Conditions: Chalazion
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 263
Healthy volunteers: no

Brief summary:
This protocol for SUN-131 1.5% TDS is developed for the treatment of chalazion. SUN-131 1.5% TDS is designed for local delivery of a corticosteroid, to the upper or lower eyelid. The purpose of this study is to evaluate the efficacy and safety of SUN-131 1.5% TDS as compared with placebo TDS in the treatment of a chalazion.

Detailed description:

Arms:
arm 1: None arm 2: None

Interventions: intervention 1: SUN-131 1.5% TDS intervention 2: Placebo TDS
Intervention descriptions: intervention 1: SUN-131 1.5% TDS will be worn for 14 days intervention 2: No active substance; Placebo TDS will be worn each day for 14 days

Protocol document:
Prot_SAP_000.pdf: 
NCT03248440 
 
Protocol Number: SUN-131-03 
 
Study Title:  
A Multi-Center, Double-Masked, Randomized, Placebo-Controlled 
Evaluation of the Safety and Efficacy of SUN 131 Transdermal System 
(TDS) as Compared to Placebo TDS in Patients with a Chalazion 
 
Protocol Version & Date: Version 2.0: 30 Aug 2018 


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CLINICAL STUDY PROTOCOL 
 
Study Title: 
A Multi-Center, Double-Masked, Randomized, Placebo-
Controlled Evaluation of the Safety and Efficacy of 
SUN-131 Transdermal System (TDS) as Compared to 
Placebo TDS in Patients with a Chalazion 
Protocol Number: 
SUN-131-03 
Study Drug: 
SUN-131 1.5% TDS 
US IND Number: 
115225 
Indication: 
Treatment of a Chalazion 
Sponsor: 
Senju USA, Inc. 
Development Phase: 
Phase 3 
Sponsor's Responsible 
Medical Monitor: 
 
 
 
 
 
 
Contact Information: 
Senju USA, Inc. 
21700 Oxnard Street, Suite 1070  
Woodland Hills, CA 91367 
Phone: (818) 719-7190 
 
Protocol Version & Date: Version 2.0: 30 Aug 2018 
 
CONFIDENTIAL 
This is a Senju USA, Inc. document that contains confidential information. It is intended solely 
for the recipient clinical investigator(s) and must not be disclosed to any other party. This 
material may be used only for evaluating or conducting clinical investigations; any other 
proposed use requires written consent from Senju USA, Inc. 
 
 
 


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PROTOCOL APPROVAL PAGE 
 
Document Number: SUN-131-03 Protocol (SUN-131-03) 
Document Title:  
A Multi-Center, Double-Masked, Randomized, Placebo-Controlled 
Evaluation of the Safety and Efficacy of SUN-131 Transdermal 
System (TDS) as Compared to Placebo TDS in Patients with a 
Chalazion 
Protocol Version: 
Version 2.0 
Protocol Date: 
30 AUG 2018 
 
This protocol has been fully reviewed by the study sponsor, Senju USA, Inc., and has been 
approved by the sponsor. The following persons contributed to the writing and/or approval 
of this protocol: 
 
 
Signature: 
___________________________________________ Date: ______________ 
 
 
 
 
 
 
 
 
 
 
 
 
Signature: 
___________________________________________ Date: ______________ 
 
 
Takahiro Ogawa, PhD 
 
 
President 
 
 
Senju USA, Inc. 
 
 
 


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TABLE OF CONTENTS 
PROTOCOL APPROVAL PAGE ...............................................................................................2 
LIST OF TABLES .........................................................................................................................6 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ............................................7 
INVESTIGATOR STATEMENT ................................................................................................9 
SYNOPSIS ....................................................................................................................................11 
1 
INTRODUCTION............................................................................................................19 
1.1 
Phase 1 Clinical Evaluation of the SUN-131 TDS: ...............................................21 
1.2 
Phase 2 Clinical Evaluation of the SUN-131 TDS: ...............................................24 
2 
STUDY OBJECTIVES ....................................................................................................25 
3 
INVESTIGATIONAL PLAN .........................................................................................25 
3.1 
Overall Study Design and Plan ..............................................................................25 
3.2 
Rationale of the Study Design ...............................................................................26 
3.3 
Duration of Application Exposure .........................................................................27 
3.4 
Schedule of Assessments .......................................................................................27 
3.4.1 
Visit 1 (Screening /Baseline: Day 1) .....................................................27 
3.4.2 
Visits 2-3 (Treatment Period: Days 8 ± 1 and 15 ± 1) ..........................28 
3.4.3 
Telephone Contact (Follow-Up: Day 22 ± 3) .......................................29 
3.5 
Outcome Measures.................................................................................................29 
3.5.1 
Primary Outcome Measure ...................................................................29 
3.5.2 
Key Secondary Outcome Measures ......................................................29 
3.5.3 
Additional Secondary Outcome Measures ............................................30 
3.5.4 
Safety Analysis .....................................................................................30 
3.5.5 
Other Measures .....................................................................................31 
4 
DISCUSSION OF STUDY DESIGN ..............................................................................31 
4.1 
Selection of Study Population ................................................................................31 
4.1.1 
Inclusion Criteria ...................................................................................31 
4.1.2 
Exclusion Criteria..................................................................................33 
4.1.3 
Removal of Subjects from Treatment or Assessment ...........................34 
4.1.4 
Subject Identification ............................................................................35 
4.1.5 
Early Exit Procedures ............................................................................35 
4.2 
Treatments..............................................................................................................36 
4.2.1 
Treatments Administered ......................................................................36 
4.3 
Product Characteristics ..........................................................................................36 
4.3.1 
Storage and Labeling.............................................................................36 


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4.3.2 
Directions for Administration and Removal .........................................37 
4.4 
Method of Randomization and Treatment Assignment .........................................40 
4.4.1 
Selection of Dose Used in the Study .....................................................40 
4.4.2 
Masking .................................................................................................40 
4.5 
Prior Medication ....................................................................................................41 
4.6 
Concomitant Medications ......................................................................................41 
4.7 
Treatment Compliance ...........................................................................................42 
4.7.1 
Study Drug Accountability ...................................................................42 
4.7.2 
Return and Disposition of Clinical Supplies .........................................42 
4.8 
Dietary or Other Protocol Restrictions ..................................................................42 
5 
EFFICACY AND SAFETY VARIABLES ....................................................................43 
5.1 
Adverse Events (see Section 6)..............................................................................43 
5.2 
Ocular Safety Assessments ....................................................................................43 
5.3 
Skin Irritation Assessment (TDS Related Skin Irritation) .....................................44 
5.4 
Patch Adhesion Evaluation ....................................................................................44 
5.5 
Ocular and Skin Comfort Query ............................................................................44 
5.6 
Presence of a Chalazion .........................................................................................45 
5.7 
Size of the Chalazion .............................................................................................45 
5.8 
Erythema of the Chalazion.....................................................................................45 
5.9 
Pain Associated with Chalazion Assessment .........................................................46 
5.10 
Appropriateness of Measurements .........................................................................46 
5.11 
Primary Efficacy Variables ....................................................................................47 
5.12 
Secondary Efficacy Variables ................................................................................47 
5.13 
Drug Plasma Concentration Measurements ...........................................................47 
6 
ADVERSE EVENTS .......................................................................................................47 
6.1 
Serious Adverse Events .........................................................................................49 
7 
STATISTICAL METHODS AND DETERMINATION OF SAMPLE SIZE ...........51 
7.1 
Statistical and Analytical Plans ..............................................................................51 
7.1.1 
Analytical Populations ..........................................................................51 
7.1.2 
Analysis of Subject Disposition ............................................................52 
7.1.3 
Analysis of Demographic and Background Characteristics ..................52 
7.1.4 
Analysis of Study Medication Compliance and Exposure ....................52 
7.1.5 
Analysis of Efficacy ..............................................................................52 
7.1.6 
Analysis of Safety and Other Measures ................................................53 
7.1.7 
Determination of Sample Size ..............................................................54 
7.1.8 
Methods for Handling Missing Data .....................................................54 


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8 
ETHICS ............................................................................................................................54 
8.1 
Institutional Review Board or Ethics Committee ..................................................54 
8.2 
Ethical Conduct of Study .......................................................................................55 
8.3 
Subject Information and Informed Consent ...........................................................55 
9 
INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE ...................55 
10 
ELECTRONIC CASE REPORT FORMS AND SOURCE DOCUMENTS .............56 
11 
STUDY MONITORING AND AUDITING ..................................................................56 
12 
RETENTION OF RECORDS ........................................................................................57 
13 
DISCLOSURE OF DATA ...............................................................................................57 
14 
REFERENCES .................................................................................................................57 
 


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LIST OF TABLES 
Table 1: Schedule of Events ...........................................................................................................16 
Table 2: Dermal Response Scale (Draize) .....................................................................................44 
Table 3: Erythema of the Study Chalazion ....................................................................................45 
 
 
 


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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation 
Definition 
ADL 
Activities of Daily Living 
AE 
Adverse Event 
CFR 
Code of Federal Regulation 
CR 
Complete Response 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CTCAE 
Common Terminology Criteria for Adverse Events 
EC 
Ethics Committee 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
eDCF 
Electronic Data Clarification Form 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation  
IOP 
Intraocular Pressure 
IP 
Investigational Product 
IRB 
Institutional Review Board 
ITT 
Intent-to-Treat 
IUD 
Intrauterine Device 
IWRS 
Interactive Web-Based Response System 
LC/MS-MS 
Liquid Chromatography-Mass Spectrometry 
LLOQ 
Lower Limit of Quantification 
MAD 
Multiple Ascending Dose 
MKP-1 
Mitogen-Activated Protein Kinase Phosphatase-1 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
Modified Intent-to-Treat 
NCI 
National Cancer Institute 
PI 
Principal Investigator 


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Abbreviation 
Definition 
PP 
Per-Protocol 
PRO 
Patient Reported Outcome 
REB 
Research Ethics Board 
SAD 
Single Application Dose 
SAE 
Serious Adverse Event 
SoC 
Standard of Care 
SOC 
System Organ Class 
TDS 
Transdermal System 
TEAE 
Treatment Emergent Adverse Event 
US 
United States 
VA 
Visual Acuity 
VAS 
Visual Analog Scale 
WHO 
World Health Organization 
 
 
 


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INVESTIGATOR STATEMENT 
I have read and understand the protocol and agree to implement the study in accordance with the 
procedures set forth in the protocol and in accordance with the sponsor's guidelines, all 
applicable government regulations, and the International Council for Harmonisation Good 
Clinical Practice Guidelines E6 (ICH GCP). 
I will maintain accurate source documents from which data are entered onto electronic case 
report forms and accurate drug accountability records that show the receipt and disposition of all 
study drugs. 
I will provide adequate protocol training to my associates, colleagues, and employees assisting in 
the conduct of the study.  
I will obtain Institutional Review Board/Ethics Committee (IRB/EC) approval of the protocol 
and Informed Consent Form (ICF) prior to enrollment of subjects in the study. I understand that 
any modifications to the protocol made during the course of the study must first be approved by 
the IRB/EC prior to implementation except when such modification is made to remove an 
immediate hazard to the subject. 
I will ensure that a fully executed IRB approved ICF is obtained from each subject prior to 
initiation of any study procedures.  
I will report (within 24 hours) any serious adverse event (SAE), regardless of relationship to 
study drug, or pregnancy that occurs during the course of the study, in accordance with the 
procedures described in Section 6 of the protocol. I will notify the sponsor if I become aware that 
a partner of a study subject becomes pregnant while the subject was receiving this study drug. 
I will submit all protocol inclusion/exclusion violations to the medical monitor for approval prior 
to enrollment of the subject in the study. 
I will allow the sponsor, Senju USA, Inc. and its agents, as well as the United States (US) Food 
and Drug Administration (FDA) and other regulatory agencies to inspect study facilities and 
pertinent records at reasonable times and in a reasonable manner, ensuring subject 
confidentiality. If I am notified that this study is to be inspected by a regulatory agency, I will 
notify the sponsor as soon as possible thereafter (no later than 1 week). 
This protocol contains information that is proprietary to Senju USA, Inc. The information 
contained herein is provided for the purpose of conducting a clinical trial for Senju USA, Inc. 
The contents of this protocol may be disclosed to study personnel under your supervision and to 
your IRB/EC. The contents of this protocol may not be disclosed to any other parties (unless 
such disclosure is required by government regulations or laws) without the prior written approval 
of Senju USA, Inc. 


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__________________________________________ 
_______________________ 
Investigator’s Signature 
 
 
 
 
Date 
 


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SYNOPSIS 
Study Title 
(Protocol 
Number) 
A Multi-Center, Double-Masked, Randomized, Placebo-Controlled Evaluation of 
the Safety and Efficacy of SUN-131 Transdermal System (TDS) as Compared to 
Placebo TDS in Patients with a Chalazion (SUN-131-03) 
Phase 
Phase 3 
Study Drug 
SUN-131 1.5% TDS 
Objectives 
To evaluate the efficacy and safety of SUN-131 1.5% TDS as compared with placebo 
TDS in the treatment of chalazion 
Study Design 
This is a prospective multi-center, double-masked, randomized, placebo-controlled 
clinical trial. Subjects will be centrally randomly assigned in a 1:1 ratio to receive 
one of the following treatments in the affected eyelid: 
SUN-131 1.5% TDS (n = 130) 
Placebo TDS (n = 130) 
The randomization will be stratified by age group (<12 years, ≥12 years). All study 
drug will be worn for a minimum of 16 hours and a maximum of 24 hours each day 
for 14 days.  
The following items will be assessed at screening/baseline and at 30 minutes to 
1 hour after patch removal on Days 8 ± 1 and 15 ± 1. 
• 
Presence of a chalazion by examination (clinical assessment) 
• 
 
• 
Erythema of the chalazion site itself as measured by a 5-point scale (0 = no 
sign of erythema, 1 = slight erythema, 2 = mild erythema, 3 = moderate 
erythema, 4 = severe erythema) 
• 
Pain in study eyelid and eye of the study eyelid related to chalazion as 
measured by Visual Analog Scale (VAS) of 100 mm 
Patient Reported Outcome (PRO) will be assessed by a self-evaluation diary of 
chalazion (present or absent), completed daily by the subjects from Day 1 through 
Day 15 ± 1. 
Sample Size 
Approximately 260 subjects will be randomized. 
Study 
Population 
Male or female subjects aged ≥ 6 years with a chalazion 
Inclusion 
Criteria 
Subjects eligible to participate in the study must meet all of the following criteria: 
1. Subjects aged ≥ 6 years of either sex and of any race. 
2. Subjects with a diagnosis of a single chalazion with visible granuloma in the 
study eyelid. Study eyelid may be either an upper or lower eyelid. 
3. Subjects with a chalazion with the granuloma area (height x width) ≤ 36 mm2 
when measured by a caliper. 
4. Subjects with chalazion erythema score of ≥ 1 (as graded on a 5-point scale: 
0 = no erythema, 1 = slight erythema, 2 = mild erythema, 3 = moderate 
erythema, 4 = severe erythema). 
5. Chalazion intended for study treatment present for no more than 21 days based 
on patient history on Day 1. 
6. Normal eyelid function without active signs of eye/eyelid infection in either 
eye. 


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7. Must be willing and able to correctly apply and wear a transdermal patch to the 
eyelid for minimum of 16 hours and a maximum of 24 hours each day for the 
entire study treatment period, or have someone (guardian/caregiver) in the 
household who is willing and able to correctly apply a transdermal patch for the 
subject. 
8. Female subjects must be 1-year postmenopausal, surgically sterilized or, if of 
childbearing potential, must have a negative urine pregnancy test on Day 1, and 
must agree to use a method of contraception for the entire study period. 
Approved methods of contraception include: abstinence, oral contraceptives, an 
intrauterine device (IUD) with spermicide, a female condom with spermicide, a 
diaphragm with spermicide, a cervical cap with spermicide, use of a condom 
with spermicide by sexual partner or a sterile sexual partner. 
9. If male, subjects must be sterile or willing to use an approved method of 
contraception for the entire study period. Males must be willing to refrain from 
sperm donation for the entire study period. 
10. Are able and willing to attend all study visits and follow all study-related 
instructions. 
11. Have signed written informed consent before undergoing any study-related 
procedures and is willing to comply with all study procedures; or signed written 
consent from parent or legal guardian if the subject is a minor and signed 
written assent from subject, if appropriate. 
12. Avoid wearing contact lenses in the study eye or using any new facial cosmetic 
products during the study period. 
13. Avoid wearing any make-up, ointment, or moisturizer on the study eyelid where 
the study drug is applied (mascara on the eyelash is allowed) during the entire 
study period. 
14. Ability to reliably report symptoms. 
Exclusion 
Criteria 
Subjects who meet the following criteria are not eligible to participate in this study: 
1. Chalazion that has atypical features (a recurring chalazion at the same spot, 
abnormal surrounding lid tissue, associated loss of tissues). 
2. History of chalazion incision and curettage in study eyelid. 
3. Chalazion at the eyelid margin (≤ 2 mm distant from the edge of the study 
eyelid margin). 
4. Multiple chalazia in the study eyelid or in any non-study eyelid(s). A single 
chalazion in any non-study eyelid(s) is(are) allowed. 
5. Chalazion on the eyelid that was previously screen failed. Re-screening of the 
same subject is allowed only once. 
6. Chalazion on the same eyelid or the opposing eyelid (i.e. same side) of the 
eyelid which was previously enrolled.  Re-entry of the same subject is allowed 
only once. 
7. Active ocular or eyelid infection (bacterial, viral, or fungal), or condition in the 
study eye/eyelid that in the investigator’s opinion could affect the subject’s 
health or the study parameters. 
8. Presence of hordeolum in any one eyelid. 
9. An abnormal skin condition on the study eyelid region (e.g., eczema, psoriasis, 
atopic dermatitis, etc.) where the study drug will be applied. 
10. Intraocular pressure (IOP) greater than 22 mmHg in either eye. 
11. Diagnosed with glaucoma in either eye. 
12. History of steroid-induced elevation of IOP. 


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13. Use of systemic (intravenous, intramuscular, oral), ophthalmic, or 
dermatological corticosteroids or immunosuppressant within 4 weeks prior to 
Day 1 and throughout the study period. Inhalant, intranasal, intra-articular, and 
perianal steroids are permitted. 
14. Use of systemic or ophthalmic azithromycin in either eye within 5 weeks prior 
to Day 1 and throughout the study period, use of  other systemic or ophthalmic 
macrolides (e.g. erythromycin, clarithromycin, etc.) in either eye within 2 weeks 
prior to Day 1 and throughout the study period, and use of tetracyclines (e.g. 
tetracycline, doxycycline, etc.) in either eye within 2 weeks prior to Day 1 and 
throughout the study period.  
15. Use of periocular or intraocular corticosteroid injection or corticosteroid depot 
in either eye within 9 weeks prior to Day 1 and throughout the study period.  
16. Female subjects who are pregnant or lactating. 
17. Known allergy or sensitization to the test article or any formulation 
components. 
18. History or evidence of ocular surgery in either eye or eyelid within the past 
3 months. 
19. History of refractive surgery in either eye within the past 6 months.  
20. Planned surgery (ocular in either eye or eyelid or systemic) during the entire 
study period. 
21. Participation in an investigational study within 30 days prior to Day 1. 
22. Have any ocular condition in either eye that requires chronic use of topical 
ophthalmic medication (e.g., glaucoma, dry eye, allergic conjunctivitis) with 
exception of over-the-counter artificial tears or lubricant eye drops, anti-
histamine drops, or that, in the investigator’s opinion, supports the safe use of 
the study drug. 
23. History of any previous functional or cosmetic eyelid surgery (including 
blepharopigmentation) in the study eyelid. 
24. Any other condition that, in the opinion of the investigator, renders the subject 
unsuitable for study participation. 
Dosage and 
Administration 
of Study Drug 
This study will consist of up to 3 visits and one telephone contact occurring over a 
maximum 25-day period. Subjects (or the caregiver) will apply the study drug on 
the study eyelid daily in the clinic or at home after completing training at the site. 
Subjects will keep the study drug on the eyelid for a minimum of 16 hours and a 
maximum of 24 hours each day for 14 days. Gently cleanse the study eyelid and 
allow it to dry for approximately 30 minutes before applying a new study drug. On 
Days 8 ± 1 and 15 ± 1, the study drug should not be replaced with to a new study 
drug in the morning of the visit to ensure the study drug is worn for a minimum of 
12 hours before removal by the investigator at the site. The subject may wear the 
study drug over 24 hours on these visit days if necessary. On Day 8 ± 1, subjects 
should apply a new study drug after completion of evaluations to ensure the study 
drug is worn for minimum of 16 hours on that day. The subject can then return to 
their normal schedule of study drug removal and replacement. Subjects will 
document time/date of each application and removal in the diary as well as any 
unusual events. 
Efficacy 
Measures 
The following items will be assessed at screening/baseline (Day 1), at 30 minutes to 
1 hour after patch removal on Days 8 ± 1, and 15 ± 1. 
• 
Presence of a chalazion by examination (clinical assessment) 
• 
 


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• 
Erythema of the chalazion site itself as measured by the 5-point scale 
• 
Pain in study eyelid and the eye of the study eyelid related to chalazion as 
measured by VAS of 100 mm 
PRO will be assessed by self-evaluation diary of chalazion (present or absent), 
completed daily by the subjects from Day 1 through Day 15 ± 1. 
Primary Outcome Measure: 
Signs (Objective) 
• 
Complete Response (CR) of the study chalazion by Day 15 ± 1. 
Complete response is defined as the absence of any significant clinical signs of a 
chalazion, based on clinical judgment by an investigator. Scarring or skin defects 
resulting from healing of the chalazion are possible and allowed upon CR. 
 
 
 
 
Additional Secondary Outcome Measures: 
Signs (Objective) 
• 
Change in size of the study chalazion from baseline to Days 8 ± 1 and 
15 ± 1. 
• 
Change in erythema of the study chalazion from baseline to Days 8 ± 1 and 
15 ± 1. 
Symptoms (Subjective) 
• 
Change in pain associated with the study chalazion in the study eye and 
eyelid assessed in VAS from baseline to Days 8 ± 1 and 15 ± 1. 
Safety Measures 
Adverse events (AEs) (observed or reported verbally or via diary) will be obtained 
following the first study drug application on Day 1 through Day 22 ± 3. 
The following assessments will be done in both eyes at baseline (pre-dose on Day 1), 
and after patch removal on Days 8 ± 1 and 15 ± 1. 
• 
Visual acuity (Snellen charts) 
• 
Slit-lamp biomicroscopy (lid, conjunctiva, cornea, anterior chamber and 
lens) 
• 
IOP measurement (Goldmann tonometer,Tono-Pen, or iCARE) 
Skin irritation of the TDS application site will be assessed in the study eyelid by the 
investigator at baseline (pre-dose on Day 1) and 30 minutes to 1 hour after patch 
removal by the study staff on Days 8 ± 1 and 15 ± 1 by using the 5-point Draize 
scale (0: No evidence of erythema, 1: Very slight erythema, 2: Well defined 
erythema, 3: Moderate to severe erythema, 4: Severe erythema [beet redness] to 
slight eschar formation [injuries in depth]). 


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Other Measures 
• 
Patch adhesion will be assessed by the investigator prior to patch removal on 
Days 8 ± 1 and 15 ± 1 in the study eyelid only. (0: ≥ 90% adhered, 1: ≥ 75% to 
< 90% adhered, 2: ≥ 50% to < 75% adhered, 3: < 50% adhered, 4: patch 
completely off the skin). 
• 
Ocular and skin comfort query of the eye of the study eyelid and the study 
eyelid (comfort from study drug application) as measured in VAS of 100 mm 
length are to be conducted at baseline (Day 1 prior to study drug application), 
and prior to patch removal on Days 8 ± 1 and 15 ± 1. 
• 
Residual drug content of the used study drug collected at the site on Days 8 ± 1 
and 15 ± 1 will be evaluated. 
Study Duration 
It is planned that each subject will participate in the study for a maximum of 25 days. 
Overall duration of the study will be approximately 10 months, depending on the rate 
of enrollment and number of subjects enrolled. 
Study Centers 
Up to 67 clinical sites 








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1 
INTRODUCTION 
A chalazion, also known as a Meibomian gland lipogranuloma, is a cyst in the eyelid that is 
caused by a blocked Meibomian gland, in the upper or lower eyelid, that causes an inflammatory 
response. The Meibomian glands are responsible for excreting sebum and meibum that help 
lubricate the skin, eyelash hairs, and eyes. Chalazia are generally subacute dermal inflammations 
that are often uncomfortable and in rare cases can cause astigmatism that may require surgical 
treatment. Clinical signs and symptoms of a chalazion include swelling on the eyelid, eyelid 
tenderness, and irritation to the eye. 
There are no current US FDA-approved products specifically to treat chalazion, however, typical 
treatments range from simple interventions, such as hot compresses, to more serious chalazion 
that require treatment with an injection of corticosteroid into edema or require surgical removal 
of the chalazion. Given no specific product is approved to target the chalazion in the eyelid 
subdermal region, off-label treatments with corticosteroid ophthalmic ointments and eye drops 
are common. These treatments often expose the eye to significant doses of corticosteroid and fail 
to adequately target the Meibomian gland, thus giving a less optimal effect and more risk of AEs 
like increase of IOP induced by steroid eye drops. 
The anti-inflammatory and immunosuppressive effects of glucocorticoids, such as 
 
, rely on several molecular mechanisms, that have been elucidated by basic research 
(1). Three main mechanisms include direct effects on gene expression by the binding of 
glucocorticoid receptors to glucocorticoid-responsive elements (i.e., the induction of annexin I 
and mitogen-activated protein kinase phosphatase 1 [MKP-1]), indirect effects on gene 
expression through the interactions of glucocorticoid receptors with other transcription factors 
(i.e., NF-kB and activator protein 1), and glucocorticoid receptor–mediated effects on second-
messenger cascades (i.e., the PI3K–Akt–eNOS pathway). Unfortunately, because some of these 
mechanisms are also involved in systemic physiologic signaling rather than inflammatory 
signaling, the therapeutic effects of systemic glucocorticoids in inflammation are often 
accompanied by clinically significant side effects when given in the systemic circulation. Given 
that the target indication is a chalazion, targeting the application of 
 to the 
site of inflammation is considered the most effective approach with the least potential for 
systemic or ocular side effects. 
The SUN-131 (
) TDS is designed for local delivery of a corticosteroid, 
, to the upper or lower eyelid. This TDS is specially engineered to gently 
adhere to the eyelid and is shaped to fit the contours of the eye. The backing and adhesives used 
are also designed to allow removal of the patch without causing irritation and to be flexible for 
adequate comfort. Thus, targeted local delivery of 
 to treat the chalazion 
can be achieved from this unique transdermal design without significant exposure of the active 
agent to the eye, as with ointment or drops. Thus, this is considered a dermal application of a 


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TDS to treat a local extra-ocular disease in the eyelid. The low local dose also will minimize any 
potential for systemic exposure and minimize exposure to the eye.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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1.1 
Phase 1 Clinical Evaluation of the SUN-131 TDS: 
The safety and performance of the SUN-131 TDS was assessed in a single-center, randomized, 
double-masked, placebo-controlled Phase 1 clinical trial that included 2 parts. Part 1 evaluated a 
single dose application of SUN-131 TDS at 3 concentrations to evaluate safety and tolerability as 
compared to placebo. Part 2 evaluated multiple-dose administration of 2 concentrations SUN-
131 TDS for 14 consecutive days as compared to placebo TDS. 
In Part 1, adult healthy subjects were randomly assigned to receive one of the following study 
drug doses on both upper and lower eyelids in the right or left eye: 
• SUN-131 0.2% TDS (n = 8) 
• SUN-131 0.7% TDS (n = 8) 
• SUN-131 1.5% TDS (n = 8) 
• Placebo TDS (contralateral eye for each subject, n = 24) 
Each subject was randomized to wear 2 active patches on the upper and lower eyelids of the right 
or left eye. Two placebo patches were worn on the upper and lower eyelid of the contralateral 
eye. Thus, a total of 4 patches were administered, with 2 active and 2 placebo patches on each 
eye. All patches were worn for 24 hours (e.g., 08:00 to 08:00 the following day). Given that 
clinically significant systemic levels of 
 were not expected after single 
application of the SUN-131 TDS, and the safety of topical clobetasol propionate creams with 
greater anticipated exposure did not lead to significant plasma levels, pharmacokinetic sampling 
was not conducted in this initial safety assessment. 
In Part 2 of the study, the 2 highest strength concentrations of the SUN-131 TDS (i.e. 0.7% and 
1.5%) were chosen for further evaluation through multiple-dose application. Adult healthy 
subjects were randomized to wear one active patch on either the upper or lower eyelid of the 
right or left eye daily for 14 days. A placebo patch was worn on the contralateral eyelid in the 
same location. The SUN-131 TDS concentrations planned for this study were: 
• SUN-131 0.7% TDS (n = 8) 
• SUN-131 1.5% TDS (n = 8) 


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• Placebo TDS (contralateral eye for each subject, n = 16) 
All patches were worn for 16 ± 2 hours (approximately 16:00 to 08:00 the following day). 
Subjects were retained in the clinic overnight on Days 1 and 14 of this study for evaluation and 
pharmacokinetic sampling. Subjects on Day 1 had their patches applied by trained study 
personnel at the site and they were instructed on the proper technique to apply the patch at home. 
Limited pharmacokinetic sampling was taken prior to dosing and approximately 8, 12, and 
16 hours after patch application on Days 1 and 2. On Day 14, the subject again had the patches 
applied by study personnel for the final day of evaluation and pharmacokinetic sampling. 
Pharmacokinetic sampling for Days 14 and 15 included plasma samples taken prior to dosing 
and approximately 8, 12, 16, and 24 hours after patch application. 
In Part 1 (single-application) of this study a total of 24 subjects enrolled and received study drug 
and were included in the safety analysis data set for the single application. All 24 subjects who 
initiated the scheduled single application in Part 1 completed the study and there were no missed 
doses of study medication. Eleven of the dosed subjects enrolled in the single application portion 
of this study (Part 1) were Black (11 of 24 subjects, 45.8%), 9 were White (9 of 24 subjects, 
37.5%), and 4 were Asian (4 of 24 subjects, 16.7%). Subjects ranged in age from 23 to 65 years. 
Among these subjects were 54.2% (13 of 24) were male and 45.8% (11 of 24) were female. 
In Part 2 of this study a total of 16 subjects enrolled and received study drug and were included 
in the safety analysis data set for repeated application. A total of 16 subjects who initiated the 
scheduled repeated application in Part 2 completed the study and there were no missed doses of 
study medication. Seven (7) of the dosed subjects enrolled in the repeated application portion of 
this study (Part 2) were Black (7 of 16 subjects, 43.8%), 7 were White (7 of 16 subjects, 43.8%), 
and 2 were Asian (2 of 16 subjects, 12.5%). Subjects ranged in age from 24 to 58 years. Among 
these subjects, 18.8% (3 of 16) were male and 81.3% (13 of 16) were female. There were no 
statistically significant imbalances in baseline characteristics across groups in the trial. 
In the SUN-131 0.7% TDS group most subjects (5 of 8) demonstrated systemic exposure to 
 below the limit of quantification (< 10.0 pg/mL) of the liquid 
chromatography-mass spectrometry (LC/MS-MS) bioanalytical method. One subject (R24103) 
had detectable, but low, levels of 
 in plasma after 12 hours (10.1 pg/mL) 
and 16 hours (13.5 pg/mL) on Day 1. Three subjects (R24101, R24103, and R24107) had 
detectable levels ranging from 10.5 pg/mL to 15.8 pg/mL on Day 14 with the peak plasma levels 
observed in all cases at 16 hours after patch application. 
In the SUN-131 1.5% TDS group, all subjects demonstrated at least low level systemic 
exposure to 
. Six (6) of 8 subjects had plasma levels of between 
10.1 and 19.1 pg/mL on Day 1 with the peak plasma levels usually occurring after 16 hours. Four 
(4) of 8 subjects (R25102, R25103, R25105, and R25107) had plasma levels between 11.0 and 
17.3 pg/mL on Day 14 with peak levels around 16 hours. One subject, who did not demonstrate 


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systemic levels of exposure through 16 hours on Day 14, demonstrated a low level of 
 
 exposure (10.5 pg/mL) at 24 hours after patch application on Day 14. 
The systemic exposure to 
 was very low throughout the study. While 
detectable levels of 
 (> 10.0 pg/mL) could be found, these levels generally 
were less than 20 pg/mL, which is approximately 30- to 790-fold lower than the exposure after 
application of 
 reported in the literature. There was no 
indication of accumulation with repeat application of the SUN-131 TDS. 
SUN-131 TDS exhibited excellent adhesion in both the single application and multiple 
application dose groups. In the multiple application dose groups where subjects self-administered 
the SUN-131 TDS at home for 12 of 14 days, of all patches administered there were 2 events 
(0.4% of patch applications) where there was complete patch detachment. This includes a fall-off 
of a placebo TDS on Day 2 and a SUN-131 0.7% TDS on Day 2. There were 5 events of slight 
lifting of the study drug (score 1: < 25%) reported, of which 4 of these events were in the 
placebo group. There were 2 event of moderate lifting (score 2: 25% to 50%) with one in the 
SUN-131 1.5% TDS group on Day 15 and one in the SUN-131 1.5% TDS group on Day 4. 
Overall, there were 224 applications of SUN-131 TDS in the multiple administration groups 
(Part 2) of which there was 1 event (0.45% of applications) of fall-off, 2 events (0.9% of 
applications) of moderate lifting (25% to 50% lifted), and 1 event (0.45% of applications) of 
slight lifting (< 25%) of the patch. In comparison, there were 224 applications of placebo TDS in 
the multiple administration groups (Part 2) of which there was 1 event (0.45% of applications) of 
fall-off and 4 events (1.8% of applications) of slight lifting (< 25%) of the placebo patch. 
Overall, 1 of 24 subjects (4.2%) in the single application treatment portion of the trial (Part 1) 
reported at least 1 treatment emergent adverse event (TEAE). The TEAE was considered mild 
(1 event, 4.2%) in severity. No subjects experienced TEAEs that were considered at least 
possibly treatment-related by the investigator. The highest percentage of subject-reported TEAEs 
was classified in the Medical Dictionary for Regulatory Activities (MedDRA) System Organ 
Class (SOC) of Eye disorders (4.2%). 
Across treatment groups in the single application portion of the study (Part 1), the highest 
percentage of TEAEs were in the SUN-131 0.2% TDS (1 subject, 12.5%). There were no 
subjects who experienced a TEAE that was considered even possibly related to study medication. 
There were no TEAEs that were severe and no SAEs occurred in the single application portion of 
the study. 
Overall, 3 of 16 subjects (18.8%) in the repeated application treatment groups reported at least 
1 TEAE. There was a total of 5 TEAEs reports in the 3 subjects who experienced an event. A 
total of 1 of 16 subjects (6.3%) experienced a TEAE (eye pain) that was considered at least 
possibly treatment-related by the investigator. The highest percentage of subjects reported 
TEAEs classified in the SOC of Nervous system disorders (3 events of headache: 18.8%), 


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followed by Eye disorders (1 event of eye pain: 6.3%) and Musculoskeletal and connective tissue 
disorders (1 event of neck pain: 6.3%). 
Across treatment groups in the repeated application, the highest percentage of TEAEs were in 
the SUN-131 0.7% TDS group (2 subjects, 25.0%), and the SUN-131 1.5% TDS group 
(1 subject, 12.5%). 
Among events that were considered at least possibly related in the repeated application 
treatment, there was 1 subject (6.3%) who experienced a related TEAE (eye pain) in the 
SUN-131 0.7% TDS group. There were no events in the SUN-131 1.5% TDS group that were 
considered possibly related to study medication. There were no TEAEs that were severe and no 
SAEs occurred in the single application portion of the study. 
There were no notable findings or changes in safety assessments including visual acuity (VA), 
slit-lamp biomicroscopy, IOP, skin irritation, or tolerability assessed by ocular and skin comfort 
questionnaires. 
Overall, the SUN-131 TDS appeared to deliver adequate drug amounts to the eyelid without 
notable side effects, skin irritation, skin discomfort or other safety concerns. The performance of 
the SUN-131 TDS with regards to adhesion and drug delivery was considered excellent. The 
systemic exposure to 
 was well below levels considered safe after 
administration of topical 
  
1.2 
Phase 2 Clinical Evaluation of the SUN-131 TDS: 
Senju has more recently completed a Phase 2, multi-center, randomized, placebo-controlled 
clinical trial in adult subjects with a chalazion. Subjects were randomly assigned to receive either 
SUN-131 1.5% TDS or placebo TDS in a 1:1 ratio. All patches were worn for 16 ± 4 hours each 
day for 21 days. A total of 69 subjects were enrolled in the trial and 58 completed the trial. There 
were 11 subjects, 6 in the SUN-131 1.5% TDS group and 5 in the placebo TDS group, who 
discontinued the study for non-safety-related reasons. Of the 69 subjects enrolled, 68 received 
either the SUN-131 1.5 % TDS or the placebo TDS and thus were evaluable for safety. A total of 
35 subjects received at least one dose of active SUN-131 1.5% TDS, of which 29 subjects 
completed the study with all doses through Day 21. A total of 33 subjects received at least one 
dose of placebo TDS of which 29 subjects completed the study with all doses through Day 21. 
Overall, the safety of the SUN-131 1.5% TDS was excellent with no clinically meaningful 
product-related adverse effects. There were no notable changes in VA, slit-lamp biomicroscopy, 
IOP, skin irritation or ocular and skin discomfort. Twenty-four (24) of 68 subjects (35.3%) 
experienced at least 1 TEAE in the study. Eight (8) subjects (11.8%) experienced TEAEs that 
were considered treatment-related by the investigator. The most frequently experienced TEAEs 
overall in the study were chalazion (3 subjects; 4.4%) and eye pruritus (3 subjects, 4.4%). Thus, 
the SUN-131 1.5% TDS demonstrated a good safety profile for the intended indication. 


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2 
STUDY OBJECTIVES 
To evaluate the efficacy and safety of SUN-131 1.5% TDS as compared with placebo TDS in the 
treatment of chalazion based on the proportion of subjects who have CR. Complete response is 
defined as the absence of any significant clinical signs of a chalazion, based on clinical judgment 
by an investigator, with possible scarring or skin defects resulting from healing of the chalazion 
allowed. 
3 
INVESTIGATIONAL PLAN 
3.1 
Overall Study Design and Plan 
This is a multi-center, double-masked, randomized, placebo-controlled evaluation of the safety 
and efficacy of SUN-131 1.5% TDS as compared to placebo TDS in subjects with a chalazion. 
Subjects who may be enrolled will have only one eyelid having a single chalazion with a single 
visible granuloma, and its size ≤ 36 mm2 and erythema scale score ≥ 1. 
Subjects meeting all inclusion and exclusion criteria will be centrally randomly assigned to 
receive one of the following treatments in the affected eyelid: 
• SUN-131 1.5% TDS (n = 130) 
• Placebo TDS (n = 130) 
The randomization will be stratified by age group (<12 years, ≥12 years). 
Subjects will be trained to apply the placebo TDS during screening. Subjects (or the 
guardian/caregiver) will apply the study drug on the study eyelid daily for 14 days. At baseline 
prior to application of the study drug, subjects will be assessed in both eyes for VA, slit-lamp 
biomicroscopy, IOP measurement, skin and ocular comfort query of the study eyelid and eye of 
the study eyelid, and skin irritation of study drug application site separate from the chalazion on 
the study eyelid. The chalazion site itself will also be assessed for erythema, pain related to the 


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chalazion, and the size of the chalazion by measuring the height and width of the chalazion with 
a caliper. A photograph of the chalazion at baseline will also be taken prior to first application of 
the study drug. 
On Day 1, the subject may apply the first study drug in the clinic or at home depending on the 
anticipated schedule for study drug application for the entire treatment period. On Days 8 ± 1 
and 15 ± 1, the study drug should not be replaced with a new study drug in the morning of the 
visit to ensure the study drug is worn for minimum of 12 hours before removal by the 
investigator at the site. The subject may wear the study drug over 24 hours on these visit days if 
necessary. On Day 8 ± 1, subjects should apply a new study drug after completion of evaluations 
to ensure the study drug is worn for minimum of 16 hours on that day. The subject can then 
return to their normal schedule of study drug removal and replacement.  
All subjects will return to the site on Days 8 ± 1 and 15 ± 1 for evaluations. Subjects should not 
remove their patch on Days 8 ± 1 and 15 ± 1 prior to the clinic visit. During these visits, the 
subject will complete the ocular/skin comfort query for the study eyelid and eye of the study 
eyelid prior to removal of the patch. The study drug will then be removed by the investigator to 
assess the level of skin irritation of the study eyelid associated with the study drug. Adverse 
events, concomitant medication use, and therapy are queried. Ocular safety examinations 
including VA, slit-lamp biomicroscopy, and IOP measurement will be performed in both eyes. A 
clinical evaluation will also be performed to determine if the chalazion is still present. If the 
chalazion is still present, the chalazion site will also be assessed for erythema of the chalazion 
site itself, pain related to the chalazion in the study eyelid and eye of the study eyelid, and the 
size of the chalazion by measuring the height and width of the chalazion with a caliper. Subjects 
will provide daily self-evaluation of the study chalazion from Day 1 through Day 15.  
On Day 22 ± 3, the subject will be contacted by telephone to obtain AEs and any concomitant 
medications and therapy taken since the last visit.  
There will be no safety data monitoring, nor any special steering or evaluation committees for 
this study. Data review and safety assessments will be conducted by the medical monitor 
periodically throughout the trial and at the study conclusion. 
3.2 
Rationale of the Study Design 
This is a prospective multi-center, double-masked, randomized, placebo-controlled clinical trial. 
Subjects will be centrally randomly assigned in 1:1 ratio to receive either a SUN-131 1.5% TDS 
or placebo TDS on the eyelid affected by the chalazion. The primary purpose of the study is to 
evaluate the efficacy and safety of the SUN-131 1.5% TDS as compared with placebo TDS in 
the treatment of chalazion. 


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The use of a placebo TDS as the control allows for the proper assessment of efficacy and any 
ocular or dermal irritation due to the study drug materials or adhesive, as opposed to the active 
SUN-131 1.5% TDS. 
3.3 
Duration of Application Exposure 
SUN-131 1.5% TDS or placebo TDS will be applied for a minimum of 16 hours and a maximum 
of 24 hours each day for 14 days. On Day 8 ± 1, subjects may apply a new study drug after 
completion of evaluations to ensure the study drug is worn for a minimum of 16 hours each day. 
On Days 8 ± 1 and 15 ± 1, the study drug should not be replaced with a new study drug in the 
morning of the visit to ensure the study drug is worn for a minimum of 12 hours before removal 
by the investigator at the site. The subject may wear the study drug over 24 hours on these visit 
days if necessary. On Day 8 ± 1, subjects should apply a new study drug after completion of 
evaluations to ensure the study drug is worn for minimum of 16 hours on that day. The subject 
can then return to their normal schedule of study drug removal and replacement. Dosing should 
not be discontinued unless there is an AE that warrants stopping treatment. If the absence of the 
chalazion is observed prior to Day 14, dosing should be continued until Day 14 to ensure 
complete resolution of the chalazion. Complete response is defined as the absence of any 
significant clinical signs of a chalazion with possible scarring or skin defects resulting from 
healing of the chalazion allowed. 
3.4 
Schedule of Assessments 
3.4.1 Visit 1 (Screening /Baseline: Day 1)  
Subjects will sign an ICF prior to any study-specific procedures (note: Standard of Care [SoC] 
assessments may be done prior to signing the ICF and incorporated into the study if within the 
allowed screening process). Where appropriate, study subjects who are < 18 years of age should 
assent to enroll in the study (with age of assent to be determined by the IRB and be consistent 
with local legal requirements). Demographics, medical and ocular history, and any concomitant 
medication and therapy use will be documented. The ocular history will include any previously 
diagnosed ophthalmic abnormalities and ocular surgeries (including laser procedures). The 
subject, if female, will be tested to confirm she is not pregnant using an in-house US FDA-
approved home urine pregnancy test. The presence of a chalazion will be confirmed as well as 
the size of the chalazion, erythema of the chalazion itself, and pain related to chalazion in the 
study eyelid and eye of the study eyelid as part of the screening procedure. A photograph of the 
chalazion at baseline will also be taken prior to first study drug application. Subjects will also be 
trained on study drug application at baseline to confirm their ability to apply the patch at home. 
Training with training patches should only be conducted on the non-study eyelids. When 
considering enrollment of younger children, and the chalazion is on the upper eyelid, the eyelid 
size with the eyes closed should be evaluated and ensure that the study drug can be applied 
securely.  


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Ocular safety examinations including VA, slit-lamp biomicroscopy, and IOP measurement in 
both eyes, skin irritation assessment of the skin around the chalazion, size of chalazion, erythema 
of the chalazion itself, pain related to chalazion, and ocular/skin comfort query of the study 
eyelid/eye will be obtained at baseline prior to the application of the first study drug. 
Concomitant medications will also be evaluated at baseline. Adverse events will be evaluated 
following the first study drug application on Day 1. First study drug application may be done at 
the site or by the subject/caregiver at home depending on the anticipated dosing schedule. 
Subjects meeting all inclusion criteria and none of the exclusion criteria will be enrolled into the 
study. Training will be conducted on study procedures and on the appropriate method to apply 
and remove the study drug. Subjects will be centrally randomly assigned in a 1:1 ratio to receive 
SUN-131 1.5% TDS or placebo TDS applied to the study eyelid affected by the chalazion. The 
randomization will be stratified by age group (<12 years, ≥12 years). Subjects will receive a 
1-week supply of study drug, including backup study drug, and be instructed to wear the study 
drug daily for a minimum of 16 hours and a maximum of 24 hours, and gently cleanse and wipe 
the study eyelid and to allow it to dry for approximately 30 minutes before applying a new study 
drug. 
Subjects will continue to apply the study drug each day on the study eyelid for the full treatment 
period. Subjects will record the time of study drug application, study drug removal, and any 
unusual events or patch adhesion issues in a daily subject diary, as well as any missed/fall-
off/misapplications. Subjects will keep all used and unused study drug in a provided container 
and return to the sites.  
3.4.2 Visits 2-3 (Treatment Period: Days 8 ± 1 and 15 ± 1) 
Subjects will return to the study site on Days 8 ± 1 and 15 ± 1 prior to removal of the patch from 
Days 7 ± 1 and 14 ± 1. On Days 8 ± 1 and 15 ± 1, the study drug should not be replaced with a 
new study drug in the morning of the visit to ensure the study drug is worn for a minimum of 12 
hours before removal by the investigator at the site. The subject may wear the study drug over 24 
hours on these visit days if necessary. On Day 8 ± 1, subjects should apply a new study drug 
after completion of evaluations to ensure the study drug is worn for a minimum of 16 hours on 
that day. The subject can then return to their normal schedule of study drug removal and 
replacement. Subjects will be queried for AEs and concomitant medication use and therapy. 
Study drug accountability is done by collecting all of the used and unused study drug and 
reviewing the subject diary. Prior to removal of the patch the investigator will evaluate the patch 
adhesion. The investigator will remove the study drug and assess the level of skin irritation of the 
eyelid where the study drug was placed, excluding the site of the chalazion. The removed study 
drug will be placed in a provided container and retained for collection by Senju. The subject will 
complete an ocular and skin comfort query of the study eyelid and eye of the study eyelid. 
Ocular examinations for safety will be performed in both eyes, including VA, slit-lamp 
biomicroscopy, and IOP measurement.  


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The investigator will also evaluate if the study chalazion is still present. If the study chalazion is 
still present, erythema associated with the chalazion site itself will be assessed, the subject will 
be asked to assess the pain associated with the chalazion, and the size of the chalazion will be 
evaluated (
). If the investigator judges that the chalazion is not present, 
other evaluations of chalazion (size, pain, and erythema) will not be not performed. Evaluation 
of the chalazion should be done by the same investigator as much as possible.  
Subjects will be provided with another 1-week supply of study drug including backup study drug 
on Day 8 ± 1. Subjects will return the subject diary on Day 15 ± 1. 
See the section on Early Exit Procedures in handling of early termination.  
3.4.3 Telephone Contact (Follow-Up: Day 22 ± 3) 
Subjects will be contacted by telephone on Day 22 ± 3 and will be queried for AEs and 
concomitant medication and therapy use.  
3.5 
Outcome Measures 
The following items will be assessed at screening/baseline (Day 1), and at 30 minutes and 1 hour 
after patch removal on Days 8 ± 1 and 15 ± 1. 
• Presence of a chalazion by examination (clinical assessment) 
 
• Erythema of the chalazion site itself 
• Pain related to chalazion in the study eyelid and eye of the study eyelid 
• Presence of a chalazion (daily patient reported outcome) 
3.5.1 Primary Outcome Measure 
• CR of the study chalazion by Day 15 ± 1. Complete response is defined as the absence of 
any significant clinical signs of a chalazion, based on clinical judgment by an 
investigator. Scarring or skin defects resulting from healing of the chalazion are possible 
and allowed upon CR. 
The assessment of CR should be done by the same investigator as much as possible.  
3.5.2 Key Secondary Outcome Measures 
 
 


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3.5.3 Additional Secondary Outcome Measures 
• Change in size of the chalazion from baseline to Days 8 ± 1 and 15 ± 1. Size of the 
chalazion will be assessed using a caliper provided for the study and measured as height 
and width in mm. 
 
See 
Section 5.7 for full-scale information. 
• Change in erythema of the study chalazion from baseline to Days 8 ± 1 and 15 ± 1. 
Erythema of the chalazion site itself will be assessed using a 5-point scale (i.e., 0 = no 
erythema to 4 = severe erythema). See Section 5.8 for full-scale information. 
• Change in pain associated with the study chalazion in the study eyelid and eye of the 
study eyelid assessed in VAS from baseline to Days 8 ± 1 and 15 ± 1. Pain associated 
with the chalazion in the study eye and eyelid will be assessed at baseline (pre-dose on 
Day 1), and on Days 8 ± 1 and 15 ± 1. Pain assessments will be done at the clinical site 
using a 100 mm VAS. See Section 5.9 for full-scale information. 
The assessment of the chalazion should be done by the same investigator as much as possible 
throughout the study period.  
3.5.4 Safety Analysis 
Safety assessments for this study include:  
• Adverse events (observed or reported verbally or via diary) will be obtained following 
first study drug application on Day 1 though the follow-up period on Day 22 ± 3. 
• Ocular safety: The following assessments will be done in both eyes at baseline (pre-dose 
on Day 1) and after patch removal on Days 8 ± 1 and 15 ± 1:  
o Visual acuity (Snellen chart) 
o Slit-lamp biomicroscopy (lid, conjunctiva, cornea, anterior chamber and lens) 
o IOP measurement (Goldmann tonometer,Tono-Pen, or iCARE) 
• Skin irritation (from study drug): Skin irritation of the study drug application site will be 
assessed by the investigator at baseline (pre-dose on Day 1), and after patch removal on 
Days 8 ± 1 and 15 ± 1. On Days 8 ± 1 and 15 ± 1 assessments will be conducted 
30 minutes to 1 hour after patch removal by the study staff in the clinic. Skin irritation is 
evaluated based on a 5 point Draize scale, where 0 = no evidence of erythema to 
4 = severe erythema (beet redness) to slight eschar formation (injuries in depth). See 
Section 5.3 for full details of the scale. Skin irritation should be assessed by the same 
investigator and the same time of the day throughout the study period as much as 
possible.  


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3.5.5 Other Measures 
• Tolerability: Ocular and skin comfort will be assessed in eye of the study eyelid and the 
study eyelid on Day 1 prior to study drug application and prior to patch removal on Days 
8 ± 1 and 15 ± 1 using the following scales (See Section 5.2 for full details). Subjects will 
be assessed the following questions: 
o Ocular comfort query in eye of the study eyelid (VAS with 0 mm = very 
comfortable and 100 mm = very uncomfortable) 
o Skin comfort query in the study eyelid (VAS with 0 mm = very comfortable and 
100 mm = very uncomfortable) 
• Patch adhesion: will be assessed in the study eyelid only prior to patch removal on Days 
8 ± 1 and 15 ± 1. Scale is provided in Section 5.4 and is scored as 0: ≥ 90% adhered, 
1: ≥ 75% to < 90% adhered, 2: ≥ 50% to < 75% adhered, 3: < 50% adhered, 4: patch 
detached (patch completely off the skin). This assessment should be done by the same 
investigator and at the same time of the day throughout the study period as much as 
possible.  
• Residual drug content: will be measured from the used study drug removed by the 
investigator and collected at the site on Days 8 ± 1 and 15 ± 1.  
4 
DISCUSSION OF STUDY DESIGN 
 
 
 
 
 
 
 
 
  
 
 
 
4.1 
Selection of Study Population 
Male or female subjects aged ≥ 6 years with a chalazion will be selected for this study.  
4.1.1 Inclusion Criteria 
Subjects eligible to participate in the study must meet all of the following criteria:  


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1. Subjects aged ≥ 6 years of either sex and of any race 
2. Subjects with a diagnosis of a single chalazion with visible granuloma in the study eyelid. 
Study eyelid may be either an upper or lower eyelid.  
3. Subjects with a chalazion with the granuloma area (height x width) ≤ 36 mm2 when 
measured by a caliper.  
4. Subjects with chalazion erythema score of ≥ 1 (as graded on a 5-point scale: 0 = no signs 
of erythema, 1 = slight erythema, 2 = mild erythema, 3 = moderate erythema, 4 = severe 
erythema). 
5. Chalazion intended for study treatment present for no more than 21 days based on patient 
history on Day 1.  
6. Normal eyelid function without active signs of eye and eyelid infection in either eye. 
7. Must be willing and able to correctly apply and wear a transdermal patch to the eyelid for 
minimum of 16 hours and maximum of 24 hours each day for the entire study treatment 
period, or have someone (guardian/caregiver) in the household who is willing and able to 
correctly apply the transdermal patch for the subject. 
8. Female subjects must be 1-year postmenopausal, surgically sterilized, or women of 
childbearing potential must have a negative urine pregnancy test on Day 1, and must 
agree to use a method of contraception for the entire study period. Approved methods of 
contraception include: abstinence, oral contraceptives, an IUD with spermicide, a female 
condom with spermicide, a diaphragm with spermicide, a cervical cap with spermicide, 
use of a condom with spermicide by sexual partner, or a sterile sexual partner.  
9. If male, subjects must be sterile or willing to use an approved method of contraception 
for the entire study period. Males must be willing to refrain from sperm donation for the 
entire study period.  
10. Are able and willing to attend all study visits and follow all study-related instructions. 
11. Have signed written informed consent before undergoing any study-related procedures 
and is willing to comply with all study procedures; or signed written consent from parent 
or legal guardian if the subject is a minor and signed written assent from subject, if 
appropriate.  
12. Avoid wearing contact lenses in the study eye or using any new facial cosmetic products 
during the study period.  
13. Avoid wearing any make-up, ointment, moisturizer on the study eyelid where the study 
drug is applied (mascara on the eyelash is allowed) during the entire study period.  
14. Ability to reliably report symptoms. 


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4.1.2 Exclusion Criteria 
Subjects who meet the following criteria are not eligible to participate in this study: 
1. Chalazion that has atypical features (a recurring chalazion at the same spot, abnormal 
surrounding lid tissue, associated loss of tissues). 
2. History of chalazion incision and curettage in study eyelid. 
3. Chalazion at the eyelid margin (≤ 2 mm distant from the edge of the study eyelid 
margin). 
4. Multiple chalazia in the study eyelid or in any non-study eyelid(s).  A single chalazion in 
any non-study eyelid(s) is(are) allowed. .  
5. Chalazion on an eyelid that was previously screen failed. Re-screening of the same 
subject is allowed only once.  
6. Chalazion on the opposing eyelid (i.e. same side) of an eyelid which was previously 
enrolled. Re-entry of the same subject is allowed only once. 
7. Active ocular or eyelid infection (bacterial, viral, or fungal), any ocular or eyelid 
condition in the study eyelid/eye of study eyelid that in the investigator’s opinion could 
affect the subject’s health or the study parameters. 
8. Presence of hordeolum in any one eyelid. 
9. An abnormal skin condition on the study eyelid region (e.g., eczema, psoriasis, atopic 
dermatitis, etc.) where the study drug will be applied. 
10. Intraocular pressure greater than 22 mmHg in either eye. 
11. Diagnosed with glaucoma in either eye. 
12. History of steroid-induced elevation of IOP. 
13. Use of systemic (intravenous, intramuscular, oral), ophthalmic, or dermatological 
corticosteroids or immunosuppressant within 4 weeks prior to Day 1 and throughout the 
study period. Inhalant, intranasal intra-articular, and perianal steroids are permitted.  
14. Use of systemic or ophthalmic azithromycin in either eye within 5 weeks prior to Day 1 
and throughout the study period, use of other systemic or ophthalmic macrolides (e.g. 
erythromycin, clarithromycin, etc.) in either eye within 2 weeks prior to Day 1 and 


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throughout the study period, and use of tetracyclines (e.g. tetracyclines, doxycyclines, 
etc.) in either eye within 2 weeks prior to Day 1 and throughout the study period. 
15. Use of periocular or intraocular corticosteroid injection or corticosteroid depot in either 
eye within 9 weeks prior to Day 1 and throughout the study period. 
16. Female subjects who are pregnant or lactating.  
17. Known allergy or sensitization to the test article or any formulation components. 
18. History or evidence of ocular surgery in either eye or eyelid within the past 3 months. 
19. History of refractive surgery in the either eye within the past 6 months.  
20. Planned surgery (ocular in either eye or eyelid or systemic) during the entire study 
period.  
21. Participation in an investigational study within 30 days prior to Day 1. 
22. Have any ocular condition in either eye that requires chronic use of topical ophthalmic 
medications (e.g., glaucoma, dry eye, allergic conjunctivitis) with exception of over-the-
counter artificial tears or lubricant eye drops, anti-histamine drops, or that, in the 
investigator’s opinion, supports the safe use of the study drug. 
23. History of any previous functional or cosmetic eyelid surgery (including 
blepharopigmentation) in the study eyelid. 
24. Any other condition that, in the opinion of the investigator, renders the subject unsuitable 
for study participation.  
4.1.3 Removal of Subjects from Treatment or Assessment 
Subjects may withdraw their consent to participate in this study at any time without prejudice. 
The investigator must withdraw from the study any subject who requests to be withdrawn. The 
medical monitor must be notified of all subject withdrawals within 24 hours by telephone 
or email.  
In addition, the investigator may withdraw a subject from the study for any of the following 
reasons: 
• A protocol violation occurs, 
• The subject is lost to follow-up, 
• A serious or intolerable AE occurs, or 
• The sponsor or investigator terminates the study. 


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The sponsor may withdraw a subject for noncompliance with use of study medication if they do 
not apply the study drug for a minimum of 16 hours and a maximum of 24 hours for at least 80% 
of the time required (or at least 5 days per week) and miss more than 2 of 7 days of application in 
the trial. Senju also reserves the right to discontinue the study at any time for either clinical or 
administrative reasons. 
If a subject fails to return for scheduled visits, a documented effort must be made to determine 
the reason. If the subject cannot be reached by telephone after 2 attempts, a certified letter should 
be sent to the subject (or the subject’s legally authorized representative, if appropriate) 
requesting contact with the investigator. Attempts to contact the subject should be documented in 
the study records. 
Prior to enrollment into the study, the investigator or designee must explain to each subject that 
the subject’s protected health information obtained during the study may be shared with the 
study sponsor, regulatory agencies, and the IRB or EC in order to analyze and evaluate study 
results. It is the investigator’s (or designee’s) responsibility to obtain written permission to use 
protected health information per country-specific regulations. If permission to use protected 
health information is withdrawn, it is the investigator’s responsibility to obtain a written request, 
as well as to ensure that no further data will be collected from the subject and the subject will be 
removed from the study. 
4.1.4 Subject Identification 
Each subject will be assigned a unique subject identifier. This unique identifier will be shown on 
all electronic Case Report Form (eCRF) pages within the Electronic Data Capture (EDC) system. 
4.1.5 Early Exit Procedures 
In the event of an early withdrawal of a subject the following procedures should be followed. 
• If voluntary withdrawal from the trial, the subject will be asked to complete all final visit 
assessments (Early Termination Visit Assessment). 
o If the subject does not agree and withdraws consent, only data up to the time that 
the subject has withdrawn consent may be used and no other assessments should 
be performed. If SoC evaluations are required for safety reasons these may be 
conducted with consent of the subject. 
o If the subject agrees to have assessments prior to exiting the study and 
withdrawing consent, the subject will receive all assessments listed in Early 
Termination of the Schedule of Events. 










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4.4 
Method of Randomization and Treatment Assignment 
Each subject who is entered into the study will be assigned a screening number. The screening 
number will consist of the 2-digit site number (##) and a 3-digit sequential number (XXX). The 
subject screening number (##-XXX) becomes the subject identifier.  
For subjects who meet the criteria for randomization, a treatment group randomization code will 
be assigned to that subject number via an Interactive Web Response System (IWRS). Subjects 
will then be centrally randomized in a 1:1 ratio to either SUN-131 1.5% TDS or placebo TDS. 
The randomization will be stratified by age group (<12 years, ≥12 years).  
Re-screening of the same subject that has previously screen failed is allowed only once. Re-entry 
of the same subject that was previously randomized is allowed only once. A new subject number 
will be issued when the same subject is re-screened or re-enrolled for the study.  
The study drug kit will be coded with a three-digit (YYY) kit number. After randomization on 
Day 1, the IWRS will assign a study drug kit to a subject. On Day 1, the subject will receive a 
1-week supply of study drug including backup study drug. On Day 8 ± 1, the subject will visit 
the site, return all used and unused study drug, and be provided with another 1-week supply of 
study drug including backup study drug. On Day 15 ± 1, the subject will visit the site and return 
used and unused study drug. 
4.4.1 Selection of Dose Used in the Study 
All subjects assigned to the active treatment group will apply SUN-131 1.5% TDS to the study 
eyelid with a chalazion. This concentration and dose was selected based on the preliminary 
Phase 1 and Phase 2 studies conducted (SUN-131-01, SUN-131-02) that demonstrated excellent 
safety and comfort at this concentration. This is the maximum concentration tested in Phase 1 
clinical trials. 
4.4.2 Masking 
Placebo TDS are manufactured to be the same patch weight and to be identical in appearance to 
the SUN-131 1.5% TDS, utilizing the same release liner, backing, and packaging components. 
Subjects will be assigned a study drug kit by the IWRS according to the randomization schedule. 
Investigators, subjects, and all study personnel (sites and sponsor) will be masked as to the 
identification of the active and placebo study drug. 
Procedures will be in place for unmasking and are to be utilized only in the event of emergency 
or life-threatening condition where the medical management would be dictated by knowing the 
treatment status of the subject. The randomization code will be provided through the IWRS. The 
reason for treatment unmasking should be clearly explained and justified in the eCRF. The date 
on which the code was broken together with the identity of the person responsible must be 


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documented. The investigator should immediately contact the medical monitor via phone before 
unmasking a subject, unless it is not possible to do so without risk to the subject. 
Subjects that are unmasked will be allowed to continue their participation in the study at the 
investigator’s discretion, but the data may be excluded from the per-protocol analyses. 
4.5 
Prior Medication 
On screening, site staff will review medication use to check for eligibility for the study. Use of 
medication listed below in the defined timeframe will exclude the subject from study 
participation. 
• Use of systemic (intravenous, intramuscular, oral), ophthalmic, dermatological 
corticosteroids or immunosuppressant within 4 weeks prior to Day 1 and throughout the 
study period. Inhalant, intranasal, intra-articular, and perianal steroids are permitted. 
• Use of systemic or ophthalmic azithromycin in either eye within 5 weeks prior to Day 1 
and throughout the study period. 
• Use of other systemic or ophthalmic macrolides (e.g. erythromycin, clarithromycin, etc.) 
in either eye within 2 weeks prior to Day 1 and throughout the study period. 
• Use of tetracyclines (e.g. tetracyclines, doxycycline, etc.) in either eye within 2 weeks 
prior to Day 1 and throughout the study period.  
• Use of periocular or intraocular corticosteroid injection or corticosteroid depot in either 
eye within 9 weeks prior to Day 1 and throughout the study period.  
4.6 
Concomitant Medications 
Subjects will be allowed to use over-the-counter artificial tears or lubricant eye drops, over-the- 
counter anti-histamine drops administered by instillation into either eye, during the study as well 
as use of fluorescein sodium and benoxinate hydrochloride solution products (used when 
measuring IOP). 
Use of periocular or intraocular (in either eye or eyelid), systemic (intravenous, intramuscular, 
oral), and dermatological corticosteroids during the study period will be prohibited. Inhalant, 
intranasal, intra-articular, and perianal steroids are permitted. 
Use of systemic or ophthalmicmacrolides and tetracyclines in either eye will be prohibited 
during the study period. 
Site staff will review ocular and non-ocular concomitant medication use at Visit 1 during subject 
screening. The use of any concurrent medication, prescription, or over-the-counter, will be 
recorded on the subject’s source document and corresponding CRF along with the reason the 
medication will be taken. 


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4.7 
Treatment Compliance 
In this study, treatment will consist of wearing a total of 14 study drug for a minimum of 16 
hours and maximum of 24 hours each day for 14 days. On Days 8 ± 1 and 15 ± 1, the study drug 
should not be replaced with a new study drug in the morning of the visit to ensure the study drug 
is worn for a minimum of 12 hours before removal by the investigator at the site. The subject 
may wear the study drug over 24 hours on these visit days if necessary. On Day 8 ± 1, subjects 
should apply a new study drug after completion of evaluations to ensure the study drug is worn 
for a minimum of 16 hours on that day. The subject can then return to their normal schedule of 
study drug removal and replacement. Subjects will record the time of application and time of 
removal of each study drug daily, any mis-application and fall-off as well as any unusual events 
in the electronic subject diary. Treatment compliance will also be assessed based on a subject 
diary, and all used and unused study drug returned at each visit. 
 
 
 
4.7.1 Study Drug Accountability 
The Principal Investigator (PI) or designee is responsible for maintaining accurate records 
(including dates and quantities) of study drug received, subjects to whom study drug is dispensed 
(subject-by-subject dose specific accounting), and study drug lost or accidentally or deliberately 
destroyed. The PI or designee must retain all unused or expired study supplies until a Senju-
designated Clinical Research Associate (CRA) has confirmed the accountability data. 
4.7.2 Return and Disposition of Clinical Supplies 
All used and unused study drug will be returned by the subjects and must be kept in a secure 
location for accountability and reconciliation by the Senju-designated CRA. The investigator or 
designee must provide an explanation for any destroyed or missing study drug or study materials. 
Used study drug and unused study drug returned by the subjects are reconciled by the site against 
the study drug application and removal diary completed by the subjects. The Senju-designated 
CRA must account for all study drugs in a formal reconciliation process prior to return of study 
drug to the drug depot. 
All study drug and related materials should be stored, inventoried, reconciled, and returned, 
according to applicable state and federal regulations and study procedures. 
4.8 
Dietary or Other Protocol Restrictions 
No dietary restrictions will be imposed on study subjects. 


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Subjects will be asked not to take any other treatments for the chalazion or apply warm 
compresses to the study eyelid while in the SUN-131-03 trial. Subjects will also be asked to 
avoid wearing contact lenses and new facial cosmetic products during the study trial period. 
Subjects will be asked to avoid wearing any make-up, ointment, or moisturizer on the study 
eyelid with mascara on the eyelashes allowed during the study period.  
5 
EFFICACY AND SAFETY VARIABLES 
5.1 
Adverse Events (see Section 6) 
For subjects who are experiencing ongoing unresolved and possibly related TEAEs at the time of 
study completion or early discontinuation from the study, it will be recommended that the 
investigator schedule an appropriate follow-up visit in order to determine the event outcome. If 
the outcome of the related TEAE cannot be determined during the follow-up visit, the 
investigator will make reasonable attempts to contact the subject via telephone, post, or certified 
mail for up to 30 days after study completion or early discontinuation from the study to assess 
the outcome of the event. Any additional data will be documented and made available to the 
sponsor. The sponsor medical monitor will determine when the data needs to be documented on 
the CRFs. 
5.2 
Ocular Safety Assessments 
All ocular safety evaluations will be performed on both subject eyes at baseline (pre-dose on 
Day 1) and after the study drug removal on Days 8 ± 1 and 15 ± 1. 
Intraocular pressure measurement (Goldmann applanation tonometry) should be done after the 
evaluations on chalazion and photography of chalazion and slit-lamp biomicroscopy evaluation 
are completed. All IOP pressure will be recorded in mmHg. To avoid IOP changes due to the 
diurnal rhythm, the IOP measurements should be performed at approximately the same time of 
the day on Days 1, 8 ± 1, and 15 ± 1. For subjects aged ≤ 12 years who have difficulty with 
Goldmann, Tono-Pen or iCARE may be used to measure IOP throughout the study. The same 
instrument should be used for measurement of the IOP for the study for each subject. 
Visual acuity evaluation will be performed at all study visits with Snellen eye chart at 20 feet (6 
meters). If the corrected or uncorrected VA is 20/40 or better, no additional refraction is 
necessary. If corrected or uncorrected VA is worse than 20/40, then an updated refraction must 
be performed. This refraction must be used for all VA assessments during the study. The subject 
must wear the same glasses, if applicable, at each visit. For subjects with surgical monovision 
correction, VA assessment may be conducted in the near vision eye with a near vision reading 
card held at approximately 14 inches from the subject’s eye. 


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5.3 
Skin Irritation Assessment (TDS Related Skin Irritation) 
The investigator will assess skin irritation of the site application area for the TDS separate from 
the area affected by the study chalazion (i.e., excluding the chalazion itself) on the study eyelid. 
This skin assessment of the surrounding area will be conducted at baseline (pre-dose on Day 1) 
and after the study drug removal on Days 8 ± 1 and 15 ± 1. On Days 8 ± 1 and 15 ± 1, 
assessments will be conducted approximately 30 minutes to 1 hour after study drug removal in 
the clinic. This evaluation should be done by the same investigator throughout the study period 
as much as possible. 
Table 2: Dermal Response Scale (Draize) 
Score 
Score Description 
0 
No evidence of erythema 
1 
Very slight erythema  
2 
Well defined erythema 
3 
Moderate to severe erythema 
4 
Severe erythema (beet redness) to slight eschar formation (injuries in depth) 
5.4 
Patch Adhesion Evaluation 
The patch adhesion will be evaluated by the investigator using the following 5-point scale prior 
to patch removal on Days 8 ± 1 and 15 ± 1 in the study eyelid only. This evaluation should be 
done by the same investigator throughout the study period as much as possible. 
0 = ≥90% adhered (essentially no lift off of the skin) 
1 = ≥ 75% to < 90% adhered (some edges only lifting off the skin) 
2 = ≥ 50% to < 75% adhered (less than half the system lifting off the skin)  
3 = < 50% adhered (more than half the system lifting off the skin without falling off)  
4 = patch detached (patch completely off the skin)  
5.5 
Ocular and Skin Comfort Query 
Subjects will be asked to assess the ocular and skin comfort query of the eye of the study eyelid 
and study eyelid prior to application of the first study drug at baseline (Day 1) and prior to patch 
removal on Days 8 ± 1 and 15 ± 1 using a subjective 100 mm Visual Analog Scale (VAS) where 
0 mm = very comfortable and 100 mm = very uncomfortable. There will be no descriptors for 
numbers other than 0 mm and 100 mm on the scale and meaning of the extreme ends of the 
scale. VAS scores will be collected electronically as part of the subject electronic diary. 


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5.6 
Presence of a Chalazion 
The presence or complete absence of a chalazion on the study eyelid will be evaluated by the 
investigator at each study visit at screening/baseline (Day 1), and at 30 minutes to 1 hour after 
patch removal on Days 8 ± 1 and 15 ± 1. Absence of a chalazion is determined by the 
investigator’s clinical judgment and may accompany scarring or skin defects resulting from 
healing of the chalazion. This evaluation should be done by the same investigator throughout the 
study period as much as possible.  
Subjects will also document in their subject electronic diary if the chalazion is still present or not 
daily from Day 1 through Day 15 ± 1.  
5.7 
Size of the Chalazion 
The size of the chalazion on the study eyelid will be evaluated by the investigator at each study 
visit at screening/baseline (Day 1), and at 30 minutes to 1 hour after patch removal on Days 8 ± 1 
and 15 ± 1. The size will be measured 
 
 
The size will not be 
evaluated on Days 8 ± 1 and 15 ± 1 if the study chalazion is determined to be absent. This 
evaluation should be done by the same investigator throughout the study period as much as 
possible.  
5.8 
Erythema of the Chalazion 
The investigator will assess erythema of the chalazion on the study eyelid at each study visit at 
screening/baseline (Day 1), and at 30 minutes to 1 hour after patch removal on Days 8 ± 1 and 
15 ± 1. The quantitative scale for this assessment is described below (Table 3). This evaluation 
should be done by the same investigator throughout the study period as much as possible.  
Table 3: Erythema of the Study Chalazion 
Score 
Score Description 
0 
No signs of erythema 
1 
Slight erythema 
2 
Mild erythema 
3 
Moderate erythema 
4 
Severe erythema 
 


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5.9 
Pain Associated with Chalazion Assessment 
Subjects will be asked to assess the pain associated with the chalazion using a VAS. The VAS 
will be specific for pain associated with the chalazion by asking the following questions: “How 
intense is your pain associated with the chalazion in your eyelid” and “How intense is your pain 
associated with the chalazion in your eye”. For each question, a 100 mm VAS will be used with 
no numbers or hash marks. This assessment will be done at screening/baseline (Day 1), and at 30 
minutes to 1 hour after patch removal on Days 8 ± 1 and 15 ± 1. The pain will not be evaluated if 
the study chalazion is determined to be absent. The VAS scores will be collected electronically 
as part of the subject electronic diary. 
5.10 Appropriateness of Measurements 
The ocular safety measurements used in the study (AEs, VA, slit-lamp biomicroscopy, IOP 
measurement) are generally recognized as reliable, accurate, and relevant in assessing the safety 
of topical ophthalmic pharmaceutical drugs. 
This is the first study to evaluate a transdermal delivery methodology for ophthalmic medication; 
it is thus considered appropriate to capture the subject’s impressions of ocular and dermal 
comfort during and after wearing the study drug. For both assessments, the subjects will use a 
100 mm VAS, where 0 mm = very comfortable and 100 mm = very uncomfortable, to rate the 
comfort. 
The Draize scale that will be used for scoring dermal response (see Table 2) caused by the study 
drug, as well as the scale that will be used to evaluate patch adhesion (see Section 5.4), have 
been widely used by all regulatory authorities for evaluation of skin irritation (4). 
The primary endpoints are clinical evaluation of the eyelid and determination of the presence or 
absence of a chalazion. While slight scarring or distortion of the skin may remain due to the 
granuloma, the assessment of healing of the chalazion will be based on clinical judgment. 
Subjects who exhibit a complete resolution of the chalazion based on clinical examination at any 
time in the study will be considered a CR. 
The secondary outcome measures include time to CR of the chalazion as documented by the 
subject in the patient diary. The size of the study chalazion will also be evaluated and its 
rationale given that complete resolution may not occur; however, the size of the chalazion may 
be significantly reduced with treatment. The erythema of the chalazion site itself will also be 
assessed using a 5-point scale common in ophthalmology for evaluating the redness of the 
chalazion. In some cases, the chalazion can cause pain either in the eyelid or the eye itself. As 
such, a pain VAS will be used to ask the subject to assess either the pain in the eyelid caused by 
the chalazion or the pain in the eye itself that may occur due to pressure on the eye from the 
chalazion. 


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5.11 Primary Efficacy Variables 
The primary efficacy variables in this trial are the CR of the study chalazion by Day 15 ± 1. 
Complete response is defined as the absence of any significant clinical signs of a chalazion, 
based on clinical judgment by an investigator. Scarring or skin defects resulting from healing of 
the chalazion are possible and allowed upon CR.  
5.12 Secondary Efficacy Variables 
 
 
 
 
 
  
5.13 Drug Plasma Concentration Measurements 
No pharmacokinetic sampling will be taken in this protocol. 
6 
ADVERSE EVENTS 
An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with 
the use of a study drug or other protocol-imposed intervention, regardless of attribution. An AE 
may include intercurrent illnesses or injuries that represent an exacerbation (increase in 
frequency, severity, or specificity) of pre-existing conditions (e.g., worsening of asthma). 
The reporting period for AEs (non-serious and serious) starts after the first study drug application 
on Day 1 and ends at Follow-Up Telephone Contact (Day 22 ± 3).  
The investigator will assess AEs for severity, for relationship to investigational product (IP), and 
as to whether the event meets one or more of the definitions of a serious adverse event (SAE) 
(see Section 6.1). 
Whenever possible, it is preferable to record a diagnosis as the AE term rather than a series of 
symptoms relating to a diagnosis. AEs will be graded according to the National Cancer Institute 
(NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. The investigator will 
determine the severity of each AE based on NCI CTCAE criteria and will record the grade of the 
event on the source documents and AE CRF.  


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NCI CTCAE 
Grade 
Common Term 
Description 
1 
Mild 
Mild; asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated. 
2 
Moderate 
Moderate; minimal, local or noninvasive intervention indicated; 
limiting age-appropriate instrumental Activities of Daily Living 
(ADL). 
3 
Severe 
Severe or medically significant but not immediately life-
threatening; hospitalization or prolongation of hospitalization 
indicated; disabling; limiting self-care ADL. 
4 
Life-Threatening 
Life-threatening consequences; urgent intervention indicated. 
5 
Death 
Outcome of AE was death. 
*Please note: severity of an event does not necessarily correlate to the event being defined as a Serious Adverse 
Event (SAE). 
The investigator will determine the relationship of an AE to the IP and will record it on the 
source documents and AE CRF, using the categories defined below. 


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Causality 
Category 
Description 
Unlikely 
A clinical event, including laboratory test abnormality, with a temporal 
relationship to drug administration which makes a causal relationship 
improbable, and in which other drugs, chemicals or underlying disease 
provide plausible explanations. For the purpose of this protocol, the term 
unlikely will be considered not related to study medication and an 
“Adverse Event”. 
Possible 
A clinical event, including laboratory test abnormality, with a reasonable 
time sequence to administrations of the drug, but which could also be 
explained by concurrent disease or other drugs or chemicals. Information 
on drug withdrawal may be lacking or unclear. For the purpose of this 
protocol an event that has possible relationship to study medication will be 
defined as a “Suspected Adverse Drug Reaction”. 
Probable 
A clinical event, including laboratory test abnormality, with a reasonable 
time sequence to administration of the drug, unlikely to be attributed to 
concurrent disease or other drugs or chemicals, and which follows a 
clinically reasonable response on withdrawal. For the purpose of this 
protocol an event that has probable relationship to study medication will 
be defined as an “Adverse Drug Reaction”.  
In order to classify AEs and diseases, preferred terms will be assigned by the sponsor or its 
designee to the original terms entered on the CRF, using MedDRA (version 19.1). 
An Unexpected AE is defined as an adverse reaction, the nature or severity of which is not 
consistent with the product information provided in the Investigator’s Brochure. 
The medical monitor, in consultation with the investigator, will be responsible for determining 
without unmasking the subject, whether an AE is clinically significant for the subject or the 
study overall.  
Should a pregnancy occur, it must be reported and recorded on the pregnancy form. Treatment 
should be stopped at the time when the pregnancy is reported. Pregnancy in itself is not regarded 
as an AE. 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.  
6.1 
Serious Adverse Events 
An SAE is defined as any AE that: 


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• Results in death (i.e., the AE actually causes or leads to death); 
• Is life-threatening (i.e., the AE, in the view of the investigator, places the subject at 
immediate risk of death. It does not include an AE that, had it occurred in a more severe 
form, might have caused death); 
• Requires or prolongs in-patient hospitalization; 
• Results in persistent or significant disability or incapacity (i.e., the AE results in 
substantial disruption of the subject’s ability to conduct normal life functions);  
• Results in a congenital anomaly or birth defect in a neonate/infant born to a mother 
exposed to IP prior to conception or during pregnancy; 
• Is considered a significant medical event by the investigator based on medical judgment 
(e.g., may jeopardize the subject or require medical or surgical intervention to prevent 1 
of the outcomes listed above). 
The reporting period for SAEs will begin after the first study drug application on Day 1 and 
continue through Day 22 ± 3. Serious AEs reported to the investigator outside of this reporting 
period will be reported to Senju or the medical monitor, if, in the investigator’s judgment, the 
event has any bearing on the study data. SAEs must be followed by the investigator until 
resolution, or until the subject is lost to follow-up, even if this extends beyond the study-
reporting period. Resolution of an SAE is defined as the return to baseline status or stabilization 
of the condition with the expectation that it will remain chronic. 
Any SAE, whether or not considered a suspected adverse drug reaction, will be reported 
immediately (within 24 hours of learning of the event) by fax or email using the study-specific 
SAE Report Form. In addition to the outcome of the SAE, any medication or other therapeutic 
measures used to treat the event will be recorded on the appropriate CRF page(s). Investigators 
should not wait to collect additional information that fully documents the event before notifying 
Senju of an SAE. Senju may be required to report certain SAEs to regulatory authorities within 
7 calendar days of being notified about the event; therefore, it is important that Investigators 
submit additional information requested by Senju as soon as it becomes available. 
Reporting of SAEs to the IRB/EC will be done in compliance with the standard operating 
procedures and policies of the IRB/EC and with applicable regulatory requirements. Adequate 
documentation must be obtained by Senju showing that the IRB/EC is properly and promptly 
notified as required. 
The SAE form must be either faxed to +1-877-464-7787 or emailed within 24 hours to 
INCDrugSafety@incresearch.com. 


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The investigator is encouraged to discuss with the medical monitor any AEs for which the issue 
of seriousness is unclear or questioned. Contact information for the medical monitor is as 
follows: 
Medical Monitor: 
 
Cellular: 
 
Email: 
 
7 
STATISTICAL METHODS AND DETERMINATION OF SAMPLE SIZE 
7.1 
Statistical and Analytical Plans 
All data collected on CRFs will be presented in data listings. The primary and secondary 
endpoints for this trial will be evaluated using the Intent-to-Treat (ITT) population with the 
Modified Intent-to-Treat (mITT) performed as a sensitivity analysis. The safety analyses will be 
carried out using the safety population. Comfort scores (ocular, skin, and the average of both), 
patch adhesion, and residual drug content will be analyzed using the ITT population (and mITT 
and Per-Protocol [PP] populations if there are subjects with protocol deviations or incomplete 
data). In general, the grade for each measure in each eye will be used for analysis of treatment 
effects unless otherwise specified. All analyses will be conducted in a validated instance of SAS 
9.1 or higher. 
7.1.1 Analytical Populations 
• Intent-to-Treat: The ITT population will include all randomized subjects. All primary 
and secondary efficacy analyses are to be on the ITT population. 
• Modified Intent-to-Treat: The mITT population will include all randomized subjects 
with at least one post-baseline primary outcome assessment. Results of the efficacy 
analyses based on the mITT population will be presented as a sensitivity analysis. 
Treatment assignments in the mITT population will be based on the treatment to which 
the subject was randomized. 
• Safety: The safety population will include all randomized subjects who received the 
study drug. Treatment assignments in the safety population will be based on the treatment 
that was received (if different from the randomized treatment). 
• Per-Protocol: The PP population will exclude from mITT population those subjects who 
have major protocol violations. Major protocol violations include violation of entry 
criteria, receiving the incorrect randomization, noncompliance with study drug 
administration (missing the study drug administration more than 80% of study drug or 
failure to apply the study drug for at least 5 days per week and miss more than 2 of 7 days 
of application), and the use of prohibited medications. Treatment assignments in the PP 
population will be based on the treatment that was received (if different from the 
randomized treatment). 


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7.1.2 Analysis of Subject Disposition 
Disposition will be summarized for subjects enrolled into the study. For the subjects who are 
enrolled, summaries will be presented for the number and percentage of subjects who completed 
the study and for those who prematurely withdrew. The reason for withdrawal will be 
summarized by number and percent for subjects who prematurely withdrew. Visit attendance 
will be summarized for all enrolled subjects. 
A list of subjects with protocol violations and their specific violations will also be provided. A 
separate listing will indicate all mis-assignments or out of sequence assignments of study drug 
according to the randomization code list and the reason for the error. 
7.1.3 Analysis of Demographic and Background Characteristics 
The demographic data will be summarized for the ITT population. Demographic data (age, 
gender, ethnicity, race, iris color, chalazion onset, chalazion erythema score at baseline) will be 
presented for each group (SUN-131 1.5% TDS and placebo TDS), and for all enrolled subjects 
combined. Baseline medical history will be summarized and a subject listing will be provided. A 
summary of all prior and concomitant medications will be presented in tabular form by 
therapeutic drug class and generic drug name using the World Health Organization (WHO) Drug 
classification. A summary of all prior and concomitant therapy will be summarized. Ocular and 
non-ocular medical histories will be presented in Appendices. 
7.1.4 Analysis of Study Medication Compliance and Exposure 
Study medication compliance entails wearing the study drug for minimum of 16 hours and 
maximum of 24 hours each day for 14 days. Compliance will be assessed through Visit 3 by 
patch adhesion assessments carried out by the investigator, by subject diaries and by collection 
of all used and unused study drug. The patch adhesion scores and their changes from baseline 
will be summarized by treatment group using descriptive statistics (number of subjects, mean, 
median, range, and standard deviation). Exposure of the study will be summarized by treatment 
group using descriptive statistics (number of subjects, number of study drug applied, number of 
days applied, number of hours applied, mean, median, and standard deviation).  
7.1.5 Analysis of Efficacy 
7.1.5.1 Primary Efficacy Analysis 
The primary analysis will compare the proportions of subjects in the 2 groups who experience 
CR of the study chalazion on or before Day 15 ± 1. CR is defined as the absence of any 
significant clinical signs of a chalazion with possible scaring or skin defects resulting from 
healing of the chalazion allowed. The primary analysis will be conducted using Pearson’s chi-
square test (two-sided) at the alpha = 0.05 level of significance. 


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7.1.5.2 Key Secondary Analyses 
 
 
 
 
 
 
  
7.1.5.3 Other Efficacy Analyses 
All quantitative secondary endpoints will be analyzed using the two-sample t-test (parametric) 
and the Wilcoxon-Mann-Whitney test (nonparametric). Secondary endpoints that are defined as 
time-to-event variables will be summarized using the Kaplan-Meier method; the log-rank test 
will be used to compare the distributions in the 2 groups. The primary and secondary endpoints 
will also be analyzed in the PP population. All secondary analyses will be conducted using two-
sided tests at the alpha = 0.05 level of significance. 
7.1.6 Analysis of Safety and Other Measures 
Safety measures include AEs, ocular examinations and assessments (VA, slit-lamp 
biomicroscopy, IOP measurement), and skin irritation assessments.  
The number and percentage of subjects reporting AEs during the study will be tabulated by 
MedDRA SOC and by preferred term within each organ. The AE tables will be separately 
presented by ocular and non-ocular. Ocular AEs will be tabulated by maximum severity and 
maximum relationship to treatment. For non-ocular AEs, tables will be generated in the same 
fashion of ocular AE tables, if necessary. System organ classes summary will be listed with eye 
disorders first, followed by SOCs listed in order of descending frequency for all subjects. 
Preferred terms will be listed in order of descending frequency within each SOC. Summaries and 
listings will be provided for subjects reporting SAEs, subjects experiencing AEs related to study 
medication, and subjects withdrawing due to an AE. The percentages of specific AEs between 
treatments may be analyzed using Fisher’s exact test if they are extremely unbalanced between 
groups. 
Slit-lamp biomicroscopy will be performed at baseline (pre-dose on Day 1) and just after patch 
removal on Days 8 ± 1 and 15 ± 1. All biomicroscopy findings will be graded Normal, Abnormal 
(not clinically significant), or Abnormal (clinically significant) by the investigator. The 
frequency distribution (number and percentage) of findings in each treatment group at baseline 
will be tabulated along with the frequency distribution at each time point. The percentages of 
slit-lamp biomicroscopy findings between treatments may be analyzed by using Pearson’s chi-
Square test or Fisher’s exact test, if necessary, at each time point.  


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Visual acuity, IOP, ocular comfort score, skin comfort score, and the patch adhesion assessment 
score will be summarized using descriptive statistics (number of subjects, mean, median, range, 
and standard deviation) at each time point. The SUN-131 1.5% TDS will be compared to the 
placebo TDS results at each time point. The changes from baseline (Day 1) will be calculated 
and the groups compared. A paired t-test will be used to compare the treatment groups at each 
time point. Additionally, a Wilcoxon signed-rank test may be used for analysis of the skin 
irritation scores if the distribution of data appeared to be not normally distributed. All statistical 
testing will be evaluated using a level of significance (α) of 0.05. 
7.1.7 Determination of Sample Size 
 
 
 
 
 
 
 
 
7.1.8 Methods for Handling Missing Data 
The primary endpoint is defined as CR by Day 15 ± 1. For this endpoint, if a subject has missing 
data at the specified time point, but is known to be a complete responder at an earlier assessment, 
the subject will be defined as having CR. However, a subject whose prior status is unknown will 
be defined to be a non-responder. Subjects with missing data at Day 8 and Day 15 will be 
considered non-responders. Subjects with missing data at Day 8 but with data at Day 15 will be 
assigned as a responder or non-responder based on their Day 15 results. Subjects who are 
responders on Day 8 will be considered responders for the purposes of the trial regardless of the 
Day 15 evaluation. 
For all time-to-event endpoints, subjects who do not achieve the endpoint will be censored at the 
date of their last assessment. 
For quantitative secondary endpoints, missing data will not be imputed. 
8 
ETHICS 
8.1 
Institutional Review Board or Ethics Committee 
Prior to initiating the study, the investigator will obtain written confirmation that the IRB or EC 
is properly constituted and compliant with all US FDA requirements and local regulations. A 
copy of the confirmation from the IRB/EC will be provided to Senju or its designee. The PI will 


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provide the IRB/EC with all appropriate material, including the protocol, IB, the ICF, and any 
other written information provided to the subjects, including all consent forms translated to a 
language other than the native language of the clinical site. The study will not be initiated until 
appropriate IRB/EC approval of the protocol, the ICF, and all subject recruitment materials are 
obtained in writing by the PI and copies are received at Senju or its designee. The approval 
document should refer to the study by protocol title and Senju, protocol number (if possible), 
identify the documents reviewed, and include the date of the review and approval. Appropriate 
reports on the progress of the study will be provided to the IRB/EC or Research Ethics Board 
(REB) and Senju or its designee by the PI in accordance with applicable governmental 
regulations and in agreement with policy established by Senju. 
8.2 
Ethical Conduct of Study 
This study will be conducted in accordance with the Declaration of Helsinki and GCP according 
to ICH guidelines. Specifically, this study is based on adequately performed laboratory and 
animal experimentation; the study will be conducted under a protocol reviewed and approved by 
an IRB/EC; the study will be conducted by scientifically and medically qualified persons; the 
benefits of the study are in proportion to the risks; the rights and welfare of the subjects will be 
respected; the physicians conducting the study do not find the hazards to outweigh the potential 
benefits; and each subject, or his/her legally authorized representative will provide written, 
informed consent before any study-related tests or evaluations are performed. 
8.3 
Subject Information and Informed Consent 
A properly written and executed ICF, in compliance with the Declaration of Helsinki, ICH GCP 
and US Code of Federal Regulations (CFR) for Protection of Human Subjects (21 Code Federal 
Regulation CFR50.25, CFR50.27, and CFR Part 56, Subpart A), and other applicable local 
regulations, will be obtained for each subject prior to entering the subject into the study. The 
investigator will prepare the ICF and provide the document to Senju or its designee for approval 
prior to submission to the IRB/EC. Senju and the IRB/EC must approve the document before it is 
implemented. If a subject is unable to sign the ICF, a legal representative may sign for the 
subject. The investigator will provide copies of the signed ICF to each subject (or the subject’s 
legal representative) and will maintain the original in the subject’s record file. 
9 
INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE 
Prior to beginning the study, the PI at each site must provide to Senju or its designee a fully 
executed and signed Form FDA 1572. All sub-Investigators must be listed on Form FDA 1572. 
The study will be administered and monitored by employees or representatives of Senju. CRAs 
will monitor site on a periodic basis and perform verification of source documentation for each 
subject as well as other required review processes. Senju’s designee will be responsible for the 
timely reporting of SAEs to appropriate regulatory authorities as required. 


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10 ELECTRONIC CASE REPORT FORMS AND SOURCE DOCUMENTS 
Electronic case report forms will be provided for each subject. The investigator must review and 
sign the completed eCRFs to verify their accuracy. 
Unless explicitly allowed in the eCRF instructions, blank data fields are not acceptable. If 
corrections are made after review and approval by the investigator, he or she must confirm and 
endorse the changes. The study staff will be queried for clarification regarding incomplete 
entries.  
Senju’s policy is that study data on the eCRFs must be verifiable to the source data, which 
necessitates access to all original recordings, laboratory reports, and subject records. In addition, 
all source data should be attributable (signed and dated). The investigator must therefore agree to 
allow direct access to all source data. Subjects (or their legal representatives) must also allow 
access to their medical records, and subjects will be informed of this and will confirm their 
agreement when giving informed consent. If an investigator or institution refuses to allow access 
to subject records because of confidentiality, arrangements must be made to allow an “interview” 
style of data verification. 
A CRA designated by Senju will compare the eCRFs with the original source documents at the 
study site and evaluate the eCRFs for completeness and accuracy. If necessary, the study site 
personnel will be contacted for corrections and/or clarifications. The investigator or designee 
must also review and sign all electronic Data Clarification Forms (eDCFs) or the corrections to 
the eCRFs to verify their accuracy prior to submission to Senju or its designee. Data that are 
modified via eDCFs must be supported in the source documents. 
Designated site personnel must complete eCRFs as soon as possible after a subject visit, and the 
forms must be available for review at the next scheduled monitoring visit. 
11 STUDY MONITORING AND AUDITING 
Qualified individuals designated by Senju will monitor all aspects of the study according to GCP 
and standard operating procedures for compliance with applicable government regulations. The 
PI agrees to allow these Senju-designated CRAs direct access to the clinical supplies, dispensing, 
and storage areas and to the clinical files, including original medical records of the study 
subjects. The PI and staff are responsible for being present or available for consultation during 
routinely scheduled site visits conducted by Senju or its designees. 
Members of Senju GCP Compliance Department or designees may conduct an audit of a clinical 
site at any time during or after completion of the study. The PI will be informed if an audit is to 
take place and advised as to the scope of the audit. Representatives of the FDA or other 
regulatory agencies may also conduct an audit of the study. If informed of such an inspection, the 


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PI should notify Senju immediately. The PI will ensure that the auditors have access to the 
clinical supplies, study site facilities, original source documentation, and all study files. 
12 RETENTION OF RECORDS 
The PI must retain all study records required by Senju and by the applicable regulations in a 
secure and safe facility. The PI must notify Senju of any change in the location, disposition, or 
custody of the study files. The PI/institution must take measures to prevent accidental or 
premature destruction of essential documents, that is, documents that individually and 
collectively permit evaluation of the conduct of a study and the quality of the data produced, 
including paper copies of study records (e.g., subject charts) as well as any original source 
documents that are electronic as required by applicable regulatory requirements.  
All study records must be retained for at least 2 years after the last approval of a marketing 
application in the US or an ICH region and until (1) there are no pending or contemplated 
marketing applications in the US or an ICH region or (2) at least 2 years have elapsed since the 
formal discontinuation of clinical development of the IP. No records relating to this study should 
be disposed of without the written approval of Senju. It is the responsibility of Senju to inform 
the PI/institution as to when these documents no longer need to be retained. 
13 DISCLOSURE OF DATA 
Subject medical information obtained by this study is confidential, and disclosure to third parties 
other than those noted below is prohibited. 
Upon the subject’s permission, medical information may be given to his or her personal 
physician or other appropriate medical personnel responsible for his or her welfare. 
Data generated by this study must be available for inspection upon request by representatives of 
the US FDA, national and local health authorities, Senju and the IRB for each study site, if 
appropriate. 
14 REFERENCES 
1. Rhen T, Cidlowski JA. Antiinflammatory action of glucocorticoids--new mechanisms for old 
drugs. N Engl J Med. 2005;353(16):1711-23. 
2. Ho SY, Lai JL. Subcutaneous steroid injection as treatment for chalazion: prospective case 
series. Hong Kong Med J. 2002;8(1):18-20. 
3. Tahir MZ, Rehman M, Ahmad I, Aqbal A, Hussain I. Effectiveness of Intralesional 
Triamcinolone Acetonide in the treatment of Chalazion. Pak J Ophthalmol. 2015;31(1). 


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4. Draize JH. Dermal toxicity. Appraisal of Chemicals in Food, Drugs and Cosmetics: The 
Association of Food and Drug Officials of the United States (3rd printing 1975); 1959. p. 46-
59.