=US, st=FL, l=Sanford, o=Hill Dermaceuticals, Inc, cn=Rosario 
Ramirez, email=nini.ramirez@hillderm.com 
Reason: I am approving this document 
Date: 2019.05.09 12:40:09 -04'00'


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STUDY ACKNOWLEDGMENT 
Protocol number: HD-MCZ-PHII-DRF062016 Version 6 
I have read this protocol and commit to conduct the study as outlined herein. I agree to comply 
with all applicable regulations and to conduct the study as described in the protocol.  
________________________________________ 
_____________________ 
Investigator’s signature 
Date 
________________________________________ 
Investigator’s printed name 


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SYNOPSIS 
Name of Sponsor/Company: Hill Dermaceuticals, Inc. 
Name of Finished Product: Miconazole oil 
Name of Active Ingredient: 2% miconazole 
Study Title: 
Dose-Ranging Study of the Efficacy and Safety of Miconazole Oil Used for 7 or 14 Day 
Compared with Vehicle in the Treatment of Otomycosis 
Study Number: HD-MCZ-PHII-DRF062016 
Study Center(s): Up to 10 study centers in the United States (US) 
Number of Subjects Planned: Approximately 75 
Study Period: 
The study duration for each subject will be up to 30 days (up to 14 days of treatment, and 8 
days of follow-up, including the visit window of up to 8 additional days after the scheduled day 
to complete the final visit) 
Phase of Development: 2 
Objectives: 
• Obtain preliminary evidence of the efficacy and safety of miconazole oil compared with 
vehicle over a 14-day treatment duration 
• Descriptively compare the efficacy and safety of miconazole oil over 7 versus 14 days  
Design and Methodology: 
This study is a randomized, partially masked, multiple-dose, parallel-group design study 
conducted at up to 10 study centers in the US. Approximately 75 male or female subjects with 
otomycosis will receive study drug. Subjects will be randomly assigned in a 1:1:1 ratio to 
receive miconazole oil [administered as 5 drops per ear at ~30 mg per drop instilled into the 
external ear canal of the ear(s) affected by otomycosis] for 7 or 14 days, or vehicle for 14 days. 
During the study it is planned to assess treatment allocation to ensure that there is a sufficient 
number of subjects within each group for the primary analysis. If deemed necessary, future 
randomizations may be adjusted. For subjects assigned to the 14-day treatment duration with 
either miconazole oil or vehicle, the contents of the study drug will be masked to both the 
subject and the investigator and study staff (i.e., double-blind), but the treatment duration 
assigned to each subject (7 or 14 days) will be unmasked to both the subject and the 
investigator and study staff.  
At Screening/Baseline (Day 1), potentially eligible subjects will provide informed consent, and 
subjects will undergo screening evaluations to include a physical examination, an assessment 
of the signs and symptoms of otomycosis (pruritus, debris, visual examination for presence of 
fungal elements, and pain), and an evaluation of medical history. Urine will be obtained for 
pregnancy screening in female subjects of childbearing potential. Prior and concomitant 
medications will be reported. Subjects with positive signs and symptoms of otomycosis and 
who meet all other eligibility criteria will be entered into the study, and a subject global 
assessment of disease will be performed. Fungal and bacterial cultures of the affected ear(s) 
will be taken, then debris will be cleaned from the affected ear(s) following the site’s normal 
procedures. The subject will then begin treatment with study drug. The subject or caregiver will 
instill the first dose of study drug at the site, under the supervision of the investigator or site 
personnel. Adverse events (AEs) will then be assessed. The subject will then leave the clinic 
and continue to administer the study drug twice per day as instructed. Subjects will be 
instructed to avoid getting water in the ear, to consider drying excessive water in the ear by 


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Name of Sponsor/Company: Hill Dermaceuticals, Inc. 
Name of Finished Product: Miconazole oil 
Name of Active Ingredient: 2% miconazole 
using a blow dryer, and to place a Vaseline-impregnated cotton ball over the affected ear(s) to 
help keep water out of the ear while bathing or showering. 
 
All subjects will return to the clinic on Day 8. For subjects randomized to the 7-day treatment 
duration, this visit will constitute the End of Treatment Visit, with procedures performed as 
described for that visit below. Subjects randomized to 7-day treatment will not administer study 
drug on Day 8. For all other subjects, for whom this visit will constitute an On Treatment Visit, a 
clinical evaluation of the signs and symptoms of otomycosis, a subject global assessment, a 
cleaning of the affected ear(s) (following the site’s normal procedures), and an assessment of 
AEs and concomitant medications will be performed, and these subjects will continue to 
administer the study drug twice per day, up through Day 14, following the same instructions as 
provided at the Screening/Baseline Visit on Day 1. 
All subjects will return to the clinic on Day 15. For subjects randomized to the 7-day treatment 
duration, this visit will constitute the Test of Cure Visit, with procedures performed as described 
for the Test of Cure Visit below. For subjects randomized to the 14-day treatment duration, this 
visit will constitute the End of Treatment Visit, with procedures performed as described for the 
End of Treatment Visit below. 
Subjects randomized to the 14-day treatment durations will return to the clinic on Day 22, for 
the Test of Cure Visit, with procedures performed as described for the Test of Cure Visit below.  
Procedures performed at the End of Treatment Visit will include an assessment for clinical 
signs and symptoms of otomycosis, a subject global assessment, and a fungal culture of the 
affected ear(s). For subjects randomized to the 7-day treatment duration, subjects will have the 
affected ear(s) cleaned according to the site’s normal procedures at this visit, after the efficacy 
procedures have been completed. AEs and concomitant medications will also be assessed, 
and the subject will return all unused study drug. 
Procedures performed at the Test of Cure Visit will include an assessment of clinical signs and 
symptoms of otomycosis, a subject global assessment, and a fungal culture of the affected 
ear(s). AEs and concomitant medications will also be assessed. A urine pregnancy test will be 
performed in women of childbearing potential. 
Study Visits: 
Screening/Baseline (1 visit); On Treatment (up to 1 visit); End of Treatment (1 visit); Test of 
Cure (1 visit) 
Efficacy Evaluations: 
• Clinical signs and symptoms of otomycosis (pruritus; debris; presence of fungal elements; 
pain) 
• Fungal culture 
• Subject global assessment 
Safety Evaluations: 
• AEs 


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Name of Sponsor/Company: Hill Dermaceuticals, Inc. 
Name of Finished Product: Miconazole oil 
Name of Active Ingredient: 2% miconazole 
Key Inclusion Criteria: 
Male or non-pregnant, non-lactating females with a clinical diagnosis of uncomplicated 
otomycosis of the external ear only, with an intact tympanic membrane, who are in general 
good health as determined by medical examination and medical history, and who are free of 
clinically significant disease, including diabetes mellitus, that is not well-controlled or that could 
interfere with the study, will be included in the study.  
Key Exclusion Criteria: 
Subjects with any other dermatoses or conditions of the ear that may interfere with the 
evaluation of otomycosis, including concomitant otic infections (including bacterial infection) 
that require antimicrobial treatment, disease that has spread beyond the external ear(s), or 
pre-existing skin atrophy of the affected ear(s); tympanostomy tube or perforated tympanic 
membrane in the ear(s) that will be treated with study drug; history of prior surgery directly 
affecting and compromising the external auditory canal and/or tympanic membrane of the 
ear(s) that will be treated with study drug, except for prior tympanostomy tube(s) that have 
already been removed and completely healed; use of any topical medicated treatments for 
otomycosis within 14 days of study entry; use of any systemic antifungal therapy within 28 
days of study entry, warfarin within 28 days of study entry, immunosuppressive or immune-
stimulating drugs within 28 days of study entry, or systemic steroids within 3 months of study 
entry; fever of ≥100°F at study entry; recurrent otomycosis that has been unresponsive to 
previous antifungal treatment; known hypersensitivity to any of the components in the test 
formulation; and participation in another investigative trial within 28 days of study entry will be 
excluded from the study. 
Test Product, Dose, and Mode of Administration: 
Miconazole oil (7-day and 14-day treatment durations) 
Active ingredient: 2% miconazole 
Other ingredients: refined peanut oil, mineral oil, oleth-2, and isopropyl myristate 
Mode of administration: subjects will be seated and then instructed to tilt their heads so that 
the affected ear is facing up. The subject or caregiver will then gently pull the ear lobe 
backward and upward and apply 5 drops of miconazole oil into the ear. The subject will be 
instructed to keep the head tilted with the ear facing up for approximately 1 minute to allow the 
miconazole oil to penetrate lower into the ear canal. If both ears are being treated, the process 
will then be repeated for the other ear after a 5-minute wait.  
Reference Product, Dose, and Mode of Administration: 
Vehicle (14-day treatment duration) 
Active ingredient: none (vehicle group) 
Other ingredients: refined peanut oil, mineral oil, oleth-2, and isopropyl myristate 
Mode of administration: same as described for the test product.  
Statistical Analyses: 
The primary and secondary endpoints will be based on the investigator reporting of signs and 
symptoms. Other efficacy endpoints will be based on the subject reporting of the symptom of 
pruritus. 
Descriptive statistics will be presented for the signs and symptoms of otomycosis for the study 
ear at each evaluation and will include the number and percentage of subjects in each 
category. Subject assessments for the study ear for pruritus will also be summarized. No 


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Name of Sponsor/Company: Hill Dermaceuticals, Inc. 
Name of Finished Product: Miconazole oil 
Name of Active Ingredient: 2% miconazole 
imputation will be made for missing data. 
The primary efficacy endpoint will be the percentage of subjects at the Test of Cure Visit with 
“therapeutic cure,” defined as a negative mycological culture plus “clinical cure.” Clinical cure is 
defined as the absence of all otomycosis signs and symptoms according to the scales for each 
individual sign or symptom and with absence defined as a score of 0 on each of the scales for 
pruritus, debris, fungal elements, and pain. 
Other efficacy endpoints will include: 
• Percentage of subjects with clinical cure at the Test of Cure Visit 
• Percentage of subjects with a negative fungal culture at the Test of Cure Visit 
• Percentage of subjects with a negative fungal culture at the Test of Cure visit as well as 
individual sign or symptom score of 0 or 1 on each of the scales for pruritus and debris and 
a score of 0 on each of the scales for fungal elements and pain. 
• Percentage of subjects with individual signs or symptoms with a score of 0 or 1 on each of 
the scales for pruritus and debris and a score of 0 on each of the scales for fungal elements 
and pain. 
• Subject global assessments at Baseline and Test of Cure as well as categorical shifts in the 
subject global assessment scale scores from the Screening/Baseline to the Test of Cure 
Visit 
• If feasible, analyses may also be conducted by fungal organism isolated at 
Screening/Baseline. 
The primary population for all efficacy analyses will be the modified intent-to-treat (MITT) 
population, defined as all subjects who were randomized, dispensed study drug, and with a 
clinical diagnosis of otomycosis confirmed by a positive fungal culture. 
In cases of bilateral otomycosis, the ear with the worse infection at Screening/Baseline, as 
assessed by the investigator by taking into account both clinical signs and symptoms and 
fungal culture results, will be used as the study ear for efficacy analyses. If both ears are 
determined by the investigator to have the same degree of infection at Screening/Baseline, the 
left ear will be used as the study ear for the purposes of efficacy analyses. 
The primary population for all safety analyses will be the safety population, defined as all 
randomized subjects who received at least one dose of study drug and had at least one post-
Baseline safety assessment.  
All AEs occurring during the study will be recorded and classified using terminology from the 
Medical Dictionary for Regulatory Activities (MedDRA). All reported treatment-emergent 
adverse events (TEAEs), defined as any AE with an onset on or after the date of first study 
drug application, will be summarized by treatment group. Summaries will provide the number 
of subjects reporting TEAEs, system organ class, preferred term, severity, and relationship to 
study drug. When summarizing TEAEs by severity or relationship to study drug, each subject 
will be counted only once within a system organ class or a preferred term using the event with 
the greatest severity or causality, respectively, within each category. All reported SAEs will be 
summarized by the number of subjects reporting the event, system organ class, preferred 
term, severity, and relationship to study drug. 
All efficacy and safety analyses and comparisons between groups will be descriptive in nature, 
with no formal hypothesis testing performed. 


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Name of Sponsor/Company: Hill Dermaceuticals, Inc. 
Name of Finished Product: Miconazole oil 
Name of Active Ingredient: 2% miconazole 
Sample Size: 
The sample size for this study is not based on statistical considerations and is instead intended 
to be a reasonable number of subjects upon which to gather preliminary information on the 
efficacy and safety of miconazole oil when administered via the otic route to subjects with 
otomycosis. 
Interim Treatment Allocation Assessment(s): 
A subject’s MITT status (specifically positive fungal culture at baseline) is determined only 
following randomization, which may result in imbalance between treatment groups. Therefore, 
at least one assessment during the conduct of the study is planned to ensure that there is a 
sufficient number of subjects within each group for the primary analysis. Once at least 10 MITT 
subjects have been enrolled in the 7-Day active group, the numbers of MITT subjects in the 
14-Day active group and the 14-Day vehicle group will be determined by an unblinded 
statistician; no persons involved in the day to day conduct of the study will be unblinded. 
Randomization allocation for future subjects may be adjusted if deemed necessary to achieve 
minimum number of subjects within each arm.  


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TABLE OF CONTENTS 
1 
INTRODUCTION ................................................................................................................ 13 
1.1 
Brief Background Information ....................................................................................... 13 
1.2 
Compliance with Good Clinical Practice ....................................................................... 14 
1.3 
Justification of the Study, Risks, Dose, and Inclusion of Subjects with Peanut 
Allergy .......................................................................................................................... 14 
1.3.1 
Study and Risks ..................................................................................................... 14 
1.3.2 
Dose ....................................................................................................................... 16 
1.3.3 
Inclusion of Subjects with Peanut Allergy ............................................................... 16 
2 
OBJECTIVES AND RATIONALE ...................................................................................... 16 
3 
STUDY DESIGN ................................................................................................................ 17 
3.1 
Number of Subjects ...................................................................................................... 18 
3.2 
Investigators ................................................................................................................. 18 
3.3 
Study Duration ............................................................................................................. 19 
4 
STUDY SUBJECTS ........................................................................................................... 20 
4.1 
Inclusion Criteria .......................................................................................................... 20 
4.2 
Exclusion Criteria ......................................................................................................... 21 
4.3 
Subject Completion ...................................................................................................... 21 
4.4 
Subject Discontinuation ................................................................................................ 21 
4.5 
Subjects Lost to Follow-Up ........................................................................................... 22 
5 
CONCOMITANT THERAPIES ........................................................................................... 23 
5.1 
Permitted Medications .................................................................................................. 23 
5.2 
Prohibited Medications ................................................................................................. 23 
6 
STUDY SCHEDULE .......................................................................................................... 24 
6.1 
Study Flow Chart .......................................................................................................... 24 
6.2 
Study Visits .................................................................................................................. 25 
6.2.1 
Screening / Baseline .............................................................................................. 25 
6.2.2 
On Treatment ......................................................................................................... 26 
6.3 
End of Treatment ......................................................................................................... 27 
6.4 
Test of Cure ................................................................................................................. 27 
6.5 
Unscheduled Study Visits............................................................................................. 28 
6.6 
Post-Study Follow-Up................................................................................................... 28 
6.7 
Missed Visits ................................................................................................................ 28 
6.8 
Subject Completion ...................................................................................................... 28 
6.9 
Early Study Termination ............................................................................................... 28 
7 
STUDY PROCEDURES ..................................................................................................... 29 
7.1 
Medical/Medication History .......................................................................................... 29 
7.2 
Physical Examination ................................................................................................... 29 
7.3 
Urine Pregnancy Test................................................................................................... 29 
7.4 
Otomycosis Signs and Symptoms ................................................................................ 29 
7.4.1 
Pruritus ................................................................................................................... 29 
7.4.1.1 
Subject Assessment ......................................................................................... 29 
7.4.1.2 
Investigator Assessment .................................................................................. 30 
7.4.2 
Debris ..................................................................................................................... 30 
7.4.3 
Presence of Fungal Elements ................................................................................ 31 
7.4.4 
Pain ........................................................................................................................ 31 
7.5 
Subject Global Assessment ......................................................................................... 32 
7.6 
Microbial Culture .......................................................................................................... 32 


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7.7 
Ear Cleaning ................................................................................................................ 32 
7.8 
Adverse Event Evaluations .......................................................................................... 32 
7.9 
Randomization ............................................................................................................. 32 
7.10 
Study Drug Administration............................................................................................ 32 
7.11 
Treatment Compliance ................................................................................................. 33 
7.12 
Protocol Deviations ...................................................................................................... 33 
8 
ADVERSE EVENTS .......................................................................................................... 34 
8.1 
Definition of an Adverse Event ..................................................................................... 34 
8.1.1 
Definition of a Serious Adverse Event .................................................................... 34 
8.2 
Severity of Adverse Events .......................................................................................... 35 
8.3 
Relationship of Adverse Events to Study Drug ............................................................ 35 
8.4 
Documentation of Adverse Events ............................................................................... 35 
8.4.1 
Additional Reporting Requirements for Serious Adverse Events ........................... 36 
8.5 
Pregnancy .................................................................................................................... 37 
8.6 
Study Contacts ............................................................................................................. 37 
9 
STUDY TREATMENTS ..................................................................................................... 38 
9.1 
Description of Study Drug ............................................................................................ 38 
9.1.1 
Administration ......................................................................................................... 38 
9.2 
Randomization ............................................................................................................. 38 
9.3 
Masking/Unmasking ..................................................................................................... 38 
9.4 
Study Drug Handling and Dispensing .......................................................................... 39 
9.4.1 
Packaging and Labeling ......................................................................................... 39 
9.4.2 
Storage ................................................................................................................... 39 
9.5 
Accountability ............................................................................................................... 40 
9.6 
Return and Destruction ................................................................................................ 40 
10 
STATISTICAL CONSIDERATIONS .................................................................................. 41 
10.1 
Study Endpoints ........................................................................................................... 41 
10.1.1 
Primary Efficacy Endpoint ...................................................................................... 41 
10.1.2 
Secondary Efficacy Endpoints ................................................................................ 41 
10.1.3 
Other Efficacy Endpoints ........................................................................................ 42 
10.1.4 
Safety Endpoints .................................................................................................... 42 
10.2 
Hypotheses .................................................................................................................. 42 
10.3 
Sample Size ................................................................................................................. 42 
10.4 
Study Populations ........................................................................................................ 42 
10.4.1 
Intent-to-Treat Population ....................................................................................... 42 
10.4.2 
Modified Intent-to-Treat Population ........................................................................ 42 
10.4.3 
Per Protocol Population .......................................................................................... 43 
10.4.4 
Safety Population ................................................................................................... 43 
10.5 
Statistical Methods ....................................................................................................... 43 
10.5.1 
Efficacy Analyses ................................................................................................... 43 
10.5.2 
Safety Analyses ...................................................................................................... 44 
10.5.3 
Subject Demographics and Baseline Characteristics ............................................. 44 
10.5.4 
Missing Data ........................................................................................................... 44 
10.5.5 
Interim Treatment Allocation Assessment(s) .......................................................... 44 
11 
ADMINISTRATIVE CONSIDERATIONS ........................................................................... 45 
11.1 
Institutional Review Board ............................................................................................ 45 
11.2 
Ethics ........................................................................................................................... 45 
11.3 
Informed Consent and Assent ...................................................................................... 45 
11.4 
Confidentiality of Subject Information ........................................................................... 46 


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11.5 
Study Monitoring .......................................................................................................... 46 
11.6 
Case Report Form Requirements ................................................................................ 47 
11.7 
Quality Assurance Audits ............................................................................................. 48 
11.8 
Records Retention........................................................................................................ 48 
11.9 
Publication of Results ................................................................................................... 48 
12 
REFERENCES ................................................................................................................... 49 
13 
SUMMARY OF PROTOCOL AMENDMENTS .................................................................. 50 
13.1 
Amendment 1 Version 2 14 February 2017 ................................................................. 50 
13.2 
Amendment 2 Version 3 14 June 2017 ........................................................................ 58 
13.3 
Amendment 3 Version 4, 11 October 2017 .................................................................. 60 
13.4 
Amendment 4 Version 5, 11 May 2018 ........................................................................ 61 
13.5 
Amendment 5 Version 6, 17 April 2019 ........................................................................ 62 
LIST OF TABLES 
Table 1 
Study Schedule ...................................................................................................... 24 
 
 


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LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
AE 
Adverse event 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
ICH 
International Conference on Harmonisation 
IRB 
Institutional review board 
ITT 
Intent-to-treat 
IUD 
Intrauterine device 
LOCF 
Last Observation Carried Forward 
MedDRA 
Medical Dictionary for Regulatory Activities 
MIC 
Minimum inhibitory concentration 
MITT 
Modified intent-to-treat 
OTC 
Over the counter 
PP 
Per protocol 
SAE 
Serious adverse event 
TEAE 
Treatment-emergent adverse event 
US 
United States 
 


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1 
INTRODUCTION 
1.1 
Brief Background Information 
Miconazole is an imidazole antifungal agent that has been available by prescription and over the 
counter (OTC), in different formulations, for many years. It is commonly used for different types 
of fungal skin infections, such as Candida, ringworm, jock itch, athlete’s foot, nail fungus, 
vaginal yeast infections, and oropharyngeal candidiasis. Formulations containing up to 4% 
miconazole nitrate have been approved for OTC use as topical antifungal agents in cream, 
ointment, powder, or gel dosage forms. The 2% formulation is commonly used for 
dermatophytic infections. 
While antifungal agents including miconazole are used in practice for the treatment of fungal 
otitis externa (also called otomycosis), there are currently no treatments approved by the United 
States (US) Food and Drug Administration (FDA) for this indication in humans. Miconazole is 
currently FDA-approved as a component of two veterinary combination products (Surolan and 
Easotic) administered otically to dogs for the treatment of canine otitis externa caused by 
susceptible strains of yeast and bacteria. Each veterinary product contains miconazole in 
combination with an antibacterial agent and a corticosteroid. The concentration of miconazole 
present in Surolan (23 mg/mL miconazole nitrate) is similar to the 2% concentration of 
miconazole planned for use in humans in this study. The concentration of miconazole present in 
Easotic is 15.1 mg/mL miconazole nitrate, which equates to approximately 1.5% miconazole. 
While the causative organism of canine otitis externa, Malassezia pachydermatis, is not typically 
associated with human otomycosis in the US, it is expected that human otomycosis, which is 
most commonly associated with organisms from the Candida and Aspergillus genera, would 
respond to concentrations of miconazole similar to those used in dogs. 
The mechanisms of action of miconazole when used topically for the treatment of fungal 
infections involve its actions against the fungal organisms, rather than their human host. 
Miconazole targets the cytochrome P450-dependent enzyme 14-α-sterol demethylase, an enzyme 
that is also involved in mammalian cholesterol synthesis, resulting in inhibition of ergosterol 
biosynthesis in the cell membrane. Because ergosterol is an important component of the cell 
membrane, inhibition of its synthesis inhibits fungal cell growth [Vandenbosch 2012]. In 
addition to its activity toward the enzyme 14-α-sterol demethylase, miconazole also leads to 
increased reactive oxygen species in fungal organisms, which appears to result in fungicidal 
activity [Vandenbosch 2010; Musaji 2010]. 
The mechanisms of action of miconazole against fungi in general appear to be applicable to 
fungi associated with otomycosis, in that miconazole has been demonstrated to have activity 
against some clinical isolates of fungi associated with human otomycosis in the US in vitro 
[Bassiouny 1986; Stern 1988]. Clinical studies of 2% miconazole conducted outside of the 
United States also suggest the efficacy of miconazole in the treatment of human otomycosis 
[Kiakojuri 2007; Vennewald 2010; Navaneethan 2015]. 
The purpose of this study is to gather preliminary data on the efficacy and safety of 2% 
miconazole oil after topical otic administration in subjects with otomycosis. A 14-day regimen of 


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twice-daily administration of 2% miconazole oil will be descriptively compared with the same 
treatment regimen using the product vehicle. Furthermore, the 14-day regimen of 2% miconazole 
oil will be compared with a 7-day regimen, to gather preliminary dose-ranging data regarding the 
duration of treatment. The 2% concentration of miconazole is selected for this study due to the 
results of an internal study conducted by the sponsor in vitro demonstrating greater zones of 
inhibition against Candida and Aspergillus using the 2% concentration compared with the 1% 
concentration. Furthermore, the 2% miconazole concentration is commonly used for 
dermatophyte infections, and topical application is expected to be ≥1000-fold the minimum 
inhibitory concentrations (MICs) of the Candida and Aspergillus organisms most commonly 
associated with human otomycosis in the US. 
1.2 
Compliance with Good Clinical Practice 
The investigator and all study staff will conduct the study in compliance with this protocol and 
FDA regulations, all applicable federal, state, and local laws, rules and regulations relating to the 
conduct of a clinical study, the ethical principles of the Declaration of Helsinki, and the current 
International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) guidelines.  
1.3 
Justification of the Study, Risks, Dose, and Inclusion of Subjects with 
Peanut Allergy 
1.3.1 
Study and Risks 
Miconazole has been approved by the US FDA since 1974 and achieved OTC status for some 
indications when FDA issued a final monograph for miconazole on September 23, 1993. 
Miconazole is FDA-approved as a prescription for other indications. Approved routes of 
administration in humans have included systemic (intravenous) routes, as well as a variety of 
topical routes (dermatologic, intravaginal, and buccal). 
Miconazole has not been FDA-approved for otic administration for any indication in humans, but 
clinical studies in other countries of otically-administered miconazole have been conducted and 
support the efficacy of miconazole in the treatment of otomycosis [Kiakojuri 2007; Vennewald 
2010; Navaneethan 2015]. In vitro evidence exists of the susceptibility of clinical isolates from 
patients with otomycosis to miconazole, including one study of isolates from patients with 
otomycosis in the US [Bassiouny 1986; Stern 1988]. These results, along with the potential 
complications of untreated otomycosis, suggest a potential benefit to patients to study 
miconazole administered otically for the treatment of otomycosis. 
The safety of miconazole as a topical dermal application is supported by its OTC approval for 
dermal conditions. Side effects of topical application to the skin may include blistering, burning, 
redness, skin rash, or other sign of skin irritation [PubMed Health 2015]. Side effects mentioned 
in the Monistat 1 consumer information leaflet include burning, itching, irritation, swelling, 
hives, skin rash, abdominal pain, and abdominal cramping. Other possible local effects of 
miconazole which may provide benefit in otomycosis may include anti-inflammatory activity at 
the skin, and possible restoration of skin barrier function in some circumstances of skin injury 
[Xhauflaire-Uhoda 2006; Liebel 2006]. 


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Evidence supporting the safety of miconazole administered by the otic route comes largely from 
nonclinical studies. The possibility exists that miconazole could access the middle ear through 
the tympanic membrane, then diffuse through the round window membrane of the middle ear to 
reach and damage the cochlea. Miconazole appeared to be non-ototoxic when instilled at a 2% 
concentration directly into the round window niche of guinea pigs three times over the course of 
a week [Tom 2000]. Miconazole oil, instilled at 1% and 2% concentrations to guinea pigs twice 
daily over a period of 14 days in a nonclinical study conducted by the sponsor, also generally 
failed to demonstrate ototoxicity, although minor hair cell loss was observed in 1 animal in each 
of the 1% and 2% miconazole groups. Bilateral hearing loss, as assessed by increases in auditory 
brainstem responses, was observed in all animals in the miconazole vehicle group as well as in 
each of the 1% and 2% miconazole groups, but not in the saline control group. These results 
suggest that the hearing loss was due to the miconazole oil vehicle, rather than the miconazole 
itself. Because this hearing loss was generally not associated with hair cell loss, it is believed that 
this hearing loss was caused by instillation of a relatively large volume of product in a small 
animal (resulting in physical blockage of conduction), rather than actual damage to the ear 
caused by miconazole or the miconazole vehicle. Refer to the Investigator’s Brochure (IB) for 
miconazole oil [Investigator’s Brochure for miconazole oil 2016] for more information on the 
14-day study of miconazole oil in guinea pigs. 
The bilateral hearing loss observed in guinea pigs after a 14-day treatment with miconazole oil 
and its vehicle is not expected to occur in humans at the doses and volumes of study drug 
planned for clinical use. The miconazole oil vehicle is almost identical to that of another product 
manufactured by the sponsor and approved for topical otic administration (DermOtic™, 
containing 0.01% fluocinolone acetonide and used for the treatment of chronic eczematous 
external otitis). No subjects randomized to the DermOtic group of the clinical studies reported 
hearing loss, and no post-marketing reports of hearing loss have been received since DermOtic’s 
approval in 2005. 
The non-ototoxicity of the active ingredient, miconazole, is also supported in another species of 
animal by FDA approval of miconazole in two combination products (Surolan, which contains 
approximately 2% miconazole, and Easotic, which contains approximately 1.5% miconazole) 
administered by the otic route for the treatment of canine otitis externa caused by susceptible 
strains of yeast and bacteria. In the studies of Surolan in which hearing loss was assessed, 
hearing loss was only reported in 3 of 161 dogs (1.9%) and with apparent reversibility in the 2 
dogs for which follow-up information was available and normal hearing was demonstrated at a 
later date. 
Systemic effects of miconazole are generally not expected after topical otic administration. 
Systemic absorption of miconazole and distribution to locations other than the skin have been 
demonstrated to be low after topical dermal administration, as has been reported for other 
miconazole-containing products such as the Vusion™ topical ointment used for the treatment of 
diaper dermatitis complicated by candidiasis in children. Thus, although some potential systemic 
effects of miconazole have been reported and the liver has been identified in prior FDA 
miconazole product approvals to be the main toxicological target of systemic miconazole; these 
effects are generally not expected after topical otic administration of the doses planned for this 
study. 


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1.3.2 
Dose 
The 2% dose was selected for this study based on its widespread use in clinical practice in a 
variety of antifungal products already approved by FDA, and the larger zones of inhibition of 2% 
compared with 1% miconazole when incubated with two organisms commonly associated with 
otomycosis (Candida albicans and Aspergillus niger) in a sponsor-conducted study in vitro. The 
use of 5 drops of product (at ~30 mg per drop) is based on the estimated volume of the human 
external ear canal, and the amount believed to be needed to fully coat the canal. The 5 drops 
planned for this study is the same as that used for DermOtic in the treatment of chronic 
eczematous external otitis. It is noted that the dose regimen for Floxin™ otic solution (0.3% 
ofloxacin), an FDA-approved product for the treatment of bacterial otitis externa, is 10 drops in 
adults and children >13 years. Floxin is aqueous and may not adhere as well to the ear canal as 
the oil-based miconazole oil. The twice-daily dosing was selected based on evidence that 
miconazole may not maintain bioactivity in the stratum corneum for a full 24 hours [Pershing 
1994]. 
1.3.3 
Inclusion of Subjects with Peanut Allergy 
Miconazole oil contains refined peanut oil. Inclusion in this study of subjects with peanut allergy 
is justified by studies and publications documenting safe use of the refined peanut oil, as well as 
products containing the refined peanut oil (such as DermOtic, which is the same product as the 
Derma-Smoothe/FS for which two safety studies were performed in subjects with known 
hypersensitivity to peanuts) [Yunginger 2001; Paller 2003]. Reports also exist of subjects with 
known peanut allergy who have continued to safely use products such as Derma-Smoothe/FS 
even after an anaphylactic reaction to peanuts [Paller 2003]. The refined peanut oil used in the 
Derma-Smoothe/FS, DermOtic, and miconazole oil products has been treated to remove the 
peanut proteins which are generally responsible for allergic reactions to peanuts. Thus, the 
inclusion of subjects with peanut allergy in this study is not expected to pose an excessive risk to 
these subjects. 
2 
OBJECTIVES AND RATIONALE 
The objectives of the study are to: 
• Obtain preliminary evidence of the efficacy and safety of miconazole oil compared with 
vehicle over a 14-day treatment duration. 
• Descriptively compare the efficacy and safety of miconazole oil over treatment durations of 7 
versus 14 days. 


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3 
STUDY DESIGN 
This study is a randomized, partially masked, multiple-dose, parallel-group design study 
conducted at up to 10 study centers in the US. Approximately 75 male or female subjects with 
otomycosis will receive study drug. Subjects will be randomly assigned in a 1:1:1 ratio to receive 
miconazole oil [administered as 5 drops per ear at ~30 mg per drop instilled into the external ear 
canal of the ear(s) affected by otomycosis] for 7 or 14 days, or vehicle for 14 days. Interim 
assessments are planned to ensure that there is a sufficient number of subjects within each group 
for the primary analysis. If deemed necessary the randomization ratio may be adjusted following 
the interim assessments; see Section 10.5.5 for details. For subjects assigned to the 14-day 
treatment duration with either miconazole oil or vehicle, the contents of the study drug will be 
masked to both the subject and the investigator and study staff (i.e., double-blind), but the 
treatment duration assigned to each subject (7 or 14 days) will be unmasked to both the subject 
and the investigator and study staff.  
At Screening/Baseline (Day 1), potentially eligible subjects will provide informed consent, and 
subjects will undergo screening evaluations to include a physical examination, an assessment of 
the signs and symptoms of otomycosis (pruritus, debris, visual examination for presence of 
fungal elements, and pain), and an evaluation of medical history. Urine will be obtained for 
pregnancy screening in female subjects of childbearing potential. Prior and concomitant 
medications will be reported. Subjects with positive signs and symptoms of otomycosis and who 
meet all other eligibility criteria will be entered into the study, and a subject global assessment of 
disease will be performed. Fungal and bacterial cultures of the affected ear(s) will be taken, then 
debris will be cleaned from the affected ear(s) following the site’s normal procedures. The 
subject will then begin treatment with study drug. The subject or caregiver will instill the first 
dose of study drug at the site, under the supervision of the investigator or site personnel. Adverse 
events (AEs) will then be assessed. The subject will then leave the clinic and continue to 
administer the study drug twice per day as instructed. While in the study, subjects will be 
instructed to avoid getting water in the ear, to consider drying excessive water in the ear by using 
a blow dryer, and to place a Vaseline-impregnated cotton ball over the affected ear(s) to help 
keep water out of the ear while bathing or showering. 
All subjects will return to the clinic on Day 8. For subjects randomized to the 7-day treatment 
duration, this visit will constitute the End of Treatment Visit, with procedures performed as 
described for that visit below. Subjects randomized to the 7-day treatment duration will not 
administer study drug on the day of this visit. For all other subjects, for whom this visit will 
constitute an On Treatment Visit, a clinical evaluation of the signs and symptoms of otomycosis, 
a subject global assessment, a cleaning of the affected ear(s) (following the site’s normal 
procedures), and an assessment of AEs and concomitant medications will be performed, and 
these subjects will continue to administer the study drug twice per day, up through Day 14, 
following the same instructions as provided at the Screening/Baseline Visit on Day 1. 
All subjects will return to the clinic on Day 15. For subjects randomized to the 7-day treatment 
duration, this visit will constitute the Test of Cure Visit, with procedures performed as described 
for the Test of Cure Visit below. For subjects randomized to the 14-day treatment duration, this 
visit will constitute the End of Treatment Visit, with procedures performed as described for the 


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End of Treatment Visit below. Subjects randomized to the 14-day treatment duration will not 
administer study drug on the day of this visit. 
Subjects randomized to the 14-day durations will return to the clinic on Day 22 for the Test of 
Cure Visit, with procedures performed as described for the Test of Cure Visit below.  
Procedures performed at the End of Treatment Visit will include an assessment for clinical signs 
and symptoms of otomycosis, a subject global assessment, and a fungal culture of the affected 
ear(s). For subjects randomized to the 7-day treatment duration, subjects will have the affected 
ear(s) cleaned according to the site’s normal procedures at this visit, after the efficacy procedures 
have been completed. AEs and concomitant medications will also be assessed, and the subject 
will return all study drug.  
Procedures performed at the Test of Cure Visit will include an assessment of clinical signs and 
symptoms of otomycosis, a subject global assessment, and a fungal culture of the affected ear(s). 
AEs and concomitant medications will also be assessed. A urine pregnancy test will be 
performed in women of childbearing potential. 
Efficacy assessments will include fungal culture of the affected ear(s), assessments of clinical 
signs and symptoms of otomycosis, and a subject global assessment. In cases of bilateral 
otomycosis, both ears will be treated and evaluated by the investigator, but the ear with the worse 
infection at Screening/Baseline, as assessed by the investigator by taking into account both 
clinical signs and symptoms and fungal culture results, will be used as the study ear for efficacy 
analyses. If both ears are determined by the investigator to have the same degree of infection at 
Screening/Baseline, the left ear will be used as the study ear for the purposes of efficacy 
analyses. 
Safety assessments will include AEs. 
3.1 
Number of Subjects 
Approximately 75 eligible subjects are planned to be enrolled in order to achieve approximately 
10 subjects per group (randomized in a 1:1:1 ratio to the 7-day active, 14-day active, and 14-day 
vehicle treatment groups) with a positive fungal culture at baseline and who have completed the 
Test of Cure Visit. 
3.2 
Investigators 
The study will be conducted at up to 10 investigative sites located in the US. 
The study will be conducted by investigators who are determined by the sponsor to be suitably 
qualified by training and experience to conduct this study in compliance with all applicable GCP 
and FDA federal regulations or local regulations. Sub-investigators will be identified on the 
Form FDA 1572. 


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3.3 
Study Duration 
The total duration of the study for a subject from screening until the last visit will be up to 30 
days (including the visit window of up to 8 additional days after the scheduled day to complete 
the final visit). 


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4 
STUDY SUBJECTS 
4.1 
Inclusion Criteria 
In order to be eligible for the study, subjects must meet all of the following criteria: 
1. Male or non-pregnant, non-lactating females 
2. Diagnosis of uncomplicated otomycosis of the external ear only, in the ear(s) that will be 
treated with study drug, with a score for fungal elements of >0 in each ear to be treated with 
study drug (see Section 7.4 for definitions of the scores for each of the otomycosis signs and 
symptoms). Subjects must also have at least two of the following signs or symptoms of 
otomycosis in each ear to be treated with study drug: pruritus, >1; debris, >1; or pain, >0. 
3. General good health as determined by medical examination and medical history, and who are 
free of clinically significant disease, including diabetes mellitus that is not well-controlled or 
that could interfere with the study 
4. Females of childbearing potential must have had a negative urine pregnancy test at 
Screening/Baseline and must agree to use an effective method of contraception (as defined in 
Section 8.5) from Screening/Baseline up through the Test of Cure Visit (see Section 6). 
Females of childbearing potential include any female who has experienced menarche and 
who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation 
or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea >12 consecutive 
months). Females who are using oral, implanted, or injectable contraceptive hormones, an 
intrauterine device (IUD), barrier methods (diaphragm, condoms, spermicide) to prevent 
pregnancy, practicing abstinence or where partner is sterile (e.g., vasectomy), should be 
considered to be of childbearing potential 
5. Subjects and/or their caregivers (as appropriate for the age of the subject) must have full 
legal capacity to volunteer 
6. Subjects and/or their caregivers must have completed an appropriately administered 
institutional review board (IRB)-approved informed consent and assent (as applicable) prior 
to any study related procedures 
7. Subjects and their caregivers (as applicable) must agree to comply with all requirements of 
the protocol 
8. For subjects with only one ear meeting all study eligibility criteria, the subject will be eligible 
for the study, and the ear meeting all eligibility criteria will be treated with study drug and 
considered to be the study ear for the purposes of study evaluations. In case of bilateral 
otomycosis in which both ears meet all study eligibility criteria, the subject will be eligible 
for the study, both ears may be treated with study drug, and the worse ear will be considered 
to be the study ear for the purposes of study evaluations. If both ears meet study eligibility 
criteria and are determined by the investigator to have the same degree of infection at 
Screening/Baseline, the left ear will be considered to be the study ear for the purposes of 
study evaluations. 


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4.2 
Exclusion Criteria 
Subjects meeting any of the following criteria will not be eligible for the study: 
1. Any other dermatoses or conditions of the ear that may interfere with the evaluation of
otomycosis, including concomitant otic infections (including bacterial infection) that require
antimicrobial treatment, disease that has spread beyond the external ear(s), or pre-existing
skin atrophy of the affected ear(s) that will be treated with study drug
2. Tympanostomy tube or perforated tympanic membrane in the ear(s) that will be treated with
study drug
3. History of prior surgery directly affecting and compromising the external auditory canal and/or
tympanic membrane of the ear(s) that will be treated with study drug, except for prior
tympanostomy tube(s) that have already been removed and completely healed
4. Use of any topical medicated treatments for otomycosis within 14 days of study entry
5. Use of any systemic antifungal therapy within 28 days of study entry, warfarin within 28
days of study entry, immunosuppressive or immune-stimulating drugs within 28 days of
study entry, or systemic steroids within 3 months of study entry
6. Fever of ≥100°F at study entry
7. Recurrent otomycosis that has been unresponsive to previous antifungal treatment
8. Known hypersensitivity to any of the components in the test formulation
9. Participation in another investigative trial within 28 days of study entry.
4.3 
Subject Completion 
The subject has completed the study when the Test of Cure Visit is completed. Subjects 
who require further follow-up for an AE will be followed according to Section 8.4. 
4.4 
Subject Discontinuation 
A subject MAY be withdrawn from the study (at the discretion of the investigator, sponsor, 
and/or IRB) prior to study completion for any of the following reasons, including, but not limited 
to: 
•
A serious adverse event (SAE) occurring during the course of the study which precludes
continued follow-up
•
Intercurrent illness which may, in the investigator’s opinion, significantly affect study
assessments
•
Failure to follow required study procedures
A subject MUST be discontinued prior to the final study visit for any of the following reasons: 
•
Whenever the subject decides it is in his/her best interest to withdraw
•
Whenever the investigator decides it is in the subject’s best interest to be withdrawn


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Prior to discontinuing a subject, every effort should be made to contact the subject, schedule a 
final study visit, and obtain as much follow-up data as possible. If possible, the assessment 
schedule for the Test of Cure Visit should be performed, and an effort should be made to collect 
all study drug. 
Due to the time required to obtain fungal culture results from Screening/Baseline, subjects will 
be enrolled into the study based on a clinical diagnosis of otomycosis (including the visible 
presence of fungal elements at Screening/Baseline), without a requirement for a positive fungal 
culture. Subjects who end up with a negative Screening/Baseline fungal culture will not be 
discontinued from the study, but these subjects will not be included in the primary efficacy 
analysis. Because the sponsor’s goal is to obtain approximately 10 subjects per group who meet 
both criteria of having a positive fungal culture at Screening/Baseline and completing the Test of 
Cure Visit, the number of subjects enrolled into the study may be adjusted depending on the rates 
of negative fungal culture at Screening/Baseline and of discontinuation or loss to follow-up. 
Subject discontinuations will be documented clearly on the applicable electronic case report form 
(eCRF). Subjects who discontinue from the study will not be replaced, but additional subjects 
may be enrolled and randomized if it appears that approximately 75 subjects is insufficient to 
meet the sponsor’s goal of approximately 10 subjects per group who meet both criteria of having 
a positive fungal culture at Screening/Baseline and completing the Test of Cure Visit. 
4.5 
Subjects Lost to Follow-up 
An effort must be made to contact subjects who do not return for scheduled visits, to schedule 
the visit and/or obtain as much follow-up data as possible. At least three telephone calls must be 
placed to the subject at the first missed visit, to attempt to get the subject to complete the visit 
and to gather as much follow-up data as possible. At least three telephone calls must also be 
placed to the subject for any subsequent missed visits after an attended visit, to attempt to get the 
subject to complete the visit and to gather as much follow-up data as possible. Subjects who miss 
a visit may still be scheduled for a subsequent visit. Subjects who cannot be contacted via three 
telephone calls to schedule a missed visit may be considered lost to follow-up and discontinued 
from the study. 
All follow-up attempts will be documented and kept with the subject’s source documentation, 
and the applicable eCRFs will be completed. The date a subject will be considered lost to follow-
up will be the date of the last non-missing visit. 


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5 
CONCOMITANT THERAPIES 
All concomitant therapies must be recorded on the eCRF. All therapies within 28 days prior to 
Day 1 must also be recorded on the eCRF. 
Every effort should be made to keep concomitant therapy and dosing constant during the study. 
Any changes in concomitant therapies during the study must be recorded on the eCRF at each 
visit. The reason for any change in concomitant therapies should be reported as, or in 
conjunction with, an AE except as noted below:  
• Prophylactic therapies, such as vaccines, must be recorded on the eCRF but should not be 
reported as AEs.  
• Changes in therapy for pre-existing conditions that are not related to a worsening of the 
condition must be reported on the eCRF but should not be reported as AEs. The condition 
must be reported on the eCRF as part of the subject’s medical history.  
5.1 
Permitted Medications 
Therapies (medication and non-medication therapies) not restricted by the protocol may be used 
during the study for the treatment or prevention of disease or to maintain good health. Vitamins 
and mineral supplements are permitted at dosages considered by the investigator as reasonable 
for maintaining good health. Non-prohibited chronic therapies being used at Screening/Baseline 
may be continued. 
5.2 
Prohibited Medications 
Other than the study drug, no other topical medications are allowed to be used in the ears. Other 
prohibited treatments include systemic antifungal therapy, warfarin, immunosuppressive or 
immune-stimulating drugs, and systemic steroids. 


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6 
STUDY SCHEDULE 
6.1 
Study Flow Chart 
The study schedule is presented in Table 1. 
Table 1 
Study Schedule 
Evaluations and Procedures: 
Screening/ 
Baseline 
Day 1 
On  
Treatment a 
Day 8 c 
End of 
Treatment a 
Day 8 or 15 d 
Test of  
Cure b 
Day 15 or 22 e 
Informed consent/assent 
X 
 
 
 
Inclusion/exclusion criteria 
X 
 
 
 
Medical/medication history 
X 
 
 
 
Physical examination 
X 
 
 
 
Otomycosis signs and symptoms 
X 
X 
X 
X 
Urine pregnancy test f 
X 
 
 
X 
Randomization 
X 
 
 
 
Dispensation of study drug 
X 
 
 
 
Dispensation of subject diary 
X 
 
 
 
Collection of subject diary 
 
X 
X 
 
Administration of study drug at site 
X 
 
 
 
Weighing of study drug 
X 
X 
X 
 
Collection of study drug 
 
 
X 
 
Subject global assessment 
X 
X 
X 
X 
Microbial culture g 
X 
 
X 
X 
Ear cleaning 
X 
X 
X h 
 
AE evaluations 
X 
X 
X 
X 
Concomitant medications review 
X 
X 
X 
X 
a. This visit may occur up to 3 days later than the specified day. 
b. This visit may occur up to 1 day sooner or up to 8 days later than the specified day.  
c. For subjects randomized to the 14-day durations, the Day 8 visit constitutes an On Treatment Visit; for subjects 
randomized to the 7-day group, the Day 8 visit constitutes the End of Treatment Visit with those procedures 
performed instead 
d. The End of Treatment Visit is scheduled to occur on Day 8 for subjects randomized to the 7-day treatment 
duration, and on Day 15 for subjects randomized to the 14-day treatment durations 
e. The Test of Cure Visit is scheduled to occur on Day 15 for subjects randomized to the 7-day treatment duration, 
or on Day 22 for subjects randomized to the 14-day treatment durations. In case of early termination, the 
assessments planned for the Test of Cure Visit should be performed if possible 
f. Females of childbearing potential only 
g. For both fungi and bacteria at the Screening/Baseline visit and for fungi only at the End of Treatment and Test of 
Cure visits 
h. To be performed in subjects randomized to the 7-day group only, and after all efficacy assessments (otomycosis 
signs and symptoms, subject global assessment, and microbial culture) have already been performed 


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6.2 
Study Visits 
Prior to the signing of informed consent and assent (as applicable), the investigator or designee 
will explain the purpose of the study, procedures, and subject responsibilities to the potential 
study subject and/or caregiver (as applicable). The subject’s and/or caregiver’s willingness and 
ability to meet the follow-up requirements of the study will be determined. 
The schedule of visits is presented in Table 1. Details about study procedures and how they are 
to be performed are presented in Section 7. 
6.2.1 
Screening / Baseline 
Screening procedures will occur prior to randomization and will include: 
• Informed consent and assent (as applicable) 
• Medical history 
• Prior and concomitant medications 
• Physical examination 
• Urine pregnancy test (in female subjects of childbearing potential only) 
• Otomycosis signs and symptoms 
• Determination of subject eligibility for the study 
Subjects who are eligible for the study will undergo the following additional procedures: 
• Subject global assessment 
• Microbial culture (fungi and bacteria) 
• Ear cleaning 
• Randomization 
• Weighing of study drug, followed by dispensation of study drug to subject 
• Dispensation of subject diary to subject. 
• Administration of the first dose by the subject or caregiver under the supervision of the 
investigator or other study personnel 
• Collection of AE information, with the time of AEs to be reported as occurring either 
before or after the first dose of study drug 
• Subject instruction about the date on which they are to stop administering study drug 
(after all doses have been administered on Day 7 for the 7-day group, and after all doses 
have been administered on Day 14 for the 14-day groups; subjects will be instructed that 
study drug should be stopped on the appropriate date regardless of the date for which the 
next visit is scheduled) 


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• Subjects will be instructed to bring their bottle of study drug and the diary to the site for 
their next visit 
6.2.2 
On Treatment 
These visits may occur up to 3 days later than the specified day. Subjects randomized to the 7-
day group will not have any On Treatment visits and will instead proceed directly to the 
procedures specified for the End of Treatment Visit. Subjects randomized to the 14-day groups 
will have one On Treatment visit on Day 8. 
Subjects will be instructed not to administer any study drug on the day of this visit until after the 
visit has occurred, if the visit is scheduled for the morning. If the visit is scheduled for the 
afternoon, subjects will be instructed that the morning dose of the study drug can be administered 
prior to the visit. 
The following procedures and evaluations will occur during the On Treatment visits: 
• Otomycosis signs and symptoms 
• Subject global assessment 
• Ear cleaning 
• AE evaluation 
• Review of concomitant medications 
• Weighing of study drug and return of the bottle of study drug to the subject 
• Review of subject diary.  
• Subject reminder to continue to administer their assigned study drug twice daily up 
through the date on which they are to stop administering study drug (after all doses have 
been administered on Day 14; study drug should be stopped on the appropriate date 
regardless of the date for which the next visit is scheduled) 
• Subjects will be instructed to bring their bottle of study drug and the diary to the site for 
their next visit 


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6.3 
End of Treatment 
This visit may occur up to 3 days later than the specified day. Subjects randomized to the 7-day 
group will have the End of Treatment Visit on Day 8, and subjects randomized to the 14-day 
groups will have the End of Treatment Visit on Day 15. 
The following procedures and evaluations will occur during the End of Treatment visits: 
• Otomycosis signs and symptoms 
• Subject global assessment 
• Microbial (fungal) culture 
• Ear cleaning (in subjects randomized to the 7-day group only) 
• AE evaluation 
• Review of concomitant medications 
• Collection of subject diary 
• Collection/weighing of study drug  
6.4 
Test of Cure 
This visit may occur up to 1 day sooner or up to 8 days later than the specified day. Subjects 
randomized to the 7-day group will have the Test of Cure Visit on Day 15, and subjects 
randomized to the 14-day groups will have the Test of Cure Visit on Day 22. 
The following procedures and evaluations will occur during the Test of Cure Visit: 
• Otomycosis signs and symptoms 
• Subject global assessment 
• Microbial (fungal) culture 
• AE evaluation 
• Review of concomitant medications 
• Urine pregnancy test (in female subjects of childbearing potential only) 
In case of early termination, the procedures planned for the Test of Cure Visit should be 
performed if possible. 


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6.5 
Unscheduled Study Visits 
Additional visits may be scheduled, as necessary, to ensure the safety and well-being of subjects. 
All additional examinations should be fully documented in the source files and eCRFs, as 
appropriate. Visits that fall outside the designated scheduled visit window but that are intended 
to fulfill scheduled visit requirements will be collected and transcribed to the appropriate 
scheduled visit eCRF. 
If a subject is seen for multiple visits during a given visit time frame, the data from the visit(s) 
that are intended to meet the protocol requirements for the scheduled visit should be captured on 
the visit eCRF. Any other data from any additional visits within a scheduled visit interval will be 
captured elsewhere on the eCRF. 
6.6 
Post-study Follow-up 
If a subject requires further follow-up of AEs upon discontinuation or completion of the study, 
the investigator should schedule post-study follow-up visits, as necessary. 
6.7 
Missed Visits 
If a subject misses any scheduled follow-up visit and cannot be seen prior to the start of the visit 
range for the next scheduled follow-up visit, the visit is considered missed. 
6.8 
Subject Completion 
The subject has completed the study when the Test of Cure Visit is completed. Subjects who 
require further follow-up for an AE will be followed according to Section 6.6. 
6.9 
Early Study Termination 
The sponsor reserves the right to terminate this study prematurely. If during the study it becomes 
evident to the sponsor that the study should be stopped prematurely, the study will be terminated 
and appropriate notification will be given to the investigator, IRB, and FDA, as applicable. The 
sponsor or designee will instruct the investigator to stop randomizing subjects and to arrange for 
study closeout at the site. 


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7 
STUDY PROCEDURES 
The required study procedures are detailed in this section. The timeline for these procedures is 
presented in Section 6. 
7.1 
Medical/Medication History 
At Screening/Baseline, the investigator or designee will interview each subject and obtain a 
complete medical and medication history, including a history of all surgeries and past medical 
procedures. The subject must not require any treatment or medication for concurrent illnesses as 
specified by the inclusion and exclusion criteria or anticipate the need for any excluded 
concomitant medications. 
7.2 
Physical Examination 
At Screening/Baseline, the investigator or designee will perform a complete physical 
examination to include the following: general appearance; head, eyes, ears, nose, throat; neck; 
cardiovascular; lungs; abdomen; lymph nodes; extremities; neurological; skin; and 
musculoskeletal. 
7.3 
Urine Pregnancy Test 
The urine pregnancy test (performed in females of childbearing potential only) must have a 
minimum sensitivity of 25 mIU of β-hCG/mL of urine. 
7.4 
Otomycosis Signs and Symptoms 
The signs and symptoms of otomycosis will be assessed according to the scales for pruritus (see 
Section 7.4.1), debris (see Section 7.4.2), presence of fungal elements (see Section 7.4.3), and 
pain (see Section 7.4.4). The same evaluator should assess each subject for signs and symptoms 
of otomycosis at each visit throughout the subject’s participation in the study, if possible. 
7.4.1 
Pruritus 
7.4.1.1 
Subject Assessment 
Subjects or their caregivers (as appropriate, based on the age of the subject) will be handed a 
questionnaire for each ear being treated with study drug and asked to indicate the choice that 
most closely reflects the severity of itching in the ear over the last 24 hours. Choices and scores 
will be according to the following scale:  
Score 
Category 
Description 
0 
None 
No itching 
1 
Mild 
Occasional itch, not interfering with daily activities 
2 
Moderate 
Fairly persistent itch, partially tolerated; sleep is not interrupted 
3 
Severe 
Intolerable, constant itch; sleep is interrupted 


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7.4.1.2 
Investigator Assessment 
After subjects have completed the questionnaire described in Section 7.4.1.1, subjects or their 
caregivers (as appropriate, based on the age of the subject) will be asked by the investigator (or 
designee) about the severity of itching present in each ear being treated with study drug. 
Questions such as the following will be used in order to gather information for this assessment: 
“Have you had itching in your ear over the last day or so?” 
“Over the last 24 hours, has your itching interfered with your daily activities?” 
“Over the last 24 hours, has your itching been bad enough to keep you awake?” 
“Over the last 24 hours, would you describe your itching as intolerable or constant?” 
The investigator will then score the symptom of pruritus for each ear being treated with study 
drug, taking into consideration the subject’s and/or caregiver’s answers and the investigator’s 
observations of the subject. Scores will be according to the same scale as described in Section 
7.4.1.1. 
7.4.2 
Debris 
Upon otoscopic examination, the investigator will score the amount of debris present in each ear 
being treated with study drug. Scores will be according to the following scale: 
Score 
Category 
Description 
0 
None 
No debris present 
1 
Scant 
Debris minimally present, but with no notable occlusion of external ear 
canal 
2 
Moderate 
Debris present with partial occlusion of external ear canal; tympanic 
membrane can be visualized 
3 
Heavy 
Complete occlusion of ear canal; tympanic membrane cannot be 
visualized 


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7.4.3 
Presence of Fungal Elements 
Upon otoscopic examination, the investigator will assess the presence of fungal elements in each 
ear being treated with study drug. Scores will be according to the following scale: 
Score 
Category 
Description 
0 
Absent 
No fungal elements present on visual inspection with otoscope 
1 
Present 
Fungal elements present on visual inspection with otoscope, such as 
visualization of white filaments in debris; black, gray, bluish, yellow, 
or white discharge; white debris with hyphae; or moist white plugs 
with black debris; or other observations that in the investigator’s 
judgment are indicative of the presence of fungus 
7.4.4 
Pain 
Subjects or their caregivers (as appropriate, based on the age of the subject) will be asked by the 
investigator (or designee) whether pain is present in each ear being treated with study drug. 
Questions such as the following will be used in order to gather information for this assessment: 
“Over the last 24 hours, has your ear hurt?” 
“Over the last 24 hours, has your pain been constant?” 
“Over the last 24 hours, would you characterize your pain as more dull or sharp?” 
“Over the last 24 hours, have you had pain when your earlobe or the front part of your ear is 
touched?” 
“Over the last 24 hours, have you felt pain inside your ear?” 
“Over the last 24 hours, have you felt pain on the outside of your ear?” 
The investigator will then score the symptom of pain for each ear being treated with study drug, 
taking into consideration the subject’s and/or caregiver’s answers and the investigator’s 
observations of the subject. Scores will be according to the following scale: 
Score 
Category 
Description 
0 
Absent 
No pain 
1 
Present 
Pain present, easily tolerated to intolerable 


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7.5 
Subject Global Assessment 
Subjects or their caregivers (as appropriate, based on the age of the subject) will be asked to 
choose among the following three options to assess the overall level of discomfort in each ear 
being treated with study drug. Subjects or their caregivers will be handed a questionnaire for 
each ear being treated with study drug and asked to indicate the choice that most closely reflects 
the subject's situation with the ear. Choices and scores will be according to the following scale: 
Score 
Category 
Description 
0 
None 
My ear is not causing me any discomfort and is not stopping me from 
my normal activities 
1 
Minor 
My ear is slightly uncomfortable, but it is not for the most part 
stopping me from my normal activities 
2 
Moderate 
My ear is uncomfortable, and it is stopping me from at least some of 
my normal activities 
7.6 
Microbial Culture 
At designated visits, the investigator or designee will obtain a sample from the external ear to be 
sent to a laboratory for microbial culture (for both fungi and bacteria at the Screening/Baseline 
visit and for fungi only at the End of Treatment and Test of Cure visits). Techniques for 
obtaining and handling the sample and sending it to the laboratory will be described in a separate 
laboratory manual. If both ears will be treated with study drug, both ears will be cultured. 
7.7 
Ear Cleaning 
At designated visits, the investigator or designee will clean the ear(s) that are being/have been 
treated with study drug, according to the site’s normal procedures. Ear(s) being treated will be 
cleaned at the designated visits even if they appear clear of debris. In cases in which the 
investigator would normally not clean the ear because it appears to be clear, this cleaning may be 
minimal. All ear cleaning will be documented in the eCRF. 
7.8 
Adverse Event Evaluations 
See Section 8. 
7.9 
Randomization 
See Section 9.2. 
7.10 Study Drug Administration 
See Section 9.1.1. 


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7.11 Treatment Compliance 
Subjects or their caregivers (as appropriate) will complete a diary documenting each study drug 
administration. Additionally, each bottle of study drug will be weighed by the investigator or 
designee before dispensation to the subject and at each visit in which the used bottle is brought to 
the site. 
7.12 Protocol Deviations 
The IRB-approved protocol must be followed except in the case of a change that is intended to 
eliminate an immediate risk to subjects. 
The date of, nature of, and reason for deviations will be documented and explained by the 
investigator in all cases. Significant or major protocol deviations impacting the safety of the 
subject or the integrity of the study must be reported by the investigator to the sponsor and/or its 
designee and to the IRB immediately. Reporting of all other protocol deviations must adhere to 
the requirements of the governing IRB. 
All changes to the protocol will be made by the sponsor or designee as an approved amendment 
to the protocol, submitted to the FDA, and approved by the IRB prior to implementation. New or 
altered consent forms required by the IRB due to a protocol revision must be signed by all 
subjects currently enrolled in the study and must be used for any subsequent subject enrollment. 


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8 
ADVERSE EVENTS 
8.1 
Definition of an Adverse Event 
An AE is any untoward medical occurrence in a subject or clinical investigation subject 
administered a study drug and which does not necessarily have a causal relationship with the 
study drug. An AE can therefore be any unfavorable and unintended sign (including a clinically 
significant abnormal laboratory finding), symptom, or disease temporally associated with the use 
of an investigational or marketed study drug, whether or not considered related to the 
investigational or marketed study drug. AEs include any illness, sign, or symptom that has 
appeared or worsened during the course of the clinical trial, regardless of causal relationship to 
the study drug. Study drug includes the investigational drug under evaluation and the comparator 
product. 
Medical conditions/diseases present before signing the informed consent form are only 
considered AEs if they worsen after the informed consent form is signed.  
AEs may be either spontaneously reported or elicited during questioning and examination of a 
subject. At each examination or visit, study personnel will ask each subject the following 
question, “Have you had any problems since we last spoke?” If known, the investigator should 
report the diagnosis of the underlying illness or disorder, rather than its individual symptoms. 
8.1.1 
Definition of a Serious Adverse Event 
An SAE is any untoward medical occurrence occurring at any dose that results in any of the 
following outcomes: 
• Results in death 
• Is life-threatening (defined as an event in which the subject was at risk of death at the 
time of the event; it does not refer to an event which hypothetically might have caused 
death if it were more severe) 
• Requires inpatient hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant disability/incapacity 
• Is a congenital anomaly/birth defect 
• Is an important medical event (defined as a medical event(s) that may not be immediately 
life-threatening or result in death or hospitalization but, based upon appropriate medical 
and scientific judgment may jeopardize the patient/subject or may require medical or 
surgical intervention to prevent one of the other serious outcomes listed in the definition 
above). Examples of such events include, but are not limited to: allergic bronchospasm 
requiring intensive treatment in an emergency room or at home; blood dyscrasia or 
convulsions that do not result in inpatient hospitalization; the development of drug 
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Treatment on an outpatient emergency basis that does not result in hospital admission, or a 
hospitalization that is elective or is a preplanned treatment for a pre-existing condition that has 
not worsened since the start of the study, is not considered an SAE. 
8.2 
Severity of Adverse Events 
The severity of an AE will be determined by the investigator according to the following 
definitions: 
• Mild: Awareness of event, but easily tolerated and does not disrupt usual activity 
• Moderate: Discomfort sufficient to cause interference with usual activity 
• Severe: Incapacitating, with inability to perform usual activities 
8.3 
Relationship of Adverse Events to Study Drug 
The relationship of AEs to the study drug will be assessed by the investigator according to the 
following definitions: 
• Not suspected: The temporal relationship of the event to the study drug makes a causal 
relationship unlikely, or, other drugs, therapeutic interventions or underlying conditions 
provide a sufficient explanation for the observed event. 
• Suspected: The temporal relationship of the event to the study drug makes a causal 
relationship possible or other drugs, therapeutic interventions or underlying conditions do 
not provide a sufficient explanation for the observed event. 
If there is any valid reason, even if undetermined, for suspecting a possible cause-and-effect 
relationship between the study drug and the occurrence of the AE, then the AE should be 
considered “suspected.” 
If the relationship between the AE and the study drug is determined by the sponsor to be 
“suspected,” the event will be considered to be related to the study drug for the purposes of 
expedited regulatory reporting. 
8.4 
Documentation of Adverse Events 
All AEs must be completely recorded on the Adverse Events section of the eCRF. The collection 
of AE information should begin after the subject has signed informed consent and continue up 
through the Test of Cure Visit. Subjects experiencing AEs that cause interruption or 
discontinuation of study drug, or those experiencing AEs that are present at the end of their 
participation in the study or that resulted in permanent discontinuation will receive follow-up as 
appropriate until the AEs have either resolved or have stabilized. 
For each AE, the Investigator will evaluate and report the following: 
• Onset (date); 
• Resolution (date); 
• Severity grade (mild, moderate, severe); 


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• Relationship to study drug (not suspected, suspected); 
• Action taken (none, study drug temporarily interrupted, study drug permanently 
discontinued, concomitant medication taken, hospitalization/prolonged hospitalization, 
other); 
• Serious (yes/no); 
• Whether the AE occurred at the study drug application site (yes/no); 
• For AEs of the ear, which ear (left, right, or both) was affected. 
8.4.1 
Additional Reporting Requirements for Serious Adverse Events 
All SAEs that occur from the time the subject has signed the informed consent until the Test of 
Cure Visit will be reported. Additionally, any SAEs “suspected” to be related to the study drug 
and discovered by the investigator at any time after the study should be reported. Each of these 
SAEs must be reported to the sponsor’s designee within 24 hours of the occurrence of the SAE, 
or within 24 hours of learning of the SAE. Information on recurrent episodes, complications, or 
progression of the initial SAE must also be reported within 24 hours of the investigator receiving 
the information.  
Reporting may be by telephone, confirmed facsimile transmission, or confirmed email to the 
medical monitor. The investigator must assess the relationship of the SAE to study drug and 
must complete the SAE form. If only limited information is initially available, follow-up reports 
are required. Follow-up information (e.g., discharge summary) will be retained in the subject’s 
chart and a copy (with the subject’s personal information removed and with the subject identified 
only by subject number) will be sent by confirmed facsimile transmission or confirmed email to 
the medical monitor. In the event of death, if an autopsy is performed, a copy of the report (with 
the subject’s personal information removed and with the subject identified only by subject 
number) should be sent to the medical monitor. 
As required and after the sponsor’s review and determination of causality, the sponsor and/or 
designee will notify investigators of all AEs that are serious, unexpected, and considered by the 
investigator to have a suspected relationship to the study drug. This notification will be in the 
form of an update to the Investigator’s Brochure (i.e., “15-day letter”). An AE, whether serious 
or non-serious, is designated unexpected (unlabeled) if it is not reported in the clinical safety 
section of the Investigator’s Brochure or if the event is of greater frequency, specificity or 
severity.  
Upon receiving such notices, the investigator must review and retain the notice with the 
Investigator’s Brochure and immediately submit a copy of this information to the responsible 
IRB according to local regulations. The investigator and IRB will determine if the informed 
consent requires revision. The investigator should also comply with the IRB procedures for 
reporting any other safety information. Follow-up reports should be submitted when requested or 
when pertinent information becomes available. 


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The sponsor will report all SAEs to the US FDA on the appropriate schedule depending on the 
event’s expectedness and relationship to study drug based on the available information as 
presented in the Investigator’s Brochure.  
Any SAE occurring after the Test of Cure Visit and which is not considered to be of “suspected” 
relationship to study drug does not need to be reported. 
8.5 
Pregnancy 
Females of childbearing potential, as defined in Section 4.1, must use an effective method of 
contraception from screening up through the Test of Cure Visit. Acceptable methods include the 
use of at least one of the following: 1) IUD; 2) hormonal contraceptives (oral, injectable, 
implant, or ring); 3) barrier contraceptives (condom or diaphragm) with spermicide; or 4) 
abstinence. 
Should a pregnancy occur, it must be reported and recorded on the pregnancy form and sent by 
confirmed facsimile or confirmed email to the medical monitor, as well as documented in the 
eCRF. Pregnancy in itself is not regarded as an AE unless there is a suspicion that the study drug 
product may have interfered with the effectiveness of a contraceptive medication. 
The outcome of all pregnancies (spontaneous miscarriage, elective termination, normal birth, or 
congenital abnormality) must be followed up and documented even if the subject was 
discontinued from the study. 
8.6 
Study Contacts 
Study contacts will be provided in a separate document. 


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9 
STUDY TREATMENTS 
9.1 
Description of Study Drug 
Miconazole oil contains the active ingredient, 2% miconazole, formulated in an oil vehicle 
containing refined peanut oil, light mineral oil, oleth-2, and isopropyl myristate. For subjects 
randomized to the 14-day groups, 2% miconazole oil will be compared descriptively against the 
oil vehicle, which will not contain miconazole and will instead contain a greater amount of 
refined peanut oil and mineral oil to account for the absence of the miconazole. 
Study drug will be supplied in bottles containing ~20 grams of product. The dispensing tip will 
deliver approximately 30 mg of product per drop. 
9.1.1 
Administration 
Subjects will be seated or lying on one side with the head positioned so the ear being treated is 
facing up. If both ears are being treated, the ear that appears to have less severe disease will be 
treated first. The subject or caregiver will gently pull the ear lobe backward and upward and 
apply 5 drops of miconazole oil into the ear. The subject will be instructed to keep the head 
positioned with the ear facing up for approximately 1 minute to allow the miconazole oil to coat 
the ear canal. After 1 minute, the subject can then straighten his/her head, and excess material 
dripping out of the ear can be gently patted using a clean cotton ball. 
If both ears are being treated, the subject will then wait at least 5 minutes, then repeat this 
procedure for the second ear. 
While on study treatment, subjects will be instructed to avoid getting water in the ear, to consider 
drying excessive water in the ear by using a blow dryer, and to place a Vaseline-impregnated 
cotton ball over the affected ear(s) to help keep water out of the ear(s) while bathing or 
showering. Subjects will be asked to avoid bathing or shower for at least 30 minutes after 
applying study drug. 
9.2 
Randomization 
Subjects will be randomized in a 1:1:1 ratio to one of three groups: 1) 7-day treatment with 
miconazole oil; 2) 14-day treatment with miconazole oil; or 3) 14-day treatment with miconazole 
oil vehicle. Interim assessments are planned to ensure that there is a sufficient number of subjects 
within each group for the primary analysis. If deemed necessary the randomization ratio may be 
adjusted following the interim assessments; see Section 10.5.5 for details. 
9.3 
Masking/Unmasking 
The duration of treatment will not be masked. For subjects randomized to the 14-day treatment 
durations, the contents of the study drug (miconazole oil versus vehicle) will be masked. 
Randomized study drug will be packaged in identical bottles and will be labeled with a 
randomization number rather than the contents of the bottle. 


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For subjects randomized to the 14-day durations, if it becomes necessary to unmask a subject’s 
treatment assignment in case of emergency, the investigator should contact the sponsor. A person 
at the sponsor organization who is not otherwise involved with the study will maintain a 
randomization list that will enable that person to inform the investigator of the subject’s 
treatment allocation. The treatment allocation is to be obtained only if a medical emergency 
exists and knowledge of the medication being taken will influence the medical management of 
the subject. 
9.4 
Study Drug Handling and Dispensing 
9.4.1 
Packaging and Labeling 
The miconazole oil and the oil vehicle will be manufactured, packaged and labeled by Hill 
Dermaceuticals, Inc. It will be packaged in dropper bottles, each of which will contain ~20 
grams of study drug. The dropper will dispense approximately 30 mg per drop. 
The Study drug and Vehicle will be packaged in primary bottle and provided in identical study 
drug kits. Each kit will contain the investigational drug product (or placebo product), reserve 
identical drug product (or placebo product), bag of cotton balls, and Vaseline jelly. The subject 
will be dispensed the kit (minus the reserve product) at Baseline only. The dropper bottles will 
be weighed with the cap on prior to dispensing. If the subject loses a bottle (lost or damaged), the 
reserve bottle will be dispensed using a replacement process as defined in the randomization 
plan. Each drug kit dispensed will be documented on the drug accountability log. Labels on the 
drug kit will contain the following information: 
• Protocol Number 
• Subject Number  
• Space for entry of the subject initials 
• Space for entry of date dispensed 
• A statement reading, “For otic use only. Avoid contact with eyes and lips” 
• A statement reading, “Store at controlled room temperature 20°C to 25°C (68°F to 77°F) 
with excursions permitted between 15°C to 30°C (59°F to 86°F)”  
• A statement indicating the sponsor, Hill Dermaceuticals 
• A statement indicating the quantity of product (20 grams) 
• A statement reading, “Caution: New Drug - Limited by Federal Law to Investigational 
Use” 
• A statement reading, “Keep out of Reach of Children 
9.4.2 
Storage 
The study drug is to be stored at room temperature (20°C to 25°C, or 68°F to 77°F), with 
excursions permitted between 15°C and 30°C (59°F and 86°F). All investigational study drug 
must be stored in a secure facility, with access limited to the investigator and authorized staff. 


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9.5 
Accountability 
The investigator or designee (e.g, study coordinator or pharmacist) is responsible for ensuring 
storage as per the label on the study drug and adequate accountability of all used and unused 
study drug. Adequate accountability includes acknowledgment of receipt of each shipment of 
study drug (quantity and condition), records of administration (including container number, date 
administered, subject number, and the initials of the person administering the drug), and 
documentation of quantities returned to the sponsor (or designee). 
At time points during the course of the study and/or upon completion of the study, the sponsor or 
designee will review and verify the investigator's accountability records.  
9.6 
Return and Destruction 
At the completion of the study, following verification of the investigator’s accountability records 
by the sponsor and/or designee, all study drug must be returned to the sponsor or designee. This 
would include study drug returned by the subjects at the completion of the study, and reserve 
products that were not used. 


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10 STATISTICAL CONSIDERATIONS 
10.1 Study Endpoints 
The primary and secondary endpoints will be based on the investigator reporting of signs and 
symptoms for the study ear. Other efficacy endpoints will be based on the subject reporting of 
the symptom of pruritus. 
Descriptive statistics will be presented for the signs and symptoms of otomycosis for the study 
ear at each evaluation and will include the number and percentage of subjects in each category. 
Subject assessments for the study ear for pruritus will also be summarized. No imputation will be 
made for missing data.  
10.1.1 
Primary Efficacy Endpoint 
The primary efficacy endpoint will be the percentage of subjects at the Test of Cure Visit with 
“therapeutic cure,” defined as a negative mycological culture plus “clinical cure” for the study 
ear.  Clinical cure is defined as the absence of all otomycosis signs and symptoms based on 
Investigator assessment according to the scales for each individual sign or symptom and with 
absence defined as a score of 0 on each of the scales for pruritus, debris, fungal elements, and 
pain). See Section 7.4 for the scales for each otomycosis sign and symptom. 
10.1.2 
Secondary Efficacy Endpoints 
Secondary efficacy endpoints will include the following: 
• Percentage of subjects with clinical cure at the Test of Cure Visit 
• Percentage of subjects with a negative fungal culture at the Test of Cure Visit 
• Percentage of subjects with a negative fungal culture at the Test of Cure visit as well as 
individual sign or symptom score of 0 or 1 on each of the scales for pruritus and debris 
and a score of 0 on each of the scales for fungal elements and pain. 
• Percentage of subjects with individual signs or symptoms with a score of 0 or 1 on each 
of the scales for pruritus and debris and a score of 0 on each of the scales for fungal 
elements and pain. 
• Subject global assessments at Baseline and Test of Cure as well as categorical shifts in 
the subject global assessment scale scores from the Screening/Baseline to the Test of 
Cure Visit. 
• If feasible, analyses may also be conducted by fungal organism isolated at 
Screening/Baseline. 


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10.1.3 
Other Efficacy Endpoints 
Other efficacy endpoints based on subject reporting of pruritus will include the following: 
•
Subject therapeutic cure (defined as a negative mycological culture plus clinical cure) at
the Test of Cure visit for the study ear based on subject assessment of pruritus. Clinical
cure is defined as the absence of all otomycosis signs and symptoms according to the
scales for each individual sign or symptom and with absence defined as a score of 0 on
each of the scales for pruritus, debris, fungal elements, and pain.
10.1.4 
Safety Endpoints 
Safety endpoints will be the percentage of subjects with treatment-emergent AEs, with 
treatment-emergent defined as occurring upon or after administration of the first dose of study 
drug. 
10.2 Hypotheses 
No formal hypotheses will be tested in this study. Descriptive comparisons will be made between 
the miconazole oil and the oil vehicle groups for subjects randomized to the 14-day groups. 
Additionally, descriptive comparisons will be made between the 7-day and 14-day groups for 
subjects randomized to the miconazole oil treatment. 
10.3 Sample Size 
The sample size for this study is not based on statistical considerations and is instead intended to 
be a reasonable number of subjects upon which to gather preliminary information on the efficacy 
and safety of miconazole oil when administered via the otic route to subjects with otomycosis. 
10.4 Study Populations 
10.4.1 
Intent-to-treat Population 
The intent-to-treat (ITT) population will be defined as all subjects who were randomized and 
dispensed study medication. 
10.4.2 
Modified Intent-to-treat Population 
The modified intent-to-treat (MITT) population will be a subset of the ITT population. The 
MITT population will include subjects who were randomized, dispensed study drug, and with a 
clinical diagnosis of otomycosis confirmed by a positive fungal culture 


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10.4.3 
Per Protocol Population 
The per protocol (PP) population will be a subset of the MITT population and will include all 
subjects who complete the Test of Cure visit without any major protocol violations. The PP 
population will include subjects in the MITT population who did not meet any of the following 
criteria: 
• Violated the inclusion/exclusion criteria 
• Used an interfering concomitant medication 
• Did not attend the Test of Cure visit 
• Did not attend the End of Treatment visit 
• Have not been compliant with the dosing regimen (i.e., subjects must have received 
80%-120% of the expected applications of study medication in the study ear during 
participation in the study) 
• Out of visit window at the Test of Cure Visit (-1/+8 days) 
Subjects who discontinue from the study due to an adverse event related to study treatment, 
documented lack of treatment effect, or worsening of condition will be included in the PP 
population. Prior to breaking the blind, other additional criteria may be added to the list to 
accommodate for unforeseen events that occurred during the conduct of the trial that result in 
noteworthy study protocol violations. 
10.4.4 
Safety Population 
The safety population will include all randomized subjects who received at least one dose of 
study drug and had at least one post-Baseline safety assessment.  
10.5 Statistical Methods 
Details of statistical analyses will be provided in a separate statistical analysis plan. 
10.5.1 
Efficacy Analyses 
The primary population for all efficacy analyses will be the MITT population (see Section 10.4). 
Efficacy endpoints will also be summarized for the PP population and will be considered 
supportive. 
The sample size N, frequency, and percent of subjects who demonstrate a positive outcome for 
each efficacy endpoint will be presented for the primary efficacy parameter as well as all 
secondary efficacy parameters. 
In cases of bilateral otomycosis, the ear with the worse infection at Screening/Baseline, as 
assessed by the investigator by taking into account both clinical signs and symptoms and fungal 
culture results, will be used as the study ear for efficacy analyses. If both ears are determined by 


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the investigator to have the same degree of infection at Screening/Baseline, the left ear will be 
used as the study ear for the purposes of efficacy analyses. 
10.5.2 
Safety Analyses 
Safety summaries will be conducted using the safety population (see Section 10.4.4). All AEs 
occurring during the study will be recorded and classified using terminology from the Medical 
Dictionary for Regulatory Activities (MedDRA). All reported treatment-emergent adverse events 
(TEAEs), defined as any AE with an onset on or after the date of first study drug application, 
will be summarized by treatment group. Summaries will provide the number of subjects 
reporting TEAEs, system organ class, preferred term, severity, and relationship to study drug. 
When summarizing TEAEs by severity or relationship to study drug, each subject will be 
counted only once within a system organ class or a preferred term using the event with the 
greatest severity or causality, respectively, within each category. All reported SAEs will be 
summarized by the number of subjects reporting the event, system organ class, preferred term, 
severity, and relationship to study drug. 
All information pertaining to AEs noted during the study will be listed by treatment group and 
subject and will include a verbatim description of the event as reported by the investigator, as 
well as the preferred term, system organ class, start date, stop date (if stopped), seriousness, 
severity, action taken regarding the study drug, corrective treatment, outcome, and relationship to 
the study drug. In addition, a listing of subjects who prematurely discontinue from the study due 
to AEs will be provided as well as a listing of subjects who report an SAE. 
10.5.3 
Subject Demographics and Baseline Characteristics 
Subject demographic and baseline characteristics will be summarized descriptively for the 
MITT, PP, and Safety populations and will be supported with individual subject data listings. 
10.5.4 
Missing Data 
Missing values from the Test of Cure visit from which the dichotomized Therapeutic Cure is 
derived will be imputed using last observation carried forward (LOCF) method. 
10.5.5 
Interim Treatment Allocation Assessment(s) 
A subject’s MITT status (specifically positive fungal culture at baseline) is determined only 
following randomization, which may result in imbalance between treatment groups. Therefore, at 
least one assessment during the conduct of the study is planned to ensure that there is a sufficient 
number of subjects within each group for the primary analysis. Once at least 10 MITT subjects 
have been enrolled in the 7-Day active group, the numbers of MITT subjects in the 14-Day 
active group and the 14-Day vehicle group will be determined by an unblinded statistician; no 
persons involved in the day to day conduct of the study will be unblinded. Randomization 
allocation for future subjects may be adjusted if deemed necessary to achieve minimum number 
of subjects within each arm. 
Full details will be provided in the SAP. 


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11 ADMINISTRATIVE CONSIDERATIONS 
11.1 Institutional Review Board 
The protocol, informed consent documents, any information provided to subjects, recruitment 
advertisements and any amendments to these items will have IRB approval prior to their use in 
the study.  
Before study initiation, this protocol, the miconazole oil Investigator’s Brochure, the informed 
consent form, any other written information given to subjects, and any advertisement for subject 
recruitment must have IRB approval. Documentation of IRB approval must be sent to the 
sponsor or designee before study drug will be shipped to the site. The investigator should also 
provide the miconazole oil Investigator’s Brochure to the IRB. 
The investigator must provide the IRB with reports, updates, and other information (e.g., safety 
updates, protocol amendments, and administrative letters) according to regulatory requirements 
and Institution procedures. The IRB must be notified of completion or termination of the study. 
Copies of all correspondence with the IRB regarding this study must be sent to the sponsor or its 
designee. Additionally, the clinical site must maintain an accurate and complete record of all 
reports, documents, and other submissions made to the IRB concerning this protocol. 
11.2 Ethics 
The investigator and all study staff will conduct the study in compliance with this protocol and 
compliance with FDA regulations, all applicable federal, state, and local laws, rules and 
regulations relating to the conduct of the clinical study, the ethical principles of the Declaration 
of Helsinki, and the current ICH GCP guidelines. 
The rights, safety, and wellbeing of the study subjects are the most important considerations and 
prevail over the interests of science and society. 
All personnel involved in the conduct of this study must be qualified by education, training 
and/or experience to perform their assigned responsibilities. 
11.3 Informed Consent and Assent 
Voluntary informed consent and assent (as applicable) will be given by every subject and/or the 
subject’s legal representative (as applicable) prior to the initiation of any study related 
procedures. The IRB-approved consent and assent forms must include all elements required by 
FDA, state, and local regulations, and may include appropriate additional elements. Sample 
informed consent and assent forms containing the required elements of informed consent or 
assent (as applicable) will be provided by the sponsor or designee. Any changes made to this 
sample must be approved by the sponsor or its designee prior to submission to the IRB. After 
approval by the sponsor or its designee, the informed consent and assent forms must be 
submitted to and approved by the IRB. 


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The informed consent and assent forms must be written in a language in which the subject is 
fluent. Regulations require that foreign language informed consent and assent forms be 
submitted to the IRB for approval. The foreign language translation is required to contain a 
statement of certification of the translation. The investigator must forward a copy of the consent 
form, the certified foreign language translation, and an IRB approval letter to the sponsor. 
The investigator/designee will explain the study to each potential subject and/or the subject’s 
legal representative (as applicable) prior to the screening evaluation, and the subject and/or the 
subject’s legal representative (as applicable) must indicate voluntary consent by signing and 
dating the approved informed consent form. The consent process will be conducted prior to the 
start of any study-related procedure. The investigator must retain the original and provide the 
subject and/or the subject’s legal representative (as applicable) with a copy of the consent 
form(s). 
The investigator will maintain documentation that informed consent and assent (as applicable) 
was obtained prior to the initiation of any study-related procedures. 
11.4 Confidentiality of Subject Information 
Subject data recorded on eCRFs during the study will be documented in a coded fashion, and all 
communications and reports regarding this study will identify subjects only by their subject 
numbers. Complete subject identification will be kept by the investigator for purposes of long-
term follow-up, if needed. This information, as well as all medical information resulting from a 
subject’s participation in this study, will be treated with strict adherence to professional standards 
of confidentiality. Confidentiality of subject records must be maintained to ensure adherence to 
applicable local privacy regulations. 
Data generated for the study should be stored in a limited-access file area and be accessible only 
to the investigator and authorized personnel, the sponsor and its designee(s), the IRB, and FDA 
or other relevant regulatory authorities. Medical information resulting from a subject’s 
participation in this study may be given to the subject’s personal physician or to the appropriate 
medical personnel responsible for the subject’s welfare, but no information that can be related to 
a specific individual subject will be released or used in any fashion without the signed written 
consent of that subject. 
11.5 Study Monitoring 
Representatives of the sponsor and designee(s) must be allowed to visit all study sites, to review 
study records and to directly compare them with source documents (including, but not limited to 
patient and hospital records), to discuss the study conduct with the investigator and study staff 
and to verify that the investigator, study staff and facilities remain acceptable for the conduct of 
the study. Representatives of government regulatory authorities (i.e. FDA) may also evaluate the 
study records, source documents, investigator, study staff and facilities. All data generated 
during this study and the medical records/documents from which they originated are subject to 
inspection by the sponsor, its designee(s), the FDA, and other regulatory agencies. 


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Prior to the start of the study, the sponsor and/or its designee will review the protocol, eCRF, 
regulatory obligations, and other material or equipment relevant to the conduct of the study with 
the investigator and relevant study site personnel.  
Monitoring visits and telephone consultations will occur as necessary, during the course of the 
investigation to verify the following: 
• the rights and well-being of subjects are protected 
• the conduct of the investigation is in compliance with the currently approved 
protocol/amendment, ICH GCPs, and IRB requirements 
• the integrity of the data, including adequate study documentation 
• the facilities remain acceptable 
• the investigator and site personnel remain qualified and able to conduct the study 
• study drug accountability 
The investigator must immediately notify the sponsor of any audits by any regulatory agency, 
and must promptly provide copies of any audit reports. 
11.6 Case Report Form Requirements 
Paper source documents will be created and retained at the clinical site.  
Electronic case report forms (eCRFs) will be used to record subject data during the course of the 
study. The investigator and study site personnel will be responsible for completing the eCRFs. 
The investigator is required to verify that all of the requested information is accurately recorded 
in the eCRFs. All information requested in the eCRFs needs to be entered, including subject 
identification, date(s), assessment values, etc. Any omission or discrepancy will require 
explanation. 
The sponsor or designee will review the data recorded in the eCRFs utilizing original source 
documentation, as applicable. Discrepant findings will be queried within the electronic data 
capture (EDC) system. The investigator and study site personnel will be responsible for 
answering all queries. Data reconciliation will be performed between the EDC data and the 
external data reported by the central laboratory. Any discrepancies in the data will be queried 
first with the clinical site and second with the central laboratory. 
A copy of the eCRFs or archive of eCRFs will be retained by the investigator, who must ensure 
that it is stored in a secure place. 


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11.7 Quality Assurance Audits 
Representatives from the sponsor and/or a third party selected by the sponsor or designee may 
conduct a quality assurance audit of this study at any time during or after completion of the 
study. The Investigator will be given adequate notice if he/she is selected for an audit. During the 
audit, the investigator must provide the auditor with direct access to all relevant documents and 
discuss any findings with the auditor. 
In the event of an inspection by the FDA or other regulatory authority, the investigator must give 
the inspector direct access to relevant documents and discuss any findings with the inspector. If 
an inspection is requested by a regulatory authority and/or IRB, the investigator must inform the 
sponsor immediately that this request has been made. 
11.8 Records Retention 
The investigator must retain all study-related records for at least 2 years after a marketing 
application is approved for the drug. If an application is not approved for the drug, the 
investigator must retain all study-related records until at least 2 years after shipment and delivery 
of the drug for investigational use is discontinued, and FDA or regulatory agencies have been so 
notified. 
The investigator must contact the sponsor prior to destroying any records associated with this 
study.  
If the location of the study files changes from the address noted on the Form FDA 1572, written 
notification of the new location must be given to the sponsor. In the event the investigator 
withdraws from participation in the study, study records will be transferred to a mutually agreed 
upon designee. The investigator must provide written notice to the sponsor of such transfer. 
11.9 Publication of Results 
All information concerning miconazole oil including study data and sponsor operations including 
but not limited to formulation information, manufacturing processes, basic scientific data, and 
patent applications will be regarded as confidential and will remain the sole property of the 
sponsor. The investigator agrees to use this information solely for the purposes of accomplishing 
this study and agrees not to use it for any other purposes without the written consent of the 
sponsor. 
Study-related information must not be published or presented by the investigator without prior 
consultation with and written agreement from the sponsor. 


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12 REFERENCES 
Bassiouny A, Kamel T, Moawad MK, Hindawy DS. Broad spectrum antifungal agents in 
otomycosis. J Laryngol Otol. 1986 Aug;100(8):867-73. 
Kiakojuri K, Roushan MR, Sepidgar SA. Suction clearance and 2% topical miconazole versus 
the same combination with acidic drops in the treatment of otomycosis. Southeast Asian J 
Trop Med Public Health. 2007 Jul;38(4):749-53. 
Investigator’s brochure for miconazole oil. Version 1, dated January, 2016. 
Liebel F, Lyte P, Garay M, Babad J, Southall MD. Anti-inflammatory and anti-itch activity of 
sertaconazole nitrate. Arch Dermatol Res. 2006 Sep;298(4):191-9. 
Musaji N. Antifungal drug resistance: not all azoles are equal. Expert Rev Anti Infect Ther. 2010 
May;8(5):515-6. 
Navaneethan N, YaadhavaKrishnan RP. Type of Antifungals: Does it Matter in Empirical 
Treatment of Otomycosis? Indian J Otolaryngol Head Neck Surg. 2015 Mar;67(1):64-7. 
Paller AS, Nimmagadda S, Schachner L, Mallory SB, Kahn T, Willis I, Eichenfield LF. 
Fluocinolone acetonide 0.01% in peanut oil: therapy for childhood atopic dermatitis, even in 
patients who are peanut sensitive. J Am Acad Dermatol. 2003 Apr;48(4):569-77. 
Pershing LK, Corlett J, Jorgensen C. In vivo pharmacokinetics and pharmacodynamics of topical 
ketoconazole and miconazole in human stratum corneum. Antimicrob Agents Chemother. 
1994 Jan;38(1):90-5. 
Pubmed Health, 2015. 
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0044877/#DDIC601941.side_effects_secti
on. Published Oct 1, 2015. Accessed Dec 5, 2015. 
Stern JC, Shah MK, Lucente FE. In vitro effectiveness of 13 agents in otomycosis and review of 
the literature. Laryngoscope. 1988 Nov;98(11):1173-7. 
Tom LW. Ototoxicity of common topical antimycotic preparations. Laryngoscope. 2000 
Apr;110(4):509-16. 
Vandenbosch D, Bink A, Govaert G, Cammue BP, Nelis HJ, Thevissen K, Coenye T. 
Phytosphingosine-1-phosphate is a signaling molecule involved in miconazole resistance in 
sessile Candida albicans cells. Antimicrob Agents Chemother. 2012 May;56(5):2290-4. 
Vandenbosch D, Braeckmans K, Nelis HJ, Coenye T. Fungicidal activity of miconazole against 
Candida spp. biofilms. J Antimicrob Chemother. 2010 Apr;65(4):694-700. 
Vennewald I, Klemm E. Otomycosis: Diagnosis and treatment. Clin Dermatol. 2010 Mar 
4;28(2):202-11. 
Yunginger JW, Calobrisi SD. Investigation of the allergenicity of a refined peanut oil-containing 
topical dermatologic agent in persons who are sensitive to peanuts. Cutis. 2001 
Aug;68(2):153-5. 
Xhauflaire-Uhoda E, Vroome V, Cauwenbergh G, Piérard GE. Dynamics of skin barrier repair 
following topical applications of miconazole nitrate. Skin Pharmacol Physiol. 
2006;19(5):290-4. 


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13 SUMMARY OF PROTOCOL AMENDMENTS 
13.1 Amendment 1 Version 2 14 February 2017 
This amendment reflects updates and revisions based on comments and feedback received from 
the Agency. In addition, corrections to inconsistencies throughout the protocol, minor changes to 
study conduct, and administrative changes (i.e., typographical/grammatical, abbreviations) have 
been made based on CRO and Investigator feedback. 
As summary of changes is provided below. New/changes in text are bolded. Deletions are struck 
through. Sections that are new or have been completely revised only a short description is 
provided. 
Global Changes: 
Administrative changes for typographical / grammatical errors, updates to list of abbreviations and 
abbreviations throughout text 
Title, Protocol Approval, and Study Acknowledgment Pages: 
Updated to reflect protocol version and date change 
Synopsis 
Study Number: 
HD-MCZ-PHII-DRF062016 
Study Period: 
The study duration for each subject will be up to 29 30 days (up to 14 days of treatment, and 7 8 days of 
follow-up, including the visit window of up to 8 additional days after the scheduled day to complete the 
final visit) 
Design and Methodology: 
…..Subjects will be randomly assigned in a 1:1:1 ratio to receive miconazole oil [administered as 5 
drops per ear at ~30 µL mg per drop instilled into the external ear canal of the ear(s) affected by 
otomycosis] for 7 or 14 days, or vehicle for 14 days….  
….. 
At Screening/Baseline (Day 1), potentially eligible subjects will provide informed consent, and subjects 
will undergo screening evaluations to include a physical examination, an assessment of the signs and 
symptoms of otomycosis (pruritus, debris, visual examination for presence of fungal elements, and 
pain), and an evaluation of adverse events (AEs). medical history. Urine will be obtained for pregnancy 
screening in female subjects of childbearing potential. Prior and concomitant medications will be 
reported. Subjects with positive signs and symptoms of otomycosis and who meet all other eligibility 
criteria will be entered into the study, and a subject global assessment of disease will be performed. A 
culture Fungal and bacterial cultures of the affected ear(s) will be taken, then debris will be cleaned 
from the affected ear(s) following the site’s normal procedures…… 
…… 
All subjects will return to the clinic on Day 8. For subjects randomized to the 7-day treatment duration, 
this visit will constitute the End of Treatment Visit, with procedures performed as described for that 
visit below. Subjects randomized to 7-day treatment will not administer study drug on Day 8.  
…… 
Procedures performed at the End of Treatment Visit will include an assessment for clinical signs and 
symptoms of otomycosis, a subject global assessment, and a fungal culture of the affected ear(s).  


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….. 
Procedures performed at the Test of Cure Visit will include an assessment of clinical signs and 
symptoms of otomycosis, a subject global assessment, and a fungal culture of the affected ear(s).  
Key Exclusion Criteria: 
….use of any systemic antifungal therapy within 28 days of study entry, warfarin within 28 days of 
study entry, immunosuppressive or immune-stimulating drugs within 28 days of study entry, or 
systemic steroids within 3 months of study entry; …. 
Test Product, Dose, and Mode of Administration: 
Miconazole oil (7-day and 14-day treatment duration durations) 
Statistical Analyses: 
The primary and secondary endpoints will be based on the investigator reporting of signs and 
symptoms. Other efficacy endpoints will be based on the subject reporting of the symptom of 
pruritus. 
Descriptive statistics will be presented for the signs and symptoms of otomycosis for the study ear 
at each evaluation and will include the number and percentage of subjects in each category. 
Subject assessments for the study ear for pruritus will also be summarized. No imputation will be 
made for missing data. 
The primary efficacy endpoint will be the percentage of subjects at the Test of Cure Visit with 
“therapeutic cure,” defined as a negative mycological culture plus “clinical cure.” Clinical cure is 
defined as the absence of all otomycosis signs and symptoms according to the scales for each individual 
sign or symptom and with absence defined as scores a score of 0 or 1 on each of the scales for pruritus 
and, debris, and scores of 0 on each of the scales for fungal elements, and pain. 
Other efficacy endpoints will include: 
• Percentage of subjects with clinical cure at the Test of Cure Visit 
• Percentage of subjects with a negative fungal culture at the Test of Cure Visit 
• Percentage of subjects with a negative fungal culture at the Test of Cure visit as well as 
individual sign or symptom score of 0 or 1 on each of the scales for pruritus and debris and a 
score of 0 on each of the scales for fungal elements and pain. at the Test of Cure Visit 
• Percentage of subjects with a score of 0 or 1 for debris at the Test of Cure Visit 
• Percentage of subjects with individual signs or symptoms with a score of 0 or 1 on each of the 
scales for pruritus and debris and a score of 0 on each of the scales for fungal elements and 
pain the fungal elements at the Test of Cure Visit 
• Percentage of subjects with a score of 0 for pain at the Test of Cure Visit 
• Subject global assessments at Baseline and Test of Cure as well as categorical shifts in the 
subject global assessment scale scores from the Screening/Baseline to the Test of Cure Visit 
• Percentages of subjects with categorical shifts on the subject global assessment scale from the 
Screening/Baseline to the Test of Cure Visit 
• If feasible, analyses may also be conducted by fungal organism isolated at Screening/Baseline. 
The primary population for all efficacy analyses will be the modified intent-to-treat (MITT) population, 
defined as all subjects who were randomized, dispensed study drug, and with a clinical diagnosis of 
otomycosis and confirmed by a positive fungal culture at Screening/Baseline who received at least one 
dose of study drug. 
…. 


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The primary population for all safety analyses will be the safety population, defined as all randomized 
subjects who received at least one dose of study drug and had at least one post-Baseline safety 
assessment. Safety analyses will include the percentages of subjects with treatment-emergent AEs, 
classified on the basis of Medical Dictionary for Regulatory Affairs (MedDRA) terminology. 
Treatment-emergent AEs will be defined as those occurring upon or after administration of the first dose 
of study drug. 
All AEs occurring during the study will be recorded and classified using terminology from the 
Medical Dictionary for Regulatory Activities (MedDRA). All reported treatment-emergent 
adverse events (TEAEs), defined as any AE with an onset on or after the date of first study drug 
application, will be summarized by treatment group. Summaries will provide the number of 
subjects reporting TEAEs, system organ class, preferred term, severity, and relationship to study 
drug. When summarizing TEAEs by severity or relationship to study drug, each subject will be 
counted only once within a system organ class or a preferred term using the event with the 
greatest severity or causality, respectively, within each category. All reported SAEs will be 
summarized by the number of subjects reporting the event, system organ class, preferred term, 
severity, and relationship to study drug. 
1.3.2. Dose 
……The use of 5 drops of product (at ~30 µL mg per drop) is based on the estimated volume of the 
human external ear canal, and the amount believed to be needed to fully coat the canal. ….. 
3 
Study Design 
….. 
At Screening/Baseline (Day 1), potentially eligible subjects will provide informed consent, and subjects 
will undergo screening evaluations to include a physical examination, an assessment of the signs and 
symptoms of otomycosis (pruritus, debris, visual examination for presence of fungal elements, and 
pain), and an evaluation of adverse events (AEs). medical history. Urine will be obtained for pregnancy 
screening in female subjects of childbearing potential. Prior and concomitant medications will be 
reported. Subjects with positive signs and symptoms of otomycosis and who meet all other eligibility 
criteria will be entered into the study, and a subject global assessment of disease will be performed. A 
culture Fungal and bacterial cultures of the affected ear(s) will be taken, then debris will be cleaned 
from the affected ear(s) following the site’s normal procedures…… 
All subjects will return to the clinic on Day 8. For subjects randomized to the 7-day treatment duration, 
this visit will constitute the End of Treatment Visit, with procedures performed as described for that 
visit below. Subjects randomized to the 7-day treatment duration will not administer study drug 
on the day of this visit. …. 
…..For subjects randomized to the 14-day treatment duration, this visit will constitute the End of 
Treatment Visit, with procedures performed as described for the End of Treatment Visit below. 
Subjects randomized to the 14-day treatment duration will not administer study drug on the day 
of this visit. 
….. 
Procedures performed at the End of Treatment Visit will include an assessment for clinical signs and 
symptoms of otomycosis, a subject global assessment, and a fungal culture of the affected ear(s). 
….AEs and concomitant medications will also be assessed, and the subject will return all unused study 
drug.  
….. 
Procedures performed at the Test of Cure Visit will include an assessment of clinical signs and 
symptoms of otomycosis, a subject global assessment, and a fungal culture of the affected ear(s). … 
 


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Efficacy assessments will include fungal culture of the affected ear(s), assessments of clinical signs and 
symptoms of otomycosis, and a subject global assessment.  
3.1 
Study Duration 
The total duration of the study for a subject from screening until the last visit will be up to 29 30 days 
(including the visit window of up to 8 additional days after the scheduled day to complete the final 
visit). 
4.2 
Exclusion Criteria 
5. 
Use of any systemic antifungal therapy within 28 days of study entry, warfarin within 28 days of 
study entry, immunosuppressive or immune-stimulating drugs within 28 days of study entry, 
or systemic steroids within 3 months of study entry 
4.4 
Subject Discontinuation 
.…. 
…..If possible, the assessment schedule for the Test of Cure Visit should be performed, and an effort 
should be made to collect all unused study drug. 
….. 
Subject discontinuations will be documented clearly on the applicable CRFelectronic case report form 
(eCRF).  
5.2 
Prohibited Medications 
Other than the study drug, no other topical medications are allowed to be used in the ears. Other 
prohibited treatments include systemic antifungal therapy, warfarin, immunosuppressive or immune-
stimulating drugs, and systemic steroids. 
Table 1 
Study Schedule 
Addition of:  
Dispensation of subject diary to Screening/Baseline Day1 
Collection of subject diary to On Treatment Day 8 and End of Treatment Day 8 or 15 
Change in assessments:  
Collection of unused study drug 
FungalMicrobial culture, and addition of footnote g. for this assessment: For both fungi and 
bacteria at the Screening/Baseline visit and for fungi only at the End of Treatment and Test of 
Cure visits 
Change to footnotes:  
a. This visit may occur up to 1 day sooner or up to 3 days later than the specified day. 
h. To be performed in subjects randomized to the 7-day group only, and after all efficacy assessments 
(otomycosis signs and symptoms, subject global assessment, and fungalmicrobial culture) have 
already been performed 
6.2.1 
Screening/Baseline 
…. 
Subjects who are eligible for the study will undergo the following additional procedures: 
• 
…. 
• 
FungalMicrobial culture (fungi and bacteria) 
• 
…. 
• 
Dispensation of subject diary to subject. 
• 
…. 
• 
Subject instruction about the date on which they are to stop administering study drug (after all 
doses have been administered on Day 7 for the 7-day group, and after all doses have been 


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administered on Day 14 for the 14-day groups; subjects will be instructed that study drug should 
be stopped on the appropriate date regardless of the date for which the next visit is scheduled) 
• 
Subjects will be instructed to bring their bottle of study drug and the diary to the site for their 
next visit 
6.2.2 
On Treatment 
These visits may occur up to 1 day sooner or up to 3 days later than the specified day. Subjects 
randomized to the 7-day group will not have any On Treatment visits and will instead proceed directly 
to the procedures specified for the End of Treatment Visit. Subjects randomized to the 14-day groups 
will have one On Treatment visit on Day 8. 
Subjects will be instructed not to administer any study drug on the day of this visit until after the visit 
has occurred, if the visit is scheduled for the morning. If the visit is scheduled for the afternoon, 
subjects will be instructed that the morning dose of the study drug can be administered prior to 
the visit. 
The following procedures and evaluations will occur during the On Treatment visits: 
• 
….. 
• 
Ear cleaning (on Day 8 only) 
• 
…. 
• 
Weighing of study drug and return of the bottle of study drug to the subject 
• 
Collection of unused study drug 
• 
Dispensation of study drug 
• 
For subjects randomized to the 14-day groups,  
• 
Review of subject diary.  
• 
Subject reminder to continue to administer their assigned study drug twice daily up through the 
date on which they are to stop administering study drug (after all doses have been administered 
on Day 14; study drug should be stopped on the appropriate date regardless of the date for which 
the next visit is scheduled) 
• 
Subjects randomized to the 14-day groups will be instructed to bring their bottle of study drug 
and the diary to the site for their next visit 
6.3 
End of Treatment 
This visit may occur up to 1 day sooner or up to 3 days later than the specified day. Subjects 
randomized to the 7-day group will have the End of Treatment Visit on Day 8, and subjects randomized 
to the 14-day groups will have the End of Treatment Visit on Day 15. 
The following procedures and evaluations will occur during the OnEnd of Treatment visits: 
• 
….. 
• 
FungalMicrobial (fungal) culture 
• 
….. 
• 
Collection of unused study drugsubject diary 
• 
Collection/weighing of study drug  
6.4 
Test of Cure 
The following procedures and evaluations will occur during the Test of Cure Visit: 
• 
…. 
• 
FungalMicrobial (fungal) culture  
• 
Ear cleaning (in subjects randomized to the 7-day group only) 
7.4.1 
Pruritus 
Text revised and updated including addition of: 
Section 7.4.1.1 Subject Assessment 


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Section 7.4.1.2 Investigator Assessment 
7.4.3 
Presence of Fungal Elements 
Score 1 updated:  
Fungal elements present on visual inspection with otoscope, such as visualization of white 
filaments in debris; black, gray, bluish, yellow, or white discharge; white debris with 
hyphae; or moist white plugs with black debris; or other observations that in the 
investigator’s judgment are indicative of the presence of fungus 
7.4.3 
Pain 
Text and sample questions revised 
7.5 
Global Assessment 
….Subjects or their caregivers will be handed a questionnaire for each ear being treated with study drug 
and asked to indicate the choice that most closely reflects the (or their dependent’s, as 
appropriate)subject's situation with the ear.  
7.6 
Fungal Microbial Culture 
At designated visits, the investigator or designee will obtain a sample from the external ear to be sent to 
a laboratory for fungal culture.microbial culture (for both fungi and bacteria at the 
Screening/Baseline visit and for fungi only at the End of Treatment and Test of Cure visits). 
Techniques for obtaining and handling the sample and sending it to the laboratory will be described in a 
separate laboratory manual. 
7.11 
Treatment Compliance 
Subjects or their caregivers (as appropriate) will complete a diary of documenting the time and amount 
of each study drug administration.  
8.1 
Definition of Adverse Events 
…. 
Medical conditions/diseases present before signing the informed consent form are only considered AEs 
if they worsen after the informed consent form is signed. Abnormal or out-of-range laboratory test 
results constitute AEs only if they induce clinical signs or symptoms, are considered clinically 
significant, or require therapy. 
8.5 
Pregnancy 
Females of childbearing potential, as defined in Section 4.1, must use an effective method of 
contraception from screening up through the final visit (Day 8).Test of Cure Visit.  
9.1 
Description of Study Drug 
….For subjects randomized to the 14-day groups, 2% miconazole oil will be compared descriptively 
against the oil vehicle, which will not contain miconazole and will instead contain a greater amount of 
refined peanut oil and mineral oil to account for the absence of the miconazole. 
Study drug will be supplied in bottles containing ~20 mLgrams of product. The dispensing tip will 
deliver approximately 30 µLmg of product per drop. 
9.4.1 
Packaging and Labeling 
The miconazole oil and the oil vehicle will be manufactured, packaged and labeled by Hill 
Dermaceuticals, Inc. It will be packaged in dropper bottles, each of which will contain ~20 mLgrams of 
study drug. The dropper will dispense approximately 30 µLmg per drop. 
Addition of text describing study drug packaging and labeling 


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9.5 
Accountability 
…..Adequate accountability includes acknowledgment of receipt of each shipment of study drug 
(quantity and condition), records of administration (including container number, date administered, 
subject number, and the initials of the person administering the drug), and documentation of quantities 
either returned to the sponsor (or designee) or destroyed). 
9.6 
Return and Destruction 
At the completion of the study, following verification of the investigator’s accountability records by the 
sponsor and/or designee, all unused study drug must either be returned to the sponsor or designee, or 
destroyed according instructions from. This would include study drug returned by the sponsor or 
designeesubjects at the completion of the study, and reserve products that were not used. 
10.1 
Study Endpoints 
Addition of new text describing primary and secondary endpoints 
10.1.1 Primary Efficacy Endpoints 
The primary efficacy endpoint will be the percentage of subjects at the Test of Cure Visit with 
“therapeutic cure,” defined as a negative mycological culture plus “clinical cure” for the study ear.  
Clinical cure is defined as the absence of all otomycosis signs and symptoms based on Investigator 
assessment according to the scales for each individual sign or symptom and with absence defined as 
scores of 0 or 1 on each of the scales for pruritus and debris, and scoresa score of 0 on each of the scales 
for pruritus, debris, fungal elements, and pain). See Section 7.4 for the scales for each otomycosis sign 
and symptom. 
10.1.2 Secondary Efficacy Endpoints 
• …… 
• Percentage of subjects with a negative fungal culture at the Test of Cure visit as well as 
individual sign or symptom score of 0 or 1 on each of the scales for pruritus and debris and a 
score of 0 on each of the scales for fungal elements and pain. at the Test of Cure Visit 
• Percentage of subjects with a score of 0 or 1 for debris at the Test of Cure Visit 
• Percentage of subjects with individual signs or symptoms with a score of 0 or 1 on each of the 
scales for pruritus and debris and a score of 0 on each of the scales for fungal elements and 
pain the fungal elements at the Test of Cure Visit 
• Percentage of subjects with a score of 0 for pain at the Test of Cure Visit 
• Subject global assessments at Baseline and Test of Cure as well as categorical shifts in the 
subject global assessment scale scores from the Screening/Baseline to the Test of Cure Visit 
• Percentages of subjects with categorical shifts on the subject global assessment scale from the 
Screening/Baseline to the Test of Cure Visit 
10.1.3 Other Efficacy Endpoints (new section) 
Addition of description of other efficacy endpoints 
10.4.1 Intent-to-Treat Population 
The intent-to-treat (ITT) population will be defined as all subjects with a clinical diagnosis of 
otomycosis at Screening/Baseline who received at least one dose of study drugwho were randomized 
and dispensed study medication. 
10.4.2 Modified Intent-to-Treat Population 
The modified intent-to-treat (MITT) population will be a subset of the primaryITT population for all 
efficacy analyses and . The MITT population will be defined as allinclude subjects who were 


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randomized, dispensed study drug, and with a clinical diagnosis of otomycosis andconfirmed by a 
positive fungal culture at Screening/Baseline who received at least one dose of study drug. 
10.4.3 Per Protocol Population 
Revised description of per protocol population including specific criteria  
10.4.4 Safety Population 
The safety population will be the primary population for safety analyses and will include all randomized 
subjects who received at least one dose of study drug and had at least one post-Baseline safety 
assessment. 
10.5.1 Efficacy Analysis 
The primary population for all efficacy analyses will be the MITT population (see Section 10.4). 
Efficacy parametersendpoints will also be assessed secondarilysummarized for the PP population and 
will be considered supportive 
10.5.2 Safety Analysis 
Revised description of safety analysis  
10.5.3 Subject Demographics and Baseline Characteristics 
Subject demographic and baseline characteristics will be summarized descriptively for the MITT, PP, 
and Safety populations and will be supported with individual subject data listings. 
10.5.4 Missing Data 
Addition of description of process for handling missing data 
11.1 
Institutional Review Board 
…. 
…..The investigator should also provide the miconazole oil Investigator’s Brochure and a copy of the 
Monistat 1 Consumer Information Leaflet to the IRB. 
11.6 
Case Report Form Requirements 
Revised description of CRFs including addition of eCRFs  


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13.2 Amendment 2 Version 3 14 June 2017 
This amendment changes the inclusion criteria to require subjects to have a score of >0 for the 
otomycosis sign of fungal elements in each ear to be treated with study drug, in addition to 
having at least two of the following signs or symptoms of otomycosis in each ear to be treated 
with study drug: pruritus, >1; debris >1; or pain >0. Clarifications have also been added in 
multiple places to further emphasize the existing wording contained in Section 4.4 (Subject 
Discontinuation) indicating that the Test of Cure procedures should be performed for subjects 
who prematurely discontinue from the study if possible. A clarification has also been added to 
Section 7.6 to emphasize that if both ears will be treated with study drug, both ears will be 
cultured. 
As summary of changes is provided below. New/changes in text are bolded. Deletions are struck 
through. 
Title, Protocol Approval, and Study Acknowledgment Pages: 
Updated to reflect protocol version and date change and to remove the second signature block on the 
Protocol Approval page 
Section 4.1 Inclusion Criteria 
2. Diagnosis of uncomplicated otomycosis of the external ear only, in the ear(s) that will be treated with 
study drug, with the subject score for at least two of the signs or symptoms of otomycosis to be 
elevated, defined as scores of the following (see Section 7.4 for definitions of the scores): pruritus, >1; 
debris, >1; fungal elements, >0; or pain, >0. a score for fungal elements of >0 in each ear to be 
treated with study drug (see Section 7.4 for definitions of the scores for each of the otomycosis 
signs and symptoms). Subjects must also have at least two of the following signs or symptoms of 
otomycosis in each ear to be treated with study drug: pruritus, >1; debris, >1; or pain, >0. 
Table 1 Study Schedule Footnote e 
e. The Test of Cure Visit is scheduled to occur on Day 15 for subjects randomized to the 7-day 
treatment duration, or on Day 22 for subjects randomized to the 14-day treatment durations. In case of 
early termination, the assessments planned for the Test of Cure Visit should be performed if 
possible 
Section 6.4 Test of Cure 
This visit may occur up to 1 day sooner or up to 8 days later than the specified day. Subjects 
randomized to the 7-day group will have the Test of Cure Visit on Day 15, and subjects randomized to 
the 14-day groups will have the Test of Cure Visit on Day 22. 
The following procedures and evaluations will occur during the Test of Cure Visit: 
• 
Otomycosis signs and symptoms 
• 
Subject global assessment 
• 
Microbial (fungal) culture 
• 
AE evaluation 
• 
Review of concomitant medications 
• 
Urine pregnancy test (in female subjects of childbearing potential only) 
In case of early termination, the procedures planned for the Test of Cure Visit should be 
performed if possible. 


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Section 7.6 Microbial Culture 
At designated visits, the investigator or designee will obtain a sample from the external ear to be sent to 
a laboratory for microbial culture (for both fungi and bacteria at the Screening/Baseline visit and for 
fungi only at the End of Treatment and Test of Cure visits). Techniques for obtaining and handling the 
sample and sending it to the laboratory will be described in a separate laboratory manual. If both ears 
will be treated with study drug, both ears will be cultured. 


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13.3 Amendment 3 Version 4 11 October 2017 
This amendment changes and clarifies the exclusion criteria.   Exclusion criterion #3 was changed to, 
“History of prior surgery directly affecting and compromising the external auditory canal and/or 
tympanic membrane of the ear(s) that will be treated with study drug, except for prior 
tympanostomy tube(s) that have already been removed and completely healed,” to clarify the type of 
surgery that will disqualify a subject from the study. Clarification has also been added to Section 4.4 
(Subject Discontinuation) to emphasize that the visible presence of fungal elements at Screening/Baseline 
is required, to be enrolled into the study. 
The summary of changes is provided below. New/changes in text are bolded. Deletions are struck 
through. 
Header, Title, Protocol Approval, and Study Acknowledgment Pages: 
Updated to reflect protocol version and date change. 
Synopsis 
Key Exclusion Criteria: 
…tympanostomy tube or perforated tympanic membrane in the ear(s) that will be treated with study
drug; history of prior surgery directly affecting and compromising the external auditory canal 
and/or tympanic membrane of the ear(s) that will be treated with study drug, except for prior 
tympanostomy tube(s) that have already been removed and completely healed… 
Section 3 STUDY DESIGN 
…While in the study, subjects Subjects will be instructed to avoid getting water in the ear, to consider
drying excessive water in the ear by using a blow dryer, and to place a Vaseline-impregnated cotton ball 
over the affected ear(s) to help keep water out of the ear while bathing or showering… 
Section 4.2 Exclusion Criteria 
3. History of prior surgery directly affecting and compromising the external auditory canal and/or
tympanic membrane of the ear(s) that will be treated with study drug, except for prior tympanostomy 
tube(s) that have already been removed and completely healed 
Section 4.4 Subject Discontinuation 
Due to the time required to obtain fungal culture results from Screening/Baseline, subjects will be 
enrolled into the study based on a clinical diagnosis of otomycosis (including the visible presence of 
fungal elements at Screening/Baseline), without a requirement for a positive fungal culture. Subjects 
who end up with a negative Screening/Baseline fungal culture will not be discontinued from the study, 
but these subjects will not be included in the primary efficacy analysis. 


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13.4 Amendment 4 Version 5 11 May 2018 
This amendment increases the number of subjects planned, from 36 to 75. This change is being 
implemented to account for a lower than planned percentage of subjects who meet both 
parameters of having a positive fungal culture at Screening/Baseline and completing the Test of 
Cure visit. This amendment also makes corrections to the Study Schedule (Table 1) and to the 
description of study procedures to be performed at Screening/Baseline (Section 6.2.1) to indicate 
that study drug is to be weighed at the Screening/Baseline visit before dispensing study drug to 
the subject; these corrections are for consistency with the Treatment Compliance section (Section 
7.11) which requires the study drug to be weighed by the investigator or designee before 
dispensation to the subject.   
A summary of changes is provided below. New/changes in text are bolded. Deletions are struck 
through. 
Header, Title, Protocol Approval, and Study Acknowledgment Pages: 
Updated to reflect protocol version and date change. 
Synopsis 
Number of Subjects Planned 
Approximately 3675 
Design and Methodology 
This study is a randomized, partially masked, multiple-dose, parallel-group design study conducted at 
up to 10 study centers in the US. Approximately 3675 male or female subjects with otomycosis will 
receive study drug…. 
Section 3 STUDY DESIGN 
This study is a randomized, partially masked, multiple-dose, parallel-group design study conducted at 
up to 10 study centers in the US. Approximately 3675 male or female subjects with otomycosis will 
receive study drug….  
Section 3.1 Number of Subjects 
Approximately 3675 eligible subjects are planned to be enrolled in order to achieve approximately 10 
subjects per group (randomized in a 1:1:1 ratio to the 7-day active, 14-day active, and 14-day vehicle 
treatment groups) with a positive fungal culture at baseline and who have completed the Test of Cure 
Visit. 
Section 4.4 Subject Discontinuation 
Subject discontinuations will be documented clearly on the applicable electronic case report form 
(eCRF). Subjects who discontinue from the study will not be replaced, but additional subjects may be 
enrolled and randomized if it appears that approximately 3675 subjects is insufficient to meet the 
sponsor’s goal of approximately 10 subjects per group who meet both criteria of having a positive 
fungal culture at Screening/Baseline and completing the Test of Cure Visit. 
Table 1 Study Schedule 
An “X” has been added to the row “Weighing of study drug” under the “Screening/Baseline/Day 1” 
column to indicate that study drug is to be weighed at this visit. 
Section 6.2.1 Screening / Baseline 
•
Randomization and dispensation of study drug
•
Weighing of study drug, followed by dispensation of study drug to subject
•
Dispensation of subject diary to subject.


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13.5 Amendment 5 Version 6 17 April 2019 
This amendment contains the inclusion of an interim analysis to ensure that there is a sufficient 
number of subjects within each group for the primary analysis. A subject’s MITT status 
(specifically positive fungal culture at baseline) is determined only following randomization, 
which may result in imbalance between treatment groups. Therefore, at least one assessment 
during the conduct of the study is planned to ensure that there is a sufficient number of subjects 
within each group for the primary analysis. Once at least 10 MITT subjects have been enrolled in 
the 7-Day active group, the numbers of MITT subjects in the 14-Day active group and the 14-
Day vehicle group will be determined by an unblinded statistician; no persons involved in the 
day to day conduct of the study will be unblinded. Randomization allocation for future subjects 
may be adjusted if deemed necessary to achieve minimum number of subjects within each arm. 
Full details will be provided in the SAP. 
A summary of changes is provided below. New/changes in text are bolded. Deletions are struck 
through. 
Header, Title, Protocol Approval, and Study Acknowledgment Pages: 
Updated to reflect protocol version and date change. 
Synopsis 
Design and Methodology 
This study is a randomized, partially masked, multiple-dose, parallel-group design study conducted at 
up to 10 study centers in the US. Approximately 75 male or female subjects with otomycosis will 
receive study drug. Subjects will be randomly assigned in a 1:1:1 ratio to receive miconazole oil 
[administered as 5 drops per ear at ~30 mg per drop instilled into the external ear canal of the ear(s) 
affected by otomycosis] for 7 or 14 days, or vehicle for 14 days. During the study it is planned to 
assess treatment allocation to ensure that there is a sufficient number of subjects within each 
group for the primary analysis. If deemed necessary, future randomizations may be adjusted. For 
subjects assigned to the 14-day treatment duration with either miconazole oil or vehicle, the contents of 
the study drug will be masked to both the subject and the investigator and study staff (i.e., double-
blind), but the treatment duration assigned to each subject (7 or 14 days) will be unmasked to both the 
subject and the investigator and study staff. 
Interim Treatment Allocation Assessment(s) 
A subject’s MITT status (specifically positive fungal culture at baseline) is determined only 
following randomization, which may result in imbalance between treatment groups. Therefore, at 
least one assessment during the conduct of the study is planned to ensure that there is a sufficient 
number of subjects within each group for the primary analysis. Once at least 10 MITT subjects 
have been enrolled in the 7-Day active group, the numbers of MITT subjects in the 14-Day active 
group and the 14-Day vehicle group will be determined by an unblinded statistician; no persons 
involved in the day to day conduct of the study will be unblinded. Randomization allocation for 
future subjects may be adjusted if deemed necessary to achieve minimum number of subjects 
within each arm. 


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List of Abbreviations 
MCMC  
 
Markov Chain Monte Carlo 
LOCF  
 
 
Last Observation Carried Forward 
 
Section 3 Study Design 
This study is a randomized, partially masked, multiple-dose, parallel-group design study conducted at 
up to 10 study centers in the US. Approximately 75 male or female subjects with otomycosis will 
receive study drug. Subjects will be randomly assigned in a 1:1:1 ratio to receive miconazole oil 
[administered as 5 drops per ear at ~30 mg per drop instilled into the external ear canal of the ear(s) 
affected by otomycosis] for 7 or 14 days, or vehicle for 14 days. Interim assessments are planned to 
ensure that there is a sufficient number of subjects within each group for the primary analysis. If 
deemed necessary the randomization ratio may be adjusted following the interim assessments; see 
Section 10.5.5 for details. For subjects assigned to the 14-day treatment duration with either 
miconazole oil or vehicle, the contents of the study drug will be masked to both the subject and the 
investigator and study staff (i.e., double-blind), but the treatment duration assigned to each subject (7 or 
14 days) will be unmasked to both the subject and the investigator and study staff. 
 
Section 9.2 Randomization 
Subjects will be randomized in a 1:1:1 ratio to one of three groups: 1) 7-day treatment with miconazole 
oil; 2) 14-day treatment with miconazole oil; or 3) 14-day treatment with miconazole oil vehicle. 
Interim assessments are planned to ensure that there is a sufficient number of subjects within 
each group for the primary analysis. If deemed necessary the randomization ratio may be 
adjusted following the interim assessments; see Section 10.5.5 for details. 
 
Section 10.5.4 Missing Data 
Missing values from the Test of Cure visit from which the dichotomized Therapeutic Cure is derived 
will be imputed using last observation carried forward (LOCF) method.estimated by Markov 
Chain Monte Carlo (MCMC). The pattern of missing observations in each treatment group cannot 
influence the missing value estimation in the other because the imputation will be conducted 
independently for each treatment group. 
Multiple imputation and subsequent summarization will involve 4 principal tasks: 
Calculate the number of missing Test of Cure values to be estimated by MCMC in each treatment 
group. Let nmiss be the maximum number of missing Test of Cure values among the treatment groups. 
For each treatment group, create a data set containing subjects with observed values and those needing 
estimation by MCMC. The missing Therapeutic Cure values in each data set will be filled in using the 
MCMC method ‘5 x nmiss’ times to generate ‘5 x nmiss’ data sets. The resulting data set for each 
treatment group will be combined into 1 complete data set for each imputation.  
Syntax (14 day treatment groups) : 
proc mi data=datain out=dataout seed=&seed. nimpute=5xnmiss <options>; 
where trtpn=(2 or 3); 
mcmc chain=multiple; 
var baseline, Day 8, Day 15, Day 22); 
run; 
Syntax (7 day treatment groups) : 
proc mi data=datain out=dataout seed=&seed. nimpute=5xnmiss <options>; 


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where trtpn=(1); 
mcmc chain=multiple; 
var baseline, Day 8, Day 15); 
run; 
For each complete data set, the dichotomous success rate will be computed.  
The results from each complete dataset will be averaged and presented. 
A total of 15 random seeds will be needed to impute Therapeutic Cure for the three treatment groups. 
Those 15 random seeds have been pre-specified by using a random number generator: 
Culture; Miconazole oil 7-day: Seed=1673675075 
Culture; Miconazole oil 14-day: Seed=1973865476 
Culture; Vehicle 14-day: Seed=1984342934 
Pruritus; Miconazole oil 7-day: Seed= 1032756100 
Pruritus; Miconazole oil 14-day: Seed=548516766  
Pruritus; Vehicle 14-day: Seed= 1352599714 
Debris; Miconazole oil 7-day: Seed=90285723 
Debris; Miconazole oil 14-day: Seed=739430049  
Debris; Vehicle 14-day: Seed=143241952  
Fungal elements; Miconazole oil 7-day: Seed=1177358335 
Fungal elements; Miconazole oil 14-day: Seed=521921209  
Fungal elements; Vehicle 14-day: Seed=131606110  
Pain; Miconazole oil 7-day: Seed=665476352 
Pain; Miconazole oil 14-day: Seed=476181336 
Pain; Vehicle 14-day: Seed=1305387803 
If multiple imputation is impaired due to not sufficient missing data to allow for multiple imputation to 
be performed, multiple imputation may be performed on the computed endpoint rather than the 
individual efficacy assessments. If multiple imputation is still not possible, other sensitivity methods 
may be used such as imputing failure for any missing Therapeutic Cure determinations. 
 
Section 10.5.5 Interim Treatment Allocation Assessment(s) 
A subject’s MITT status (specifically positive fungal culture at baseline) is determined only 
following randomization, which may result in imbalance between treatment groups. Therefore, at 
least one assessment during the conduct of the study is planned to ensure that there is a sufficient 
number of subjects within each group for the primary analysis. Once at least 10 MITT subjects 
have been enrolled in the 7-Day active group, the numbers of MITT subjects in the 14-Day active 
group and the 14-Day vehicle group will be determined by an unblinded statistician; no persons 
involved in the day to day conduct of the study will be unblinded. Randomization allocation for 
future subjects may be adjusted if deemed necessary to achieve minimum number of subjects 
within each arm.  
Full details will be provided in the SAP. 

SAP_001.pdf: 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
Page 1 of 105 
CONFIDENTIAL 
STATISTICAL ANALYSIS PLAN 
Protocol Number: HD-MCZ-PHII-DRF062016 
Study Title: Dose-Ranging Study of the Efficacy and Safety of Miconazole Oil Used for 7 
or 14 Days Compared with Vehicle in the Treatment of Otomycosis 
Development Phase of Study: 2 
Sponsor: Hill Dermaceuticals, Inc. 
Sponsor Contact: Rosario G. Ramirez, MD 
Statistical Analysis Plan based on Protocol Version: 17 April 2019/ Version 6 
Statistical Analysis Plan Date: 30 May 2019 
Statistical Analysis Plan Version: v1 




 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 3 of 105 
CONFIDENTIAL 
TABLE OF CONTENTS 
1. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ....................................5 
2. 
INTRODUCTION .................................................................................................................6 
3. 
STUDY OBJECTIVES .........................................................................................................7 
4. 
STUDY DESIGN ...................................................................................................................7 
5. 
EFFICACY AND SAFETY ENDPOINTS .........................................................................9 
5.1. Efficacy Endpoints ..........................................................................................................9 
5.1.1. 
Primary Efficacy Endpoints ..............................................................................9 
5.1.2. 
Secondary Efficacy Endpoints ........................................................................10 
5.1.3. 
Additional Efficacy Endpoints ........................................................................10 
5.2. Safety Endpoints ...........................................................................................................10 
6. 
STATISTICAL AND ANALYTICAL PLANS ................................................................11 
6.1. General Methodology ...................................................................................................11 
6.1.1. 
Statistical Analysis ..........................................................................................11 
6.1.2. 
Baseline Definition ..........................................................................................11 
6.1.3. 
Visit Mapping ..................................................................................................11 
6.1.4. 
Adjustments for Covariates .............................................................................12 
6.1.5. 
Handling of Dropouts or Missing Data ...........................................................12 
6.1.6. 
Interim Analyses and Data Monitoring ...........................................................12 
6.1.7. 
Multicenter Studies ..........................................................................................13 
6.1.8. 
Multiple Comparisons/Multiplicity .................................................................13 
6.1.9. 
Use of an Efficacy Subset of Subjects .............................................................14 
6.1.10. 
Active-Control Studies Intended to Show Equivalence ..................................14 
6.1.11. 
Examination of Subgroups ..............................................................................14 
6.2. Disposition of Subjects .................................................................................................14 
6.3. Protocol Deviations .......................................................................................................14 
6.4. Data Sets Analyzed .......................................................................................................14 
6.4.1. 
Intent-to-Treat (ITT) Population .....................................................................15 
6.4.2. 
Modified Intent-to-Treat (MITT) Population ..................................................15 
6.4.3. 
Per-Protocol (PP) Population ..........................................................................15 
6.4.4. 
Safety Population ............................................................................................15 
6.5. Demographic and Other Baseline Characteristics ........................................................16 
6.6. Prior and Concomitant Medications .............................................................................16 


 
 
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CONFIDENTIAL 
6.7. Analysis of Efficacy ......................................................................................................16 
6.7.1. 
Primary Efficacy Analysis ...............................................................................16 
6.7.2. 
Secondary Efficacy Analysis ...........................................................................17 
6.7.3. 
Other Efficacy Analysis ..................................................................................18 
6.8. Safety Evaluation ..........................................................................................................18 
6.8.1. 
Extent of Exposure ..........................................................................................18 
6.8.2. 
Medical History ...............................................................................................19 
6.8.3. 
Adverse Events ................................................................................................19 
6.8.4. 
Clinical Laboratory Evaluation .......................................................................19 
6.8.5. 
Physical Examination ......................................................................................19 
7. 
DETERMINATION OF SAMPLE SIZE .........................................................................19 
8. 
CHANGES IN THE PLANNED ANALYSES..................................................................19 
9. 
INDEX OF PLANNED TABLES ......................................................................................20 
10. INDEX OF PLANNED LISTINGS ...................................................................................80 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
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CONFIDENTIAL 
1. LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
AE(s) 
adverse event(s) 
ATC 
Anatomical Therapeutic Chemical 
BID 
twice daily 
CRF(s) 
case report form(s) 
eCRF(s) 
electronic case report form(s) 
FDA 
Food and Drug Administration 
ITT 
intent-to-treat 
 
 
LOCF 
last observation carried forward 
 
 
MedDRA 
Medical Dictionary for Regulatory Activities 
MIC 
Minimum inhibitory concentration 
MITT 
Modified intent-to-treat 
n 
number of observations 
N 
number of subjects (sample size) 
OTC 
over-the-counter 
PP 
per-protocol 
QST 
QST Consultations, Ltd. 
SAE(s) 
serious adverse event(s) 
SAS® 
Statistical Analysis System (SAS® Institute Inc., Cary, NC) 
SD 
standard deviation 
SOP(s) 
Standard Operating Procedures 
TEAE(s) 
treatment-emergent adverse event(s) 
US 
United States 
WHO 
World Health Organization 
WHO-DDE 
World Health Organization Drug Dictionary 
 
 
 
 
 


 
 
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2. INTRODUCTION 
Otomycosis is a fungal otitis associated with organisms from the Candida and Aspergillus 
genera. The signs and symptoms of otomycosis are pruritus, debris, the presence of fungal 
elements, and pain. While antifungal agents including miconazole are used in practice for the 
treatment of fungal otitis externa (also called otomycosis), there are currently no treatments 
approved by the United States (US) Food and Drug Administration (FDA) for this indication in 
humans. Miconazole is an imidazole antifungal agent that has been available by prescription and 
over the counter (OTC), in different formulations, for many years. It is commonly used for 
different types of fungal skin infections, such as Candida, ringworm, jock itch, athlete’s foot, 
nail fungus, vaginal yeast infections, and oropharyngeal candidiasis. The purpose of this study is 
to gather preliminary data on the efficacy and safety of 2% miconazole oil after topical otic 
administration in subjects with otomycosis. The objectives of the study are to obtain preliminary 
evidence of the efficacy and safety of miconazole oil compared with vehicle over a 14-day 
treatment duration; and descriptively compare the efficacy and safety of miconazole oil over 
treatment durations of 7 versus 14 days. Approximately 75 male or female subjects with 
otomycosis will receive study drug. Subjects will be randomly assigned in a 1:1:1 ratio to receive 
miconazole oil [administered as 5 drops per ear at ~30 mg per drop instilled into the external ear 
canal of the ear(s) affected by otomycosis] for 7 or 14 days, or vehicle for 14 days. Efficacy 
assessments will include fungal culture of the affected ear(s), assessments of clinical signs and 
symptoms of otomycosis, and a subject global assessment. In cases of bilateral otomycosis, both 
ears will be treated and evaluated by the investigator, but the ear with the worse infection at 
Screening/Baseline, as assessed by the investigator by taking into account both clinical signs and 
symptoms and fungal culture results, will be used as the study ear for efficacy analyses. If both 
ears are determined by the investigator to have the same degree of infection at 
Screening/Baseline, the left ear will be used as the study ear for the purposes of efficacy 
analyses. 
Hill Dermaceuticals, Inc. is pursuing the development of Miconazole as a topically applied 
ergosterol biosynthesis inhibitor for the treatment of otomycosis. The mechanisms of action of 
miconazole when used topically for the treatment of fungal infections involve its actions against 
the fungal organisms, rather than their human host. Miconazole targets the cytochrome P450-
dependent enzyme 14-α-sterol demethylase, an enzyme that is also involved in mammalian 
cholesterol synthesis, resulting in inhibition of ergosterol biosynthesis in the cell membrane. 
While miconazole has not been FDA-approved for otic administration for any indication in 
humans, clinical studies in other countries of otically-administered miconazole have been 
conducted and support the efficacy of miconazole in the treatment of otomycosis. The 2% 
concentration of miconazole is selected for this study due to the results of an internal study 


 
 
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conducted by the sponsor in vitro demonstrating greater zones of inhibition against Candida and 
Aspergillus using the 2% concentration compared with the 1% concentration. Furthermore, the 
2% miconazole concentration is commonly used for dermatophyte infections, and topical 
application is expected to be ≥1000-fold the minimum inhibitory concentrations (MICs) of the 
Candida and Aspergillus organisms most commonly associated with human otomycosis in the 
US. Miconazole at a strength of 2.0% has been selected as the concentration to take forward in 
Phase 2 development.  
This study, HD-MCZ-PHII-DRF062016, is one of the confirmatory Phase 2 trials being 
conducted to assess the efficacy and safety of Miconazole in subjects with otomycosis. 
3. STUDY OBJECTIVES 
The objective of this study will be to assess the efficacy and safety of Miconazole oil compared 
to a placebo oil vehicle when applied twice daily (BID) for 14 days in subjects with otomycosis. 
Descriptively compare the efficacy and safety of miconazole oil over treatment durations of 7 
versus 14 days. 
4. STUDY DESIGN 
4.1. 
Overall Study Design 
This study is a randomized, partially blinded, multiple-dose, parallel-group design study 
conducted at up to 10 study centers in the US. Approximately 75 male or female subjects with 
otomycosis will receive study drug. Subjects will be randomly assigned in a 1:1:1 ratio to receive 
miconazole oil [administered as 5 drops per ear at ~30 mg per drop instilled into the external ear 
canal of the ear(s) affected by otomycosis] for 7 or 14 days, or vehicle for 14 days. Interim 
assessments are planned to ensure that there is a sufficient number of subjects within each group 
for the primary analysis. If deemed necessary the randomization ratio may be adjusted following 
the interim assessments, see section 6.1.6 for details. For subjects assigned to the 14-day 
treatment duration with either miconazole oil or vehicle, the contents of the study drug will be 
blinded to both the subject and the investigator and study staff (i.e., double-blind), but the 
treatment duration assigned to each subject (7 or 14 days) will be unblinded to both the subject 
and the investigator and study staff.  
At Screening/Baseline (Day 1), the subject will then begin treatment with study drug. All 
subjects will return to the clinic on Day 8. For subjects randomized to the 7-day treatment 
duration, this visit will constitute the End of Treatment Visit. Subjects randomized to the 7-day 
treatment duration will not administer study drug on the day of this visit.  All other subjects will 


 
 
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continue to administer the study drug twice per day, up through Day 14, following the same 
instructions as provided at the Screening/Baseline Visit on Day 1. 
All subjects will return to the clinic on Day 15. For subjects randomized to the 7-day treatment 
duration, this visit will constitute the Test of Cure Visit. For subjects randomized to the 14-day 
treatment duration, this visit will constitute the End of Treatment Visit. Subjects randomized to 
the 14-day treatment duration will not administer study drug on the day of this visit. Subjects 
randomized to the 14-day durations will return to the clinic on Day 22 for the Test of Cure Visit.  
Efficacy assessments will include fungal culture of the affected ear(s), assessments of clinical 
signs and symptoms of otomycosis, and a subject global assessment. In cases of bilateral 
otomycosis, both ears will be treated and evaluated by the investigator, but the ear with the worse 
infection at Screening/Baseline, as assessed by the investigator by taking into account both 
clinical signs and symptoms and fungal culture results, will be used as the study ear for efficacy 
analyses. If both ears are determined by the investigator to have the same degree of infection at 
Screening/Baseline, the left ear will be used as the study ear for the purposes of efficacy 
analyses. 
Safety assessments will include AEs. 
4.1.1. 
Schedule of Visits and Assessments 
The study schedule can be found in Section 6.1 of the protocol. 
4.1.2. 
Method of Assigning Subjects to Treatment Groups 
A randomization schedule will be generated in SAS® using PROC PLAN by a member in the 
QST Consultations, Ltd. (QST) Statistical Services department who is not associated with the 
conduct or analysis of the study. The randomization schedule will be stratified by site and 
separate lists will be produced for each site. Sites will receive sequentially numbered kits 
randomized in blocks of six in a 1:1:1 ratio. 
At the Baseline/Day 1 visit, qualified subjects will be assigned to the lowest numerically 
available kit at the time of randomization. The assignment of the lowest numerically available kit 
number must be strictly adhered to as it is the method of randomization for this study. The kit 
number will be recorded in the electronic case report form (eCRF).  Subjects will be randomized 
in a 1:1:1 ratio to one of three groups: 1) 7-day treatment with miconazole oil; 2) 14-day 
treatment with miconazole oil; or 3) 14-day treatment with miconazole oil vehicle. 


 
 
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4.1.3. 
Blinding 
The Sponsor, the clinical research organization, the investigator, study site personnel and 
subjects will be blinded to the treatment assignment if the subject is randomized to a 14-day 
treatment group. Otherwise subjects in the 7 day treatment group will unblinded. The 
randomization schedule will be kept strictly confidential and accessible only to authorized 
persons.  Only when the study has been completed, the populations determined, and the study 
database locked will the randomization schedule be made available for analysis. 
The integrity of this clinical study must be maintained by observing the treatment blind.  If an 
adverse event occurs which cannot be managed without knowing whether the subject is receiving 
active study drug or vehicle solution, the investigator should contact the unblinded sponsor staff 
to obtain treatment assignment information.  The Medical Monitor must be notified whenever 
study medication is unblinded, preferably prior to unblinding a subject. The duration of treatment 
will not be blinded. For subjects randomized to the 14-day treatment durations, the contents of 
the study drug (miconazole oil versus vehicle) will be blinded. Randomized study drug will be 
packaged in identical bottles and will be labeled with a randomization number rather than the 
contents of the bottle. 
For subjects randomized to the 14-day durations, if it becomes necessary to unblind a subject’s 
treatment assignment in case of emergency, the investigator should contact the unblinded 
sponsor staff. A person at the sponsor organization who is not otherwise involved with the study 
will maintain a randomization list that will enable that person to inform the investigator of the 
subject’s treatment allocation. The treatment allocation is to be obtained only if a medical 
emergency exists and knowledge of the medication being taken will influence the medical 
management of the subject. 
5. EFFICACY AND SAFETY ENDPOINTS 
5.1. Efficacy Endpoints 
The primary and secondary endpoints will be based on the investigator reporting of signs and 
symptoms for the study ear. Other efficacy endpoints will be based on the subject reporting of 
the symptom of pruritus. 
5.1.1. 
Primary Efficacy Endpoints 
The primary efficacy endpoint is 
• The percentage of subjects at the Test of Cure Visit with “therapeutic cure,” defined as a 
negative mycological [fungal] culture plus “clinical cure” for the study ear.  Clinical cure 


 
 
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is defined as the absence of all otomycosis signs and symptoms based on Investigator 
assessment according to the scales for each individual sign or symptom and with absence 
defined as a score of 0 on each of the scales for pruritus, debris, fungal elements, and 
pain. 
5.1.2. 
Secondary Efficacy Endpoints 
The secondary efficacy endpoints are as follows:  
• Percentage of subjects with clinical cure at the Test of Cure Visit 
• Percentage of subjects with a negative fungal culture at the Test of Cure Visit 
• Percentage of subjects with a negative fungal culture at the Test of Cure visit as well as 
individual sign or symptom score of 0 or 1 on each of the scales for pruritus and debris 
and a score of 0 on each of the scales for fungal elements and pain. 
• Percentage of subjects with individual signs or symptoms with a score of 0 or 1 on each 
of the scales for pruritus and debris and a score of 0 on each of the scales for fungal 
elements and pain. 
• Subject global assessments at Baseline and Test of Cure as well as categorical shifts in 
the subject global assessment scale scores from the Screening/Baseline to the Test of 
Cure Visit. 
Analyses may also be conducted by fungal organism isolated at Screening/Baseline if a common 
organism is isolated by at least 5 subjects. 
5.1.3. 
Additional Efficacy Endpoints 
Other efficacy endpoints based on subject reporting of pruritus will include the following: 
• Subject therapeutic cure (defined as a negative mycological culture plus clinical cure) at 
the Test of Cure Visit for the study ear based on subject assessment of pruritus. Clinical 
cure is defined as the absence of all otomycosis signs and symptoms according to the 
scales for each individual sign or symptom and with absence defined as a score of 0 on 
each of the scales for pruritus, debris, fungal elements, and pain. 
5.2. Safety Endpoints 
Safety endpoints will be the percentage of subjects with treatment-emergent AEs, with 
treatment-emergent defined as occurring upon or after administration of the first dose of study 
drug. 


 
 
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6. STATISTICAL AND ANALYTICAL PLANS 
6.1. General Methodology 
All statistical processing will be performed using SAS® unless otherwise stated. No interim 
analyses are planned.  
No formal hypotheses will be tested in this study.  Descriptive comparisons will be made 
between the micronazole oil and the oil vehicle groups for subjects randomized to the 14-day 
groups.  Additionally, descriptive comparisons will be made between the 7-day and 14-day 
groups for subject’s randomized to the miconazole oil treatment.  
Descriptive statistics will be used to provide an overview of the efficacy and safety results. For 
categorical parameters, the number and percentage of subjects in each category will be 
presented. For continuous parameters, descriptive statistics will include n (number of subjects), 
mean, standard deviation (SD), median, minimum, and maximum.  
The primary method of handling missing efficacy data will be the method of last observation 
carried forward (LOCF) imputation.  
6.1.1. 
Statistical Analysis 
All analyses will be performed by QST using SAS® Version 9.3 or later.  All summary tables 
and data listings will be prepared utilizing SAS® software. 
The standard operating procedures (SOPs) of QST will be followed in the creation and quality 
control of all data displays and analyses. 
6.1.2. 
Baseline Definition 
Baseline is defined as the last non-missing assessment prior to first dose of study drug.   
6.1.3. 
Visit Mapping 
Data will be summarized based on nominal visit indications with the exception of data captured 
at early termination and unscheduled visits. Data from early termination and unscheduled visits 
will be summarized based on mapped visit values.  The analysis windows for early termination 
and unscheduled visits are presented in the following table.   
Analysis Windows for Efficacy and Safety Assessments 
Scheduled Visit 
Target Study Day 
Analysis Window 
(Days) 
Day 8 
8 
4 to 11 


 
 
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Day 15 
15 
12 to 18 
Day 22 
22 
19 to 30 
 
Data collected at early termination and unscheduled visits prior to study day 4 will not be 
analyzed, with the exception of those identified as baseline values.  Data collected at early 
termination and unscheduled visits after study day 30 will not be included in the analyses.   
The definition for the study day included in each analysis window is defined as below: 
 
Study Day prior to Baseline Visit = Visit Date – Baseline Visit Date 
 
Study Day on or after Baseline Visit = Visit Date – Baseline Visit Date + 1 
If an assessment’s mapped visit is a visit at which the subject has data from a scheduled visit, or 
if no analyses are planned for the assessment at the mapped visit, the data collected at the early 
termination or unscheduled visit will not be included in analyses.   
In the event of multiple values from unscheduled or early termination assessments within an 
analysis window, the value closest to the scheduled visit target study day will be used for 
analyses.  If two values tie as closest to the time point (for example, one value is before and the 
other value is after the time point), then the later value will be selected.  
Data collected at all visits will be included in the data listings with visit presented as reported by 
the site. 
6.1.4. 
Adjustments for Covariates 
Not applicable to this study. 
6.1.5. 
Handling of Dropouts or Missing Data 
Missing values from the Test of Cure visit from which the dichotomized Therapeutic Cure is 
derived will be imputed using LOCF method. 
6.1.6. 
Interim Analyses and Data Monitoring 
An interim assessment of the treatment allocation will be performed to ensure that there is a 
sufficient number of subjects within and across treatment arms. A subject’s MITT status 
(specifically positive fungal culture at baseline) is determined only after randomization which 
may result in an imbalance between treatment groups. Therefore, at least one assessment during 
the conduct of the study is planned to ensure that there is a sufficient number of subjects within 
each group for the primary analysis. Once at least 10 MITT subjects have been enrolled in the 7-
Day active group, the numbers of MITT subjects in the 14-Day active group and the 14-Day 


 
 
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vehicle group will be determined by an unblinded statistician; no persons involved in the day to 
day conduct of the study will be unblinded. Randomization allocation for future subjects may be 
adjusted if deemed necessary to achieve minimum number of subjects within each arm. At the 
time of the assessment, the 7-Day active kits will be removed from the randomization schedule 
for future subjects and the table below will be used as a guide for adjustments to the 
randomization allocation of 14-Day kits for future subjects. This assessment may be repeated in 
order to ascertain that a minimum enrollment of MITT subjects is met for each treatment group 
before study end. 
14-Day Active 
14-Day Vehicle 
Action 
≥ e + 3 
≤ e – 3 
Skip 14-Day Active kits 
≥ e + 2 
e - 2 
Skip 14-Day Active kits with the exception of one kit at 
each site. One of the four lowest 14-Day Active kit 
numbers will be selected at random to remain in the 
schedule for each site.  
e – 1 to e + 2 
e – 1 to e + 2 
No action 
e - 2 
≥ e + 2 
Skip 14-Day Vehicle kits with the exception of one kit at 
each site. One of the four lowest 14-Day Active kit 
numbers will be selected at random to remain in the 
schedule for each site.  
≤  e - 3 
≥ e + 3 
Skip 14-Day Vehicle kits 
Note: e represents the expected number of subjects based on a 1:1 ratio and the current number 
of MITT subjects between the 14-Day active and 14-Day vehicle groups. e = ½ * (Current 
number of MITT subjects between the 14-Day groups), non-integer results will be rounded 
down to the nearest integer. When determining an action the conditions of both the 14-Day 
Active and 14-Day Vehicle columns must be met. 
 
6.1.7. 
Multicenter Studies 
Not applicable to this study. 
6.1.8. 
Multiple Comparisons/Multiplicity 
No adjustments for multiple comparisons or multiplicity will be made. 


 
 
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6.1.9. 
Use of an Efficacy Subset of Subjects 
Subjects with a clinical diagnosis of otomycosis confirmed by a positive fungal culture, who are 
randomized to study drug, have received at least one dose of study medication, and who do not 
have major protocol deviations will form the Per Protocol (PP) Population.  The major protocol 
deviations will be defined at the time of evaluability evaluation, the time between the database 
soft lock and hard lock before unblinding. 
Excluding subjects who have major protocol deviations will decrease the variability in treatment 
response and will allow for a better determination of dose-response relationship of miconazole. 
6.1.10. 
Active-Control Studies Intended to Show Equivalence 
Not applicable to this study. 
6.1.11. 
Examination of Subgroups 
Not applicable to this study. 
6.2. Disposition of Subjects 
The number of subjects included in each analysis population (randomized, ITT, MITT, safety, 
PP) will be summarized by treatment group.  The number of subjects who completed and 
discontinued (including the reasons for discontinuation) will be summarized for each treatment 
group. 
The ear being treated (Left, Right, Both) will be summarized by treatment group as well as an 
indication of worse ear if “Both” is selected for the ear being treated. 
Subjects who are excluded from an analysis population will be summarized by the reasons for 
exclusion based on primary reason for exclusion. 
6.3. Protocol Deviations 
Protocol deviations will not be entered into the database.  Deviations leading to exclusion from 
analysis populations will be identified. Protocol deviations will be presented in a by-subject 
listing. 
6.4. Data Sets Analyzed 
Subjects will be summarized based on the primary reason for exclusion.  Below is the order to be 
used in summaries:  


 
 
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6.4.1. 
Intent-to-Treat (ITT) Population 
All subjects who were randomized and dispensed study drug will be included in the ITT 
population. 
6.4.2. 
Modified Intent-to-Treat (MITT) Population 
All subjects in the ITT population with a clinical diagnosis of otomycosis confirmed by positive 
fungal culture will be included in the MITT population and analyzed according to the treatment 
group they were randomized.  All efficacy analyses will be presented using the MITT 
population. 
6.4.3. 
Per-Protocol (PP) Population 
The PP population will be a subset of the MITT population and will include all subjects who 
complete the Test of Cure visit without any major protocol violations. The PP population will 
include subjects in the MITT population who did not meet any of the following criteria: 
• Violated the inclusion/exclusion criteria 
• Used an interfering concomitant medication 
• Did not attend the Test of Cure visit 
• Did not attend the End of Treatment visit 
• Have not been compliant with the dosing regimen (i.e., subjects must have received 
80%-120% of the expected applications of study medication in the study ear during 
participation in the study) 
• Out of visit window at the Test of Cure Visit (-1/+8 days) 
Subjects who discontinue from the study due to an adverse event related to study treatment, 
documented lack of treatment effect, or worsening of condition will be included in the PP 
population. Prior to breaking the blind, other additional criteria may be added to the list to 
accommodate for unforeseen events that occurred during the conduct of the trial that result in 
noteworthy study protocol violations. 
All efficacy analyses will be performed on the PP population. 
6.4.4. Safety Population 
All subjects in the ITT population who received at least one dose of the study drug and had at 
least one post-Baseline safety assessment will be included in the safety population and analyzed 


 
 
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according to the treatment group they received.  All safety analyses will be performed using the 
safety population. 
 
6.5. Demographic and Other Baseline Characteristics 
All demographic and baseline characteristic summaries will be done for the MITT, PP, and 
safety populations. 
Sex, race, and ethnicity will be summarized by counts and percentages.  Age will be summarized 
with descriptive statistics. 
Baseline mycological culture, signs and symptoms of otomycosis, and subject global assessment 
will be summarized with descriptive statistics.   
Medical histories will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA) dictionary and presented in a by-subject listing. 
6.6. Prior and Concomitant Medications 
Concomitant medications will be coded to preferred name and Anatomical Therapeutic Chemical 
(ATC) classification of ingredients using the World Health Organization (WHO) Drug dictionary 
(WHO-DDE)  
Counts and percentages will be provided to summarize the use of medications other than the 
study drug reported throughout the study.  The number and percent of subjects who took other 
therapy will be shown by ATC level 2 term and preferred name.  Medications which start prior to 
first dose will be considered prior medications. Ongoing medications and medications ending 
after the date of first dose will be considered concomitant medications.  Medications which are 
both prior and concomitant will be included in both summaries.  Incomplete start and end dates 
which could be either prior to first dose or after first dose will be considered prior to first dose. 
A by-subject listing of all prior and concomitant medications will be presented.  
6.7. Analysis of Efficacy 
6.7.1. 
Primary Efficacy Analysis 
The primary population for all efficacy analyses will be the MITT population.  Efficacy 
endpoints will also be summarized for the PP population and will be considered supportive. 
The percentage of subjects who demonstrate a positive outcome for each efficacy endpoint will 
be presented for the primary efficacy parameter as well as all secondary efficacy parameters. 


 
 
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In cases of bilateral otomycosis, the ear with the worse infection at Screening/Baseline, as 
assessed by the investigator by taking into account both clinical signs and symptoms and fungal 
culture results, will be used as the study ear for efficacy analyses. If both ears are determined by 
the investigator to have the same degree of infection at Screening/Baseline, the left ear will be 
used as the study ear for the purposes of efficacy analyses. 
The Test of Cure Visit is scheduled to occur on Day 15 for subjects randomized to the 7-day 
treatment duration, or on Day 22 for subjects randomized to the 14-day treatment durations. 
The percentage of subjects with “therapeutic cure” at the Test of Cure Visit will be presented by 
treatment group.  Subjects are defined as reaching “therapeutic cure” if they have a negative 
mycological culture plus “clinical cure” for the study ear, where “clinical cure” is defined as the 
absence of all otomycosis signs and symptoms based on Investigator assessment according to the 
scales for each individual sign or symptom and with absence defined as score of 0 on each of the 
scales for pruritus, debris, fungal elements, and pain.   
In addition otomycosis signs and symptoms will be presented as the percentage of subjects with 
occurrences by treatment arm, assessor type (subject or investigator assessment), and visit. 
Subject assessments will be summarized for pruritus only.   
6.7.2. 
Secondary Efficacy Analysis 
The percentage of subjects with clinical cure at the Test of Cure visit will be presented by 
treatment group.    
The same analysis will be done for the following endpoints: 
• Percentage of subjects with a negative fungal culture at the Test of Cure Visit 
• Percentage of subjects with a negative fungal culture at the Test of Cure visit as well as 
individual sign or symptom score of 0 or 1 on each of the scales for pruritus and debris 
and a score of 0 on each of the scales for fungal elements and pain. 
• Percentage of subjects with individual signs or symptoms with a score of 0 or 1 on each 
of the scales for pruritus and debris and a score of 0 on each of the scales for fungal 
elements and pain. 
• Frequency counts and percentages will be presented for the subject global assessments at 
Screening/Baseline and Test of Cure by treatment group.  A categorical shift analysis 
(with categories of None, Minor, and Moderate) in the subject global assessment scale 
scores from the Screening/Baseline to the Test of Cure Visit will also be presented 
similarly.  Only subjects with results at both the Screening/Baseline and the Test of Cure 
Visit will be considered in the shift analysis.  


 
 
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In addition the subject global assessment will be presented in frequency counts and percentages 
for all study visits. 
If feasible, analyses may also be conducted by fungal organism isolated at Screening/Baseline. 
The secondary efficacy analysis will be presented on both the MITT and PP populations. 
6.7.3. 
Other Efficacy Analysis 
The counts and percentages of subjects with “subject therapeutic cure” at the Test of Cure Visit 
will be presented by treatment group.  Subjects are defined as reaching “subject therapeutic cure” 
if they have a negative mycological culture plus “subject clinical cure” for the study ear, where 
“subject clinical cure” is defined as the absence of all otomycosis signs and symptoms based on 
subject assessed pruritus.    
6.8. Safety Evaluation 
6.8.1. 
Extent of Exposure 
The extent of exposure to study drug in each treatment group will be summarized by total 
number of days of exposure, total number of applications, number of missed applications and 
number and percentage of subjects who are compliant. A subject will be considered compliant 
with the dosing regimen if the subject applied 80% to 120% of the expected number of 
applications while enrolled in the study. 
Days of exposure = Date of last study application – Date of first study application + 1 
Total Number of Applications: 
2*(Date of Last Application – Date of First Application + 1) – (Number of doses missed as 
collected on the case report form (CRF)) + (Number of extra doses as collected on the CRF) 
Total Number of Expected Applications: 
2*(End of Treatment Visit Date – Date of Randomization).   
If the total number of expected applications exceeds 14 for the 7-Day treatment group then the 
total number of expected applications will be set to 14. If the total number of expected 
applications exceeds 28 for the 14-Day treatment group then the total number of expected 
applications will be set to 28. 
Compliance will be calculated as a percentage as 100 times the total number of applications 
divided by the total number of expected applications. 


 
 
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6.8.2. 
Medical History 
Medical history results will only be shown in a by-subject listing.  
6.8.3. 
Adverse Events 
All AEs that occur during the study will be recorded and classified on the basis of MedDRA 
terminology. Treatment-emergent AEs (TEAEs) are defined as AEs with an onset on or after the 
date of the first study drug application.  
TEAEs will be summarized by treatment group, the number of subjects reporting a TEAE, 
system organ class, preferred name, severity, relationship to study drug (causality), and 
seriousness. When summarizing AEs by severity and relationship, each subject will be counted 
once within a system organ class or a preferred term by using the event with the highest severity 
and greatest relationship within each classification. 
Serious AEs (SAEs) will be summarized by treatment group, severity and relationship to study 
drug, and individual SAEs will be listed by subject. In addition, a list of subjects who 
prematurely discontinue from the study due to an AE will be provided. 
No statistical inference between treatments will be performed on adverse events. 
Listings will be presented for all adverse events as well as for serious adverse events, and 
adverse events leading to discontinuation from the study.  
6.8.4. 
Clinical Laboratory Evaluation 
Urine pregnancy test results will only be shown in a by-subject listing. 
6.8.5. 
Physical Examination 
Physical examination data will be presented in a by-subject listing.  
7. DETERMINATION OF SAMPLE SIZE 
The sample size for this study is not based on statistical considerations and is instead intended to 
be a reasonable number of subjects upon which to gather preliminary information on the efficacy 
and safety of miconazole oil when administered via the otic route to subjects with otomycosis. 
8. CHANGES IN THE PLANNED ANALYSES 
There are no changes in the conduct of the study or planned analyses. 
 
 


 
 
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9. INDEX OF PLANNED TABLES 
Table 14.0.1: Summary of Subject Enrollment and Evaluability ..................................................22 
Table 14.0.2: Summary of Subjects Excluded from Analyses (Randomized Subjects) ................23 
Table 14.0.3: Summary of Subject Treatment Completion/Discontinuation 
(Randomized Subjects) .........................................................................24 
Table 14.1.1.1: Summary of Subject Demographics (Modified Intent-To-Treat Population) ......25 
Table 14.1.1.2: Summary of Subject Demographics (Per-Protocol Population) ...........................26 
Table 14.1.1.3: Summary of Subject Demographics (Safety Population) .....................................27 
Table 14.1.2.1: Subject Baseline Characteristics (Modified Intent-To-Treat Population) ............28 
Table 14.1.2.2: Subject Baseline Characteristics (Per-Protocol Population).................................30 
Table 14.1.2.3: Subject Baseline Characteristics (Safety Population)...........................................32 
Table 14.2.1.1: Summary of Primary Efficacy Endpoint: Therapeutic Cure at Test of Cure 
(Modified Intent-to-Treat Population) ..................................................34 
Table 14.2.1.2: Summary of Primary Efficacy Endpoint: Therapeutic Cure at Test of Cure (Per-
Protocol Population) .............................................................................35 
Table 14.2.2.1.1: Summary of Secondary Efficacy Endpoints: Mycological Culture and 
Individual Signs and Symptoms  (Modified Intent-to-Treat 
Population) ............................................................................................36 
Table 14.2.2.1.2: Summary of Secondary Efficacy Endpoints: Mycological Culture and 
Individual Signs and Symptoms Endpoints (Per-Protocol Population) 37 
Table 14.2.2.2.1: Summary of Secondary Efficacy Endpoint: Subject Global Assessment 
(Modified Intent-to-Treat Population) ..................................................38 
Table 14.2.2.2.2: Summary of Secondary Efficacy Endpoint: Subject Global Assessment (Per-
Protocol Population) .............................................................................39 
Table 14.2.2.3.1: Otomycosis Mycological Culture Through Time (Modified Intent-To-
Treat Population) ...................................................................................40 
Table 14.2.2.3.2: Otomycosis Mycological Culture Through Time (Per-Protocol Population)....41 
Table 14.2.2.4.1: Investigator Assessed Pruritus Through Time (Modified Intent-To-
Treat Population) ...................................................................................42 
Table 14.2.2.4.2: Investigator Assessed Pruritus Through Time (Per-Protocol Population) ........44 
Table 14.2.2.5.1: Debris Through Time (Modified Intent-To-Treat Population) ..........................46 
Table 14.2.2.5.2: Debris Through Time (Per-Protocol Population) ..............................................48 
Table 14.2.2.6.1: Presence of Fungal Elements Through Time (Modified Intent-To-
Treat Population) ...................................................................................50 


 
 
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Table 14.2.2.6.2: Presence of Fungal Elements Through Time (Per-Protocol Population) ..........51 
Table 14.2.2.7.1: Pain Through Time (Modified Intent-to-Treat Population) ...............................52 
Table 14.2.2.7.2: Pain Through Time (Per-Protocol Population) ..................................................53 
Table 14.2.2.8.1: Subject Global Assessment Through Time (Modified Intent-To-
Treat Population) ...................................................................................54 
Table 14.2.2.8.2: Subject Global Assessment Through Time (Per-Protocol Population) .............55 
Table 14.2.3.1.1: Summary of Other Efficacy Endpoint: Subject Therapeutic Cure at Test of 
Cure (Modified Intent-to-Treat Population)..........................................56 
Table 14.2.3.1.2: Summary of Other Efficacy Endpoint: Subject Therapeutic Cure at Test of 
Cure (Per-Protocol Population) .............................................................57 
Table 14.2.3.2.1: Subject Assessed Pruritus Through Time (Modified Intent-To-
Treat Population) ...................................................................................58 
Table 14.2.3.2.2: Subject Assessed Pruritus Through Time (Per-Protocol Population) ................60 
Table 14.3.1.1: Summary of Extent of Exposure (Modified Intent-To-Treat Population) ............62 
Table 14.3.1.2: Summary of Extent of Exposure (Per-Protocol Population) ................................63 
Table 14.3.1.3: Summary of Extent of Exposure (Safety Population) ..........................................64 
Table 14.3.2.1: Summary of Treatment-Emergent Adverse Event Characteristics (Safety 
Population) ............................................................................................65 
Table 14.3.2.2: Summary of Treatment-Emergent Adverse Events Leading to Permanent 
Withdrawal of Study Drug and/or Early Discontinuation From Study 
(Safety Population)................................................................................69 
Table 14.3.2.3: Summary of Treatment-Emergent Adverse Events (Safety Population) ..............70 
Table 14.3.2.4: Summary of Treatment-Emergent Adverse Events by Severity (Safety 
Population) ............................................................................................71 
Table 14.3.2.5: Summary of Treatment-Emergent Adverse Events by Relationship to Study Drug 
(Safety Population)................................................................................72 
Table 14.3.3.1: Summary of Treatment-Emergent Serious Adverse Event Characteristics (Safety 
Population) ............................................................................................73 
Table 14.3.3.2: Summary of Treatment-Emergent Serious Adverse Events (Safety Population) .77 
Table 14.3.3.3: Summary of Treatment-Emergent Serious Adverse Events by Severity (Safety 
Population) ............................................................................................78 
Table 14.3.3.4: Summary of Treatment-Emergent Serious Adverse Events by Relationship to 
Study Drug (Safety Population) ............................................................79 
 
 


 
 
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Table 14.0.1: Summary of Subject Enrollment and Evaluability 
 
 
7-Day Miconazole Oil 
  
14-Day Miconazole Oil 
  
14-Day Vehicle Oil 
 
Number of Subjects Randomized 
xx 
xx 
xx 
Number of Subjects Excluded from the ITT Population 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Number of Subjects Included in the ITT Population 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Number of Subjects Excluded from the MITT Population 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Number of Subjects Included in the MITT Population 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Number of Subjects Excluded from the Safety Population 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Number of Subjects Included in the Safety Population 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Number of Subjects Excluded from the PP Population 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Number of Subjects Included in the PP Population 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.0.2: Summary of Subjects Excluded from Analyses 
(Randomized Subjects) 
 
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Number of Subjects Excluded from the ITT Population 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Reason for Exclusion from the ITT Population 
Not Dispensed Study Drug 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Number of Subjects Excluded from the MITT Population 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Reason for Exclusion from the MITT Population 
Not Dispensed Study Drug 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
No Positive Otomycosis Diagnosis 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Number of Subjects Excluded from the Safety Population 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Reason for Exclusion from the Safety Population 
Not Dispensed Study Drug 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
No Post Baseline Assessment 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Number of Subjects Excluded from the PP Population 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Reason for Exclusion from the PP Population 
Not Dispensed Study Drug 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
No Positive Otomycosis Diagnosis 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Violated the inclusion/exclusion criteria 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Used an interfering concomitant medication 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Did not attend the Test of Cure Visit 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Have not been compliant with the dosing regimen 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Out of visit window at the Test of Cure Visit 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.0.3: Summary of Subject Treatment Completion/Discontinuation 
(Randomized Subjects) 
 
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Completed Study 
Yes 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
No 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Reason for Discontinuation 
Adverse Event 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Lost To Follow-Up 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Pregnancy 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Protocol Deviation 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Withdrawal by Subject 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Withdrawal by Parent/Guardian 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Physician Decision 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Study Terminated by Sponsor 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Othera 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a See Listing 16.2.1.2 for other discontinuation reasons. 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.1.1.1: Summary of Subject Demographics 
(Modified Intent-To-Treat Population) 
 
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Age (years) 
n 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
Sex 
n 
xx 
xx 
xx 
Male 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Female 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Ethnicity 
n 
xx 
xx 
xx 
Hispanic or Latino 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Not Hispanic or Latino 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Race 
n 
xx 
xx 
xx 
American Indian or Alaska Native 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Asian 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Black or African American 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Native Hawaiian or Other Pacific Islander 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
White 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Othera 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a See Listing 16.2.4.1 for a complete list of all other races. 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.1.1.2: Summary of Subject Demographics 
(Per-Protocol Population) 
 
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Age (years) 
n 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
Sex 
n 
xx 
xx 
xx 
Male 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Female 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Ethnicity 
n 
xx 
xx 
xx 
Hispanic or Latino 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Not Hispanic or Latino 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Race 
n 
xx 
xx 
xx 
American Indian or Alaska Native 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Asian 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Black or African American 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Native Hawaiian or Other Pacific Islander 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
White 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Othera 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a See Listing 16.2.4.1 for a complete list of all other races. 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.1.1.3: Summary of Subject Demographics 
(Safety Population) 
 
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Age (years) 
n 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
Sex 
n 
xx 
xx 
xx 
Male 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Female 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Ethnicity 
n 
xx 
xx 
xx 
Hispanic or Latino 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Not Hispanic or Latino 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Race 
n 
xx 
xx 
xx 
American Indian or Alaska Native 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Asian 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Black or African American 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Native Hawaiian or Other Pacific Islander 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
White 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Othera 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a See Listing 16.2.4.1 for a complete list of all other races. 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.1.2.1: Subject Baseline Characteristics 
(Modified Intent-To-Treat Population) 
(Page 1 of 2) 
 
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Otomycosis Mycological Culture 
n 
xx 
xx 
xx 
Positive  
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Negative 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Pruritus 
Subject Assessed 
n 
xx 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Mild  
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Investigator Assessed 
n 
xx 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Mild  
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Table only includes assessments of the study ear. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.1.2.1: Subject Baseline Characteristics 
(Modified Intent-To-Treat Population) 
(Page 2 of 2) 
 
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Debris 
n 
xx 
xx 
xx 
None  
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Scant 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Heavy 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Presence of Fungal Elements 
n 
xx 
xx 
xx 
Absent 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Present 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Pain 
n 
xx 
xx 
xx 
Absent 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Present 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Subject Global Assessment 
n 
xx 
xx 
xx 
None  
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Minor 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Table only includes assessments of the study ear. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.1.2.2: Subject Baseline Characteristics 
(Per-Protocol Population) 
(Page 1 of 2) 
 
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Otomycosis Mycological Culture 
n 
xx 
xx 
xx 
Positive  
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Negative 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Pruritus 
Subject Assessed 
n 
xx 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Mild  
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Investigator Assessed 
n 
xx 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Mild  
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Table only includes assessments of the study ear. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.1.2.2: Subject Baseline Characteristics 
(Per-Protocol Population) 
(Page 2 of 2) 
 
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Debris 
n 
xx 
xx 
xx 
None  
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Scant 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Heavy 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Presence of Fungal Elements 
n 
xx 
xx 
xx 
Absent 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Present 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Pain 
n 
xx 
xx 
xx 
Absent 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Present 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Subject Global Assessment 
n 
xx 
xx 
xx 
None  
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Minor 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Table only includes assessments of the study ear. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.1.2.3: Subject Baseline Characteristics 
(Safety Population) 
(Page 1 of 2) 
 
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Otomycosis Mycological Culture 
n 
xx 
xx 
xx 
Positive  
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Negative 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Pruritus 
Subject Assessed 
n 
xx 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Mild  
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Investigator Assessed 
n 
xx 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Mild  
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Table only includes assessments of the study ear. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.1.2.3: Subject Baseline Characteristics 
(Safety Population) 
(Page 2 of 2) 
 
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Debris 
n 
xx 
xx 
xx 
None  
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Scant 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Heavy 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Presence of Fungal Elements 
n 
xx 
xx 
xx 
Absent 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Present 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Pain 
n 
xx 
xx 
xx 
Absent 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Present 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Subject Global Assessment 
n 
xx 
xx 
xx 
None  
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Minor 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Table only includes assessments of the study ear. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 34 of 105 
CONFIDENTIAL 
 
Table 14.2.1.1: Summary of Primary Efficacy Endpoint: Therapeutic Cure at Test of Cure 
(Modified Intent-to-Treat Population) 
 
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Therapeutic Cure a at Test of Cure 
Achieved 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Not Achieved 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a Therapeutic Cure is defined as a negative mycological culture plus Clinical Cure for the study ear. Clinical Cure is defined as the absence of all otomycosis  
  signs and symptoms based on Investigator assessment according to the scales for each individual sign or symptom and with absence defined as a score of 0 on  
  each of the scales for pruritus, debris, fungal elements, and pain.  
Note: Last observation carried forward (LOCF) used to impute missing values.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 35 of 105 
CONFIDENTIAL 
Table 14.2.1.2: Summary of Primary Efficacy Endpoint: Therapeutic Cure at Test of Cure 
(Per-Protocol Population) 
 
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Therapeutic Cure a at Test of Cure 
Achieved 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Not Achieved 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a Therapeutic Cure is defined as a negative mycological culture plus Clinical Cure for the study ear. Clinical Cure is defined as the absence of all otomycosis  
  signs and symptoms based on Investigator assessment according to the scales for each individual sign or symptom and with absence defined as a score of 0 on  
  each of the scales for pruritus, debris, fungal elements, and pain.  
Note: Last observation carried forward (LOCF) used to impute missing values.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 36 of 105 
CONFIDENTIAL 
Table 14.2.2.1.1: Summary of Secondary Efficacy Endpoints: Mycological Culture and Individual Signs and Symptoms  
(Modified Intent-to-Treat Population) 
 
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Clinical Cure a at Test of Cure 
Achieved 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Not Achieved 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Negative Mycological Culture at Test of Cure 
Achieved 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Not Achieved 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Negative Mycological Culture and Individual Sign or 
Symptom Score of 0 or 1 on each of the Scales for Pruritus 
and Debris and a Score of 0 on each of the Scales for Fungal 
Elements and Pain at Test of Cure. 
Achieved 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Not Achieved 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Individual Sign or Symptom Score of 0 or 1 on each of the 
Scales for Pruritus and Debris and a Score of 0 on each of the 
Scales for Fungal Elements and Pain at Test of Cure.  
Achieved 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Not Achieved 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a Clinical Cure is defined as the absence of all otomycosis signs and symptoms based on Investigator assessment according to the scales for each individual sign  
or symptom and with absence defined as a score of 0 on each of the scales for pruritus, debris, fungal elements, and pain.  
Note: Last observation carried forward (LOCF) used to impute missing values.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 37 of 105 
CONFIDENTIAL 
Table 14.2.2.1.2: Summary of Secondary Efficacy Endpoints: Mycological Culture and Individual Signs and Symptoms Endpoints 
(Per-Protocol Population) 
  
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Clinical Cure a at Test of Cure 
Achieved 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Not Achieved 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Negative Mycological Culture at Test of Cure 
Achieved 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Not Achieved 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Negative Mycological Culture and Individual Sign or 
Symptom Score of 0 or 1 on each of the Scales for Pruritus 
and Debris and a Score of 0 on each of the Scales for Fungal 
Elements and Pain at Test of Cure. 
Achieved 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Not Achieved 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Individual Sign or Symptom Score of 0 or 1 on each of the 
Scales for Pruritus and Debris and a Score of 0 on each of the 
Scales for Fungal Elements and Pain at Test of Cure.  
Achieved 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Not Achieved 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a Clinical Cure is defined as the absence of all otomycosis signs and symptoms based on Investigator assessment according to the scales for each individual sign  
or symptom and with absence defined as a score of 0 on each of the scales for pruritus, debris, fungal elements, and pain.  
Note: Last observation carried forward used to impute missing values.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 38 of 105 
CONFIDENTIAL 
Table 14.2.2.2.1: Summary of Secondary Efficacy Endpoint: Subject Global Assessment 
(Modified Intent-to-Treat Population) 
 
 
7-Day Miconazole Oil (N=xx) 
  
14-Day Miconazole Oil (N=xx) 
  
14-Day Vehicle Oil (N=xx) 
 
Subject Global Assessment 
  
 
Baseline   Test of Cure   
 
Baseline   Test of Cure   
 
Baseline   Test of Cure  
n 
xx  
xx  
xx  
xx 
xx 
xx 
None 
xx ( xx.x%) xx ( xx.x%) 
xx ( xx.x%) xx ( xx.x%) 
xx ( xx.x%) xx ( xx.x%) 
Minor 
xx ( xx.x%) xx ( xx.x%) 
xx ( xx.x%) xx ( xx.x%) 
xx ( xx.x%) xx ( xx.x%) 
Moderate 
xx ( xx.x%) xx ( xx.x%) 
xx ( xx.x%) xx ( xx.x%) 
xx ( xx.x%) xx ( xx.x%) 
 
Test of Cure 
  
Test of Cure 
  
Test of Cure 
 
Baseline 
 
None 
  
Minor 
  Moderate   
None 
  
Minor 
  Moderate   
None 
  
Minor 
  Moderate  
None 
xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) 
Minor 
xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) 
Moderate xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) 
 
 
Note: No imputation of missing values. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
  
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 39 of 105 
CONFIDENTIAL 
Table 14.2.2.2.2: Summary of Secondary Efficacy Endpoint: Subject Global Assessment 
(Per-Protocol Population) 
 
 
7-Day Miconazole Oil (N=xx) 
  
14-Day Miconazole Oil (N=xx) 
  
14-Day Vehicle Oil (N=xx) 
 
Subject Global Assessment 
  
 
Baseline   Test of Cure   
 
Baseline   Test of Cure   
 
Baseline   Test of Cure  
n 
xx  
xx  
xx  
xx 
xx 
xx 
None 
xx ( xx.x%) xx ( xx.x%) 
xx ( xx.x%) xx ( xx.x%) 
xx ( xx.x%) xx ( xx.x%) 
Minor 
xx ( xx.x%) xx ( xx.x%) 
xx ( xx.x%) xx ( xx.x%) 
xx ( xx.x%) xx ( xx.x%) 
Moderate 
xx ( xx.x%) xx ( xx.x%) 
xx ( xx.x%) xx ( xx.x%) 
xx ( xx.x%) xx ( xx.x%) 
 
Test of Cure 
  
Test of Cure 
  
Test of Cure 
 
Baseline 
 
None 
  
Minor 
  Moderate   
None 
  
Minor 
  Moderate   
None 
  
Minor 
  Moderate  
None 
xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) 
Minor 
xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) 
Moderate xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) xx ( xx.x%) 
 
 
Note: No imputation of missing values. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 40 of 105 
CONFIDENTIAL 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Table 14.2.2.3.1: Otomycosis Mycological Culture Through Time 
(Modified Intent-To-Treat Population) 
 
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Otomycosis Mycological Culture 
Baseline 
n 
xx 
xx 
xx 
Positive 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Negative 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
On Treatment 
n 
NA 
xx 
xx 
Positive 
xx ( xx.x%) 
xx ( xx.x%) 
Negative 
xx ( xx.x%) 
xx ( xx.x%) 
End of Treatment 
n 
xx 
xx 
xx 
Positive 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Negative 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Test of Cure 
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: Subjects in the 14-day treatment duration will have the follow-up visit schedule On Treatment – Day 8, End of Treatment – Day 15, and Test of Cure –  
       Day 22. Subjects in the 7-day treatment durations will have the follow-up visit schedule End of Treatment – Day 8, and Test of Cure – Day 15.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 41 of 105 
CONFIDENTIAL 
 
 
Table 14.2.2.3.2: Otomycosis Mycological Culture Through Time 
(Per-Protocol Population) 
 
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Otomycosis Mycological Culture 
Baseline 
n 
xx 
xx 
xx 
Positive 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Negative 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
On Treatment 
n 
NA 
xx 
xx 
Positive 
xx ( xx.x%) 
xx ( xx.x%) 
Negative 
xx ( xx.x%) 
xx ( xx.x%) 
End of Treatment 
n 
xx 
xx 
xx 
Positive 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Negative 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Test of Cure 
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: Subjects in the 14-day treatment duration will have the follow-up visit schedule On Treatment – Day 8, End of Treatment – Day 15, and Test of Cure –  
       Day 22. Subjects in the 7-day treatment durations will have the follow-up visit schedule End of Treatment – Day 8, and Test of Cure – Day 15.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 42 of 105 
CONFIDENTIAL 
Table 14.2.2.4.1: Investigator Assessed Pruritus Through Time 
(Modified Intent-To-Treat Population) 
(Page 1 of 2) 
  
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Investigator Assessed Pruritus  
Baseline 
n 
xx 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
On Treatment 
n 
NA 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
Mild 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
End of Treatment 
n 
xx 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Subjects in the 14-day treatment duration will have the follow-up visit schedule On Treatment – Day 8, End of Treatment – Day 15, and Test of Cure –  
       Day 22. Subjects in the 7-day treatment durations will have the follow-up visit schedule End of Treatment – Day 8, and Test of Cure – Day 15.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 43 of 105 
CONFIDENTIAL 
Table 14.2.2.4.1: Investigator Assessed Pruritus Through Time 
(Modified Intent-To-Treat Population) 
(Page 2 of 2) 
  
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Investigator Pruritus  
Test of Cure 
n 
xx 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Subjects in the 14-day treatment duration will have the follow-up visit schedule On Treatment – Day 8, End of Treatment – Day 15, and Test of Cure –  
       Day 22. Subjects in the 7-day treatment durations will have the follow-up visit schedule End of Treatment – Day 8, and Test of Cure – Day 15.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 44 of 105 
CONFIDENTIAL 
Table 14.2.2.4.2: Investigator Assessed Pruritus Through Time 
(Per-Protocol Population) 
(Page 1 of 2) 
  
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Investigator Assessed Pruritus  
Baseline 
n 
xx 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
On Treatment 
n 
NA 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
Mild 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
End of Treatment 
n 
xx 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Subjects in the 14-day treatment duration will have the follow-up visit schedule On Treatment – Day 8, End of Treatment – Day 15, and Test of Cure –  
       Day 22. Subjects in the 7-day treatment durations will have the follow-up visit schedule End of Treatment – Day 8, and Test of Cure – Day 15.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 45 of 105 
CONFIDENTIAL 
Table 14.2.2.4.2: Investigator Assessed Pruritus Through Time 
(Per-Protocol Population) 
(Page 2 of 2) 
  
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Investigator Pruritus  
Test of Cure 
n 
xx 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Subjects in the 14-day treatment duration will have the follow-up visit schedule On Treatment – Day 8, End of Treatment – Day 15, and Test of Cure –  
       Day 22. Subjects in the 7-day treatment durations will have the follow-up visit schedule End of Treatment – Day 8, and Test of Cure – Day 15.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 46 of 105 
CONFIDENTIAL 
Table 14.2.2.5.1: Debris Through Time 
(Modified Intent-To-Treat Population) 
(Page 1 of 2) 
  
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Debris 
Baseline 
n 
xx 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Scant 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Heavy 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
On Treatment 
n 
NA 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
Scant 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
Heavy 
xx ( xx.x%) 
xx ( xx.x%) 
End of Treatment 
n 
xx 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Scant 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Heavy 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Subjects in the 14-day treatment duration will have the follow-up visit schedule On Treatment – Day 8, End of Treatment – Day 15, and Test of Cure –  
       Day 22. Subjects in the 7-day treatment durations will have the follow-up visit schedule End of Treatment – Day 8, and Test of Cure – Day 15.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 47 of 105 
CONFIDENTIAL 
Table 14.2.2.5.1: Debris Through Time 
(Modified Intent-To-Treat Population) 
(Page 2 of 2) 
  
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Debris 
Test of Cure 
n 
xx 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Scant 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Heavy 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Subjects in the 14-day treatment duration will have the follow-up visit schedule On Treatment – Day 8, End of Treatment – Day 15, and Test of Cure –  
       Day 22. Subjects in the 7-day treatment durations will have the follow-up visit schedule End of Treatment – Day 8, and Test of Cure – Day 15.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 48 of 105 
CONFIDENTIAL 
 
 
Table 14.2.2.5.2: Debris Through Time 
(Per-Protocol Population) 
(Page 1 of 2) 
  
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Debris 
Baseline 
n 
xx 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Scant 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Heavy 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
On Treatment 
n 
NA 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
Scant 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
Heavy 
xx ( xx.x%) 
xx ( xx.x%) 
End of Treatment 
n 
xx 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Scant 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Heavy 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Subjects in the 14-day treatment duration will have the follow-up visit schedule On Treatment – Day 8, End of Treatment – Day 15, and Test of Cure –  
       Day 22. Subjects in the 7-day treatment durations will have the follow-up visit schedule End of Treatment – Day 8, and Test of Cure – Day 15.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 49 of 105 
CONFIDENTIAL 
Table 14.2.2.5.2: Debris Through Time 
(Per-Protocol Population) 
(Page 2 of 2) 
  
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Debris 
Test of Cure 
n 
xx 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Scant 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Heavy 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Subjects in the 14-day treatment duration will have the follow-up visit schedule On Treatment – Day 8, End of Treatment – Day 15, and Test of Cure –  
       Day 22. Subjects in the 7-day treatment durations will have the follow-up visit schedule End of Treatment – Day 8, and Test of Cure – Day 15.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 50 of 105 
CONFIDENTIAL 
 
Table 14.2.2.6.1: Presence of Fungal Elements Through Time 
(Modified Intent-To-Treat Population) 
  
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Presence of Fungal Elements  
Baseline 
n 
xx 
xx 
xx 
Absent 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Present 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
On Treatment 
n 
NA 
xx 
xx 
Absent 
xx ( xx.x%) 
xx ( xx.x%) 
Present 
xx ( xx.x%) 
xx ( xx.x%) 
End of Treatment 
n 
xx 
xx 
xx 
Absent 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Present 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Test of Cure 
n 
xx 
xx 
xx 
Absent 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Present 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Subjects in the 14-day treatment duration will have the follow-up visit schedule On Treatment – Day 8, End of Treatment – Day 15, and Test of Cure –  
       Day 22. Subjects in the 7-day treatment durations will have the follow-up visit schedule End of Treatment – Day 8, and Test of Cure – Day 15.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 51 of 105 
CONFIDENTIAL 
 
Table 14.2.2.6.2: Presence of Fungal Elements Through Time 
(Per-Protocol Population) 
  
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Presence of Fungal Elements  
Baseline 
n 
xx 
xx 
xx 
Absent 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Present 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
On Treatment 
n 
NA 
xx 
xx 
Absent 
xx ( xx.x%) 
xx ( xx.x%) 
Present 
xx ( xx.x%) 
xx ( xx.x%) 
End of Treatment 
n 
xx 
xx 
xx 
Absent 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Present 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Test of Cure 
n 
xx 
xx 
xx 
Absent 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Present 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Subjects in the 14-day treatment duration will have the follow-up visit schedule On Treatment – Day 8, End of Treatment – Day 15, and Test of Cure –  
       Day 22. Subjects in the 7-day treatment durations will have the follow-up visit schedule End of Treatment – Day 8, and Test of Cure – Day 15.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 52 of 105 
CONFIDENTIAL 
Table 14.2.2.7.1: Pain Through Time 
(Modified Intent-to-Treat Population) 
  
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Pain 
Baseline 
n 
xx 
xx 
xx 
Absent 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Present 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
On Treatment 
n 
NA 
xx 
xx 
Absent 
xx ( xx.x%) 
xx ( xx.x%) 
Present 
xx ( xx.x%) 
xx ( xx.x%) 
End of Treatment 
n 
xx 
xx 
xx 
Absent 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Present 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Test of Cure 
n 
xx 
xx 
xx 
Absent 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Present 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Subjects in the 14-day treatment duration will have the follow-up visit schedule On Treatment – Day 8, End of Treatment – Day 15, and Test of Cure –  
       Day 22. Subjects in the 7-day treatment durations will have the follow-up visit schedule End of Treatment – Day 8, and Test of Cure – Day 15.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 53 of 105 
CONFIDENTIAL 
 
Table 14.2.2.7.2: Pain Through Time 
(Per-Protocol Population) 
  
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Pain 
Baseline 
n 
xx 
xx 
xx 
Absent 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Present 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
On Treatment 
n 
NA 
xx 
xx 
Absent 
xx ( xx.x%) 
xx ( xx.x%) 
Present 
xx ( xx.x%) 
xx ( xx.x%) 
End of Treatment 
n 
xx 
xx 
xx 
Absent 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Present 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Test of Cure 
n 
xx 
xx 
xx 
Absent 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Present 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Subjects in the 14-day treatment duration will have the follow-up visit schedule On Treatment – Day 8, End of Treatment – Day 15, and Test of Cure –  
       Day 22. Subjects in the 7-day treatment durations will have the follow-up visit schedule End of Treatment – Day 8, and Test of Cure – Day 15.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 54 of 105 
CONFIDENTIAL 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Table 14.2.2.8.1: Subject Global Assessment Through Time 
(Modified Intent-To-Treat Population) 
 
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Subject Global Assessment 
Baseline 
n 
xx 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Minor 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
On Treatment 
n 
NA 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
Minor 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
End of Treatment 
n 
xx 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Minor 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Test of Cure 
n 
xx 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Minor 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Subjects in the 14-day treatment duration will have the follow-up visit schedule On Treatment – Day 8, End of Treatment – Day 15, and Test of Cure –  
       Day 22. Subjects in the 7-day treatment durations will have the follow-up visit schedule End of Treatment – Day 8, and Test of Cure – Day 15.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 55 of 105 
CONFIDENTIAL 
 
 
Table 14.2.2.8.2: Subject Global Assessment Through Time 
(Per-Protocol Population) 
 
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Subject Global Assessment 
Baseline 
n 
xx 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Minor 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
On Treatment 
n 
NA 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
Minor 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
End of Treatment 
n 
xx 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Minor 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Test of Cure 
n 
xx 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Minor 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Subjects in the 14-day treatment duration will have the follow-up visit schedule On Treatment – Day 8, End of Treatment – Day 15, and Test of Cure –  
       Day 22. Subjects in the 7-day treatment durations will have the follow-up visit schedule End of Treatment – Day 8, and Test of Cure – Day 15.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 56 of 105 
CONFIDENTIAL 
Table 14.2.3.1.1: Summary of Other Efficacy Endpoint: Subject Therapeutic Cure at Test of Cure 
(Modified Intent-to-Treat Population) 
 
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Subject Therapeutic Cure a at Test of Cure 
Achieved 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Not Achieved 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a Therapeutic Cure is defined as a negative mycological culture plus Clinical Cure based on subject assessment of pruritus for the study ear. Clinical Cure is  
defined as the absence of all otomycosis signs and symptoms based on Investigator assessment according to the scales for each individual sign or symptom and 
with absence defined as a score of 0 on each of the scales for pruritus, debris, fungal elements, and pain.  
Note: Last observation carried forward used to impute missing values. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 57 of 105 
CONFIDENTIAL 
 
Table 14.2.3.1.2: Summary of Other Efficacy Endpoint: Subject Therapeutic Cure at Test of Cure 
(Per-Protocol Population) 
 
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Subject Therapeutic Cure a at Test of Cure 
Achieved 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Not Achieved 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a Therapeutic Cure is defined as a negative mycological culture plus Clinical Cure based on subject assessment of pruritus for the study ear. Clinical Cure is  
defined as the absence of all otomycosis signs and symptoms based on Investigator assessment according to the scales for each individual sign or symptom and 
with absence defined as a score of 0 on each of the scales for pruritus, debris, fungal elements, and pain.  
Note: Last observation carried forward used to impute missing values. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 58 of 105 
CONFIDENTIAL 
Table 14.2.3.2.1: Subject Assessed Pruritus Through Time 
(Modified Intent-To-Treat Population) 
(Page 1 of 2)  
  
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Subject Assessed Pruritus  
Baseline 
n 
xx 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
On Treatment 
n 
NA 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
Mild 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
End of Treatment 
n 
xx 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Subjects in the 14-day treatment duration will have the follow-up visit schedule On Treatment – Day 8, End of Treatment – Day 15, and Test of Cure –  
       Day 22. Subjects in the 7-day treatment durations will have the follow-up visit schedule End of Treatment – Day 8, and Test of Cure – Day 15.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 59 of 105 
CONFIDENTIAL 
Table 14.2.3.2.1: Subject Assessed Pruritus Through Time 
(Modified Intent-To-Treat Population) 
(Page 2 of 2)  
  
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Subject Assessed Pruritus (cont.) 
Test of Cure 
n 
xx 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Subjects in the 14-day treatment duration will have the follow-up visit schedule On Treatment – Day 8, End of Treatment – Day 15, and Test of Cure –  
       Day 22. Subjects in the 7-day treatment durations will have the follow-up visit schedule End of Treatment – Day 8, and Test of Cure – Day 15.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 60 of 105 
CONFIDENTIAL 
 
Table 14.2.3.2.2: Subject Assessed Pruritus Through Time 
(Per-Protocol Population) 
(Page 1 of 2)  
  
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Subject Assessed Pruritus  
Baseline 
n 
xx 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
On Treatment 
n 
NA 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
Mild 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
End of Treatment 
n 
xx 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Subjects in the 14-day treatment duration will have the follow-up visit schedule On Treatment – Day 8, End of Treatment – Day 15, and Test of Cure –  
       Day 22. Subjects in the 7-day treatment durations will have the follow-up visit schedule End of Treatment – Day 8, and Test of Cure – Day 15.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 61 of 105 
CONFIDENTIAL 
Table 14.2.3.2.2: Subject Assessed Pruritus Through Time 
(Per-Protocol Population) 
(Page 2 of 2)  
  
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Subject Assessed Pruritus (cont.) 
Test of Cure 
n 
xx 
xx 
xx 
None 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Subjects in the 14-day treatment duration will have the follow-up visit schedule On Treatment – Day 8, End of Treatment – Day 15, and Test of Cure –  
       Day 22. Subjects in the 7-day treatment durations will have the follow-up visit schedule End of Treatment – Day 8, and Test of Cure – Day 15.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 62 of 105 
CONFIDENTIAL 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Table 14.3.1.1: Summary of Extent of Exposure 
(Modified Intent-To-Treat Population) 
 
 
 
 
Total Amount of 
 Study Drug Used (g)  
 
Total Number of 
 Days of Exposure  
 
Total Number  
 
of Applications 
 
 
Total Number of 
 Missed Applications   
Complianta 
 
7-Day Miconazole Oil (N=xx) 
n 
xx 
xx 
xx 
xx 
Yes 
xx ( xx.x%) 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
No 
xx ( xx.x%) 
SD 
xx.x 
xx.x 
xx.x 
xx.x 
Median 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
14-Day Miconazole Oil (N=xx) 
n 
xx 
xx 
xx 
xx 
Yes 
xx ( xx.x%) 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
No 
xx ( xx.x%) 
SD 
xx.x 
xx.x 
xx.x 
xx.x 
Median 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
14-Day Vehicle Oil (N=xx) 
n 
xx 
xx 
xx 
xx 
Yes 
xx ( xx.x%) 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
No 
xx ( xx.x%) 
SD 
xx.x 
xx.x 
xx.x 
xx.x 
Median 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
 
 
a A subject was considered compliant with the dosing regimen if the subject applied at least 80% but no more than 120% of the expected applications while 
enrolled in the study. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 63 of 105 
CONFIDENTIAL 
Table 14.3.1.2: Summary of Extent of Exposure 
(Per-Protocol Population) 
 
 
 
 
Total Amount of 
 Study Drug Used (g)  
 
Total Number of 
 Days of Exposure  
 
Total Number  
 
of Applications 
 
 
Total Number of 
 Missed Applications   
Complianta 
 
7-Day Miconazole Oil (N=xx) 
n 
xx 
xx 
xx 
xx 
Yes 
xx ( xx.x%) 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
No 
xx ( xx.x%) 
SD 
xx.x 
xx.x 
xx.x 
xx.x 
Median 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
14-Day Miconazole Oil (N=xx) 
n 
xx 
xx 
xx 
xx 
Yes 
xx ( xx.x%) 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
No 
xx ( xx.x%) 
SD 
xx.x 
xx.x 
xx.x 
xx.x 
Median 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
14-Day Vehicle Oil (N=xx) 
n 
xx 
xx 
xx 
xx 
Yes 
xx ( xx.x%) 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
No 
xx ( xx.x%) 
SD 
xx.x 
xx.x 
xx.x 
xx.x 
Median 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
 
 
a A subject was considered compliant with the dosing regimen if the subject applied at least 80% but no more than 120% of the expected applications while 
enrolled in the study. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 64 of 105 
CONFIDENTIAL 
Table 14.3.1.3: Summary of Extent of Exposure 
(Safety Population) 
 
 
 
 
Total Amount of 
 Study Drug Used (g)  
 
Total Number of 
 Days of Exposure  
 
Total Number  
 
of Applications 
 
 
Total Number of 
 Missed Applications   
Complianta 
 
7-Day Miconazole Oil (N=xx) 
n 
xx 
xx 
xx 
xx 
Yes 
xx ( xx.x%) 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
No 
xx ( xx.x%) 
SD 
xx.x 
xx.x 
xx.x 
xx.x 
Median 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
14-Day Miconazole Oil (N=xx) 
n 
xx 
xx 
xx 
xx 
Yes 
xx ( xx.x%) 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
No 
xx ( xx.x%) 
SD 
xx.x 
xx.x 
xx.x 
xx.x 
Median 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
14-Day Vehicle Oil (N=xx) 
n 
xx 
xx 
xx 
xx 
Yes 
xx ( xx.x%) 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
No 
xx ( xx.x%) 
SD 
xx.x 
xx.x 
xx.x 
xx.x 
Median 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
 
 
a A subject was considered compliant with the dosing regimen if the subject applied at least 80% but no more than 120% of the expected applications while 
enrolled in the study. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 65 of 105 
CONFIDENTIAL 
 
 
 
 
 
 
 
 
Table 14.3.2.1: Summary of Treatment-Emergent Adverse Event Characteristics 
(Safety Population) 
(Page 1 of 4) 
  
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Number (%) of Subjects Reporting At Least One Adverse 
Event 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Number (%) of Subjects Reporting At Least One Serious 
Adverse Event 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Number (%) of Subjects who Died 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Number (%) of Subjects who Discontinued Study Drug due to 
Adverse Event 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
By Subject 
Maximum Severity 
Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Strongest Relationship to Study Drug 
Not Suspected 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Suspected 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Treatment-emergent adverse events are those with an onset on or after the date of first study drug application. 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 66 of 105 
CONFIDENTIAL 
Table 14.3.2.1: Summary of Treatment-Emergent Adverse Event Characteristics 
(Safety Population) 
(Page 2 of 4) 
  
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
By Subject 
Maximum Severity within Relationship to Study Drug 
Not Suspected 
Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Suspected 
Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Treatment-emergent adverse events are those with an onset on or after the date of first study drug application. 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 67 of 105 
CONFIDENTIAL 
Table 14.3.2.1: Summary of Treatment-Emergent Adverse Event Characteristics 
(Safety Population) 
(Page 3 of 4) 
  
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Number Events Reported 
xx 
xx 
xx 
By Event 
Serious 
No 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Yes 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Death 
No 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Yes 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Discontinuation of Study Drug 
No 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Yes 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Severity 
Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Relationship to Study Drug 
Not Suspected 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Suspected 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Treatment-emergent adverse events are those with an onset on or after the date of first study drug application. 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 68 of 105 
CONFIDENTIAL 
Table 14.3.2.1: Summary of Treatment-Emergent Adverse Event Characteristics 
(Safety Population) 
(Page 4 of 4) 
  
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
By Event 
Severity within Relationship to Study Drug 
Not Suspected 
Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Suspected 
Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Treatment-emergent adverse events are those with an onset on or after the date of first study drug application. 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
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CONFIDENTIAL 
Table 14.3.2.2: Summary of Treatment-Emergent Adverse Events Leading to Permanent Withdrawal of Study Drug and/or Early Discontinuation From Study 
(Safety Population) 
(Page 1 of xx) 
  
System Organ Classa 
Preferred Term 
 
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
System Organ Class 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Preferred Term 
xx ( xx.x%) 
xx ( xx.x%) 
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: Treatment-emergent adverse events are those with an onset on or after the date of first study drug application. 
Note: MedDRA dictionary (Version 20.1) 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 70 of 105 
CONFIDENTIAL 
Table 14.3.2.3: Summary of Treatment-Emergent Adverse Events 
(Safety Population) 
(Page 1 of xx) 
  
System Organ Classa 
Preferred Term 
 
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
System Organ Class 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Preferred Term 
xx ( xx.x%) 
xx ( xx.x%) 
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: Treatment-emergent adverse events are those with an onset on or after the date of first study drug application. 
Note: MedDRA dictionary (Version 20.1) 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 71 of 105 
CONFIDENTIAL 
Table 14.3.2.4: Summary of Treatment-Emergent Adverse Events by Severity 
(Safety Population) 
(Page 1 of xx) 
  
System Organ Classa 
Preferred Term 
 Severity 
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
System Organ Class 
Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Preferred Term 
Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
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: Treatment-emergent adverse events are those with an onset on or after the date of first study drug application. 
Note: MedDRA dictionary (Version 20.1) 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 72 of 105 
CONFIDENTIAL 
Table 14.3.2.5: Summary of Treatment-Emergent Adverse Events by Relationship to Study Drug 
(Safety Population) 
(Page 1 of xx) 
  
System Organ Classa 
Preferred Term 
 Relationship 
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
System Organ Class 
Not Suspected 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Suspected 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Preferred Term 
Not Suspected 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Suspected 
xx ( xx.x%) 
xx ( xx.x%) 
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 strongest reported relationship. 
 
Note: Treatment-emergent adverse events are those with an onset on or after the date of first study drug application. 
Note: MedDRA dictionary (Version 20.1) 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 73 of 105 
CONFIDENTIAL 
Table 14.3.3.1: Summary of Treatment-Emergent Serious Adverse Event Characteristics 
(Safety Population) 
(Page 1 of 4) 
  
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Number (%) of Subjects Reporting At Least One Serious 
Adverse Event 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Number (%) of Subjects who Died 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Number (%) of Subjects who Discontinued Study Drug due to 
Adverse Event 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
By Subject 
Maximum Severity 
Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Strongest Relationship to Study Drug 
Not Suspected 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Suspected 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Treatment-emergent adverse events are those with an onset on or after the date of first study drug application. 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 74 of 105 
CONFIDENTIAL 
Table 14.3.3.1: Summary of Treatment-Emergent Serious Adverse Event Characteristics 
(Safety Population) 
(Page 2 of 4) 
  
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
By Subject 
Maximum Severity within Relationship to Study Drug 
Not Suspected 
Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Suspected 
Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Treatment-emergent adverse events are those with an onset on or after the date of first study drug application. 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 75 of 105 
CONFIDENTIAL 
Table 14.3.3.1: Summary of Treatment-Emergent Serious Adverse Event Characteristics 
(Safety Population) 
(Page 3 of 4) 
  
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Number of Serious Events Reported 
xx 
xx 
xx 
By Event 
Death 
No 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Yes 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Discontinuation of Study Drug 
No 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Yes 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Severity 
Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Relationship to Study Drug 
Not Suspected 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Suspected 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Treatment-emergent adverse events are those with an onset on or after the date of first study drug application. 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 76 of 105 
CONFIDENTIAL 
Table 14.3.3.1: Summary of Treatment-Emergent Serious Adverse Event Characteristics 
(Safety Population) 
(Page 4 of 4) 
  
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
Severity within Relationship to Study Drug 
By Event 
Not Suspected 
Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Suspected 
Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Treatment-emergent adverse events are those with an onset on or after the date of first study drug application. 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
Statistical Analysis Plan 
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Version: 1 
Date: 30 MAY 2019 
     
Page 77 of 105 
CONFIDENTIAL 
Table 14.3.3.2: Summary of Treatment-Emergent Serious Adverse Events 
(Safety Population) 
(Page 1 of xx) 
  
System Organ Classa 
Preferred Term 
 
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
System Organ Class 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Preferred Term 
xx ( xx.x%) 
xx ( xx.x%) 
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: Treatment-emergent adverse events are those with an onset on or after the date of first study drug application. 
Note: MedDRA dictionary (Version 20.1) 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 78 of 105 
CONFIDENTIAL 
Table 14.3.3.3: Summary of Treatment-Emergent Serious Adverse Events by Severity 
(Safety Population) 
(Page 1 of xx) 
  
System Organ Classa 
Preferred Term 
 Severity 
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
System Organ Class 
Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Preferred Term 
Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
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: Treatment-emergent adverse events are those with an onset on or after the date of first study drug application. 
Note: MedDRA dictionary (Version 20.1) 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 1 
Date: 30 MAY 2019 
     
Page 79 of 105 
CONFIDENTIAL 
Table 14.3.3.4: Summary of Treatment-Emergent Serious Adverse Events by Relationship to Study Drug 
(Safety Population) 
(Page 1 of xx) 
  
System Organ Classa 
Preferred Term 
 Relationship 
 
7-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Miconazole Oil 
 
(N=xx) 
 
 
14-Day Vehicle Oil 
 
(N=xx) 
 
System Organ Class 
Not Suspected 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Suspected 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Preferred Term 
Not Suspected 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Suspected 
xx ( xx.x%) 
xx ( xx.x%) 
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 strongest reported relationship. 
 
Note: Treatment-emergent adverse events are those with an onset on or after the date of first study drug application. 
Note: MedDRA dictionary (Version 20.1) 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 0.03 
Date: DD MAY 2019 
     
Page 80 of 105 
CONFIDENTIAL 
10.  INDEX OF PLANNED LISTINGS 
Listing 16.1.7: Randomization Scheme .........................................................................................81 
Listing 16.2.1.1: End of Study Information ...................................................................................82 
Listing 16.2.1.2: Discontinued Subjects ........................................................................................83 
Listing 16.2.1.3: Screen Failures ...................................................................................................84 
Listing 16.2.2.1: Inclusion/Exclusion Criteria Violations .............................................................85 
Listing 16.2.3: Analysis Populations .............................................................................................86 
Listing 16.2.4.1: Subject Demographic Information .....................................................................87 
Listing 16.2.4.2.1: Unique Medical History Coded to MedDRA System Organ Classes and 
Preferred Terms .....................................................................................88 
Listing 16.2.4.2.2: Medical History ...............................................................................................89 
Listing 16.2.4.3: Physical Examination .........................................................................................90 
Listing 16.2.4.3.1: Unique Medication Names Coded to WHO-DDE ATC Level 2 Terms and 
Preferred Names ....................................................................................91 
Listing 16.2.4.3.2: Prior and Concomitant Medications ................................................................92 
Listing 16.2.4.4: Prior and Concomitant Procedures/Therapies ....................................................93 
Listing 16.2.5.1: Study Visit Compliance ......................................................................................94 
Listing 16.2.5.2: Subject Dosing Compliance ...............................................................................95 
Listing 16.2.5.3: Missed/Extra Doses ............................................................................................96 
Listing 16.2.5.4: Study Drug Dispensing and Return ....................................................................97 
Listing 16.2.6.1: Otomycosis Signs and Symptoms ......................................................................98 
Listing 16.2.6.2: Subject Global Assessment ................................................................................99 
Listing 16.2.7.2.1: Unique Adverse Events Coded to MedDRA System Organ Classes and 
Preferred Terms ...................................................................................100 
Listing 16.2.7.2.2: Pre-Treatment Adverse Events ......................................................................101 
Listing 16.2.7.2.3: Treatment-Emergent Adverse Events ............................................................102 
Listing 16.2.7.2.4: Serious Adverse Events .................................................................................103 
Listing 16.2.8.1.1: Urine Pregnancy Test Results .......................................................................104 
Listing 16.2.8.2.1: Microbial Culture Results..............................................................................105 
 
 
 


 
 
Statistical Analysis Plan 
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Version: 0.03 
Date: DD MAY 2019 
     
Page 81 of 105 
CONFIDENTIAL 
Listing 16.1.7: Randomization Scheme 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
  Subject     Age/Sex      Eval             Randomization Date       Assigned Arm           Treated Ear(s)        Worse Ear 
______________________________________________________________________________________________________________________________________ 
 
  xxxxxx      xxxx         xxxxxxxxx        xxxxxxxxxx               xxxxxxx xxxxxx         xxxx                  xxx xxxxx xxxx xxxx 
                                                                                                                  xxxxx xxxxxxxxx 
 
  xxxxxx      xxxx         xxxxxxxxx        xxxxxxxxxx               xxxxxxx xxxxxx         xxxxx 
                                                                          
                                                                          
  xxxxxx      xxxx         xxxxxxxxx        xxxxxxxxxx               xxxxxxx xxxxxx         xxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 


 
 
Statistical Analysis Plan 
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Version: 0.03 
Date: DD MAY 2019 
     
Page 82 of 105 
CONFIDENTIAL 
Listing 16.2.1.1: End of Study Information 
                                                            Treatment Arm 
                                                           (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
                                                                                                                       Date of Study 
                                   Date of       Date of                                 Reason for Study               Completion/ 
                                 First Dose   Last Dose of  Reason for                   Completion/                  Discontinuation 
Subject    Age/Sex    Eval      of Study Drug  Study Drug   End of Treatment             Discontinuation                   (Day)¹ 
______________________________________________________________________________________________________________________________________ 
 
xxxxxx      xxxx      xxxxxxxxx  xxxxxxxxxx    xxxxxxxxxx   xxxxxxxxx                    xxxxxxxxx                    xxxxxxxxxx xxxx 
 
xxxxxx      xxxx      xxxxxxxxx  xxxxxxxxxx    xxxxxxxxxx   xxxxxxxxx                    xxxxxxxxx                    xxxxxxxxxx xxxx 
 
xxxxxx      xxxx      xxxxxxxxx  xxxxxxxxxx    xxxxxxxxxx   xxxxxxxxx                    xxxxxxxxx                    xxxxxxxxxx xxxx 
 
xxxxxx      xxxx      xxxxxxxxx  xxxxxxxxxx    xxxxxxxxxx   xxxxxxxxx                    xxxxxxxxx                    xxxxxxxxxx xxxx 
 
xxxxxx      xxxx      xxxxxxxxx  xxxxxxxxxx    xxxxxxxxxx   xxxxxxxxx                    xxxxxxxxx                    xxxxxxxxxx xxxx 
 
xxxxxx      xxxx      xxxxxxxxx  xxxxxxxxxx    xxxxxxxxxx   xxxxxxxxx                    xxxxxxxxx                    xxxxxxxxxx xxxx 
 
xxxxxx      xxxx      xxxxx      xxxxxxxxxx    xxxxxxxxxx   xxxxxxxxx                    xxxxxxxxx                    xxxxxxxxxx xxxx 
 
xxxxxx      xxxx      xxxxxxxxx  xxxxxxxxxx    xxxxxxxxxx   xxxxxxxxx                    xxxxxxxxx                    xxxxxxxxxx xxxx 
 
xxxxxx      xxxx      xxxxxxxxx  xxxxxxxxxx    xxxxxxxxxx   xxxxxxxxx                    xxxxxxxxx                    xxxxxxxxxx xxxx 
 
xxxxxx      xxxx      xxxxxxxxx  xxxxxxxxxx    xxxxxxxxxx   xxxxxxxxx                    xxxxxxxxx                    xxxxxxxxxx xxxx 
 
xxxxxx      xxxx      xxxxx      xxxxxxxxxx    xxxxxxxxxx   xxxx xx xxxxxxxxx            xxxx xx xxxxxxxxx            xxxxxxxxxx xxxx 
 
xxxxxx      xxxx      xxxxxxxxx  xxxxxxxxxx    xxxxxxxxxx   xxxxxxxxx                    xxxxxxxxx                    xxxxxxxxxx xxxx 
 
xxxxxx      xxxx      xxxxxxxxx  xxxxxxxxxx    xxxxxxxxxx   xxxxxxxxx                    xxxxxxxxx                    xxxxxxxxxx xxxx 
 
xxxxxx      xxxx      xxxxx      xxxxxxxxxx    xxxxxxxxxx   xxxxxxxx xxxxxxxxx x xxx     xxxxxxxx xxxxxxxxx x xxx     xxxxxxxxxx xxxx 
                                                            xxxxxxxxxx                   xxxxxxxxxx 
 
xxxxxx      xxxx      xxxxxxxxx  xxxxxxxxxx    xxxxxxxxxx   xxxxxxxxx                    xxxxxxxxx                    xxxxxxxxxx xxxx 
______________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date - date of first dose for dates prior to first dose.  Otherwise, day is calculated as 
  date - date of first dose + 1 for dates on or after first dose. 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 0.03 
Date: DD MAY 2019 
     
Page 83 of 105 
CONFIDENTIAL 
Listing 16.2.1.2: Discontinued Subjects 
Treatment Arm 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
                                                                                                                       Date of Study 
                                   Date of       Date of                                 Reason for Study               Completion/ 
                                 First Dose   Last Dose of  Reason for                   Completion/                  Discontinuation 
Subject    Age/Sex    Eval      of Study Drug  Study Drug   End of Treatment             Discontinuation                   (Day)¹ 
______________________________________________________________________________________________________________________________________ 
 
xxxxxx      xxxx      xxxxxxxxx  xxxxxxxxxx    xxxxxxxxxx   xxxxxxxxx                    xxxxxxxxx                    xxxxxxxxxx xxxx 
 
xxxxxx      xxxx      xxxxxxxxx  xxxxxxxxxx    xxxxxxxxxx   xxxxxxxxx                    xxxxxxxxx                    xxxxxxxxxx xxxx 
 
xxxxxx      xxxx      xxxxxxxxx  xxxxxxxxxx    xxxxxxxxxx   xxxxxxxxx                    xxxxxxxxx                    xxxxxxxxxx xxxx 
 
xxxxxx      xxxx      xxxxxxxxx  xxxxxxxxxx    xxxxxxxxxx   xxxxxxxxx                    xxxxxxxxx                    xxxxxxxxxx xxxx 
 
xxxxxx      xxxx      xxxxxxxxx  xxxxxxxxxx    xxxxxxxxxx   xxxxxxxxx                    xxxxxxxxx                    xxxxxxxxxx xxxx 
 
xxxxxx      xxxx      xxxxxxxxx  xxxxxxxxxx    xxxxxxxxxx   xxxxxxxxx                    xxxxxxxxx                    xxxxxxxxxx xxxx 
 
xxxxxx      xxxx      xxxxx      xxxxxxxxxx    xxxxxxxxxx   xxxxxxxxx                    xxxxxxxxx                    xxxxxxxxxx xxxx 
 
xxxxxx      xxxx      xxxxxxxxx  xxxxxxxxxx    xxxxxxxxxx   xxxxxxxxx                    xxxxxxxxx                    xxxxxxxxxx xxxx 
 
xxxxxx      xxxx      xxxxxxxxx  xxxxxxxxxx    xxxxxxxxxx   xxxxxxxxx                    xxxxxxxxx                    xxxxxxxxxx xxxx 
 
xxxxxx      xxxx      xxxxxxxxx  xxxxxxxxxx    xxxxxxxxxx   xxxxxxxxx                    xxxxxxxxx                    xxxxxxxxxx xxxx 
 
xxxxxx      xxxx      xxxxx      xxxxxxxxxx    xxxxxxxxxx   xxxx xx xxxxxxxxx            xxxx xx xxxxxxxxx            xxxxxxxxxx xxxx 
 
xxxxxx      xxxx      xxxxxxxxx  xxxxxxxxxx    xxxxxxxxxx   xxxxxxxxx                    xxxxxxxxx                    xxxxxxxxxx xxxx 
 
xxxxxx      xxxx      xxxxxxxxx  xxxxxxxxxx    xxxxxxxxxx   xxxxxxxxx                    xxxxxxxxx                    xxxxxxxxxx xxxx 
 
xxxxxx      xxxx      xxxxx      xxxxxxxxxx    xxxxxxxxxx   xxxxxxxx xxxxxxxxx x xxx     xxxxxxxx xxxxxxxxx x xxx     xxxxxxxxxx xxxx 
                                                            xxxxxxxxxx                   xxxxxxxxxx 
 
xxxxxx      xxxx      xxxxxxxxx  xxxxxxxxxx    xxxxxxxxxx   xxxxxxxxx                    xxxxxxxxx                    xxxxxxxxxx xxxx 
______________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date - date of first dose for dates prior to first dose.  Otherwise, day is calculated as 
  date - date of first dose + 1 for dates on or after first dose. 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 0.03 
Date: DD MAY 2019 
     
Page 84 of 105 
CONFIDENTIAL 
Listing 16.2.1.3: Screen Failures 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
   
 
 
 
 
 
  Failed Inclusion/  
                            Date of            Met Exclusion 
Subject       Age/Sex       Screen Failure     Criteria            Criteria 
 
 
Other Reason for Screen Failure 
______________________________________________________________________________________________________________________________________ 
 
xxxxxx        xxxxxxxx      xxxxxxxxxx         xxx 
           xxxxxxxxx xxxxxxxx x 
 
 
xxxxxx        xxxxxxxx      xxxxxxxxxx         xx 
 
 
 
 
 
 
xxxxx xxxx xxxx xx xxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 0.03 
Date: DD MAY 2019 
     
Page 85 of 105 
CONFIDENTIAL 
Listing 16.2.2.1: Inclusion/Exclusion Criteria Violations 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
                                 Date            Criteria 
Subject   Age/Sex     Eval       Assessed        Failed      Description 
______________________________________________________________________________________________________________________________________ 
 
xxxxxx     xxxx       xxxxxxxxx  xxxxxxxxxx      xxxxx       xxxxx xxx xx xxxxxxxx xxxx xxxxxxxxxxxxxxxxxxx xxxxxxxx xxxxxxxxxx 
 
xxxxxx     xxxx       xxxxxxxxx  xxxxxxxxxx      xxxxx       xxxxx xxx xx xxxxxxxx xxxx xxxx x xxxxxxxx xxxxxxxxxx xxxx 
 
xxxxxx     xxxx       xxxxxxxxx  xxxxxxxxxx      xxxxx       xxxxx xx xxxxxxxxx xx xxxxxx xxx xx xxxxxxxx xxxx xxxxxxxxxxxxxxxxxxx  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 0.03 
Date: DD MAY 2019 
     
Page 86 of 105 
CONFIDENTIAL 
Listing 16.2.3: Analysis Populations 
Treatment Arm 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
Subject   Age/Sex     Population                      Included     Reason(s) Excluded                           Exceptions 
______________________________________________________________________________________________________________________________________ 
 
xxxxxx     xxxx       Intent-to-Treat                 xxx 
                      Modified Intent-to-Treat        xxx 
                      Per-Protocol                    xxx 
                      Safety                          xxx 
 
xxxxxx     xxxx       Intent-to-Treat                 xxx 
                      Modified Intent-to-Treat        xxx 
                      Per-Protocol                    xx           xxxx xxxxxxxxx xxxxx xxx xx xxxxxx xxxxxx           
                      Safety                          xxx            
 
xxxxxx     xxxx       Intent-to-Treat                 xxx 
                      Modified Intent-to-Treat        xxx 
                      Per-Protocol                    xxx 
                      Safety                          xxx        
 
xxxxxx     xxxx       Intent-to-Treat                 xxx 
                      Modified Intent-to-Treat        xxx 
                      Per-Protocol                    xxx 
                      Safety                          xxx           
 
xxxxxx     xxxx       Intent-to-Treat                 xxx 
                      Modified Intent-to-Treat        xxx 
                      Per-Protocol                    xxx 
                      Safety                          xxx         
 
xxxxxx     xxxx       Intent-to-Treat                 xxx 
                      Modified Intent-to-Treat        xxx 
                      Safety                          xxx            
                      Per-Protocol                    xxx            
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 0.03 
Date: DD MAY 2019 
     
Page 87 of 105 
CONFIDENTIAL 
 
Listing 16.2.4.1: Subject Demographic Information 
Treatment Arm 
(Page xx of yy) 
 
 _____________________________________________________________________________________________________________________________________ 
 
                                                                                  C: Childbearing 
                                                                                     Potential         P: Protocol Version                  
                             A: Age         R: Race                               B: Method of         I: Informed Consent Date     
 Subject       Eval          S: Sex         E: Ethnicity        Date of Birth        Contraception     A: Informed Assent Date           
 _____________________________________________________________________________________________________________________________________ 
 
 xxxxxx        xxxxxxxxx     A: xx          R: xxxxx            xxxxxxxxxx        C: xx                P: xxxxxxx x               
                             S: xxxx        E: xxxxxxxx xx                        B:                   I: xxxxxxxxxx                          
                                               xxxxxx                                                  A: xx 
 
 
 xxxxxx        xxxxxxxxx     A: xx          R: xxxxxxx          xxxxxxxxxx        C: xxx               P: xxxxxxx x             
                             S: xxxxxx      E: xxx xxxxxxxx                       B: xxxx xxxxxxxxx    I: xxxxxxxxxx                         
                                               xx xxxxxx                                               A: xx 
 
 xxxxxx        xxxxxxxxx     A: xx          R: xxxxx            xxxxxxxxxx        C: xx                P: xxxxxxx x                        
                             S: xxxx        E: xxx xxxxxxxx                       B:                   I: xxxxxxxxxx                           
                                               xx xxxxxx                                               A: xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 _____________________________________________________________________________________________________________________________________ 
 SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 0.03 
Date: DD MAY 2019 
     
Page 88 of 105 
CONFIDENTIAL 
Listing 16.2.4.2.1: Unique Medical History Coded to MedDRA System Organ Classes and Preferred Terms 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
MedDRA System Organ Class                     MedDRA Preferred Term                       Condition or Surgery Verbatim Term 
______________________________________________________________________________________________________________________________________ 
 
xxxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx          xxxx xxxxxxxxxx xxxxxxx                     xxxx xxxxxxxxxx xxxxxx 
 
                                              xxxxxxxxxxxxxxx                             xxxxxxxxxxxxxxx 
 
xxxxxxx xxxxxxxxx                             xxxxxxxxxx                                  xxxxxxx xxxxxxxxx 
 
                                              xxxxxx xxxxxxxxxxxx                         xxxxxx xxxxxxxxxx 
 
                                                                                          xxxxxx xxxxxxxxxxxx 
 
                                              xxxxxxxxxxxxxxxx xxxxx xxxxx xxxxxx         xxx xxxxxx xx xxxxx 
 
                                              xxxxxx xxxxxx xxxxx xxxxx                   xxxxx xxxxxx xxxxxx xxxxx 
 
                                              xxxxxxx xxxxxxx xxxxxxxxxx                  xxxxxxxxxx xxxxx xxxxxxx 
 
                                              xxxxxxxxxxxxxx xxxxxxxx                     xxxxxxxxxxxxxx xxxxxxxx 
 
                                              xxxxxxxx xxxxxx xxxxxxx                     xxxxxxxx xxxxxx xxxxxxx 
 
                                              xxxxxxxxxx xxxxxxxxxx                       xxxxxxxxxx xxxxxxx 
 
                                                                                          xxxxxxxxxx xxxxxxxxxx 
 
                                              xxxxxxxxxxx xxxxxxxx                        xxxxxxxxxxx xxxxxxxx xxxxxxxx xx 
                                                                                          xxxxxxxxxxx xxxxxx 
 
                                              xxxxxxxxx xxxxx xxxxxxxxxxxx                xxxx xxxxxxxxx xxxxxxxxxxxxx 
 
xxxxxxxxxxx xxxxxxxx xxx xxxxxxx xxxxxxxxx    xxxxxxxxxxxxxxxxxxx xxxxxxxx xxxxxxxxx      xxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxxxxxx 
 
                                              xxxxxxxx xxxxxxxxxx xxxxxxxx                xxxxxxxxxx 
 
xxx xxx xxxxxxxxx xxxxxxxxx                   xxxxxxxx                                    xxxxxxx xxxx 
 
______________________________________________________________________________________________________________________________________ 
Note: System Organ Class and Preferred Term from MedDRA Version 20.1. 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 0.03 
Date: DD MAY 2019 
     
Page 89 of 105 
CONFIDENTIAL 
Listing 16.2.4.2.2: Medical History 
Treatment Arm 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
                                           
                               Condition or Surgery               Physical      P: MedDRA Preferred Term                 S: Start Date 
Subject   Age/Sex   Eval       Verbatim Term                      Exam Finding  S: MedDRA System Organ Class             E: End Date 
______________________________________________________________________________________________________________________________________ 
 
xxxxxx     xxxx     xxxxxxxxxx xxxxxx                             xxx           P: xxxxxx                                S: xxxx 
                                                                                S: xxxxxxxxxxxx xxxxxxxx xxx xxxxxxxxxxx E: xxxxxxx 
                                                                                   xxxxxxxxx 
 
                               xxxxxxx xxxxxx                     xx            P: xxxxxxx                               S: xxxxxxx 
                                                                                S: xxxxxxxxxx xxx xxxxxxxxx xxxxxxxxx    E: xxxxxxx 
 
                               xxxxxxxxxxxxxx                     xx            P: xxxxxxxxxxxxx                         S: xxxx 
                                                                                S: xxxxxx xxxxxxxxxxxxx                  E: xxxxxxx 
 
                               xxxxxxxxx                          xx                                                     S: xxxx 
                                                                                                                         E: xxxxxxx 
 
xxxxxx     xxxx     xxxxxxxxxx xxxx xxxxxxxxxxx                   xxx           P: xxxxx xxxxxxxxxxx xxxxxxxxx           S: xxxx 
                                                                                S: xxxxxxxxxxxxxx                        E: xxxxxxx 
 
                               xxxxxxxxx                          xx                                                     S: xxxx 
                                                                                                                         E: xxxxxxx 
 
                               xxxxxxxx xxxxxxxxx                 xx            P: xxxxxxxx xxxxxxx                      S: xxxx 
                                                                                S: xxxxxx xxxxxx xxxxxxxxx               E: xxxxxxx 
 
                               xxxxxxxxx                          xx            P: xxxxxxxxx                             S: xxxx 
                                                                                S: xxxxxxxx xxx xxxxxxx xxxxxxxxxx       E: xxxx 
 
xxxxxx     xxxx     xxxxxxxxxx xxxxxxxxxxxxxxxxx xxxxx xxx        xx            P: xxxxxx xxxxxxxxx                      S: xxxx 
                                                                                S: xxxxxxxx xxx xxxxxxx xxxxxxxxxx       E: xxxx 
 
                               xxxx xxxxxx xxxxxxx xxxx xxxx      xx            P: xxxxxxx xxxx xxxxxxxx                 S: xxxx 
                                                                                S: xxxxxxxxxxxxxxx xxx xxxxxxxxxx xxxxxx E: xxxx 
                                                                                   xxxxxxxxx 
 
______________________________________________________________________________________________________________________________________ 
Note: System Organ Class and Preferred Term from MedDRA Version 20.1. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Verbatim Term, Start Date, and End Date. 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 0.03 
Date: DD MAY 2019 
     
Page 90 of 105 
CONFIDENTIAL 
Listing 16.2.4.3: Physical Examination 
Treatment Arm 
(Page xx of yy) 
 
_____________________________________________________________________________________________________________________________________ 
                                                                                                            
                                                                                                       Physical Exam 
Subject       Age/Sex       Eval             Visit                   Date                              Performed 
_____________________________________________________________________________________________________________________________________ 
 
xxxxxx        xxxx          xxxxxxxx         xxxxxxxx                xxxxxxxxxx                        xxx 
 
                                             xxxxxxxxxxx             xxxxxxxxxx                        xx 
 
 
 
xxxxxx        xxxx          xxxxxxxx         xxxxxxxx                xxxxxxxxxx                        xx 
          
                                             xxxxxxxxxxx             xxxxxxxxxx                        xxx 
  
                                             xxxxxxxxxxx             xxxxxxxxxx                        xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 _____________________________________________________________________________________________________________________________________ 
 ¹ Day is calculated as date – date of first dose for dates prior to first dose.  Otherwise, day is calculated as 
   date – date of first dose + 1 for dates on or after first dose. 
 SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME)  
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 0.03 
Date: DD MAY 2019 
     
Page 91 of 105 
CONFIDENTIAL 
 
Listing 16.2.4.3.1: Unique Medication Names Coded to WHO-DDE ATC Level 2 Terms and Preferred Names 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
                                                                                                      I: Indication 
ATC Level 2 Term                 Standardized Medication Name           Medication Name               R: Route      
_____________________________________________________________________________________________________________________________________ 
 
xxxxxxxxxxxxxx                   xxxxxxxxxxxxxx                         xxxxxxxx                      I: xxxxxxxxxxx 
                                                                                                      R: xxxxxxxxxxx 
 
                                                                        xxxxxxxxx                     I: xxxxxxxxxxx 
                                                                                                      R: xxxxxxxxxxx 
 
 
xxxxxxxxxxxxxx                   xxxxxxxxxxxxxx                         xxxxxxxx                      I: xxxxxxxxxxx 
                                                                                                      R: xxxxxxxxxxx 
 
                                                                        xxxxxxxxx                     I: xxxxxxxxxxx 
                                                                                                      R: xxxxxxxxxxx 
                                                                                                               
 
             
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
                                                             
______________________________________________________________________________________________________________________________________ 
Note: Standardized Medication Name and ATC Level 2 Term map to the WHO-DDE (Version March 1, 2017). 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by ATC Level 2 Term, Standardized Medication Name, Medication Name, Indication, and Route. 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 0.03 
Date: DD MAY 2019 
     
Page 92 of 105 
CONFIDENTIAL 
 
Listing 16.2.4.3.2: Prior and Concomitant Medications 
Treatment Arm 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
                                                    
                                                                                                               D: Dose 
S: Subject          M: Medication Name               P: Standardized             F: Date of First Dose         U: Units 
A: Age/Sex          I: Indication                       Medication Name          S: Start Date (Day)¹          F: Frequency 
E: Eval             A: Applied at Dosing Site        A: ATC Level 2 Term         E: End Date (Day)¹            O: Route           
______________________________________________________________________________________________________________________________________ 
 
S: xxxxxx           M: xxxxxxxxxxxxx                 P: xxxxxxxxxxxxx            F: xxxxxxxxxx                 D: xx                
A: xxxx             I: xxxxxxxx                      A: xxxxxxxxxxxxx            S: xxxxxxxxxx                 U: xx 
E: xxxxxxxxx        A: xx                                                        E: xxxxxxx                    F: xxxx 
                                                                                                               O: xxxxxx  
                                                                                                               
 
                    M: xxxxxxxxxxxxx                 P: xxxxxxxxxxxxx            F: xxxxxxxxxx                 D: xxxxx             
                    I: xxxxxxxx                      A: xxxxxxxxxxxxx            S: xxxxxxxxxx                 U: xx 
                    A: xxx                                                       E: xxxxxxx                    F: xx 
                                                                                                               O: xxxx 
                                                                                                               
 
S: xxxxxx           M: xxxxxxxxxxxxx                 P: xxxxxxxxxxxxx            F: xxxxxxxxxx                 D: xxx               
A: xxxx             I: xxxxxxxx                      A: xxxxxxxxxxxxx            S: xxxxxxxxxx                 U: xx 
E: xxxxxxxxx        A: xx                                                        E: xxxxxxx                    F: xx 
                                                                                                               O: xxxx 
                                                                                                               
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date – date of first dose for dates prior to first dose.  Otherwise, day is calculated as 
  date – date of first dose + 1 for dates on or after first dose. 
Note: Standardized Medication Name and ATC Level 2 Term map to the WHO-DDE (Version March 1, 2017). 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Start Date, End Date, Medication Name, Indication, and Route. 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 0.03 
Date: DD MAY 2019 
     
Page 93 of 105 
CONFIDENTIAL 
Listing 16.2.4.4: Prior and Concomitant Procedures/Therapies 
Treatment Arm 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
                                                                                                                                     
                                                                                  
                                                          Procedure/                        Applied at       S: Start Date (Day)¹    
Subject    Age/Sex    Eval         Date of First Dose     Theraphy           Indication     Dosing Site      E: End Date (Day)¹  
    
 
 
    
______________________________________________________________________________________________________________________________________ 
  
xxxxxx     xxxx       xxxxxxxxx    xxxxxxxxxx             xxxxxxxxxxxxx      xxxxxxxx       xx               S: xxxxxxxxxx xxxx                  
                                                                                                             E: xxxxxxx                 
                                                                                                                                                  
                                                          xxxxxxxxxxxxx      xxxxxxxx       xxx              S: xxxxxxxxxx xxxx                 
                                                                                                             E: xxxxxxx xxxx                     
                                                                                                                                                       
xxxxxx     xxxx       xxxxxxxxx    xxxxxxxxxx             xxxxxxxxxxxxx      xxxxxxxx       xx               S: xxxxxxxxxx xxxx                 
                                                                                                             E: xxxxxxx xxxx                     
                                                                                        
                                                            
                                                                                         
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date – date of first dose for dates prior to first dose.  Otherwise, day is calculated as 
  date – date of first dose + 1 for dates on or after first dose. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Start Date, End Date, Medication Name, Indication, and Route. 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 0.03 
Date: DD MAY 2019 
     
Page 94 of 105 
CONFIDENTIAL 
Listing 16.2.5.1: Study Visit Compliance 
Treatment Arm 
(Page xx of yy) 
 
 _____________________________________________________________________________________________________________________________________ 
 
                                                                                                               
                                                                  Study    Within         Visit Not Done/                Ear(s) 
 Subject  Age/Sex  Eval        Visit              Visit Date      Day¹     Visit Window   Reason for Unscheduled Visit   Cleaned 
 _____________________________________________________________________________________________________________________________________ 
 
 xxxxxx    xxxx    xxxxxxxx    xxxxxxxxx            xxxxxxxxxx      xx       xxx                                         xxxxx xxxxxx 
 
                               xxxxxxxx             xxxxxxxxxx      xx       xxx                                         xxxx 
 
                               xxxxxx               xxxxxxxxxx      xx       xxx                                         xxxx 
 
 
 xxxxxx    xxxx    xxxxxxxx    xxxxxxxxx            xxxxxxxxxx      xx       xxx                                         xxxxxx xxxxx 
 
                               xxxxxxxx             xxxxxxxxxx      xx       xxx                                         xxxx 
 
                               xxxxxx               xxxxxxxxxx      xx       xxx                                         xxxxx 
 
                               xxxxxx               xxxxxxxxxx      xx       xxx                                         xxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date - baseline date for dates prior to baseline visit.  Otherwise, day is calculated as 
  date - Baseline date + 1 for dates on or after baseline visit. 
 SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME)  


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 0.03 
Date: DD MAY 2019 
     
Page 95 of 105 
CONFIDENTIAL 
Listing 16.2.5.2: Subject Dosing Compliance 
Treatment Arm 
(Page xx of yy) 
 
 _____________________________________________________________________________________________________________________________________ 
                                                                                                       
                                     F: Date of          Number                         Amount      
                                        First Dose       of Days      Calculated1       of Study      
                                     L: Date of            of          Number of         Drug        Percent                   
 Subject    Age/Sex    Eval             Last Dose       Exposure      Applications      Used (g)     Compliant      Compliant?²   
 _____________________________________________________________________________________________________________________________________ 
 
 xxxxxx     xxxx       xxxxxxxxx     F: xxxxxxxxxx        xx             xx              xxxx        xxx            xxx         
                                     L: xxxxxxxxxx   
 
 xxxxxx     xxxx       xxxxxxxxx     F: xxxxxxxxxx        xx             xx              xxxx        xxx            xxx          
                                     L: xxxxxxxxxx   
 
 xxxxxx     xxxx       xxxxxxxxx     F: xxxxxxxxxx        xx             xx              xxxx        xxx            xxx          
                                     L: xxxxxxxxxx   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 _____________________________________________________________________________________________________________________________________ 
 ¹ The number of applications will be calculated by 
   2*(Date of Last Dose – Date of First Dose + 1) – (Number of Doses Missed) + (Number of Extra Doses). 
 ² A subject was considered compliant with the dosing regimen if the subject applied 80% to 120% of the total number of expected 
   doses during the treatment period. 
 SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing Format May Be Altered on Confirmation of Dosing Data Capture. 
                                                 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 0.03 
Date: DD MAY 2019 
     
Page 96 of 105 
CONFIDENTIAL 
Listing 16.2.5.3: Missed/Extra Doses 
Treatment Arm 
(Page xx of yy) 
 
 _____________________________________________________________________________________________________________________________________ 
  
                                                                 Treatment       Date of Missed/        Number of         Number of 
 Subject      Age/Sex     Eval            Date of First Dose     Ear(s)          Extra Dose             Missed Doses      Extra Doses 
 _____________________________________________________________________________________________________________________________________ 
 
 xxxxxx       xxxx        xxxxxxxxx       xxxxxxxxxx             xxxx            xxxxxxxxxx                 x                       
 
 
 xxxxxx       xxxx        xxxxxxxxx       xxxxxxxxxx             xxxxx           xxxxxxxxxx                                    x              
                                                                 xxxx            xxxxxxxxxx                 x                 
 
 
 xxxxxx       xxxx        xxxxxxxxx       xxxxxxxxxx             xxxx            xxxxxxxxxx                 x                         
                                                                 xxxx            xxxxxxxxxx                 x                
                                                                 xxxx            xxxxxxxxxx                                    x 
                                          
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 _____________________________________________________________________________________________________________________________________ 
 SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 0.03 
Date: DD MAY 2019 
     
Page 97 of 105 
CONFIDENTIAL 
Listing 16.2.5.4: Study Drug Dispensing and Return 
Treatment Arm 
(Page xx of yy) 
 
 _____________________________________________________________________________________________________________________________________  
                                    
                                    Kit         Bottle     Date            Dispense                 Return         Return      
 Subject   Age/Sex    Eval          Number      Number     Dispensed       Weight                   Date           Weight      
 _____________________________________________________________________________________________________________________________________ 
 
 xxxxxx    xxxx       xxxxxxxxx     xxxxx         x        xxxxxxxxxx      xxx                      xxxxxxxxxx     xxx xxxx               
 
 xxxxxx    xxxx       xxxxxxxxx     xxxxx         x        xxxxxxxxxx      xxxxx                    xxxxxxxxxx     xxxxx 
 
 xxxxxx    xxxx       xxxxxxxxx     xxxxx         x        xxxxxxxxxx      xxxxx                    xxxxxxxxxx     xxxxx 
 
 xxxxxx    xxxx       xxxxxxxxx     xxxxx         x        xxxxxxxxxx      xxxxx                    xxxxxxxxxx     xxxxx 
 
 xxxxxx    xxxx       xxxxxxxxx     xxxxx         x        xxxxxxxxxx      xxxxx                    xxxxxxxxxx     xxxxxx 
 
 xxxxxx    xxxx       xxxxxxxxx     xxxxx         x        xxxxxxxxxx      xxx                      xxxxxxxxxx     xxx xxxx    
 
 xxxxxx    xxxx       xxxxxxxxx     xxxxx         x        xxxxxxxxxx      xxxxx                    xxxxxxxxxx     xxxxx 
 
 xxxxxx    xxxx       xxxxxxxxx     xxxxx         x        xxxxxxxxxx      xxxxx                    xxxxxxxxxx     xxxxx 
 
 xxxxxx    xxxx       xxxxxxxxx     xxxxx         x        xxxxxxxxxx      xxxxx                    xxxxxxxxxx     xxxxx 
 
 xxxxxx    xxxx       xxxxxxxxx     xxxxx         x        xxxxxxxxxx      xxxxx                    xxxxxxxxxx     xxxxxx 
 
 
 
 
 
 
 
 
 
 
 _____________________________________________________________________________________________________________________________________ 
 SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 0.03 
Date: DD MAY 2019 
     
Page 98 of 105 
CONFIDENTIAL 
 
Listing 16.2.6.1: Otomycosis Signs and Symptoms 
Treatment Arm 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
S: Subject 
A: Age/Sex         V: Visit                         Investigator                                        Presence of                  
E: Eval            D: Date          Assesor         Initals         Ear        Pruritus     Debris      Fungal Elements     Pain       
______________________________________________________________________________________________________________________________________ 
   
S: xxxxxx          V: xxxxxxxxxx    xxxxxxx                         xxxx       xxxxxxxx     
A: xxxx            D: xxxxxxxxxx                 
E: xxxxxxxxx        
                   V: xxx xx        xxxxxxxxxxxx    xxx             xxxx       xxxxxxxx     xxxxxxxx    xxxxxx              xxxxxxxx 
                   D: xxxxxxxxxx    
    
                   V: xxx xx        xxxxxxxxxxxx    xxx             xxxx       xxxxxxxx     xxxxxxxx    xxxxxx              xxxxxxxx 
                   D: xxxxxxxxxx 
 
 
S: xxxxxx          V: xxxxxxxxxx    xxxxxxx                         xxxx       xxxxxxxx     
A: xxxx            D: xxxxxxxxxx                 
E: xxxxxxxxx        
                   V: xxx xx        xxxxxxxxxxxx    xxx             xxxx       xxxxxxxx     xxxxxxxx    xxxxxx              xxxxxxxx 
                   D: xxxxxxxxxx    
    
                   V: xxx xx        xxxxxxxxxxxx    xxx             xxxx       xxxxxxxx     xxxxxxxx    xxxxxx              xxxxxxxx 
                   D: xxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 0.03 
Date: DD MAY 2019 
     
Page 99 of 105 
CONFIDENTIAL 
Listing 16.2.6.2: Subject Global Assessment 
Treatment Arm 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
Subject          Age/Sex             Eval                  Date             Visit          Ear       Subject Global Assessment 
______________________________________________________________________________________________________________________________________ 
   
xxxxxx           xxxxx               xxxxxxxxxxxxx         xxxxxxxxxx       xxxxxxxx       xxxx      x x xxxxxxxx          
                                                                                           xxxxx     x x xxxxxxxx  
                                                           xxxxxxxxxx       xxxxxxxx       xxxx      x x xxxxxxxx  
                                                                                           xxxxx     x x xxxxxxxx  
                                                           xxxxxxxxxx       xxx xx         xxxx      x x xxxxxxxx  
                                                                                           xxxxx     x x xxxxxxxx 
                                                           xxxxxxxxxx       xxx xx         xxxx      x x xxxxxxxx  
                                                                                           xxxxx     x x xxxxxxxx 
 
xxxxxx           xxxxx               xxxxxxxxxxxxx         xxxxxxxxxx       xxxxxxxx       xxxx      x x xxxxxxxx          
                                                                                           xxxxx     x x xxxxxxxx  
                                                           xxxxxxxxxx       xxxxxxxx       xxxx      x x xxxxxxxx  
                                                                                           xxxxx     x x xxxxxxxx  
                                                           xxxxxxxxxx       xxx xx         xxxx      x x xxxxxxxx  
                                                                                           xxxxx     x x xxxxxxxx 
                                                           xxxxxxxxxx       xxx xx         xxxx      x x xxxxxxxx  
                                                                                           xxxxx     x x xxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 
 
 
 
                  
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 0.03 
Date: DD MAY 2019 
     
Page 100 of 105 
CONFIDENTIAL 
Listing 16.2.7.2.1: Unique Adverse Events Coded to MedDRA System Organ Classes and Preferred Terms 
(Page xx of yy) 
 
 _____________________________________________________________________________________________________________________________________ 
 
 MedDRA System Organ Class                    MedDRA Preferred Term                        Adverse Event 
 _____________________________________________________________________________________________________________________________________ 
 
 xxxxx xxxxx xxxxx                            xxxxx xxxxx xxxxx                            xxxxxxxxxx 
 
                                                                                           xxxxxxxx xxxxxxxx xxxxxxxxxxx 
 
                                                                                           xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxxxx 
 
 
                                              xxxxx xxxxx xxxxx                            xxxxxxxxxx 
 
                                                                                           xxxxxxxx xxxxxxxx xxxxxxxxxxx 
 
                                                                                           xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxxxx 
 
                                                                                            
                                              xxxxxxxxxx                                   xxxxx xxxxx xxxxx                             
 
                                                                                           xxxxxxxx xxxxxxxx xxxxxxxxxxx 
 
                                                                                           xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 _____________________________________________________________________________________________________________________________________ 
 Note: System Organ Class and Preferred Term map to MedDRA (Version 20.1). 
 SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by MedDRA System Organ Class, Preferred Term, and Adverse Event. 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 0.03 
Date: DD MAY 2019 
     
Page 101 of 105 
CONFIDENTIAL 
Listing 16.2.7.2.2: Pre-Treatment Adverse Events 
Treatment Arm 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
                                                                            E: Occur on the Ear                                                 
                                                                            D: Occur at Dosing Site                
                 A: Adverse Event             F: Date of First Dose         S: Severity                    S: Serious            
S: Subject          Description               S: Start Date (Day)¹          R: Relationship to             A: Action Taken 
A: Age/Sex       C: System Organ Class        E: End Date (Day)¹               Study Drug                  T: Other Action                    
E: Eval          P: Preferred Term            B: When Did The AE Begin      O: Outcome                     D: Cause Discontinuation 
______________________________________________________________________________________________________________________________________ 
 
S: xxxxxx        A: xxxxxxxxxxxxxxx           F: xxxxxxxxxx                 E: xxxxxxxx xxx xxx xxxxx xx   S: xx 
A: xxxx          C: xxxxxxxxxxxxxxx           S: xxxxxxxxxx                    xx xxx xxxx                 A: xxxx xxx xxxxxxx 
E: xxxxxxxxx     P: xxxxxxxxxxxxxxx           E: xxxxxxxxxx                 D: xx                          T: xxxxxxxxxxx xxxxx xxxxx         
                                              B: xxxxxxxxxxx xxxxx          S: xxxxxxxx                    D: xx 
                                                 xxxx xx xxxxx xxxx         R: xxx xxxxxxxxx                
                                                                            O: xxxxxxxxxxxxxxxxxx      
                                                                               xxxx xxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
Note: System Organ Class and Preferred Term map to MedDRA (Version 20.1). 
¹ Day is calculated as date – date of first dose for dates prior to first dose.  Otherwise, day is calculated as 
  date – date of first dose + 1 for dates on or after first dose. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Start Date, End Date, and Adverse Event Description. 
 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 0.03 
Date: DD MAY 2019 
     
Page 102 of 105 
CONFIDENTIAL 
Listing 16.2.7.2.3: Treatment-Emergent Adverse Events 
Treatment Arm 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
                                                                            E: Occur on the Ear                                                 
                                                                            D: Occur at Dosing Site                
                 A: Adverse Event             F: Date of First Dose         S: Severity                    S: Serious            
S: Subject          Description               S: Start Date (Day)¹          R: Relationship to             A: Action Taken 
A: Age/Sex       C: System Organ Class        E: End Date (Day)¹               Study Drug                  T: Other Action                    
E: Eval          P: Preferred Term            B: When Did The AE Begin      O: Outcome                     D: Cause Discontinuation 
______________________________________________________________________________________________________________________________________ 
 
S: xxxxxx        A: xxxxxxxxxxxxxxx           F: xxxxxxxxxx                 E: xxxxxxxx xxx xxx xxxxx xx   S: xx 
A: xxxx          C: xxxxxxxxxxxxxxx           S: xxxxxxxxxx                    xx xxx xxxx                 A: xxxx xxx xxxxxxx 
E: xxxxxxxxx     P: xxxxxxxxxxxxxxx           E: xxxxxxxxxx                 D: xx                          T: xxxxxxxxxxx xxxxx xxxxx         
                                              B: xxxxxxxxxxx xxxxx          S: xxxxxxxx                    D: xx 
                                                 xxxx xx xxxxx xxxx         R: xxx xxxxxxxxx                
                                                                            O: xxxxxxxxxxxxxxxxxx      
                                                                               xxxx xxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
Note: System Organ Class and Preferred Term map to MedDRA (Version 20.1). 
¹ Day is calculated as date – date of first dose for dates prior to first dose.  Otherwise, day is calculated as 
  date – date of first dose + 1 for dates on or after first dose. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Start Date, End Date, and Adverse Event Description. 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 0.03 
Date: DD MAY 2019 
     
Page 103 of 105 
CONFIDENTIAL 
Listing 16.2.7.2.4: Serious Adverse Events 
Treatment Arm 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
                                                                            E: Occur on the Ear                                                 
                                                                            D: Occur at Dosing Site                
                 A: Adverse Event             F: Date of First Dose         S: Severity                    S: Serious            
S: Subject          Description               S: Start Date (Day)¹          R: Relationship to             A: Action Taken 
A: Age/Sex       C: System Organ Class        E: End Date (Day)¹               Study Drug                  T: Other Action                    
E: Eval          P: Preferred Term            B: When Did The AE Begin      O: Outcome                     D: Cause Discontinuation 
______________________________________________________________________________________________________________________________________ 
 
S: xxxxxx        A: xxxxxxxxxxxxxxx           F: xxxxxxxxxx                 E: xxxxxxxx xxx xxx xxxxx xx   S: xxx 
A: xxxx          C: xxxxxxxxxxxxxxx           S: xxxxxxxxxx                    xx xxx xxxx                 A: xxxx xxx xxxxxxx 
E: xxxxxxxxx     P: xxxxxxxxxxxxxxx           E: xxxxxxxxxx                 D: xx                          T: xxxxxxxxxxx xxxxx xxxxx         
                                              B: xxxxxxxxxxx xxxxx          S: xxxxxxxx                    D: xx 
                                                 xxxx xx xxxxx xxxx         R: xxx xxxxxxxxx                
                                                                            O: xxxxxxxxxxxxxxxxxx      
                                                                               xxxx xxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
Note: System Organ Class and Preferred Term map to MedDRA (Version 20.1). 
¹ Day is calculated as date – date of first dose for dates prior to first dose.  Otherwise, day is calculated as 
  date – date of first dose + 1 for dates on or after first dose. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Start Date, End Date, and Adverse Event Description. 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 0.03 
Date: DD MAY 2019 
     
Page 104 of 105 
CONFIDENTIAL 
Listing 16.2.8.1.1: Urine Pregnancy Test Results 
Treatment Arm 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
  
 Subject     Age/Sex          Eval                   Visit                     Date                  Results     
______________________________________________________________________________________________________________________________________ 
 
 xxxxxx      xxxx             xxxxxxxxx              xxxxxxxxx                 xxxxxxxxxx           xxxxxxxx 
                                                     xxxxxxxxx                 xxxxxxxxxx           xxxxxxxx 
                                                     xxxxxx                    xxxxxxxxxx           xxxxxxxx 
                                                     xxxxxx                    xxxxxxxxxx           xxx xxxx             
                                                     xxxxxx                    xxxxxxxxxx           xxxxxxxx 
                                                     xxxxxxxxxxxxxx            xxxxxxxxxx           xxxxxxxx 
                              
 xxxxxx      xxxx             xxxxxxxxx              xxxxxxxxx                 xxxxxxxxxx           xxxxxxxx 
                                                     xxxxxxxx                  xxxxxxxxxx           xxxxxxxx 
                                                     xxxxxx                    xxxxxxxxxx           xxxxxxxx 
                                                     xxxxxx                    xxxxxxxxxx           xxxxxxxx 
                                                     xxxxxx                    xxxxxxxxxx           xxxxxxxx 
                                                     xxxxxxxxxxxxxx            xxxxxxxxxx           xxxxxxxx 
                              
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
Statistical Analysis Plan 
Hill Dermaceuticals, Inc. HD-MCZ-PHII-DRF062016 
Version: 0.03 
Date: DD MAY 2019 
     
Page 105 of 105 
CONFIDENTIAL 
Listing 16.2.8.2.1: Microbial Culture Results 
Treatment Arm 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
    
                                                                            
Subject       Age/Sex    Eval           Ear           Date            Visit                Culture Type     Results        
______________________________________________________________________________________________________________________________________ 
 
xxxxxx        xxxx       xxxxxxxxx      xxxxx         xxxxxxxxxx      xxxxxxxx             xxxxxx           xxxxx xxxxxxx xxxx xxxxx 
                                                                                           xxxxxxxx         xxxxx xxxxxxx xxxx 
                                                      xxxxxxxxxx      xxx xx xxxxxxxxx     xxxxxx           xx xxxxx xxxxxxxxx 
 
 
xxxxxx        xxxx       xxxxxxxxx      xxxxx         xxxxxxxxxx      xxxxxxxx             xxxxxxxxx        xxxxx xxxxxxx xxxx xxxxx 
                                                                                           xxxxxxxx         xxxxx xxxxxxx xxxx 
                                                      xxxxxxxxxx      xxx xx xxxxxxxxx     xxxxxxxxx        xxxxx xxxxxxx xxxx xxxxx 
                                                      xxxxxxxxxx      xxx xx xxxxxxxxx     xxxxxx           xx xxxxx xxxxxxxxx 
          
         
         
                              
 
 
 
 
 
 
 
 
 
 
 
 
 
 
                             
 
 
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Visit, Date, Category, and Lab Test.