Clinical Evaluation of an Investigational Lipid Drop in Non-contact Lens Wearing Patients
Conditions: Visual Acuity
Sponsor: Johnson & Johnson Vision Care, Inc.

Johnson & Johnson Vision Care, Inc.
Clinical Study Protocol
Clinical Evaluation of an Investigational Lipid Drop in Non-contact Lens Wearing Patients
Protocol Number CR-6328
Version: 4.0
Date: 13 August 2019
Investigational Products: Investigational lipid eye drops and blink® Tears Eye Drops
Key Words: artificial tears, dispensing, Visual Analogue Scale (VAS) comfort, dry eye,
subject-reported ocular symptoms (SROS)
Statement of Compliance to protocol, GCP and applicable regulatory guidelines:
This trial will be conducted in compliance with the protocol, ISO 141551 the International 
Conference for Harmonization Good Clinical Practice E6 (ICH-GCP)2, the Declaration of 
Helsinki3, and all applicable regulatory requirements.
Confidentiality Statement:
This document contains confidential information, which should not be copied, referred to, 
released or published without written approval from Johnson & Johnson Vision Care, Inc.  
The information may not be disclosed to others except to the extent necessary to obtain 
Institutional Review Board/Independent Ethics Committee approval and informed consent, 
or as required by International, Federal and State Laws, as applicable. Persons to whom 
this information is disclosed must be informed that this information is privileged and 
confidential and that it should not be further disclosed without the written permission of 
Johnson & Johnson Vision Care, Inc.  Any supplemental information that may be added to 
this document is also confidential and proprietary to Johnson & Johnson Vision Care, Inc. 
and must be kept in confidence in the same manner as the contents of this document.
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TABLE OF CONTENTS
PROTOCOL TITLE, NUMBER, VERSION......................................................................6 
SPONSOR NAME AND ADDRESS..................................................................................6 
MEDICAL MONITOR........................................................................................................6 
AUTHORIZED SIGNATURES..........................................................................................7 
SYNOPSIS...........................................................................................................................9 
COMMONLY USED ABBREVIATIONS AND DEFINITIONS OF TERMS ...............15 
1. 
INTRODUCTION AND BACKGROUND ..............................................................16 
1.1. 
Name and Descriptions of Investigational Products ...........................................16 
1.2. 
Intended Use of Investigational Products............................................................16 
1.3. 
Summary of Findings from Nonclinical Studies.................................................16 
1.4. 
Summary of Known Risks and Benefits to Human Subjects..............................16 
1.5. 
Relevant Literature References and Prior Clinical Data Relevant to Proposed 
Clinical Study.................................................................................................................17 
2. 
STUDY OBJECTIVES, ENDPOINTS AND HYPOTHESES .................................17 
2.1. 
Objectives............................................................................................................17 
2.2. 
Endpoints.............................................................................................................17 
2.3. 
Hypotheses ..........................................................................................................18 
3. 
TARGETED STUDY POPULATION......................................................................18 
3.1. 
General Characteristics .......................................................................................18 
3.2. 
Inclusion Criteria.................................................................................................18 
3.3. 
Exclusion Criteria................................................................................................19 
3.4. 
Enrollment Strategy.............................................................................................19 
4. 
STUDY DESIGN AND RATIONALE.....................................................................20 
4.1. 
Description of Study Design ...............................................................................20 
4.2. 
Study Design Rationale.......................................................................................20 
4.3. 
Enrollment Target and Study Duration...............................................................20 
5. 
TEST ARTICLE ALLOCATION AND MASKING................................................21 
5.1. 
Test Article Allocation........................................................................................21 
5.2. 
Masking...............................................................................................................21 
5.3. 
Procedures for Maintaining and Breaking the Masking......................................21 
6. 
STUDY INTERVENTION........................................................................................22 
6.1. 
Identity of Test Articles.......................................................................................22 
6.2. 
Ancillary Supplies/Products................................................................................23 
6.3. 
Administration of Test Articles...........................................................................23 
6.4. 
Packaging and Labeling ......................................................................................23 
6.5. 
Storage Conditions..............................................................................................24 
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6.6. 
Collection and Storage of Samples .....................................................................24 
6.7. 
Accountability of Test Articles ...........................................................................24 
7. 
STUDY EVALUATIONS.........................................................................................25 
7.1. 
Time and Event Schedule....................................................................................25 
7.2. 
Detailed Study Procedures ..................................................................................26 
VISIT 1 ......................................................................................................................26 
VISIT 2 ......................................................................................................................28 
VISIT 3 ......................................................................................................................30 
FINAL EVALUATION.............................................................................................30 
7.3. 
Unscheduled Visits..............................................................................................31 
7.4. 
Laboratory Procedures ........................................................................................32 
8. 
SUBJECTS COMPLETION/WITHDRAWAL.........................................................32 
8.1. 
Completion Criteria.............................................................................................32 
8.2. 
Withdrawal/Discontinuation from the Study ......................................................32 
9. 
PRE-STUDY AND CONCOMITANT INTERVENTION/MEDICATION ............33 
10. 
DEVIATIONS FROM THE PROTOCOL.............................................................33 
11. 
STUDY TERMINATION ......................................................................................34 
12. 
PROCEDURE FOR HANDLING PRODUCT QUALITY COMPLAINTS.........34 
13. 
ADVERSE EVENTS..............................................................................................35 
13.1. 
Definitions and Classifications........................................................................35 
13.2. 
Assessing Adverse Events...............................................................................37 
13.2.1.    Causality Assessment ......................................................................................38 
13.2.2.    Severity Assessment........................................................................................38 
13.3. 
Documentation and Follow-Up of Adverse Events.........................................38 
13.4. 
Reporting Adverse Events...............................................................................40 
13.4.1.    Reporting Adverse Events to Sponsor.............................................................40 
13.4.2. Reporting Adverse Events to the Responsible IEC/IRB and Health 
Authorities..........................................................................................................................41 
13.4.3.    Event of Special Interest..................................................................................41 
13.5. 
Reporting of Pregnancy...................................................................................41 
14. 
STATISTICAL METHODS...................................................................................41 
14.1. 
General Considerations....................................................................................41 
14.2. 
Sample Size Justification.................................................................................41 
14.3. 
Analysis Populations .......................................................................................42 
14.4. 
Level of Statistical Significance......................................................................42 
14.5. 
Primary Analysis .............................................................................................42 
14.6. 
Secondary Analysis .........................................................................................43 
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14.7. 
Other Exploratory Analyses ............................................................................44 
14.8. 
Interim Analysis ..............................................................................................44 
14.9. 
Procedure for Handling Missing Data and Drop-Outs ....................................44 
14.10. 
Procedure for Reporting Deviations from Statistical Plan ..............................44 
15. 
DATA HANDLING AND RECORD KEEPING/ARCHIVING...........................44 
15.1. 
Electronic Case Report Form/Data Collection ................................................44 
15.2. 
Subject Record.................................................................................................45 
16. 
DATA MANAGEMENT........................................................................................45 
16.1. 
Access to Source Data/Document ...................................................................45 
16.2. 
Confidentiality of Information.........................................................................46 
16.3. 
Data Quality Assurance...................................................................................46 
17. 
MONITORING.......................................................................................................46 
18. 
ETHICAL AND REGULATORY ASPECTS .......................................................47 
18.1. 
Study-Specific Design Considerations ............................................................47 
18.2. 
Investigator Responsibility..............................................................................47 
18.3. 
Independent Ethics Committee or Institutional Review Board (IEC/IRB) .....47 
18.4. 
Informed Consent ............................................................................................48 
18.5. 
Privacy of Personal Data .................................................................................49 
19. 
STUDY RECORD RETENTION...........................................................................50 
20. 
FINANCIAL CONSIDERATIONS .......................................................................50 
21. 
PUBLICATION......................................................................................................50 
22. 
REFERENCES .......................................................................................................51 
APPENDIX A: PATIENT REPORTED OUTCOMES (STUDY QUESTIONNAIRES).53 
APPENDIX B: PATIENT INSTRUCTION GUIDE ........................................................65 
APPENDIX C: PACKAGE INSERT (APPROVED PRODUCT)....................................66 
APPENDIX D: MEDMONT ASSESSMENT PROCEDURE..........................................68 
APPENDIX E: 
..................................73 
 EXPANDED CORNEAL STAINING ASSESSMENT..................................74 
 SUBJECT REPORTED OCULAR SYMPTOMS/PROBLEMS.....................79 
 BIOMICROSCOPY SCALE ...........................................................................81 
 DISTANCE AND NEAR VISUAL ACUITY.................................................87 
 PATIENT REPORTED OUTCOMES.............................................................92 
PROTOCOL COMPLIANCE INVESTIGATOR(S) SIGNATURE PAGE .....................94 
 
 
 
 
 
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TABLE OF CONTENTS
Figure 1: Study Flowchart .................................................................................................14 
TABLE OF CONTENTS
Table 1: Target number of subjects by arm and site..........................................................20 
Table 2: Ancillary Supplies ...............................................................................................23 
Table 3: Time and Events ..................................................................................................25 
 
 
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PROTOCOL TITLE, NUMBER, VERSION 
Title: Clinical Evaluation of an Investigational Lipid Drop in Non-contact Lens Wearing 
Patients
Protocol Number: CR-6328
Version: 4.0
Date:  13 August 2019
SPONSOR NAME AND ADDRESS 
Johnson & Johnson Vision Care, Inc. (JJV)
7500 Centurion Parkway 
Jacksonville, FL 32256
MEDICAL MONITOR 
The Medical Monitor must be notified by the clinical institution/site by e-mail, fax, or 
telephone within 24 hours of learning of a Serious Adverse Event. The Medical Monitor 
may be contacted during business hours for adverse event questions. General study related 
questions should be directed towards your assigned clinical research associate.
The Medical Monitoring Plan is maintained as a separate document and included in the 
Trial Master File.
 
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AUTHORIZED SIGNATURES 
The signature below constitutes the approval of this protocol and the attachments, and 
provides the necessary assurances that this trial will be conducted according to all 
stipulations of the protocol, including all statements regarding confidentiality, and 
according to local legal and regulatory requirements and applicable U.S. federal 
regulations,4 ICH guidelines,2 ISO 14155,1 and the Declaration of Helsinki.3
Author/Study 
Responsible 
Clinician
See Electronic Signature Report
DATE
Clinical Operations 
Manager
See Electronic Signature Report
DATE
Biostatistician
See Electronic Signature Report
DATE
Data Management 
See Electronic Signature Report
DATE
Fellow Reviewer
See Electronic Signature Report
DATE
Approver
See Electronic Signature Report
DATE
Approver
See Electronic Signature Report
DATE
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SYNOPSIS  
Protocol Title
Clinical Evaluation of an Investigational Lipid Drop in 
Non-contact Lens Wearing Patients
Sponsor
JJV, 7500 Centurion Parkway, Jacksonville, FL  32256
Clinical Phase
Confirmatory, Phase 1
Trial Registration
This study will be registered on ClinicalTrials.gov based on 
the following: this confirmatory study meets the criteria for 
registration in
Test Article(s)
Two artificial tears products:
x
Investigational lipid eye drops – 9618X (Test)
x
Blink® Tears eye drops (Control)
Treatment dosage
Dosage: Instill 1-2 drops OU 3-4 times a day.  
Objectives 
The objective of this study is to evaluate the safety and the 
efficacy of the Investigational lipid eye drops (Test) by
comparison with blink® Tears eye drops (Control).
This study is being conducted to support product 
registration in the Europe Union.
Study Endpoints
Primary endpoint(s):
x
Change in overall ocular comfort from baseline at 
30-Day follow-up using VAS
Secondary endpoint(s):
x
Corneal staining Grade 2 or higher using FDA scale
x
Change in overall quality of vision from baseline at 
7-Day and 30-Day follow-up collected using VAS
x
Subject’s reported ocular symptoms (yes/no)
x
Change in overall ocular comfort from baseline at 
7-Day follow-up collected using VAS
Other Endpoint(s)
x
Tear film break up time 
x
Slit Lamp Findings using FDA scale
x
End of day ocular comfort
x
Snellen best corrected distance visual acuity
x
Subjective Evaluation of Symptom of Dryness
x
Adverse Events
x
Number and reasons for discontinuation will be 
monitored.
Study Design
This is a 30-Day, multi-site, double masked, bilateral,
active-controlled, 2-Arm parallel group study. Subjects are 
scheduled for 3 study visits (screening/baseline, 7-Day and 
30-Day follow-up visits) over a period of one month.
Sample Size
Approximately 150 subjects (60 per arm) will be enrolled 
and approximately 112 subjects (56 per arm) are targeted to 
complete the study.
Study Duration
The study will last approximately 2 months and include a 
1-month enrollment period.
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Anticipated Study 
Population
Non-contact lens wearers 18-69 years of age with self-
reported symptoms of ocular dryness or irritation and/or the 
use of artificial tears in the last 3 months. 
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Eligibility Criteria
Potential subjects must satisfy all the following criteria to 
be enrolled in the study:
1. Subjects must be at least 18 years of age and no 
more than 69 years of age (inclusive).
2. Subjects must be non-contact lens wearers.
3. Subjects must achieve visual acuity of 20/30 or 
better in each eye, either unaided or best corrected.
4. Subjects must possess a functional/usable pair of 
spectacles and bring them to the visit (only if 
applicable - to the investigator’s discretion). 
5. Self-reported symptoms of ocular dryness or 
irritation and/or the use of artificial tears in the last 
3 months.  
6. Subjects must read, understand, and sign the 
Statement of Informed Consent
7. Subjects must appear able and willing to adhere to 
the instructions set forth in this clinical protocol.
Potential subjects who meet any of the following criteria 
will be excluded from participating in the study: 
1. Currently pregnant or breast-feeding.
2. Diabetes.
3. Any ocular or systemic allergies or disease which 
may interfere with the clinical trial (at the discretion 
of the investigator).
4. Any systemic disease, autoimmune disease, or use 
of medication which may interfere with the clinical 
trial (at the discretion of the investigator).
5. Any infectious diseases (e.g. hepatitis, tuberculosis) 
or a contagious immunosuppressive disease (e.g. 
HIV), by self-report.
6. Any Grade 3 or greater biomicroscopy findings (this 
includes, corneal edema, corneal staining, corneal 
vascularization, 
conjunctival 
injection, 
tarsal 
abnormalities, bulbar injection) on the FDA
classification scale.
7. Any active ocular abnormalities/conditions that 
may interfere with the clinical trial (this includes, 
but not limited to, chalazia, recurrent styles, 
pterygium, infection, etc.).
8. Any corneal distortion due to previous rigid gas 
permeable lens wear, surgery or pathology.
9. History of any ocular or corneal surgery (e.g. RK, 
PRK, LASIK) 
10. Participation in any pharmaceutical or medical 
device related clinical trial within 30 days prior to 
study enrollment.
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11. History of binocular vision abnormality or 
strabismus.
12. Habitual wearers of soft contact lenses within the 
past 1 month or rigid gas permeable lens within the 
past 3 months
13. Current habitual use of Prescription Medication to
treat dry eye or ocular discomfort, ocular steroids, 
or any medication (RX or OTC) that would interfere 
with the clinical study (at the discretion of the 
investigator)
14. Employees of investigational clinic (investigator, 
coordinator, and technician etc) or family members 
of an employee of the clinical site by self-report.
In addition to the above criteria, patients with any 
allergy or sensitivity to ingredients that this product 
may contain (Castor Oil, Polyoxyl 40 Hydrogenated 
Castor Oil, Sodium Chlorite, Boric Acid, Sodium 
Borate Decahydrate, Sodium Chloride, Potassium 
Chloride, Calcium Chloride Dihydrate, Magnesium 
Chloride Hexahydrate, Polyethylene Glycol 400,
Sodium Hyaluronate, Purified Water) should not 
participate in the study.
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Disallowed 
Medications/Interventions Current habitual use of Prescription Medicines to treat dry 
eye or ocular discomfort, ocular steroids, or any medication 
(RX or OTC) that would interfere with the clinical study (at 
the discretion of the investigator).
Measurements and 
Procedures
Subjective assessment of ocular comfort using visual 
analog scale (VAS), subjective evaluation of symptom of 
dryness, Snellen visual acuity, slit lamp finding using FDA 
scale, tear film break time, subjective reported ocular 
symptoms.
Microbiology or Other 
Laboratory Testing
None
Study Termination
The occurrence of one or more Unanticipated Adverse 
Device Effect (UADE), or any SAE where relationship to 
study agent cannot be ruled out, will result in stopping 
further dispensing investigational product.  In the event of 
a UADE or SAE, the Sponsor Medical Monitor may 
unmask the treatment regimen of subject(s) and may 
discuss this with the Principal Investigator before any
further subjects are enrolled.
Ancillary Supplies/ 
Study-Specific Materials
ScleralFil (Bausch + Lomb), LacriPure (Menicon), 
Fluorescein (Akorn, Inc.) or other
country-specific 
alternative approved by the sponsor.
Principal Investigator(s) 
and Study 
Institution(s)/Site(s)
A full list of Principal Investigators, clinical sites, and 
institutions is kept separately from the Study Protocol and 
is included in the study Trial Master File.  
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COMMONLY USED ABBREVIATIONS AND DEFINITIONS OF TERMS 
ADD
Plus Power Required For Near Use
ADE
Adverse Device Effect
AE
Adverse Event/Adverse Experience
BCVA
Best Corrected Visual Acuity
BSCVA
Best Spectacle Corrected Visual Acuity
CE
Conformité Européene
CEH
Consumer Eye Health
CFR
Code of Federal Regulations
COAS
Complete Ophthalmic Analysis System
COM
Clinical Operations Manager
CRA
Clinical Research Associate
CRF
Case Report Form
CRO
Contract Research Organization
CT
Center Thickness
D
Diopter
DMC
Data Monitoring Committee
eCRF
Electronic Case Report Form
EDC
Electronic Data Capture
ETDRS
Early Treatment Diabetic Retinopathy Study
FDA
Food and Drug Administration
GCP
Good Clinical Practice
HIPAA
Health Insurance Portability and Accountability Act
IB
Investigator’s Brochure
ICF
Informed Consent Form
ICH
International Council for Harmonization
IDE
Investigational Device Exemption
IEC
Independent Ethics Committee
IRB
Institutional Review Board
ISO
International Organization for Standardization
ITT
Intent-to-Treat
JJV
Johnson & Johnson Vision, Inc.
LC
Limbus Center
LogMAR
Logarithm of Minimal Angle of Resolution
MedDRA©
Medical Dictionary for Regulatory Activities
MOP
Manual of Procedures
NIH
National Institutes of Health
OD
Right Eye
OHRP
Office for Human Research Protections
OHSR
Office for Human Subjects Research
OS
Left Eye
OSDI
Ocular Surface Disease Index
OU
Both Eyes
PD
Protocol Deviation
PHI
Protected Health Information
PI
Principal Investigator
PIG
Patient Instruction Guide
PQC
Product Quality Complaint
PRO
Patient Reported Outcome
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QA
Quality Assurance
QC
Quality Control
SAE
Serious Adverse Event/Serious Adverse Experience
SAP
Statistical Analysis Plan
SAS
Statistical Analysis System
SD
Standard Deviation
SOP
Standard Operating Procedure
UADE
Unanticipated Adverse Device Effect
USADE
Unanticipated Serious Adverse Device Effect
VA
Visual Acuity
1.
INTRODUCTION AND BACKGROUND 
It is estimated that over 16 million US adults have been diagnosed with dry eye.5 Artificial 
tears are often used to treat symptoms of ocular dryness and discomfort.  Most of the major 
artificial tear companies have some type of lipid product to address lipid deficient tear 
films, however JJV CEH does not currently have a lipid-like drop in our portfolio. 
This study will be conducted at up to 7 clinical sites in the United States and will include
one investigational lipid eye drop (9618X) and one marketed (CE marked) artificial tears 
(blink® Tears).  By developing a lipid-like drop addition to the CEH portfolio it would 
continue to live into the JJV Eye Health Mission.
1.1.
Name and Descriptions of Investigational Products  
The products used in this clinical study are listed below:
x
Investigational lipid eye drops 9618X (Test)
x
Blink® tears eye drops (Control)
1.2.
Intended Use of Investigational Products 
One of the products is an investigational, preserved lipid drop, and the other product is an
FDA and CE approved and marketed eye drop, available over the counter (without a 
prescription).  They will be used as indicated on-label to reduce symptoms of ocular 
dryness. Subjects will be required to use the 1-2 drops in both eyes 3-4 times a day. 
The intended use of the study artificial tears is treatment of subjects with symptoms of 
ocular dryness.
1.3.
Summary of Findings from Nonclinical Studies 
See the Investigator’s Brochure.
1.4.
Summary of Known Risks and Benefits to Human Subjects 
The following risks/adverse events can be associated with using artificial tears, in general:
x
There may be less comfort than when the drop was first placed on the eye.
x
The eyes may burn, sting and/or itch.
x
There may be a feeling of something in the eye (foreign body, scratched area).
x
There may be the potential for some temporary impairment due to peripheral 
infiltrates, peripheral corneal ulcers and corneal erosion.  
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x
There may be the potential for other physiological observations, such as local or 
generalized edema, corneal neovascularization, corneal staining, injection, tarsal 
abnormalities, iritis and conjunctivitis, some of which are clinically acceptable in 
low amounts.
x
There may be excessive watering, unusual eye secretions, or redness of the eye.
x
Poor visual acuity, blurred vision, rainbows or halos around objects, photo-phobia,
or dry eyes may also occur if the drops are used continuously or for too long a time.
There is no direct benefit to the subject for participating in the study, although they will be 
able to try out new artificial tears.  The information from this study will aid if the further 
development and design of new artificial tears.
For the most comprehensive clinical information regarding the artificial tears refer to the 
package inserts
1.5.
Relevant Literature References and Prior Clinical Data Relevant to Proposed 
Clinical Study 
Refer to the Investigator’s Brochure and package insert 
 for additional 
information.  
2.
STUDY OBJECTIVES, ENDPOINTS AND HYPOTHESES 
2.1.
Objectives  
The objective of this study is to evaluate the safety and efficacy of the investigational lipid 
eye drops (Test) by comparison with blink® Tears eye drops (Control).
This study is being conducted with the primary intent to support registrations in Europe.
2.2.
Endpoints  
Primary Endpoint:
The primary endpoint in this study is change in overall ocular comfort score from baseline 
at 30-Day follow-up. Subjective overall ocular comfort will be assessed at baseline, 7-Day 
and 30-Day follow-up using a Visual Analogue Scale (VAS)6,7 with continuous scale from 
0 (extremely uncomfortable) to 100 (extremely comfortable). 
Secondary endpoints: 
x
Corneal staining Grade 2 or higher using FDA scale
x
Change in overall quality of vision from baseline at 7-Day and 30-Day follow-up
using VAS
x
Subject’s reported ocular symptoms (yes/no)
x
Change in overall ocular comfort from baseline at 7-Day follow-up using VAS
Other Endpoints:
x
Tear film break up time 
x
Slit lamp findings using FDA scale
x
End of day ocular comfort
x
Snellen best corrected distance visual acuity
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x
Subjective evaluation of symptom of dryness
x
Adverse Events
x
Number and reasons for discontinuation will be monitored.
2.3.
Hypotheses 
Primary hypotheses:
1. The Test eye drops will be non-inferior to the Control eye drops with respect to 
change in ocular comfort from baseline at 30-Day follow-up. A non-inferiority 
margin of -20 point ocular comfort VAS scale will be used.
Secondary hypotheses:
1. The proportion of eyes with Grade 2 or higher corneal staining in the Test group
will be no different to that in the Control group.
2. The change in overall quality of vision from baseline at 7-Day and 30-Day 
follow-up of the Test eye drops will be no different to that of the Control eye drops.
3. The proportion of eyes with reported ocular symptoms in the Test group will be no 
different to that in the Control group.
4. The Test eye drops will be non-inferior to the Control eye drops with respect to 
change in ocular comfort from baseline at 7-Day follow-up. A non-inferiority 
margin of -20 point ocular comfort VAS scale will be used. 
3.
TARGETED STUDY POPULATION 
3.1.
General Characteristics  
The study populations will be healthy non-contact lens wearers between 18-69 years of age
from up to 7 sites in the US.
3.2.
Inclusion Criteria 
Potential subjects must satisfy all the following criteria to be enrolled in the study:
1. Subjects must be at least 18 years of age and no more than 69 years of age 
(inclusive).
2. Subjects must be non-contact lens wearers.
3. Subjects must achieve visual acuity of 20/30 or better in each eye, either unaided or 
best corrected.
4. Subjects must possess a functional/usable pair of spectacles and bring them to every
visit (only if applicable - to the investigators discretion). 
5. Self-reported symptoms of ocular dryness or irritation and/or the use of artificial 
tears in the last 3 months.  
6. Subjects must read, understand, and sign the Statement of Informed Consent.
7. Subjects must appear able and willing to adhere to the instructions set forth in this 
clinical protocol.
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3.3.
Exclusion Criteria 
Potential subjects who meet any of the following criteria will be excluded from 
participating in the study: 
1. Currently pregnant or breast-feeding.
2. Diabetes.
3. Any ocular or systemic allergies or disease which may interfere with the clinical 
trial (at the investigator’s discretion).
4. Any systemic disease, autoimmune disease, or use of medication which may 
interfere with the clinical trial (at the investigator’s discretion).
5. Any infectious diseases (e.g. hepatitis, tuberculosis) or a contagious 
immunosuppressive disease (e.g. HIV), by self-report.
6. Any Grade 3 or greater biomicroscopy findings (this includes, corneal edema, 
corneal 
staining, 
corneal 
vascularization, 
conjunctival 
injection, 
tarsal 
abnormalities, bulbar injection) on the FDA scale.
7. Any active ocular abnormalities/conditions that may interfere with the clinical trial 
(this includes, but not limited to, chalazia, recurrent styles, pterygium, infection, 
etc.).
8. Any corneal distortion due to previous rigid gas permeable lens wear, surgery or 
pathology.
9. History of any ocular or corneal surgery (e.g. RK, PRK, LASIK).
10. Participation in any pharmaceutical or medical device related clinical trial within 
30 days prior to study enrollment.
11. History of binocular vision abnormality or strabismus.
12. Habitual wearers of soft contact lenses in the past 1 month or rigid gas permeable 
lens within the past 3 months.
13. Current habitual use of Prescription Medicines to treat dry eye or ocular discomfort,
ocular steroids, or any medication (RX or OTC) that would interfere with the 
clinical study (at the discretion of the investigator).
14. Employees of investigational clinic (investigator, coordinator, and technician, etc.)
or family member of an employee of the clinical site by self-report.
In addition to the above criteria, patients with any allergy or sensitivity to ingredients 
that this product may contain (Castor Oil, Polyoxyl 40 Hydrogenated Castor Oil,
Sodium Chlorite, Boric Acid, Sodium Borate Decahydrate, Sodium Chloride,
Potassium Chloride, Calcium Chloride Dihydrate, Magnesium Chloride Hexahydrate,
Polyethylene Glycol 400, Sodium Hyaluronate, Purified Water) should not participate 
in the study.
3.4.
Enrollment Strategy 
Study subjects will be recruited from the clinical site’s subject database and/or utilizing 
Independent Ethics Committee (IEC) or Institutional Review Board (IRB) approved 
materials. 
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4.
STUDY DESIGN AND RATIONALE 
4.1.
Description of Study Design 
This is a 30-Day multi-site, randomized, double masked, bilateral, controlled, 2-Arm
parallel group study. Approximately 150 subjects will be screened and randomly assigned 
to either Test or Control group (60 subjects/arm). The goal is for a sample size of 112 after 
subjects who withdraw or are lost-to-follow-up. Subjects are scheduled for 3 study visits 
(screening/baseline, 7-Day and 30-Day follow-up visits) over a period of one month.
At Visit 1, subjects will be consented and screened for inclusion/exclusion criteria.  If a 
subject is found to meet all eligibility criteria, they will be dispensed with artificial tears 
eye drops based on the randomization scheme; otherwise, the subject will be discontinued 
from the study. Subjects will be dispensed with their randomly assigned eye drops and 
instructed to use them in both eyes, 3-4 times a day over a 7±1 day period. The follow-up
evaluation (Visit 2) will occur 7±1 days after Visit 1.
At Visit 2, VAS and PRO questionnaires, SROS and slit lamp findings will be evaluated, 
and the subject will be dispensed with a new bottle of drops. Subjects will be instructed to 
use them in both eyes 3-4 times a day until the next scheduled study visit. Visit 3 will take 
place 30+/-2 days after Visit 1.
At Visit 3, VAS and PRO questionnaires, SROS, NITBUT and slit lamp findings will be 
evaluated, and the subject will have a final evaluation before exiting from the study. 
4.2.
Study Design Rationale 
Randomized, double masked, controlled designs are the gold standard to perform 
scientifically sound evaluations of the intervention by reducing bias associated with the 
conduct and interpretation of a clinical trial and avoiding confounding from other factors.
A 30 Day period is recommended for follow up in pivotal studies8, and is an appropriate 
review period based on studies which recognize the impact of cyclical changes to tear 
quality in female subjects.9
4.3.
Enrollment Target and Study Duration 
A total of up to 150 subjects will be enrolled (informed consent signed) and randomized 
(60 per arm) from up to 7 clinical sites in the US. The goal is for a sample size of 112
subjects (56 per arm) after subjects who withdraw or are lost to follow-up.
The Investigator is responsible for ensuring that all subjects entering the study conform to 
subject selection criteria. The number of subjects targeted for randomization and 
completion are as follows:
Table 1: Target number of subjects by arm and site
Test
Control
Total
Randomization 
60
60
120
Completion
56
56
112
Number of sites
7
7
7
Number of subjects/site 
Min-Max
8-13
8-13
16-26
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The study will last approximately 2 months and include a 1-month enrollment period.
Once the informed consent has been signed the subject will be considered enrolled.
An additional subject may be enrolled if a subject discontinues from the study prematurely. 
5.
TEST ARTICLE ALLOCATION AND MASKING 
5.1.
Test Article Allocation  
Subjects will be randomly assigned to either Test or Control group based on a computer-
generated randomization schedule prepared before the start of the study. 
The 
randomization will be stratified by investigational site and randomly permuted blocks of 4
assignments will be used within each study site. The randomization scheme will be 
generated using the PROC PLAN procedure from the Statistical Analysis System (SAS)
Software version 9.4 or higher 10
The study site will follow the randomization scheme provided and will complete enrollment 
according to the randomization list and will not pre-select or assign subjects. The 
assignment of the subjects must be performed at the first baseline visit (Visit 1). The 
following must have occurred prior to randomization:
x
Informed consent has been obtained
x
Subject meets all the inclusion / exclusion criteria
x
Subject history and baseline information has been collected
5.2.
Masking 
This is a double-masked study where subjects and the investigators are masked to the 
identity of the eye drops during the study period. Every attempt will be made to keep the 
other clinical trial personnel involved in the study (e.g., Data management, Biostatistician) 
unaware of the identity of the test articles.
The identity of the investigational products will be masked by over labeling the eye drop 
bottles with a label containing the study number, expiration date and the randomization 
codes. Only the personnel involved in the over labeling and the unmasked Statistician 
generating the randomization scheme will have access to the decode information translating 
the randomization codes into Test and Control eye drops. The medical monitor will also
have access to the decode information in case breaking the mask is necessary for the urgent 
medical treatment of a subject. 
5.3.
Procedures for Maintaining and Breaking the Masking 
Under normal circumstances, the mask should not be broken until all subjects have 
completed the study and the database is finalized. Otherwise, the mask should be broken 
only if specific emergency treatment/course of action would be dictated by knowing the 
treatment status of the subject. In such cases, the Investigator may, in an emergency, contact 
the medical monitor.  In the event the mask is broken, the Sponsor must be informed as 
soon as possible. The date, time, and reason for the unmasking must be documented in the 
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subject record. The Investigator is also advised not to reveal the study treatment assignment 
to the clinical site or Sponsor personnel. 
When dispensing test articles, the following steps should be followed to maintain 
randomization codes:
1. Investigator or designee (documented on the Delegation Log) will consult the
randomization scheme to obtain the test article assignment for that subject prior to 
dispensing
2. Investigator or designee will record the subject’s number on the appropriate line of 
the randomization scheme 
3. Investigator or designee will pull the appropriate test articles from the study supply.  
All test articles that are opened, whether dispensed (placed/fit on eye or dispensed 
outside the clinical site) or not, must be recorded on the Test Article Accountability 
Log in the “Dispensed” section
6.
STUDY INTERVENTION 
6.1.
Identity of Test Articles 
Table 2: Artificial Tears 
Test 
Control 
Solution 
Name/Description
Investigational lipid eye drops
(9618X)
Blink® Tears
Manufacturer
Johnson & Johnson Vision,
Inc
Johnson & Johnson Vision, Inc
Ingredients
Castor Oil, Polyoxyl 40 
Hydrogenated Castor Oil,
Sodium Chlorite, Boric Acid,
Sodium Borate Decahydrate,
Sodium Chloride, Potassium 
Chloride, Calcium Chloride 
Dihydrate, Magnesium 
Chloride Hexahydrate,
Polyethylene Glycol 400,
Sodium Hyaluronate, Purified 
Water
Sodium Chlorite
Boric Acid
Sodium Borate Decahydrate
Sodium Chloride
Potassium Chloride
Calcium Chloride Dihydrate
Magnesium Chloride 
Hexahydrate
Polyethylene Glycol 400
Sodium Hyaluronate
Purified Water
Packaging Form
Over-Labeled
Over-Labeled
 
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6.2.
Ancillary Supplies/Products  
ScleralFil (Bausch + Lomb), LacriPure (Menicon) and Fluorescein (Akorn, Inc.), or other
country-specific alternative approved by the sponsor.
Table 2: Ancillary Supplies
Solution
Solution Name/Description
ScleralFil 
(or 
other sponsor-
approved 
product)
Lacripure 
(or 
other sponsor-
approved 
product)
Fluorescein (or 
other sponsor-
approved 
product)
Manufacturer
Bausch + Lomb
Menicon
Akorn, Inc
Preservative
None
None
None
Other distinguishing items (dye, 
packaging, approval status, etc.)
NA
NA
D&C 
Yellow 
No. 8, 0.6 mg
Sodium fluorescein dye will be used for biomicroscopy, as needed. Sterile, preservative-
free, saline may be used in this clinical study to rinse each eye.
6.3.
Administration of Test Articles 
Test articles will be dispensed to subject meeting all eligibility requirements, including any 
dispensing requirements set forth in this clinical protocol. Subjects will be dispensed an 
adequate supply of test articles to complete the study. Lost or damaged test articles will 
not be replaced at the discretion of the Investigator and/or the Sponsor.
6.4.
Packaging and Labeling 
The test articles will be packaged in bottles as the primary packaging. The test article will 
be over-labeled to mask the subject to the identity.
The test articles will be in 
investigational cartons sealed with a tamper evident seal, commercial cartons, or in plastic 
bags as the secondary packaging form.  The labels for the primary and secondary packages 
will contain the following message, in accordance with JJV over-labeling procedures for 
masked studies involving marketed products: “For Use in Clinical Study CR-6328 Only, 
Not for Resale. Product Conforms to with CE Mark Requirements.” The labels will also 
contain the product code, lot number, expiration date and the clinical study number. 
 
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6.5.
Storage Conditions 
Test articles will be maintained at ambient temperatures at the clinical site. Test articles 
must be kept under secure conditions.
6.6.
Collection and Storage of Samples 
When possible, any test article associated with an Adverse Events and/or a Product Quality 
Complaint must be retained pending directions from the sponsor for potential return back 
to JJV.
6.7.
Accountability of Test Articles 
JJV will provide the Investigator with sufficient quantities of study articles and supplies to 
complete the investigation.  The Investigator is asked to retain all shipment documentation 
for the test article accountability records. 
Test article must be kept in a locked storage room, accessible only to those assigned by the 
Investigator for dispensing. The Investigator may delegate this activity to authorized study 
site personnel listed on the Site Delegation Log.  All test articles must be accounted.  This 
includes:
1. What was dispensed for the subject 
2. What was returned to the Investigator unused
3. The number and reason for unplanned replacements  
The Investigator will collect all unused test articles from the subjects at the end of the 
subject’s participation. Subject returned unused test articles must be separated from the 
clinical study inventory of un-dispensed test articles and must be labeled with the subject 
number and date of return.  Following final reconciliation of test articles by the monitor, 
the Investigator or monitor will return all unused test articles to JJV.
If there is a discrepancy between the shipment documents and the contents, contact the 
study monitor immediately.
  
 
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x
Subject not successfully dispensed due to lack of efficacy or safety
For discontinued subjects, the Investigator will:
x
Complete the current visit (scheduled or unscheduled)
x
Complete the Final Evaluation, indicating the reason that the subject was 
discontinued from the study
x
Collect used test article(s) (brought to the visit) from the subject and discard them, 
unless otherwise stated in Section 7.2
x
Collect all unused test article(s) from the subject
An additional subject may be enrolled if a subject discontinues from the study prematurely. 
In cases where a subject is lost to follow-up, every possible effort must be made to contact 
the subject and determine the reason for discontinuation/withdrawal.  The measures taken 
to follow up must be documented including two written attempts and a certified letter (or 
equivalent) as the final attempt. 
9.
PRE-STUDY AND CONCOMITANT INTERVENTION/MEDICATION 
Concomitant medications will be documented during screening and updated during the 
study.  Disallowed medications for this study include: Current habitual use of Prescription 
Only Medicines for dry eye or ocular discomfort, ocular steroids, or any medication (RX 
or OTC) that would interfere with the clinical study (at the discretion of the investigator).
Concomitant therapies that are disallowed include: Current habitual use of Prescription 
Only Medicines for dry eye or ocular discomfort, ocular steroids, or any medication (RX 
or OTC) that would interfere with the clinical study (at the discretion of the investigator).
10. DEVIATIONS FROM THE PROTOCOL 
Investigator will notify study sponsor upon identification of a protocol deviation. Major 
protocol deviations must be reported to the sponsor within 24 hours after discovery of the 
protocol deviation.  The Investigator will report deviations per IRB/IEC requirements.  All 
deviations will be tracked and corrective actions implemented as appropriate. 
If it becomes necessary for the Investigator to implement a deviation to eliminate an 
immediate hazard to the trial subject, the Investigator may implement the deviation 
immediately without notification to the sponsor. Within 24 hours after the implemented 
deviation, the Investigator must notify and provide the rationale to the Sponsor and, as 
required, the IEC/IRB. 
The prescribed visit window for Visit 2 is 7 +/- 1 days from Visit 1 (Day 0), and for Visit 
3 is 30 +/- 2 days from Visit 1. Subjects that complete Visit 2 five (5) days or nine (9) days 
from Visit 1, or complete Visit 3 twenty-seven (27) or thirty-three (33) days from Visit 1,
will be categorized as a minor protocol deviation. Subjects completing Visit 2 at 4 days or 
earlier or 9 days or later from Visit 1 will be categorized as a major protocol deviation. 
Subject completing Visit 3 at 27 days or earlier, or 34 days or later from Visit 1 and these 
subjects or completing Visit 3 at 27 days or earlier will also be categorized as a major 
 
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protocol deviation. These subjects with major PDs will be excluded from the primary study 
analysis.
11. STUDY TERMINATION 
The occurrence of one or more Unanticipated Serious Adverse Device Effect (USADE), or 
any SAE where the relationship to study agent cannot be ruled out, may result in stopping 
further dispensing of test article.  In the event of a USADE or SAE, the Sponsor may 
unmask the treatment regimen for the subject(s) and will discuss this with the Investigator 
before any further subjects are enrolled.
The Sponsor will determine when a study will be stopped.  The Principal Investigator 
always has the discretion to initiate stopping the study based on patient safety or if 
information indicates the study’s results are compromised.
JJV reserves the right to terminate the study at any time for any reason.  Additionally, the 
IEC/IRB reserves the right to terminate the study if an unreasonable risk is determined.  
The study can be terminated by the Principal Investigator at the individual clinical site due 
to specific clinical observations, if in their opinion, after a discussion with JJV, it is 
determined that it would be unwise to continue at the clinical site.   
JJV (and the IEC/IRB and DMC, if applicable) will evaluate all adverse events.  If it is 
determined that an adverse event presents an unreasonable risk, the investigation, or that 
part of the investigation presenting the risk, will be terminated, as soon as possible.
Should the study be terminated (either prematurely or as scheduled), the Investigator will 
notify the IEC/IRB and Regulatory Authority as required by local regulatory requirements.
12. PROCEDURE FOR HANDLING PRODUCT QUALITY COMPLAINTS 
A Product Quality Complaint (PQC) refers to any written, electronic, or oral 
communication that alleges deficiencies related to the identity, quality, durability, 
reliability, safety, effectiveness or performance of test articles after they have been released 
for clinical trial use.  
Potential complaints may come from a variety of sources including but not limited to 
subjects, clinical research associates (CRA), clinical operations managers (COM), medical 
monitors, and site personnel, etc. The following are not considered PQCs:
x
Subject satisfaction inquiries reported via “Subjective Questionnaires” and “Patient 
Reported Outcomes (PRO)”
x
Clinical test articles that are stored improperly or damaged after receipt at the 
investigational site
x
Artificial tear replacements that occur due to loss/run out
x
Damage deemed by clinicians or clinical staff to be caused by handling by the user, 
and not indicative of a quality deficiency, only in situations where there is no 
deficiency alleged by the subject
Within 24 hours of site personnel becoming aware that a PQC has occurred, the PQC must 
be recorded in the EDC system, which will trigger an automatic email notification to the 
 
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appropriate COM/CRA and Clinical QA representative. In cases where the EDC system in 
use is not configured to send automatic notifications or when an EDC system is not used, 
the COM/CRA is responsible for notifying Clinical QA upon discovery that a PQC has 
occurred.  
Upon receipt of the EDC notification, the COM/CRA will contact the study site to collect 
additional information which will include:
x
Date the complaint was received/recorded in the EDC System (Date of Sponsor 
Awareness)
x
Who received the complaint
x
Study number
x
Clinical site information (contact name, site ID, telephone number)
x
Lot number(s)
x
Unique Subject Identifier(s)
x
Indication of who first observed complaint (site personnel or subject)
x
OD/OS indication, along with whether the drops were inserted
x
Any related AE number, if applicable
x
Detailed complaint description (scheduled/unscheduled visit, symptoms, resolution 
of symptoms, etc.)
x
Eye Care Provider objective (slit lamp) findings if applicable
x
Confirmation of product availability for return (and tracking information, if 
available), or rationale if product is not available for return 
Once a complaint is received, it will be assessed by the COM, CRA, or trained site 
personnel to determine if it is an Adverse Event/Serious Adverse Event (AE/SAE).  If the 
complaint results in an AE/SAE, the COM/CRA, or trained site personnel will follow 
Section 13 of this protocol. If the AE/SAE was potentially the result of a product quality 
related deficiency, these procedures also applies and will be executed in parallel.  
In some cases, a PQC form may be generated in EDC by the site in error.  In this event, the 
PQC forms will be marked “Intentionally Left Blank” or “ILB”.  Justification for ILB must 
be documented.
13. ADVERSE EVENTS 
13.1. Definitions and Classifications 
Adverse Event (AE) – An AE is “any untoward medical occurrence, unintended disease 
or injury, or untoward clinical signs (including abnormal laboratory findings) in subjects, 
users or other persons, whether or not related to the investigational medical device. 
Note 1 to entry: This definition includes events related to the investigational medical 
device or the comparator.
Note 2 to entry: This definition includes events related to the procedures involved.
Note 3 to entry: For users or other persons, this definition is restricted to events related to 
investigational medical devices.”1
An AE includes any condition (including a pre-existing condition) that:
 
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1. Was not present prior to the study, but appeared or reappeared following initiation 
of the study 
2. Was present prior to the study but worsened during the study. This would include 
any condition resulting from concomitant illnesses, reactions to concomitant 
medications, or progression of disease states 
3. Pregnancy must be documented as an adverse event and must be reported to the 
clinical monitor and to the Sponsor immediately upon learning of the event
Serious Adverse Event (SAE) – An SAE is any untoward medical occurrence that:
x
Results in death
x
Is life threatening
x
Requires in-patient hospitalization or prolongation of existing hospitalization
x
Results in persistent or significant disability/incapacity (e.g., a sight threatening 
event, a significant persistent or permanent change, impairment, damage, or 
disruption to the subject’s body)
x
Is a congenital anomaly/birth defect, or
x
Requires intervention to prevent permanent damage (the use of the test article 
resulting in a condition which requires medical or surgical intervention to preclude 
permanent impairment of the body structure or a body function).  Important medical 
events that may not result in death, be life-threatening, or require hospitalization 
may be considered an SAE when, based upon appropriate medical judgment, they 
may jeopardize the patient or subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in the above definition
Diagnoses and conditions that are considered Ocular Serious Adverse Events include, but 
not limited to:
x
Microbial Keratitis (MK)
x
Iritis (including cells in the anterior chamber)
x
Permanent decrease in best spectacle corrected visual acuity equivalent to 2 acuity 
lines or greater
x
Central Corneal Opacity
x
Central Corneal Neovascularization
x
Uveitis
x
Endophthalmitis
x
Hypopyon
x
Hyphemia
x
Penetration of Bowman’s Membrane
x
Persistent Epithelial Defect
x
Limbal cell Damage leading to Conjunctivalization
Significant Adverse Events – Those events that are usually symptomatic and warrant 
discontinuation (temporary or permanent) of the test article (excluding Serious Adverse 
Events).  
Diagnoses and conditions that are considered Ocular Significant Adverse Events include, 
but not limited to the following:
x
Significant Infiltrative Events (SIE)
x
Keratoconjunctivitis (toxic or infectious)
x
Chemical Keratitis 
 
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x
Any Temporary Loss of >2 Lines of BSCVA
x
Other Grade 3 or higher corneal findings, such as abrasions or edema
x
Corneal events - e.g. Epidemic Keratoconjunctivitis (EKC)
x
Asymptomatic Corneal Scar
x
Any corneal event which necessitates temporary lens discontinuation >2 weeks
Non-Significant Adverse Events – Those conditions that are usually asymptomatic and 
usually do not warrant discontinuation (temporary or permanent) of the test article.  
However, the Investigator may choose to treat as a precautionary measure.  
Diagnoses and conditions that are considered Ocular Non-Significant Adverse Events 
include, but not limited to the following:
x
Non-signifiant Infiltrative Event (NSIE)
x
Papillary Conjunctivitis
x
Corneal abrasions
x
Superficial Punctate Keratitis (SPK)
x
Conjunctivitis: Bacterial, Viral, Allergic
x
Blepharitis
x
Meibomianitis
x
Contact Dermatitis
x
Localized Allergic Reactions or infections
x
Temporary visual disturbances (blurriness)
x
Any corneal event not explicitly defined as serious or significant adverse event, 
which necessitates temporary discontinuation of the drops <2 weeks
Adverse Device Effect (ADE) – An ADE is an “adverse event related to the use of an 
investigational medical device.
Note 1 to entry: This definition includes adverse events resulting from insufficient or 
inadequate instructions for use, deployment, implantation, installation, or operation, or 
any malfunction of the investigational medical device.
Note 2 to entry: This definition includes any event resulting from use error or from 
intentional misuse of the investigational medical device.”1
Unanticipated Adverse Device Effect (UADE) – Any serious adverse effect on health or 
safety or any life-threatening problem or death caused by, or associated with, the test
article, if that effect, problem, or death was not previously identified in nature, severity, or 
degree of incidence in the investigational plan, Investigator’s Brochure or protocol, or any 
other unanticipated serious problem associated with the test article that relates to the rights, 
safety and welfare of subjects.
13.2. Assessing Adverse Events 
In conjunction with the medical monitor, the Investigator will evaluate adverse events to 
ensure the events are categorized correctly.  Elements of categorization will include:
x
Seriousness/Classifications (see definition in Section 13.1)
x
Causality or Relatedness – i.e. the relationship between the test article, study 
treatment or study procedures and the adverse event (not related; unlikely related; 
possibly related; related - see definition in Section 13.2.1)
 
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x
Adverse Event Severity – Adverse event severity is used to assess the degree of 
intensity of the adverse event (mild; moderate; severe for all events - see definition 
in Section 0)
x
Outcome – not recovered or not resolved; recovering or resolving; recovered or 
resolved with sequelae; recovered or resolved; death related to adverse event;
unknown
x
Actions Taken – none; temporarily discontinued; permanently discontinued; other
13.2.1. Causality Assessment 
Causality Assessment – A determination of the relationship between an adverse event and 
the test article. The test article relationship for each adverse event should be determined by 
the investigator using these explanations:
x
Not Related- An adverse event that is not related to the use of the test article, study 
treatment or study procedures
x
Unlikely Related – An adverse event for which an alternative explanation is more 
likely, e.g. concomitant treatment, concomitant disease(s), or the relationship of 
time suggests that a causal relationship is not likely
x
Possibly Related – An adverse event that might be due to the use of the test article, 
or to the study treatment or study procedures. An alternative explanation, e.g. 
concomitant treatment, concomitant disease(s), is inconclusive.  The relationship in 
time is reasonable.  Therefore, the causal relationship cannot be excluded
x
Related – An adverse event that is listed as a possible adverse effect (device) or 
adverse reaction (drug) and cannot be reasonably explained by an alternative 
explanation, e.g. concomitant treatment of concomitant disease(s).  The relationship 
in time is very suggestive, e.g. it is confirmed by de-challenge and re-challenge
13.2.2. Severity Assessment 
Severity Assessment – A qualitative assessment of the degree of intensity of an adverse 
event as determined by the Investigator or reported to him/her by the subject.  The 
assessment of severity is made irrespective of test article, study treatment or study 
procedure relationship or seriousness of the event and should be evaluated according to the 
following scale:
x
Mild – Event is noticeable to the subject, but is easily tolerated and does not 
interfere with the subject’s daily activities
x
Moderate – Event is bothersome, possible requiring additional therapy, and may 
interfere with the subject’s daily activities
x
Severe – Event is intolerable, necessitates additional therapy or alteration of therapy 
and interferes with the subject’s daily activities
13.3. Documentation and Follow-Up of Adverse Events 
The recording and documenting of adverse events (ocular and non-ocular) begins when the 
subjects are exposed to the test article, study treatment or study procedure.  Adverse events 
reported before the use of test article, start of study treatment, or study procedures will be 
recorded as medical history. However, if the condition deteriorates at any time during the 
study it will be recorded and reported as an AE. Untoward medical events reported after 
the subject’s exit from the study will be recorded as adverse events at the discretion of the 
Investigator.
 
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Upon finding an adverse event, the Principal Investigator will document the condition in 
the subject record and in the eCRFs. He/she will complete the Adverse Event /eCRF.  
Complete descriptions of all adverse events must be available in the subject record. All 
Adverse Events including local and systemic reactions not meeting the criteria for “serious 
adverse events” shall be captured on the appropriate case report form or electronic data 
system. All adverse events occurring while the subject is enrolled in the study must be 
documented appropriately regardless of relationship.  
It is the Investigator’s responsibility to maintain documentation of each reported adverse 
event. All adverse events will be followed in accordance with applicable licensing 
requirements.  Such documentation will include the following:
x
Adverse event (diagnosis not symptom)
x
Drawings or photographs (where appropriate) that detail the finding (e.g., size, 
location, and depth, etc.) 
x
Date the clinical site was notified 
x
Date and time of onset
x
Date and time of resolution
x
Adverse event classification, severity, and relationship to test articles, as applicable
x
Treatment regimen instituted, including concomitant medications prescribed, in 
accordance with applicable licensing requirements
x
Any referral to another health care provider if needed
x
Outcome, ocular damage (if any)
x
Likely etiology
x
Best corrected visual acuity at the discovery of the event and upon conclusion of 
the event
In addition, if an infiltrate(s) is present, he/she will complete the Corneal Infiltrate 
Assessment eCRF.  Where necessary, a culture of the corneal lesion will be collected to 
determine if the infection is microbial in nature.  If cultures are collected, the date of culture 
collection and laboratory utilized will be recorded. 
Changes in the severity of an AE shall be documented to allow an assessment of the 
duration of the event at each level of intensity to be performed.  Adverse events 
characterized as intermittent require documentation of the onset and duration of each 
episode. Changes in the assessment of relationship to the Test Article shall also be clearly 
documented.
Subjects who present with an adverse event shall be followed by the Investigator, within 
licensure, until all signs and symptoms have returned to pre-treatment status, stabilized, or 
been satisfactorily resolved.  If further treatment beyond licensure is required, the patient 
will be referred to the appropriate health care provider.  The Investigator will use his/her 
clinical judgment as to whether a subject reporting with an adverse event will continue in 
the study.  If a subject is discontinued from the study, it will be the responsibility of the 
Investigator to record the reason for discontinuation.  The Investigator will also document 
the adverse event appropriately and complete the Adverse Event eCRF. Any subjects with 
ongoing adverse events related to the test article, study treatment or study procedures, as 
of the final study visit date, should be followed to resolution of the adverse event or until 
referral to an appropriate health care provider, as recommended by the Investigator. Non-
 
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ocular adverse events that are not related to the test article, study treatment, or study 
procedures may be recorded as “ongoing” without further follow-up.
13.4. Reporting Adverse Events  
The Investigator will notify the Sponsor of an adverse event by e-mail, facsimile, or 
telephone as soon as possible and no later than 24 hours from discovery for any serious 
/significant adverse events, and 2 days from discovery for any non-significant adverse 
event.  In addition, a written report will be submitted by the Principal Investigator to the 
IEC/IRB according to their requirements (Section 13.4.2).  The report will comment 
whether or not the adverse event was considered to be related to the test article, study 
treatment or study procedures.
13.4.1. Reporting Adverse Events to Sponsor 
Serious/Significant Adverse Events
The Investigator will inform the sponsor of all serious/significant adverse events occurring 
during the study period as soon as possible by e-mail, fax, or telephone, but no later than 
24 hours following discovery of the event.  The Investigator is obligated to pursue and 
obtain information requested by the Sponsor in addition to that information reported on the 
eCRF. All subjects experiencing a serious/significant adverse event must be followed up 
and all outcomes must be reported.
When medically necessary, the Investigator may break the randomization code to 
determine the identity of the treatment that the subject received.  The Sponsor and study 
monitor should be notified prior to unmasking the test articles.
In the event of a serious/significant adverse event, the Investigator must:
x
Notify the Sponsor immediately
x
Obtain and maintain in the subject’s records all pertinent medical information and 
medical judgment for colleagues who assisted in the treatment and follow-up of the 
subject
x
Provide the Sponsor with a complete case history which includes a statement as to 
whether the event was or was not related to the use of the test article
x
Notify the IEC/IRB as required by the IEC/IRB reporting procedure according to 
national regulations
Unanticipated (Serious) Adverse Device Effect (UADE)
In the event of an Unanticipated (Serious) Adverse Device Effect (UADE), the Investigator
will submit a report of the UADE to the Sponsor and IEC/IRB as soon as possible, but no 
later than 24 hours after the Investigator first learns of the effect.  This report is in addition 
to the immediate notification mentioned above.
The Sponsor must conduct an evaluation of the UADE and must report the results of the 
evaluation to FDA, the IEC/IRB and participating Investigators within 10 working days 
after the Sponsor first receives notification of the effect.
Non-Serious Adverse Events
All non-serious adverse events, including non-serious adverse device effects, will be 
reported to the sponsor by the Investigator no later than 2 days from discovery.
 
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13.4.2. Reporting Adverse Events to the Responsible IEC/IRB and Health Authorities 
Adverse events that meet the IEC/IRB requirements for reporting must be reported within 
the IEC/IRB’s written guidelines. Each clinical site will refer to and follow any guidelines 
set forth by their Approving IEC/IRB. Each clinical site will refer to and follow any 
guidelines set forth by their local governing Health Authorities.
The Sponsor will report applicable Adverse Events to the local health authorities according 
the written guidelines, including reporting timelines. 
13.4.3. Event of Special Interest 
None.
13.5. Reporting of Pregnancy 
Subjects reporting pregnancy (by self-report) during the course of the study will be 
discontinued after the event is recorded as an Adverse Event.  Once discontinued, pregnant 
participants and their fetuses will not be monitored for study related purposes.  At the 
Investigator’s discretion, the study participant may be followed by the Investigator through 
delivery. However, this data will not be collected as part of the clinical study database.  
Pregnant participants are not discontinued from contact lens or solution related studies for 
safety concerns, but due to general concerns relating to pregnancy and contact lens use.  
Specifically, pregnant women are discontinued due to fluctuations in refractive error and/or 
visual acuity that occur secondary to systemic hormonal changes, and not due to unforeseen 
health risks to the mother or fetus.
14. STATISTICAL METHODS 
14.1. General Considerations 
Statistical Analysis will be undertaken by the sponsor or under the authority of the sponsor. 
A general description of the statistical methods to be implemented in this clinical trial is 
outlined below. More details will be provided in the stand-alone Statistical Analysis Plan 
(SAP). The SAP will be finalized and signed prior to the database lock.
All data summaries and statistical analyses will be performed using the SAS software 
Version 9.4 or higher10. Throughout the analysis of data, the results for each subject/eye 
will be used when available for summarization and statistical analysis.  
Summary tables (descriptive statistics and/or frequency tables) will be provided for all 
baseline variables, efficacy variables and safety variables as appropriate.  Continuous 
variables will be summarized with descriptive statistics (n, mean, standard deviation [SD],
median, minimum and maximum). Frequency count and percentage of subjects or eyes 
within each category will be provided for categorical data.
14.2. Sample Size Justification 
The sample size was calculated to test for non-inferiority of the Test relative to Control eye 
drops with respect to the ocular comfort score using VAS with a minimum power of 85%
and a two-sided type I error of 0.05. Assuming a difference between the Test and Control 
of 20, a common standard deviation (SD) of 35, the estimated sample size for non-
 
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inferiority was 56 per treatment group using two-sample t-test. The sample size calculation 
was performed using the SAS procedure PROC POWER. The common standard deviation 
considered was based on results from 
 in which the estimated 
standard deviation of change in ocular end of day comfort from baseline at 30-day in the 
control group was estimated to be 2.53 in a VAS scale from 0 to 10 
 We increased the standard deviation by one unit in case more variation 
will be observed in the Test group. Therefore, the standard deviation used in the sample 
calculation was 35 in a VAS scale from 0 to 100 (35 = 10*(2.5 + 1)).      
The plan is to enroll 150 eligible subjects (60 per arm) with a target completion of 112 (56 
per arm). During the enrollment period, the subject dropout rate will be closely monitored, 
if unexpectedly high dropout rate is observed (>10%) in certain arm(s), the targeted total 
enrollment number might be increased accordingly in order to ensure a minimum of 56
subjects per group to complete the 1-month follow-up.
14.3. Analysis Populations 
The following analysis populations will be used in the analysis and presentation of the 
data.
Safety Population:
All subjects who were administered any test article excluding subjects who drop out prior 
to administering any test article. At least one observation for safety endpoints should be 
recorded (e.g. slit lamp findings, ocular symptoms, etc.).
Intent-to-Treat (ITT) Population:
All randomized subjects regardless of actual treatment and subsequent withdrawal from 
study or deviation from protocol. Subject will be analyzed as per randomized treatment.
Per-Protocol (PP) Population: 
All subjects who have successfully completed all visits and did not substantially deviate 
from the protocol as determined by the trial cohort review committee prior to database lock. 
Justification of excluding subjects with protocol deviations from the Per-Protocol 
Population set will be documented in a memo to file. Per Protocol will be the primary 
analysis population.
14.4. Level of Statistical Significance 
All planned analysis will be conducted with an overall type I error rate of 5%. Unless 
otherwise specified, all statistical tests will be 2-sided.
14.5. Primary Analysis  
Ocular Comfort (VAS) Score:
Ocular comfort scores will be analyzed using a linear mixed model for repeated measures 
to test for the difference between the Test and Control eye drops. The regression model 
will include treatment group (Test, Control), time (0, 7-Day and 30-Day) and group by time 
interaction as fixed effect factors; and investigational site as random effect. Age and gender 
will be included in the model when appropriate. The correlation between measurements
from the same subject across time will be modeled using unstructured (UN) variance-
covariance matrix.
If the estimation algorithm does not converge, then a Compound 
Symmetry matrix (CS) will be used. The log-likelihood ratio test will be used to test for the 
 
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homogeneity between the residual covariance structures across treatment groups. The 
Kenward and Roger method 11 will be used to calculate the denominator degree of freedom.
Hypothesis Testing: 
The null and alternative hypotheses for non-inferiority of Test relative to Control are as 
follows:
ܪ଴: ∆ ≤−20
ܪ஺: ∆ > −20,
where ∆is the difference between treatment groups in mean change from baseline at 30-
Day follow-up (Test minus Control). The non-inferiority test will be based on the least
square mean change difference and corresponding 95% confidence interval from the final 
model.
The lower bound of the 95% confidence interval will be compared to the 
non-inferiority margin of -20. If the lower bound is greater than -20, the null hypothesis 
will be rejected, and the Test will be considered non-inferior to Control. The primary 
analysis will be conducted on the Per-Protocol Population. As sensitivity analysis will be 
conducted on the ITT Population.
14.6. Secondary Analysis  
Corneal Staining (Grade 2 or higher):
Corneal staining response using FDA grading scale (i.e. Grade 0 = None, Grade 1 = Trace, 
Grade 2 = Mild, Grade 3 = Moderate and Grade 4 = Severe) will be first categorized into a 
binary outcome as 1 if any grade 2 or higher corneal staining otherwise 0. Events occurring 
during an unscheduled visit will be counted in the subsequent visit. For example, if a
Grade 2 corneal staining was reported at an unscheduled visit between Visit 1 and Visit 2, 
it would be counted in Visit 2.  Eyes with multiple reports will be counted only once at 
each visit for the analysis purpose. The binary outcome will be then analyzed using a
generalized linear mixed model for binary data.
The regression model will include 
treatment group (Test, Control), time (0, 7-Day and 30-Day) and group by time interaction 
as fixed effect factors; and investigational site and subject as random effects (G-side).
Baseline values, age and gender will be included in the model as fixed covariates when 
appropriate. The correlation between measurements from the same subject/eye across time 
will be modeled using UN variance-covariance matrix (R-side). If the estimation algorithm 
does not converge, then a compound symmetry structure (CS) will be used.  The Kenward 
and Roger method 11will be used to calculate the denominator degree of freedom.
Hypothesis Testing: 
The null and alternative hypotheses for no difference of Test relative to Control are as 
follows:
ܪ଴: ܱܴ= 1
ܪ஺: ܱܴ ≠1,
where ܱܴis odds ratio of having a Grade 2 or higher corneal staining in the Test group 
over the Control group.
 
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Comparison between the Test and Control will be conducted at each follow-up visit and 
across all visits.
The test for no difference will be based on the estimated OR and 
corresponding 95% confidence interval from the final model. The null hypothesis will be 
rejected in favor of the alternative if 1 does not fall within the 95% confidence interval of 
OR. The corneal staining analysis will be conducted on the Safety Population.
Overall Quality of Vision Score:
Overall quality of vision will be analyzed using the same statistical model described in the 
primary analysis. Comparisons between Test and Control will be carried using t-tests on 
least square mean differences of change in quality of vision from baseline at 7-Day and 
30-Day follow-up.
The overall quality of vision analysis will be conducted on the 
Per-Protocol Population.
Subject reported Ocular symptoms (yes/No)
Reported ocular symptoms, problems or complaints (0 = No, 1 = Yes) at any visit will be 
analyzed using the same method described above for corneal staining. The reported ocular 
analysis will be conducted on the Safety Population.
14.7. Other Exploratory Analyses  
No exploratory analyses are planned for this study. Further analysis will be conducted at 
the discretion of the study responsible clinician at the end of the study if necessary. 
14.8. Interim Analysis 
No interim analysis is planned in this study. 
14.9. Procedure for Handling Missing Data and Drop-Outs 
Missing or spurious values will not be imputed as the number of missing values is expected 
to be low. The count of observed values will be included in the summary tables and listings. 
Subject dropout is expected to be one of the main reasons of missing data in this clinical 
trial. Past clinical trials don’t provide the evidence that subject dropout is systematic or not-
at-random. To evaluate the impact of missing data, a sensitivity analysis will be conducted 
using multiple imputation methods.
14.10. Procedure for Reporting Deviations from Statistical Plan 
The analysis will be conducted according to that specified in the above sections.  There are 
no known reasons for which it is planned to deviate from these analysis methods.  If for 
any reason a change is made, the change will be documented in the study report along with 
a justification for the change.
15. DATA HANDLING AND RECORD KEEPING/ARCHIVING 
15.1. Electronic Case Report Form/Data Collection 
The data for this study will be captured on electronic case report forms (eCRFs) using an 
EDC system (Bioclinica). An authorized data originator will enter study data into the 
eCRFs using the EDC system.  Data collected on equipment that is not captured in EDC 
 
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will be formatted to the specification of the JJV database manager and sent to JJV for 
analysis. 
External Date Sources for this study include: Not Applicable 
The clinical data will be recorded on dedicated eCRFs specifically designed to match the 
study procedures for each visit.  Once completed, the eCRFs will be reviewed for accuracy 
and completeness and signed by the Investigator.  The sponsor or sponsor’s representatives 
will be authorized to gain access to the subject recordation for the purposes of monitoring 
and auditing the study. 
Edit checks, electronic queries, and audit trails are built into the system to ensure accurate 
and complete data collection. Data will be transmitted from the clinical site to a secure 
central database as forms are completed or updated, ensuring information accuracy, 
security, and confidentiality. After the final database lock, the Investigator will be provided 
with Individual Patient Profiles (IPP) including the full audit trail on electronic media in 
PDF format for all of the study data. The IPP must be retained in the study files as a certified 
copy of the source data for the study. 
The content and structure of the eCRFs are compliant with ISO14155:2011.1
15.2. Subject Record 
At a minimum, subject record should be available for the following: 
x
subject identification
x
eligibility
x
study identification
x
study discussion
x
provision of and date of informed consent
x
visit dates
x
results of safety and efficacy parameters as required by the protocol
x
a record of all adverse events
x
follow-up of adverse events
x
medical history and concomitant medication
x
test article receipt/dispensing/return records
x
date of study completion
x
reason for early discontinuation of test article or withdrawal from the study, if 
applicable
The subject record is the eCRF or an external record.  The author of an entry in the subject 
record must be identifiable.  The first point of entry is considered to be the source record.
Adverse event notes must be reviewed and initialed by the Investigator.
16. DATA MANAGEMENT 
16.1. Access to Source Data/Document 
The Investigator/Institution will permit trial-related monitoring, audits, IEC/IRB review 
and regulatory inspection(s) by providing direct access to source data/documents.  Should 
 
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the clinical site be contacted for an audit by an IEC/IRB or regulatory authority, JJV must 
be contacted and notified in writing within 24 hours.
16.2. Confidentiality of Information 
Information concerning the investigational product and patent application processes, 
scientific data or other pertinent information is confidential and remains the property of 
JJV.  The Investigator may use this information for the purposes of the study only. It is 
understood by the Investigator that JJV will use information developed in this clinical study 
in connection with the development of the investigational product and therefore may 
disclose it as required to other clinical investigators and to regulatory agencies. In order to 
allow the use of the information derived from this clinical study, the Investigator 
understands that he/she has an obligation to provide complete test results and all data 
developed during this study to the Sponsor.
16.3. Data Quality Assurance 
Steps will be taken to ensure the accuracy and reliability of data, include the selection of 
qualified investigators and appropriate clinical sites and review of protocol procedures with 
the Principal Investigator.  The Principal Investigator, in turn, must ensure that all Sub-
Investigators and clinical site personnel are familiar with the protocol and all study-specific 
procedures and have appropriate knowledge of the study article.
Training on case report form completion will be provided to clinical site personnel before 
the start of the study.  The Sponsor will review case report forms for accuracy and 
completeness remotely during the conduct of the study, during monitoring visits, and after 
transmission to data management.  Any data discrepancies will be resolved with the 
Investigator or designee, as appropriate.
Quality Assurance representatives from JJV may visit clinical sites to review data produced 
during the study and to access compliance with applicable regulations pertaining to the 
conduct of clinical trials.  The clinical sites will provide direct access to study-related 
source data/documents and reports for the purpose of monitoring and auditing by JJV and 
for inspection by local and regulatory authorities.
17. MONITORING 
The study monitors will maintain close contact with the Principal Investigator and the 
Investigator’s designated clinical site personnel.  The monitor’s responsibilities will 
include:
x
Ensuring that the investigation is being conducted according to the protocol, any 
subsequent amendments, and regulatory requirements are maintained
x
Ensuring the rights and wellbeing of subjects are protected
x
Ensuring adequate resources, including facilities, laboratories, equipment, and 
qualified clinical site personnel
x
Ensuring that protocol deviations are documented with corrective action plans, as 
applicable
x
Ensuring that the clinical site has sufficient test article and supplies
x
Clarifying questions regarding the study
x
Resolving study issues or problems that may arise
 
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x
Reviewing of study records and source documentation verification in accordance 
with the monitoring plan
18. ETHICAL AND REGULATORY ASPECTS 
18.1. Study-Specific Design Considerations 
Potential subjects will be fully informed of the risks and requirements of the study and, 
during the study, subjects will be given any new information that may affect their decision 
to continue participation.  Subjects will be told that their consent to participate in the study 
is voluntary and may be withdrawn at any time with no reason given and without penalty 
or loss of benefits to which they would otherwise be entitled.  Only subjects who are fully 
able to understand the risks, benefits, and potential adverse events of the study, and provide 
their consent voluntarily will be enrolled.
18.2. Investigator Responsibility 
The Principal Investigator is responsible for ensuring that the clinical study is performed 
in accordance with the signed agreement, the investigational plan, Section 4 of the ICH E6 
guidelines on Good Clinical Practice (GCP),2 and applicable regulatory requirements.  GCP 
is an international ethical and scientific quality standard for designing, conducting, 
recording, and reporting studies that involve the participation of human subjects. 
Compliance with this standard provides public assurance that the rights, safety, and well-
being of study subjects are protected, consistent with the principles of the Declaration of 
Helsinki 64th WMA General Assembly 20133 and that the clinical study data are credible.  
The Investigator must maintain clinical study files in accordance with Section 8 of the ICH 
E6 guidelines on Good Clinical Practice (GCP),2 and applicable regulatory requirements.
18.3. Independent Ethics Committee or Institutional Review Board (IEC/IRB) 
Before the start of the study, the Investigator (or Sponsor when applicable) will provide the 
IEC/IRB with current and complete copies of the following documents (where applicable):
x
Final protocol and, if applicable, amendments
x
Sponsor-approved informed consent form (and any other written materials to be 
provided to the subjects)
x
Investigator’s Brochure (or equivalent information) and amendments
x
Sponsor-approved subject recruitment materials
x
Information on compensation for study-related injuries or payment to subjects for 
participation in the study
x
Investigator’s curriculum vitae, clinical licenses, or equivalent information (unless 
not required, as documented by IEC/IRB)
x
Information regarding funding, name of the Sponsor, institutional affiliations, other 
potential conflicts of interest, and incentives for subjects
x
Any other documents that the IEC/IRB requests to fulfill its obligation
This study will be undertaken only after IEC/IRB has given full approval of the final 
protocol, amendments (if any), the informed consent form, applicable recruiting materials, 
and subject compensation programs, and the Sponsor has received a copy of this approval. 
This approval letter must be dated and must clearly identify the documents being approved.
 
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During the study, the Investigator (or Sponsor when applicable) will send the following 
documents to the IEC/IRB for their review and approval, where appropriate:
x
Protocol amendments
x
Revision(s) to informed consent form and any other written materials to be provided 
to subjects
x
If applicable, new or revised subject recruitment materials approved by the Sponsor
x
Revisions to compensation for study-related injuries or payment to subjects for 
participation in the study
x
Investigator’s Brochure amendments or new edition(s)
x
Summaries of the status of the study (at least annually or at intervals stipulated in 
guidelines of the IEC/IRB)
x
Reports of adverse events that are serious, unanticipated, and associated with the 
test articles, according to the IRB’s requirements
x
New information that may adversely affect the safety of the subjects or the conduct 
of the study
x
Major protocol deviations as required by the IEC/IRB
x
Report of deaths of subjects under the Investigator's care
x
Notification if a new Investigator is responsible for the study at the clinical site
x
Any other requirements of the IEC/IRB
For protocol amendments that increase subject risk, the amendment and applicable 
informed consent form revisions must be submitted promptly to the IEC/IRB for review 
and approval before implementation of the change(s).
At least once a year, the IEC/IRB will review and reapprove this clinical study. This request 
should be documented in writing.
At the end of the study, the Investigator (or Sponsor where required) will notify the 
IEC/IRB about the study completion.  Documentation of this notification must be retained 
at the clinical site and a copy provided to the CRO or Sponsor as applicable.
18.4. Informed Consent 
Each subject must give written consent according to local requirements after the nature of 
the study has been fully explained. The consent form must be signed before performance 
of any study-related activity. The consent form that is used must be approved by both the 
Sponsor and by the reviewing IEC/IRB. The informed consent is in accordance with 
principles that originated in the Declaration of Helsinki3, current ICH2 and ISO 141551
guidelines, applicable regulatory requirements, and Sponsor Policy.
Before entry into the study, the Investigator or an authorized member of the clinical site 
personnel must explain to potential subject the aims, methods, reasonably anticipated 
benefits, and potential hazards of the study, and any discomfort it may entail. Subjects will 
be informed that their participation is voluntary and that they may withdraw consent to 
participate at any time. 
The subject will be given sufficient time to read the informed consent form and the 
opportunity to ask questions. After this explanation and before entry into the study, consent 
should be appropriately recorded by means of the subject's dated signature. After having 
obtained the consent, a copy of the informed consent form must be given to the subject.
 
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18.5. Privacy of Personal Data 
The collection, processing and disclosure of personal data and medical information related 
to the Study Subject, and personal data related to Principal Investigator and any clinical 
site personnel (e.g., name, clinic address and phone number, curriculum vitae) is subject to 
compliance with the Health Information Portability and Accountability Act (HIPAA)12 in 
the United States and other applicable personal data protection and security laws and 
regulations.  Appropriate measures will be employed to safeguard these data, to maintain 
the confidentiality of the person’s related health and medical information, to properly 
inform the concerned persons about the collection and processing of their personal data, to 
grant them reasonable access to their personal data and to prevent access by unauthorized 
persons.
All information obtained during the course of the investigation will be regarded as 
confidential. All personal data gathered in this trial will be treated in strictest confidence 
by Investigators, monitors, Sponsor’s personnel and IEC/IRB.  No data will be disclosed 
to any third party without the express permission of the subject concerned, with the 
exception of Sponsor personnel (monitor, auditor), IEC/IRB and regulatory organizations 
in the context of their investigation related activities that, as part of the investigation will 
have access to the CRFs and subject records.
The collection and processing of personal data from subjects enrolled in this study will be 
limited to those data that are necessary to investigate the efficacy, safety, quality, and utility 
of the investigational product(s) used in this study.
These data must be collected and processed with adequate precautions to ensure 
confidentiality and compliance with applicable data privacy protection laws and 
regulations.
The Sponsor ensures that the personal data will be:
x
processed fairly and lawfully
x
collected for specified, explicit, and legitimate purposes and not further processed 
in a way incompatible with these purposes
x
adequate, relevant, and not excessive in relation to said purposes
x
accurate and, where necessary, kept current
Explicit consent for the processing of personal data will be obtained from the participating 
subject before collection of data. Such consent should also address the transfer of the data 
to other entities and to other countries.
The subject has the right to request through the Investigator access to his personal data and 
the right to request rectification of any data that are not correct or complete. Reasonable 
steps should be taken to respond to such a request, taking into consideration the nature of 
the request, the conditions of the study, and the applicable laws and regulations.
Appropriate technical and organizational measures to protect the personal data against 
unauthorized disclosures or access, accidental or unlawful destruction, or accidental loss or 
alteration must be put in place. Sponsor personnel whose responsibilities require access to 
personal data agree to keep the identity of study subjects confidential.
 
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19. STUDY RECORD RETENTION 
In compliance with the ICH/GCP guidelines,2 the Investigator/Institution will maintain all 
CRFs and all subject records that support the data collected from each subject, as well as 
all study documents as specified in ICH/GCP2 and all study documents as specified by the 
applicable regulatory requirement(s). The Investigator/Institution will take measures to 
prevent accidental or premature destruction of these documents.
Essential documents must be retained until at least two (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 until at least two (2) years have elapsed since 
the formal discontinuation of clinical development of the investigational product. These 
documents will be retained for a longer period if required by the applicable regulatory 
requirements or instructed by 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.
If the responsible Investigator retires, relocates, or for other reasons withdraws from the 
responsibility of keeping the study records, custody must be transferred to a person who 
will accept the responsibility. The Sponsor must be notified in writing of the name and 
address of the new custodian. Under no circumstance shall the Investigator relocate or 
dispose of any study documents before having obtained written approval from the Sponsor.
If it becomes necessary for the Sponsor or the appropriate regulatory authority to review 
any documentation relating to this study, the Investigator must permit access to such 
reports.
If the Investigator has a question regarding retention of study records, he/she should contact 
JJV.
20. FINANCIAL CONSIDERATIONS 
Remuneration for study services and expenses will be set forth in detail in the Clinical 
Research Agreement.  The Research Agreement will be signed by the Principal Investigator 
and a JJV management representative prior to study initiation.
JJV reserves the right to withhold remuneration for costs associated with protocol 
violations such as:
x
Continuing an ineligible subject in the study
x
Scheduling a study visit outside the subject’s acceptable visit range
JJV reserves the right to withhold final remuneration until all study related activities have 
been completed, such as:
x
Query resolution
x
Case Report Form signature
x
Completion of any follow-up action items 
21. PUBLICATION 
This study will be registered on ClinicalTrials.gov based on the following: This
confirmatory study meets the registration requirements in
 
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22. REFERENCES 
1.
ISO14155:2011: Clinical investigation of Medical Devices for Human Subjects-
Good Clinical Practice. Available at: https://www.iso.org/standard/45557.html
2.
International Conference on Harmonization Good Clinical Practice E6 (ICH-
GCP) Available at:  
http://www.ich.org/products/guidelines/efficacy/article/efficacy-guidelines.html
3.
Declaration of Helsinki - Ethical principles for Medical Research Involving 
Human Subjects.  Available at:  https://www.wma.net/policies-post/wma-
declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-
subjects/
4.
United States (US) Code of Federal Regulations (CFR)  Available at : 
https://www.gpo.gov/fdsys/browse/collectionCfr.action?collectionCode=CFR
5.
Farrand KF, Fridman M, Stillman IÖ, Schaumberg DA. Prevalence of Diagnosed 
Dry Eye Disease in the United States Among Adults Aged 18 Years and Older. 
American Journal of Ophthalmology. 2017;182:90-98.
6.
Pearce E, Jobson A, Tandon S, KJ. B. Dry Eye Questionnaires: A comparison of 
the Responses Made to Visual Analogue Scale Questionnaires With Those made 
to Category Based Questionnaires. IOVS. 2005;46(13):4452.
7.
Klimek L, Bergmann K-C, Biedermann T, et al. Visual analogue scales (VAS): 
Measuring instruments for the documentation of symptoms and therapy 
monitoring in cases of allergic rhinitis in everyday health care: Position Paper of 
the German Society of Allergology (AeDA) and the German Society of Allergy 
and Clinical Immunology (DGAKI), ENT Section, in collaboration with the 
working group on Clinical Immunology, Allergology and Environmental 
Medicine of the German Society of Otorhinolaryngology, Head and Neck Surgery 
(DGHNOKHC). Allergo J Int. 2017;26(1):16-24.
8.
ISO 11980:2012 Ophthalmic optics- Contact Lenses and Contact Lens Care 
Products.- Guidance for Clinical Investigations.  Available at: 
https://www.iso.org/standard/61825.html
9.
Versura P, Fresina M, Campos EC. Ocular surface changes over the menstrual 
cycle in women with and without dry eye. Gynecological endocrinology : the 
official journal of the International Society of Gynecological Endocrinology. 
2007;23(7):385-390.
10.
SAS Institute Inc: SAS® 9.4 Statements: Reference, Third Edition. Cary, NC: 
SAS Institute Inc; 2014.
11.
Kenward MG, Roger JH. An improved approximation to the precision of fixed 
effects from restricted maximum likelihood. Computational Statistics & Data 
Analysis. 2009;53(7):2583-2595.
 
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12.
Data Protection Act. Available at:  
http://www.legislation.gov.uk/ukpga/1998/29/contents
 
 
 
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APPENDIX A: PATIENT REPORTED OUTCOMES (STUDY 
QUESTIONNAIRES) 
 
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APPENDIX B: PATIENT INSTRUCTION GUIDE  
 
Patient Instruction Guide will be provided separately. 
 
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APPENDIX C: PACKAGE INSERT (APPROVED PRODUCT) 
 
 
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Drug Facts
Active Ingredient  
Purpose
Polyethylene Glycol 400 0.25% . . . . . . . Eye lubricant
Uses  ■  For the temporary relief of burning, 
irritation, and discomfort due to dryness of the eye or 
exposure to wind or sun.
■  May be used as a protectant against further irritation. 
Warnings
■  For external use only.
■  To avoid contamination, do not touch tip of 
container to any surface. Replace cap after using. 
■  Do not use if solution changes color or becomes cloudy.
Stop use and ask a doctor if:
You experience eye pain, changes in vision, continued 
redness or irritation of the eye, or if the condition 
worsens or persists for more than 72 hours.
Keep out of the reach of children.
If swallowed, get medical help or contact a Poison 
Control Center right away. 
Directions
Instill 1 or 2 drops in the affected eye(s) as needed or 
as directed by your eye care professional.
Inactive Ingredients 
Boric Acid; Calcium Chloride; Magnesium Chloride; 
Potassium Chloride; Puriﬁed Water; Sodium Borate; 
Sodium Chloride; Sodium Chlorite (OcuPure® brand) 
as a preservative; Sodium Hyaluronate. 
Other Information
Use only if tape seals on top and bottom ﬂaps are intact.
RETAIN THIS CARTON FOR FUTURE REFERENCE.
Lubricating Eye Drops
blink
ting Eye Drops
Tears
Tears
Discard solution 90 days after opening
Product of China made in accordance with US FDA guidelines
Blink is a trademark of Johnson & Johnson Surgical Vision, Inc.
No. 93286BT
© Johnson & Johnson 
Surgical Vision, Inc. 2017
Santa Ana, CA 92705
AM60870US12C
9587X
Revision Date: 07/2018
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APPENDIX D: MEDMONT ASSESSMENT PROCEDURE 
 
 
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APPENDIX E: 
 
 
x
 Expanded Corneal Staining assessment
x
 Subject reported Ocular Symptoms/Problems
x
 Biomicroscopy Scale
x
Distance and Near Visual Acuity Evaluation
x
 Patient Reported Outcomes
 
 
 
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 EXPANDED CORNEAL STAINING ASSESSMENT 
 
 
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 SUBJECT REPORTED OCULAR SYMPTOMS/PROBLEMS 
 
 
 
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 BIOMICROSCOPY SCALE 
 
 
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 DISTANCE AND NEAR VISUAL ACUITY 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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 PATIENT REPORTED OUTCOMES 
 
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PROTOCOL COMPLIANCE INVESTIGATOR(S) SIGNATURE PAGE 
Protocol Number and Title: CR-6328 Clinical Evaluation of an Investigational Lipid Drop 
in Non-contact Lens Wearing Patients
Version and Date: 4.0 13 August 2019
I have read and understand the protocol specified above and agree on its content.  
I agree to conduct this study according to ISO 14155,1 GCP and ICH guidelines, 2 the 
Declaration of Helsinki, 3 United States (US) Code of Federal Regulations (CFR),4 and the
pertinent individual country laws/regulations and to comply with its obligations, subject to 
ethical and safety considerations. The Principal Investigator is responsible for ensuring that 
all clinical site personnel, including Sub-Investigators adhere to all ICH2 regulations and 
GCP guidelines regarding clinical trials during and after study completion.
I will assure that no deviation from, or changes to the protocol will take place without prior 
agreement from the Sponsor and documented approval from the Institutional Review Board 
(IRB), except where necessary to eliminate an immediate hazard(s) to the trial participants.
I am responsible for ensuring that all clinical site personnel including Sub-Investigators 
adhere to all ICH2 regulations and GCP guidelines regarding clinical trials during and after 
study completion.
All clinical site personnel involved in the conduct of this study have completed Human 
Subjects Protection Training. 
I agree to ensure that all clinical site personnel involved in the conduct of this study are 
informed about their obligations in meeting the above commitments.
I shall not disclose the information contained in this protocol or any results obtained from 
this study without written authorization.
Principal 
Investigator:
Signature
Date
Name and Professional Position (Printed)
Institution/Site:
Institution/Site Name
Institution/Site Address
 
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