Conditions: Dry Eye Disease
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 123
Healthy volunteers: no

Brief summary:
The objective of this study is to evaluate the chronic safety and effectiveness of OC-01 Nasal Spray as compared to placebo on signs of dry eye disease (DED).

Detailed description:
Study OPP-004 was a Phase 2, single-center, randomized, masked (including subjects, Investigators, and study site personnel), placebo-controlled study designed to evaluate the safety and efficacy of OC-01 (varenicline) nasal spray in adult subjects with DED. The study planned to randomize approximately 120 subjects at least 22 years of age with a physicians' diagnosis of Dry Eye Disease and meeting all other study eligibility criteria to receive an application of OC-01 or placebo BID for 12 weeks. Subjects who terminated early during the application period were asked to complete safety assessments (if the subjects agree) prior to study exit. Subjects who were terminated early from the study were not replaced.

Arms:
arm 1: OC-01 (varenicline) nasal spray, 0.6 mg/mL arm 2: OC-01 (varenicline) nasal spray, 1.2 mg/mL arm 3: vehicle control

Interventions: intervention 1: OC-01 0.1% 0.6 mg/ml intervention 2: OC-01 (varenicline) nasal spray: 0.2 % (1.2 mg/ml) intervention 3: placebo comparator
Intervention descriptions: intervention 1: OC-01 (varenicline) nasal spray: 0.1 % (0.6 mg/ml) intervention 2: OC-01 (varenicline) nasal spray: 0.2 % (1.2 mg/ml) intervention 3: vehicle control

Protocol document:
Prot_000.pdf: 
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Clinical Trial Protocol  
 
 
Protocol Title: 
 
Single Center, Randomized, Controlled, Single-Masked 
Clinical Trial to Evaluate the Chronic Efficacy of OC-01 
Nasal Spray on Signs of Dry Eye Disease (The MYSTIC 
Study) 
Protocol Number: 
OPP-004 
Study Phase: 
2 
Product Name: 
OC-01 Nasal Spray 
Indication: 
Dry Eye Disease  
Investigators: 
Single Center  
 
Sponsor: 
Oyster Point Pharma, Inc. 
700 Alexander Park Dr 
Suite 301 
Princeton, NJ 08540 
 
 
 
Date 
Original Protocol 
(Version 1): 
12 April 2018 
Amendment #1 
(Version 2) 
15 May 2018 
Amendment #2 
(Version 3) 
11 July 2018 
Amendment #3 
(Version 4) 
 
14 November 2018 
Amendment #4 
(Version 5) 
07 March 2019 
Confidentiality Statement  
This protocol contains confidential, proprietary information of Oyster Point Pharma, Inc.  
Further dissemination, distribution or copying of this protocol or its contents is strictly 
prohibited. 


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SPONSOR PERSONNEL 
Chief Executive Officer 
 
  
 
  
Clinical Development 
 
  
 
 
Principal Investigator 
  
 
 
 
 
 
 
 
 
 
 


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SYNOPSIS  
Protocol Title: 
Single Center, Randomized, Controlled, Single-Masked Clinical 
Trial to Evaluate the Chronic Efficacy of OC-01 Nasal Spray on 
Signs of Dry Eye Disease 
Protocol Number: 
OPP-004 
Investigational 
Product:  
OC-01 Nasal Spray 
Study Objective: 
The objective of this study is to evaluate the chronic safety and 
effectiveness of OC-01 Nasal Spray as compared to placebo on 
signs of dry eye disease (DED) 
 
Overall Study Design 
Structure: 
A Phase 2, single-center, randomized, controlled, single-masked 
study 
Duration: 
Six study visits over approximately 3 months 
Controls: 
Placebo (OC-01 Vehicle Nasal Spray) 
Dosing Regimen:  
Intranasal Spray delivered BID 
Summary of Visit 
Schedule: 
x Visit 1 = Day 1, Screening, Randomization, and Treatment 
(Schirmer’s Test Evaluation) 
x Visit 2 = Day 7 ± 2, Treatment (Schirmer’s Test Evaluation) 
x Visit 3 = Day 14 ± 2, Treatment (Schirmer’s Test Evaluation) 
x Visit 4 = Day 28 ± 2, Treatment (Schirmer’s Test Evaluation) 
x Visit 5 = Day 56 ± 2, Treatment (Schirmer’s Test Evaluation) 
x Visit 6 = Day 84 ± 2, Treatment (Schirmer’s Test Evaluation) 
Measures Taken to 
Reduce Bias: 
This is a randomized, controlled, single-masked study 
Study Population Characteristics 
Number of Subjects: 
Approximately 120 
Condition/Disease: 
Dry Eye Disease  
Inclusion Criteria:  
Subjects must: 
1. 
 
2. Have used and/or desired to us an artificial tear substitute for 
dry eye symptoms within 6 months prior to Visit 1 








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Analysis Populations: 
ï Intent-to-Treat Population – The intent-to-treat (ITT) population includes 
all randomized subjects. Subjects in the ITT population will be analyzed 
as randomized. 
ï Per Protocol Population – The per protocol (PP) population includes subjects in 
the ITT population who do not have significant protocol deviations and who 
complete the study. Protocol deviations will be assessed prior to database lock 
and unmasking. Subjects in the PP population will be analyzed as treated.  
ï Safety Population – The safety population includes all subjects who have 
received at least one dose of the investigational product. Subjects in the Safety 
population will be analyzed as treated. 
Sample Size: 
The sample size for this study is not based on statistical power considerations. It is expected 
that approximately 40 subjects will be enrolled in each arm, for a total of approximately 120 
randomized subjects.  
 
Safety Variables:  
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
dictionary. Frequencies and percentages of subjects with treatment-emergent AEs (TEAEs), 
serious TEAEs, and TEAEs causing premature discontinuation will be provided by treatment 
group. An AE is treatment emergent if it occurs or worsens after the first dose of study 
treatment. Furthermore, frequencies will be given of subjects with TEAEs by system organ 
class, by system organ class and preferred term, by system organ class, preferred term and 
maximal severity, by system organ class, preferred term and strongest relationship, and by 
system organ class, preferred term, maximal severity, and strongest relationship. Separate 
analyses will be performed for ocular specific and all AEs (including systemic).  
Other safety endpoints including visual acuity, slit-lamp biomicroscopy and intranasal 
examination will be summarized by treatment group and visit using descriptive statistics. 
Changes or shifts from baseline will also be summarized where appropriate. For assessments 
performed by eye, study eye and fellow eye will be summarized separately. In addition, shifts 
from baseline to worst on-treatment value for ocular safety assessments will be summarized.  
 
Efficacy Analyses: 
Schirmer’s Test will be summarized by visit, time point (where appropriate) and treatment 
with descriptive statistics (n, mean, median, standard deviation, minimum and maximum). 
An analysis of covariance (
 model will be used to compare results from 
Schirmer’s Test concurrent with treatment between each dose of OC-01 Nasal Spray and 
placebo treatment groups. The 
 model will include baseline Schirmer’s Test 
(captured at Screening), treatment and study site as covariates. Least Squares Means (LS 
 Means) for each treatment, the corresponding 95% confidence intervals (CIs), and the  
estimated treatment differences between each dose of OC-01 Nasal Spray and placebo will be 
calculated from this 
 model. In addition, the study site by treatment interaction will be 
explored in a separate model to evaluate how the treatment effect may differ across study sites.  


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The analyses will be performed on the ITT population on observed data. Two-sample t-tests and 
non-parametric Wilcoxon rank sum tests will be used to compare treatments as unadjusted 
sensitivity analyses. Sensitivity analyses will also be performed on the ITT population with 
multiple imputation (MI) to impute missing data, as well as the PP population with observed 
data only.  
 
Summary of Known and Potential Risks and Benefits to Human Subjects 
There are no known risks with the instillation of OC-01 Nasal Spray.  


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1. 
TABLE OF CONTENTS 
TABLE OF CONTENTS 
SYNOPSIS .......................................................................................................................................3 
1. 
TABLE OF CONTENTS .....................................................................................................9 
2. 
LIST OF ABBREVIATIONS ............................................................................................13 
3. 
INTRODUCTION .............................................................................................................14 
4. 
STUDY OBJECTIVE ........................................................................................................15 
5. 
CLINICAL HYPOTHESES ..............................................................................................15 
6. 
OVERALL STUDY DESIGN ...........................................................................................15 
7. 
STUDY POPULATION ....................................................................................................16 
7.1. 
Number of Subjects............................................................................................................16 
7.2. 
Study Population Characteristics .......................................................................................16 
7.3. 
Inclusion Criteria ...............................................................................................................16 
7.4. 
Exclusion Criteria ..............................................................................................................17 
7.5. 
Withdrawal Criteria ...........................................................................................................18 
8. 
STUDY PARAMETERS ...................................................................................................19 
8.1. 
Safety Measures .................................................................................................................19 
8.2. 
Efficacy Measures ..............................................................................................................19 
8.3. 
Other Measures ..................................................................................................................19 
9. 
STUDY MATERIALS ......................................................................................................19 
9.1. 
Study Drug(s) .....................................................................................................................19 
9.1.1. Formulations ......................................................................................................................19 
9.1.2. Dispensation Schedule .......................................................................................................19 
9.1.3. Instructions for Use ............................................................................................................19 
9.2. 
Other Study Supplies .........................................................................................................25 
10. 
STUDY METHODS AND PROCEDURES .....................................................................26 
10.1. Participant Entry Procedures..............................................................................................26 
10.1.1. Overview ............................................................................................................................26 
10.1.2. Informed Consent...............................................................................................................26 
10.1.3. Washout Intervals ..............................................................................................................26 
10.1.4. Procedures for Final Study Entry .......................................................................................26 


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10.1.5. Methods for Assignment to Treatment Groups .................................................................26 
10.2. Concurrent Therapies .........................................................................................................26 
10.2.1. Prohibited Medications/Treatments ...................................................................................27 
10.2.2. Escape Medications ...........................................................................................................27 
10.2.3. Special Diet or Activities ...................................................................................................27 
10.3. Examination Procedures ....................................................................................................27 
10.3.1. Procedures to be Performed at Each Study Visit with Regard to Study 
Objectives(s) ......................................................................................................................27 
10.4. Schedule of Visits, Measurements and Dosing..................................................................29 
10.4.1. Scheduled Visits.................................................................................................................29 
10.4.2. Unscheduled Visits ............................................................................................................29 
10.5. Compliance with Protocol..................................................................................................30 
10.6. Subject Disposition ............................................................................................................30 
10.6.1. Completed Subjects ...........................................................................................................30 
10.6.2. Discontinued Subjects ........................................................................................................30 
10.7. Study Termination .............................................................................................................30 
10.8. Study Duration ...................................................................................................................30 
10.9. Monitoring and Quality Assurance ....................................................................................30 
11. 
ADVERSE EVENTS .........................................................................................................31 
11.1. Adverse Event ....................................................................................................................31 
11.1.1. Severity ..............................................................................................................................31 
11.1.2. Relationship to Study Drug ................................................................................................31 
11.1.3. Expectedness ......................................................................................................................32 
11.2. Serious Adverse Events .....................................................................................................32 
11.3. Procedures for Reporting Adverse Events .........................................................................33 
11.3.1. Reporting a Suspected Unexpected Adverse Reaction ......................................................33 
11.3.2. Reporting a Serious Adverse Event ...................................................................................33 
11.4. Procedures for Unmasking of Study Drug .........................................................................34 
11.5. Type and Duration of the Follow-up of Subjects after Adverse Events ............................34 
12. 
STATISTICAL HYPOTHESES AND METHODS OF ANALYSES ..............................34 
12.1. Analysis Populations ..........................................................................................................34 
12.2. Statistical Hypotheses ........................................................................................................35 


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12.3. Sample Size ........................................................................................................................35 
12.4. Statistical Analysis .............................................................................................................35 
12.4.1. General Considerations ......................................................................................................35 
12.4.2. Unit of Analysis .................................................................................................................35 
12.4.3. Missing Data ......................................................................................................................35 
12.4.4. Multiplicity Consideration .................................................................................................36 
12.4.5. Efficacy Analyses ..............................................................................................................36 
12.4.6. Safety Variables .................................................................................................................36 
13. 
COMPLIANCE WITH GOOD CLINICAL PRACTICES, ETHICAL 
CONSIDERATIONS, AND ADMINISTRATIVE ISSUES .............................................37 
13.1. Protection of Human Subjects ...........................................................................................37 
13.1.1. Subject Informed Consent..................................................................................................37 
13.1.2. Institutional Review Board Approval ................................................................................37 
13.2. Ethical Conduct of Study ...................................................................................................37 
13.3. Subject Confidentiality ......................................................................................................37 
13.4. Documentation ...................................................................................................................38 
13.4.1. Retention of Documentation ..............................................................................................38 
13.5. Labeling, Packaging, Storage, Accountability, and Return or Disposal of Study 
Drug ...................................................................................................................................38 
13.5.1. Labeling/Packaging............................................................................................................38 
13.5.2. Storage of Investigational Drug / Placebo .........................................................................39 
13.5.3. Accountability of Study Drug ............................................................................................39 
13.5.4. Return or Disposal of Study Drug .....................................................................................39 
13.6. Recording of Data on Source Documents and Electronic Case Reports Forms ................39 
13.7. Handling of Biological Specimens ....................................................................................39 
13.8. Publications ........................................................................................................................39 
14. 
REFERENCES ..................................................................................................................41 
15. 
APPENDICES ...................................................................................................................44 
APPENDIX 1: SCHEDULE OF VISITS AND MEASUREMENTS ...........................................44 
APPENDIX 2: EXAMINATION PROCEDURES, TESTS, EQUIPMENT, AND 
TECHNIQUES ..................................................................................................................45 
Visual Acuity Procedures ..............................................................................................................45 


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Slit Lamp Biomicroscopy ..............................................................................................................46 
Corneal Fluorescein Staining .........................................................................................................46 
Intranasal Examination ..................................................................................................................47 
Schirmer’s Test with Topical Anesthesia ......................................................................................47 
APPENDIX 3: SPONSOR APPROVALS ....................................................................................49 
APPENDIX 4: INVESTIGATOR’S SIGNATURE ......................................................................50 
 


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2. 
LIST OF ABBREVIATIONS 
AE 
Adverse event 
ANCOVA 
Analysis of covariance 
BCVA 
Best corrected visual acuity  
BID 
Two times a day 
CAE® 
Controlled adverse environment 
CFR 
Code of Federal Regulations 
CI 
Confidence interval 
CRF 
Case report form 
EDS 
Eye Dryness Score 
DED 
Dry eye disease 
HIPAA 
Health Information Portability and Accountability Act 
IB 
Investigator’s Brochure 
ICF 
Informed consent form 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 
ITT 
Intention to Treat 
logMAR 
Logarithm of the minimum angle of resolution 
LS 
Least Square 
MAD 
Mucosal Atomization Device 
MedDRA 
Medical Dictionary for Regulatory Activities 
MI 
Multiple imputation 
μL 
microliter 
mm 
Millimeter 
nAChR 
Nicotinic acetylcholine receptor 
PP 
Per Protocol 
SAE 
Serious adverse event 
TEAE 
Treatment-emergent adverse event 
US 
United States 
 












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8. 
STUDY PARAMETERS  
8.1. 
Safety Measures 
x Adverse Events 
8.2. 
Efficacy Measures 
The following endpoints will be tested:Schirmer’s Test at Visit 6 (Day 84) 
x Schirmer’s Test at Visit 6 (Day 84) 
8.3. 
Other Measures 
Urine pregnancy test (Visit 1 and Visit 6/ET) (if applicable) 
9. 
STUDY MATERIALS 
9.1. 
Study Drug(s) 
9.1.1. 
Formulations  
x Placebo (vehicle) delivered as a 50 microliter (μL) intranasal spray in each nostril 
BID 
x 0.1% OC-01 (varenicline tartrate) delivered as a 50 microliter (μL) intranasal spray in 
each nostril BID 
x 0.2% OC-01 (varenicline tartrate) delivered as a 50 microliter (μL) intranasal spray in 
each nostril BID 
9.1.2. 
Dispensation Schedule  
x At Visit 1, qualified subjects will be randomized and the first dose of study drug will 
be administered in office. 
x At Visit 2, Visit 3, Visit 4, Visit 5, and Visit 6 the first daily dose of study drug will 
be administered in office concurrent with Schirmer’s testing. 
x At study Days 2-6, 8-13, 15-27, 29-55, and 57-83 subjects will self-administer OC-01 
BID as a 50 μL intranasal spray in each nostril. 
9.1.3. 
Instructions for Use 
General Appearance 
x OC-01/Placebo will be formulated at the desired concentration depending upon dose 
group assignment in phosphate buffered saline as a sterile aqueous solution, and 
presented in a multi-use preservative-free nasal pump. 












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10. 
STUDY METHODS AND PROCEDURES 
10.1. 
Participant Entry Procedures  
10.1.1. 
Overview  
Participants as defined by the criteria in Section 7.3 and Section 7.4 will be considered for entry 
into this study.  
10.1.2. 
Informed Consent  
Prior to a participant’s participation in the trial (i.e., prior to study-related procedures), the study 
will be discussed with each potential participant and participants wishing to participate must be 
administered and provide written informed consent using an Institutional Review Board (IRB) or 
Independent Ethics Committee (IEC)-approved informed consent form (ICF). The ICF must be 
the most recent version that has received approval by a properly constituted IRB/IEC.  
10.1.3. 
Washout Intervals  
Prohibited medications, treatments, and activities are outlined in the Exclusion Criteria 
(Section 7.4).  
10.1.4. 
Procedures for Final Study Entry 
Subjects must meet all inclusion criteria and none of the exclusion criteria.  
10.1.5. 
Methods for Assignment to Treatment Groups 
Each subject who enters the screening period for the study (defined as the point at which the 
subject signs the informed consent form (ICF) receives a unique subject identification number 
before any study-related activities/procedures are performed.  This number will be used to 
identify the subject throughout the clinical study and must be used on all study documentation 
related to that subject.   
The subject identification number must remain constant throughout the entire clinical study.  
This number will not necessarily be the same as the randomization number. 
Subjects who meet the eligibility requirements will be randomly assigned to 1 of 3 treatment 
groups. 
10.2. 
Concurrent Therapies  
The use of any concurrent medication, prescription or over-the-counter, is to be recorded on the 
subject’s source document and corresponding eCRF along with the reason the medication was 
taken.  
Concurrent enrollment in another investigational drug or device study is not permitted.  


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10.2.1. 
Prohibited Medications/Treatments  
Disallowed medications/treatments during the study are outlined in the Exclusion Criteria 
(Section 7.4) 
10.2.2. 
Escape Medications 
No escape medications are required for this study.  
10.2.3. 
Special Diet or Activities  
No special diets or activities are required for this study.  
10.3. 
Examination Procedures  
10.3.1. 
Procedures to be Performed at Each Study Visit with Regard to Study 
Objectives(s) 
The following procedures will be performed (see Appendix 2 for description).  
Screening/Visit 1 (Day 1): Screening and Schirmer’s Test Evaluation  
x Informed consent/Health Information Portability and Accountability Act (HIPAA) 
consent 
x Demographic data, medical history, prior medication (s), and ocular history 
x Eligibility Criteria  
x Urine pregnancy test (if applicable) 
x BCVA (pre-and post-treatment) 
x Slit lamp biomicroscopy (pre-and post-treatment) 
x Corneal fluorescein staining 
x Schirmer’s Test3  
x Schirmer’s Test with nasal stimulation (cotton swab)4 
x Intranasal examination  
x Randomization 
x Dispense new study drug/placebo intranasal applicator 
x Administration of study drug/placebo 
x Concomitant Medications 
                                                 
3 Procedure will occur prior to treatment and after corneal fluorescein staining and post treatment   
4 Schirmer’s test with nasal stimulation will occur 10 minutes after the first Schirmer’s test  


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x AE Query 
 
Visit 2 (Day 7 ±2): Schirmer’s Test Evaluation 
x BCVA (pre-and post-treatment) 
x Slit lamp biomicroscopy (pre-and post-treatment) 
x Administration of study drug/placebo 
x Schirmer’s Test (concurrent with treatment) 
x Concomitant Medications 
x AE Query 
Visit 3 (Day 14 ±2): Schirmer’s Test Evaluation 
x BCVA (pre-and post-treatment) 
x Slit lamp biomicroscopy (pre-and post-treatment) 
x Administration of study drug/placebo 
x Schirmer’s Test (concurrent with treatment) 
x Dispense new study drug/placebo intranasal applicator 
x Concomitant Medications 
x AE Query 
Visit 4 (Day 28 ±2): Schirmer’s Test Evaluation 
x BCVA (pre-and post-treatment) 
x Slit lamp biomicroscopy (pre-and post-treatment) 
x Administration of study drug/placebo 
x Schirmer’s Test (concurrent with treatment) 
x Dispense new study drug/placebo intranasal applicator 
x Concomitant Medications 
x AE Query 
Visit 5 (Day 56 ±2): Schirmer’s Test Evaluation 
x BCVA (pre-and post-treatment) 
x Slit lamp biomicroscopy (pre-and post-treatment) 
x Administration of study drug/placebo 
x Corneal fluorescein staining 
x Schirmer’s Test (concurrent with treatment) 


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x Dispense new study drug/placebo intranasal applicator 
x Concomitant Medications 
x AE Query 
 
Visit 6 (Day 84 ±2): Schirmer’s Test Evaluation 
x Urine pregnancy test (if applicable) 
x Intranasal examination 
x BCVA (pre-and post-treatment) 
x Slit lamp biomicroscopy (pre-and post-treatment) 
x Administration of study drug/placebo 
x Schirmer’s Test (concurrent with treatment) 
x Concomitant Medications 
x AE Query 
10.4. 
Schedule of Visits, Measurements and Dosing 
10.4.1. 
Scheduled Visits 
Refer to Appendix 1 for a schedule of visits and measurements.  
10.4.2. 
Unscheduled Visits  
These visits may be performed in order to ensure subject safety. All procedures performed at an 
unscheduled visit will be recorded in the source documents and on the Unscheduled Visit eCRF 
pages. Any procedure indicated in the eCRF that is not performed should be indicated as “Not 
done.” 
Evaluations that may be conducted at an Unscheduled Visit include: 
x Slit-lamp Biomicroscopy; 
x Visual Acuity; 
x Intranasal Examination; 
x Urine Pregnancy Test (if applicable); 
x Assessment of AEs; 
x Assessment of concurrent medications and/or treatments; and 
x Any other assessments needed in the judgment of the investigator. 






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x Probable: When there are good reasons and sufficient documentation to assume a 
causal relationship in the sense of plausible, conceivable, likely but not necessarily 
highly probable 
x Possible: When there is sufficient information to accept the possibility of a causal 
relationship in the sense of not impossible and not unlikely, although the connection 
is uncertain or doubtful, for example; due to missing data or insufficient evidence. 
x None: When there is sufficient information to accept a lack of a causal relationship, in 
the sense of impossible and improbable. 
x Unclassified: When the causal relationship is not assessable for whatever reason due 
to insufficient evidence, conflicting data or poor documentation. 
11.1.3. 
Expectedness  
The expectedness of an AE should be determined based upon existing safety information about 
the study drug using these explanations: 
x Unexpected: An AE that is not listed in the Investigator’s Brochure (IB) or is not 
listed at the specificity or severity that has been observed. 
x Expected: An AE that is listed in the IB at the specificity and severity that has been 
observed. 
x Not Applicable: Any AE that is unrelated to the study drug. 
AEs that are mentioned in the IB as occurring with a class of drugs or as anticipated from the 
pharmacological properties of the drug but are not specifically mentioned as occurring with the 
particular drug under investigation are to be considered unexpected. 
The investigator should initially classify the expectedness of an AE, but the final classification is 
subject to the Medical Monitor’s determination. 
11.2. 
Serious Adverse Events  
An AE is considered serious (SAE) if, in the view of either the Investigator or Sponsor, it results 
in any of the following outcomes: 
x Death 
x A life-threatening AE 
Note:  An AE is considered “life-threatening” if, in the view of either the Investigator or 
Sponsor, its occurrence places the patient or subject at immediate risk of death.  It does not 
include an AE that, had it occurred in a more severe form, might have caused death. 
x Inpatient hospitalization or prolongation of existing hospitalization 
Note:  The term “inpatient hospitalization” refers to any inpatient admission (even if less than 24 
hours).  For chronic or long-term inpatients, inpatient admission includes transfer within the 
hospital to an acute/intensive care inpatient unit.  Inpatient hospitalization does not include:  
emergency room visits; outpatient/same-day/ambulatory procedures; observation/short stay 


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units; rehabilitation facilities; hospice facilities; nursing homes; or clinical research/phase 1 
units. 
Note:  The term “prolongation of existing hospitalization” refers to any extension of an inpatient 
hospitalization beyond the stay anticipated or required for the reason for the initial admission as 
determined by the investigator or treating physician. 
x A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
Note:  An SAE specifically related to visual threat would be interpreted as any potential 
impairment or damage to the subject’s eyes (e.g., hemorrhage, retinal detachment, central 
corneal ulcer or damage to the optic nerve). 
x A congenital anomaly/birth defect. 
Important medical events that may not result in death, are life-threatening, or require 
hospitalization may be considered serious 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 this definition. 
11.3. 
Procedures for Reporting Adverse Events  
All AEs and their outcomes must be reported to the Sponsor and the IRB/IEC as required by the 
IRB/IEC, federal, state, or local regulations and governing health authorities and recorded on the 
appropriate eCRF. 
11.3.1. 
Reporting a Suspected Unexpected Adverse Reaction  
All AEs that are ‘suspected’ and ‘unexpected’ are to be reported to the Sponsor and the IRB/IEC 
as required by the IRB/IEC, federal, state, or local regulations and governing health authorities. 
11.3.2. 
Reporting a Serious Adverse Event 
To ensure subject safety, all SAEs, regardless of relationship to the study drug, must be 
immediately reported.  All information relevant to the SAE must be recorded on the appropriate 
CRFs.  The investigator is obligated to pursue and obtain information requested by the Sponsor 
in addition to that information reported on the CRF.  All subjects experiencing a SAE must be 
followed up and the outcome reported. 
In the event of a SAE, the Investigator must notify the Sponsor immediately; obtain and maintain 
in his/her files all pertinent medical records, information, and medical judgments from 
colleagues who assisted in the treatment and follow-up of the subject; provide Sponsor with a 
complete case history, which includes a statement as to whether the event was or was not 
suspected to be related to the use of the study drug; and inform the IRB/IEC of the SAE within 
their guidelines for reporting SAEs. 








OC-01 Intranasal Spray  
 
 
 
 
Sponsor: Oyster Point Pharma, Inc.  
OPP-004 
 
07 March 2019 
Amendment #4 
 
 
 
Page 37 of 50 
 
13. 
COMPLIANCE WITH GOOD CLINICAL PRACTICES, 
ETHICAL CONSIDERATIONS, AND ADMINISTRATIVE 
ISSUES  
This study will be conducted in compliance with the protocol, Good Clinical Practices, including 
the International Conference on Harmonization (ICH) Guidelines, and in general, consistent with 
the Declaration of Helsinki.  In addition, all applicable local, state, and federal requirements 
relevant to the use of study drugs in the countries involved will be adhered to. 
13.1. 
Protection of Human Subjects 
13.1.1. 
Subject Informed Consent  
Informed consent/assent must take place before any study specific procedures are initiated.  
Signed and dated written informed consent must be obtained from each subject and/or from the 
subject’s parent or legal guardian prior to enrollment into the study.  If the subject is under the 
legal age of consent, the consent form must be signed by a legal guardian or as required by state 
and/or local laws and regulations. 
All informed consent/assent forms must be approved for use by the Sponsor/Investigator and 
receive approval/favorable opinion from an IRB/IEC prior to their use.  If the consent form 
requires revision (e.g., due to a protocol amendment or significant new safety information), it is 
the investigator’s responsibility to ensure that the amended informed consent is reviewed and 
approved by the Sponsor prior to submission to the governing IRB/IEC and that it is read, signed 
and dated by all subjects subsequently enrolled in the study as well as those currently enrolled in 
the study. 
If informed consent is taken under special circumstances (oral informed consent), then the 
procedures to be followed must be determined by the Sponsorand provided in writing by the 
Sponsor prior to the consent process. 
13.1.2. 
Institutional Review Board Approval  
This study is to be conducted in accordance with IRB/IEC regulations [U.S. 21 Code of Federal 
regulations (CFR) Part 56.103].  The investigator must obtain appropriate IRB/EC approval 
before initiating the study and re-approval at least annually. 
Only an IRB/IEC-approved version of the informed consent form will be used. 
13.2. 
Ethical Conduct of Study  
This study will be conducted in accordance with the ethical principles that originated with the 
Declaration of Helsinki. 
13.3. 
Subject Confidentiality  
All personal study subject data collected and processed for the purposes of this study should be 
maintained by the investigator and his/her staff with adequate precautions as to ensure that the 
confidentiality of the data in accordance with local, state, and federal laws and regulations. 


OC-01 Intranasal Spray  
 
 
 
 
Sponsor: Oyster Point Pharma, Inc.  
OPP-004 
 
07 March 2019 
Amendment #4 
 
 
 
Page 38 of 50 
 
Monitors, auditors and other authorized representatives of Oyster Point Pharma, the IRB/IEC 
approving this study, the Comisión Federal para la Protección contra Riesgos Sanitarios 
(COFEPRIS), the Food and Drug Administration (FDA), the Department of Health and Human 
Services, other domestic government agencies, and other foreign regulatory agencies will be 
granted direct access to the study subject’s original medical and study records for verification of 
the data and/or clinical trial procedures.  Access to this information will be permitted to the 
aforementioned individuals to the extent permitted by law. 
A report of the results of this study may be published or sent to the appropriate health authorities 
in any country in which the study drug may ultimately be marketed, but the subject’s identity 
will not be disclosed in these documents. 
13.4. 
Documentation  
Source documents may include a subject’s medical records, hospital charts, clinic charts, the 
investigator’s study subject files, as well as the results of diagnostic tests such as X-rays, 
laboratory tests, and electrocardiograms.  The investigator’s copy of the CRFs serves as the 
investigator’s record of a subject’s study-related data. 
13.4.1. 
Retention of Documentation  
All study related correspondence, subject records, consent forms, record of the distribution and 
use of all study drug and copies of CRFs should be maintained on file for at least two 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 years have elapsed 
since the formal discontinuation of clinical development of the study drug. These documents will 
be retained for a longer period if required by the applicable regulatory requirements or by an 
agreement with the Sponsor.  It is the responsibility of the Sponsor to inform the 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 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. 
13.5. 
Labeling, Packaging, Storage, Accountability, and Return or 
Disposal of Study Drug 
13.5.1. 
Labeling/Packaging 
Investigational drug will be provided in multi-use intranasal applicator that will be assigned at 
randomization for use during the first 14 days of study.  A second multi-use intranasal applicator 
will be provided at Visit 3 (Day 14) for use during days 14-27, multi-use intranasal applicators 
three and four will be provided at Visit 4 (Day 28) for use during days 28-55, multi-use 
intranasal applicators five and six will be provided at Visit 5 (Day 56) for use during days 56-84. 


OC-01 Intranasal Spray  
 
 
 
 
Sponsor: Oyster Point Pharma, Inc.  
OPP-004 
 
07 March 2019 
Amendment #4 
 
 
 
Page 39 of 50 
 
13.5.2. 
Storage of Investigational Drug / Placebo 
The investigational drug / placebo must be stored in a secure area accessible only to the 
investigator and his/her designee(s). Study drug(s) must be refrigerated (2-8°C, Do Not Freeze), 
protected from light, and secured at the investigational site in a locked container.  
13.5.3. 
Accountability of Study Drug 
The investigational drug / placebo is only prescribed by the principal investigator or his/her 
named sub investigator(s),and is to only be used in accordance with this protocol. The study 
drugs must only be distributed to subjects properly qualified under this protocol to receive study 
drug.  The investigator must keep an accurate accounting of the study drugs by maintaining a 
detailed inventory. This includes the amount of study drugs received by the site, amount 
dispensed to subjects, amount returned to the site by the subjects, and the amount returned to the 
Sponsor upon the completion of the study.  
13.5.4. 
Return or Disposal of Study Drug 
All study drugs will be returned to the Sponsor or their designee for destruction. 
13.6. 
Recording of Data on Source Documents and Electronic Case 
Reports Forms 
All subject data will be captured in the subject source documents which will be transcribed in the 
eCRFs. The investigator is responsible for ensuring that study data is completely and accurately 
recorded on each subject’s eCRF, source documents, and all study-related materials. All study 
data should also be attributable, legible, contemporaneous, and original. Recorded datum should 
only be corrected in a manner that does not obliterate, destroy, or render illegible the previous 
entry (e.g., by drawing a single line through the incorrect entry and writing the revision next to 
the corrected data). An individual who has corrected a data entry should make clear who made 
the correction and when, by adding to the correction his/her initials as well as the date of the 
correction.  
Data entry of all enrolled and randomized subjects will use software that conforms to 21 CFR 
Part 11 requirements, and will be performed only by staff who have been trained on the system 
and have access to the system. Data will not be entered for screen failure subjects. An audit trail 
will be maintained within the electronic system to capture all changes made within the eCRF 
database. After the end of the study and database lock, copies of all applicable subjects’ eCRFs 
will be provided to each Investigator Site to be maintained on file by the Investigator. 
13.7. 
Handling of Biological Specimens  
Not applicable for this study.  
13.8. 
Publications 
The study will be documented in a final report, which will contain appropriate statistical analysis 
and medical overview. No individual site or Investigator may publish or present any results from 
the study until a joint, multi-center publication of the trial results is made by Sponsor in 


OC-01 Intranasal Spray  
 
 
 
 
Sponsor: Oyster Point Pharma, Inc.  
OPP-004 
 
07 March 2019 
Amendment #4 
 
 
 
Page 40 of 50 
 
conjunction with various participating Investigators and appropriate sites contributing data and 
comments. Subsequently, individual Investigators may request to publish or present results from 
the trial; however, approval will be at the sole discretion of the Sponsor. Should the foregoing 
language be in conflict with the language addressing publication in the clinical trial agreement, 
the language in the Clinical Trial Agreement will prevail.  
 










OC-01 Intranasal Spray  
 
 
 
 
Sponsor: Oyster Point Pharma, Inc.  
OPP-004 
 
07 March 2019 
Amendment #4 
 
 
 
Page 45 of 50 
 
APPENDIX 2: EXAMINATION PROCEDURES, TESTS, EQUIPMENT, 
AND TECHNIQUES  
The following examination procedures, tests, equipment and techniques are listed in this 
Appendix:  
Visual Acuity Procedures  
LogMAR visual acuity must be assessed using an ETDRS chart. The procedure used will be 
consistent with the recommendations provided for using the ETDRS eye chart. Visual acuity 
should be evaluated at the beginning of each visit in the study (i.e., prior to slit lamp 
examination). Participants should use the most recent correction to attain their corrected distance 
visual acuity (CDVA); if they forget their spectacles, this prescription can be placed in a trial 
frame. 
Equipment 
The visual acuity chart to be used is the ETDRS chart. If smaller reproduction (18" by 18", e.g., 
from Prevent Blindness) wall charts are used, the participant viewing distance should be exactly 
10 feet (or as specified by the manufacturer). In ALL cases, for purposes of standardizing the 
testing conditions during the study, all sites must use only ETDRS Series 2000 Chart 1 & 2, and 
the right eye should be tested first. For reflectance (wall) charts, the chart should be placed 
frontally and be well illuminated. 
Measurement Technique 
The chart should be at a comfortable viewing angle. The right eye should be tested first. The 
participant should attempt to read each letter, line-by-line, left to right, beginning with line 1 at 
the top of the chart. The participant should be told that the chart has letters only, no numbers. If 
the participant reads a number, s/he should be reminded that the chart contains no numbers, and 
the examiner should then request a letter in lieu of the number. The participant should be asked 
to read slowly, so as to achieve the best identification of each letter. S/he is not to proceed to the 
next letter until s/he has given a definite response. 
If the participant changes a response (e.g., 'that was a "C" not an "O"') before s/he has read aloud 
the next letter, then the change must be accepted. If the participant changes a response having 
read the next letter, then the change is not accepted. The examiner should never point to the chart 
or to specific letters on the chart during the test. 
A maximum effort should be made to identify each letter on the chart. When the participant says 
s/he cannot read a letter, s/he should be encouraged to guess. If the participant identifies a letter 
as one of two letters, s/he should be asked to choose one letter and, if necessary, to guess. When 
it becomes evident that no further meaningful readings can be made, despite encouragement to 
read or guess, the examiner should stop the test for that eye. However, all letters on the last line 
should be attempted as letter difficulties vary and the last may be the only one read correctly. 
The number of letters missed or read incorrectly should be noted. 


OC-01 Intranasal Spray  
 
 
 
 
Sponsor: Oyster Point Pharma, Inc.  
OPP-004 
 
07 March 2019 
Amendment #4 
 
 
 
Page 46 of 50 
 
LogMAR Visual Acuity Calculations 
The last line in which a letter is read correctly will be taken as the base logMAR reading. To this 
value will be added the number "N x 0.02" where 'N' represents the total number of letters 
missed up to and including the last line read. This total sum represents the logMAR visual acuity 
for that eye. 
Example: Participant correctly reads 4 of 5 letters on the 0.2 line, and 2 of 5 letters on the 0.1 
line. 
Base logMAR 
= 0.1 
N (total number of letters incorrect on line 0.2 as well as 0.1) 
= 4 
N x T (T=0.02) 
= 0.08 
Base logMAR + (N x T) 
= 0.1 + 0.08 
logMAR visual acuity 
= 0.18 
Repeat the procedure for the left eye. 
In order to provide standardized and well-controlled assessments of visual acuity during the 
study, all visual acuity assessments at a single site must be consistently done using the same 
lighting conditions and same correction if possible during the entire study. If the same correction 
cannot be used (i.e., a participant broke his/her glasses), the reason for the change in correction 
should be documented. 
Note: A clinically significant visual acuity decrease (defined as an increase of 0.22 or greater in 
logMAR score) from the Screening Visit (Visit 1) should be evaluated by the Investigator as a 
potential AE. 
Slit Lamp Biomicroscopy  
Slit lamp biomicroscopy will be performed during the study. Observations will be graded as 
Normal or Abnormal. Abnormal findings, which are clinically significant, will be described.  
Corneal Fluorescein Staining  
The examiner should instill 5 PL of 2% preservative-free sodium fluorescein solution into the 
inferior conjunctival cul-de-sac of each eye. Alternatively, corneal staining can be assessed using 
1.0 mg sodium fluorescein strips. After moistening the tip of the strip with sterile buffered saline, 
the excess is shaken into a waste bin with a sharp flick. The lower lid is then pulled down and the 
flat end of the tip should be gently applied to the inferior tarsal conjunctiva with the intent of not 
inducing reflex tearing and instilling a very small volume of dye.  
The participant will be instructed to blink naturally several times without forced closure of the 
eyelid to distribute the fluorescein. In order to achieve maximum fluorescence, the examiner 
should wait at least two minutes after instillation before evaluating corneal fluorescein staining. 




OC-01 Intranasal Spray  
 
 
 
 
Sponsor: Oyster Point Pharma, Inc.  
OPP-004 
 
07 March 2019 
Amendment #4 
 
 
 
Page 48 of 50 
 
1. Topical anesthetic drops such as 0.5% proparacaine hydrochloride or equivalent should 
be instilled in both eyes of the participant. 
2. The participant will be instructed to keep the eyes gently closed for one minute.   
3. After opening the eyes and allowing the eyes to recover for approximately one additional 
minute, excess moisture in the inferior fornix is gently removed with a spear. 
4. Schirmer’s strips (35 mm x 5 mm size filter paper strip) will be placed in each eye at the 
junction of the middle and lateral thirds of the lower eye lid.  
5. Under ambient light, the participant will be instructed to look forward and to blink 
normally during the course of the test. The test should be performed in a room with no 
direct air on the participant’s face. 
6. The Schirmer’s strips should remain in place until five minutes have elapsed or both 
strips have reached maximum score. 
7. After five minutes, strips will be removed from both eyes and the amount of wetting will 
be recorded. The strips should be taped to the CRF.   
Schirmer’s test using cotton swab nasal stimulation   
At the Screening Visit, the Schirmer’s test should be performed using cotton swab nasal 
stimulation. New anesthetic drops should be instilled following the same procedure specified in 
steps #1 to 3 above. 
1. With new strips in place, the examiner should insert cotton swabs in the participant’s two 
nostrils simultaneously and gently probe both nasal middle turbinates for approximately 
30 seconds. After this, the examiner can simply hold the swabs in place, applying gentle 
pressure, and repeat probing intermittently as necessary.   
2. Alternatively, the participant can be instructed to hold the cotton swabs and gently probe 
both nasal turbinates simultaneously, resting intermittently before probing again.  The 
examiner should continuously coach the participant on how to perform this test properly.  
3. The Schirmer’s strips should remain in place until five minutes have elapsed or both 
strips have reached maximum score. 
Both Schirmer’s scores will be recorded and verified that they meet the inclusion criteria.   




OC-01 Intranasal Spray  
 
 
 
 
Sponsor: Oyster Point Pharma, Inc.  
OPP-004 
 
07 March 2019 
Amendment #4 
 
 
 
Page 50 of 50 
 
APPENDIX 4: INVESTIGATOR’S SIGNATURE  
Protocol Title: 
Single Center, Randomized, Controlled, Single-Masked Clinical 
Trial to Evaluate the Chronic Efficacy of OC-01 Nasal Spray on 
Signs of Dry Eye Disease (The MYSTIC Study) 
Protocol Number: 
OPP-004 
 
 
I agree to implement and conduct the study diligently and in strict compliance with the protocol, 
good clinical practices and all applicable laws and regulations. I agree to maintain all 
information supplied by Oyster Point Pharma in confidence and, when this information is 
submitted to an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) or 
another group, it will be submitted with a designation that the material is confidential. 
I have read this protocol in its entirety, including the above statement, and I agree to all aspects. 
Signed: 
 
 
Date:  
 
 
Name:  
 
 
 
Title:  
 
 
 
Site:  
 
 
 
Address:  
 
 
 
Phone Number:  
 
 
 

SAP_001.pdf: 
Page 1 of 19
Oyster Point Pharma, Inc.
Clinical Protocol: OPP-004:
Phase 2, Single Center, Randomized, Controlled, Single-
Masked Clinical Trial to Evaluate the Chronic Efficacy of 
OC-01 Nasal Spray on Signs of Dry Eye Disease 
(The MYSTIC Study)
Statistical Analysis Plan
Version 2.0
December 23, 2019


Page 2 of 19
Revision History
Version
Version Date
Author
Summary of Changes Made
Draft 0.1
October 30, 2019
New Document
Draft 0.2
November 12,
2019
Modified based on Sponsor’s 
comment
Draft 0.3
November 18,
2019
Modified based on Sponsor’s 
comment: Added the percent of 
VXEMHFWV ZKR DFKLHYH   PP
improvement in Schirmer’s Test 
Score (STS)
Draft 0.4
(V2.0)
December 23,
2019
Modified based on Sponsor’s 
comment: Delete the percent of 
VXEMHFWV ZKR DFKLHYH   PP
improvement in Schirmer’s Test 
Score (STS)




Page 4 of 19
Contents 
1 
Synopsis.................................................................................................................................. 6 
2 
Abbreviations.......................................................................................................................... 7 
3 
Introduction............................................................................................................................. 8 
4 
Study objective ....................................................................................................................... 8 
5 
Study Design........................................................................................................................... 8 
6 
Primary Safety, Efficacy and Other measures........................................................................ 8 
6.1 
Safety Measures ............................................................................................................... 8 
6.2 
Efficacy Endpoint............................................................................................................. 9 
6.3 
Other Efficacy Endpoints................................................................................................. 9 
6.4 
Other Measures ................................................................................................................ 9 
7 
Sample Size............................................................................................................................. 9 
8 
Statistical Hypothesis Testing............................................................................................... 10 
9 
Statistical Analysis................................................................................................................ 10 
9.1 
General Consideration.................................................................................................... 10 
9.2 
Analysis Populations...................................................................................................... 10 
9.2.1 
Intention-to-treat (ITT) population ......................................................................... 10 
9.2.2 
Per protocol population (PP)................................................................................... 11 
9.2.3 
Safety population .................................................................................................... 11 
9.3 
Unit of Analysis ............................................................................................................. 11 
9.4 
Definition of Study Day or Dosing Day ........................................................................ 11 
9.5 
Missing and Partial Data................................................................................................ 11 
9.6 
Protocol Deviations........................................................................................................ 12 
9.7 
Subjects Disposition....................................................................................................... 13 
9.8 
Demographics and Baseline Characteristics .................................................................. 13 
9.9 
Medical, Ocular and Dry Eye History............................................................................ 14 
9.10 
Treatment Exposure.................................................................................................... 14 
10 Ocular Assessments .............................................................................................................. 14 
10.1 
Schirmer’s Test........................................................................................................... 14 


Page 5 of 19
10.2 
BCVA....................................................................................
10.3 
Corneal Fluorescein Staining ..................................................................................... 15 
10.4 
Slit Lamp Biomicroscopy........................................................................................... 15 
11 Intranasal Examination ......................................................................................................... 15 
12
Efficacy Analysis.................................................................................................................. 15
12.1 
Primary Efficacy Endpoint......................................................................................... 15 
12.2 
Other Efficacy Endpoints ........................................................................................... 16 
12.3 
Missing Efficacy Data Handling ................................................................................ 17 
13 Safety Analysis ..................................................................................................................... 17 
13.1 
Adverse Events........................................................................................................... 17 
13.2 
Prior and Concomitant Medications........................................................................... 18 
13.3 
Other Safety Endpoints............................................................................................... 18 
Appendix 1   Schedule of Visits and Measurements .................................................................... 19 




Page 7 of 19
2 Abbreviations
AE
adverse event
ANCOVA
analysis of covariance
BCVA
best corrected visual acuity
BID
twice daily
CAE®
Controlled Adverse Environment®
CFR
Code of Federal Regulations
CI
confidence interval
CRF
case report form
DED
dry eye disease
EDS
Eye Dryness Score
HIPAA
Health Information Portability and Accountability Act
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Conference on Harmonization
IEC
Independent Ethics Committee
IRB
institutional review board
ITT
intent-to-treat
LS
least square
MAD
mucosal atomization device
MedDRA
medical dictionary for regulatory activities
MI
multiple imputation
μL
microliter
mm
millimeter
nAChR
nicotinic acetylcholine receptor
PP
per protocol
SAE
serious adverse event
TEAE
treatment-emergent adverse event
US
United States
WHO
World Health Organization
















Page 15 of 19
subject broke his/her glasses), the reason for the change in correction should be documented. 
BCVA will be summarized by visit and by treatment group for both study and fellow eyes.
Abnormal clinically significant findings will be described. Shifts from baseline including 
normal to abnormal (not clinically significant), and normal to abnormal (clinically 
significant) will be presented using counts and percentages
10.3 Corneal Fluorescein Staining
Corneal fluorescein staining will be performed, and data will be collected at Visits 1 and 5.
Corneal fluorescein staining will be assessed for both the study and fellow eye. Staining will 
be graded using the National Eye Institute (NEI)/Industry Workshop Scale. Examiners will 
score each of five areas on the cornea of each eye: 1 – Central; 2 – Superior; 3 – Temporal; 4 
– Nasal; 5 – Inferior. A standardized grading system of 0-3 will be used for each of the five 
areas. The corneal fluorescein staining score will be described by visit, treatment, study eye, 
and fellow eye with summary statistics. Specifically, scores will be presented by each of the 
five cornea areas and total scores for all corneal areas.
10.4 Slit Lamp Biomicroscopy
The slit lamp biomicroscope will be performed at Visit 1, Visit 2, Visit 3, Visit 4, Visit 5 and 
Visit 6. A slit lamp will be used for external examination and biomicroscopy. The eyelids, 
cornea, conjunctiva, anterior chamber, iris, and lens will be examined at each visit. Slit lamp 
biomicroscopy results will be summarized for each treatment group for the study and fellow 
eye by visit using discrete summary statistics. Abnormal clinically significant findings will 
be described. Shifts from baseline including normal to abnormal (not clinically significant), 
and normal to abnormal (clinically significant) will be presented using counts and 
percentages
11 Intranasal Examination
Intranasal assessments collected at the screening visit (Visit 1) and at Visit 6, and the early 
termination visit will be summarized by treatment group with counts and percentages. Shifts 
from baseline of normal to abnormal (not clinically significant) and normal to abnormal 
(clinically significant) will be presented using counts and percentages.
12 Efficacy Analysis
12.1 Primary Efficacy Endpoint 
The primary efficacy endpoint is mean change from baseline in Schirmer’s Test at Day 84 
(Visit 6).








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