A 90-Day, Open-Label, Multi-Site, Pilot Study Evaluating the Safety and Intraocular Lowering Effect of Delivering Travoprost Using a Punctal Plug Delivery System (Evolute®) in Subjects With Elevated Intraocular Pressure
Conditions: Elevated Intraocular Pressure (IOP)
Sponsor: Mati Therapeutics Inc.

 
This document is a confidential communication of Mati Therapeutics Inc.  Acceptance of this document 
constitutes an agreement by the recipient that the contents will not be disclosed to any unauthorized personnel 
without the prior written authorization of Mati Therapeutics Inc. 
 
 
Mati Therapeutics Inc. 
101 Colorado St., Suite 2409 
Austin, TX  78701 
  
 
 
CONFIDENTIAL 
The following contains confidential, proprietary information which is 
the property of Mati Therapeutics 
 
 
 
 
PROTOCOL:  CLINICAL STUDY TGLA-2021-01 
 
 
 
 
A 90-Day, Open-Label, Multi-Site, Pilot Study Evaluating 
the Safety and Intraocular Lowering Effect of Delivering 
Travoprost using a Punctal Plug Delivery System 
(Evolute®) in Subjects with Elevated Intraocular Pressure 
 
 
 
 
Protocol Version 3:  08 April 2022 
Travoprost Punctal Plug Delivery System, 166 µg/L67 
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Study Protocol TGLA-2021-01 
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TABLE OF CONTENTS 
 
PROTOCOL APPROVAL .....................................................................................................6 
ABBREVIATIONS AND DEFINITIONS .............................................................................9 
STUDY SYNOPSIS ...............................................................................................................10 
1 
KEY ROLES ..............................................................................................................16 
2 
INTRODUCTION: BACKGROUND AND INFORMATION AND SCIENTIFIC 
RATIONALE .............................................................................................................17 
2.1 
Background Information ..............................................................................................17 
2.2 
Rationale ......................................................................................................................18 
2.3 
Potential Risks and Benefits ........................................................................................19 
2.3.1 Known Potential Risks .................................................................................................19 
2.3.2 Known Potential Benefits ............................................................................................20 
3 
OBJECTIVES AND PURPOSE ...............................................................................20 
4 
STUDY DESIGN AND ENDPOINTS ......................................................................20 
4.1 
Description of the Study Design ..................................................................................20 
4.2 
Study Endpoints ...........................................................................................................21 
4.2.1 Primary Endpoint .........................................................................................................21 
4.2.2 Other Data Endpoints ...................................................................................................21 
4.2.3 Safety Endpoints ..........................................................................................................21 
5 
STUDY ENROLLMENT AND WITHDRAWAL ..................................................21 
5.1 
Study Population ..........................................................................................................21 
5.2 
Study Inclusion/Exclusion Criteria ..............................................................................21 
5.2.1 Study Screening Phase Criteria ....................................................................................21 
5.2.2 Washout Phase - Criteria .............................................................................................24 
5.2.3 Study Treatment Phase Criteria ...................................................................................24 
5.3 
Strategies for Recruitment and Retention ....................................................................25 
5.4 
Study Subject Withdrawal or Termination Criteria .....................................................25 
5.4.1 Reasons for Termination, Discontinuation or Disqualified .........................................26 
5.4.2 Reasons for Termination ..............................................................................................26 
5.4.3 Handling of Study Subject Termination, Discontinued or Disqualified ......................27 
5.5 
Premature Termination or Suspension of Study or Study Site ....................................27 
6 
STUDY AGENT AND PROCEDURES...................................................................28 
6.1 
Study Treatment ...........................................................................................................28 
6.1.1 Route of Administration ..............................................................................................28 
6.1.2 Formulation, Appearance, Packaging and Labeling ....................................................28 
6.1.3 Product Storage and Stability.......................................................................................30 
6.1.4 Starting Dose ................................................................................................................30 
6.1.5 Preparations and Insertion of a Travoprost Evolute ....................................................30 

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6.1.6 Instructions for Study Subjects after Travoprost Evolute Insertion .............................31 
6.1.7 Procedure for the Removal of a Travoprost Evolute (Appendix E for detailed 
instructions)..................................................................................................................31 
6.1.8 Unable to Insert/Extruded/Lost Travoprost Evolute® ..................................................32 
6.1.9 Duration of Therapy .....................................................................................................32 
6.2 
Study Plug Accountability Procedures ........................................................................33 
7 
STUDY PROCEDURES AND SCHEDULE ...........................................................33 
7.1 
Protocol Amendments ..................................................................................................33 
7.2 
Study Procedures/Evaluations .....................................................................................33 
7.2.1 Study Specific Procedures ...........................................................................................33 
7.2.2 Standard of Care Procedures ........................................................................................35 
7.3 
Laboratory Procedures/Evaluations .............................................................................35 
7.4 
Study Visit Phases/Schedule ........................................................................................35 
7.4.1 Visit 1 - Screening Phase (Qualification Visit)............................................................35 
7.4.2 Washout Phase (Six-week duration) ............................................................................36 
7.4.3 Treatment Phase (Visits 2, 3, 4, 5, 6 & 7) ....................................................................36 
7.5 
Unscheduled Visit ........................................................................................................42 
7.6 
Early Exit Visit (Disqualified, Discontinued or Terminated Study Subject) ...............42 
7.7 
Emergency Anaphylactic or Overdose Procedures, Dose Modifications ....................42 
7.8 
Concomitant Medication ..............................................................................................43 
7.8.1 Pre-Study Concomitant Medication Use .....................................................................43 
7.8.2 Concomitant Medication Use during Study .................................................................43 
7.9 
Prohibited Medications, Treatments and Procedures ...................................................43 
7.9.1 Prohibited Medications ................................................................................................43 
7.9.2 Prohibited Treatments ..................................................................................................44 
7.9.3 Prohibited Procedures ..................................................................................................44 
7.10 
Rescue Medication(s)...................................................................................................44 
7.10.1 Administration of a Rescue Medications .....................................................................44 
8 
ASSESSMENT OF SAFEETY .................................................................................44 
8.1 
Safety Variables ...........................................................................................................44 
8.2 
Definitions....................................................................................................................45 
8.2.1 Adverse Event ..............................................................................................................45 
8.2.2 Serious Adverse Event .................................................................................................45 
8.3 
Adverse Event Descriptions .........................................................................................46 
8.3.1 Intensity........................................................................................................................46 
8.3.2 Relationship to Study Treatment .................................................................................46 
8.4 
Follow-up for Adverse Event Definitions....................................................................47 
8.5 
Pregnancy Follow-up ...................................................................................................47 
8.6 
Reporting of Technical Complaint...............................................................................47 
8.6.1 Definitions....................................................................................................................47 
8.6.2 Reporting of Technical Complaints .............................................................................47 
8.6.3 Punctal Plug Delivery System Serious Adverse Events and Technical Complaints ...48 
8.6.4 Anticipated Adverse Event ..........................................................................................49 
8.7 
Reporting Procedures ...................................................................................................49 
8.7.1 Adverse Event Reporting .............................................................................................49 

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8.7.2 Serious Adverse Event Reporting ................................................................................49 
8.7.3 Unanticipated Problem Reporting................................................................................51 
8.7.4 Events of Special Interest.............................................................................................51 
8.8 
Halting Rules ...............................................................................................................51 
8.9 
Safety Oversight...........................................................................................................51 
9 
CLINICAL MONITORING .....................................................................................51 
10 
STATISTICAL CONSIDERATIONS .....................................................................53 
10.1 
Statistical and Analytical Plans ....................................................................................53 
10.2 
Statistical Hypotheses ..................................................................................................53 
10.3 
Analysis of Datasets .....................................................................................................53 
10.4 
Description of Statistical Methods ...............................................................................53 
10.4.1 General Approach ........................................................................................................53 
10.4.2 Analysis of Primary Study Variable ............................................................................53 
10.4.3 Other Data Endpoints ...................................................................................................53 
10.4.4 Safety Analyses ............................................................................................................54 
10.4.5 Adherence and Retention Analyses .............................................................................54 
10.4.6 Baseline Descriptive Statistics .....................................................................................54 
10.4.7 Planned Interim Analyses ............................................................................................54 
10.4.8 Tabulation of Individual Response Data......................................................................54 
10.4.9 Exploratory Analyses ...................................................................................................54 
10.5 
Sample Size ..................................................................................................................55 
10.6 
Measures to Minimize Bias .........................................................................................55 
10.6.1 Enrollment....................................................................................................................55 
10.6.2 Evaluation of the Success of Blinding/Masking Treatment ........................................55 
11 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS .................55 
11.1 
Source Documentation .................................................................................................55 
11.2 
Access and Retention of Study Records ......................................................................56 
11.3 
Subject Confidentiality ................................................................................................56 
11.4 
Case Report Form Completion ....................................................................................56 
11.5 
Investigator Study Summary........................................................................................57 
12 
QUALITY ASSURANCE AND QUALITY CONTROL .......................................57 
13 
ETHICS/PROTECTION OF HUMAN SUBJECTS ..............................................57 
13.1 
Ethical Standard ...........................................................................................................57 
13.2 
Institutional Review Board ..........................................................................................58 
13.3 
Informed Consent Process ...........................................................................................58 
13.3.1 Consent Procedures and Documentation .....................................................................58 
13.3.2 Other Informational Documents Provided to Participants ...........................................58 
13.4 
Participant and Data Confidentiality ............................................................................59 
13.4.1 Research Use of Stored Human Samples, Specimens or Data ....................................59 
14 
DATA HANDLING AND RECORD KEEPING ....................................................59 
14.1 
Data Collection and Management Responsibilities .....................................................59 
14.2 
Study Records Retention..............................................................................................59 

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14.3 
Protocol Deviations ......................................................................................................59 
14.4 
Publications and Data Sharing Policy ..........................................................................59 
15 
LITERATURE REFERENCES ...............................................................................61 
16 
APPENDICES ............................................................................................................61 
 
 
 

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STATEMENT OF COMPLIANCE 
Mati Therapeutics Inc. Protocol TGLA-2021-01 
A 90-Day, Open-Label, Multi-Site, Pilot Study Evaluating the Safety and Intraocular  
Lowering Effect of Delivering Travoprost using a Punctal Plug Delivery System  
(Evolute®) in Subjects with Elevated Intraocular Pressure 
Protocol Version 3:  08 Apr 2022 
Sponsor and Medical Monitor Approval: 
 
 
Signature: 
 ___________________________________________ 
Date: _____________  
Dr. Robert Williams, M.D., Medical Monitor 
Investigator Agreement: 
I have read this protocol in its entirety and agree to: 
a. Implementing and conducting this study in strict compliance with this agreement; the protocol; 
ICH guidelines for Good Clinical Practices and all other applicable regulatory requirements.   
b. No deviation from, or changes to the protocol will take place without prior agreement from the 
sponsor and documented approval from an Institutional Review Board (IRB)/Independent 
Ethics Committee (IEC), except where necessary to eliminate an immediate hazard(s) to the 
study participants. 
c. Obtain written Informed Consent (IC) that is IRB/IEC approved, from each prospective study 
subject at screening and prior to any study specific examination/test. 
d. Obtain authorization for use/disclosure of health information (HIPAA authorization) 
e. Maintain reliable study device dispensing log, receipt and return shipping records, and to store 
study supplies in a secure, locked facility accessible only to authorized study personnel  
f. Maintain adequate and accurate source documents in accordance with Food and Drug 
Administration (FDA) regulations (e.g., CRFs, consent forms, AE/SAE and ADE/SADE 
forms, IRB/IEC documentation, and study supply records). Keep source documentation for the 
maximum period of time permitted by the hospital, institution, or private practice. In addition, 
will notify the Sponsor immediately if any documents are to be destroyed, transferred to a 
different facility or owner 
g. Maintain all information supplied by Mati Therapeutics Inc. in confidence and, when this 
information is submitted to an independent IRB/IEC or any other group, it will be submitted 
with a designation that the material is confidential. 
h. Attempt to complete the study within the time designated. 
 

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By signing this “STATEMENT OF AGREEMENT”, the Investigator grants permission to 
personnel from the Sponsor, its representatives, third parties and appropriate regulatory authorities 
for on-site monitoring and review of all appropriate study documentation, as well as on-site review 
of the procedures employed in data collection, where clinically appropriate. 
 
 
 
 
 
Investigator Signature:   _____________________________________Date: ___________  
“TYPE/Print Name of INVESTIGATOR” 
 
 
 
 
 
Acknowledged By/Sponsor’s Representative Signature:  
 
 
Representative Signature:   ___________________________________Date: ___________  
“TYPE/Print Name of Representative” 
 
 

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ABBREVIATIONS AND DEFINITIONS 
ADE 
Adverse Device Effect 
AE 
Adverse Effect 
BCDVA 
Best-Corrected Distance Visual Acuity 
BP 
Blood Pressure 
BT 
Body Temperature (Fahrenheit) 
CDC 
Center for Disease Control 
CRA  
Clinical Research Associate  
CFR  
Code of Federal Regulations  
CRF 
Case Report Form  
CRC 
Clinical Research Coordinator 
Evolute® 
Punctal Plug Delivery System 
FDA  
Food and Drug Administration  
GCP  
Good Clinical Practice  
HIPAA  
Health Insurance Portability and Accountability Act  
ICF 
Informed Consent Form 
ICH  
International Conference on Harmonisation  
ICH E6  
International Conference on Harmonisation Guidance for Industry Good 
Clinical Practice: Consolidated Guidance  
IEC 
Independent Ethics Committee  
IOP 
Intraocular Pressure 
IRB 
Investigational Review Board  
ITT 
Intent-to-treat 
MedDRA 
Medical Dictionary for Regulatory Activities 
mmHg 
Millimeters of Mercury 
NCR  
No Carbon Required  
NDE 
Non-drug eluting 
NSR 
Non-Significant Risk 
PP 
Per Protocol 
QC  
Quality Control  
OH  
Ocular Hypertension 
OTC 
Over-the-Counter 
POAG 
Primary Open-Angle Glaucoma 
PPDS 
Punctal Plug Delivery System 
SADE  
Serious Adverse Device Event  
SAE  
Serious Adverse Event  
Study Subject 
An individual that has signed a HIPAA and study consent form 
Subject 
Individual being considered for enrollment in to the study  
UP 
Unanticipated Problem  
VA 
Visual Acuity 
 
 

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STUDY SYNOPSIS 
STUDY PROTOCOL NUMBER: TGLA-2021-01 
STUDY PROTOCOL TITLE: A 90-Day, Open-Label, Multi-Site, Pilot Study Evaluating the 
Safety and Intraocular Lowering Effect of Delivering Travoprost using a Punctal Plug Delivery 
System (Evolute®) in Subjects with Elevated Intraocular Pressure 
SPONSOR: Mati Therapeutics Inc. 
INVESTIGATIONAL PRODUCT, OPEN-LABEL: The Travoprost Evolute (Travoprost 
Punctal Plug Delivery System) is an L-shaped, silicone punctal plug with a drug eluting core that 
contains travoprost (active). The Travoprost Evolute is pre-loaded onto a disposable inserter tip 
and individually packaged and sterilized to prevent contamination. The Travoprost Evolute is 
stored at refrigerated temperature.   
Travoprost Evolute System  
 
NUMBER OF SITES: Up to 8 sites within the U.S.A. 
STUDY POPULATION: Up to 30 qualified male or female subjects (~30 qualified eyes) who 
have given HIPAA and informed consent, have met all screening, washout and treatment phase 
inclusion/exclusion criteria of the study, will be enrolled and will receive a Travoprost Evolute 
inserted in to the lower punctum of each eye.  
STUDY OBJECTIVE: Using a punctal plug delivery system (Evolute) to deliver a hypotensive 
(travoprost) drug to the eye, evaluate the safety and ocular effects of a Travoprost Evolute system 
in reducing intraocular pressure in individuals diagnosed with OAG or OH. 
STUDY DESIGN: This is a pilot, open-label, multi-center clinical study. Each potential subject 
that has given HIPAA and informed consent and has meet all screening inclusion/exclusion criteria 
will undergo a six-week washout phase where they will discontinue the use of their topical 
hypotensive medication. In addition, during the washout phase, each potential study subject will 
also discontinue the use of all prohibited systemic medications. 
After the six-week washout, each potential subject will return for a baseline visit (Visit 2). 
Investigators will verify that a potential subject has discontinued the use of their topical 
hypotensive medication(s) and all their prohibited systemic medications for the last 6 weeks. In 
addition, each subject will have discontinued the use of all other ocular drops, gels or ointments 
24 hours prior to the visit (Visit 2) and continues to meet all screening and washout criteria. After 
completing the baseline examination, each potential subject that meet all baseline 
Drug Core
Polymer Sleeve
Cyanoacrylate film
Drug Insert Slot
Drug Insert
Punctum Plug
Final Drug Product

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inclusion/exclusion for the treatment phase of the study will have his/her lower puncta of each eye 
inserted with a Travoprost Evolute®. Each study subject will be instructed to return to the 
investigator’s office the next day, seven, 28, 60 and 90 after the insertion of their plugs for follow-
up examinations. 
SUBJECT SELECTION: The following are inclusion and exclusion criteria for a prospective 
study subject 
i. Screening Phase 
a. INCLUSION Criteria: The following are requirements a subject must meet in order to be 
considered for inclusion into the screening phase of the study: 
1. Male or female subject, 18 years of age or older at the time of the screening examination 
and has been diagnosed with bilateral OAG or OH 
2. A subject must be able and willing to read, comprehend and give authorization for 
Use/Disclosure of Health Information (HIPAA) and informed consent 
3. A subject must not have taken any ocular hypertension medication(s) within the last 12 
hours of the screening visit unless in the opinion of the screening physician it poses an 
undue risk. 
4. A subject must be willing to have the lower puncta of each eye inserted with a study 
plug 
5. A subject’s screening visit (pre-washout) IOPs, measured between 8:00 and 10:00 AM, 
is less than 22 mmHg in both eyes 
6. A subject IOPs are currently controlled (< 22 mm Hg) with a topical prostaglandin or 
in conjunction with one other topical ocular hypotensive drug, not including any fixed-
combination formulations (i.e., Cosopt, Combigan, Azarga, etc.), in both eyes for at 
least one month 
7. A subject must be willing to comply with study instructions and agree to complete the 
entire course of the study 
8. A subject must agree to make all office appointments and have all office visits occur 
between 8:00 and 10:00 AM 
9. Women of child-bearing potential must not be pregnant or lactating, must have a 
negative pregnancy test at screening and must be practicing an adequate method of 
birth control, including intrauterine device (IUD); oral, dermal (“patch”), implant or 
injected contraceptives; tubal ligation; or barrier methods with spermicide 
10. A subject has a Best-Corrected Distance (Glasses), pinhole visual acuity of 20/100 
(Snellen) or better in both eyes 
11. A subject has documented perimetry results within the last 6 months prior to the 
Screening Visit for both eyes 
NOTE: If perimetry measurement are older than 6 months, perform automated 
perimetry at the screening visit 
12. A subject has documented central corneal thickness measurements between >500 µm 
and <600 µm in both eyes 
NOTE: if corneal thickness data is not available, measure corneal thickness of each eye 
using pachymetry at the screening visit 
b. EXCLUSION Criteria: If any of the below criteria apply to a potential study subject, the 
subject does not qualify for enrollment into the screening phase of the study: 

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1. A subject with a history of non-response to topical prostaglandin eye drops for 
OAG/OH 
2. A subject with angle-closure glaucoma, neovascular glaucoma, traumatic glaucoma or 
iridocorneal endothelium syndrome in either eye 
3. A subject with a known sensitivity to travoprost, fluorescein, topical anesthetic, 
silicone, any inactive ingredient of the Travoprost Evolute® or any other products 
required for study procedures 
4. A subject with > 0.9 vertical cup or completely notched optic nerve head rim in either 
eye 
5. A subject with any functionally significant visual field loss or progressive field loss 
within the last year in either eye  
6. A subject with a history of complications, AEs, trauma or disease in the nasolacrimal 
area, whether or not it was due to punctal plug wear, including but not limited to 
dacryocystitis, inflammation or canaliculitis in either eye 
7. A subject with a history of intolerance to punctal plugs or a known sensitivity to any 
inactive ingredient of the punctal plug, silicone, topical anesthetic, or any other 
products required for the study 
8. A subject with structural lid abnormalities (i.e., ectropion, entropion) in either eye 
9. A subject with an active lid disease in either eye (i.e., moderate or severe blepharitis, 
meibomianitis) that requires medical treatment 
10. A subject with any clinically significant (moderate or severe) lid, conjunctival or 
corneal findings in either eye at the screening visit 
11. A subject with a history of chronic/recurrent inflammatory eye disease (i.e., scleritis, 
uveitis, herpes keratitis) in either eye 
12. A subject who would require the use of any ocular medication(s), an over-the-counter 
drop(s), ointment(s) or gel(s), other than the study hypotensive medication(s) in 
either eye during the study period 
13. A subject who has had any ophthalmic surgical procedures (i.e., glaucoma laser, 
minimally invasive glaucoma surgery, cataract, refractive, etc.) in either eye within 
the last six months or will require ophthalmic surgery before completing the study 
14. A subject with a history of penetrating keratoplasty in either eye 
15. A subject requiring the use of a contact lens in either eye at any time during the study 
period 
16. A subject with advanced diabetic retinopathy, branch retinal vein occlusion or central 
retinal vein occlusion in either eye 
17. A subject with a history of macular edema in either eye 
18. A subject currently on any systemic medication [i.e., beta-blocker, carbonic anhydrase 
inhibitors, corticosteroids (including dermal), etc.] that may have an effect on the 
subject's IOP, or who will require its use during the study period  
NOTE: An inhaled steroid, systemic beta-blocker or β-adrenoceptor 
antagonist may be permitted, providing the subject has maintained a 
stable dosage regimen for at least the last three months 
19. A subject with an uncontrolled systemic disease or a medical condition that may 
increase the risk associated with study participation or administration of study 
treatment or that may interfere with the interpretation of study results (e.g., 

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autoimmune disease if the subject is on chronic medications and has ocular 
involvement; host-versus-graft disease) 
20. A subject currently participating or has participated within the last 30 days prior to the 
start of this study in a drug, device or other investigational research study. 
ii Washout Phase 
After the screening phase (process), each subject meeting all screening inclusion/exclusion 
criteria must be willing to: 
1. DISCONTINUE the use of his/her topical hypotensive medication(s) for the next six-
weeks and not to use his/her hypotensive medication for the duration of the study 
2. DISCONTINUE the use of all other ocular drops, gels or ointments that have not been 
prescribed by the investigator, 24 hours prior to Visit 2 and for the duration of the study 
3. DISCONTINUE the use of all systemic medication that are PROHIBITED by the protocol 
for the duration of the study. Systemic medication(s) being used by a subject at the 
Screening visit and is permitted by the protocol, may continue the medication(s), 
however the concentration and dosing frequency must remain the same throughout 
the washout and treatment phases of the study. 
iii. Treatment Phase 
a. INCLUSION Criteria: After the washout phase, the following are requirements a subject 
must meet in order to be considered for enrollment into the treatment phase of the study: 
1. After the six-week washout phase, the subject continues to meet all screening and 
washout inclusion/exclusion study criteria 
2. After the six-week washout phase, subject’s Baseline (Visit 2) IOP measured between 
8:00 and 10:00 AM, is between ≥ 23 and < 34 mmHg in at least one eye 
3. Subject’s Baseline (Visit 2, morning average) IOP is > 5 mmHg from the subject’s 
SCREENING (pre-washout) IOP in at least one eye whose Baseline IOP is between 
> 23 and < 34 mmHg 
4. Investigator is able to dilate the lower puncta of each eye to 1.0 mm, and insert a study 
plug into each puncta. 
b. EXCLUSION Criteria: If any of the below criteria apply to a study subject that has 
completed the washout period, the subject does not qualify for enrollment into the 
treatment phase of the study: 
1. A subject who no longer meets all the screening and washout study criteria 
2. A subject who cannot be successfully inserted with a Travoprost Evolute® in the 
lower puncta of each eye, even if only one eye qualifies for enrollment. 
STUDY VARIABLES: The following will be performed and/or recorded during the course of the 
study: 
a. Obtain written HIPAA and Informed Consent 
b. Verify a subject has not used any hypotensive ocular drops within the last 12 hours prior to 
the screening visit or at any time during the washout or treatment phases of the study 
c. Record any changes in the subject's use of any concomitant medications or ocular drops, gels 
or ointments during the course of the study 
d. Record subject’s demographic data and medical history for past 6 months 

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e. Perform a urine pregnancy test on a female subject of child-bearing potential at their screening 
and last study visits 
f. Measure subject’s temperature, heart rate and blood pressure 
g. Record subject’s Best-Corrected (Glasses) Distance or Pinhole Visual Acuity 
h. Verify documented automated perimetry results have been measured in the last 6 months 
NOTE: If perimetry measurement are older than 6 months, perform automated perimetry 
at the screening visit. 
i. Verify corneal thickness measurements are documented in the subject’s chart 
NOTE: if corneal thickness data is not available, measure corneal thickness of each eye 
using pachymetry at the screening visit 
j. Perform a slit-lamp examination of each eye 
k. Perform a non-dilated fundus exam of each eye, including the evaluation of the lens 
l. Perform IOP measurements of each eye 
m. Dilate lower punctum to 1.0 mm and insert a study plug in to the lower puncta of each eye 
n. Evaluate the study plug position in each eye using the slit-lamp 
o. Record any Adverse Events/Adverse Device Events. 
Study Duration: 
The approximate study duration is 12 months. Study projected to start 1st 
Qtr. 2021 
Study Outcome Endpoint:  
Primary Endpoint: 
Change in IOP from the baseline visit to Days seven, 28, 60 and 90. 
Other Collected Data: Changes in IOP and percent change between the screening and the baseline 
visits (after washout phase, prior to insertion of any Travoprost Evolute®), 
percent of screened patients that qualified for washout phase, percent of 
patients that entered the washout phase that qualified for the treatment 
phase, enrollment rates (rates in to each phase of the study), number and 
percent of study subjects whose IOPs were >34 mmHg at Visit 2, number 
and percent of eyes that extruded a study plug, number of eyes investigators 
were unable to dilate or insert a study plug, listing of reasons why patients 
failed to qualify. 
Safety Endpoint 
Safety variables include any reported AEs/SAEs. Safety variables will also 
include any clinically significant changes in IOP, BCDVA, slit-lamp 
findings, ocular tearing and comfort, blood pressure, heart rate, temperature, 
Travoprost Evolute® inspections/extrusions.  Safety analyses will be 
performed on all subjects who enter the washout phase of the study. 
Subjects that were inserted with a study plug will be subgrouped and 
summarized separately. 
Sample Size  
 
     Determination: 
Since this is a pilot study, no formal sample size estimation will be 
performed. 
 

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Schedule of Assessments, Events 
Visit Examination Parameters 
 
Visit 1 
Screening 
 
Visit 2 
(Day 0) 
 
Visit 3 
(Day1) 
 
Visit 4 
(Day 7) 
 
Visit 5 
(Day28) 
 
Visit 6 
(Day 60) 
 
Visit 7 
(Day 90) 
Informed Consent/HIPAA 
 
     
 
 
 
 
 
 
 
 
 
 
 
 
Medical Hx (past 6 months)/Demographic Data 
 
     
 
    A  
 
 
 
 
 
 
 
 
 
Urine Pregnancy Test  
(Only women of childbearing potential)  
    B 
 
 
 
 
 
 
 
 
 
 
 
    B 
Concomitant Med Use 
 
     
 
     
 
     
 
     
 
     
 
     
 
     
BT (temperature), BP (blood pressure), HR (heart rate) 
 
     
 
     
 
     
 
     
 
     
 
     
 
     
Evaluate study plug position prior to any eye exam 
 
 
 
    *  
     
 
     
 
     
 
     
 
     
Best-Corrected Distance (Glasses) or Pinhole VA 
 
     
 
     
 
     
 
     
 
     
 
     
 
     
Automated Perimetry  
(Not required if measured in last 6 months)  
     
 
 
 
 
 
 
 
 
 
 
 
 
Pachymetry 
(Not required if documented in patient’s chart)  
     
 
 
 
 
 
 
 
 
 
 
 
 
Slit-Lamp Examination 
 
     
 
     
 
     
 
     
 
     
 
     
 
     
IOP (Goldmann) Evaluation  
(To be measured between 8 and 10 am)  
     
 
     
 
     
 
     
 
     
 
     
 
     
Non-Dilated Fundus Examination  
(Include evaluation of the LENS)  
     
 
 
 
 
 
 
 
 
 
 
 
 
Begin Six-Week Washout 
(D/C all topical drops, gels, ointments)  
     
 
 
 
 
 
 
 
 
 
 
 
 
Punctal Size Evaluation, Dilation of Lower Puncta 
 
 
 
     
 
 
 
 
 
 
 
 
 
 
Insertion of Punctal Plugs 
 
 
 
     
 
 
 
 
 
 
 
 
 
 
**Punctal Plug Extrusion 
 
 
 
 
 
   C 
 
   C,D  
   C,D  
   C,D  
     
Removal of Punctal Plugs after eye exam completed 
 
 
 
 
 
 
 
 
 
 
 
 
 
     
Adverse Event/Adverse Device Event Recording 
 
 
 
     
 
     
 
     
 
     
 
     
 
     
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Keys to Abbreviations: 
A 
= Verify no change in medical history, subject still meets all study inclusion/exclusion criteria 
B 
= If performed at the screening visit, must be performed when subject exit the study  
C 
= In a subject where both eyes qualified at Visit 2, if a plug is extruded in one eye, plug is to be replaced and subject continues in the study 
D 
= In a subject where only one eye qualified at Visit 2, if the plug is extruded in the qualified eye, the subject will be DISCONTINUED and replaced.  In a subject where both eyes qualified, if a 
plug is extruded in one eye, then extruded again or in the fellow eye, the subject will be DISCONTINUED and replaced 
* 
= Plug position evaluated after eye exam and plug insertion 
 
= If subject EXITs the study after visit 2, but before visit 7, subject must return to Investigator’s office to have plugs removed  
 
Body Temperature: 
Temperature maybe taken using a non-contact (Infrared) thermometer or orally. Oral temperatures should not be taken within five minutes of ingestion of any food or drink 
Heart Rate: 
Heart rate taken in the sitting position after subject has rested for 5 minutes. Recorded values can be obtained electronically (automated) or manually (observed for 30 seconds or more) 
Blood Pressure: 
Blood pressure, taken in the sitting position after subject has rested for 5 minutes. Recorded values can be obtained electronically (automated) or manually  
Plug Position Evaluation: 
Position of the plug will be evaluated as either: Normal, Present but requires adjustment, Extruded/Recovered, Extruded/Lost, Other 
Slit-Lamp Exam: 
Evaluation will include the Lids (Upper & Lower), Conjunctiva (Bulbar & Palpebral) and the Cornea. SL Findings will be graded on a 5-point scale:   
     0 = None, 1 = Trace, 2 = Mild, 3 = Moderate, 4 = Severe 
IOP Evaluation: 
Goldmann applanation tonometry will be used for measuring IOP. Just prior to the start of the study, the tonometer should be calibrated. IOP of each eye will be measured twice, 
     alternating between the eyes. The average of the two measurements will be used for analysis. However, if there is a > ± 3 mmHg difference between the 1st and 2nd measurement  
     for an eye, a 3rd measurement will be taken and the average of the two closest values of the three will be used for analysis for that eye. 
 

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1 KEY ROLES 
Sponsor: Mati Therapeutics Inc. (Headquarters) 
101 Colorado, Apt 2409 
 
Austin, TX 78701 
 
512 329-6360 
 
Sponsor Personnel: 
Clinical Trial 
Deepank Utkhede 
      Coordinator: Chief Scientific Officer 
 
Mati Therapeutics Canada Inc. (R&D Branch) 
 
201-4475 Wayburne Drive 
 
Burnaby, BC V5G 4X4 
 
Cell: 
778.991-3301 
Fax:  604 637-8747 
 
dutkhede@matitherapeutics.com 
 
Study Monitor/  
Daniel Schwob 
Biostatistician: 
D’Ellis Group, Inc. 
 
26741 Portola Pkwy, Ste 1E 717 
 
Foothill Ranch, CA 92610 
 
Office:  949.916-2800 
Cell:  949.735-1320 
 
dschwob@dellisgroup.com 
 
Regulatory 
Caroline Stokl, Ph.D., 
Specialist: 
Consultant, Regulatory Affairs 
 
201-4475 Wayburne Drive 
 
Burnaby, BC V5G 4X4 
 
Office: 604.983-9103 
 
cstokl@matitherapeutics.com 
 
Medical Monitor: Robert Williams, MD 
 
89 Wilks Way 
 
Friday Harbor, WA 98250 
 
Office: 360.378-7916 
Cell: 360.298-5325 
 
iopdoc1@gmail.com  
 
Emergency  
24-hour Adverse Event/Adverse Device Event  
FAX Number: 
FAX: 
360.282-6871 
 
Robert Williams, MD 
 
Office: 360.378-7916 
Cell: 360.298-5325 
 
Deepank Utkhede 
 
Cell: 
778.991-3301 
Fax:  604 637-8747 
 
Daniel Schwob 
 
Office: 949.916-2800 
Cell: 949.735-1320 
 
 

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2 INTRODUCTION: BACKGROUND AND INFORMATION AND SCIENTIFIC 
RATIONALE 
This study will be conducted in compliance with the protocol, International Conference on 
Harmonization (ICH), Good Clinical Practice (GCP) guidelines and applicable regulatory 
requirements. 
2.1 Background Information 
Open-angle glaucoma (OAG) is a chronic ocular disorder characterized by elevated intraocular 
pressure (IOP) with clinical signs of visual field loss and/or optic nerve damage with patients rarely 
experience any ocular symptoms. If the condition is left untreated, irreversible vision loss due to 
optic nerve damage will occur. The effect of elevated IOP on the optic nerve is gradual, leading to 
vision loss that patients may not realizes until they have irreversibly lost a majority of their vision. 
Based on estimates from the World Health Organization and the Glaucoma Foundation, this 
chronic disease is believed to affect approximately 67 to 105 million people worldwide 
(Leonard 2002) and is the leading cause of irreversible blindness worldwide. In 2011, 2.71 million 
people in the United States had OAG, by 2050 it is estimated that 6.3 million people in the United 
States will have OAG.  
Treatment however of OAG/OH by nature is a disease where compliance tends to be a significant 
problem due to the fact patients lack positive feedback from treatment. Treatment benefits with 
topical hypotensive medications are designed to prevent worsening rather than improving visual 
function by reducing IOP, which is not noticeable by patients. 
Treatment compliance is therefore a key issue in the successful control of OAG/OH and the 
prevention of vision loss. Traditionally, the term compliance has been employed to mean the extent 
to which a patient remembers and complies with the physician's advice of when, and amount of 
medication to use. When treating a condition with an ocular drop from a bottle, treatment also 
depends upon the patients’ physical ability to properly instill/place the correct amount of the 
medication/drop on the eye. A patients’ ability to correctly self-administer ocular drops can be 
affected by a number of factors such as coordination, manual dexterity, n, good vision, all of which 
tend to decrease in aging glaucoma patients, and the presence of co-morbid conditions (Choy et 
al. 2019). Study has also shown that adding a second medication is associated with a statistically 
significant decrease in compliance (Robin 2005). 
Effective treatment of OAG/OH is compounded if the drop is not appropriately placed on the eye. 
The ideal location for instilling/placing of an eye drop is in the eyelid cul-de-sac, or directly onto 
the surface of the eye. Due to patients having difficulty holding the eyelid open or unable to control 
reflex blinking during installation, results in many missed glaucoma eye drops over time and can 
lead to suboptimal treatment or costly wasting of medication. In addition, many OAG/OH patients, 
find it difficult applying the correct amount of pressure to the bottle to release only one drop at a 
time.  

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2.3 Potential Risks and Benefits 
2.3.1 Known Potential Risks 
Potential risks associated with the use of a Travoprost Evolute is not fully known. The risk 
associated with using a study plug to deliver a sustained release of travoprost are anticipated to be 
similar than those observed for travoprost ophthalmic solutions (TRAVATAN®, TRAVATAN Z® 
or IZBA®) or the use of silicone punctal plugs. However, the combination of travoprost with a 
punctal plug may have unforeseen risks.  
In a 3-month clinical trial involving 422 patients exposed to QD dosing of travoprost ophthalmic 
solution, 0.004% and 442 patients exposed to QD dosing of travoprost ophthalmic solution 
0.003%, the most common ocular adverse reaction noted during the trial was ocular hyperemia. 
Other reported ocular adverse events reported at lower incident rates are listed in Table 1. 
TABLE 1 
Ocular Adverse Events Observed in Controlled Clinical Trial with Travoprost 
Ophthalmic Solutions 0.004% and 0.003% (TRAVATAN®, TRAVATAN Z® or IZBA®) 
30-50% of Subjects 
 
5 to 10% of Subjects 
 
1 to 4% of Subjects 
 Ocular Hyperemia 
 *Ocular hyperemia in 
 IZBA controlled  
 studies noted at 12% 
 
 Decreased VA 
 Eye Discomfort 
 Foreign Body Sensation 
 Pain 
 Pruritus 
 
 Abnormal Vision 
 Blepharitis 
 Blurred Vision 
 Cataract 
Cells  
 Conjunctivitis 
  
 Dry Eye 
 Iris Discoloration 
 Keratitis 
 Lid Margin Crusting 
 Ocular Inflammation 
 Photophobia 
 Subconjunctival Hemorrhage 
 Tearing 
 
TRAVATAN® may gradually change eye color, increasing the amount of brown pigmentation in 
the iris by increasing the number of melanosomes (pigment granules) in melanocytes. The long-
term effects on the melanocytes and the consequences of potential injury to the melanocytes and/or 
deposition of pigment granules to other areas of the eye are currently unknown. The change in iris 
color occurs slowly and may not be noticeable for months to years. Patients should be informed of 
the possibility of iris color change. TRAVATAN, TRAVATAN Z® or IZBA® product labels are 
provided in Appendices I, J & K.  

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Primary risk factors for silicone punctal plugs for use in humans are ocular discomfort, epiphora, 
loss of plug, ocular inflammation, and subconjunctival hemorrhage. Less common, but serious, 
side effects are pyogenic granuloma, damage to the muscle at the opening of the punctum, 
canaliculitis, or migration of the plug into the canalicula requiring irrigation or surgery. In previous 
studies using models of the proprietary plugs, adverse reactions (AEs) were noted in subjects, 
including device migration, lacrimation increased, ocular discomfort, eye irritation, conjunctival 
hyperemia, inflammation of lacrimal passage, eye pain, and eyelid edema. 
2.3.2 Known Potential Benefits 
The potential benefit of the Travoprost Evolute® is the ability to deliver a sustain release of 
travoprost over a 90-day period, reducing a patient’s elevated IOP while eliminating his/her need 
to remember to correctly self-administer an eye drop on a daily basis at a specific time of day. 
Additional benefits would include, relieving the difficulty some patients have instilling an ocular 
drop, or the uncertainty they may have if they properly instilled his/her drops. Uncertainty of drop 
instillation can lead to either under dosing (drop instilled improperly) or overdosing, patient 
instilled first drop properly however, believes drop was not dosed properly and instills a second 
drop. 
A summary of known benefits to humans of 0.004% or 0.003% travoprost ophthalmic drops can 
be found in the TRAVATAN®, TRAVATAN Z® or IZBA® prescribing information (see Appendices 
I, J & K). 
3 OBJECTIVES AND PURPOSE 
Past clinical studies with topical dosing of 0.004% and 0.003% ophthalmic solutions of travoprost 
(TRAVATAN/TRAVATAN Z and IZBA) have demonstrated the safety and efficacy of travoprost 
ocular drops in the reduction of elevated intraocular pressure in patients with open-angle glaucoma 
or ocular hypertension. The objective for this study is to evaluate the use of a punctal plug delivery 
system that can deliver a sustained, safe and effective concentration of travoprost to a subject with 
OAG/OH that can reduce elevated intraocular pressure. 
4 STUDY DESIGN AND ENDPOINTS 
4.1 Description of the Study Design 
This is a pilot, open-label, multi-center clinical study. Each potential subject that has given HIPAA 
and informed consent and has meet all screening inclusion/exclusion criteria will discontinue the 
use of his/her topical hypotensive medication(s) for the next six-weeks. In addition, during this 
period a potential study subject will also discontinue the use of all prohibited systemic medications, 
and all other ocular drops, gels or ointments that have not been prescribed by the investigator 24-
hours prior to Visit 2. 

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4.2 Study Endpoints 
The study will be complete when up to 30 study subjects (~30 qualified eyes) have been evaluated 
at Visit 7 (Day 90 ± 7 days post plug insertion) or have been terminated from the study. 
4.2.1 Primary Endpoint 
The primary variable will be IOP changes from baseline to Days seven, 28, 60 and 90. Primary 
analysis time point will be IOPs obtain between 8:00 and 10:00 am. Observed IOP and percent 
change from baseline in IOP will also be analyzed. 
4.2.2 Other Data Endpoints 
Secondary variables will look at changes in IOP and percent change between the screening and the 
baseline visits (after washout phase, prior to insertion of any Travoprost Evolute®), percent of 
screened patients that qualified for washout phase, percent of patients that entered the washout 
phase that qualified for the treatment phase, enrollment rates (rates in to each phase of the study), 
number and percent of study subjects whose IOPs were >34 mmHg at Visit 2, number and percent 
of eyes that extruded a Travoprost Evolute, number of eyes investigators were unable to dilate or 
insert a study plug, listing of reasons why patients failed to qualify. 
4.2.3 Safety Endpoints 
Safety variables include any reported AEs/SAEs. Safety variables will also include clinically 
significant changes in IOP, BCDVA, slit-lamp findings, ocular tearing and comfort, blood 
pressure, heart rate, temperature, and Travoprost Evolute® inspections/extrusions. Safety analyses 
will be performed on all subjects who enter the washout phase of the study. Subjects that were 
inserted with a study plug will be subgrouped and summarized separately. 
5 STUDY ENROLLMENT AND WITHDRAWAL 
5.1 Study Population 
Up to 30 qualified male or female subjects (~30 qualified eyes) who have given HIPAA and 
informed consent, have met all screening and washout criteria, will be enrolled into the treatment 
phase of the study and have a Travoprost Evolute inserted into the lower punctum of each eye. All 
study plugs will remain in the study subject’s lower puncta for a period of 90 + 7 days after 
insertion. 
5.2 Study Inclusion/Exclusion Criteria 
5.2.1 Study Screening Phase Criteria 
The following are criteria a potential study subject must meet in order to be considered for 
enrollment into the study screening phase of the study. 

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5.2.1.1 Screening Phase - Inclusion Criteria 
The following are requirements a subject must meet in order to be considered for inclusion into 
the study screening phases of the study: 
1. Male or female subject, 18 years of age or older at the time of the screening examination and 
has been diagnosed with bilateral OAG or OH 
2. A subject must be able and willing to read, comprehend and give Authorization for 
Use/Disclosure of Health Information (HIPAA) and informed consent 
3. A subject must not have taken any ocular hypertension medication(s) within 12 hours of the 
screening visit 
4. A subject must be willing to have the lower puncta of each eye inserted with a study plug 
5. A subject’s screening visit (pre-washout) IOPs, measured between 8:00 and 10:00 AM, is less 
than 22 mmHg in both eyes 
6. A subject IOPs are currently controlled (< 22 mm Hg) with a topical prostaglandin or in 
conjunction with one other topical ocular hypotensive drug, not including any fixed-
combination formulations (i.e., Cosopt, Combigan, Azarga, etc.), in both eyes for at least one 
month 
7. A subject must be willing to comply with study instructions and agree to complete the entire 
course of the study 
 
8. A subject must agree to make all office appointments and have all office visits occur between 
8:00 and 10:00 AM 
9. Women of child-bearing potential must not be pregnant or lactating, must have a negative 
pregnancy test at screening and must be practicing an adequate method of birth control, 
including intrauterine device (IUD); oral, dermal (“patch”), implant or injected 
contraceptives; tubal ligation; or barrier methods with spermicide 
10. A subject has a Best-Corrected Distance (Glasses), pinhole visual acuity of 20/100 (Snellen) 
or better in both eyes 
11. A subject has documented perimetry results within the last 6 months prior to the Screening 
Visit for both eyes 
NOTE: If perimetry measurement are older than 6 months, perform automated perimetry 
at the screening visit 
12. A subject has documented central corneal thickness measurements between >500 µm and 
<600 µm in both eyes 
NOTE: if corneal thickness data is not available, measure corneal thickness of each eye 
using pachymetry at the screening visit 

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5.2.1.2 Screening Phase - EXCLUSION Criteria 
If any of the below criteria apply to a potential study subject, the subject does not qualify for 
enrollment into the screening phase of the study: 
1. A subject with a history of non-response to topical prostaglandin eye drops for OAG/OH 
2. A subject with angle-closure glaucoma, neovascular glaucoma, traumatic glaucoma or 
iridocorneal endothelium syndrome in either eye 
3. A subject with a known sensitivity to travoprost, fluorescein, topical anesthetic, silicone, any 
inactive ingredient of the Travoprost Evolute® or any other products required for study 
procedures 
4. A subject with > 0.9 vertical cup or completely notched optic nerve head rim in either eye 
5. A subject with any functionally significant visual field loss or progressive field loss within 
the last year in either eye  
6. A subject with a history of complications, AEs, trauma or disease in the nasolacrimal area, 
whether or not it was due to punctal plug wear, including but not limited to dacryocystitis, 
inflammation or canaliculitis in either eye 
7. A subject with a history of intolerance to punctal plugs or a known sensitivity to any inactive 
ingredient of the punctal plug, silicone, topical anesthetic, or any other products required for 
the study 
8. A subject with structural lid abnormalities (i.e., ectropion, entropion) in either eye 
9. A subject with an active lid disease in either eye (i.e., moderate or severe blepharitis, 
meibomianitis) that requires medical treatment 
10. A subject with any clinically significant (moderate or severe) lid, conjunctival or corneal 
findings in either study eye at the screening visit 
11. A subject with a history of chronic/recurrent inflammatory eye disease (i.e., scleritis, uveitis, 
herpes keratitis) in either eye 
12. A subject who would require the use of any ocular medication(s), an over-the-counter 
drop(s), ointment(s) or gel(s), other than the study hypotensive medication(s) in either eye 
during the study period 
13. A subject who has had any ophthalmic surgical procedures (i.e., glaucoma laser, minimally 
invasive glaucoma surgery, cataract, refractive, etc.) in either eye within the last six months 
or will require ophthalmic surgery before completing the study 
14. A subject with a history of penetrating keratoplasty in either eye 
15. A subject requiring the use of a contact lens in either eye at any time during the study period 
16. A subject with advanced diabetic retinopathy, branch retinal vein occlusion or central retinal 
vein occlusion in either eye 
17. A subject with a history of macular edema in either eye 

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18. A subject currently on any systemic medication [i.e., beta-blocker, carbonic anhydrase 
inhibitors, corticosteroids (including dermal), etc.] that may have an effect on the subject's 
IOP, or who will require its use during the study period (NOTE: an inhaled steroid, systemic 
beta-blocker or β-adrenoceptor antagonist may be permitted, providing the subject has 
maintained a stable dosage regimen for at least the last three months) 
19. A subject with an uncontrolled systemic disease or a medical condition that may increase the 
risk associated with study participation or administration of study treatment or that may 
interfere with the interpretation of study results (e.g., autoimmune disease if the subject is on 
chronic medications and has ocular involvement; host-versus-graft disease) 
20. A subject currently participating or has participated within the last 30 days prior to the start 
of this study in a drug, device or other investigational research study. 
5.2.2 Washout Phase - Criteria 
After the screening phase (process), each subject meeting all screening inclusion/exclusion criteria 
must be willing to: 
1) DISCONTINUE the use of his/her hypotensive medication for the next six-weeks (Note: If 
desired, an investigator can perform the six-week washout by placing the subject on mono-
therapy with a topical CAI for 5 weeks, then during the last week, discontinue the use of the 
topical CAI). Each subject will be instructed not to use his/her hypotensive medication for the 
duration of the study 
2) DISCONTINUE the use of all other ocular drops, gels or ointments that have not been 
prescribed by the investigator, 24 hours prior to Visit 2 and for the duration of the study 
3) DISCONTINUE all systemic medication that are PROHIBITED by the protocol for the 
duration of the study. Systemic medication(s) being used by a subject at the Screening visit 
and is permitted by the protocol, may continue the medication(s), however the concentration 
and dosing frequency should remain the same throughout the washout and treatment phase of 
the study 
5.2.3 Study Treatment Phase Criteria 
5.2.3.1 Treatment Phase - INCLUSION Criteria: 
After the washout phase, the following are requirements a subject must meet in order to be 
considered for enrollment into the treatment phase of the study:  
1) After the six-week washout phase, the subject continues to meet all screening phase 
inclusion/exclusion criteria 
2) After the six-week washout phase, subject’s Baseline (Visit 2) IOP, measured between 8:00 
and 10:00 AM, is ≥ 23.0 and < 34.0 mmHg in at least one eye 

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3) Subject’s Baseline (Visit 2, morning average) IOP is > 5 mmHg from the subject’s 
SCREENING (pre-washout) IOP in at least one eye whose Baseline IOP is between > 23 and 
< 34 mmHg. 
4) Investigator is able to dilate the lower puncta of each eye to 1.0 mm, and insert a study plug 
into each puncta. 
5.2.3.2 Treatment Phase - EXCLUSION Criteria 
If any of the below criteria apply to a study subject that has completed the washout period, the 
subject does not qualify for enrollment into the treatment phase of the study: 
1) A subject who no longer meets all the screening and washout study criteria 
2) A subject who cannot be successfully inserted with a Travoprost Evolute® in the lower 
puncta of each eye, even if only one eye qualifies for enrollment. 
5.3 Strategies for Recruitment and Retention 
To increase study subject enrollment and retention in the study, sites should dedicate an individual 
[Clinical Research Coordinator (CRC)] who is well informed regarding the study design, required 
inclusion/exclusion criteria and visit schedule, as the main contact who is readily available to 
answer all potential subject questions and/or concerns about participating in the clinical study. The 
CRC should be prepared to discuss with a potential study subject the differences in the amount of 
time, examination procedures and visit schedule they would experience if they agreed to 
participate in the study. In addition, should a subject agree to participate in the study, the CRC 
would be readily available as his/her main contact person while participating in the study. 
To encourage recruitment and retention of a study subject, sites should offer a subject 
reimbursement for transportation cost (e.g. Uber, Lyft) and a stipend for his/her time and effort for 
participation, offer less waiting time in the doctor’s office by scheduling more flexible and reliable 
appointment times. In addition, discuss the advantages of participating in the study by not having 
to remember to instilling his/her medication over the study period.  
5.4 Study Subject Withdrawal or Termination Criteria 
Each study subject will be informed that they are free to withdraw from the study at any time 
however, if they have been inserted with study plugs, they must return to the investigator’s office 
to have the study plugs removed. The Investigator in consultation with the Medical Monitor, or 
the Medical Monitor may exercise his or her medical judgment to terminate a study subject’s 
participation in the study, if it is in the best interest of the study subject. A terminated study subject 
will be followed through Day 90 or until the condition has resolved or has become medically 
stable. 
 

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Medical Monitoring for this study will be conducted by: 
Robert Williams, MD 
Phone (Office):  360.378-7916 
Phone (Cell):  
360.298-5325 
Email: 
iopdoc1@gmail.com 
The name of the Medical Monitor and contact information will be provided to each study site.  
Mati Therapeutics Inc. reserves the right to terminate the study at any time. Every effort will be 
made to collect all data required by the protocol during or following the study subject’s early 
termination visit. 
5.4.1 Reasons for Termination, Discontinuation or Disqualified 
At a study subject’s last visit (scheduled or unscheduled), a study subject will have his/her 
study punctal plugs removed and a study exit case report form (CRF) must be completed, 
whether or not the study subject completed the final study visit (Visit 7, day 90 ± 7 post-insertion). 
The reason for any early exiting from the study will be indicated on the study exit form and all 
efforts will be made to complete and report the observations as thoroughly as possible. The primary 
reason for a study subject early exiting the study should be selected from the following standard 
categories (see Sections 5.4.2 below). 
5.4.2 Reasons for Termination 
A study subject will be terminated from the study if in the Investigators medical judgment, it was 
in the best interest of the study subject that developed or reported: a) a lack of efficacy, b) reported 
a serious AE/ADEs, regardless of relation to the study drug/device or has died.  
5.4.2.1 Reasons for Discontinuation 
A study subject will be discontinued from the study: a) if the Investigator is unable to sufficiently 
dilate the punctum or insert a punctal plug in to the lower punctum of either eye, b) if a subject has 
extruded a plug and a new plug cannot be re-inserted, c) if during the course of the study a subject 
has extruded a plug from each eye, d) if a subject has extruded a plug more than once from the 
same eye e) in a subject where only one eye qualified at Visit 2, if the plug is extruded in the 
qualified eye, f) if a subject has used a prohibited concomitant ocular or systemic 
(OTC/prescription) medication/therapy, g) if a subject is non-compliant and has missed scheduled 
study visits, h) for personal reasons, i) has relocated out of the area or has a desired to withdraw 
from further participation in the study in the absence of a medical need as determined by the 
Investigator. Other reason – the study subject was discontinued for a reason other than those listed 
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5.4.2.2 Reasons for Disqualification 
A study subject will be disqualified from the study if there was a failure to obtain written informed 
consent or HIPAA Authorization, improper entry (did not meet all study inclusion/exclusion 
criteria), had a positive pregnancy test (at Visit 1).  
5.4.3 Handling of Study Subject Termination, Discontinued or Disqualified 
5.4.3.1 Handling of Terminated Study Subject 
A terminated study subject will return to the clinic for an end of study safety evaluation and the 
removal of his/her punctal plugs. A terminated study subject will receive appropriate treatment at 
the discretion of the Investigator. Notification of termination will be clearly documented on the 
appropriate Case Report Form. A terminated study subject is considered to have completed the 
study and will NOT be replaced. 
5.4.3.2 Handling of Discontinued Study Subject 
A study subject may voluntarily discontinue (withdraw) from the study at any time they choose. 
Notification of discontinuation will be clearly documented on the appropriate Case Report Form. 
If a study subject elects to withdraw from the study during the study treatment phase, the 
Investigator will make every effort to have the study subject return to the clinic for an end of study 
safety evaluation and the removal of the subject’s punctal plugs. A study subject who is 
discontinued from the study will be replaced. 
5.4.3.3 Handling of Disqualified Study Subject 
Notification of disqualification will be clearly documented on the appropriate Case Report Form. 
If a study subject was inserted with punctal plugs, the Investigator will make every effort to have 
the study subject return to the clinic for an end of study safety evaluation and the removal of the 
punctal plugs. A study subject disqualified from the study will be replaced. 
5.5 Premature Termination or Suspension of Study or Study Site 
Mati Therapeutics Inc. reserves the right to terminate or suspended the study at any time. Every 
effort will be made to collect all data required by the protocol during or following the study 
subject’s early termination visit. 
If representatives of Mati Therapeutics Inc., the Principal Investigator, the Study Monitor (Clinical 
Research Associate [CRA]), the Medical Monitor, or the FDA officials discover conditions arising 
during the study that indicate that the study should be halted or that participation by the study 
center should be terminated, this action may be taken after appropriate consultation with 
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Monitor. Conditions that may warrant termination of the study include, but are not limited to the 
following: 
a. The discovery of an unexpected, serious, or unacceptable risk to a study subject enrolled in the 
study 
b. A decision on the part of Mati Therapeutics Inc. to suspend or discontinue testing, evaluation, 
or development of the product 
c. Failure of the Principal Investigator to enroll study subjects into the study at an acceptable rate 
d. Failure of the Principal Investigator to comply with pertinent FDA regulations and ICH 
Guidelines 
e. Submission of knowingly false information from the research facility to Mati Therapeutics 
Inc., or designee, the CRA, the Medical Monitor, or the FDA 
f. Insufficient adherence to protocol requirements.  
Study termination and follow-up will be performed in compliance with the conditions set forth in 
21 CFR 312.50 and 21 CFR 312.56. 
6 STUDY AGENT AND PROCEDURES 
6.1 Study Treatment 
Each investigational site will be assigned a site ID number (e.g., 100, 200 . . . 500). As a study 
subject qualifies for enrollment in to the screening phase of the study, they will be sequentially 
assigned a study ID number that corresponds with the site ID number (e.g., site ID = 100, subject 
sequentially assign numbers 101, 102, . . . 110). If the potential subject does not qualify after the 
washout phase, the subject ID number will be retired. A subject that has a Travoprost Evolute® 
successfully inserted into the lower puncta of each eye, will be identified throughout the treatment 
period of the study by his/her assigned subject ID number and initials. 
6.1.1 Route of Administration 
Each study subject that qualifies for the treatment phase of the study will have the lower puncta of 
each eye inserted with a Travoprost Evolute® (see Appendices F and G for plug insertion details). 
Each study plug has a drug insert which contains a drug load of 166 µg of travoprost. 
If the investigator is unable to insert a study plug in both eyes, the subject will be discontinued 
from the study and his/her subject ID number will be retired. 
6.1.2 Formulation, Appearance, Packaging and Labeling 
6.1.2.1 Formulation 
The punctal plug components of the Travoprost Evolute (Figure 2) device consist of an inactive 
medical-grade silicone with a 2% green colorant throughout the plug (colorant allows for ease of 

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identification and evaluation of plug placement). The drug insert components of the study plug is 
a thin-walled polyimide tube (core) filled with a solid sustained release matrix containing a drug 
load of 166 µg of travoprost (active ingredient). The drug insert is held in place via an interference 
fit between its outer and inner diameters of the punctal plug bore. 
Figure 2: Travoprost Evolute System (L-shape plug Model L67) 
 
6.1.2.2 Appearance 
All Travoprost Evolute are L-shaped and will be provided preloaded on a two-part insertion tool, 
as shown in Figure 3. 
Figure 3: Preloaded Insertion Tool with an L-Shaped Travoprost Evolute 
 
 
6.1.2.3 Packaging 
A pre-loaded Travoprost Evolute® will be supplied preloaded onto the inserter tip in a preformed 
rigid tray. Tray will be sealed with a foil laminate lid, heat sealed onto the tray and sterilized.  
6.1.2.4 Labeling 
Each tray containing a Travoprost Evolute will be labeled with an investigational drug statement 
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6.1.3 Product Storage and Stability 
All used and unused study plug products must be stored in a secure area with controlled access. 
All plugs must be stored at refrigerated temperature (2° - 8°C). All study punctal plug delivery 
system products have a retest date indicated on their label. 
6.1.4 Starting Dose 
Upon insertion of a Travoprost Evolute, the drug insert contains a drug load of 166 µg with a drug 
elution rate of 1 to 2 µg per day.  
6.1.5 Preparations and Insertion of a Travoprost Evolute 
The Travoprost Evolute is for single-patient use only. The procedures for inserting a study plug 
are similar to those for commercial silicone plugs and procedures for insertion of a study plug are 
detailed in Appendices F & G. If the size of the study subject puncta has not be measured, gauge 
(Appendix E) the size of each punctum prior to dilating. 
6.1.5.1 Determining Punctum Size (see Appendix E for detailed instructions) 
Anesthetize the area around the lower punctum of each eye. Use a Coroneo Punctal Gauge 
(Figure 5) to determine the size of the punctum.  
NOTE: Measurement of the punctum size should be evaluated prior to dilating the 
punctum. 
6.1.5.2 Dilation of the Lower Punctum (Appendix F for detailed instructions) 
Prior to inserting a Travoprost Evolute, it is required that the lower punctum must be dilated to 
at least 1.0 mm. While dilating, prepare the study plug to be inserted in the lower punctum of the 
study subject’s eye. 
a. If required, measurement of the punctum size should be evaluated prior to dilating the 
punctum. 
b. Procedure for dilating the punctum to at least 1.0 mm and inserting a study punctal plug should 
be performed on one eye at a time 
c. Anesthetize the area around the lower punctum, place a drop of topical anesthetic on the eye 
to be inserted. Then add lidocaine gel on a cotton-tipped swab and placing the swab directly 
on the lower punctum 
d. Use the Coroneo Punctal Gauge to dilate the punctum. The punctum must be dilated to at 
least 1.0 mm. Once the punctum is dilated to 1.0 mm, leave dilator in place for 15 to 30 
seconds to allow the sphincter to fully relax. 
NOTE: For small puncta, hold and rotate the dilator in the punctum and canaliculus for as 
long as required to achieve dilation to 1.0 mm. This may take some considerable 

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time. Dilation may require very firm pressure however; care must be taken NOT 
to apply excessive force to dilate the punctum. Add more anesthesia if needed. 
6.1.5.3 Procedure for Insertion of a Travoprost Evolute® (Appendix G for detailed instructions) 
Lubricants are NOT to be used to insert a Travoprost Evolute. Physicians inserting the study 
plug will have been briefed with the instructions and guidelines. It is recommended that the 
punctum be dilated to at least 1 mm prior to attempting insertion. After insertion, a slit-lamp will 
be used to verify the Travoprost Evolute is appropriately positioned.  
NOTE: The punctum may constrict before the plug can be inserted, additional dilation 
would then be required. If a plug is partially inserted (e.g., cap not flush with the 
lid margin) the plug should be removed and the punctum re-dilated or dilated to a 
larger diameter.  
If the Travoprost Evolute cannot be inserted after a few attempts with gentle dilation, the subject 
is not eligible for the study.   
6.1.6 Instructions for Study Subjects after Travoprost Evolute Insertion 
A subject should be instructed not to attempt to remove or adjust the Travoprost Evolute on his/her 
own. In addition, instruct the subject to restrict eye rubbing, swimming, scuba diving, or other 
actions or activities that may result in physical manipulation of the eye region. 
6.1.7 Procedure for the Removal of a Travoprost Evolute (Appendix E for detailed instructions) 
The Travoprost Evolute should be removed from the study subject’s lower puncta using sterile 
ophthalmic forceps, such as Castroviejo Suture forceps (Appendix H, Figure 6) or similar toothed 
forceps, with a gentle tugging motion. A drop of anesthetic may be administered if necessary.  
NOTE: Removal of a Travoprost Evolute immediately after insertion may result in 
the cap of the plug being torn off; the Investigator should wait at least 24 hours 
after insertion before attempting to remove a study plug. Use of a jeweler’s forceps 
is not advisable 
a. Care must be taken not to grasp the outermost edge of the cap on the punctal plug as this may 
cause the cap to tear and separate 
b. The motion to remove the plug should be towards the medial canthus (not up or temporally) 
If the cap becomes separated, try to remove the plug using toothed 0.12 forceps (0.12 Castroviejo 
forceps or similar) by grasping the neck of the plug through the punctum. If this is not possible, 
and only if you feel comfortable doing so, you may attempt to irrigate the canal until the plug 
flushes out of the nasolacrimal duct.  

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NOTE: Study plugs are larger than commercially available silicone plugs and may become 
lodged in the canal more easily. Referral to tertiary care is advised in cases where 
the plug cannot be retrieved by massaging/milking through the punctal opening or 
by irrigation.  
6.1.8 Unable to Insert/Extruded/Lost Travoprost Evolute® 
If either eye of a study subject cannot be dilated to at least 1 mm, the subject will not be eligible 
for the study. 
6.1.8.1 Unable to Insert Travoprost Evolute 
If a Travoprost Evolute cannot be inserted after a few attempts with dilation, the subject will not 
be eligible for the study. Lubricants are NOT to be used.  
NOTE: If the first attempt to insert a plug was successful however, the investigator is 
unable to insert the second plug, the first plug will be removed and the subject will 
be discontinued from the study. Removal of a Travoprost Evolute immediately 
after insertion may result in the cap of the plug being torn off; the Investigator 
should wait at least 24 hours after insertion of the study plug. Retain the plug for 
accountability of investigational supplies. 
6.1.8.2 Extrusion of a Travoprost Evolute 
A study subject that has noticed a study plug has been extruded or lost during the treatment phase, 
the study subject should immediately contact the Investigator and/or his/her staff and return to the 
Investigator’s office as soon as possible. If the study subject can find the extruded plug, they should 
return with the plug where the Investigator and/or his/her staff will collect and retained the plug 
for investigational supply accountability. If the return plug has torn or has separated, report this as 
a technical complaint (Section 8.6). If a study plug has been lost, the Investigator will retro-
illuminate or palpate the canaliculi to confirm the plug has not migrated into the canal. Information 
regarding the loss of any plug must be recorded in the source documents, CRFs and Accountability 
Logs. 
If a single plug has been extruded during the study, the Investigator will re-insert a new plug and 
instruct the study subject to return to the investigator office based on their originally study visit(s) 
scheduled. At any time during the study, a study subject experiences a second extrusions or an 
extrusion in the fellow eye, the study subject will return to the Investigator’s office as soon as 
possible and will have the remaining plug removed. The study subject will be discontinued from 
the study and WILL be replaced. 
6.1.9 Duration of Therapy 
Each subject will have a Travoprost Evolute® inserted in to the lower punctum of each eye. The 
study plug will remain in the study subject’s lower puncta for a period of 90 ± 7 days. 

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6.2 Study Plug Accountability Procedures 
The Investigator is responsible for maintaining the study treatment (punctal plugs) accountability 
log, which will contain inventory records acknowledging the receipt and dispensing of all study 
plugs. The study center will keep a complete accounting of all used, unused, damaged, extruded 
and lost study plugs. All lost/extruded study plugs must be recorded into the accountability log 
and on the CRFs of the study subject who lost/extruded a study plug, noting the suspected date the 
study plug was lost/extruded.  
All used and unused study plugs must be accounted for and kept in the designated secure area at 
the study center until the Sponsor provides instructions for the return of all study materials. Final 
accountability for investigational study plugs will be verified by the Sponsor and/or their 
representatives and considered complete when the study plugs are no longer actively used and all 
study plugs (used, unused, extruded, lost) have been accounted for and returned to the Sponsor. 
7 STUDY PROCEDURES AND SCHEDULE 
Data will be captured and compiled using procedures developed by representatives of Mati 
Therapeutics Inc. All requested study data must be recorded clearly on study NCR CRFs and other 
study forms, as required. An explanation must be provided for all missing data. Only the 
Investigator or his/her staff members who are identified on the Study Personnel Delegation of 
Authority form may enter or correct data on a CRF. Incomplete or inconsistent data on the CRFs 
will result in data queries that will require resolution by the Investigator. 
7.1 Protocol Amendments 
Modification of the protocol is prohibited without prior written agreement in the form of a protocol 
amendment. All amendments will be created by the Sponsor and must be approved by the IRB 
prior to implementation except when required to mitigate immediate safety risks or when the 
changes involve only logistical or administrative revisions. 
7.2 Study Procedures/Evaluations 
7.2.1 Study Specific Procedures 
Procedures that are required during the course of the study include (Appendix C for details): 
a. Informed consent and HIPAA authorization: The Investigator and or qualified staff will 
review and answer any questions a potential study subject may have regarding the study, the 
consent or HIPAA authorization forms. Prior to the initiation of any study specific activities, 
the subject must sign both documents 
b. WOMEN OF CHILDBEARING POTENTIAL, urine pregnancy tests are required at the 
screening visit and when the female subject exits the study 
c. Record subject’s demographic data and medical history for the previous 6 months  

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d. Concomitant Medication use: All prescription systemic, ophthalmic and over-the-counter 
concomitant medications that will be used by the study subject will be documented. The 
medication name, start and stop dates, indication, dose, route of administration and any dosing 
alterations during the study period must be documented on the Concomitant Medications CRF 
e. Verify a subject has followed all instructions regarding the discontinuation of any hypotensive 
ocular medication during the course of the study 
f. Vital Signs (Temperature, Blood Pressure and Heart Rate): Throughout the study vital signs 
will be taken with the subject in the sitting position after the subject has rested five minutes. 
Techniques used to collect vital signs should remain consistent throughout the study 
- Temperature maybe taken using a non-contact (Infrared) thermometer or orally. Oral 
temperatures should not be taken within five minutes of ingestion of any food or drink 
- Blood pressure may be determined manually with a blood pressure cuff and auscultation 
or with an automated Blood Pressure monitor 
- Heart rates may be determined electronically with an automated Blood Pressure monitor. 
Manually obtained heart rates should be recorded after a minimum of 30 seconds of 
observation. 
g. Best-Corrected Distance Visual Acuity testing: Visual acuity with correction (e.g., wearing 
glasses) will be measured using a Snellen chart. Pinhole visual acuity will be measured using 
a Snellen chart while the subject is looking through a pinhole occluder. The test distance and 
lighting conditions specified for the Investigator’s chart must be used and kept constant 
throughout the study  
h. Automated Perimetry (visual fields) will be measured using a Humphrey's Visual Field 
Analyzer (manufactured by Carl Zeiss Meditec Inc., Dublin, CA) with at least a standard full-
threshold 24-2 program or Swedish interactive threshold algorithm (SITA) program. Visual 
fields measured and documented up to SIX months before the Screening Visit are 
acceptable to fulfill the screening criteria 
i. Pachymetry can be measured by contact methods, such as ultrasound and confocal 
microscopy (CONFOSCAN), noncontact methods such as optical biometry with a single 
Scheimpflug camera (such as SIRIUS or PENTACAM), dual Scheimpflug camera (such as 
GALILEI), or Optical Coherence Tomography (OCT), such as Visante. Past corneal 
thickness measurement documented in the subject’s chart are acceptable to fulfill the 
screening criteria 
j. Slit-Lamp Examination: Examination will include assessment of the lid, conjunctiva and 
cornea. Grading of slit-lamp findings are defined in Appendix C. 
k. Perform a NON-DILATED fundus exam of each eye. Using an ophthalmoscope, the 
investigator will examine the back part of the eye (fundus), including the retina, optic disc, 
choroid and blood vessels and evaluation of the lens 
l. Goldmann applanation tonometry will be used for measuring IOP. IOPs will be measured in 
the morning between 8:00 and 10:00 am. The IOP of each eye will be measured twice, 
alternating between the eyes. However, if the second measurement is ≥ ± 3 mmHg from the 
first measurement for an eye, a third measurement will be taken. All measurements taken will 

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be recorded. In the case of two measurements, the average of the two values will be used for 
analysis, and in the case of three measurements, the average of the two closest values of the 
three will be used for analysis for that eye at that specific time point. 
NOTE: Just prior to the start of the study, the tonometer should be calibrated. 
m. Punctal size evaluation and dilation of the punctum (see Appendices E & F for details), 
n. Insertion and removal of study punctal plugs (see Appendix G & H for details)  
o. Adverse Event/Adverse Device Event reporting, Section 8.7 of the protocol for details: To 
optimize consistency of AE/ADE reporting across centers, the study subject will be asked a 
standard question to elicit any AE/ADEs. At each study visit or telephone evaluation of the 
study subject, study personnel will ask the following question: 
“Have you had any problems since your last visit?” 
7.2.2 Standard of Care Procedures 
At any study visit (scheduled or unscheduled), in addition to study specific examinations the 
Investigator will perform their standard evaluations for an OAG or OH patient. 
7.3 Laboratory Procedures/Evaluations 
Not applicable 
7.4 Study Visit Phases/Schedule 
7.4.1 Visit 1 - Screening Phase (Qualification Visit) 
At this visit, prior to any study specific procedure or examination, a subject must read, comprehend 
and give written Authorization for Use/Disclosure of Health Information (HIPAA) and Informed 
Consent to participate in the study. Once all forms have been signed, the investigator and/or his or 
her staff will perform the following screening assessments/examinations.  
a. Verify a subject has not used any hypotensive ocular drops within the last 12 hours of the 
screening visit 
b. A female subject of child-bearing potential will have a urine pregnancy test performed 
c. Record subject’s demographic data and medical history for past 6 months 
d. Measure subject’s temperature, heart rate and blood pressure 
e. Record subject’s Best-Corrected (Glasses) Distance or Pinhole Visual Acuity 
f. Verify automated perimetry results have been measured and documented in the subject’s chart 
within the last 6 months 
NOTE: If perimetry measurement are older than 6 months, perform automated perimetry 
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g. Verify corneal thickness measurements are documented in the subject’s chart 
NOTE: If corneal thickness data is not available, measure corneal thickness of each eye 
using contact or non-contact pachymetry at the screening visit 
h. Perform a slit-lamp examination of each eye 
i. Perform a non-dilated fundus exam of each eye, including the evaluation of the lens 
j. Record IOP measurement of each eye 
k. Record concomitant medication use 
If at any time during the screening examination it is determined a subject does not meet a screening 
inclusion/exclusion criterion, at that point any additional screening assessments-examinations will 
be discontinued.  
After the screening procedures and examinations have been completed, each qualified subject that 
meets all study inclusion/exclusion criteria will be asked to enter the washout phase of the study 
and will be sequentially assigned an ID number (Section 6.1). In addition, the ID number and the 
study subject initials will be recorded on study case report forms, in lieu of recording his/her name, 
in order to maintain subject confidentiality.   
7.4.2 Washout Phase (Six-week duration) 
During the washout phase of the study, each subject will be instructed to discontinue the use of 
his/her topical hypotensive medication(s) for the next six-weeks. In addition, the subject will be 
instructed not to use any other ocular drops, gels or ointments 24 hours prior to the Baseline visit 
(Visit 2) in his/her eyes that have not been prescribed by the investigator. 
Systemic or topical medications that are being used at the Screening Visit, that are considered 
necessary for the subject’s welfare and are PERMITTED by the protocol (Sections 5.2.1), may 
continue to be used as long as the concentration and dosing frequency of the medication(s) will 
remain the same throughout the entire duration of the study.  
Systemic medications that are PROHIBITED by the protocol, must be discontinued during the 
washout phase. All ocular drops, gels or ointments being used by the subject must be discontinued 
24 hours prior to Visit 2. Should the subject qualify for the treatment phase of the study, they will 
be asked to continue for an additional 90 ± 7 days not to use any systemic or topical medications 
during the treatment phase of the study. 
7.4.3 Treatment Phase (Visits 2, 3, 4, 5, 6 & 7) 
At the completion of the washout phase (6-weeks) each subject that continues to meet all study 
screening, washout and baseline criteria will have the lower puncta of each eye inserted with a 
Travoprost Evolute® and scheduled to return to the investigator’s office for follow-up 
examinations at one, seven, 28, 60 and 90 days after insertion of the study plugs.  

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7.4.3.1 Visit 2 - Day 0, Plug Insertion Visit (Baseline) 
Qualified subject will undergo the following: 
a. Verify a subject has not used any hypotensive ocular drops during the washout phase 
b. Verify whether there are any changes in the medical history and confirm the subject still meets 
all study inclusion/exclusion criteria 
c. Record any addition, discontinuation or changes in the subject's use of any concomitant 
medications or ocular drops, gels or ointments during study washout phase 
d. Record subject’s temperature, heart rate and blood pressure 
e. Record subject’s Best-Corrected (Glasses) Distance or Pinhole Visual Acuity 
f. Perform a slit-lamp examination of each eye 
g. Record IOP measurement for each eye  
h. Record any Adverse Events/Adverse Device Event. 
After the baseline procedures and examinations have been completed, a subject that meets the 
baseline IOP inclusion criteria (Section 5.2.3) will have their punctal size of each eye evaluated 
and will be inserted with a Travoprost Evolute into the lower puncta of each eye even if only one 
eye qualifies. 
i. Dilate the lower puncta to 1.0 mm and insert a study plug into the lower punctum of each eye 
(refer to Sections 6.1.5.2 & 6.1.5.3 for details regarding punctum dilation and punctal plug 
insertion techniques) 
j. Evaluate after insertion, the position of the study plugs in each eye using the slit-lamp 
NOTE: At the conclusion of the visit a subject does not meet all treatment 
inclusion/exclusion criteria or the investigator is unable to insert a Travoprost 
Evolute into the lower puncta of each eye, the study subject will be discontinued 
from the study. The subject ID number will be retired. If the investigator was 
able to insert only one study plug, the one inserted study plug must be removed 
(Section 5.4) 
Each study subject will be instructed not to attempt to remove or adjust the punctal plug on his/her 
own. In addition, encourage each study subject to restrict eye rubbing, swimming, scuba diving, 
or other actions or activities that may result in physical manipulation of the eye region 
Each study subject will be scheduled to return the next day for a follow-up study examination 
(Visit 3, day 1 post-plug insertion).   
NOTE: At any time during the treatment phase, a study subject has noticed a plug has been 
extruded or lost they should immediately contact the Investigator and/or his/her 
staff and return to the Investigator’s office as soon as possible (Section 6.1.8.2).   

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7.4.3.2 Visit 3 - Day 1, Post-Plug Insertion 
a. Verify a subject has not used any hypotensive ocular drops since his/her last visit 
b. Record any addition, discontinuation or changes in the subject's use of any concomitant 
medications or ocular drops, gels or ointments since his/her last visit 
c. Record subject’s temperature, heart rate and blood pressure 
d. Record subject’s Best-Corrected (Glasses) Distance or Pinhole Visual Acuity 
e. Evaluate the position of each Travoprost Evolute® using the slit-lamp 
f. Perform a slit-lamp examination of each eye 
g. Record IOP measurement for each eye 
h. Record any Adverse Events/Adverse Device Event 
NOTE: Should a study subject exit the study early (after Visit 2 and before Visit 7), the 
subject must undergo all test and procedures scheduled for Visit 7 (Final Visit). 
7.4.3.3 Visit 4 - Day 7 ± 1, Post-Plug Insertion 
a. Verify a subject has not used any hypotensive ocular drops since his/her last visit 
b. Record any addition, discontinuation or changes in the subject's use of any concomitant 
medications or ocular drops, gels or ointments since his/her last visit 
c. Record subject’s temperature, heart rate and blood pressure 
d. Record subject’s Best-Corrected (Glasses) Distance or Pinhole Visual Acuity 
e. Evaluate the position of each Travoprost Evolute® using the slit-lamp 
f. Perform a slit-lamp examination of each eye 
g. Record IOP measurement for each eye 
h. Record any Adverse Events/Adverse Device Event 
NOTE: Should a study subject exit the study early (after Visit 2 and before Visit 7), the 
subject must undergo all test and procedures scheduled for Visit 7 (Final Visit). 
7.4.3.4 Visit 5 - Day 28 ± 3, Post-Plug Insertion 
i. Verify a subject has not used any hypotensive ocular drops since his/her last visit 
j. Record any addition, discontinuation or changes in the subject's use of any concomitant 
medications or ocular drops, gels or ointments since his/her last visit 
k. Record subject’s temperature, heart rate and blood pressure 
l. Record subject’s Best-Corrected (Glasses) Distance or Pinhole Visual Acuity 
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n. Perform a slit-lamp examination of each eye 
o. Record IOP measurement for each eye 
p. Record any Adverse Events/Adverse Device Event 
NOTE: Should a study subject exit the study early (after Visit 2 and before Visit 7), the 
subject must undergo all test and procedures scheduled for Visit 7 (Final Visit). 
7.4.3.5 Visit 6 - Day 60 ± 5, Post-Plug Insertion 
q. Verify a subject has not used any hypotensive ocular drops since his/her last visit 
r. Record any addition, discontinuation or changes in the subject's use of any concomitant 
medications or ocular drops, gels or ointments since his/her last visit 
s. Record subject’s temperature, heart rate and blood pressure 
t. Record subject’s Best-Corrected (Glasses) Distance or Pinhole Visual Acuity 
u. Evaluate the position of each Travoprost Evolute® using the slit-lamp 
v. Perform a slit-lamp examination of each eye 
w. Record IOP measurement for each eye 
x. Record any Adverse Events/Adverse Device Event 
NOTE: Should a study subject exit the study early (after Visit 2 and before Visit 7), the 
subject must undergo all test and procedures scheduled for Visit 7 (Final Visit). 
7.4.3.6 Visit 7 - Day 90 + 7, Post-Plug Insertion (Final Study Visit) 
At this visit the following will be performed and recorded: 
a. Verify a subject has not used any hypotensive ocular drops since his/her last visit 
b. Record any addition, discontinuation or changes in the subject's use of any concomitant 
medications or ocular drops, gels or ointments since his/her last visit 
c. If performed at SCREENING Visit, perform a urine pregnancy test on a female subject of 
child-bearing potential 
d. Record subject’s temperature, heart rate and blood pressure 
e. Record subject’s Best-Corrected (Glasses) Distance or Pinhole Visual Acuity 
f. Evaluate the position of each Travoprost Evolute using the slit-lamp prior to removal of the 
plug 
g. Perform a slit-lamp examination of each eye prior to study plug removal 
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i. Removal of the study plug from each eye (refer to Section 6.1.7 for details regarding removal 
of a punctal plug) 
j. Record any reported Adverse Events/Adverse Device Event 
An exit form will be completed at the final study examination (Visit 7), or whenever the study 
subject completes or leaves the study for any reason.   
NOTE: The day each Travoprost Evolute® are removed with no addition follow-up 
required, will be the study subject’s official exit date from the study.  However, if 
the subject is exiting from the study due to an AE/SAE or ADE/SADE, the 
study subject will be followed and exam findings recorded by the investigator 
until the AE/SAE or ADE/SADE has resolved or has become medically stable.   
 

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Schedule of Assessments, Events 
Visit Examination Parameters 
 
Visit 1 
Screening 
 
Visit 2 
(Day 0) 
 
Visit 3 
(Day1) 
 
Visit 4 
(Day 7) 
 
Visit 5 
(Day28) 
 
Visit 6  
(Day 60) 
 
Visit 7  
(Day 90) 
Informed Consent/HIPAA 
 
     
 
 
 
 
 
 
 
 
 
 
 
 
Medical Hx (past 6 months)/Demographic Data 
 
     
 
    A  
 
 
 
 
 
 
 
 
 
Urine Pregnancy Test  
(Only women of childbearing potential)  
    B 
 
 
 
 
 
 
 
 
 
 
 
    B 
Concomitant Med Use 
 
     
 
     
 
     
 
     
 
     
 
     
 
     
BT (temperature), BP (blood pressure), HR (heart rate) 
 
     
 
     
 
     
 
     
 
     
 
     
 
     
Evaluate study plug position prior to any eye exam 
 
 
 
    *  
     
 
     
 
     
 
     
 
     
Best-Corrected Distance (Glasses) or Pinhole VA 
 
     
 
     
 
     
 
     
 
     
 
     
 
     
Automated Perimetry  
(Not required if measured in last 6 months)  
     
 
 
 
 
 
 
 
 
 
 
 
 
Pachymetry 
(Not required if documented in patient’s chart)  
     
 
 
 
 
 
 
 
 
 
 
 
 
Slit-Lamp Examination 
 
     
 
     
 
     
 
     
 
     
 
     
 
     
IOP (Goldmann) Evaluation  
(To be measured between 8 and 10 am)  
     
 
     
 
     
 
     
 
     
 
     
 
     
Non-Dilated Fundus Examination  
(Include evaluation of the LENS)  
     
 
 
 
 
 
 
 
 
 
 
 
 
Begin Six-Week Washout 
(D/C all topical drops, gels, ointments)  
     
 
 
 
 
 
 
 
 
 
 
 
 
Punctal Size Evaluation, Dilation of Lower Puncta 
 
 
 
     
 
 
 
 
 
 
 
 
 
 
Insertion of Punctal Plugs 
 
 
 
     
 
 
 
 
 
 
 
 
 
 
**Punctal Plug Extrusion 
 
 
 
 
 
   C 
 
   C,D  
   C,D  
   C,D  
     
Removal of Punctal Plugs after eye exam completed 
 
 
 
 
 
 
 
 
 
 
 
 
 
     
Adverse Event/Adverse Device Event Recording 
 
 
 
     
 
     
 
     
 
     
 
     
 
     
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Keys to Abbreviations: 
A 
= Verify no change in medical history, subject still meets all study inclusion/exclusion criteria 
B 
= If performed at the screening visit, must be performed when subject exit the study  
C 
= In a subject where both eyes qualified at Visit 2, if a plug is extruded in one eye, plug is to be replaced and subject continues in the study 
D 
= In a subject where only one eye qualified at Visit 2, if the plug is extruded in the qualified eye, the subject will be DISCONTINUED and replaced.  In a subject where both eyes qualified, if a 
plug is extruded in one eye, then extruded again or in the fellow eye, the subject will be DISCONTINUED and replaced 
* 
= Plug position evaluated after eye exam and plug insertion 
 
= If subject EXITs the study after visit 2, but before visit 7, subject must return to Investigator’s office to have plugs removed  
 
Body Temperature: 
Temperature maybe taken using a non-contact (Infrared) thermometer or orally. Oral temperatures should not be taken within five minutes of ingestion of any food or drink 
Heart Rate: 
Heart rate taken in the sitting position after subject has rested for 5 minutes. Recorded values can be obtained electronically (automated) or manually (observed for 30 seconds or more) 
Blood Pressure: 
Blood pressure, taken in the sitting position after subject has rested for 5 minutes. Recorded values can be obtained electronically (automated) or manually  
Plug Position Evaluation: 
Position of the plug will be evaluated as either: Normal, Present but requires adjustment, Extruded/Recovered, Extruded/Lost, Other 
Slit-Lamp Exam: 
Evaluation will include the Lids (Upper & Lower), Conjunctiva (Bulbar & Palpebral) and the Cornea. SL Findings will be graded on a 5-point scale:   
     0 = None, 1 = Trace, 2 = Mild, 3 = Moderate, 4 = Severe 
IOP Evaluation: 
Goldmann applanation tonometry will be used for measuring IOP. Just prior to the start of the study, the tonometer should be calibrated. IOP of each eye will be measured twice, 
     alternating between the eyes. The average of the two measurements will be used for analysis. However, if there is a > ± 3 mmHg difference between the 1st and 2nd measurement  
     for an eye, a 3rd measurement will be taken and the average of the two closest values of the three will be used for analysis for that eye. 
 

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7.5 Unscheduled Visit 
The investigator has the option of bringing a study subject back in for an unscheduled visit any 
time during the washout or treatment phase of the study for safety reasons (e.g., subject complaint 
of moderate or severe ocular symptoms, an AE). An unscheduled visit CRF should be completed. 
At minimum the investigator should record the following: 
a. Record any change in concomitant medication use 
b. Inspection of both punctal plugs via the slit-lamp 
c. Slit-Lamp examination, both eyes 
d. Measure IOP, both eyes 
e. Recording of any reported adverse events/adverse device events 
7.6 Early Exit Visit (Disqualified, Discontinued or Terminated Study Subject) 
Any study subject exiting the study early must undergo all test and procedures scheduled for Visit 
7 (Day 90 ± 7 days, post-plug insertion) and all results recorded on the appropriate CRFs.   
NOTE: Refer to Section 7.4.3.6 for details on procedures and examination to take place 
on the final study subject visit  
An exit CRF (Case Report Form) will be completed whenever the study subject completes or 
leaves the study for any reason. A study subject will be exited from the study on the day the 
Travoprost Evolute® are removed from both eyes with no additional follow-up required. However, 
if the subject is exiting from the study due to an AE/ADE, the study subject will be followed 
and exam findings recorded by the investigator until the AE/ADE has resolved or has become 
medically stable.   
7.7 Emergency Anaphylactic or Overdose Procedures, Dose Modifications 
Dose modification of the study drug/device is not possible or required in this study.   
NOTE: Use caution when inserting a study plug to a subject who has previously exhibited 
sensitivities to phenylacetic acid derivatives and salicylate hypersensitivity as the 
potential for cross-sensitivity exists. This study is not expected to cause AEs 
different in type or intensity from those previously reported in published clinical 
research literature regarding the use of topical travoprost ophthalmic solutions 
0.004% & 0.003% (TRAVATAN®, TRAVATAN Z®, IZBA®). Refer to the 
Investigator Brochure and Appendices I, J & K for additional information. 
Should a subject experience a significant medical issue, the subject may be treated according to 
the Investigator’s medical judgment. Any changes, discontinuation or addition of a topical or 
systemic medication(s) must be recorded on the Concomitant Medication CRF. 

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7.8 Concomitant Medication 
During the washout and treatment phases of the study, each subject will be instructed not to use 
any other ocular drops, gels or ointments in his or her eyes that have not been prescribed by the 
investigator. Systemic or topical medications that are being used at the Screening Visit, that are 
considered necessary for the subject’s welfare and are permitted by the protocol (Section 5.2.1.2 
for details), may continue to be used as long as the concentration and dosing frequency of the 
medication(s) remains the same throughout the entire washout and treatment phases of the study.  
7.8.1 Pre-Study Concomitant Medication Use 
Pre-study concomitant medication is defined as a prescription and/or an over-the-counter (OTC) 
medication taken within 2 months (whether continuing or not) prior to Visit 1 (Screening Visit). 
All prior medications must be documented on the Concomitant Medications CRF. 
7.8.2 Concomitant Medication Use during Study 
Each study subject will be instructed not to use any other ocular drops, gels or ointments in his/her 
eyes that have not been prescribed by the Investigator. Systemic medications being used at 
screening visit that are permitted by the study protocol (see inclusion/exclusion criteria for details), 
are considered necessary for the study subject’s welfare, and will not interfere with the study may 
be used.   
All prescription systemic, ophthalmic and over-the-counter concomitant medications used during 
the washout and treatment phase of the study, that are considered necessary for the study subject’s 
welfare, and will not interfere with the study, may be used but must be documented on the 
Concomitant Medication CRF. The use of all concomitant medications during the study, except 
for routine medications given for ocular study procedures required by the protocol (i.e., topical 
anesthetic for plug insertion), will be documented. The medication name, start and stop dates, 
indication, dose, route of administration and any dosing alterations must be documented on the 
Concomitant Medications CRF through completion of the last study visit. 
Systemic or topical medications that are being used at the Screening Visit, that are considered 
necessary for the subject’s welfare and are permitted by the protocol (Section 5.2.1.2, criteria 12 
& 18, for details), may continue to be used as long as the concentration and dosing frequency of 
the medication(s) will remain the same throughout the entire duration of the study.  
7.9 Prohibited Medications, Treatments and Procedures 
7.9.1 Prohibited Medications 
After the screening visit, the use of any ocular drops, gels or ointments in either eye is prohibited, 
with the exception for routine topical medication given for an ocular study procedure(s) that is 
required by the protocol (i.e., topical anesthetic). Systemic or topical medications being used at 

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the Baseline Visit that are permitted by the protocol (Section 5.2.1.2, criteria 12 & 18, for details), 
are considered necessary for the subject’s welfare, and will not interfere with the study may be 
used.   
7.9.2 Prohibited Treatments 
The following are prohibited during the study washout and treatment periods: 
a. Use of homeopathic remedies (e.g., gingko biloba, cayenne pepper, bilberry, etc.) 
b. Significant changes to eating or drinking habits (i.e., begin a diet, increase or decrease alcohol, 
caffeine or water intake, etc.) 
c. Significant changes in physical exercise/yoga 
d. Use of marijuana 
7.9.3 Prohibited Procedures 
The following procedures are prohibited during the study washout and treatment periods: 
a. Laser trabeculoplasty 
b. Trabeculectomy 
c. Tube shunt surgery 
d. Cataract surgery 
7.10 Rescue Medication(s) 
7.10.1 Administration of a Rescue Medications 
A subject with an elevated IOP (>34 mmHg) or undue medical risk in either eye should be 
prescribed his/her glaucoma regimen they were using prior to entering the study The use of a 
rescue medication will be considered prohibited medication and will be considered a protocol 
deviation and the study subject will be terminated from the study. Reason for termination on the 
exit form should be listed as “due to lack of efficacy”. 
8 ASSESSMENT OF SAFEETY 
8.1 Safety Variables 
Safety variables for this study will include any reported AE/ADE and rescue medication use. 
Safety variables will also include clinically significant changes in IOP, BCDVA, slit-lamp 
findings, ocular tearing and comfort, blood pressure, heart rate, temperature, extrusion of a 
Travoprost Evolute®, or technical issues with the study plug (e.g., cap of study plug tears or 
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To optimize consistency of AE/SAE reporting across sites, the study subject will be asked a 
standard question to elicit any AE/SAE. At each study visit or telephone evaluation of the study 
subject, study personnel will ask the following question:   
"Have you had any problems since your last visit?" 
8.2 Definitions 
8.2.1 Adverse Event 
Adverse Event (AE): any unanticipated sign (including a clinically significant abnormal laboratory 
finding), symptom, or disease temporally associated with the administration of a medicinal 
product, whether or not considered related to the investigational product or device.  
Medical conditions or diseases present before a subject starts study treatment are only considered 
AEs if they worsen after the subject starts study treatment.  
8.2.2 Serious Adverse Event 
Serious Adverse Event (SAE): defined as any AE that (at any dose): 
• Results in death 
• Is life-threatening. NOTE: The term "life-threatening" refers to an event in which the subject 
was at risk of death at the time of the event; it does not refer to an event which hypothetically 
might have caused death if it were more intense 
• Requires inpatient hospitalization or prolongs existing hospitalization 
• Results in persistent or significant disability/incapacity 
• Is a congenital anomaly/birth defect 
• May jeopardize the subject or may require intervention to prevent one of the outcomes listed 
above. Medical and scientific judgment should be exercised in deciding if these events should 
be considered serious. Examples of such events are intensive treatment in an emergency room 
or at home for allergic bronchospasm, blood dyscrasias or convulsions that do not result in 
hospitalization, or development of drug dependency or drug abuse. 
In addition, an AE that results in overdose or produces congenital abnormality or cancer is always 
considered an SAE. 
A subject admitted to a hospital as a result of an AE, even if released on the same day, would 
qualify for inpatient hospitalization. An emergency room visit that results in admission to the 
hospital would also qualify for inpatient hospitalization. However, emergency room visits that do 
not result in admission to the hospital would not qualify for inpatient hospitalization and, instead, 
should be evaluated for one of the other criteria for SAEs (e.g., life-threatening AE or medically 
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Hospitalization scheduled before a subject enrolls in the study is not the result of a 
treatment-emergent AE, and therefore events leading to such hospitalization will not be considered 
study AEs or SAEs. During the study, if a subject has elective surgery for a condition present at 
screening into the study, and the condition did not worsen during the study, the reason for elective 
surgery, and resulting hospitalization (if applicable), should not be considered or reported as an 
SAE. Surgery or hospitalization should always be reported as an outcome of an AE. For AEs that 
result in persistent or significant disability/incapacity, refers to a substantial disruption of a 
subject's ability to carry out normal life functions. 
The investigator must also submit documentation of the following to the Institutional Review 
Board, Ethics Committee, or Research Ethics Board (collectively referred to as an IRB): 
• Site-specific SAEs and follow-up: The type of serious event that must be submitted (e.g., all 
or only suspected), as well as the required timing of submission (e.g., within 10 days of 
occurrence), is defined by the IRB and regulations/guidance from regulatory authorities.  
• Any documentation provided by the Sponsor regarding reportable SAEs from the study: The 
Sponsor will provide documentation of reportable events to the investigator, as specified in 
Section 8.7. 
The investigator should ensure that the subject receives appropriate medical treatment and that the 
subject is followed up until the SAE resolves or becomes chronic, as defined in Section 8.4. 
8.3 Adverse Event Descriptions 
8.3.1 Intensity 
The intensity of AEs will be characterized as mild, moderate, or severe, as follows: 
• Mild: Usually transient, requiring no special treatment, and does not interfere with the 
subject's daily activities 
• Moderate: Introduces a low level of inconvenience or concern to the subject and may interfere 
with daily activities, but is usually ameliorated by simple therapeutic measures 
• Severe: Significantly interferes with a subject's usual daily activities and requires systemic 
drug therapy or other treatment, if available 
8.3.2 Relationship to Study Treatment 
The causal relationship to study drug or treatment will be determined by the investigator according 
to best medical judgment, as follows: 
• Suspected: There is a reasonable possibility that the AE is associated with use of the study 
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when other drugs, therapeutic interventions, or underlying conditions do not provide a 
sufficient explanation for the observed event 
• Not suspected: A relationship between the AE and the study treatment can reasonably be ruled 
out based on lack of any temporal relationship of the event to study treatment administration, 
or when the subject's underlying condition, medical history, or other therapy provide 
sufficient explanation for the observed event. 
8.4 Follow-up for Adverse Event Definitions 
Throughout the study to the final study contact, all AEs will be followed until they resolve or 
become chronic (as judged by the investigator).  
At the final study visit, new AEs, as well as follow-up information for continuing AEs, will be 
recorded in the CRF and source document. If an SAE (defined in Section 8.2.2) is unresolved at 
the final study visit, it will be followed by the investigator until it resolves or becomes chronic (as 
judged by the investigator). Follow-up data for such SAEs will be recorded in the source document 
and reported to the safety monitors (refer to Section 8.7.2). Non-serious ongoing AEs will be 
followed beyond the final study visit at the discretion of the investigator and recorded in the source 
documents.   
8.5 Pregnancy Follow-up 
If a subject becomes pregnant during the study, the investigator must inform the Sponsor and 
collect follow-up data regarding the pregnancy, birth, and status of the child. The Sponsor will 
provide special CRFs for data collection in the case of pregnancy. Follow-up should be continued 
until study close-out at the study site. After close-out, the Sponsor's Safety designee will continue 
to obtain follow-up information. 
Pregnancy should be recorded as a protocol deviation. Pregnancy is not an AE; however, any 
complication related to pregnancy would be considered an AE. 
8.6 Reporting of Technical Complaint 
8.6.1 Definitions 
A quality complaint is one that is received in writing, electronically, or orally that involves the use 
or attempted use of a Travoprost Evolute® plug that identifies any defect in the physical properties 
of the drug product (color, precipitates, viscosity, etc.) or its packaging. Technical complaints also 
include any identified customer dissatisfaction with the physical characteristic(s) of the study 
product (dispensing characteristics, labeling, packaging, etc.). 
8.6.2 Reporting of Technical Complaints 
Any technical complaint should be reported by fax to the Sponsor's Chief Scientific Officer 
(contact information below) within 24 hours. The complaint report should include the following 
information: 

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• Name of the study product 
• Strength of study product 
• Batch/lot number of study product 
• Investigator name, study site name, and contact number 
• Date the complaint occurred 
• Brief description of the complaint 
• Identity of any other investigational or commercial devices involved. 
• Study subject or another individual involved (yes/no):  
o If yes and a study subject, the investigator should report whether any AEs were associated 
with the complaint (yes/no; if a subject AE was associated with the complaint, refer to 
Sections 8.6 & 8.7 and attach the AE CRF page to the complaint) 
o If yes and another individual, the investigator should describe the situation and any ill 
effects on the health of the individual 
o If no, in the investigator's judgment, the investigator should report whether the complaint 
could reasonably cause an SAE if it recurred under circumstances that did involve a study 
subject or other person (yes/no). 
The study product and associated packaging that initiated the complaint should be returned to the 
Chief Scientific Officer (address below) for analysis. 
Mati Therapeutics Inc.  
Attn: Chief Scientific Officer 
Deepank Utkhede 
201 – 4475 Wayburne Drive 
Burnaby, BC 
Canada V5G 4X4 
Fax: 
604.637-8747 
Phone: 778.991-3301 
Any complaint about a study product must be reported regardless of whether the defect or 
deficiency had any effect on a subject or on study personnel. 
8.6.3 Punctal Plug Delivery System Serious Adverse Events and Technical Complaints 
The Sponsor will evaluate all SAE reports and technical complaints received in the study to 
determine if the report meets the definition of an unanticipated ADE. Unanticipated ADEs are 
defined as follows: 
• Any serious adverse effect on the health or safety or any life-threatening problem or death 
caused by, or associated with, a device, if that effect, problem, or death was not previously 

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identified in nature, severity, or degree of incidence in the investigational plan or application 
or any other unanticipated serious problem associated with a device that relates to the rights, 
safety, or welfare of a subject. 
If the Sponsor determines that any SAE or technical report is an unanticipated ADE, an 
investigation will begin immediately. The Sponsor will inform the investigator of any additional 
reporting requirements beyond those stated in Sections 8.6 & 8.7 as applicable. 
If the Sponsor determines that an unanticipated ADE presents an unreasonable risk to a subject, 
the Sponsor will terminate the study as soon as possible. Termination will occur no later than five 
working days after the Sponsor makes this determination and no later than 15 working days after 
the Sponsor first received notice of the effect. The Sponsor will report the results of any 
investigations to the FDA and to investigators, who will also submit the reports to his/her IRBs, 
within 10 working days after the Sponsor first received notice of the effect. 
8.6.4 Anticipated Adverse Event 
The following is a list including, but not limited to, ocular adverse events that are anticipated. Any 
event that is unlikely but anticipated must have an adverse event form completed and reported to 
Mati Therapeutics Inc. (Section 8.7 for reporting details). 
Listing of Anticipated Ocular Adverse Events 
DRUG:  
Incidence rate 30-50%: Hyperemia (*Hyperemia in IZBA controlled studies noted at 12%) 
Incidence rate 5-10%: Decreased VA, Eye Discomfort, Foreign Body Sensation, Pain, Pruritus 
Incidence rate 1-4%: 
Abnormal Vision, Blepharitis, Blurred Vision, Cataract, cells, 
Conjunctivitis, Corneal Staining, Dry Eye, eye disorder, Iris 
Discoloration, Keratitis, Lid Margin Crusting, Ocular Inflammation, 
Photophobia, Subconjunctival Hemorrhage, Tearing 
DEVICE: 
The main risks of commercial silicone punctal plugs are ocular discomfort, epiphora (watery 
eyes), loss of plug (extrusion), ocular inflammation, and subconjunctival hemorrhage. Less 
common, but serious, side effects include but are not limited to pyogenic granuloma, damage to 
the muscle at the opening of the punctum, canaliculiti or migration of the plug into the canalicula 
(requiring irrigation or surgery) 
NOTE: Patient treated with an ophthalmic solution of travoprost should be informed of the 
potential for increased brown pigmentation of the iris, periorbital and/or eyelid 
tissue, and increase growth of eyelashes in the treated eye 
8.7 Reporting Procedures 
AEs/ADEs that occur from Visit 2 through completion of the end-of-study visit must be 
documented. The Investigator will assess the AE/ADE severity and relationship to the travoprost 
Evolute®. The Investigator will follow the progress of the study subject until the AE/ADE either 
resolves or becomes medically stable. Treatments and medications required for treatment must be 
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All AEs/ADEs, regardless of severity and whether or not attributed to the drug delivery device are 
to be reported to Mati Therapeutics Inc. AEs/ADEs are also to be reported to the site IRB per the 
IRB’s reporting requirements.  
8.7.1 Adverse Event Reporting 
For each reported AE, investigators should record the following on the appropriate CRF and in the 
subject’s source documents: whether an AE is serious (yes/no), the date of onset, date resolved 
(date or ongoing), duration (minutes/hours/days), frequency (single/intermittent), severity 
(mild/moderate/severe), relationship to study treatment (suspected/not suspected), and if treatment 
was required (medication prescribed, stopped treatment, etc.). 
An adverse event that is not serious or related to the study drug or drug delivery device is to be 
reported to the designated Medical Monitor within 10 working days of the Investigator first 
becoming aware of the event. Notification will occur by recording on the appropriate CRF(s), 
scanning and email or faxing the CRF(s) of the visit in which the event is first noted. An adverse 
event is also to be reported to the reviewing IRB/IEC per their reporting requirements. 
8.7.2 Serious Adverse Event Reporting 
Any severe, serious or unexpected AE occurring during or within 15 days after the completion of 
the study, regardless of cause(s) or relationship to the study drug or the drug delivery device, an 
initial report must be made immediately (within 24 hours) once becoming aware of the event by 
telephone, facsimile, or email to the study Medical Monitor, Robert Williams, MD or the Study 
Monitor, Daniel Schwob (see contact information below).  
The Investigator must complete an SAE Report Form and send it with other relevant pages of the 
CRF to the designated Medical Monitor within 24 hours of the initial discovery of the event. The 
Investigator will also compile with urgent priority other relevant documentation (copies of test 
results, hospital discharge summary, autopsy report, etc.) and send this information to the 
designated Medical Monitor. Any SAE will be reported to the Investigator’s IRB/IEC per their 
reporting requirements. 
All SAEs will be reported to: 
Robert Williams, MD 
Daniel Schwob (back up contact) 
Medical Monitor 
Study Monitor 
Mati Therapeutics Inc. 
D’Ellis Group, Inc. 
email: iopdoc1@gmail.com 
email: dschwob@dellisgroup.com 
Phone: (Office): 360.378-7916 
Phone: (Office): 949.916-2800 
Phone: (Cell) 
360.298-5325 
Phone: (Cell) 
949.735-1320 
Fax: 
 
360.282-6871 

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8.7.3 Unanticipated Problem Reporting 
If during the study an adverse event occurs that may reasonably be regarded as study drug and/or 
study-device-related and was not previously expected in nature, severity, or degree of incidence in 
the investigation plan, the Investigator is to report the unanticipated adverse event to the designated 
Medical Monitor within 48 hours, and to the Investigator’s IRB as soon as possible, but no later 
than 10 working days, after learning of the event as required by 21CFR812.  
8.7.4 Events of Special Interest 
Not Applicable 
8.8 Halting Rules 
Collaboration between representatives of Mati Therapeutics Inc., Investigators and statisticians 
may stop the study if there is evidence of a lack of safety or efficacy associated with the study 
drug/device or if there is sufficient evidence of efficacy to warrant phase III testing. 
8.9 Safety Oversight 
This study will utilize a Medical Monitor for safety monitoring. The Medical Monitor will review 
and assess any reports of adverse events/adverse device events and, if necessary, to discuss these 
with the reporting Investigator(s). The medical monitor will also be available to answer all 
questions from Investigators. 
9 CLINICAL MONITORING 
Mati Therapeutics Inc. representative will ensure that the investigation is conducted in accordance 
with the following:  
a. GCPs as specified in ICH E6 (R2) and E8 (8.2) and 21 CFR. Parts 50, 54, 56, 312 and 812 
b. The signed Investigators' Agreement 
c. The signed IRB approved protocol for the study 
d. Any conditions imposed by the IRB 
e. The requirements of the regulations for the Protection of Human Patients (21CFR50) and all 
other applicable regulations 
Prior to initiation of the study at a site, a Mati representative will conduct a visit with the 
Investigator(s) and the study staff to ensure the following 
a. The Investigator understands the investigational status of the study material and the 
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b. The Investigator understands the protocol and understands and accepts his/her obligations in 
conducting the clinical investigation 
c. The Investigator has adequate facilities for conducting the study, and equipment and 
instrumentation required by the protocol 
d. The Investigators and his/her staff have sufficient time and access to an adequate number of 
subjects to conduct the clinical investigation. 
During the course of the investigation, a Mati representative may conduct periodic site visits and 
maintain telephone contact with the Investigators and his/her staff to verify that the study is being 
conducted in accordance with the protocol, and with any specific conditions of the IRB and clinical 
requirements. At such visits, a Mati representative will: 
a. Verify that informed consent has been obtained and documented for each study subject, in 
accordance with 21 CFR parts 50 and 56, and the requirements of the overseeing IRB and the 
Sponsor.   
b. Review and compare CRFs to source records and supporting documents to ensure that data 
recorded on the CRFs are complete, accurate, and legible 
c. Verify that any corrections to the CRFs are made with a single line strike-through of the 
incorrect entry, and entry of the correct information adjacent with initials of the individual 
making the correction and date of corrected entry 
d. Verify that there are no data omissions and that any study subject withdrawals are 
documented.   
e. Review CRFs and source records for any unanticipated AEs/ADEs, and ensure that the 
Investigators are complying with FDA and Sponsor requirements for reporting AEs/ADEs 
and SAEs/SADEs.   
f. Verify that the Investigator(s) is carrying out the agreed upon activities and has not delegated 
them to unauthorized staff and that the facilities and staff continue to be acceptable for the 
study. 
g. Verify the Investigator(s) is properly tracking study inventory and is accounting for the 
disposition of all study devices. 
h. Prepare and maintain records of each site visit, significant telephone discussion, and written 
communications with the site. These records will include such information as: 
i. Date, name, and address of the Investigator(s) and names of other staff members present 
at each meeting 
ii. A summary of the findings of the visit 
iii. A statement of any action taken by a Mati representative or Investigator(s) to correct any 
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10 STATISTICAL CONSIDERATIONS 
10.1 Statistical and Analytical Plans 
The primary analysis population will be an ITT (Intent-to-Treat) analysis for all study subjects 
who had the lower puncta of each eye inserted with a study punctal plug and had no major protocol 
violations. Individual study subjects or individual visits may be excluded if a major protocol 
violation occurs (such as violation of inclusion/exclusion criteria or non-compliance with protocol 
requirements that can potentially have significant impact on study outcomes).   
10.2 Statistical Hypotheses 
The Null Hypothesis:  
There are no differences between baseline and follow-up visit intraocular 
pressure values 
Alternative Hypothesis: There are differences between baseline and follow-up visit intraocular 
pressure values 
10.3 Analysis of Datasets 
Data will be pooled from all study sites for data analysis, unless otherwise specified.  Study dataset 
will be generated (keypunched) from original (white) case report forms (CRFs) that have been 
reviewed and collected from clinical sites. Dataset will contain rows of individual subject data; 
each row will be clearly labeled with the study subject assigned study number and initials. Each 
column of the dataset will contain a specific parameter for all study subjects.   
10.4 Description of Statistical Methods 
10.4.1 General Approach 
Descriptive statistics (i.e., mean, standard deviation, etc.) will be provided for all continuous 
variables and frequency distributions will be generated for all categorical variables collected in 
this study. Analyses of the intent-to-treat (ITT) data set, will include all data from all subjects with 
a recorded screening visit IOP OU. Per protocol (PP) analyses dataset, will exclude data from 
subjects or visits with significant protocol deviations (e.g., IOPs obtained before 8:00 AM and 
after 10:00 AM will be excluded). 
10.4.2 Analysis of Primary Study Variable 
The primary study outcome variable will be the change in IOP at Visits 4, 5, 6 and 7 (Days 7, 28, 
60 and 90 days post-insertion) compared with the Baseline IOP (Visit 2, Day 0), obtained between 
8:00 and 10:00 AM. The unit of analysis will be the study eye at visit 2 with the highest post-
washout IOP. Observed IOP and percent change from baseline in IOP will also be analyzed. 
10.4.3 Other Data Endpoints 
The following will be evaluated: 

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- Mean and percent change in Baseline IOP (post-washout) compared with Screening IOP (pre-
washout)  
- Mean and percent of patients screened vs patients that qualified for the study washout phase 
- Mean and percent of patient entered in the washout phase that qualified for the treatment phase 
- Evaluate enrollment rate of patients in to the various phases of the study (avg. number of 
patients by day/week/month) 
- Mean and percent of patients and eyes with IOPs > 34 mmHg post-washout 
- Mean and percent of patients and eyes that extruded a plug during the study treatment phase 
- Mean and percent of patients and eyes the investigator was unable to dilate to at least 1.0 mm 
- Mean and percent of patients and eyes the investigator was unable to insert with a Travoprost 
Evolute® 
- Listing of reasons why patient failed to qualify for various phases of the study 
10.4.4 Safety Analyses 
All subjects that qualify for the washout phase of the study will be evaluated. Safety variables will 
include any clinically significant changes in IOP, BCDVA, slit-lamp findings, ocular tearing and 
comfort, blood pressure, heart rate, temperature, study plug inspections/extrusions, and incidence 
and severity of any reported AEs/SAEs and ADEs/SADEs.   
10.4.5 Adherence and Retention Analyses 
Not Applicable 
10.4.6 Baseline Descriptive Statistics 
Demographic and baseline characteristics will be summarized. Counts and percentages will be 
presented for categorical variables such as gender, age group (by decade), race and ethnicity. 
Mean, standard deviation, median, minimum and maximum will be presented for continuous 
variables such as age and non-dilated punctum size. 
10.4.7 Planned Interim Analyses 
Data will be analyzed on an ongoing basis. The final analyses will be completed after the last study 
subject has completed his/her final visit and the study database has been closed. 
10.4.8 Tabulation of Individual Response Data 
Not Applicable 
10.4.9 Exploratory Analyses 
Not Applicable 

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10.5 Sample Size 
Since this is a pilot study, no formal sample size estimation will be performed.   
10.6 Measures to Minimize Bias 
Not Applicable. 
10.6.1 Enrollment 
Each investigational site will be assigned a site ID number (e.g., 100, 200 . . . 500). As a potential 
study subject qualifies to enter the study washout period, they will be sequentially assigned a study 
number that corresponds with the site ID number (e.g., 101, 102, . . . 110). If the potential subject 
does not qualify after the washout period, the subject ID number will be retired. Those subjects 
that do qualify will be identified throughout the treatment period of the study by his/her assigned 
subject ID number and initials. 
10.6.2 Evaluation of the Success of Blinding/Masking Treatment 
Not Applicable 
11 SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS 
11.1 Source Documentation 
The Investigator must maintain adequate and accurate source documents upon which CRFs for 
each study subject are based. They are to be separate and distinct from the CRFs, except for cases 
in which the Sponsor has predetermined that direct data entry into specified pages of the subject's 
CRF is appropriate. Study source documents should include detailed notes on: 
a. Study protocol number 
b. The oral and written communication with the study subject regarding the study treatment 
(including the risks and benefits of the study).   
c. The date that informed consent and HIPAA forms were signed must be recorded in the source 
documentation 
d. The study subject's medical history prior to participation in the study 
e. The study subject's basic identifying information, such as demographics, that links the 
subject's source documents with the CRFs 
f. Date of all study subject visits throughout the duration of the study 
g. Date the punctal plug was first inserted, removed and if applicable, dates of any plug that was 
extruded/loss and a new plug was re-inserted 
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i. The subject's exposure to any concomitant therapy (including start and stop dates, route of 
administration, and dosage) at each visit 
j. Blood pressure, temperature and heart rate values at each visit 
k. All reported AEs/ADEs and SAEs/SADEs 
l. All relevant observations and data on the condition of the subject throughout the study 
11.2 Access and Retention of Study Records 
The study is subject to audits by the Sponsor/designee, third parties, or by regulatory authorities. 
If such an audit occurs, the Investigator must agree to allow access to all required study subject 
records. The Investigator will notify Sponsor promptly of any FDA audits that are scheduled, and 
must forward copies of any resultant Form 483 and/or audit reports to the Sponsor promptly. 
All study records will be maintained by the Investigator at the site for a minimum of 2 years 
following the date a marketing application is approved for the drug for which the indication was 
being investigated. If no application is to be filed or the application is not approved for such 
indication, study records must be retained for at least 2 years after the investigation is discontinued 
and the FDA is notified. 
11.3 Subject Confidentiality 
All records identifying the study subject by name will be kept confidential. The Investigator will 
ensure the study subject’s anonymity is maintained throughout the course of the study. A study 
subject will be assigned a site/subject ID number to maintain study subject confidentiality. In 
particular, the Investigator will keep an enrollment log with confidential identifying information 
that corresponds to the subject numbers and initials of each study subject. A study subject name 
may possibly be disclosed to Mati Therapeutics Inc. or regulatory agencies during inspection of 
medical records related to the study, but reasonable precautions will be taken to maintain 
confidentiality of personal information to the extent permitted by applicable laws and regulations. 
If the results of the study are published, the study subject’s identity will remain confidential. 
11.4 Case Report Form Completion 
The Investigator is responsible for ensuring that data are properly recorded on each study subject’s 
case report forms and related documents. An Investigator who has signed the protocol signature 
page should personally sign completed case report forms to ensure that the observations and 
findings are recorded on the case report forms correctly and completely. Following study 
examination, investigative sites should complete and remove the yellow NCR copy of the CRF 
from the study subjects’ booklet leaving the white copy of the CRF intact inside the booklet. 
Yellow copies of completed CRFs will be mailed in on a weekly basis to the following: 
D’Ellis Group, Inc. 
Attn: Daniel Schwob 

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Foothill, Ranch, CA  92610 
The white copy of the CRF data will be reviewed against the subject’s source data by the study 
monitor(s) to ensure completeness and accuracy. After monitoring has occurred at the clinical 
site(s) and the CRFs have been submitted, additional data clarifications and/or additions may be 
needed. Data clarifications and/or additions are to be documented and will be part of each subject’s 
CRFs. 
11.5 Investigator Study Summary 
A final Investigator’s summary will be provided to Mati Therapeutics Inc. within approximately 
three months after the completion of the study. The Investigator summary should include: 
a. Investigator name and title 
b. Title of the protocol 
c. Date the clinical study began (1st enrolled study subject) and the date the last study subject 
exited the study 
d. Number of study subjects enrolled into the study, completed, discontinued, terminated, 
withdrew 
e. Brief discussion regarding any reported AEs/SAEs and ADEs/SADEs 
f. Brief discussion of clinical findings during the study. 
12 QUALITY ASSURANCE AND QUALITY CONTROL 
Investigator must grant permission to personnel from the Sponsor, its representatives, third parties 
and appropriate regulatory authorities for on-site monitoring and review of all appropriate study 
documentation, as well as on-site review of the procedures employed in data collection, where 
clinically appropriate. Study auditing, data entry, verification and validation, and subsequent 
analysis will be performed by the Sponsor or Sponsor’s designees in accordance with GCPs and 
established Standard Operating Procedures. 
13 ETHICS/PROTECTION OF HUMAN SUBJECTS 
13.1 Ethical Standard 
The Investigator agrees to conduct the study in accordance with United States Investigational New 
Drug regulations specified under 21 CFR 11, 50, 54, 56, and 312, the International Conference on 
Harmonization (ICH) Harmonized Tripartite Guideline for Good Clinical Practice (GCP), and the 
Guidelines of the Declaration of Helsinki, Finland, 1964 and its subsequent amendments (Tokyo, 
Japan, 1975; Venice, Italy, 1983; Hong Kong, 1989; Republic of South Africa, 1996; Scotland, 

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2000). The Investigator will conduct all aspects of the study in accordance with all national, state, 
and local laws of the pertinent regulatory authorities. 
13.2 Institutional Review Board 
The protocol, Informed Consent Form (ICF), and any study subject information sheet must be 
approved in writing by the appropriate IRB before the study can be initiated at a site. A copy of 
the IRB approval must be sent to the Sponsor (or designee) along with a list of the IRB members 
and their occupations/affiliations. Institutional Review Board approval is also required for any 
advertising or other material used for subject recruitment. If the protocol is amended, the 
Investigator must sign the revised protocol and submit the amendment to the IRB for review and 
approval prior to implementation of the changes specified in the amendment. The Investigator 
must report promptly to the IRB all changes in the research activity and all unanticipated problems 
involving risk to human subjects or others, including all SAEs/SADEs that have resulted in an 
expedited safety report to the FDA. No drug will be shipped to a site until IRB approval has been 
granted and the Sponsor or designee has been notified of this in writing. 
The Investigator is responsible for obtaining continued review of the clinical study, at intervals not 
to exceed 1 year or otherwise specified by the IRB. The Investigator must provide the Sponsor (or 
designee) with written documentation of the continued review. 
13.3 Informed Consent Process 
13.3.1 Consent Procedures and Documentation 
Each subject must provide written Informed Consent before any study-related procedures are 
started. It is the responsibility of the Investigator or designated staff member(s) to give a copy of 
the Informed Consent to each potential study subject and to be available to answer any questions 
the subject may have about the nature of the study and his or her participation in it. The individual 
responsible for explaining the consent form to the subject must witness the subject’s signature on 
the form. It is the responsibility of the Investigator to provide a copy of the IRB-approved consent 
form to the Sponsor (or designee) prior to the start of the study. If a protocol amendment 
substantially alters a study design or increases the potential risk to the study subject, the consent 
form must be revised and submitted to the IRB(s) for review and approval prior to implementation. 
The revised consent form must be used to obtain consent from each study subject currently in the 
study if they are affected by the amendment and from new subjects prior to enrollment in the study. 
13.3.2 Other Informational Documents Provided to Participants 
A subject to be enrolled in to the study is required to review and sign a Health Insurance Portability 
and Accountability Act (HIPAA) of 1996 authorization document. Each study subject will receive 
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13.4 Participant and Data Confidentiality 
Any party (e.g., domestic and foreign regulatory authorities, sponsor's monitors and auditors) with 
direct access will be required to take all reasonable precautions within the constraints of the 
applicable regulatory requirement(s) to maintain the confidentiality of subjects' identities and 
sponsor’s proprietary information. 
The confidentiality of records that could identify a subject will be protected, respecting the privacy 
and confidentiality rules in accordance with applicable regulatory requirement(s). 
13.4.1 Research Use of Stored Human Samples, Specimens or Data 
Not Applicable 
 
14 DATA HANDLING AND RECORD KEEPING 
14.1 Data Collection and Management Responsibilities 
The nature and location of all source documents will be identified to ensure that original data 
required to complete the CRFs exist and are accessible for verification by the site monitor. At a 
minimum, source documents should include specific data, as indicated in Section 11.1 (source 
documentation) of the protocol, for each subject. 
14.2 Study Records Retention 
The Investigator must arrange for retention of study records at the site for 2 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region, or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the study drug/device. These documents should 
be retained for a longer period, however, if required by the applicable regulatory requirements or 
by agreement with the Sponsor. The Sponsor will inform the Investigator/Institution as to when 
these documents no longer need to be retained. The Investigator will take measures to prevent any 
accidental or premature destruction of these documents. 
a. All adverse event information (adverse event forms, follow-up letters, etc.) 
b. Study subject records (source documents/CRFs) 
c. Investigational supply records/inventory 
d. IRB and regulatory approval documentation 
e. All study related correspondence 
f. All study agreements 
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h. Protocols and the reason for any deviations from the protocol 
i. Study Subject log 
j. Clinical Investigator’s Brochure 
k. Completed study subject informed consent and HIPAA forms 
l. Study subject medical chart/clinic notes. 
It is required that the author of an entry in the source documents be identifiable. Direct access to 
source documentation (medical records) must be allowed for the purpose of verifying that the data 
recorded on the CRF are consistent with the original source data. 
NOTE: These documents should be retained for a longer period if required by the 
applicable regulatory requirements or by agreement with the Sponsor. It is the 
responsibility of the Sponsor to inform the Investigator/Institution as to when these 
documents no longer need to be retained. The Investigator should take measures 
to prevent any accidental or premature destruction of these documents. 
Mati Therapeutics Inc. requires notification if the Investigator wishes to relinquish ownership of 
the data so that mutually agreed-upon arrangements can be made for transfer of ownership to a 
suitably qualified, responsible person. 
14.3 Protocol Deviations 
Any deviation from the protocol done to protect the life or physical well-being of a study subject 
in an emergency must be reported to Mati Therapeutics Inc. and the reviewing Institutional Review 
Board (IRB) as soon as possible, but no later than five working days after the deviation occurs. 
Unless it is an emergency, if the Investigator desires to modify any procedure and/or deviate from 
the design of the study, he or she must contact and obtain consent from Mati Therapeutics Inc. 
regarding the proposed changes prior to implementation. If the modifications may affect the 
scientific soundness of the study, or the rights, safety, or welfare of the study participants, approval 
by the FDA and all appropriate regulatory agencies as well as approval of the IRB is also required 
(refer to Section 13.2 for details). 
14.4 Publications and Data Sharing Policy 
All information related to this study is considered confidential information belonging to Mati 
Therapeutics Inc. Data on the use of the study drug/device and results of all clinical and laboratory 
studies are considered private and confidential. None of the details, results, or other information 
for this study shall be published or made known to a third party without written consent from Mati 
Therapeutics Inc., except for disclosure to regulatory agencies if required by law. 

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15 LITERATURE REFERENCES 
Bengtsson B, Heijl A. 2005. A long-term prospective study of risk factors for glaucomatous 
visual field loss in patients with ocular hypertension. J Glaucoma. 14(2):135-138. 
Choy BNK et al. 2019. Factors Associated with Poor Eye Drop Administration Technique and 
the Role of Patient Education among Hong Kong Elderly Population. Journal of Ophthalmology, 
vol. 2019, Article ID 5962065, 5 pages. 
Gordon MO, Beiser JA, Brandt JD, et al. 2002. The Ocular Hypertension Treatment Study: 
baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol. 
120(6):714-720. 
Kass MA, Heuer DK, Higginbotham EJ, et al. 2002. The Ocular Hypertension Treatment 
Study: a randomized trial determines that topical ocular hypotensive medication delays or 
prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 120(6):701-713. 
Leonard R. 2002. Statistics on Vision Impairment: A Resource Manual (5
th Edition). New York: 
Arlene R Gordon Research Institute of Lighthouse International. 
Leske MC, Heijl A, Hyman L, Bengtsson B, Komaroff E. 2004. Factors for progression and 
glaucoma treatment: the Early Manifest Glaucoma Trial. Curr Opin Ophthalmol. 15(2):102- 
106. 
Maier PC, Funk J, Schwarzer G, Antes G, Falck-Ytter YT. 2005. Treatment of ocular 
hypertension and open angle glaucoma: meta-analysis of randomised controlled trials. BMJ. 
331(7509):134. Epub 2005 Jul 1. 
Robin AL, Covert D. 2005. Does Adjunctive Glaucoma Therapy Affect Adherence to the Initial 
Primary Therapy? Ophthalmology. 112:863-8 
16 APPENDICES 
 
 

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Appendix A 
Page 1 of 2 
GUIDELINES FOR INFORMED CONSENT 
Both the written informed consent form and the discussion of informed consent with a potential 
study subject should include explanations of the following: 
a. The study involves research 
b. The purpose of the study 
c. The study treatment(s)  
d. The study procedures to be followed, including all invasive procedures 
e. The subject's responsibilities 
f. The aspects of the study that are experimental 
g. The reasonably foreseeable risks or inconveniences to the study subject and, when applicable, 
to an embryo, fetus, or nursing infant 
h. The reasonably expected benefits. When there is no intended clinical benefit to the study 
subject, the study subject should be made aware  
i. The alternative procedure(s) or course(s) of treatment that may be available to the subject, 
and their important potential benefits and risks 
j. The compensation and/or treatment available to the study subject in the event of study-related 
injury 
k. The anticipated prorated payment, if any, to the study subject for participating in the study 
l. The anticipated expenses, if any, to the subject for participating in the study 
m. The study subject's participation in the study is voluntary and that they may refuse to 
participate or withdraw from the study, at any time, without penalty or loss of benefits to 
which they are otherwise entitled 
n. The monitor(s), the auditor(s), the IRB/Independent Ethics Committee (IEC), and the 
regulatory authority(ies) will be granted direct access to the study subject's original medical 
records for verification of clinical study procedures and/or data, without violating the 
confidentiality of the subject, to the extent permitted by the applicable laws and regulations 
and that, by signing a written informed consent form, the subject or the subject's legally 
acceptable representative is authorizing such access 
o. The records identifying the study subject will be kept confidential and, to the extent permitted 
by the applicable laws and/or regulations, will not be made publicly available. If the results 
of the study are published, the subject’s identity will remain confidential. 
 
 

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Page 2 of 2 
p. The study subject or their legally acceptable representative will be informed in a timely 
manner if information becomes available that may be relevant to the subject's willingness 
to continue participation in the study 
q. The person(s) to contact for further information regarding the study and the rights of a study 
subject, and whom to contact in the event of study-related injury 
r. The foreseeable circumstances and/or reasons under which the subject's participation in the 
study may be terminated 
s. The expected duration of the study subject's participation in the study 
t. The approximate number of study subjects involved in the study. 
 
 
 

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Appendix B 
HIPAA Form 
PATIENT AUTHORIZATION FOR USE AND RELEASE OF HEALTH AND  
RESEARCH STUDY INFORMATION 
Study Number: 
TGLA-2021-01 
Study Title: 
A 90-Day, Open-Label, Multi-Site, Pilot Study Evaluating the Safety and 
Intraocular Lowering Effect of Delivering Travoprost using a Punctal 
Plug Delivery System (Evolute®) in Subjects with Elevated Intraocular 
Pressure 
By signing this Authorization, you agree to permit the disclosure of your confidential medical 
information by the Physician and others involved in the research to affiliates, agents and 
contractors (Sponsor) and Regulatory Authorities [e.g., the United States Food and Drug 
Administration (FDA)] for the purpose of conducting a study on a punctal plug delivery system 
design to deliver a glaucoma medication to your eye and the effect the medication has on reducing 
the pressure within your eye. Outcomes from this study may include publication of anonymous 
patient data. Such information may include, without limitation, your initials, age, race and gender. 
The Sponsor has provided financial assistance to the Physician to support these purposes. 
Furthermore, such information may be used, along with medical information of other 
individuals, in the creation and maintenance of a research database or repository for follow-up or 
retrospective research and/or statistical purposes. Such information may also be transferred to 
another country, which may have different privacy laws. Once your information has been released 
to the Sponsor, it will continue to be protected by the Sponsor’s privacy policy or by privacy 
policies that, in the Sponsor’s judgments, provide protection that is equivalent to the Sponsor’s 
privacy policy. It will not, however, have the protection of the federal privacy regulations. 
Unless another date is required by applicable law(s) your authorization will NOT expire 
because this information will be compiled into clinical research data and used for research purposes 
in the future, and you consent to the retention and future processing of your data. If your 
information is obtained in California, USA, this authorization will expire in 20 years. 
You have the right to revoke this authorization at any time, so long as you do so in writing. If 
you wish to revoke this authorization, please send a letter in which you refer to this authorization 
by the date of your signature below, to the physician conducting this trial (Doctor’s name and 
address listed below). However, please be advised that your revocation may not be effective if, in 
the meantime, the Physician has taken action in reliance on this authorization. We will honor your 
revocation to the greatest extent possible without diminishing the purposes of the trial. 
You have the right to access your data, subject to reasonable limitations, and to submit 
corrections to the Physician at the address listed below. You understand that you will not be 
allowed access to the information about you if we believe that disclosure of this information would 
jeopardize the integrity of the research efforts or other purposes of the trial. Following the 
conclusion of the trial, upon your request and under reasonable terms, you may access your 

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personal information that we retain. This information may be most readily available from the 
Physician, but the Sponsor will endeavor to provide you access to your information if necessary. 
The Physician and Sponsor will ensure that reasonable and appropriate physical, procedural, and 
technological safeguards are in place in order to protect your information from inadvertent 
destruction, disclosure or unauthorized access.  
The Physician may condition your participation in the trial on whether or not you sign this 
authorization or revoke it at a future date.  
One copy of this authorization will be kept by the Physician and the Sponsor may retain another 
copy in their files. You will receive a copy of the authorization that you have signed and dated.  
 
Physician’s Name: 
TBD, MD 
 
Address:  
TDB (Street 1) 
 
TDB (Street 2) 
 
City, State  Zip Code 
 
I have read and understand this Authorization, and agree that my medical information 
may be used and released according to the terms written above.  
 
 
____________________________ 
_______________________________ 
_______________ 
Print Name of Study Subject 
Study Subject’s Signature 
Date of Signature 
 
OR 
____________________________ 
_______________________________ 
_______________ 
Print Name of 
Signature of 
Date of Signature 
    Legally Authorized Representative 
    Legally Authorized Representative 
 
 
_________________________________________________________________________ 
Indicate Relationship to Study Subject 
 
 
 
Acknowledged by Physician 
 
 
____________________________ 
_______________________________ 
_______________ 
Print Name of Physician 
Physician Signature 
Date of Signature 
 
 

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Appendix C 
Examination Tests/Procedures and Equipment 
1. TESTS/PROCEDURES  
a. Blood Pressure and Heart Rate  
Throughout the study, vital signs (blood pressure, heart rate) will be taken with the subject 
in the sitting position after the subject has rested for at least five minutes. Blood pressures 
may be determined manually with a blood pressure cuff and auscultation or with an 
automated Blood Pressure monitor. Heart rates may be determined electronically with an 
automated Blood Pressure monitor. Manually obtained heart rates should be recorded after a 
minimum of 30 seconds of observation. 
b. Temperature  
Temperature maybe taken using a non-contact (Infrared) thermometer or orally. Oral 
temperatures should not be taken within five minutes of ingestion of any food or drink 
c. Visual Acuity 
Best-corrected distance visual acuity will be measured using a Snellen chart while the subject 
is wearing his or her glasses. Pinhole visual acuity will be measured using a Snellen chart 
while the subject is looking through a pinhole occluder. The test distance and lighting 
conditions specified for the investigator’s chart must be used and kept constant throughout 
the study. 
d. Automated Perimetry 
Full threshold visual fields will be measured using a Humphrey's Visual Field Analyzer 
(manufactured by Carl Zeiss Meditec Inc., Dublin, CA) with at least a standard full-threshold 
24-2 program or Swedish interactive threshold algorithm (SITA) program. Visual fields 
measured up to SIX months before the Screening Visit are acceptable to fulfill the screening 
procedure. 
e. Pachymetry 
Corneal thickness can be measured by contact methods, such as ultrasound and confocal 
microscopy (CONFOSCAN), noncontact methods such as optical biometry with a single 
Scheimpflug camera (such as SIRIUS or PENTACAM), dual Scheimpflug camera (such as 
GALILEI), or Optical Coherence Tomography (OCT), such as Visante. Corneal thickness 
data that is documented in the patient chart is acceptable to fulfill the screening procedure.  
f. Evaluation of Slit-Lamp Findings (Lids, Cornea, Conjunctiva) 
The severity of a sign will be graded by the investigator based on the appearance at each 
study visit using the following scale: 
NONE (0) = Normal;  
TRACE (1) = Slightly visible;  
MILD (2) = Somewhat visible and diffuse;  

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MODERATE (3) = Visible and diffuse;  
SEVERE (4) = Extremely visible and dense 
g. Intraocular Pressure Measurements 
(see Appendix D for details) 
h. Dilated Fundus Examination 
Using an ophthalmoscope, the investigator will examine the back part of the eye (fundus), 
including the retina, optic disc, choroid and blood vessels. 
i. Position Evaluation of the Study Plug 
Study plug position will be evaluated as either: 
• Normal 
• Present but requires adjustment 
• Extruded/Recovered 
• Extruded/Lost 
Other 
j. Punctal Measurements  
(see Appendix E for details) 
k. Adverse Event/Adverse Device Event 
To optimize consistency of AE reporting across centers, the subject will be asked a standard 
question to elicit any AEs. At each study visit or telephone evaluation of the subject, study 
personnel (non-observer) will ask the following question:   
"Have you had any problems since your last visit?" 
2. EQUIPMENT  
a. Coroneo Punctal Gauge 
Description 
The Coroneo Punctal Gauge (Figure 5) is designed to aid the physician in determine the size 
of the punctum. In addition, the instrument provides a simple and controlled method for 
punctal dilation prior to plug insertion. 
The system consists of a single handpiece, with gauging and dilation marks at each end. The 
instrument is manufactured from medical grade Titanium, and is autoclavable. All Coroneo 
Gauges are shipped with tip protectors which must be removed before use, cleaning, 
disinfecting, or sterilizing. 
For proper measurement and insertion of punctal plugs, the following procedures are 
recommended. A topical anesthetic for the punctum is recommended before proceeding with 
the use of this instrument. ALWAYS measure the punctum first before dilation. See 

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Appendix E for procedures to gauge the size of a punctum and Appendix F for procedures 
to dilate the punctum to at least 1.0 mm.  
 
Cleaning, disinfection and sterilization of punctal gauge 
Prior to use, the Punctal Gauge should be examined for damage and wear 
NOTE: The Coroneo Punctal Gauge is intended to contact mucous membranes only. 
Instruments that contact mucous membrane only, may have high level 
disinfection, as specified by the Center for Disease Control (CDC) and the AAMI 
Technical Information Report 12 (TIR 12). Instruments used under other 
conditions may require sterilization. 
i. Cleaning Instructions 
 Punctal gauge is to be kept moist, after usage and until cleaning is completed 
 Fresh water and an enzymatic detergent (e.g., Enzol®) are the cleaning agents 
 Punctal gauge is cleaned by soaking, coupled with brushing with a soft bristled brush, 
such as a toothbrush. Brushing should be done underwater to prevent aerosolizing 
of microorganisms 
 After cleaning, rinse the punctal gauge with a stream of fresh water. 
ii. Disinfecting Instructions 
 Soak the punctal gauge in a liquid chemical germicide solution labeled as a 
disinfection/sterilant (e.g., Cidex®) which has been approved by a competent 
authority for use in disinfecting or sterilizing medical instruments 
 Soak the punctal gauge for the time listed by the manufacture of the disinfection/sterilant 
solution 
NOTE: Disinfection/sterilant solutions are alkaline (e.g., high pH) and will affect 
anodized instruments. Do not leave anodized instruments in these solutions 
for a protracted period of time. 
 After disinfection, rinse instrument with a stream of fresh water, and dry completely 
iii. Sterilization Instructions 
 If the punctal gauge is placed in a sterilizing tray, do not allow the punctal gauge to 
touch other instruments or the sides of the tray  
 After sterilization, if the punctal gauge is not intended for immediate use, gauge must 
be wrapped in an appropriate material such as a pouch to maintain sterility 
 Chemical and biological indicators should be used to verify sterilization 
 Steam sterilization has been validated for 15 minutes, gravity cycle at 270oF (132oC). 
 
 

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b. Castroviejo Corneal Suturing Forceps 
Description 
Castroviejo Corneal Suturing Forceps are designed for handling both corneal tissue and 
suture materials during eye surgery procedures. Castroviejo Corneal Suturing Forceps have 
tying platform with Tungsten Carbide dust for additional grip and reliability. 
Manual disinfection 
Due to the potential for residual chemicals to remain on the instrument and cause an adverse 
reaction, do not use an enzymatic or liquid chemical disinfectant or sterilant when manually 
cleaned instrument.  
Drying 
Dry the instrument with a lint-free surgical wipe or blow the instrument dry with micro-filtered 
pressurized medical grade air. When blowing dry with pressurized air, ensure a secure grip on the 
instrument to avoid damage to the instrument from air pressure. 
Maintenance, Inspection and Testing 
Following cleaning, inspect the instrument to ensure that all visible soil has been removed and that 
the instrument operates as intended. A microscope should be used whenever possible.  
Packaging 
Package the instrument in a suitable sterilization pouch or instrument tray lined with soft silicone 
mats. Protective tips made of soft silicone of the proper size and thickness are recommended. 
Instruments should not be touching each other. 
 
 
 
 
 
 

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Appendix D 
Procedure for Performing Applanation Tonometry 
Goldmann applanation tonometry will be used for measuring the intraocular pressures (IOP) of 
each eye. Just prior to the start of the study, the tonometer should be calibrated and at least 
once every month during the duration of the study. 
Accurate and precise IOP readings are imperative, studies have found tight collars, ties or other 
restrictive clothing around the neck may cause an increase in venous pressure when the patient 
extends his or her neck forward, resulting in an inaccurately high IOP reading. Have a patient 
loosen any collars or neckties that may be restrictive to obtain an accurate measurement. 
The IOP of each eye will be measured by a qualified evaluator [Study investigator, Co-
investigator(s) or Sub-investigator(s)]. If there is more than one evaluator in the office, the same 
individual and the same Goldmann applanation tonometer used to measure the screening IOPs 
should be used to take measurements at all study visits.  
NOTE: Study subjects IOP measurements must be evaluated between 8:00 and 10:00 AM 
Measuring and Recording of IOPs 
A topical anesthetic will be instilled on each eye. Afterwards a fluorescein strip or drop will be 
placed onto the cul-de-sac of each eye. The IOP will be measured by the evaluator by placing the 
applanator tip on the corneal apex. When the evaluator has obtained a desired endpoint (i.e., mires 
of equal size, centered in the field, with the inner surfaces of the circles "kissing"), the tip can be 
withdrawn from the cornea (Figure 4-B). 
Figure 4 
Applanation tonometry semi-circles viewed through the Goldmann Prism 
A 
B 
C 
 
 
 
Correct end point:(diagram “B”): 
Inner edges of the semi-circles  
are just touching (“kissing”) 
After the tonometer has been withdrawn, read and record the pressure from the scale on the knob 
on the side of the tonometer, then reset the tonometer knob to "10" (NOTE: Whenever possible,  

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the same individual should perform and record the pressure values from the tonometry, at each 
time point for all subjects). 
 
The IOP of each eye will be measured twice, alternating between eyes. However, if the second 
measurement is > ± 3 mmHg from the first measurement for an eye, a third measurement will be 
taken. All measurements taken will be recorded. In the case of two measurements, the average of 
the two values will be used for analysis, and in the case of three measurements, the average of the 
two closest values of the three will be used for analysis for that eye at that specific time point. 
 
 
 

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Appendix E 
PROCEDURE FOR GAUGING (MEASURING) PUNCTUM SIZE 
The Coroneo Punctal Gage (Figure 5) is a reusable double-ended instrument that allows you to 
gauge the size of the puncta from 0.5 mm to 1.0 mm. Do not dilate the punctum before gauging 
the size of the punctum. 
Figure 5 
Coroneo Punctal Gage 
 
Expanded view of the 
punctal gauge tips 
 
NOTE: Care should be taken when gauging the punctum not to perforate the punctal 
sphincter. If the size of the study subject puncta has not be measured, gauge) the 
size of each punctum prior to dilating. 
1. The study subject may be seated at the slit-lamp or placed in a reclined position 
2. Anesthetize the area around the lower punctum  
NOTE: Placing a drop of topical anesthetic such as proparacaine or lidocaine on 
the eye to be inserted. Then adding lidocaine gel on a cotton-tipped swab 
and placing the swab directly on the lower punctum of the eye for 5 seconds 
and wait a few minutes. Past investigators have found this to be effective 
in numbing the area around the lower punctum 
3. Use slight finger traction to expose and stabilize the punctum 
4. Begin with the smallest gauge tip (0.5, 0.6, 0.7) of the Coroneo gage 
5. Gently insert the tip of the gauge in to the punctum vertically 
6. Once the horizontal canaliculus has been reached, if necessary, gently turn the instrument 
horizontally to continue inserting past the vertical canaliculus.   
7. If the instrument can be inserted past the third ring on the tip of the Coroneo gage without 
observing tightening of the punctal ring – stop and remove the gauge 
8. Repeat the above procedure using the larger end of the Coroneo gage (0.8, 0.9, 1.0) 
9. When tightening of the punctal ring is observed around the instrument read the appropriate 
size from the gauge. There are three “grooves” in each end of the gauge that correspond 
to the three sizes indicated on the handle  
10. Record the punctal size in the appropriate section of the case report form.  
If gauging the size of the punctum is immediately followed by dilating and inserting the study 
plug (PPDS), refer to Appendix F for details regarding the dilation of the lower punctum.   

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Appendix F 
 
PROCEDURE FOR DILATION OF THE PUNCTUM 
Use the Coroneo Punctal Gage (Figure 5) to dilate the punctum. If the size of the study subject 
puncta have not been measured, gauge (Appendix E) the size of each punctum prior to dilating. 
NOTE: Care should be taken when dilating the punctum not to perforate the punctal 
sphincter.  Dilating and inserting the punctal plug delivery system (PPDS) 
should be performed on ONE eye at a time. 
1. The study subject may be seated at the slit-lamp or placed in a reclined position. The 
following steps 1-6 are the same procedure used to measure (gauge) the size of the 
punctum 
2. Anesthetize the area around the lower punctum  
NOTE: Placing a drop of topical anesthetic such as proparacaine or lidocaine on 
the eye to be inserted. Then adding lidocaine gel on a cotton-tipped swab 
and placing the swab directly on the lower punctum of the eye for 5 seconds 
and wait a few minutes. Past investigators have found this to be effective 
in numbing the area around the lower punctum 
3. Use slight finger traction on the lower lid to expose and stabilize the punctum 
4. Begin with the smallest gauge tip (0.5, 0.6, 0.7) of the Coroneo gage 
5. Gently insert the tip of the gauge in to the punctum vertically 
6. Once the horizontal canaliculus has been reached, if necessary, gently turn the instrument 
horizontally to continue inserting past the vertical canaliculus as you gently dilate 
7. Once the instrument is inserted past the third ring on the tip of the Coroneo gage, repeat the 
above procedure using the larger end of the Coroneo gauge (0.8, 0.9, 1.0) 
8. The punctum must be dilated to at least 1.0 mm. Once the punctum is dilated to 1.0 mm, 
leave dilator in place for 20 to 30 seconds to allow the sphincter to fully relax. During 
this time prepare the PPDS to be inserted. 
NOTE: For small puncta, hold and rotate the dilator in the punctum and canaliculus 
for as long as required to achieve dilation to 1.0 mm. This may take some 
considerable time (1-2 minutes). Dilation may require very firm pressure 
however; care must be taken NOT to apply excessive force to dilate the 
punctum. Add more anesthesia if needed. 
Refer to Appendix G for detailed procedure for inserting the PPDS 

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Appendix G 
PROCEDURES FOR INSERTION OF A PPDS 
The procedure for inserting Mati’s PPDS punctal plug is similar to those for commercial plugs. 
Mati’s PPDS is for single-patient use only.  
NOTE:  Do not use a lubricant when inserting the plug, this may facilitate inadvertent 
plug intrusion below the punctal opening. 
1. Once the punctum has been dilated to 1.0 mm, leave the dilator in place for 20 to 30 seconds 
to allow the sphincter to fully relax. During this time prepare the PPDS to be inserted by 
removing the foil laminate lid and release the pre-loaded PPDS from the preformed rigid 
tray 
2. Remove the dilator from the punctum and immediately attempt to insert the PPDS before the 
sphincter starts to close 
3. Use slight finger traction on the lower lid to expose and stabilize the punctum, and position 
the plug end of the insertion instrument over the study subject’s punctum 
4. Insert the plug, coming straight down perpendicular to the punctum until the cap of the plug 
is flush with the lid margin 
5. Once the plug is in the proper position, release the lower lid and press the release button and 
pull the insertion instrument away from the study subject’s punctum 
After insertion, the punctal opening should be visually inspected using a slit-lamp to confirm the 
retention and proper placement of the PPDS, with the cap still visible. The position of the PPDS 
may be adjusted with forceps or the tip of the inserter if necessary. However, if unable to position 
the cap of the plug flush with the lid margin, the plug should be removed and the punctum re-
dilated or dilated to a larger diameter. Placement of the plug can then be re-attempted. Multiple 
attempts are sometimes necessary 
NOTE: Removal of a properly positioned PPDS immediately after insertion may result in 
the cap of the plug being torn off. Investigator should wait until the following day 
to allow the punctal sphincter to adjust (relax) before attempting to remove a 
PPDS. If the plug tears or separates, report this as a technical complaint (Section 
8.6.3). Retain all removed or damaged PPDS for accountability of investigational 
supplies.   
If the PPDS cannot be inserted after a few attempts with gentle dilation, the subject is not eligible 
for the study.   
 
 

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Appendix H 
PROCEDURES FOR REMOVAL OF A PPDS 
The PPDS should be removed from the study subject’s lower puncta using sterile ophthalmic 
forceps, such as Castroviejo Suture forceps (Figure 6) or similar toothed forceps. When removing 
a PPDS, if necessary, a drop of anesthetic may be administered.   
Figure 6 
Castroviejo Corneal Suturing Forceps 1x2 0.12mm 90° Straight, Titanium 
 
 
 
a. Care must be taken not to grasp the outermost edge 
of the cap on the punctal plug as this may cause the 
cap to tear and separate, making it difficult to 
remove the plug from the canaliculus and/or 
causing plug intrusion 
b. The teeth of the forceps should NOT be used to 
grasp the neck of the PPDS, but are placed on the 
far sides of the plug with the blades straddling the 
neck. The teeth of the forceps are used instead to 
prevent the blades of the forceps from sliding off 
the neck. Grasping the neck of the plug with the 
teeth may fracture or tear the plug 
Figure 7 
Punctal Plug Delivery System 
(L-shape Model L67) 
`
 
c. The first motion to remove the plug should be towards the medial canthus (not up or 
temporally), which is necessary to disengage the heel of the plug, pulling the plug out with 
a tugging motion towards the medial canthus 
NOTE: Care must be taken not to grasp the outermost edge of the cap on the punctal 
plug, as this may cause the cap to tear and separate, making it difficult to 
remove the plug from the canaliculus and/or causing plug intrusion. 
If the cap becomes separated, removal of the plug can be attempted using toothed 0.12 forceps 
(0.12 Castroviejo forceps or similar) by grasping the neck of the plug through the punctum. If this 
is not possible, and it does not appear that the plug will lodge in the canal, and only if the 
investigator feels comfortable doing so, he or she may attempt to irrigate the canal until the plug 
flushes out of the nasolacrimal duct.  

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NOTE: A PPDS is larger than commercially available silicone plugs and may become 
lodged in the canal more easily. Clinical judgment should be exercised when 
proceeding. Referral to tertiary care is advised in cases where the plug cannot be 
retrieved by massaging/milking through the punctal opening or by irrigation. Plug 
intrusion at removal, or spontaneous migration of a PPDS beyond the punctal 
opening such that massage, irrigation, or punctoplasty is required to remove it 
should be recorded as an AE. 
 
 

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Appendix I 
TRAVATAN® (travoprost ophthalmic solution) 0.004% Sterile  
DESCRIPTION 
TRAVATAN® (travoprost ophthalmic solution) 0.004% Sterile DESCRIPTION Travoprost is a 
synthetic prostaglandin F2α analogue. Its chemical name is isopropyl (Z)-7[(1R,2R,3R,5S)-3,5-
dihydroxy-2-[(1E,3R)-3-hydroxy-4-[(α,α,α- 
trifluoro-m-tolyl)oxy]-lbutenyl]cyclopentyl]-5-
heptenoate. It has a molecular formula of C26H35F3O6 and a molecular weight of 500.56.  The 
chemical structure of travoprost is:  
 
Travoprost is a clear, colorless to slightly yellow oil that is very soluble in acetonitrile, methanol, 
octanol, and chloroform. It is practically insoluble in water.  
TRAVATAN® Ophthalmic Solution 0.004% is supplied as sterile, buffered aqueous solution of 
travoprost with a pH of approximately 6.0 and an osmolality of approximately 290 mOsmol/kg.  
Each mL of TRAVATAN® 0.004% contains 40 ug travoprost. Benzalkonium chloride 0.015% is 
added as a preservative. Inactive Ingredients are: polyoxyl 40 hydrogenated castor oil, 
tromethamine, boric acid, mannitol, edetate disodium, sodium hydroxide and/or hydrochloric acid 
(to adjust pH) and purified water. 
CLINICAL PHARMACOLOGY 
Mechanism of Action  
Travoprost free acid is a selective FP prostanoid receptor agonist which is believed to reduce 
intraocular pressure by increasing uveoscleral outflow. The exact mechanism of action is unknown 
at this time.  
Pharmacokinetics/Pharmacodynamics  
Absorption:  Travoprost is absorbed through the cornea and is hydrolyzed to the active free acid. 
Data from four multiple dose pharmacokinetic studies (totaling 107 subjects) have shown that 
plasma concentrations of the free acid are below 0.01 ng/ml (the quantitation limit of the assay) in 
two-thirds of the subjects. In those individuals with quantifiable plasma concentrations (N=38), 
the mean plasma Cmax was 0.018 ± 007 ng/ml (ranged 0.01 to 0.052 ng/mL) and was reached 

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within 30 minutes.  From these studies, travoprost is estimated to have a plasma half-life of 45 
minutes. There was no difference in plasma concentrations between Days 1 and 7, indicating 
steady-state was reached early and that there was no significant accumulation. 
Metabolism: Travoprost, an isopropyl ester prodrug, is hydrolyzed by esterases in the cornea to its 
biologically active free acid. Systemically, travoprost free acid is metabolized to inactive 
metabolites via beta-oxidation of the α (carboxylic acid) chain to give the 1,2-dinor and 1,2,3,4-
tetranor analogs, via oxidation of the 15-hydroxyl moiety, as well as via reduction of the 13,14-
double bond.  
Elimination: The elimination of travoprost free acid from plasma was rapid and levels were 
generally below the limit of quantification within one hour after dosing.  The terminal elimination 
half-life of travoprost free acid was estimated from fourteen subjects and ranged from 17 minutes 
to 86 minutes with the mean half-life of 45 minutes.  Less than 2% of the topical ocular dose of 
travoprost was excreted in the urine within 4 hours as the travoprost free acid.  
Clinical Studies  
In clinical studies, patients with open-angle glaucoma or ocular hypertension and baseline pressure 
of 25 - 27 mmHg who were treated with TRAVATAN® Ophthalmic Solution 0.004% dosed once-
daily in the evening demonstrated 7 - 8 mmHg reductions in intraocular pressure. In subgroup 
analyses of these studies, mean IOP reduction in black patients was up to 1.8 mmHg greater than 
in non-black patients. It is not known at this time whether this difference is attributed to race or to 
heavily pigmented irides. In a multi-center, randomized, controlled trial, patients with mean 
baseline intraocular pressure of 24 - 26 mmHg on TIMOPTIC* 0.5% BID who were treated with 
TRAVATAN® 0.004% dosed QD adjunctively to TIMOPTIC* 0.5% BID demonstrated 6 - 7 
mmHg reductions in intraocular pressure.  
TRAVATAN® has been studied in patients with hepatic impairment and also in patients with renal 
impairment.  No clinically relevant changes in hematology, blood chemistry, urinalysis laboratory 
data were observed in these patients.  
INDICATIONS AND USAGE  
TRAVATAN® Ophthalmic Solution is indicated for the reduction of elevated intraocular pressure 
in patients with open-angle glaucoma or ocular hypertension who are intolerant of other intraocular 
pressure lowering medications or insufficiently responsive (failed to achieve target IOP 
determined after multiple measurements over time) to another intraocular pressure lowering 
medication.  
 

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CONTRAINDICATIONS  
TRAVATAN® is contraindicated in patients with hypersensitivity to travoprost, benzalkonium 
chloride or any other ingredients in this product.  
WARNINGS  
TRAVATAN® has been reported to cause changes to pigmented tissues. The most frequently 
reported changes have been increased pigmentation of the iris and periorbital tissue (eyelid) 
and increased pigmentation and growth of eyelashes. These changes may be permanent. 
TRAVATAN® may gradually change eye color, increasing the amount of brown pigmentation in 
the iris by increasing the number of melanosomes (pigment granules) in melanocytes. The long-
term effects on the melanocytes and the consequences of potential injury to the melanocytes and/or 
deposition of pigment granules to other areas of the eye are currently unknown. The change in iris 
color occurs slowly and may not be noticeable for months to years. Patients should be informed of 
the possibility of iris color change.  
Eyelid skin darkening has been reported in association with the use of TRAVATAN®.  
TRAVATAN® may gradually change eyelashes in the treated eye; these changes include 
increased length, thickness, pigmentation, and/or number of lashes.  
Patients who are expected to receive treatment in only one eye should be informed about the 
potential for increased brown pigmentation of the iris, periorbital and/or eyelid tissue, and 
eyelashes in the treated eye and thus heterochromia between the eyes. They should also be advised 
of the potential for a disparity between the eyes in length, thickness, and/or number of eyelashes. 
PRECAUTIONS  
General 
There have been reports of bacterial keratitis associated with the use of multiple-dose containers 
of topical ophthalmic products. These containers had been inadvertently contaminated by patients 
who, in most cases, had a concurrent cornea1 disease or a disruption of the epithelial surface (see 
Information for Patients).  
Patients may slowly develop increased brown pigmentation of the iris. This change may not be 
noticeable for months to years (see Warnings). Iris pigmentation changes may be more noticeable 
in patients with mixed colored irides, i.e., blue-brown, grey-brown, yellow-brown, and green-
brown; however, it has also been observed in patients with brown eyes. The color change is 
believed to be due to increased melanin content in the stromal melanocytes of the iris. The exact 
mechanism of action is unknown at this time. Typically, the brown pigmentation around the pupil 
spreads concentrically towards the periphery in affected eyes, but the entire iris or parts of it may 

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become more brownish. Until more information about increased brown pigmentation is available, 
patients should be examined regularly and, depending on the situation, treatment may be stopped 
if increased pigmentation ensues.  
TRAVATAN® should be used with caution in patients with a history of intraocular inflammation 
(iritis/uveitis) and should generally not be used in patients with active intraocular inflammation.  
Macular edema, including cystoid macular edema, has been reported during treatment with 
prostaglandin F2α analogues. These reports have mainly occurred in aphakic patients, 
pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for 
macular edema. TRAVATAN® should be used with caution in these patients.  
TRAVATAN® has not been evaluated for the treatment of angle closure, inflammatory or 
neovascular glaucoma.  
TRAVATAN® Ophthalmic Solution should not be administered while wearing contact lenses. 
Patients should be advised that TRAVATAN® contains benzalkonium chloride which may be 
absorbed by contact lenses. Contact lenses should be removed prior to the administration of the 
solution. Lenses may be reinserted 15 minutes following administration of TRAVATAN®.  
Information for Patients  
Patients should be advised concerning all the information contained in the Warnings and 
Precautions sections.  
Patients should also be instructed to avoid allowing the tip of the dispensing container to contact 
the eye or surrounding structures because this could cause the tip to become contaminated by 
common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss 
of vision may result from using contaminated solutions.  
Patients also should be advised that if they develop an intercurrent ocular condition (e.g., trauma, 
or infection) or have ocular surgery, they should immediately seek the physician’s advice 
concerning the continued use of the multi-dose container.  
Patients should be advised that if they develop any ocular reactions, particularly conjunctivitis and 
lid reactions, they should immediately seek his/her physician’s advice.  
If more than one topical ophthalmic drug is being used, the drugs should be administered at least 
five (5) minutes apart.  
Carcinogenesis, Mutagenesis, Impairment of Fertility    

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Two-year carcinogenicity studies in mice and rats at subcutaneous doses of 10, 30, or 100 
µg/kg/day did not show any evidence of carcinogenic potential.  However, at 100 µg/kg/day, male 
rats were only treated for 82 weeks, and the maximum tolerated dose (MTD) was not reached in 
the mouse study.  The high dose (100 µg/kg) corresponds to exposure levels over 400 times the 
human exposure at the maximum recommended human ocular dose (MRHOD) of 0.04 µg/kg, 
based on plasma active drug levels. Travoprost was not mutagenic in the Ames test, mouse 
micronucleus test and rat chromosome aberration assay. A slight increase in the mutant frequency 
was observed in one of two mouse lymphoma assays in the presence of rat S-9 activation enzymes.  
Travoprost did not affect mating or fertility indices in male or female rats at subcutaneous doses 
up to 10 ug/kg/day [250 times the maximum recommended human ocular dose of 0.04 ug/kg/day 
on a ug/kg basis (MRHOD)]. At 10 ug/kg/day, the mean number of corpora lutea was reduced, 
and the postimplantation losses were increased. These effects were not observed at 3 ug/kg/day 
(75 times the MRHOD).  
Pregnancy: Teratogenic Effects  
Pregnancy Category: C Travoprost was teratogenic in rats, at an intravenous (IV) dose up to 10 
ug/kg/day (250 times the MRHOD), evidenced by an increase in the incidence of skeletal 
malformations as well as external and visceral malformations, such as fused sternebrae, domed 
head and hydrocephaly. Travoprost was not teratogenic in rats at IV doses up to 3 ug/kg/day (75 
times the MRHOD), and in mice at subcutaneous doses up to 1.0 ug/kg/day (25 times the 
MRHOD). Travoprost produced an increase in postimplantation losses and a decrease in fetal 
viability in rats at IV doses > 3 ug/kg/day (75 times the MRHOD) and in mice at subcutaneous 
doses > 0.3 ug/kg/day (7.5 times the MRHOD). 
In the offspring of female rats that received travoprost subcutaneously from Day 7 of pregnancy 
to lactation Day 21 at the doses of ≥ 0.12 ug/kg/day (3 times the MRHOD), the incidence of 
postnatal mortality was increased, and neonatal body weight gain was decreased. Neonatal 
development was also affected, evidenced by delayed eye opening, pinna detachment and preputial 
separation, and by decreased motor activity.  
There are no adequate and well-controlled studies in pregnant women.  TRAVATAN® should be 
used during pregnancy only if the potential benefit justifies the potential risk to the fetus.    
Nursing Mothers  
A study in lactating rats demonstrated that radiolabeled travoprost and/or its metabolites were 
excreted in milk. It is not known whether this drug or its metabolites are excreted in human milk. 
Because many drugs are excreted in human milk, caution should be exercised when 
TRAVATAN® is administered to a nursing woman.  
Pediatric Use  
Safety and effectiveness in pediatric patients have not been established.  
 

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Geriatric Use  
No overall differences in safety or effectiveness have been observed between elderly and other 
adult patients.  
ADVERSE REACTIONS  
The most common ocular adverse event observed in controlled clinical studies with 
TRAVATAN® 0.004% was ocular hyperemia which was reported in 35 to 50% of patients. 
Approximately 3% of patients discontinued therapy due to conjunctival hyperemia.  
Ocular adverse events reported at an incidence of 5 to 10% included decreased visual acuity, eye 
discomfort, foreign body sensation, pain, and pruritus.  
Ocular adverse events reported at an incidence of 1 to 4% included, abnormal vision, blepharitis, 
blurred vision, cataract, cells, conjunctivitis, dry eye, eye disorder, flare, iris discoloration, 
keratitis, lid margin crusting, photophobia, subconjunctival hemorrhage, and tearing.  
Nonocular adverse events reported at a rate of 1 to 5% were accidental injury, angina pectoris, 
anxiety, arthritis, back pain, bradycardia, bronchitis, chest pain, cold syndrome, depression, 
dyspepsia, gastrointestinal disorder, headache, hypercholesterolemia, hypertension, hypotension, 
infection, pain, prostate disorder, sinusitis, urinary incontinence, and urinary tract infection.    
DOSAGE AND ADMINISTRATION  
The recommended dosage is one drop in the affected eye(s) once-daily in the evening. The dosage 
of TRAVATAN® should not exceed once-daily since it has been shown that more frequent 
administration may decrease the intraocular pressure lowering effect. Reduction of intraocular 
pressure starts approximately 2 hours after administration, and the maximum effect is reached after 
12 hours.  
TRAVATAN® may be used concomitantly with other topical ophthalmic drug products to lower 
intraocular pressure. If more than one topical ophthalmic drug is being used, the drugs should be 
administered at least five (5) minutes apart.  
HOW SUPPLIED  
TRAVATAN® (travoprost ophthalmic solution) 0.004% is a sterile, isotonic, buffered, preserved, 
aqueous solution of travoprost (0.04 mg/mL) supplied in Alcon’s oval DROP-TAINER® package 
system. TRAVATAN® is supplied as a 2.5 mL solution in a 4 mL and a 5 mL solution in a 7.5 
mL natural polypropylene dispenser bottle with a natural polypropylene dropper tip and a turquoise 
polypropylene overcap. Tamper evidence is provided with a shrink band around the closure and 
neck area of the package. NDC 0065-0266-25, 2.5 mL fill NDC 0065-0266-17, 2 units, 2.5 mL fill 
each NDC 0065-0266-34, 5 mL fill  
 

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Storage  
Store at 2° - 25°C (36° - 77°F).  Rx Only  
Rx Only  
U.S. Patent Nos. 5,631,287; 5,849,792; 5,889,052; 6,011,062, and 6,235,781.  
*TIMOPTIC is a registered trademark of Merck & Co., Inc.  
ALCON LOGO  
ALCON LABORATORIES, INC.   
Fort Worth, Texas 76134 USA  
©2004 Alcon, Inc. 
 
 
 

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Appendix J 
TRAVATAN Z® PACKAGE INSERT 
FULL PRESCRIBING INFORMATION  
1 INDICATIONS AND USAGE  
TRAVATAN Z® (travoprost ophthalmic solution) 0.004% is indicated for the reduction of 
elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension.  
2 DOSAGE AND ADMINISTRATION  
The recommended dosage is one drop in the affected eye(s) once daily in the evening. 
TRAVATAN Z should not be administered more than once daily since it has been shown that 
more frequent administration of prostaglandin analogs may decrease the IOP lowering effect.  
Reduction of the IOP starts approximately 2 hours after the first administration with maximum 
effect reached after 12 hours.  
TRAVATAN Z may be used concomitantly with other topical ophthalmic drug products to lower 
IOP. If more than one topical ophthalmic drug is being used, the drugs should be administered at 
least 5 minutes apart.  
3 DOSAGE FORMS AND STRENGTHS  
Ophthalmic solution containing travoprost 0.04 mg/mL.  
4 CONTRAINDICATIONS  
None.  
5 WARNINGS AND PRECAUTIONS  
5.1 Pigmentation  
Travoprost ophthalmic solution has been reported to cause changes to pigmented tissues. The most 
frequently reported changes have been increased pigmentation of the iris, periorbital tissue 
(eyelid), and eyelashes. Pigmentation is expected to increase as long as travoprost is administered. 
The pigmentation change is due to increased melanin content in the melanocytes rather than to an 
increase in the number of melanocytes. After discontinuation of travoprost, pigmentation of the 
iris is likely to be permanent, while pigmentation of the periorbital tissue and eyelash changes have 
been reported to be reversible in some patients. Patients who receive treatment should be informed 
of the possibility of increased pigmentation. The long-term effects of increased pigmentation are 
not known.  
Iris color change may not be noticeable for several months to years. Typically, the brown 
pigmentation around the pupil spreads concentrically towards the periphery of the iris and the 
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be affected by treatment. While treatment with TRAVATAN Z can be continued in patients who 
develop noticeably increased iris pigmentation, these patients should be examined regularly.  
5.2 Eyelash Changes  
TRAVATAN Z may gradually change eyelashes and vellus hair in the treated eye. These changes 
include increased length, thickness, and number of lashes. Eyelash changes are usually reversible 
upon discontinuation of treatment.  
5.3 Intraocular Inflammation  
TRAVATAN Z should be used with caution in patients with active intraocular inflammation (e.g., 
uveitis) because the inflammation may be exacerbated.  
5.4 Macular Edema  
Macular edema, including cystoid macular edema, has been reported during treatment with 
travoprost ophthalmic solution. TRAVATAN Z should be used with caution in aphakic patients, 
in pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors 
for macular edema.  
5.5 Angle-closure, Inflammatory or Neovascular Glaucoma  
TRAVATAN Z has not been evaluated for the treatment of angle-closure, inflammatory or 
neovascular glaucoma.  
5.6 Bacterial Keratitis  
There have been reports of bacterial keratitis associated with the use of multiple-dose containers 
of topical ophthalmic products. These containers had been inadvertently contaminated by patients 
who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface.  
5.7 Use with Contact Lenses  
Contact lenses should be removed prior to instillation of TRAVATAN Z and may be reinserted 15 
minutes following its administration.  
6 ADVERSE REACTIONS  
6.1 Clinical Trials  
Experience Because clinical trials are conducted under widely varying conditions, adverse reaction 
rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical 
trials of another drug and may not reflect the rates observed in practice.  
The most common adverse reaction observed in controlled clinical trials with TRAVATAN and 
TRAVATAN Z was ocular hyperemia, which was reported in 30% to 50% of patients. Up to 3% 
of patients discontinued therapy due to conjunctival hyperemia. Ocular adverse reactions reported 
at an incidence of 5% to 10% in these clinical trials included decreased visual acuity, eye 
discomfort, foreign body sensation, pain, and pruritus.  
Ocular adverse reactions reported at an incidence of 1% to 4% in clinical trials with TRAVATAN 

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or TRAVATAN Z included abnormal vision, blepharitis, blurred vision, cataract, conjunctivitis, 
corneal staining, dry eye, iris discoloration, keratitis, lid margin crusting, ocular inflammation, 
photophobia, subconjunctival hemorrhage, and tearing.  
Non-ocular adverse reactions reported at an incidence of 1% to 5% in these clinical studies were 
allergy, angina pectoris, anxiety, arthritis, back pain, bradycardia, bronchitis, chest pain, cold/flu 
syndrome, depression, dyspepsia, gastrointestinal disorder, headache, hypercholesterolemia, 
hypertension, hypotension, infection, pain, prostate disorder, sinusitis, urinary incontinence, and 
urinary tract infections.  
6.2 Postmarketing Experience  
Additional adverse reactions have been identified during post approval use of TRAVATAN or 
TRAVATAN Z in clinical practice. Because they are reported voluntarily from a population of 
unknown size, estimates of frequency cannot be made. The reactions, which have been chosen for 
inclusion due to either their seriousness, frequency of reporting, possible causal connection to 
TRAVATAN or TRAVATAN Z, or a combination of these factors, include: arrhythmia, vomiting, 
epistaxis, tachycardia, and insomnia.  
In postmarketing use with prostaglandin analogs, periorbital and lid changes including deepening 
of the eyelid sulcus have been observed.  
8 USE IN SPECIFIC POPULATIONS  
8.1 Pregnancy  
Risk Summary  
There are no adequate and well-controlled studies in pregnant women to inform a drug-associated 
risk.  
In animal reproduction studies, subcutaneous (SC) administration of travoprost to pregnant mice 
and rats throughout the period of organogenesis produced embryo-fetal lethality, spontaneous 
abortion, and premature delivery at potentially clinically relevant doses.  
Advise pregnant women of a potential risk to a fetus. Because animal reproductive studies are not 
always predictive of human response, TRAVATAN Z should be administered during pregnancy 
only if the potential benefit justifies the potential risk to the fetus.  
The background risk of major birth defects and miscarriage for the indicated population is 
unknown; however, in the U.S. general population, the estimated background risk of major birth 
defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies.  
Data  
Animal Data  
An embryo-fetal study was conducted in pregnant rats administered travoprost once daily by SC 
injection from gestation day (GD) 6 to 18, to target the period of organogenesis. At 10 mcg/kg (60 

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times the maximum recommended human ocular dose [MRHOD], based on estimated plasma 
Cmax), travoprost was teratogenic in rats, evidenced by an increase in the incidence of skeletal 
malformations as well as external and visceral malformations, including fused sternebrae, domed 
head and hydrocephaly. Travoprost caused post-implantation loss at 10 mcg/kg. The no observed 
adverse effect level (NOAEL) for post-implantation loss was 3 mcg/kg (18 times the MRHOD, 
based on estimated plasma Cmax). The maternal NOAEL was 10 mcg/kg.  
An embryo-fetal study was conducted in pregnant mice administered travoprost once daily by SC 
injection from GD 6 to 11, to target the period of organogenesis. At 1 mcg/kg (6 times the 
MRHOD, based on estimated plasma Cmax), travoprost caused postimplantation loss and 
decreased fetal weight. The no observed adverse effect level (NOAEL) for malformations was 0.3 
mcg/kg (2 times the MRHOD, based on estimated plasma Cmax). The maternal NOAEL was 1 
mcg/kg.  
Pre/postnatal studies were conducted in rats administered travoprost once daily by subcutaneous 
injection from GD 7 (early embryonic period) to postnatal Day 21 (end of lactation period). At 
doses of greater than or equal to 0.12 mcg/kg/day (0.7 times the MRHOD, based on estimated 
plasma Cmax), adverse pregnancy outcomes (embryo-fetal lethality, abortion, and early delivery), 
low-birth weight and developmental delays were observed. The NOAEL for adverse pregnancy 
outcomes, low-birth weight and developmental delay was 0.1 mcg/kg (0.6 times the MHROD, 
based on estimated plasma Cmax). The NOAEL for maternal toxicity was 0.72 mcg/kg (4 times 
the MHROD, based on estimated plasma Cmax).  
8.2 Lactation  
Risk Summary  
There are no data on the effects of travoprost on the breastfed child or milk production. It is not 
known if travoprost is present in human milk following ophthalmic administration. A study in 
lactating rats demonstrated that radio-labeled travoprost and/or its metabolites were excreted in 
milk following subcutaneous administration.  
The developmental and health benefits of breastfeeding should be considered along with the 
mother’s clinical need for TRAVATAN Z and any potential adverse effects on the breast-fed child 
from TRAVATAN Z.  
8.4 Pediatric Use  
Use in pediatric patients below the age of 16 years is not recommended because of potential safety 
concerns related to increased pigmentation following long-term chronic use.  
8.5 Geriatric Use  
No overall clinical differences in safety or effectiveness have been observed between elderly and 
other adult patients.  
8.6 Hepatic and Renal Impairment  

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Travoprost ophthalmic solution 0.004% has been studied in patients with hepatic impairment and 
also in patients with renal impairment. No clinically relevant changes in hematology, blood 
chemistry, or urinalysis laboratory data were observed in these patients.  
11 DESCRIPTION  
Travoprost 
is 
a 
synthetic 
prostaglandin 
F 
analog. 
Its 
chemical 
name 
is 
[1R-
[1α(Z),2β(1E,3R*),3α,5α]]-7-[3,5- Dihydroxy-2-[3-hydroxy-4-[3-(trifluoromethyl) phenoxy]-1-
butenyl]cyclopentyl]-5-heptenoic acid, 1- methylethylester. It has a molecular formula of 
C26H35F3O6 and a molecular weight of 500.55 g/mol. The chemical structure of travoprost is: 
 
Travoprost is a clear, colorless to slightly yellow oil that is very soluble in acetonitrile, methanol, 
octanol, and chloroform. It is practically insoluble in water.  
TRAVATAN Z is supplied as sterile, buffered aqueous solution of travoprost with a pH of 
approximately 5.7 and an osmolality of approximately 290 mOsmol/kg.  
TRAVATAN Z contains Active: travoprost 0.04 mg/mL; Inactives: polyoxyl 40 hydrogenated 
castor oil, sofZia® (boric acid, propylene glycol, sorbitol, zinc chloride), sodium hydroxide and/or 
hydrochloric acid (to adjust pH), and purified water, USP. Preserved in the bottle with an ionic 
buffered system, sofZia®.  
12 CLINICAL PHARMACOLOGY  
12.1 Mechanism of Action  
Travoprost free acid, a prostaglandin analog is a selective FP prostanoid receptor agonist, which 
is believed to reduce IOP by increasing uveoscleral outflow. The exact mechanism of action is 
unknown at this time.  
12.3 Pharmacokinetics  
Travoprost is absorbed through the cornea and is hydrolyzed to the active free acid. Data from 4 
multiple dose pharmacokinetic studies (totaling 107 subjects) have shown that plasma 
concentrations of the free acid are below 0.01 ng/mL (the quantitation limit of the assay) in two-
thirds of the subjects. In those individuals with quantifiable plasma concentrations (N = 38), the 
mean plasma Cmax was 0.018 ± 0.007 ng/mL (ranged 0.01 to 0.052 ng/mL) and was reached 

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within 30 minutes. From these studies, travoprost is estimated to have a plasma half-life of 45 
minutes. There was no difference in plasma concentrations between Days 1 and 7, indicating 
steady-state was reached early and that there was no significant accumulation.  
Travoprost, an isopropyl ester prodrug, is hydrolyzed by esterases in the cornea to its biologically 
active free acid. Systemically, travoprost free acid is metabolized to inactive metabolites via beta-
oxidation of the α (carboxylic acid) chain to give the 1,2-dinor and 1,2,3,4-tetranor analogs, via 
oxidation of the 15-hydroxyl moiety, as well as via reduction of the 13, 14 double bond.  
The elimination of travoprost free acid from plasma was rapid and levels were generally below the 
limit of quantification within one hour after dosing. The terminal elimination half-life of travoprost 
free acid was estimated from fourteen subjects and ranged from 17 minutes to 86 minutes with the 
mean half-life of 45 minutes. Less than 2% of the topical ocular dose of travoprost was excreted 
in the urine within 4 hours as the travoprost free acid.  
13 NONCLINICAL TOXICOLOGY  
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility  
Two-year carcinogenicity studies in mice and rats at subcutaneous doses of 10, 30, or 100 
mcg/kg/day did not show any evidence of carcinogenic potential. However, at 100 mcg/kg/day, 
male rats were only treated for 82 weeks, and the maximum tolerated dose (MTD) was not reached 
in the mouse study. The high dose (100 mcg/kg) corresponds to exposure levels 326 times (mouse) 
and 547 times (rat) the human exposure at the MRHOD of 0.04 mcg/kg, based on estimated plasma 
Cmax for active travoprost free acid.  
Travoprost was not mutagenic in the Ames test, mouse micronucleus test or rat chromosome 
aberration assay. A slight increase in the mutant frequency was observed in one of two mouse 
lymphoma assays in the presence of rat S-9 activation enzymes.  
Travoprost did not affect mating or fertility indices in male or female rats at subcutaneous doses 
up to 3 mcg/kg/day (18 times the MRHOD based on estimated plasma Cmax). At 10 mcg/kg/day 
(60 times the MRHOD, based on estimated plasma Cmax), the mean number of corpora lutea was 
reduced, and the post-implantation losses were increased.  
14 CLINICAL STUDIES  
In clinical studies, patients with open-angle glaucoma or ocular hypertension and baseline pressure 
of 25 to 27 mmHg, who were treated with TRAVATAN or TRAVATAN Z dosed once daily in 
the evening, demonstrated 7 to 8 mmHg reductions in IOP. In sub-group analyses of these studies, 
mean IOP reduction in black patients was up to 1.8 mmHg greater than in non-black patients. It is 
not known at this time whether this difference is attributed to race or to heavily pigmented irides.  
In a multi-center, randomized, controlled trial, patients with mean baseline IOP of 24 to 26 mmHg 
on TIMOPTIC** 0.5% twice daily who were treated with TRAVATAN dosed daily adjunctively 
to TIMOPTIC** 0.5% twice daily demonstrated 6 to 7 mmHg reductions in IOP.  

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16 HOW SUPPLIED/STORAGE AND HANDLING  
TRAVATAN Z is a sterile, isotonic, buffered, preserved, aqueous solution of travoprost (0.04 
mg/mL).  
TRAVATAN Z is supplied as a 2.5 mL solution in a 4 mL and a 5 mL solution in a 7.5 mL oval 
natural polypropylene dispenser bottle with a natural polypropylene dropper tip and a turquoise 
polypropylene or high-density polyethylene overcap. Tamper evidence is provided with a shrink 
band around the closure and neck area of the package.  
2.5 mL fill 
NDC 0065-0260-25  
5 mL fill 
NDC 0065-0260-05  
Storage:  Store at 2°C to 25°C (36°F to 77°F).  
After opening, TRAVATAN Z can be used until the expiration date on the bottle.  
17 PATIENT COUNSELING INFORMATION  
Potential for Pigmentation  
Advise the patient about the potential for increased brown pigmentation of the iris, which may be 
permanent. Inform the patient about the possibility of eyelid skin darkening, which may be 
reversible after discontinuation of TRAVATAN Z [see Warnings and Precautions (5.1)].  
Potential for Eyelash Changes  
Inform the patient about the possibility of eyelash and vellus hair changes in the treated eye during 
treatment with TRAVATAN Z. These changes may result in a disparity between eyes in length, 
thickness, pigmentation, number of eyelashes or vellus hairs, and/or direction of eyelash growth. 
Eyelash changes are usually reversible upon discontinuation of treatment [see Warnings and 
Precautions (5.2)].  
Handling the Container  
Instruct the patient to avoid allowing the tip of the dispensing container to contact the eye, 
surrounding structures, fingers, or any other surface in order to avoid contamination of the solution 
by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent 
loss of vision may result from using contaminated solutions [see Warnings and Precautions (5.6)].  
When to Seek Physician Advice  
Advise the patient that if they develop an intercurrent ocular condition (e.g., trauma or infection), 
have ocular surgery, or develop any ocular reactions, particularly conjunctivitis and eyelid 
reactions, they should immediately seek their physician's advice concerning the continued use of 
TRAVATAN Z [see Warnings and Precautions (5.3, 5.4, 5.5)].  
Use with Contact Lenses  
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minutes following its administration [see Warnings and Precautions (5.7)].  
Use with Other Ophthalmic Drugs  
If more than one topical ophthalmic drug is being used, the drugs should be administered at least 
5 minutes between applications.  
 
 

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TIMOPTIC** is a registered trademark of Merck & Co., Inc.  
Distributed by:  
Novartis Pharmaceuticals Corporation  
East Hanover, New Jersey 07936  
© Novartis  
T2020-40 
 
 

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Appendix K 
IZBA® PACKAGE INSERT 
FULL PRESCRIBING INFORMATION 
1 INDICATIONS AND USAGE 
IZBA (travoprost ophthalmic solution) 0.003% is indicated for the reduction of elevated 
intraocular pressure in patients with open-angle glaucoma or ocular hypertension.  
2 DOSAGE AND ADMINISTRATION  
The recommended dosage is one drop in the affected eye(s) once daily in the evening. IZBA 
(travoprost ophthalmic solution) 0.003% should not be administered more than once daily since it 
has been shown that more frequent administration of prostaglandin analogs may decrease the 
intraocular pressure lowering effect.  
Reduction of the intraocular pressure starts approximately 2 hours after the first administration 
with maximum effect reached after 12 hours.  
IZBA may be used concomitantly with other topical ophthalmic drug products to lower intraocular 
pressure. If more than one topical ophthalmic drug is being used, the drugs should be administered 
at least five (5) minutes apart.  
3 DOSAGE FORMS AND STRENGTHS  
Ophthalmic solution containing travoprost 0.03 mg/mL.  
4 CONTRAINDICATIONS  
None  
5 WARNINGS AND PRECAUTIONS  
5.1 Pigmentation 
Travoprost ophthalmic solution has been reported to cause changes to pigmented tissues. The most 
frequently reported changes have been increased pigmentation of the iris, periorbital tissue (eyelid) 
and eyelashes. Pigmentation is expected to increase as long as travoprost is administered. The 
pigmentation change is due to increased melanin content in the melanocytes rather than to an 
increase in the number of melanocytes. After discontinuation of travoprost, pigmentation of the 
iris is likely to be permanent, while pigmentation of the periorbital tissue and eyelash changes have 
been reported to be reversible in some patients. Patients who receive treatment should be informed 
of the possibility of increased pigmentation. The long-term effects of increased pigmentation are 
not known.  
Iris color change may not be noticeable for several months to years. Typically, the brown 
pigmentation around the pupil spreads concentrically towards the periphery of the iris and the 
entire iris or parts of the iris become more brownish. Neither nevi nor freckles of the iris appear to 
be affected by treatment. While treatment with IZBA (travoprost ophthalmic solution) 0.003% can 
be continued in patients who develop noticeably increased iris pigmentation, these patients should 

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be examined regularly. (See Patient Counseling Information, 17.1). 
5.2 Eyelash Changes  
IZBA may gradually change eyelashes and vellus hair in the treated eye. These changes include 
increased length, thickness, and number of lashes. Eyelash changes are usually reversible upon 
discontinuation of treatment.  
5.3 Intraocular Inflammation  
IZBA should be used with caution in patients with active intraocular inflammation (e.g., uveitis) 
because the inflammation may be exacerbated.  
5.4 Macular Edema  
Macular edema, including cystoid macular edema, has been reported during treatment with 
travoprost ophthalmic solution. IZBA should be used with caution in aphakic patients, in 
pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for 
macular edema.  
5.5 Bacterial Keratitis  
There have been reports of bacterial keratitis associated with the use of multiple-dose containers 
of topical ophthalmic products. These containers had been inadvertently contaminated by patients 
who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface 
(See Patient Counseling Information, 17.3).  
5.6 Use with Contact Lenses  
Contact lenses should be removed prior to instillation of IZBA and may be reinserted 15 minutes 
following its administration.  
6 ADVERSE REACTIONS 
6.1 Clinical Studies Experience 
 Because clinical studies are conducted under widely varying conditions, adverse reaction rates 
observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies 
of another drug and may not reflect the rates observed in practice.  
Different methodologies were used to collect adverse reactions during the development of 
travoprost. The most common adverse reaction observed in controlled clinical studies with 
travoprost 0.004% was ocular hyperemia. Ocular hyperemia was reported in 30 to 50% of patients 
by physician rating the severity of patient’s post treatment ocular hyperemia compared to 
standardized reference photographs and/or patients who discontinued therapy due to ocular 
hyperemia.  
In a 3-month clinical trial involving 442 patients exposed to IZBA (travoprost ophthalmic solution, 
0.003%) and 422 control patients exposed to travoprost ophthalmic solution, 0.004%, the most 
common adverse drug reaction was ocular hyperemia. This was reported in 12% of patients treated 

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with IZBA based on clinical observations and/or patient complaints. One patient (0.2%) 
discontinued treatment with IZBA due to ocular hyperemia. Rates observed in the control patients 
were comparable. 
 

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Ocular adverse reactions reported in clinical studies with travoprost ophthalmic solutions including 
IZBA at an incidence of 5% to 10% included decreased visual acuity, eye discomfort, foreign body 
sensation, pain and pruritus. Ocular adverse reactions reported at an incidence of 1 to 4% included 
abnormal vision, blepharitis, blurred vision, cataract, conjunctivitis, corneal staining, dry eye, iris 
discoloration, keratitis, lid margin crusting, ocular inflammation, photophobia, subconjunctival 
hemorrhage and tearing.  
Nonocular adverse reactions reported at an incidence of 1 to 5% in these clinical studies were 
allergy, angina pectoris, anxiety, arthritis, back pain, bradycardia, bronchitis, chest pain, cold/flu 
syndrome, depression, dyspepsia, gastrointestinal disorder, headache, hypercholesterolemia, 
hypertension, hypotension, infection, pain, prostate disorder, sinusitis, urinary incontinence and 
urinary tract infections.  
In post marketing use with prostaglandin analogs, periorbital and lid changes including deepening 
of the eyelid sulcus have been observed.  
8 USE IN SPECIFIC POPULATIONS  
8.1 Pregnancy  
Pregnancy Category C  
There are no adequate and well-controlled studies of IZBA (travoprost ophthalmic solution 
0.003%) administration in pregnant women. Malformations were observed in rats at doses that 
were 1500 times higher the maximum recommended human ocular dose (MRHOD) based on 
estimated Cmax values for the active free acid. Embryo lethality and decreased fetal/neonate 
viability were observed in mice at subcutaneous doses 9-fold higher than the MRHOD based on 
estimated Cmax for the active free acid. IZBA should be used during pregnancy only if the 
potential benefit justifies the potential risk to the fetus.  
Travoprost was teratogenic in rats, at an intravenous (IV) dose up to 10 mcg/kg/day (1500 times 
the MRHOD, evidenced by an increase in the incidence of skeletal malformations as well as 
external and visceral malformations, such as fused sternebrae, domed head and hydrocephaly. 
Travoprost did not produce malformations in rats at IV doses up to 3 mcg/kg/day (470 times the 
MRHOD), or in mice at subcutaneous doses up to 1 mcg/kg/day (9 times the MRHOD). Travoprost 
produced an increase in post-implantation losses and a decrease in fetal viability in rats at IV doses 
of 10 mcg/kg/day (1500 times the MRHOD) and in mice at subcutaneous doses of 1 mcg/kg/day 
(9 times the MRHOD).  
In the offspring of female rats that received travoprost subcutaneously from Day 7 of pregnancy 
to lactation Day 21 at doses of ≥ 0.12 mcg/kg/day (3.2 times the MRHOD), the incidence of 
postnatal mortality was increased, and neonatal body weight gain was decreased. Neonatal 
development was also affected, evidenced by delayed eye opening, pinna detachment and preputial 
separation, and by decreased motor activity. 

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8.3 Nursing Mothers  
A study in lactating rats demonstrated that radiolabeled travoprost and/or its metabolites were 
excreted in milk. It is not known whether this drug or its metabolites are excreted in human milk. 
Because many drugs are excreted in human milk, caution should be exercised when IZBA is 
administered to a nursing woman.  
8.4 Pediatric Use  
Use in pediatric patients below the age of 16 years is not recommended because of potential safety 
concerns related to increased pigmentation following long term chronic use.  
8.5 Geriatric Use  
No overall clinical differences in safety or effectiveness have been observed between elderly and 
other adult patients.  
11 DESCRIPTION Travoprost is a synthetic prostaglandin F2α analog. Its chemical name is [1R-
[1 (Z),2 (1E,3R*),3α ,5 α]]-7-[3,5-Dihydroxy-2-[3- hydroxy-4-[3-(trifluoromethyl) phenoxy]-1- 
butenyl]cyclopentyl]-5-heptenoic acid, 1-methylethylester. It has a molecular formula of 
C26H35F3O6 and a molecular weight of 500.55. The chemical structure of travoprost is: 
 
Travoprost is a clear, colorless to slightly yellow oil that is very soluble in acetonitrile, methanol, 
octanol, and chloroform. It is practically insoluble in water.  
IZBA (travoprost ophthalmic solution) 0.003% is supplied as sterile, isotonic, buffered aqueous 
solution of travoprost with a pH of approximately 6.8 and an osmolality of approximately 290 
mOsmol/kg.  
IZBA contains Active: travoprost 0.03 mg/mL; Preservative: POLYQUAD® (polyquaternium-1) 
0.01mg/mL; Inactives: boric acid, mannitol, polyoxyethylene 40 hydrogenated castor oil, 
propylene glycol, sodium chloride, sodium hydroxide and/or hydrochloric acid (to adjust pH) and 
purified water, USP.  
12 CLINICAL PHARMACOLOGY  
12.1 Mechanism of Action  
Travoprost free acid, a prostaglandin analog is a selective FP prostanoid receptor agonist which is 
believed to reduce intraocular pressure by increasing uveoscleral outflow. The exact mechanism 

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of action is unknown at this time. 
12.3 Pharmacokinetics  
Travoprost is absorbed through the cornea and is hydrolyzed to the active free acid. Data from four 
multiple dose pharmacokinetic studies using travoprost ophthalmic solution, 0.004% (totaling 107 
subjects) have shown that plasma concentrations of the free acid are below 0.01 ng/mL (the 
quantitation limit of the assay) in two-thirds of the subjects. In those individuals with quantifiable 
plasma concentrations (N=38), the mean plasma Cmax was 0.018 ± 0.007 ng/mL (ranged 0.01 to 
0.052 ng/mL) and was reached within 30 minutes. From these studies, travoprost is estimated to 
have a plasma half-life of 45 minutes. There was no difference in plasma concentrations between 
Days 1 and 7, indicating steady-state was reached early and that there was no significant 
accumulation.  
Travoprost, an isopropyl ester prodrug, is hydrolyzed by esterases in the cornea to its biologically 
active free acid. Systemically, travoprost free acid is metabolized to inactive metabolites via beta-
oxidation of the α(carboxylic acid) chain to give the 1,2-dinor and 1,2,3,4-tetranor analogs, via 
oxidation of the 15-hydroxyl moiety, as well as via reduction of the 13,14 double bond.  
The elimination of travoprost free acid from plasma was rapid and levels were generally below the 
limit of quantification within one hour after dosing. The terminal elimination half-life of travoprost 
free acid was estimated from fourteen subjects and ranged from 17 minutes to 86 minutes with the 
mean half-life of 45 minutes. Less than 2% of the topical ocular dose of travoprost was excreted 
in the urine within 4 hours as the travoprost free acid.  
13 NONCLINICAL TOXICOLOGY  
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility  
Two-year carcinogenicity studies in mice and rats at subcutaneous doses of 10, 30, or 100 
mcg/kg/day did not show any evidence of carcinogenic potential. However, at 100 mcg/kg/day, 
male rats were only treated for 82 weeks, and the maximum tolerated dose (MTD) was not reached 
in the mouse study. The high dose (100 mcg/kg) corresponds to exposure levels over 400 times 
(for the mouse) and 700 times (for the rat) of the human exposure at the maximum recommended 
human ocular dose (MRHOD) of 0.03 mcg/kg, based on estimated plasma Cmax for active free 
acid.  
Travoprost was not mutagenic in the Ames test, mouse micronucleus test or rat chromosome 
aberration assay. A slight increase in the mutant frequency was observed in one of two mouse 
lymphoma assays in the presence of rat S-9 activation enzymes.  
Travoprost did not affect mating or fertility indices in male or female rats at subcutaneous doses 
up to 10 mcg/kg/day (40 times the MRHOD based on estimated plasma Cmax for active free acid). 
At 10 mcg/kg/day, the mean number of corpora lutea was reduced, and the post implantation losses 
were increased. These effects were not observed at 3 mcg/kg/day (12 times the MRHOD). 

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14 CLINICAL STUDIES  
A single clinical trial of 3 months duration was conducted to compare the IOP-lowering effect of 
IZBA (travoprost ophthalmic solution) 0.003% to TRAVATAN (travoprost ophthalmic solution) 
0.004%, with both dosed once daily in the evening in adult patients with open angle glaucoma or 
ocular hypertension. Patient age ranged from 21 to 92 years, with a mean age of 65 years. A total 
of 864 patients (IZBA, 442 patients; TRAVATAN, 422 patients) were enrolled, with 840 (97%) 
completing through Month 3.  
Analysis was based on the intent-to-treat (ITT) population defined as all patients who received 
study drug and completed at least one scheduled on-therapy study visit.  
The least squares mean IOP (mmHg), the difference in mean IOP (IZBA minus TRAVATAN), 
and the 95% CI for the treatment difference in mean IOP at visit and time point are presented in 
Table 1. The differences in the mean IOP at all visits and time points were within ±1 mmHg, 
demonstrating equivalence of IZBA to TRAVATAN in lowering intraocular pressure.  
Table 2 presents the mean IOP change from baseline at Week 2, Week 6, and at Month 3. IZBA 
demonstrated comparable IOP reductions at all on-therapy visits and time points; the mean IOP 
reduction from baseline in the IZBA group ranged from 7.1 to 8.2 mmHg and in the TRAVATAN 
group ranged from 7.1 to 8.4 mmHg. In both treatment groups, the greatest mean IOP reduction 
was observed at the 8 AM assessment time point. 
Table 1 Mean IOP (mmHg) by Treatment Group and Treatment Difference in Mean IOP 
 
SE = Standard Error; CI = Confidence Interval * Estimates for Week 2, Week 6, and Month 3 are based on least squares means 
derived from a statistical model that accounts for correlated IOP measurements within patient where site and 8 AM baseline IOP 
stratum are in the model; estimates for Baseline visit at each time point are based on a two-sample independent t-test procedure. 
**One subject had missing data at 8 AM at Week 6; one subject had missing data at 4 PM at Month 3. 

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Table 2. IOP Change from Baseline (mmHg) 
 
*One subject had missing data at 8 AM at Week 6; one subject had missing data at 4 PM at Month 3. 
16 HOW SUPPLIED/STORAGE AND HANDLING  
IZBA (travoprost ophthalmic solution) 0.003% is a sterile, isotonic, buffered, preserved, aqueous 
solution of travoprost (0.03 mg/mL) supplied in Alcon's oval DROP-TAINER® package system.  
IZBA is supplied as a 2.5 mL solution in a 4 mL bottle and a 5 mL solution in a 7.5 mL bottle. The 
dispenser bottles are made of polypropylene and fitted with a natural color polypropylene dropper 
tip and a turquoise polypropylene over cap. Tamper evidence is provided with a shrink band around 
the closure and neck area of the package.  
2.5 mL fill NDC 0065-0000-00  
5 mL fill NDC 0065-0000-00  
Storage: Store at 2° - 25°C (36° - 77°F).  
17 PATIENT COUNSELING INFORMATION  
17.1 Potential for Pigmentation  
Advise patients about the potential for increased brown pigmentation of the iris, which may be 
permanent. Advise patients about the possibility of eyelid skin darkening, which may be reversible 
after discontinuation of IZBA (travoprost ophthalmic solution 0.003%).  
17.2 Potential for Eyelash Changes  
Advise patients about the possibility of eyelash and vellus hair changes in the treated eye during 
treatment with IZBA. These changes may result in a disparity between eyes in length, thickness, 
pigmentation, number of eyelashes or vellus hairs, and/or direction of eyelash growth. Eyelash 
changes are usually reversible upon discontinuation of treatment.  
17.3 Handling the Container  
Instruct patients to avoid allowing the tip of the dispensing container to contact the eye, 
surrounding structures, fingers, or any other surface in order to avoid contamination of the solution 
by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent 
loss of vision may result from using contaminated solutions.   
 

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17.4 When to Seek Physician Advice  
Advise patients that if they develop an intercurrent ocular condition (e.g., trauma or infection), 
have ocular surgery, or develop any ocular reactions, particularly conjunctivitis and eyelid 
reactions, they should immediately seek their physician's advice concerning the continued use of 
IZBA.  
17.5 Use with Contact Lenses  
Contact lenses should be removed prior to instillation of IZBA and may be reinserted 15 minutes 
following its administration.  
17.6 Use with Other Ophthalmic Drugs  
If more than one topical ophthalmic drug is being used, the drugs should be administered at least 
five (5) minutes between applications.  
Rx Only  
U.S. Patent Nos. 5,631,287; 5,849,792; 5,889,052; 6,011,062; 8,178,582  
ALCON®  
ALCON LABORATORIES, INC. Fort Worth, Texas 76134 USA 
© 2006, 2010, 2011, 2012, 2013 Novartis  
9007509-1111  
PRINCIPAL DISPLAY PANEL  
NDC 0065-0000-00 Rx Only  
IZBA (travoprost ophthalmic solution) 0.003%  
Alcon®                             2.5 mL