Randomized, Controlled, Multicenter, Double-Masked, Parallel, Phase 3 Trial to Evaluate the Safety and Efficacy of TP-03 for the Treatment of Demodex Blepharitis
Phase: PHASE3
Conditions: Blepharitis
Sponsor: Tarsus Pharmaceuticals, Inc.

Randomized, Controlled, Multicenter, Double-Masked, 
Parallel, Phase 3 Trial to Evaluate the Safety and 
Efficacy of TP-03 for the Treatment of Demodex 
Blepharitis (Saturn-2)  
Protocol Number: TRS-010 
IND Sponsor: Tarsus Pharmaceuticals, Inc. 
Funded by: Tarsus Pharmaceuticals, Inc. 
 
9-Dec-2021
Registration No: NCT04784091

Table of Contents 
STATEMENT OF COMPLIANCE ............................................................................................................................. 1 
1 
PROTOCOL SUMMARY ............................................................................................................................... 1 
1.1 
Synopsis ................................................................................................................................................ 1 
1.2 
Schema ................................................................................................................................................. 3 
1.3 
Schedule of Activities (SoA) ............................................................................................................... 6 
2 
INTRODUCTION ............................................................................................................................................ 6 
2.1 
Study Rationale .................................................................................................................................... 6 
2.2 
Background........................................................................................................................................... 7 
2.3 
Risk/Benefit Assessment .................................................................................................................... 9 
2.3.1 
Known Potential Risks ..................................................................................................... 9 
2.3.2 
Known Potential Benefits ................................................................................................ 9 
2.3.3 
Assessment of Potential Risks and Benefits ................................................................ 9 
3 
OBJECTIVES AND ENDPOINTS .............................................................................................................. 10 
4 
STUDY DESIGN ........................................................................................................................................... 12 
4.1 
Overall Design .................................................................................................................................... 12 
4.2 
Scientific Rationale for Study Design.............................................................................................. 12 
4.3 
Justification for Dose ......................................................................................................................... 12 
4.4 
End of Study Definition ..................................................................................................................... 13 
5 
STUDY POPULATION ................................................................................................................................ 13 
5.1 
Inclusion Criteria ................................................................................................................................ 13 
5.2 
Exclusion Criteria ............................................................................................................................... 14 
 
 
5.4 
Screen Failures .................................................................................................................................. 16 
5.5 
Strategies for Recruitment and Retention ...................................................................................... 16 
6 
STUDY TREATMENT .................................................................................................................................. 16 
6.1 
Study Treatment(s) Administration.................................................................................................. 16 
6.1.1 
Study Treatment Description ........................................................................................ 16 
6.1.2 
Dosing and Administration ............................................................................................ 18 
6.2 
Preparation/Handling/Storage/Accountability ................................................................................ 18 
6.2.1 
Acquisition and Accountability ...................................................................................... 18 
6.2.2 
Formulation, Appearance, Packaging, and Labeling ................................................ 18 
6.2.3 
Product Storage and Stability ....................................................................................... 19 
6.2.4 
Preparation ...................................................................................................................... 19 
6.3 
Participant ID Assignment and Measures to Minimize Bias: Randomization and Masking.... 19 
6.4 
Study Treatment Compliance .......................................................................................................... 19 
6.5 
Concomitant Therapy ........................................................................................................................ 20 
6.5.1 
Rescue Medicine ............................................................................................................ 20 
7 
STUDY TREATMENT DISCONTINUATION AND PARTICIPANT DISCONTINUATION ................. 20 
7.1 
Discontinuation of Study Treatment ................................................................................................ 20 
7.2 
Participant Discontinuation from the Study .................................................................................... 21 
7.3 
Lost to Follow-Up ............................................................................................................................... 21 
8 
STUDY ASSESSMENTS AND PROCEDURES ..................................................................................... 21 
8.1 
Efficacy Assessments ....................................................................................................................... 21 
8.2 
Safety and Other Assessments ....................................................................................................... 22 
8.3 
Adverse Events and Serious Adverse Events ............................................................................... 22 
8.3.1 
Definition of Adverse Events (AE) ............................................................................... 22 

  
8.3.2 
Definition of Serious Adverse Events (SAE) .............................................................. 22 
8.3.3 
Classification of an Adverse Event .............................................................................. 23 
8.3.4 
Time Period and Frequency for Event Assessment and Follow-Up ....................... 25 
8.3.5 
Adverse Event Reporting .............................................................................................. 25 
8.3.6 
Serious Adverse Event Reporting ............................................................................... 26 
8.3.7 
Reporting Events to Participants ................................................................................. 26 
8.3.8 
Events of Special Interest ............................................................................................. 26 
8.3.9 
Reporting of Pregnancy ................................................................................................ 27 
9 
STATISTICAL CONSIDERATIONS .......................................................................................................... 27 
9.1 
Statistical Hypotheses ....................................................................................................................... 27 
9.2 
Sample Size Determination .............................................................................................................. 29 
9.3 
Populations for Analyses .................................................................................................................. 30 
9.4 
Statistical Analyses............................................................................................................................ 30 
9.4.1 
General Approach .......................................................................................................... 30 
9.4.2 
Analysis of the Primary Efficacy Endpoint(s) ............................................................. 30 
9.4.3 
Analysis of the Secondary Endpoint(s) ....................................................................... 31 
 
 
9.4.5 
Safety Analyses .............................................................................................................. 31 
 
 
 
 
 
 
 
 
9.4.10 
Final Report .................................................................................................................... 32 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .............................. 32 
10.1 
Regulatory, Ethical, and Study Oversight Considerations ........................................................... 32 
10.1.1 
Informed Consent Process ........................................................................................... 32 
10.1.2 
Confidentiality and Privacy ........................................................................................... 34 
10.1.3 
Future Use of Stored Specimens and Data ............................................................... 35 
10.1.4 
Key Roles and Study Governance .............................................................................. 35 
10.1.5 
Safety Oversight ............................................................................................................. 35 
10.1.6 
Clinical Monitoring .......................................................................................................... 35 
10.1.7 
Quality Assurance and Quality Control ....................................................................... 35 
10.1.8 
Data Handling and Record Keeping ............................................................................ 36 
10.1.9 
Protocol Deviations ........................................................................................................ 37 
10.1.10 
Publication and Data Sharing Policy ........................................................................... 37 
10.1.11 
Conflict of Interest Policy .............................................................................................. 38 
10.2 
Additional Considerations ................................................................................................................. 38 
10.3 
Abbreviations ...................................................................................................................................... 38 
10.4 
Protocol Amendment History ........................................................................................................... 40 
11 
REFERENCES ............................................................................................................................................. 41 
12 
APPENDIX A: EXAMS AND PROCEDURES .......................................................................................... 43 
 
 
12.2 
Corrected Distance Visual Acuity .................................................................................................... 43 
12.3 
Slit Lamp Biomicroscopy .................................................................................................................. 45 
12.3.1 
Collarette Grading .......................................................................................................... 45 
12.3.2 
Lid Margin Erythema Grading ...................................................................................... 45 
12.3.3 
Corneal Fluorescein Staining ....................................................................................... 46 

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STATEMENT OF COMPLIANCE 
 
The trial will be carried out in accordance with International Conference on Harmonisation Good Clinical 
Practice (ICH GCP) and the following:  
 
• 
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR Part 46, 21 
CFR Part 50, 21 CFR Part 56, and 21 CFR Part 312)  
 
Investigators and clinical trial site staff who are responsible for the conduct, management, or oversight 
of clinical trials have completed Human Subjects Protection and ICH GCP Training. 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the Institutional Review Board (IRB) for review and approval.  Approval of both the 
protocol and the consent form must be obtained before any participant is enrolled.  Any amendment to 
the protocol will require review and approval by the IRB before the changes are implemented to the 
study.  In addition, all changes to the consent form will be IRB-approved; a determination will be made 
regarding whether a new consent needs to be obtained from participants who provided consent using a 
previously approved consent form. 
 
1 
 
PROTOCOL SUMMARY 
  
1.1 
SYNOPSIS  
 
Title: 
Randomized, Controlled, Multicenter, Double-Masked, Parallel, Phase 3 
Trial to Evaluate the Safety and Efficacy of TP-03 for the Treatment of 
Demodex Blepharitis (Saturn-2) 
  
Test Article: 
TP-03, lotilaner ophthalmic solution, 0.25% 
 
Study Description and 
Hypotheses: 
This Phase 3 study is a randomized, controlled, multicenter, double-
masked, parallel trial to compare the safety and efficacy of TP-03 to 
vehicle control for the treatment of Demodex blepharitis.  The 
hypothesis for the study is the proportion of participants cured at Day 43 
with treatment by TP-03, 0.25%, is greater than the proportion cured by 
treatment with vehicle.    
  
Control Article: 
Vehicle of TP-03 
 
Study Design: 
Prospective, randomized, double-masked, multicenter, two-arm, parallel 
vehicle-controlled study 
 
Objective: 
To demonstrate the safety and efficacy of TP-03, 0.25%, for the 
treatment of Demodex blepharitis 

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2.3 
RISK/BENEFIT ASSESSMENT   
 
2.3.1 KNOWN POTENTIAL RISKS  
Potential risks for participation in this study include mild: ocular irritation (inflammation), conjunctival 
hyperemia, ocular discomfort, ocular burning, ocular soreness, transitory pain, and ocular surface 
staining following instillation of TP-03 or vehicle.  Other potential risks include a mild, transitory 
medicinal taste following instillation of TP-03 or vehicle.  
 
2.3.2 KNOWN POTENTIAL BENEFITS  
Potential benefits for those participants randomized to treatment with TP-03 include a reduction in 
Demodex density and improvement in the signs of Demodex blepharitis.  Participants randomized to the 
control arm may not receive any direct benefit. 
 
2.3.3 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS  
 
 
 
  The 
benefits of treatment with an efficacious anti-infective that can eradicate Demodex folliculorum is 
believed to outweigh the potential risks. 
 

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4.4 
END OF STUDY DEFINITION 
 
A participant is considered to have completed the study if he or she has completed the last visit.  The 
end of the study is defined as completion of the last visit by all participants at all sites. 
 
5 
STUDY POPULATION 
 
5.1 
INCLUSION CRITERIA 
 
Screening is defined as the study visit where baseline assessments are performed prior to first 
administration of the study drug. 
 
Participants who participated in the Saturn-1 clinical trial should not participate in the Saturn-2 clinical 
trial.  Participants who meet all of the following criteria may be enrolled.   
 
1. Male or female, aged ≥18 years of age 
2. Be willing to sign the informed consent and deemed capable of complying with the 
requirements of the study protocol 
3. Has blepharitis*  
4. Meet all of the following criteria in at least one eye: 
a. Have more than 10 lashes with collarettes present on the upper lid (score of 2 or 
greater)  
b. Have at least mild erythema of the upper eyelid margin  
c. Have a Demodex density, upper and lower eyelids combined, of 1.5 or more mites per 
lash 
Note:  All three criteria (a to c) must be met in the same eye.  Only one eye must qualify for the 
participant to be eligible. 
 
 
 
6. Stated willingness to comply with all study procedures and availability for the duration of the 
study  
 
 
1 Perks D. (2015) AHC 2224920: 13 Week Oral (Gavage) Administration Toxicity Study in the Rat Followed by a 4-
Week Treatment-free Period. (Report No. 8275617). 
 
 

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* The blepharitis diagnosis can be made on the date of screening. 
 
 
 
 
 
 
 
 
 
5.2 
EXCLUSION CRITERIA 
 
An individual who meets any of the following criteria will be excluded from participation in this study: 
 
1. Have had prescription: systemic, nasal, inhaled, ocular topical or topical anti-inflammatory 
steroid treatment; antibacterial treatment; or antiparasitic treatment within 14 days of 
Screening  
2. Have had topical tea tree oil or hypochlorous acid treatment of the ophthalmic area within 14 
days of Screening or unwilling to forego the use of these treatments during the study 
3. Have used lid hygiene products (e.g., lid scrubs) within 14 days of Screening or unwilling to 
forego the use of lid hygiene products during the study  
4. Have initiated treatment with an ocular topical prostaglandin analogue within 30 days of 
Screening or have any plans to change or discontinue treatment during the study  
5. Have used a prostaglandin analogue to promote eyelash growth within 30 days of Screening or 
any plans to initiate treatment during the study  
6. Have used artificial eyelashes, eyelash extensions or had other cosmetic eyelash or eyelid 
procedures (e.g., eyeliner tattooing, eyelash tinting, eyelash curling perm, etc.) within 7 days of 
Screening or be unwilling to forego their use during the study  
 
 
  
8. Have an acute ocular infection or have an active ocular inflammation other than blepharitis  
 
 
 
  
11. Have hypersensitivity to lotilaner or any of the formulation components  
12. Have participated in any clinical trial with an investigational drug or device within 30 days of 
Screening or concurrent enrollment in such a trial with the exception of treatment with the 
investigational drug or device having been completed at least three months prior 
13. Be pregnant or lactating at the time of Screening 
 
 
  

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5.4 
SCREEN FAILURES 
 
Screen failures are defined as participants who consent to participate in the clinical trial but are not 
subsequently randomly assigned to the study treatment or entered in the study.  A minimal set of 
screen failure information is required to ensure transparent reporting of screen failure participants to 
meet the Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to 
respond to queries from regulatory authorities.  Minimal information includes demography, screen 
failure details, eligibility criteria, and any serious adverse event (SAE). 
 
 
 
 
 
5.5 
STRATEGIES FOR RECRUITMENT AND RETENTION 
 
It is anticipated that at least 500 patients will be screened in order to reach target enrollment.  The 
source of participants is expected to come primarily from outpatient clinics and the general public.  As 
Demodex positive patients are widely available, participants are expected to come from in-office visits of 
participating investigators.  In the general public, participants may be identified by their symptoms (e.g., 
itching and burning of the lids margins) and can be reached through print advertisements (e.g., 
newspaper, magazine advertisement, flyer, poster, etc.); social media; radio or television advertisement; 
and/or telephone screening script.   
 
As the risk to participants is considered minimal, employees of the study site and family members of site 
staff may be invited to participate in the clinical trial.  Site staff who work on the clinical trial are not 
eligible to participate. 
 
To retain participants, participants may receive visit reminders and some reimbursement for their time 
and travel expenses. 
 
In the event prohibited medications / treatments are indicated for care, participants will not be 
discontinued. 
 
6 
STUDY TREATMENT 
 
6.1 
STUDY TREATMENT(S) ADMINISTRATION 
  
6.1.1 STUDY TREATMENT DESCRIPTION 
 
TP-03 
Lotilaner is the investigational product substance.  Lotilaner is an isoxazoline and inhibits the γ-
aminobutyric acid (GABA)-gated chloride channels (GABACls) of arthropods.  The GABA-mediated 
chloride influx leads to hyperpolarization of the cellular membrane and generates an inhibitory 

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6.2.3 PRODUCT STORAGE AND STABILITY 
All preparations of both the study drug and vehicle control product should be stored at 15° to 30°C.  
There are no light or humidity requirements.  Participants will be instructed to store the study drug at 
room temperature in a climate-controlled environment (15° to 30 °C) avoiding extreme heat or cold. 
 
6.2.4 PREPARATION 
 
Not applicable. 
 
6.3 
PARTICIPANT ID ASSIGNMENT AND MEASURES TO MINIMIZE BIAS: RANDOMIZATION 
AND MASKING 
A balanced (1:1) randomization will be used for this study.  A computer-generated blocked 
randomization schedule will be generated by 
.  
 will use the randomization 
schedule to package the study drug.  The labelled study drug will be shipped to the US distribution 
center for distribution to the clinical sites. 
 
 
 
 
 
 
If a potential study participant has provided written informed consent and met all eligibility criteria, the 
participant is considered eligible to participate.  If the potential participant elects to participate in the 
study, they can continue with the Day 1 procedure or be scheduled to return for Day 1.  At Day 1, they 
will be dispensed the next available study drug bottle from the current site inventory by the Interactive 
Response Technology (IRT) system 
, which uses block 
stratification by site.  The participant will receive their assigned study drug at the completion of the Day 
1 visit and the participant will be considered enrolled in the study.  The participant will be assigned a 
unique identification number consisting of their site number followed by a hyphen and then the 
screening number.   
Throughout the study, both the participant and site personnel performing study assessments will remain 
masked to the study medication.  The active and vehicle control ophthalmic solutions will be 
indistinguishable in appearance and will be distributed in bottles identical in appearance. 
Treatment assignments should only be unmasked if needed for proper care of the participant.  Sites will 
be provided instructions on the procedure to be followed to unmask the treatment assignment for a 
participant.  Inadvertent unmasking will be reported to the sponsor and IRB as required. 
 
 
6.4 
STUDY TREATMENT COMPLIANCE 
 

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Participants will be instructed on proper instillation and storage of the study drug and provided with 
written instructions.  To assess adherence to the protocol regarding administration of the study product, 
participants will be instructed to record in a dosing compliance diary on a daily basis.  Dosing compliance 
will be assured by an in-office review of a dosing diary.  
 
 
  Participants will 
be reinstructed on dosing compliance and this will be documented in the source documents. 
 
6.5 
CONCOMITANT THERAPY 
 
For this protocol, a prescription medication is defined as a medication that can be prescribed only by a 
properly authorized/licensed clinician.  Medications to be recorded in the source document are 
concomitant prescription medications, over-the-counter medications, supplements, and relevant 
treatments and/or procedures (e.g., lid scrubs, tea tree oil, etc.).  All concomitant medications including 
over-the-counter medications and nutritional supplements used within the 30 days prior to the first visit 
will be documented.  Any changes to concomitant medication use or initiation of new medications will 
be reported throughout the study. 
 
For the duration of the study, any therapy considered necessary for the participant’s welfare may be 
given to the participant at the discretion of the investigator.  Initiation of new medications or changes to 
concomitant medications should be recorded in the source document. 
 
6.5.1 RESCUE MEDICINE 
  
No rescue medication is available for this indication. 
 
7 
STUDY TREATMENT DISCONTINUATION AND PARTICIPANT DISCONTINUATION 
 
7.1 
DISCONTINUATION OF STUDY TREATMENT 
 
Discontinuation from use of the study treatment does not mean discontinuation from the study, and 
remaining study procedures should be completed as indicated by the study protocol.  If a clinically 
significant finding is identified after enrollment, the investigator or qualified designee will determine if 
any change in participant management is needed.  Any new clinically relevant finding will be reported as 
an AE.  Participants to be discontinued for AE(s) will be followed until the event is resolved or 
considered medically stable by the investigator. 
 
The data to be collected at the time of study treatment discontinuation may include the following: 
• 
An AE assessment and performance of safety assessments including visual acuity, IOP, slit lamp 
biomicroscopy, endothelial cell density, hematology, blood chemistry, drug concentration 
analysis and urinalysis  
• 
Any follow-up evaluations required per investigator determination 
 
Temporary discontinuation of the study treatment could include the onset of such conditions as an 
allergic conjunctivitis or signs or symptoms of eyelid allergy (e.g., injection, swelling, itching, etc.).  Per 
investigator discretion, the study treatment could be discontinued until such a time that the allergic 

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21 
conjunctivitis has shown sufficient improvement such that the study treatment could be re-started.  Re-
challenging with the study treatment could help to determine if the allergic response is related to the 
study drug.    
The principal investigator reserves the right to discontinue the study at his/her site for any safety, 
ethical or administrative reason at any time. 
7.2 
PARTICIPANT DISCONTINUATION FROM THE STUDY 
 
Participants are free to discontinue from participation in the study at any time upon request.  An 
investigator may discontinue a participant from the study for the following reasons: 
 
• 
Pregnancy 
• 
If any clinical AE or other medical condition or situation occurs such that continued participation 
in the study would not be in the best interest of the participant 
• 
If the participant meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation 
• 
Reasons relating to COVID-19 
• 
Other (specify reason) 
 
The reason for participant discontinuation from the study will be recorded on the exit eCRF.  Participants 
who sign the informed consent form and are randomized but do not receive the study treatment will 
not be replaced.  Participants who sign the informed consent form, are randomized and receive the 
study treatment and subsequently discontinue, or are discontinued from the study, will not be replaced.   
 
7.3 
LOST TO FOLLOW-UP 
 
A participant will be considered lost to follow-up if he or she fails to return for their scheduled visit 
within the visit window and is unable to be contacted by the study site staff.  
 
The following actions must be taken if a participant fails to return to the clinic for a required study visit: 
• 
The site will attempt to contact the participant and reschedule the missed visit as soon as 
possible, counseling the participant on the importance of continuing the administration of the 
study drop and of maintaining the assigned visit schedule.  In addition, the site should ascertain 
if the participant wishes to and/or should continue in the study. 
• 
Before a participant is deemed lost to follow-up, the investigator or designee will make every 
effort to regain contact with the participant (where possible, three telephone calls and, if 
necessary, a certified letter to the participant’s last known mailing address or local equivalent 
methods).  These contact attempts should be documented in the participant’s medical record or 
study file.  
• 
Should the participant continue to be unreachable, he or she will be considered to have 
discontinued from the study with a primary reason of lost to follow-up. 
 
8 
STUDY ASSESSMENTS AND PROCEDURES 
  
8.1 
EFFICACY ASSESSMENTS  

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adverse events include drug deficiencies that might have led to an SAE if a) suitable action had not been 
taken or b) intervention had not been made or c) if circumstances had been less fortunate. 
 
Events that are considered sight-threatening in the opinion of the investigator will be considered SAEs. 
 
A planned hospitalization for a pre-existing condition without a serious deterioration in health is not 
considered to be an SAE.  Hospitalization for less than 24 hours is not considered an SAE unless the 
precipitating event was unanticipated and also related to the investigational drug. 
  
 
8.3.3 CLASSIFICATION OF AN ADVERSE EVENT 
  
8.3.3.1 SEVERITY OF EVENT 
 
The following guidelines will be used to describe the severity of AEs.  
 
• 
Mild – Events require minimal or no treatment and do not interfere with the participant’s daily 
activities.  
• 
Moderate – Events result in a low level of inconvenience or concern with the therapeutic 
measures.  Moderate events may cause some interference with functioning. 
• 
Severe – Events interrupt a participant’s usual daily activity and may require systemic drug 
therapy or other treatment.  Severe events are usually potentially life-threatening or 
incapacitating.   
 
Of note, the term “severe” does not necessarily equate to “serious.”  Severity is a measurement of 
intensity.  Thus, a severe reaction is not necessarily a SAE.  For example, a headache may be severe in 
intensity, but would not be serious unless it met one or more of the criteria for a serious adverse event. 
 
8.3.3.2 RELATIONSHIP TO STUDY TREATMENT 
 
All AEs must have their relationship to study treatment assessed by the clinician who examines and 
evaluates the participant based on temporal relationship and his/her clinical judgment.  The degree of 
certainty about causality will be graded using the categories below.  In a clinical trial, the study product 
must always be suspect.  
 
• 
Definitely Related – Evidence indicates a reasonable temporal sequence of the event with the 
study drug administration exists or that the association of the event with study drug 
administration is unknown and the event is not reasonably supported by other conditions such 
that: 
o There is a clinically plausible time sequence between onset of the AE and study treatment 
administration, and/or 
o There is a biologically plausible mechanism for study treatment causing or contributing to 
the AE, and 
o The AE cannot be reasonably attributed to concurrent/underlying illness, other drugs or 
procedures. 
• 
Potentially Related – Evidence indicates a possible relationship to the study drug such that: 

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24 
o The event occurs within a reasonable period of time relative to the treatment that makes a 
causal relationship possible, but plausible explanations may also be provided by other 
causes such as other drugs, products, chemicals, underlying disease, environment, etc. 
o The event is possibly related to the study treatment. 
• 
Not Related – Evidence indicates no plausible direct relationship to the study drug such that: 
o A clinically plausible temporal sequence is inconsistent with the onset of the AE and drug 
administration, and/or 
o A causal relationship is considered biologically implausible 
o The AE can be attributed to concurrent/underlying illness, other drugs or procedures. 
 
8.3.3.3 EXPECTEDNESS  
  
The investigator will be responsible for determining whether an AE is expected or unexpected.  An AE 
will be considered unexpected if the nature, severity, or frequency of the event is not consistent with 
the risk information previously described for the study treatment.  Expectedness should be determined 
if the AE is characterized as related to treatment and is serious (met one or more of the criteria for an 
SAE). 
 
8.3.3.4 OUTCOME 
The clinical outcome of an AE will be characterized as follows: 
• 
Resolved without sequelae 
• 
Resolved with sequelae (specify) 
• 
Death 
• 
Ongoing (i.e., continuing at time of study discontinuation) 
• 
Unknown 
 
8.3.3.5 TREATMENT OR ACTION TAKEN 
The clinical treatment or action taken from an AE will be characterized as follows: 
• 
None 
• 
Medical intervention 
• 
Surgical intervention 
• 
Unknown 
• 
Other (specify) 
 
8.3.3.6 ACTION TAKEN WITH INVESTIGATIONAL PRODUCT 
The action taken with the IP will be characterized as follows: 
• 
None 
• 
Drug temporarily withdrawn 
• 
Drug discontinued 
• 
Unknown 

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8.3.4 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
 
The occurrence of an AE or SAE may come to the attention of study personnel during study visits and 
interviews of a study participant presenting for medical care, or upon review by a study monitor.  At 
study visits, study personnel should pose general questions to the participant to ascertain if the 
participant experienced any issues prior to the visit.  
 
All AEs, including local and systemic reactions not meeting the criteria for SAEs, will be captured on the 
appropriate eCRF.  Information to be collected includes event description, date of onset, clinician’s 
assessment of severity, relationship to study product (assessed only by those with the training and 
authority to make a diagnosis), and date of resolution/stabilization of the event.  All AEs occurring while 
in the study must be documented appropriately regardless of relationship.   
 
Any medical condition that is present at the time that the participant is screened will be considered as 
Baseline and not reported as an AE.  However, if the study participant’s condition deteriorates at any 
time during the study, it will be recorded as an AE.  
 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the event 
at each level of severity to be performed.   
 
The investigator or designee will record all reportable events with start dates occurring any time after 
study drug is first administered until 7 (for non-serious AEs) or 30 days (for SAEs) after the last day of 
study participation.  At each study visit, the investigator will inquire about the occurrence of AE/SAEs 
since the last visit.  Events will be followed for outcome information until resolution or stabilization. 
 
Whenever possible, recognized medical terms should be used when recording AEs.  Colloquialisms 
and/or abbreviations should not be used.  Only one medical concept, preferably a diagnosis instead of 
individual symptoms, should be recorded as the event (e.g., record congestive heart failure rather than 
dyspnea, rales and cyanosis).  However, if a constellation of signs and/or symptoms cannot be medically 
characterized as a single diagnosis or syndrome at the time of reporting, each individual sign or 
symptom should be recorded as a separate AE.  A diagnosis that is subsequently established should be 
reported as follow-up information.   
 
Adverse events occurring secondary to other events (e.g., sequelae) should be identified by the primary 
cause.  A "primary" event, if clearly identifiable, should represent the most accurate clinical term to 
record as the AE event term.  For example: Orthostatic hypotension  fainting and fall to floor  head 
trauma  neck pain.  The primary event is orthostatic hypotension and the sequelae are head trauma 
and neck pain. 
 
Centralized safety oversight for this multi-site study will be provided by the Medical Monitor.    
 
8.3.5 ADVERSE EVENT REPORTING  
 
The investigator must record nonserious adverse events and submit on the eCRF in a timely manner.  
 

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8.3.9 REPORTING OF PREGNANCY  
 
Women of Childbearing Potential (WOCBP) includes any females who have experienced menarche and 
who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or 
bilateral oophorectomy) or are not postmenopausal at least 12 months since last menses.  WOCBP will 
be required to use designated methods of birth control during the course of the study.  All women who 
are pregnant, nursing an infant or planning a pregnancy during the duration of this study will be 
excluded from participation.  
 
If a participant or investigator suspects that the participant may be pregnant prior to study drug 
administration, the study drug should be withheld until the results of pregnancy testing are available.  If 
pregnancy is confirmed, the participant should not administer the study drug and should not be enrolled 
in the study. 
 
If a female participant becomes pregnant during the study, use of the study drug should be discontinued 
immediately.  The investigator will notify the sponsor (or designee) immediately after the pregnancy is 
confirmed.  The investigator will (1) obtain a consent from the female participant for pregnancy follow-
up and (2) follow the progress of the pregnancy to term.  The investigator should document the 
outcome of the pregnancy and provide a copy of the documentation to the sponsor or designee.  The 
sponsor or sponsor’s designee will be responsible for reporting to the IRB and regulatory agencies as 
appropriate. 
 
 
9 
STATISTICAL CONSIDERATIONS  
 
9.1 
STATISTICAL HYPOTHESES 
 
This study is designed to demonstrate the superiority of TP-03 to vehicle control. 
   
• 
Population:  Participants with Demodex blepharitis as defined by the enrollment criteria 
 
• 
Primary Efficacy Endpoint:  Cure based on a collarette score of 0 for the upper eyelid of the 
analysis eye at Day 43  
 
• 
Secondary Efficacy Endpoints:   
o Demodex mite eradication (mite density of 0 mites/lash) from the analysis eye at Day 43 
o Composite cure based on collarette score (0) and erythema score (0) for the upper 
eyelid of the analysis eye at Day 43 
o Erythema cure based on erythema score (0) for the upper eyelid of the analysis eye at 
Day 43 
 
• 
 
o 
 
 
 
 
 
 
 

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• 
Hypotheses: 
The primary efficacy hypothesis is:  
H01: The proportion of participants cured at Day 43, based on a collarette score of 0 for the 
upper eyelid of the analysis eye, by treatment with TP-03, 0.25%, is ≤ the proportion cured by 
treatment with vehicle.  
H11: The proportion of participants cured at Day 43, based on a collarette score of 0 for the 
upper eyelid of the analysis eye, by treatment with TP-03, 0.25%, is > the proportion cured by 
treatment with vehicle.  
The secondary efficacy hypotheses are:  
Demodex Eradication 
H02: The proportion of participants with Demodex eradicated at Day 43 (mite density of 0 
mites/lash) in the analysis eye by treatment with TP-03, 0.25%, is ≤ the proportion with 
Demodex eradicated by treatment with vehicle.  
H12: The proportion of participants with Demodex eradicated at Day 43 (mite density of 0 
mites/lash) in the analysis eye by treatment with TP-03, 0.25%, is > the proportion with 
Demodex eradicated by treatment with vehicle.  
Composite of Collarette and Erythema Cure 
H03: The proportion of participants with a composite cure, collarette score of 0 and erythema 
score of 0, for the upper eyelid of the analysis eye at Day 43 by treatment with TP-03, 0.25%, is ≤ 
the proportion with a composite cure by treatment with vehicle.  
H13: The proportion of participants with a composite cure, collarette score of 0 and erythema 
score of 0, for the upper eyelid of the analysis eye at Day 43 by treatment with TP-03, 0.25%, is > 
the proportion with a composite cure by treatment with vehicle.  
Erythema Cure 
H04: The proportion of participants with an erythema cure, score of 0, for the upper eyelid of the 
analysis eye at Day 43 by treatment with TP-03, 0.25%, is ≤ the proportion with an erythema 
cure by treatment with vehicle.  
H14: The proportion of participants with an erythema cure, score of 0, for the upper eyelid of the 
analysis eye at Day 43 by treatment with TP-03, 0.25%, is > the proportion with an erythema 
cure by treatment with vehicle.  
 
 

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9.2 
SAMPLE SIZE DETERMINATION 
 
A total sample size of 300 subjects (150 subjects per arm) yields approximately 99% power to establish 
superiority of TP-03 to vehicle in the participants meeting the primary efficacy endpoint assuming a 
response rate of 80.0% in TP-03 and 15.8% for vehicle treatments, respectively using Pearson chi-
squared to test a 1-sided hypothesis with a significance level of 0.025.  Response rates for sample size 
calculations are based upon a prior OUS clinical study of TP-03, 0.25%, for the treatment of Demodex 
blepharitis. 
 
Based on the results of a more recent Phase 2b/3 study, TRS-009 (Saturn-1), with a response rate of 
44.0% for the TP-03 treatment group and 7.4% for the vehicle treatment group, a total sample size of 
300 subjects still provides greater than 99% power. 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
The study will be considered a success and TP-03, 0.25%, will be considered superior to vehicle in clinical 
cure if H01 is rejected in favor of H11.  With this sample size, the study will have > 95% power to claim 
success for clinical cure.  A closed hierarchical testing structure will be used such that the analysis will 
first be performed for the primary efficacy endpoint. 
 
 
 
 
 
 
 
 
 
 
 
  
 
Accounting for a 30% discontinuation, approximately 209 subjects per arm (approximately 418 total) will 
be randomized.  The planned enrollment is much greater than typically planned to achieve 300 

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completed subjects due to concerns regarding the impact of COVID-19 and the possibility that up to two 
sites are unable to complete the study. 
 
9.3 
POPULATIONS FOR ANALYSES 
 
The analysis datasets will include the following:  
• 
Full Analysis Set – The full analysis set will include all randomized participants.  Participants in 
the FAS will be analyzed as randomized. 
• 
COVID-19 Analysis Set - The COVID-19 analysis set includes all randomized subjects, but excludes 
subjects that discontinued due to COVID-19 complications, subjects that would have 
discontinued due to COVID-19 had they remained on study, and subjects that had significant 
COVID-19-related protocol deviations.  Subjects that would have discontinued due to COVID-19 
had they remained on study will be determined and documented prior to unmasking.  Protocol 
deviations will be assessed prior to unmasking for their significance based on their impact to 
primary endpoint data.  Sensitivity analyses of the primary efficacy and key secondary analyses 
will be performed on the COVID-19 population and subjects will be analyzed as randomized if at 
least 5% of subjects met these criteria. 
• 
Per Protocol Set – The per-protocol (PP) set will include participants in the FAS who do not have 
significant protocol deviations that effect the primary endpoint analyses.  Protocol deviations 
will be assessed prior to unmasking.  Participants in the PP set will be analyzed as treated.  
• 
Safety Set – The safety set will include all participants who have received at least one dose of 
the investigational product.  Participants in the safety population will be analyzed as treated.  
 
9.4 
STATISTICAL ANALYSES 
 
9.4.1 GENERAL APPROACH 
 
A formal Statistical Analysis Plan (SAP) will be completed prior to unmasking of the study data.  If there 
are any discrepancies between the protocol and the SAP, the SAP will take precedence.  
Quantitative/continuous data will be summarized using descriptive statistics (n, mean, standard 
deviation, median, minimum, and maximum).  Qualitative/categorical data will be summarized using 
frequencies and percentages.  Statistical testing, unless otherwise indicated, will be performed at a 1-
sided 0.025 significance level.  
 
When applicable, two-sided 95% confidence intervals will be reported.  Baseline will be considered the 
last non-missing measure prior to initiation of study therapy.  Change from baseline will be calculated as 
follow-up visit minus baseline. 
 
9.4.2 ANALYSIS OF THE PRIMARY EFFICACY ENDPOINT(S) 
 
The primary efficacy endpoint analysis will be conducted with the FAS, with intercurrent events handled 
as described in the missing data section.  Descriptive statistics will be presented by treatment arm.  
Testing of the percentage of subjects cured at Day 43 based on the collarette grade will be completed 
using a difference of proportions test. 
 
 

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Multiplicity Adjustment  
A closed hierarchical testing structure will be used where the analysis will be performed for the primary 
efficacy endpoint and, only if successful, the analysis will be performed for the three secondary efficacy 
endpoints using the Hochberg testing strategy.  Specifically, if the null hypothesis, H01, is rejected at a 
one-sided α of 0.025, the study will be considered a success for clinical cure and the family of three 
secondary efficacy endpoints will be tested using the Hochberg testing strategy with a familywise α of 
0.025.  If the secondary endpoint with the largest p-value is significant at the 0.025 level, then all three 
secondary endpoints will be declared statistically significant.  If the secondary endpoint with the largest 
p-value is not significant at the 0.025 level, then the secondary endpoint with the next largest p-value 
will be tested at the 0.0125 level.  If this secondary endpoint is significant at the 0.0125 level, then it and 
the remaining secondary variable will be declared statistically significant.  If not, the remaining 
secondary will be tested at the 0.0083 level.  If the null hypothesis, H01 is not rejected at a one-sided α of 
0.025, testing will stop and the three secondary efficacy hypotheses will not be tested. 
  
Missing Data  
The primary efficacy analysis will be conducted with missing data and intercurrent events handled in the 
following manner:  
• 
Discontinuation of study medication and non-optimal compliance is ignored [treatment policy 
strategy].  
• 
Withdrawal due to lack of efficacy or adverse events: missing data will be imputed as failure 
[hypothetical strategy]. 
• 
Missing data without withdrawal or withdrawal due to reasons other than lack of efficacy or 
adverse events: missing data will be imputed employing Multiple Imputation (MI) using 
randomized treatment-based Markov Chain Monte Carlo (MCMC) methodology [hypothetical 
strategy].  
 
Sensitivity analysis on the primary efficacy endpoint will be performed as specified in the Statistical 
Analysis Plan (SAP).   
 
9.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
 
The statistical approach for the secondary efficacy endpoints will be the same as for the primary efficacy 
endpoint analysis. 
 
 
 
 
 
 
 
9.4.5 SAFETY ANALYSES 
 
All safety analyses will be conducted using the safety set.  Safety measures will be summarized for each 
treatment arm and visit (as appropriate) using descriptive statistics.  Adverse events will be coded using 

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the Medical Dictionary for Regulatory Activities (MedDRA).  Each MedDRA preferred term will be 
counted once only for a given participant.  The severity, frequency, relationship of AEs to study 
treatment, expectedness if serious, duration, and outcome will be presented either in a table or listing.  
Adverse events leading to premature discontinuation from the study treatment and serious treatment-
emergent AEs will be presented either in a table or a listing. 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
   
 
 
 
 
 
 
9.4.10 FINAL REPORT 
 
Once all study visits through Day 43 are complete and all associated study data has been received and 
corrected, the study data will be locked.  Once the data has been locked and all exclusions from the PP 
analysis population and participants who would have discontinued due to COVID-19 had they remained 
on study have been determined, the treatment assignments will be unmasked for analysis.  A complete 
analysis of the results will be performed and a final report will be prepared.  When the last of the Day 90 
visits have been completed and all associated study data has been received and corrected, the analysis 
of the endothelial cell density results will be performed.  A report of the endothelial cell density results 
will be prepared and the report will be submitted to the NDA. 
 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
  
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
 
10.1.1 INFORMED CONSENT PROCESS 
 
 
10.1.1.1 CONSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED TO PARTICIPANTS 
 

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Consent forms describing in detail the study treatment, study procedures, and risks are given to the 
participant and written documentation of informed consent is required prior to starting study 
treatment.  Consent materials submitted with this protocol could include questionnaires, printed or 
web-based advertisement materials, instruction sheets, and phone scripts. 
 
10.1.1.2 CONSENT PROCEDURES AND DOCUMENTATION 
 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the 
study and continues throughout the individual’s study participation.  Consent forms will be Institutional 
Review Board (IRB)-approved and the participant will be asked to read and review the document.  The 
investigator will explain the research study to the participant and answer any questions that may arise.  
A verbal explanation will be provided in terms suited to the participant’s comprehension of the 
purposes, procedures, and potential risks of the study and of their rights as research participants.  
Participants will have the opportunity to carefully review the written consent form and ask questions 
prior to signing.  The participants should have the opportunity to discuss the study with their family or 
surrogates or think about it prior to agreeing to participate.  The participant will sign the informed 
consent document prior to any procedures being done specifically for the study.  Participants must be 
informed that participation is voluntary and that they may discontinue from the study at any time, 
without prejudice.  A copy of the informed consent document will be given to the participants for their 
records.  The informed consent process will be conducted and documented in the source document 
(including the date), and the form signed, before the participant undergoes any study-specific 
procedures.  The rights and welfare of the participants will be protected by emphasizing to them that 
the quality of their medical care will not be adversely affected if they decline to participate in this study.   
 
During the informed consent process, potential study participants will be informed that they have a 50% 
chance of being assigned to the vehicle control arm. 
 
To obtain consent from speakers of languages other than English, the consent and applicable study-
related materials will be translated into a language understandable to the participant.  A member of the 
research team or non-family member interpreter will be available to interpret the initial and ongoing 
informed consent discussion for the participant.  In case of emergencies, a member of the research 
team who is fluent in the participant’s language will be available or the research team will have 24-hour 
access to a translation service that can sufficiently communicate with the participant. 
 
 
 
• 
 
 
 
 
• 
 
 
 
 
 
 
10.1.1.3 STUDY DISCONTINUATION AND CLOSURE 
 

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This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable 
cause.  Possible reasons for termination or temporary suspension of the study could include: 
 
• 
Study closure based on sponsor/funder decision, regulatory or other oversight bodies 
• 
Review of serious, unexpected, and related AEs 
• 
Noncompliance with protocol requirements 
• 
Determination of unexpected, significant or unacceptable risk to participants due to COVID-19 
     
Written notification documenting the reason for study suspension or termination will be provided by 
the suspending or terminating party to study participants, the investigator, the Investigational New Drug 
(IND) sponsor and regulatory authorities as required.  If the study is prematurely terminated or 
suspended, the principal investigator (PI) will promptly inform study participants, the Institutional 
Review Board (IRB), and sponsor, and will provide the reason(s) for the termination or suspension.  
Study participants will be contacted, as applicable, and be informed of changes to the study visit 
schedule. 
 
The study may resume once concerns about safety, protocol compliance, and data quality are 
addressed, and satisfy the sponsor, IRB and/or Food and Drug Administration (FDA). 
 
10.1.2 CONFIDENTIALITY AND PRIVACY  
 
Participant confidentiality and privacy is strictly held in trust by the participating investigators, their 
staff, and the sponsor.  This confidentiality is extended to cover testing of biological samples in addition 
to the clinical information relating to participants.  Therefore, the study protocol, documentation, data, 
and all other information generated will be held in strict confidence.  No information will be shared with 
any parties other than those specifically identified in the ICF/HIPAA signed by the subject, without 
written permission from the subject.  
 
All research activities will be conducted in as private a setting as possible. 
 
The study monitor, other authorized representatives of the sponsor, representatives of the Institutional 
Review Board (IRB), regulatory agencies or pharmaceutical company supplying study product may 
inspect all documents and records required to be maintained by the investigator, including but not 
limited to, medical records (office, clinic, or hospital) and pharmacy records for the participants in this 
study.  The clinical study site will permit access to such records. 
 
The study participant’s contact information will be securely stored at each clinical site for internal use 
during the study.  At the end of the study, all records will continue to be kept in a secure location for as 
long a period as dictated by the reviewing IRB, institutional policies, or sponsor requirements. 
 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will 
be transmitted to and stored 
 
).  This will not 
include the participant’s contact or identifying information.  Rather, individual participants and their 
research data will be identified by a unique study identification number and their initials.  The study 
data entry and study management systems used by clinical sites and by 
 research staff will be 
secured and password protected.  At the end of the study, all study databases will be de-identified and 
archived at a location specified by the sponsor. 

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10.1.4 KEY ROLES AND STUDY GOVERNANCE 
 
   
 
  
  
 
 
 
 
Study team roles and responsibilities of those involved in the conduct, management, or oversight of the 
trial will be established.  
10.1.5 SAFETY OVERSIGHT 
 
Safety oversight will be under the direction of a Medical Monitor, an individual having appropriate 
expertise.  The Medical Monitor will be independent from study conduct and free of conflict of interest. 
 
10.1.6 CLINICAL MONITORING 
 
Clinical site monitoring is conducted to ensure that the rights and well-being of trial participants are 
protected, that the reported trial data are accurate, complete, and verifiable, and that the conduct of 
the trial is in compliance with the currently approved protocol/amendment(s), with International 
Conference on Harmonisation Good Clinical Practice (ICH GCP), and with applicable regulatory 
requirement(s).   
 
• 
Monitoring for this study will be performed by
.  
• 
Details of clinical site monitoring are documented in a Clinical Monitoring Plan (CMP).  The CMP 
describes in detail who will conduct the monitoring, at what frequency monitoring will be done, 
at what level of detail monitoring will be performed, and the distribution of monitoring reports. 
 
10.1.7 QUALITY ASSURANCE AND QUALITY CONTROL 

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Each clinical site will perform internal quality management of study conduct, data and biological 
specimen collection, documentation and completion.   
 
Quality control (QC) procedures will be implemented beginning with the data entry system and data QC 
checks that will be run on the database will be generated.  Any missing data or data anomalies will be 
communicated to the site(s) for clarification/resolution. 
 
Following written Standard Operating Procedures (SOPs), the monitors will verify that the clinical trial is 
conducted and data are generated and biological specimens are collected, documented (recorded), and 
reported in compliance with the protocol, International Conference on Harmonisation Good Clinical 
Practice (ICH GCP), and applicable regulatory requirements (e.g., Good Manufacturing Practices (GMP)).  
 
The investigational site will provide direct access to all trial-related sites, source data/documents, and 
reports for the purpose of monitoring and auditing by the sponsor, and inspection by local and 
regulatory authorities. 
 
10.1.8 DATA HANDLING AND RECORD KEEPING  
  
10.1.8.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the site 
investigator.  The investigator is responsible for ensuring the accuracy, completeness, legibility, and 
timeliness of the data reported.   
  
Study participation should be captured in a participant’s medical record.  This is to ensure that anyone 
who would access the patient medical record has adequate knowledge that the patient is participating 
in a clinical trial. 
  
All source documents should be completed in a neat, legible manner to ensure accurate interpretation 
of data.  Source data are all information, original records of clinical findings, observations, or other 
activities in a clinical trial necessary for the reconstruction and evaluation of the trial.  Electronic source 
data are data initially recorded in electronic form.  Examples of source data include, but are not limited 
to, hospital records, clinical and office charts, laboratory notes, memoranda, participants’ memory aids 
or evaluation checklists, pharmacy dispensing records, audio recordings of counseling sessions, recorded 
data from automated instruments, copies or transcriptions certified after verification as being accurate 
and complete, microfiches, photographic negatives, microfilm or magnetic media, x-rays, and 
participant files and records kept at the pharmacy, at the laboratories, and medico-technical 
departments involved in the clinical trial.  Hardcopies of the study visit worksheets may be provided for 
use as source document worksheets for recording data for each participant enrolled in the study.   
  
Clinical data (including AEs and concomitant medications) and clinical laboratory data will be entered 
into 
, a 21 CFR Part 11-compliant data capture system 
managed by SDC.  The data system includes password protection and internal quality checks, such as 
automatic range checks, to identify data that appear inconsistent, incomplete, or inaccurate.  Clinical 
data will be entered directly from the source documents.  Data recorded in the electronic case report 

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form (eCRF) derived from source documents should be consistent with the data recorded on the source 
documents. 
  
Adverse events will be coded using MedDRA and concomitant medications will be coded using 
WHODrug for summarization and reporting.  
 
10.1.8.2 STUDY RECORDS RETENTION  
 
Study documents should be retained for a minimum of 2 years after the last approval of a marketing 
application and until there are no pending or contemplated marketing applications or until at least 2 
years have elapsed since the formal discontinuation of clinical development of the study 
treatment.  These documents should be retained for a longer period, however, if required by local 
regulations.  No records will be destroyed without the written consent of the sponsor.  It is the 
responsibility of the sponsor to inform the investigator when these documents no longer need to be 
retained. 
 
10.1.9 PROTOCOL DEVIATIONS  
 
A protocol deviation is any noncompliance with the clinical trial protocol, International Conference on 
Harmonisation Good Clinical Practice (ICH GCP), or Manual of Procedures requirements.  The 
noncompliance may be either on the part of the participant, the investigator, or the study site staff.  As 
a result of deviations, corrective actions are to be developed by the site and implemented promptly.  
 
These practices are consistent with ICH GCP:  
• 
4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3  
• 
5.1 Quality Assurance and Quality Control, section 5.1.1  
• 
5.20 Noncompliance, sections 5.20.1, and 5.20.2.  
 
It is the responsibility of the site investigator to use continuous vigilance to identify and report 
deviations within approximately 7 working days of identification of the protocol deviation, or within 
approximately 7 working days of the scheduled protocol-required activity.  All deviations must be 
addressed in study source documents and reported to the sponsor or its representative.  Relevant 
protocol deviations must be sent to the reviewing Institutional Review Board (IRB) per their policies.  
The site investigator is responsible for knowing and adhering to the reviewing IRB requirements.   
 
10.1.10 
PUBLICATION AND DATA SHARING POLICY 
 
This study will be conducted in accordance with the following publication and data sharing policies and 
regulations: 
 
This study will comply with the Clinical Trials Registration and Results Information Submission rule.  As 
such, this trial will be registered at ClinicalTrials.gov, and results information from this trial will be 
submitted to ClinicalTrials.gov.  In addition, every attempt will be made to publish results in peer-
reviewed journals.   
 
 
 

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IOP 
Intraocular pressure 
IP 
Investigational product 
IUPAC 
International Union of Pure and Applied Chemistry 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
LDPE 
Low-density polyethylene 
logMAR 
Logarithm of the minimum angle of resolution 
MedDRA 
Medical Dictionary for Regulatory Activities 
μL 
Microliter 
MD 
Doctor of Medicine 
NADA 
New Animal Drug Application 
NEI 
National Eye Institute 
NOAEL 
No observed adverse effect level 
OD 
Doctor of Optometry 
OUS 
Outside United States 
pH 
Potential hydrogen 
PI 
Principal Investigator 
PP 
Per protocol 
QC 
Quality Control 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SDC 
Statistics & Data Corporation 
SMO 
Site Management Organization 
SOA 
Schedule of Activities 
TID 
Three times a day 
TP-03 
Lotilaner ophthalmic solution 
TRS 
Tarsus 
US 
United States 
WOCBP 
Women of Childbearing Potential 
 
 
 

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10.4 PROTOCOL AMENDMENT HISTORY 
 
Version 
Date 
Description of Change  
Brief Rationale 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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11 REFERENCES  
 
1.  American Academy of Ophthalmology Cornea/External Disease Panel. Preferred Practice Panel 
Guidelines: Blepharitis. American Academy of Ophthalmology; 2013. www.aao.org/ppp. 
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3.  Zhao Y-E, Wu L-P, Hu L, Xu J-R. Association of Blepharitis with Demodex : A Meta-analysis. 
Ophthalmic Epidemiol. 2012;19(2):95-102. doi:10.3109/09286586.2011.642052 
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Ophthalmol. 2015;26(4):295-300. doi:10.1097/ICU.0000000000000168 
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2013;90(7):e198-205. doi:10.1097/OPX.0b013e3182968c77 

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17.  Gao Y-Y, Di Pascuale MA, Elizondo A, Tseng SCG. Clinical Treatment of Ocular Demodecosis by Lid 
Scrub With Tea Tree Oil: Cornea. 2007;26(2):136-143. doi:10.1097/01.ico.0000244870.62384.79 
18.  Filho PAN, Hazarbassanov RM, Grisolia ABD, Pazos HB, Kaiserman I, Gomes JAP. The efficacy of oral 
ivermectin for the treatment of chronic blepharitis in patients tested positive for Demodex spp. Br J 
Ophthalmol. 2011;95(6):893-895. doi:10.1136/bjo.2010.201194 
19.  Salem DA-B, El-Shazly A, Nabih N, El-Bayoumy Y, Saleh S. Evaluation of the efficacy of oral 
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Saturn-2 Trial 
 
Protocol TRS-010 
9-Dec-2021 
  
 
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