Clinical trial NCT04130802
Conditions: Inflammation Corneal Pain, Postoperative
Keywords: post-cataract, inflammation Pain post-surgery corticosteroid anterior chamber cells flares
Sponsor: Oculis
Start date: 2019-09-27; Completion date: 2020-01-31
Enrollment: 153 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The DX-216 trial is a randomized, double-masked, placebo (vehicle)-controlled study evaluating the efficacy and safety of two doses of OCS-01 compared to vehicle in the treatment of inflammation and pain following cataract surgery. The primary objective is to evaluate the efficacy and safety of OCS-01 compared to placebo and the secondary objective is to evaluate the optimal dosing frequency (once a day \[QD\] or twice a day \[BID\]).

Detailed description:
This is a multi-center, randomized, double-masked, placebo (vehicle)-controlled study, designed to evaluate the efficacy and safety of OCS-01 ophthalmic suspension (QD versus BID) compared to placebo in treating inflammation and pain following cataract surgery. Subjects will be randomized 1:1:1 to receive OCS-01 QD, OCS-01 BID, or placebo BID. Subjects will dose 1 drop in the study eye BID for 14 days, beginning 1 day post-surgery in the operated eye. The study will last up to 24 days, including a follow-up visit at Visit 7 (Day 22 ± 2).

Arms: arm 1: eye drops arm 2: eye drops arm 3: eye drops
Interventions: intervention 1: OCS-01 - Dexamethasone Cyclodextrin Nanoparticle Ophthalmic Suspension 1.5% mg/mL intervention 2: Placebo
Intervention descriptions: intervention 1: OCS-01 eye drops intervention 2: Vehicle eye drops

Protocol documents:
Prot_000.pdf: 
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Clinical Trial Protocol: 
Protocol Title: 
A Randomized, Double-masked, Vehicle-controlled Study 
Evaluating the Efficacy and Safety of Two Doses of 
OCS-01 compared to Vehicle in the Treatment of 
Inflammation and Pain Following Cataract Surgery 
IND# 
131596 
Protocol Number: 
DX216 
Study Phase: 
2 
Product Name: 
OCS-01 ophthalmic suspension 
Indication: 
Inflammation and pain following cataract surgery  
Investigator: 
Multi-center clinical investigation 
 
Sponsor: 
Oculis ehf.  
Álfheimar 74, 6. hæð 
104 Reykjavik | Iceland 
Tel. +354 546 4440 
 
Contract Research 
Organizations: 
Ora, Inc. 
300 Brickstone Square 
Andover, MA 01810 
U.S.A 
Phone: +1-978-685-8900 
 
 
 
 
 
Date 
Original Protocol: 
24 May 2019 
Amendment 1: 
08 August 2019 
 
Confidentiality Statement 
This protocol contains confidential, proprietary information of Ora, Inc. and Oculis. Further 
dissemination, distribution, or copying of this protocol or its contents is strictly prohibited. 
 
 


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ORA PERSONNEL 
Department Sr. Vice President: 
Aron Shapiro 
Office: +1-978-685-8900 ext. 9443 
Mobile: +1-978-886-2925 
Fax: +1-978-689-0020 
Email: ashapiro@oraclinical.com 
Project Manager: 
Amy Baggeroer  
Office: +1 978-332-9422 
Mobile: +1 978-409-5951 
Email: abaggeroer@oraclinical.com 
Medical Monitor 
David Hollander, M.D. 
Office: +1-978-685-8900 ext.3589 
Mobile: +1-949-231-0004 
Fax: +1-978- 689-0020 
Email:dhollander@oraclinical.com 
 
 
 
 


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1 SYNOPSIS 
Protocol Title: 
A Randomized, Double-masked, Vehicle-controlled Study 
Evaluating the Efficacy and Safety of Two Doses of OCS-01 
compared to Vehicle in the Treatment of Inflammation and Pain 
Following Cataract Surgery 
IND # 
131596 
Protocol Number: 
DX216 
 
 
Study Drugs: 
1. OCS-01 (Dexamethasone Cyclodextrin Nanoparticle 
Ophthalmic Suspension 1.5%) 
2. Placebo (vehicle for OCS-01) 
 
 
Study Phase: 
2 
 
 
Objective(s): 
The primary objective of this study is to evaluate the efficacy and 
safety of OCS-01 once a day (QD) and twice a day (BID) compared 
to placebo (vehicle) BID in the treatment of inflammation and pain 
following cataract surgery. 
The secondary objective of this study is to evaluate the optimal 
dosing frequency of OCS-01 (QD versus BID) in the treatment of 
inflammation and pain following cataract surgery. 
Overall Study Design: 
 
Structure: 
Multi-center, randomized, double-masked, placebo (vehicle)-
controlled study 
 
 
Duration: 
Approximately 20-52 days 
 
 
Controls: 
Placebo (vehicle for OCS-01) 
 
 
Dosage/Dose Regimen/ 
Instillation/ 
Application/Use: 
Subjects will be randomized to one of the following treatment 
groups in a 1:1:1 fashion: 
1. OCS-01 QD + Placebo (vehicle) QD 
2. OCS-01 BID 
3. Placebo (vehicle) BID 
Each subject will receive a master kit containing an AM dosing box 
and a PM dosing box. Each dosing box will contain 2 aluminum 
pouches with 10 single-use vials each. The master kit’s contents 
will be as follows for subjects randomized to each of the respective 
treatment arms:  
1. OCS-01 QD + Placebo (vehicle) QD  
2. OCS-01 BID  
3. Placebo (vehicle) BID  


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For masking purposes, each dosing box and the pouches within it 
will be labeled either “AM” or “PM.” Dosing boxes and pouches 
will be labeled this way regardless of whether the products within 
the 2 boxes are the same (i.e. OCS-01 BID and placebo treatment 
arms) or different (i.e. OCS-01 QD). All qualified subjects will dose 
for 14 days beginning 1 day post-surgery in the operated eye. Doses 
should be instilled at approximately 8 AM (± 2 hours) and 8 PM 
(± 2 hours), as close to 12 hours apart as possible. 
 
 
Summary of Visit 
Schedule: 
Visit 1 (Day -28 to Day -1 [prior to surgery]): Screening, baseline 
evaluations   
Visit 2 (Day 1 [18 to 30 hours post-surgery]): Review of inclusion 
and exclusion criteria, randomization, and dosing and dispensation 
of study medication 
Visit 3 (Day 2) Pain assessments (telephone call) 
Visit 4 (Day 4 ± 1): Inflammation, pain, and safety assessments  
Visit 5 (Day 8 ± 1): Inflammation, pain, and safety assessments   
Visit 6 (Day 15 ± 2): Inflammation, pain, and safety assessments  
Visit 7 (Day 22 ± 2): Inflammation, pain, and safety assessments, 
and exit visit 
 
 
Measures Taken to 
Reduce Bias: 
Randomization will be used to avoid bias in the assignment of 
subjects to treatment, to increase the likelihood that known and 
unknown subject attributes (e.g. demographics and baseline 
characteristics) are evenly balanced across treatment groups, and to 
enhance the validity of statistical comparisons across treatment 
groups. Double-masked treatment will be used to reduce the 
potential of bias during data collection and the evaluation of clinical 
endpoints. 
Study Population Characteristics: 
 
Number of Subjects: 
Approximately, 150 subjects will be randomized into the following 
groups: 
OCS-01 QD: 50 subjects 
OCS-01 BID: 50 subjects 
Placebo (vehicle) BID: 50 subjects 
 
 


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Condition/ Disease: 
Inflammation and pain following cataract surgery 
Inclusion Criteria: 
Each subject must:  
1. Provide written informed consent, approved by the 
appropriate ethics committee;  
2. Be able to comply with the study requirements and visit 
schedule; 
3. Be at least 18 years of age of either sex or any race; 
4. Be planning to undergo unilateral cataract extraction via 
phacoemulsification and posterior chamber intraocular lens 
(PCIOL) implantation in the study eye; 
5. Have an anterior chamber cell score ≥ 2 at Visit 2 (Day 1 
[18 to 30 hours post-uncomplicated cataract surgery with no 
vitreous loss]); 
6. Have a pin-hole visual acuity (VA) without any other 
correction > 20 letters (approximately 20/400) in the 
operative eye and > 35 letters (approximately 20/200) in the 
fellow eye as measured using an Early Treatment for 
Diabetic Retinopathy Study (ETDRS) chart at Visit 1 (Day -
1 to Day -28 [prior to surgery]);  
7. Have a negative urine pregnancy test at Visit 1 (Day -1 to 
Day -28 [prior to surgery]), if female of childbearing 
potential (i.e. those who have experienced menarche, who 
are not surgically sterilized [bilateral tubal ligation, 
hysterectomy, or bilateral oophorectomy] or 
post-menopausal [12 months after last menses]) and must 
use acceptable effective contraceptive measure throughout 
the study period. Acceptable effective contraceptive 
measure is defined as hormonal – oral, implantable, 
injectable, or transdermal contraceptives; mechanical – 
spermicide in conjunction with a barrier such as condom or 
diaphragm; intrauterine device (IUD); or surgical 
sterilization of partner. For non-sexually active females, 
abstinence may be regarded as an adequate method of birth 
control.  
Exclusion Criteria: 
Each subject must not: 
1. Have a known sensitivity or allergy to dexamethasone, 
corticosteroids, or any of the study medication’s 
components; 
2. Be monocular; 
3. Have any intraocular inflammation (e.g. white blood cells or 
flare) present in either eye at the Visit 1 (Day -1 to Day -28 
[prior to surgery]) slit lamp examination; 
4. Have a score > 0 on the Ocular Pain Assessment at Visit 1 
(Day -1 to Day -28 [prior to surgery]) in the study eye;  


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5. Use anti-inflammatory agents, analgesics/pain relievers 
(including opioids, narcotics, and other pain medications), 
or immunomodulating agents, systemically or in either eye, 
and/or currently using or have any historic use of 
medications for benign prostatic hyperplasia (BPH) from the 
washout period through the duration of the study. Washout 
periods for medications prior to the day of cataract surgery 
are as follows: 
a. Topical ocular steroids: 14 days; 
b. Periocular injection of any corticosteroid solution: 
28 days; 
c. Intraocular treatment with a corticosteroid including 
dexamethasone drug delivery systems: 56 days after 
implantation; fluocinolone acetonide drug delivery 
systems: 48 months after implantation; any other 
intravitreal injection: 95 days after injection; 
Note: While it is expected that subjects requiring an 
intraocular treatment with a corticosteroid will be excluded 
due to underlying exclusionary conditions, subjects who 
otherwise meet all eligibility criteria will be required to 
follow the above-mentioned washout intervals. 
d. Any systemic treatment with a corticosteroid 
including oral: 14 days; systemic or parenteral 
sustained/extended release: 180 days; 
Note: Inhaled, intranasal, and topical dermatologic steroids 
(except on the face and periocular region) are allowed. 
Topical dermatologic steroids on the face and periocular 
region require a 7 day washout. 
e. Topical ocular non-steroidal anti-inflammatory drugs 
(NSAIDs): 7 days; 
f. Systemic analgesics/pain relievers (e.g. gabapentin, 
pregabalin, and opioids): 14 days; 
Note: Use of an opioid during cataract surgery is allowed; 
g. Systemic acetaminophen, NSAIDs, acetylsalicylic 
acid, or other anti-inflammatory agents: 7 days; 
Note: Use of up to 81 mg of acetylsalicylic acid dosed once 
daily is allowed if dosage has been stable for at least 
30 days prior to surgery and will remain stable for the 
duration of the study. 
h. Medications for BPH (e.g. alpha adrenergic blocking 
agents including tamsulosin, silodosin, alfuzosin, 
and finasteride): all current or previous use of BPH 
medications excludes participation in this study.  ; 
i. Cyclosporine: 56 days or immunomodulating or 
immunosuppressive agents (e.g. calcineurin 
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of rapamycin (mTOR) inhibitors, etc.): 2 months  
j. Mast cell stabilizers or antihistamines (e.g. β2-
adrenergic agonists. cromoglicic acid, ketotifen, 
brompheniramine, cetirizine, diphenhydramine): 
7 days; 
6. Require the use of a contact lens or a collagen shield within 
72 hours prior to Visit 2 (Day 1 [18 to 30 hours post-
surgery]) or for the remainder of the study period in either 
eye;  
7. Require the use of non-diagnostic topical ophthalmic 
medications in either eye for the duration of the study with 
the exception of the following, which are allowed: 
mydriatics, anesthetics, antiseptics, balanced salt solution, 
viscoelastics, prophylactic antibiotics, non-prostaglandin 
analog intraocular pressure (IOP)-lowering agents, lid 
scrubs for mild blepharitis, or artificial tears for the 
management of dry eye (allowed topical medication should 
not be instilled at the same time as the study drug.  Study 
medication should be instilled at least 30 minutes after any 
prior allowed topical medication.  In addition, any other 
allowed topical medication should not be instilled within 2 
hours following instillation of study medication);  
8. Have an IOP ≤ 5 mmHg or ≥ 22 mmHg in either eye at Visit 
1 (Day -1 to Day -28 [prior to surgery]). Subjects taking 
IOP-lowering medication must not be on more than 1 IOP-
lowering medication. Prostaglandin analogs are not allowed 
within 4 weeks of Visit 2 (Day 1 [18 to 30 hours post-
surgery]). 
Note: Combination IOP agents count as 2 medications. 
9. Currently have or have a history of herpes keratitis in the 
study eye; 
10. Have corneal abrasions or ulcers in the study eye (not 
including the surgical clear corneal wound from cataract 
surgery); 
11. Have evidence of acute external ocular infections (bacterial, 
viral, and/or fungal such as vaccinia, varicella, and other 
viral diseases of the cornea and conjunctiva), corneal 
endothelial dystrophies, intraocular infections, dysthyroid 
ophthalmopathy, active chalazion, or uncontrolled 
blepharitis in the study eye; 
12. Have uncontrolled and clinically significant dry eye 
syndrome in the study eye (use of artificial tears is allowed); 
13. Have active or a history of chronic or recurrent 
inflammatory eye disease (e.g. iritis, scleritis, uveitis, 
iridocyclitis, or rubeosis iritis) in either the fellow eye or the 
study eye; 


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14. Have cystoid macular edema, diabetic retinopathy, or 
diabetic macular edema; compromised macular function; 
significant macular diseases; or a history of macular edema 
in the study eye; 
15. Have previous ocular trauma with visible scarring or any 
deformities due to the trauma in the study eye that in the 
opinion of the Investigator may affect the pharmacokinetics 
of the study medication, intraocular inflammation, or the 
normal healing process; 
16. Have the potential for ocular hemorrhage in the study eye 
that may interfere with evaluation of post-surgery 
inflammation; 
17. Have a planned use of femtosecond laser or any other 
ophthalmic surgical procedure (e.g. MIGS [minimally 
invasive glaucoma surgery], vitrectomy, relaxing incisions, 
iridectomy, conjunctival excisions, use of iris hooks or other 
iris dilators, etc.) in addition to the cataract extraction 
procedure via phacoemulsification and PCIOL implantation 
in the study eye; 
18. Have a planned use of anterior capsule staining for 
capsulorhexis (i.e. trypan blue) during cataract surgery; 
19. Have had corneal or retinal surgery (laser or incisional) in 
the study eye within 6 months of Visit 1 (Day -1 to Day -28 
[prior to surgery]), or be planning to have laser or incisional 
surgery during the study period in the study eye (other than 
cataract surgery); 
20. Have surgery planned or scheduled for the contralateral eye 
during the 3-week study period; 
21. Have an immunosuppressive or an autoimmune disease that 
in the opinion of the Investigator could affect intraocular 
inflammation or the normal healing process of the eye; 
22. Have active or chronic/recurrent ocular or systemic disease 
that is uncontrolled and will likely affect wound healing; 
23. Currently have a suspected or known malignancy or be 
currently receiving anti-neoplastic therapy; 
24. Have previously been enrolled in this clinical study, have 
planned to participate in another clinical trial during the 
follow-up period that could confound the treatment or 
outcomes of this investigation, or be currently in the follow-
up period of a previous clinical trial;  
25. Be enrolled in the study if the Investigator determines that 
the subject should not be included for reasons not already 
specified (e.g. systemic or other ocular disease/abnormality), 
if the health of the subject or the validity of the study 
outcomes may be compromised by the subject’s enrollment; 
26. Be a female who is currently pregnant, planning a 


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pregnancy, lactating, not using a medically acceptable form 
of birth control throughout the study duration, or have a 
positive urine pregnancy test at Visit 1 (Day -1 to Day -28 
[prior to surgery]). 
Evaluation Criteria: 
 
Efficacy Measures: 
Hierarchical Primary Efficacy Measures:  
1. Absence of anterior chamber cells (i.e. score of ‘0’) at 
Visit 6 (Day 15);  
2. Absence of pain (i.e. score of ‘0’) at Visit 4 (Day 4).  
Secondary Efficacy Measures:  
• Absence of anterior chamber cells at Visits 4, 5, and 7 
(Days 4, 8, and 22);  
• Absence of pain at Visits 3, 5, 6, and 7 (Days 2, 8, 15, and 
22);  
• Absence of flare at Visits 4, 5, 6, and 7 (Days 4, 8, 15, and 
22); 
• Absence of both anterior chamber cells and flare at Visits 4, 
5, 6, and 7 (Days 4, 8, 15, and 22);  
• Use of rescue medication on or prior to each visit and 
overall.  
Safety Measures: 
• Change from baseline of pin-hole VA (without any other 
correction) as measured on the ETDRS chart;  
• Change from baseline of IOP; 
• Adverse event (AE) rates. 
Rescue Criteria: 
• Grade ≥ 2 anterior chamber cells at Visit 5 (Day 8) (or after) 
with topical ocular steroids and/or NSAIDs; 
• Severe ocular pain at Visit 4 (Day 4) (or after) with oral 
acetaminophen. 
General Statistical Methods and Types of Analyses: 
Full Analysis Set: The full analysis set (FAS) will consist of all randomized subjects, analyzing 
subjects under the treatment to which they were randomized. 
Per Protocol Population: The per-protocol (PP) population is a subset of the FAS and includes 
subjects who remain in the study through Visit 6 (Day 15) (or who discontinue due to lack of 
efficacy or receive rescue medication prior to Visit 6 [Day 15]) with no major protocol violations 
that would affect the assessment of the primary efficacy endpoints of the study, analyzing 
subjects under the treatment received. Major protocol violations related to study inclusion or 
exclusion criteria, conduct of the trial, subject management, or subject assessment will be 
identified prior to unmasking treatment. 
Safety Population: The safety population includes all randomized subjects who receive at least 
one dose of study medication. The safety population will be analyzed as treated and will be used 
for the safety analyses. No data will be excluded for any reason. 


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Hypotheses 
Primary Endpoint: 
H011: The difference, between study eyes treated with OCS-01 BID and study eyes treated with 
placebo (vehicle), in the proportion of study eyes with absence of anterior chamber cells (score 
of ‘0’) at Visit 6 (Day 15) = 0. 
H111: The difference, between study eyes treated with OCS-01 BID and study eyes treated with 
placebo (vehicle), in the proportion of study eyes with absence of anterior chamber cells (score 
of ‘0’) at Visit 6 (Day 15) ≠ 0, with superiority claimed if the difference is greater than 0 (OCS-
01 BID – placebo [vehicle]). 
H012: The difference, between study eyes treated with OCS-01 QD and study eyes treated with 
placebo (vehicle), in the proportion of study eyes with absence of anterior chamber cells (score 
of ‘0’) at Visit 6 (Day 15) = 0. 
H112: The difference, between study eyes treated with OCS-01 QD and study eyes treated with 
placebo (vehicle), in the proportion of study eyes with absence of anterior chamber cells (score 
of ‘0’) at Visit 6 (Day 15) ≠ 0, with superiority claimed if the difference is greater than 0 (OCS-
01 QD – placebo [vehicle]). 
Hierarchical Primary Endpoint:  
H021: The difference, between study eyes treated with OCS-01 BID and study eyes treated with 
placebo (vehicle), in the proportion of study eyes with absence of pain (score of ‘0’) at Visit 4 
(Day 4) = 0. 
H121: The difference, between study eyes treated with OCS-01 BID and study eyes treated with 
placebo (vehicle), in the proportion of study eyes with absence of pain (score of ‘0’) at Visit 4 
(Day 4) ≠ 0, with superiority claimed if the difference is greater than 0 (OCS-01 BID – placebo 
[vehicle]). 
H022: The difference, between study eyes treated with OCS-01 QD and study eyes treated with 
vehicle, in the proportion of study eyes with absence of pain (score of ‘0’) at Visit 4 (Day 4) = 0. 
H122: The difference, between study eyes treated with OCS-01 QD and study eyes treated with 
vehicle, in the proportion of study eyes with absence of pain (score of ‘0’) at Visit 4 (Day 4) ≠ 0, 
with superiority claimed if the difference is greater than 0 (OCS-01 QD – placebo [vehicle]). 
Multiple comparison adjustments for testing OCS-01 BID and OCS-01 QD versus vehicle in the 
absence of anterior chamber cells will not be made (i.e. the testing of H011 versus H111 and H012 
versus H112 will both be completed at a 2-sided alpha = 0.10). A hierarchical testing strategy will 
be employed for testing absence of pain; statistical inference will only be made on the absence of 
pain endpoint if the corresponding OCS-01 dose (BID or QD) demonstrated statistical 
superiority over placebo (vehicle) in the absence of anterior chamber cells. 
Sample Size Determination 
With a total of 150 subjects (50 subjects per treatment group: OCS-01 BID, OCS-01 QD, and 
placebo [vehicle] in the FAS [i.e. 1:1:1 randomization]), the study has 85% power to detect a 
statistically significant treatment difference between OCS-01 BID and placebo and between 
OCS-01 QD and placebo for the proportion of subjects with absence of cells on post-operative 
Visit 6 (Day 15), assuming a 2-sided alpha level of 0.10, and the proportion of subjects with 
absence of cells is 0.45 (active) and 0.20 (placebo [vehicle]).  
Additionally, with this sample size, the study has 83% power to detect a statistically significant 


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treatment difference between OCS-01 (BID or QD) and placebo for the proportion of subjects 
with absence of ocular pain on post-operative Visit 4 (Day 4), assuming a 2-sided alpha level of 
0.10 and the proportion of subjects with absence of ocular pain is 0.50 (active) and 0.25 (placebo 
[vehicle]). 
General Considerations 
Summaries for continuous variables will include the sample size, mean, standard deviation, 
median, minimum, and maximum. Summaries for discrete variables will include frequencies and 
percentages. Differences between treatment groups will be calculated as OCS-01 – placebo 
(vehicle), and change from baseline will be calculated as follow-up visit – baseline. Baseline 
values will be defined as the last non-missing measure prior to initiation of study treatment. All 
efficacy analyses will use a 2-sided alpha = 0.10 test unless otherwise stated and corresponding 
2-sided 90% and 95% confidence intervals (CIs) will be presented as applicable. 
The unit of analysis in this study will be the study eye for all ocular efficacy and safety 
summaries and the subject for all non-ocular summaries. 
Handling of Missing Data 
The primary analyses of all efficacy data will use last observation carried forward (LOCF) to 
impute missing data; data for visits after a subject is discontinued for lack of efficacy or receives 
rescue medication will be imputed as failures for success/failure endpoints and will be imputed 
using LOCF for other endpoints. To check robustness of results, sensitivity analyses of the 
primary efficacy endpoints will include analyses of observed data only, imputing data from 
subject visits after discontinuation for lack of efficacy or receipt of rescue medication as failures. 
Tipping point analysis and multiple imputation methods using monotone methodology will also 
be used to impute missing data as additional sensitivity analyses. PP analyses will use observed 
data only, with the exception of subjects who have missing data due to discontinuation for lack 
of efficacy or for subjects who receive rescue medication; for these subjects, missing data after 
discontinuation or data after receiving rescue medication will be imputed as failures for 
success/failure endpoints and will be imputed using LOCF for other endpoints.  
Demographics 
Subject demographics comprising age, gender, race, and ethnicity will be presented using 
discrete or continuous summary statistics as appropriate. 
Primary Efficacy Analysis 
The hierarchical primary efficacy variables, the absence of anterior chamber cells at Visit 6 
(Day 15) and the absence of pain at Visit 4 (Day 4), will be summarized using discrete summary 
statistics, including 2-sided 95% CIs for each treatment group.   
For each OCS-01 dose (BID and QD), the primary efficacy analyses will first test the difference 
in proportion of study eyes with absence of anterior chamber cells (score of ‘0’) between OCS-
01 and placebo (vehicle) at Visit 6 (Day 15) using the Pearson chi-squared statistic (Fisher’s 
exact test will be used if any expected cell count is less than 5). 
If the proportion of study eyes with absence of anterior chamber cells (score of ‘0’) is 
statistically significantly higher for OCS-01 versus placebo (vehicle) at a 2-sided alpha = 0.10 at 
Visit 6 (Day 15) for either dose of OCS-01 (BID or QD), then the study will be considered a 
success and the hierarchical hypothesis testing will compare the proportion of study eyes with 
absence of pain (score of ‘0’) at Visit 4 (Day 4) between the corresponding OCS-01 dose and 
placebo (vehicle) using the Pearson chi-squared statistic at a 2-sided alpha=0.10 (Fisher’s exact 


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test will be used if any expected cell count is less than 5).   
Analyses will be completed primarily on the FAS and secondarily on the PP population. 
Secondary Efficacy Analysis:  
The secondary efficacy variables, the differences in proportions of study eyes with absence of 
anterior chamber cells (Visits 4, 5, and 7 [Days 4, 8, and 22]), study eyes with absence of pain 
(Visits 4, 5, and 6 [Days 8, 15, and 22]), study eyes with absence of flare (Visits 4, 5, 6, and 7 
[Days 4, 8, 15, and 22]), and study eyes with absence of both anterior chamber cells and anterior 
chamber flare (Visits 4, 5, 6, and 7 [Days 4, 8, 15, and 22]) will be summarized and analyzed 
similarly to the primary efficacy summaries and analyses. 
Use of rescue medication on or prior to each visit will be summarized by visit and overall using 
discrete summary statistics. 
Analyses will be completed primarily on the FAS and secondarily on the PP population. 
Safety Analysis: 
The primary safety analyses will summarize VA, IOP, and AEs as described below. 
VA data will be summarized at each visit, using discrete summaries including mean change from 
baseline in the number of letters and the proportion of subjects with worsening from previous 
visit of ≥ 2 lines using the ETDRS scale. 
IOP will be summarized at each visit, using continuous and discrete summary statistics, 
including mean change from baseline and the proportion of study eyes with an increase from 
baseline in IOP of 10 mmHg or more and the proportion of study eyes with IOP of 30 mmHg or 
more. 
Ocular treatment-emergent AEs (TEAEs) in the study eye for all treated subjects will be 
summarized using discrete variables at the subject and event level by system organ class (SOC) 
and preferred term (PT) for each treatment group. A TEAE will be defined as any AE that occurs 
after the treatment is initiated. An additional analysis will examine ocular AEs for the non-study 
eye. Non-ocular TEAEs will be summarized using discrete summaries at the subject and event 
level by SOC and PT for each treatment group. Treatment related ocular and non-ocular TEAEs 
will be summarized similarly. Ocular and non-ocular TEAEs will also be summarized by 
severity. 
Slit lamp biomicroscopy and dilated indirect ophthalmoscopy measures will be summarized at 
each visit including shift from baseline (as appropriate) using discrete summary statistics  


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2 TABLE OF CONTENTS 
1 
SYNOPSIS .................................................................................................................3 
2 
TABLE OF CONTENTS .......................................................................................13 
List of Abbreviations ..............................................................................................16 
3 
INTRODUCTION...................................................................................................17 
3.1 
Background ...................................................................................................17 
3.2 
Study Rationale .............................................................................................18 
3.3 
Dosage ............................................................................................................18 
3.4 
Placebo Justification .....................................................................................19 
3.4.1 Rationale ........................................................................................................19 
3.4.2 Measures To Ensure Safe Participation in the Study ...............................20 
4 
STUDY OBJECTIVES AND HYPOTHESIS ......................................................21 
4.1 
Study Objective .............................................................................................21 
4.2 
Study Hypothesis ..........................................................................................21 
5 
OVERALL STUDY DESIGN ................................................................................21 
6 
STUDY POPULATION .........................................................................................21 
6.1 
Number of Subjects (approximate) .............................................................21 
6.2 
Study Population Characteristics ...............................................................21 
6.3 
Inclusion Criteria .........................................................................................22 
6.4 
Exclusion Criteria .........................................................................................22 
6.5 
Rescue Criteria .............................................................................................25 
6.6 
Withdrawal Criteria (if applicable) ............................................................25 
7 
STUDY PARAMETERS ........................................................................................26 
7.1 
Efficacy Measures .........................................................................................26 
7.1.1   Primary Efficacy Measure ...................................................................26 
7.1.2   Secondary Efficacy Measure ...............................................................26 
7.1.3   Primary Efficacy Analyses ..................................................................26 
7.1.4   Secondary Efficacy Analyses ..............................................................26 
7.2 
Safety Measures ............................................................................................27 
8 
STUDY MATERIALS ............................................................................................27 
8.1 
Study Treatment(s) .......................................................................................27 
8.1.1   Study treatment(s) ...............................................................................27 
8.1.2   Instructions for Use and Administration .............................................27 
9 
STUDY METHODS AND PROCEDURES .........................................................28 
9.1 
Subject Entry Procedures ............................................................................28 
9.1.1   Overview .............................................................................................28 
9.1.2   Informed Consent ................................................................................28 
9.1.3   Washout Intervals ................................................................................28 
9.1.4   Procedures for Final Study Entry ........................................................28 
9.1.5   Methods for Assignment to Treatment Groups: ..................................28 
9.2 
Concurrent Therapies ..................................................................................29 
9.2.1   Prohibited Medications/Treatments.....................................................29 
9.2.2   Rescue Medications .............................................................................30 
9.2.3   Special Diet or Activities .....................................................................30 


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9.3 
Examination Procedures ..............................................................................30 
9.4 
Schedule of Visits, Measurements and Dosing ..........................................33 
9.4.1   Scheduled Visits ..................................................................................33 
9.4.2   Unscheduled Visits ..............................................................................33 
9.5 
Compliance with Protocol ............................................................................33 
9.6 
Subject Disposition .......................................................................................33 
9.6.1   Completed Subjects .............................................................................33 
9.6.2   Discontinued subjects ..........................................................................33 
9.7 
Study Termination .......................................................................................34 
9.8 
Study Duration .............................................................................................34 
9.9 
Monitoring and Quality Assurance ............................................................34 
10 
ADVERSE EVENTS ..............................................................................................34 
10.1 Adverse Event ...............................................................................................34 
10.1.1   Severity ..............................................................................................35 
10.1.2   Relationship to Study Drug ...............................................................35 
10.1.3   Expectedness .....................................................................................35 
10.2 Serious Adverse Events ................................................................................36 
10.3 Procedures for Reporting Adverse Events .................................................37 
10.3.1   Reporting a Suspected Unexpected Adverse Reaction .....................37 
10.3.2   Reporting a Serious Adverse Event ...................................................37 
10.4 Procedures for Unmasking of Study Drug .................................................37 
10.5 Type and Duration of the Follow-up of Subjects after Adverse Events ..37 
11 
STATISTICAL METHODS ..................................................................................38 
11.1 Statistical Hypotheses ...................................................................................38 
11.2 Analysis Populations ....................................................................................39 
11.3 Sample Size Determination ..........................................................................39 
11.4 Interim Analysis ...........................................................................................39 
11.5 Efficacy Analysis ...........................................................................................40 
11.5.1   General Statistical Considerations .....................................................40 
11.5.2   Primary Efficacy Analysis .................................................................40 
11.5.3   Secondary Efficacy Analyses ............................................................40 
11.6 Safety Analysis ..............................................................................................41 
11.7 Handling of Missing Data ............................................................................41 
11.8 Demographics and Medical History ...........................................................42 
12 
COMPLIANCE WITH GOOD CLINICAL PRACTICES, ETHICAL 
CONSIDERATIONS, AND ADMINISTRATIVE ISSUES ...............................42 
12.1 Protection of Human Subjects.....................................................................42 
12.1.1 Subject Informed Consent ...........................................................................42 
12.1.2   Institutional Review Board Approval ................................................42 
12.1.3   Ethical Conduct of the Study .............................................................43 
12.2 Subject Confidentiality ................................................................................43 
12.3 Documentation ..............................................................................................43 
12.3.1   Retention of Documentation..............................................................43 
12.4 Labeling, Packaging, Storage, Accountability, and Return or Disposal of Study 
Drug ...............................................................................................................44 
12.4.1   Labeling/Packaging ...........................................................................44 


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12.4.2   Storage of Study Drug .......................................................................44 
12.4.3   Accountability of Study Drug ...........................................................44 
12.4.4   Return or Disposal of Study Drug .....................................................44 
12.5 Recording of Data on Source Documents and Case Report Forms .........44 
12.6 Handling of Biological Specimens ...............................................................45 
12.7 Publications ...................................................................................................45 
REFERENCES .................................................................................................................46 
Appendix 1:  Schedule of Visits and Measurements .....................................................48 
Appendix 2:  Examination Procedures, Tests, Equipment, and Techniques .............49 
Appendix 3: Protocol Amendment Summary ...............................................................58 
Appendix 4:  Ora Approvals ...........................................................................................64 
Appendix 5:  Investigator’s Signature ...........................................................................65 
 
 
 


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List of Abbreviations 
γCD 
γ-cyclodextrin 
AE 
adverse event 
BID 
twice a day 
BPH 
benign prostatic hyperplasia 
CI 
confidence interval 
CD 
cyclodextrin 
CFR 
Code of Federal Regulations 
eCRF 
electronic case report form 
EMA 
European Medicines Agency 
ETDRS 
Early Treatment of Diabetic Retinopathy Study 
FAS 
full analysis set 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation 
IOP 
intraocular pressure 
IRB 
institutional review board 
IUD 
intrauterine device 
LOCF 
last observation carried forward 
MIGS 
minimally invasive glaucoma surgery 
mTOR 
mammalian target of rapamycin 
NSAID 
non-steroidal anti-inflammatory drug 
PCIOL 
Posterior chamber intraocular lens 
PI 
Principal Investigator 
PP 
per protocol 
PT 
preferred term 
QD 
once a day 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SOC  
system organ class 
TEAE 
treatment-emergent adverse events 
VA 
visual acuity 
 
 


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3 INTRODUCTION 
3.1 Background 
An estimated 95 million people worldwide are affected by cataracts, with cataract surgery being 
the most commonly performed surgical procedure in many countries (Liu, Wilkins et al. 2017). 
The current preferred treatments for ocular inflammation include the use of topical 
corticosteroids and/or non-steroidal anti-inflammatory drugs (NSAIDs), which may be 
contraindicated in some populations. Corticosteroids, which are considered the mainstay 
treatment for ocular inflammation, can be associated with adverse events (AEs), especially when 
frequent or prolonged dosing is needed, such as in patients where post-operative inflammation is 
severe and/or prolonged (Weber, Kodjikian et al. 2013). 
In general, drug penetration from the ocular surface via topical administration into the eye 
encounters multiple barriers. This results in a bioavailability inside the eye that is generally well 
below 5%. In spite of this very low topical bioavailability, aqueous eye drops are the patient-
preferred dosage form, especially in treatment of diseases of the anterior eye tissues, accounting 
for over 90% of the market (Loftsson and Stefansson 2017). 
Dexamethasone is a corticosteroid that has been used in the form of eye drops (Maxidex®, 
Alcon, United States of America) to treat inflammation caused by surgery, infections, or injury 
(Alcon Laboratories 2002). Dexamethasone has limited solubility in water and does not readily 
permeate from the eye’s aqueous exterior into the eye. Studies have shown that cyclodextrins 
(CDs) are able to enhance topical bioavailability of dexamethasone from aqueous eye drops 
(Usayapant, Karara et al. 1991, Kristinsson, Fridriksdottir et al. 1996, Sigurdsson, 
Konraethsdottir et al. 2007, Loftsson and Stefansson 2017). CDs have also been incorporated 
into other Food and Drug Administration (FDA) approved ophthalmic drops  to increase drug 
solubility (Alcon Laboratories 2000). Oculis is developing a novel drug delivery platform 
composed of the active ingredient, dexamethasone, and CD nanoparticles (OCS-01, previously 
called DexNP), which aid in delivery of the active pharmaceutical ingredient from the ocular 
surface to both the anterior and posterior segments of the eye. CD-based dexamethasone eye 
drop solutions have been tested in human patients and show excellent penetration into the 
anterior segment of the eye (Kristinsson, Fridriksdottir et al. 1996, Saari, Nelimarkka et al. 2006, 
Tanito, Hara et al. 2011). Some of the earliest formulations of dexamethasone CD solutions (0.32 
or 0.67% dexamethasone, 2-hydroxypropyl-β-cyclodextrin), were tested in a clinical trial 
conducted in Iceland 20 years ago (Kristinsson, Fridriksdottir et al. 1996). In 125 patients 
undergoing cataract surgery, concentrations of dexamethasone were significantly higher after 
application of dexamethasone CD suspension compared to Maxidex® (P < 0.001), indicating 
that the CD-based drug delivery system enhances both the solubility and permeability of 
dexamethasone to the anterior segment of the human eye. Notably, no toxic effects were 
observed with the use of dexamethasone CD suspension.  
In a more recent study (Johannesson, Moya-Ortega et al. 2014), levels of dexamethasone were 
assessed in the tear fluid of healthy subjects treated with a topical application of 1.5% DexNP or 
Maxidex®. Six (6) subjects received DexNP in one eye and Maxidex® in the contralateral eye. 
Results reveal that treatment with DexNP results in a 19-fold higher concentration of 
dexamethasone compared to treatment with Maxidex®. Notably, 4 hours post-instillation, the 


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concentration of dexamethasone from DexNP treatment was still 10-times higher than what was 
observed with Maxidex® treatment. These results demonstrate that dexamethasone, complexed 
with CD nanoparticles, elicits a higher concentration and longer duration of action in the tear 
fluid than the currently available product, Maxidex®. Importantly, DexNP was well tolerated by 
the subjects and no serious adverse events (SAEs) were observed.  
A study conducted by Saari et al. (Saari, Nelimarkka et al. 2006) evaluated the efficacy of an eye 
drop containing 0.7% dexamethasone-CD suspension, applied once daily, compared to a 0.1% 
dexamethasone sodium phosphate eye drops, applied three times daily for the treatment of post-
operative inflammation after cataract surgery. The dexamethasone-CD suspension was shown to 
be safe and more effective in treating post-operative inflammation, after once daily dosing, than 
0.1% dexamethasone sodium phosphate eye drops applied three times daily.  
In the human studies with DexNP to date, DexNP was well tolerated and the only AE reported 
has been a modest rise in intraocular pressure (IOP), a known side effect of dexamethasone use, 
which subsided following discontinuation of DexNP in all cases (Kristinsson, Fridriksdottir et al. 
1996) (Johannesson, Moya-Ortega et al. 2014) (Saari, Nelimarkka et al. 2006) (Tanito, Hara et 
al. 2011) (Ohira, Hara et al. 2015) (Krag and Hessellund 2014) (Shulman, Johannesson et al. 
2015). 
Building on the enhanced ocular penetration of DexNP, as well as its favorable efficacy results 
and safety profile, Oculis has developed an updated formulation, OCS-01, consisting of water 
soluble 1.5% Dexamethasone-γCD complexes to treat post-surgical inflammation. 
3.2 Study Rationale 
The trial outlined here is a randomized, double-masked, placebo (vehicle)-controlled study 
evaluating the efficacy and safety of two doses of OCS-01 compared to vehicle in the treatment 
of inflammation and pain following cataract surgery. The primary objective is to evaluate the 
efficacy and safety of OCS-01 compared to placebo and the secondary objective is to evaluate 
the optimal dosing frequency (once a day [QD] or twice a day [BID]).  
3.3 Dosage  
OCS-01 is a 1.5% w/v suspension that is equivalent to 1.5 g dexamethasone per 100 mL 
suspension. A single drop from an eye drop bottle is approximately 30 µL, and, therefore, a 
single drop of OCS-01 would contain approximately 0.45 mg of dexamethasone. Subjects in this 
study will receive either QD or BID dosing and, therefore, may receive 0.45 mg or 0.90 mg of 
dexamethasone per day. 
As a comparison, Maxidex 0.1% dexamethasone suspension is an FDA approved ophthalmic 
suspension for the treatment of steroid responsive inflammatory conditions of the palpebral and 
bulbar conjunctiva, cornea, and anterior segment of the globe, including inflammation post-
cataract surgery. In severe disease, 1-2 drops may be dosed hourly. A 0.1% suspension would 
contain 0.03 mg of dexamethasone per drop. If the maximum daily dose is applied, this would 
equate to 2 drops per hour, up to 48 drops. This could result in a maximum daily dose of 1.44 
mg. 


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Further, the 0.45 mg of dexamethasone per 30 µL drop for OCS-01 is also assuming that the 
entire drop is absorbed into the eye. The maximum capacity of the conjunctival sac is up to 
30 µL and a drop of larger volume applied to a human eye will have its excess overflowed. Thus, 
a maximum 0.45 mg of dexamethasone per drop will reach the eye. 
The dexamethasone formulation to be tested here contains natural γ-cyclodextrin (γCD). γCD 
has been evaluated previously in other dexamethasone based eye drops (DexNP) in several 
indications in clinical trials (Tanito, Hara et al. 2011, Johannesson, Hallberg et al. 2014, Ohira, 
Hara et al. 2015, Shulman, Johannesson et al. 2015). The eye drops were well tolerated and 
displayed no signs of irritation or redness. 
3.4 Placebo Justification 
This justification is based on Oculis’ interpretation and position with regard to the International 
Conference on Harmonisation (ICH) Topic E10 guideline on the “Choice of control group in 
clinical trials” (CPMP/ICH/364/96).  
3.4.1 Rationale 
The inclusion of a placebo group is considered essential to the design of the DX216 study as: 
• It provides the most rigorous evaluation of the efficacy and safety of OCS-01. 
• It is required by the FDA as a negative control in post-cataract inflammation studies. 
• It will allow indirect comparisons with Loteprednol and other studies that were recently 
conducted with a placebo design (Rajpal, Fong et al. 2013, Fong, Silverstein et al. 2018).  
The sponsor believes that placebo can be safely and ethically administered in this study with 
close monitoring and rescue criteria based on the following rationale: 
Guideline 5 of the International Ethical Guidelines for Health-related Research Involving 
Humans specifies that  a placebo-controlled trial is acceptable only if “delaying or 
withholding the established effective intervention will result in no more than a minor 
increase above minimal risk to the participant and risks are minimized, including through the 
use of effective mitigation procedures” (CIOMS 2016). For this indication, pain and 
inflammation following cataract surgery, delaying or withholding intervention will not pose 
substantial risk to the subject. Further, there are rescue criteria defined in the protocol if the 
subject is displaying Grade 2 or greater anterior cells or experiencing severe ocular pain. 
Protocol Section 6.5: Rescue Criteria: 
• Grade ≥ 2 anterior chamber cells (i.e. ≥ 11 cells on the Anterior Chamber Cells grading 
scale [see Appendix 2:  Examination Procedures, Tests, Equipment, and Techniques]) at 
Visit 5 (Day 8 ± 1) (or after) may be treated with topical ocular steroids and/or topical 
NSAIDs; 
• Severe ocular pain (i.e. 7 to 10 on the Ocular Pain Grading scale (see Appendix 2:  
Examination Procedures, Tests, Equipment, and Techniques) at Visit 4 (Day 4 ± 1) (or 
after) may be treated with oral acetaminophen. 


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In addition, several studies have been completed in both Europe and in the US to evaluate a 
study drug for ocular pain and inflammation using a placebo-controlled trial design. Some 
examples include:  
NCT00198445: Safety and Efficacy Study of Topical Bromfenac Versus Placebo to 
Treat Ocular Inflammation After Cataract Surgery 
NCT01367249: Efficacy of Bromfenac Ophthalmic Solution in Patients Undergoing 
Cataract Surgery 
NCT01426854: Nepafenac Compared to Placebo for Ocular Pain and Inflammation  
NCT01318499: Nepafenac 0.3% Two Study 
NCT00405730: Nepafenac 0.1% Eye Drops, Suspension Compared to Ketorolac 
Trometamol 0.5% Eye Drops, Solution and Placebo 
NCT00430092:  Difluprednate 0.5% Eye Drops Compared to Placebo for Inflammation 
Following Ocular Surgery  
NCT02208297: Lotemax 0.38% Gel Compared to Placebo for Inflammation and Pain 
Following Cataract Surgery 
3.4.2 Measures To Ensure Safe Participation in the Study 
Placebo-controlled studies may only be ethically conducted when patients at a controlled risk are 
included, patients are fully informed of all the potential risks, patients are carefully monitored, 
and adequate protocol safety measures are in place. In this proposed trial a number of general 
protective measures are incorporated into the study protocol with the intention to minimize the 
risk to patients.  
The following specific measures are included in the protocol: 
• Patients at low risk are selected and they will be fully informed of their chances of 
randomization to the placebo group during informed consent. 
• Patients are carefully monitored for pain and inflammation following cataract surgery. 
• The rescue and withdrawal criteria minimize patients risk and will allow proper medical 
care. 
Based on the above rationale and the measurements for a safe medical supervision for the 
patients, Oculis believes that it is scientifically and ethically appropriate to use placebo control in 
the study DX216. 


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4 STUDY OBJECTIVES AND HYPOTHESIS 
4.1 Study Objective 
The primary objective of this study is to evaluate the efficacy and safety of OCS-01 QD and BID 
compared to placebo (vehicle) BID in the treatment of inflammation and pain following cataract 
surgery. 
The secondary objective of this study is to evaluate the optimal dosing frequency of OCS-01 
(QD versus BID) in the treatment of inflammation and pain following cataract surgery. 
4.2 Study Hypothesis 
It is hypothesized that the planned QD and BID doses of OCS-01 via topical ophthalmic 
administration will be safe, effective, and well tolerated in subjects post-cataract surgery. 
5 OVERALL STUDY DESIGN 
This is a multi-center, randomized, double-masked, placebo (vehicle)-controlled study, designed 
to evaluate the efficacy and safety of OCS-01 ophthalmic suspension (QD versus BID) compared 
to placebo in treating inflammation and pain following cataract surgery.  
Subjects will be randomized 1:1:1 to receive OCS-01 QD, OCS-01 BID, or placebo BID. 
Subjects will dose 1 drop in the study eye BID for 14 days, beginning 1 day post-surgery in the 
operated eye. The study will last 20-52 days, including screening and a follow-up visit at Visit 7 
(Day 22 ± 2). 
6 STUDY POPULATION 
6.1 Number of Subjects (approximate) 
Approximately 150 subjects will be enrolled in the study. 
This is a multi-center study. 
6.2 Study Population Characteristics 
Subjects may be of either sex or any race and must be at least 18 years of age at Visit 1 (Day -1 
to Day -28 [prior to surgery]). Subjects must be planning to undergo unilateral cataract extraction 
via phacoemulsification and posterior chamber intraocular lens (PCIOL) implantation in the 
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6.3 Inclusion Criteria 
Each subject must: 
1. Provide written informed consent, approved by the appropriate ethics committee;  
2. Be able to comply with the study requirements and visit schedule; 
3. Be at least 18 years of age of either sex or any race; 
4. Be planning to undergo unilateral cataract extraction via phacoemulsification and PCIOL 
implantation in the study eye; 
5. Have an anterior chamber cell score ≥ 2 at Visit 2 (Day 1 [18 to 30 hours post-
uncomplicated cataract surgery without vitreous loss]); 
6. Have a pin-hole visual acuity (VA) without any other correction > 20 letters 
(approximately 20/400) in the operative eye and > 35 letters (approximately 20/200) in 
the fellow eye as measured using an Early Treatment for Diabetic Retinopathy Study 
(ETDRS) chart at Visit 1 (Day -1 to Day -28 [prior to surgery]);  
7. Have a negative urine pregnancy test at Visit 1 (Day -1 to Day -28 [prior to surgery]), if 
female of childbearing potential (i.e. those who have experienced menarche, who are not 
surgically sterilized [bilateral tubal ligation, hysterectomy, or bilateral oophorectomy] or 
post-menopausal [12 months after last menses]) and must use acceptable effective 
contraceptive measure throughout the study period. Acceptable effective contraceptive 
measure is defined as hormonal – oral, implantable, injectable, or transdermal 
contraceptives; mechanical – spermicide in conjunction with a barrier such as condom or 
diaphragm; intrauterine device (IUD); or surgical sterilization of partner. For non-
sexually active females, abstinence may be regarded as an adequate method of birth 
control.  
6.4 Exclusion Criteria 
Each subject must not: 
1. Have a known sensitivity or allergy to dexamethasone, corticosteroids, or any of the 
study medication’s components; 
2. Be monocular; 
3. Have any intraocular inflammation (e.g. white blood cells or flare) present in either eye at 
the Visit 1 (Day -1 to Day -28 [prior to surgery]) slit lamp examination; 
4. Have a score > 0 on the Ocular Pain Assessment at Visit 1 (Day -1 to Day -28 [prior to 
surgery]) in the study eye;  


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5. Use anti-inflammatory agents, analgesics/pain relievers (including opioids, narcotics, and 
other pain medications), or immunomodulating agents, systemically or in either eye, 
and/or currently using or have any history of use of medications for benign prostatic 
hyperplasia (BPH) from the washout period through the duration of the study. Washout 
periods for medications prior to the day of cataract surgery are as follows: 
a. Topical ocular steroids: 14 days; 
b. Periocular injection of any corticosteroid solution: 28 days; 
c. Intraocular treatment with a corticosteroid including dexamethasone drug delivery 
systems: 56 days after implantation; fluocinolone acetonide drug delivery 
systems: 48 months after implantation; any other intravitreal injection: 95 days 
after injection; 
Note: While it is expected that subjects requiring an intraocular treatment with a 
corticosteroid will be excluded due to underlying exclusionary conditions, subjects who 
otherwise meet all eligibility criteria will be required to follow the above-mentioned 
washout intervals. 
d. Any systemic treatment with a corticosteroid including oral: 14 days; systemic or 
parenteral sustained/extended release: 180 days; 
Note: Inhaled, intranasal, and topical dermatologic steroids (except on the face and 
periocular region) are allowed. Topical dermatologic steroids on the face and periocular 
region require a 7 day washout. 
e. Topical ocular NSAIDs: 7 days; 
f. Systemic analgesics/pain relievers (e.g. gabapentin, pregabalin, and opioids): 
14 days; 
Note: Use of an opioid during cataract surgery is allowed; 
g. Systemic acetaminophen, NSAIDs, acetylsalicylic acid, or other anti-
inflammatory agents: 7 days; 
Note: Use of up to 81 mg of acetylsalicylic acid dosed once daily is allowed if dosage has 
been stable for at least 30 days prior to surgery and will remain stable for the duration of 
the study. 
h. Medications for BPH (e.g. alpha adrenergic blocking agents including tamsulosin, 
silodosin, alfuzosin, and finasteride): all current or previous use of BPH 
medications excludes participation in this study.  ; 
i. Cyclosporine: 56 days or immunomodulating or immunosuppressive agents (e.g. 
calcineurin inhibitors, antiproliferative agents, mammalian target of rapamycin 
(mTOR) inhibitors, etc.): 2 months  
j. Mast cell stabilizers or anti-histamines (e.g. β2-adrenergic agonists. cromoglicic 
acid, ketotifen, brompheniramine, cetirizine, diphenhydramine): 7 days; 
6. Require the use of a contact lens or a collagen shield within 72 hours prior to Visit 2 
(Day 1 [18 to 30 hours post-surgery]) or for the remainder of the study period in either 
eye;  


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7. Require use of non-diagnostic topical ophthalmic medications in either eye for the 
duration of the study with the exception of the following, which are allowed: mydriatics, 
anesthetics, antiseptics, balanced salt solution, viscoelastics, prophylactic antibiotics, 
non-prostaglandin analog IOP-lowering agents, lid scrubs for mild blepharitis, or 
artificial tears for the management of dry eye (allowed topical medication should not be 
instilled at the same time as the study drug.  Study medication should be instilled at least 
30 minutes after any prior allowed topical medication.  In addition, any other allowed 
topical medication should not be instilled within 2 hours following instillation of study 
medication);  
8. Have an IOP ≤ 5 mmHg or ≥ 22 mmHg in either eye at Visit 1 (Day -1 to Day -28 [prior 
to surgery]). Subjects taking IOP-lowering medication must not be on more than 1 IOP-
lowering medication. Prostaglandin analogs are not allowed within 4 weeks of Visit 2 
(Day 1 [18 to 30 hours post-surgery]). 
Note: Combination IOP agents count as 2 medications. 
9. Currently have or have a history of herpes keratitis in the study eye; 
10. Have corneal abrasions or ulcers in the study eye (not including the surgical clear corneal 
wound from cataract surgery); 
11. Have evidence of acute external ocular infections (bacterial, viral, and/or fungal such as 
vaccinia, varicella, and other viral diseases of the cornea and conjunctiva), corneal 
endothelial dystrophies, intraocular infections, dysthyroid ophthalmopathy, active 
chalazion, or uncontrolled blepharitis in the study eye; 
12. Have uncontrolled and clinically significant dry eye syndrome in the study eye (use of 
artificial tears is allowed); 
13. Have active or a history of chronic or recurrent inflammatory eye disease (e.g. iritis, 
scleritis, uveitis, iridocyclitis, or rubeosis iritis) in either the fellow eye or the study eye; 
14. Have cystoid macular edema, diabetic retinopathy, or diabetic macular edema; 
compromised macular function; significant macular diseases; or a history of macular 
edema in the study eye; 
15. Have previous ocular trauma with visible scarring or any deformities due to the trauma in 
the study eye that in the opinion of the Investigator may affect the pharmacokinetics of 
the study medication, intraocular inflammation, or the normal healing process; 
16. Have the potential for ocular hemorrhage in the study eye that may interfere with 
evaluation of post-surgery inflammation; 
17. Have a planned use of femtosecond laser or any other ophthalmic surgical procedure (e.g. 
minimally invasive glaucoma surgery [MIGS], vitrectomy, relaxing incisions, iridectomy, 
conjunctival excisions, use of iris hooks or other iris dilators, etc.) in addition to the 
cataract extraction procedure via phacoemulsification and PCIOL implantation in the 
study eye; 
18. Have a planned use of anterior capsule staining for capsulorhexis (i.e. trypan blue) during 
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19. Have had corneal or retinal surgery (laser or incisional) in the study eye within 6 months 
of Visit 1 (Day -1 to Day -28 [prior to surgery]), or be planning to have laser or incisional 
surgery during the study period in the study eye (other than cataract surgery); 
20. Have surgery planned or scheduled for the contralateral eye during the 3-week study 
period; 
21. Have an immunosuppressive or an autoimmune disease that in the opinion of the 
Investigator could affect intraocular inflammation or the normal healing process of the 
eye; 
22. Have active or chronic/recurrent ocular or systemic disease that is uncontrolled and will 
likely affect wound healing; 
23. Currently have a suspected or known malignancy or be currently receiving 
anti-neoplastic therapy; 
24. Have previously been enrolled in this clinical study, have planned to participate in 
another clinical trial during the follow-up period that could confound the treatment or 
outcomes of this investigation, or be currently in the follow-up period of a previous 
clinical trial;  
25. Be enrolled in the study if the Investigator determines that the subject should not be 
included for reasons not already specified (e.g. systemic or other ocular 
disease/abnormality), if the health of the subject or the validity of the study outcomes 
may be compromised by the subject’s enrollment;  
26. Be a female who is currently pregnant, planning a pregnancy, lactating, not using a 
medically acceptable form of birth control throughout the study duration, or have a 
positive urine pregnancy test at Visit 1 (Day -1 to Day -28 [prior to surgery]). 
6.5 Rescue Criteria 
• Grade ≥ 2 anterior chamber cells (i.e. ≥ 11 cells on the Anterior Chamber Cells grading 
scale [see Appendix 2:  Examination Procedures, Tests, Equipment, and Techniques]) at 
Visit 5 (Day 8 ± 1) (or after) may be treated with topical ocular steroids and/or topical 
NSAIDs; 
• Severe ocular pain (i.e. 7 to 10 on the Ocular Pain Grading Scale [see Appendix 2:  
Examination Procedures, Tests, Equipment, and Techniques]) at Visit 4 (Day 4 ± 1) (or 
after) may be treated with oral acetaminophen. 
6.6 Withdrawal Criteria (if applicable) 
Any subject who wishes to withdraw from the study for any reason is entitled to do so at any 
time without obligation. 
Any subject who discontinues study drug or who is administered rescue therapy will remain 
enrolled in the study and continue to participate in all subsequent visits for safety and efficacy 
assessments. If a subject discontinues participation in the study early, every attempt will be made 
to complete the exit procedures required at the final study visit (Visit 7).  


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7 STUDY PARAMETERS 
7.1 Efficacy Measures 
7.1.1   Primary Efficacy Measure 
Hierarchical Primary Efficacy Measures:  
1. Absence of anterior chamber cells (i.e. score of ‘0’) at Visit 6 (Day 15);  
2. Absence of pain (i.e. score of ‘0’) at Visit 4 (Day 4).  
7.1.2   Secondary Efficacy Measure 
Secondary Efficacy Measures:  
• Absence of anterior chamber cells at Visits 4, 5, and 7 (Days 4, 8, and 22);  
• Absence of pain at Visits 3, 5, 6, and 7 (Days 2, 8, 15, and 22);  
• Absence of flare at Visits 4, 5, 6, and 7 (Days 4, 8, 15, and 22); 
• Absence of both anterior chamber cells and flare at Visits 4, 5, 6, and 7 (Days 4, 8, 15, 
and 22); 
• Use of rescue medication on or prior to each visit and overall. 
7.1.3   Primary Efficacy Analyses 
The hierarchical primary efficacy analyses are as follows:  
1. Difference between the two treatment arms in the proportion of study eyes with absence 
of anterior chamber cells (i.e. score of ‘0’) at Visit 6 (Day 15).  
If the proportion of study eyes with absence of anterior chamber cells (score of ‘0’) is 
statistically significantly higher for OCS-01 versus placebo (vehicle) at a 2-sided alpha = 0.10 at 
Visit 6 (Day 15) for either dose of OCS-01 (BID or QD), then the study will be considered a 
success and the next hierarchical hypothesis will be tested. 
2. Difference in the proportion of study eyes with absence of pain (score of ‘0’) at Visit 4 
(Day 4) between the corresponding OCS-01 dose and placebo (vehicle). 
7.1.4   Secondary Efficacy Analyses 
• Difference in the proportion of study eyes with absence of anterior chamber cells at Visits 
4, 5, and 7 (Days 4, 8, and 22). 
• Difference in the proportion of study eyes with absence of pain at Visits 5, 6, and 7 (Days 
8, 15, and 22). 
• Difference in the proportion of study eyes with absence of flare Visits 4, 5, 6, and 7 
(Days 4, 8, 15, and 22). 


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• Difference in the proportion of study eyes with absence of both anterior chamber cells 
and anterior chamber flare at Visits 4, 5, 6, and 7 (Days 4, 8, 15, and 22). 
• Use of rescue medication on or prior to each visit and overall. 
Efficacy measures will be further described in the Statistical Analysis Plan (SAP). 
7.2 Safety Measures 
Safety will be assessed by the following measures: 
• Change from baseline of pin-hole VA (without any other correction) as measured on the 
ETDRS chart 
• Change from baseline of IOP 
• AE rates 
8 STUDY MATERIALS 
8.1 Study Treatment(s) 
8.1.1   Study treatment(s) 
• OCS-01 ophthalmic suspension (QD) + Placebo (vehicle) (QD) 
• OCS-01 ophthalmic suspension (BID) 
• Placebo (vehicle) ophthalmic suspension (BID) 
8.1.2   Instructions for Use and Administration 
Each subject will receive a master kit containing an AM dosing box and a PM dosing box. Each 
dosing box will contain 2 aluminum pouches with 10 single-use vials each. The master kit’s 
contents will be as follows for subjects randomized to each of the respective treatment arms:  
• OCS-01 QD + Placebo (vehicle) QD  
• OCS-01 BID  
• Placebo (vehicle) BID  
For masking purposes, each dosing box and the pouches within it will be labeled either “AM” or 
“PM.” Dosing boxes and pouches will be labeled this way regardless of whether the product 
within the 2 boxes is the same (i.e. OCS-01 BID and placebo treatment arms) or different (i.e. 
OCS-01 QD). All qualified subjects will dose for 14 days beginning 1 day post-surgery in the 
operated eye. Doses should be instilled at approximately 8 AM (± 2 hours) and 8 PM (± 2 hours), 
as close to 12 hours apart as possible. 
For Visit 2, the first dose will be instilled at the study visit under the supervision of the study 
staff (this dosing may be out of the 8 AM [± 2 hours] dosing window). The second dose should 
be instilled into the operated eye during the PM dosing window (8 PM [± 2 hours]), regardless of 


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when dose 1 was instilled (subjects should then have instilled 2 doses on Day 1 post-cataract 
surgery).  
For all other study visits, subjects should continue to dose according to their established 
schedule. If the visit is scheduled during the time of normal dosing, the subject should bring their 
dose with them to the visit for administration. Every effort should be made to maintain dosing 
schedule/ frequency. 
9 STUDY METHODS AND PROCEDURES 
9.1 Subject Entry Procedures 
9.1.1   Overview 
Subjects as defined by the criteria in Sections 6.2, 6.3, and 6.4 will be considered for entry into 
this study. 
9.1.2   Informed Consent 
Prior to a subject’s participation in the trial (i.e. changes in a subject’s medical treatment and/or 
study related procedures), the study will be discussed with each subject, and subjects wishing to 
participate must give informed consent (and/or assent) using an informed consent form (ICF). 
The ICF must be the most recent version that has received approval/favorable review by a 
properly constituted institutional review board (IRB). 
9.1.3   Washout Intervals 
Washout periods are outlined in exclusion criteria in Section0.  
9.1.4   Procedures for Final Study Entry 
Subjects must satisfy all of the inclusion and none of the exclusion criteria in order to be entered 
into the study. 
9.1.5   Methods for Assignment to Treatment Groups: 
Each subject who signs an ICF will be assigned a screening number. Screening numbers will be 
assigned in sequential order at each site beginning with 001 and will follow the two-digit site 
number (e.g. subject 077 at Site 99 will have Screening Number 99-077). Inclusion and 
exclusion criteria will be reviewed, and qualifying subjects will be enrolled into the study. Each 
subject who qualifies for entry will be assigned a randomization number and corresponding 
treatment according to the randomization code. Study drug will be randomly assigned using a 
1:1:1 assignment ratio, stratified by site, via an interactive response system. 


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9.2 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 electronic case report form (eCRF) along with the 
reason the medication was taken. 
Concurrent enrollment in another study drug or device study is not permitted. 
9.2.1   Prohibited Medications/Treatments 
Prohibited medications and washout periods are summarized in Table 1. 
• Ocular surgical intervention scheduled on the contralateral eye within 3 weeks post-
cataract surgery; or corneal or retinal surgery (laser or incisional) in the study eye within 
6 months of Visit 1 (Day -1 to Day -28 [prior to surgery]); or laser or incisional surgery 
during the study period in the study eye (other than cataract surgery); 
• Use of a contact lens or a collagen shield 72 hours prior to Visit 2 (Day 1 [18 to 30 hours 
post-surgery]) and for the remainder of the study period in either eye;  
• Use anti-inflammatory agents, analgesics/pain relievers (including opioids, narcotics, and 
other pain medications), or immunomodulating agents, systemically or in either eye, 
and/or currently using or have any historic use of medications for benign prostatic 
hyperplasia (BPH) from the washout period through the duration of the study; 
• Non-diagnostic topical ophthalmic medications in either eye for the duration of the study 
with the exception of the following mydriatics, anesthetics, antiseptics, balanced salt 
solution, viscoelastics, prophylactic antibiotics, non-prostaglandin analog IOP lowering 
agents, lid scrubs, or artificial tears (allowed topical medication should not be instilled at 
the same time as the study drug.  Study medication should be instilled at least 30 minutes 
after any prior allowed topical medication.  In addition, any other allowed topical 
medication should not be instilled within 2 hours following instillation of study 
medication); 
• Planned use of anterior capsule staining for capsulorhexis (i.e. trypan blue) during 
cataract surgery; 
• Concurrent enrollment or enrollment within the follow-up period in another study drug or 
device study is not allowed. 
Table 1: Non-allowed Medications and Washout Periods 
Medication 
Washout Period 
Topical ocular steroids 
14 days 
Periocular injection of any corticosteroid solution 
28 days 
Intraocular treatment with a corticosteroid 
56 days after implantation 
Fluocinolone acetonide drug delivery systems 
48 months after implantation 
Intravitreal injection 
95 days after injection 
Systemic treatment with a corticosteroid including oral 
14 days 
Systemic or parenteral sustained/extended release corticosteroid 
180 days 
Topical ocular NSAIDs 
7 days 
Systemic analgesics/pain relievers (e.g. gabapentin, pregabalin, and opioids) 
14 days 


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Systemic acetaminophen, NSAIDs, acetylsalicylic acid, or other anti-inflammatory 
agents 
7 days 
BPH medication (e.g. alpha adrenergic blocking agents including tamsulosin, 
silodosin, alfuzosin, and finasteride) 
 no current or historic use 
Immunomodulating or immunosuppressive agents (e.g. cyclosporine, calcineurin 
inhibitors, antiproliferative agents, mTOR inhibitors, etc.) 
56 days 
Mast cell stabilizers or anti-histamines (e.g. β2-adrenergic agonists. cromoglicic 
acid, ketotifen, brompheniramine, cetirizine, diphenhydramine) 
7 days 
9.2.2   Rescue Medications 
• Grade ≥ 2 anterior chamber cells (i.e. ≥ 11cells on the Anterior Chamber Cells grading 
scale [see Appendix 2:  Examination Procedures, Tests, Equipment, and Techniques]) at 
Visit 5 (Day 8 ± 1) (or after) may be treated with topical ocular steroids and/or topical 
NSAIDs; 
• Severe ocular pain (i.e. 7 to 10 on the Ocular Pain Grading Scale [see Appendix 2:  
Examination Procedures, Tests, Equipment, and Techniques]) at Visit 4 (Day 4 ± 1) (or 
after) may be treated with oral acetaminophen. 
9.2.3   Special Diet or Activities 
There are no special diet or activity restrictions for this study. 
9.3 Examination Procedures 
Procedures to be performed at each study visit with regard to the study objectives are detailed in 
Appendix 2:  Examination Procedures, Tests, Equipment, and Techniques.  
Visit 1 — Screening and Baseline Evaluations (-28 to -1 days prior to surgery) 
• Informed consent/assent  
• Demographic data 
• Medical and medication history 
o Current underlying conditions, including those that began within the last 30 days, 
which may have been resolved before Visit 1 (Day -1 to Day -28 [prior to 
surgery]), must be recorded.  
o Any medications the subject is taking, as well as those the subject may have taken 
but discontinued within 30 days prior to Visit 1 (Day -1 to Day -28 [prior to 
surgery]) must be recorded. 
• Urine pregnancy test (if applicable) 
• Inclusion/exclusion criteria 
• Ocular pain (study eye only)  
• Pin-hole VA 
• Slit lamp biomicroscopy  


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• Ocular inflammation assessment of the anterior chamber cell and flare (study eye only)  
• IOP  
• Dilated indirect ophthalmoscopy  
Visit 2 — Day 1 (18 to 30 hours post-surgery) 
• Review inclusion/exclusion criteria 
• Medical and medications update 
• Ocular pain (study eye only)  
• Pin-hole VA  
• Slit lamp biomicroscopy  
• Ocular inflammation assessment of the anterior chamber cell and flare (study eye only)  
• Randomization 
• Dose and dispense study medication and dosing diary 
• Query for AEs 
Visit 3 — Day 2 (Telephone Call) 
• Ocular pain (study eye only)  
Visit 4 — Day 4 (± 1 day window) 
• Medical and medications update 
• Ocular pain (study eye only)  
• Pin-hole VA 
• Slit Lamp Biomicroscopy  
• Ocular inflammation assessment of the anterior chamber cell and flare (study eye only)  
• IOP 
• Query for AE 
Visit 5 — Day 8 (± 1 day window) 
• Medical and medications update 
• Ocular pain (study eye only)  
• Pin-hole VA  
• Slit lamp biomicroscopy  
• Ocular inflammation assessment of the anterior chamber cell and flare (study eye only)  


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• IOP 
• Query for AEs 
Visit 6 — Day 15 (± 2 day window) 
• Medical and medications update 
• Ocular pain (study eye only)  
• Pin-hole VA  
• Slit lamp biomicroscopy  
• Ocular inflammation assessment of the anterior chamber cell and flare (study eye only)  
• IOP 
• Query for AEs 
Visit 7 — Day 22 (± 2 day window) 
• Urine pregnancy test (if applicable) 
• Medical and medications update 
• Ocular pain (study eye only)  
• Pin-hole VA 
• Slit lamp biomicroscopy  
• Ocular inflammation assessment of the anterior chamber cell and flare (study eye only)  
• IOP 
• Dilated indirect ophthalmoscopy  
• Query for AEs 
• Exit from study 
AEs (both elicited and observed) will be monitored throughout the study. All AEs (both elicited 
and observed) will be promptly reviewed by the Investigator for accuracy and completeness. All 
AEs will be documented on the appropriate eCRF. 
If a female has a positive pregnancy test during the study, then the Investigator will notify the 
site’s monitor immediately. The Investigator shall request from the subject and/or the subject’s 
physician copies of all related medical reports during the pregnancy and shall document the 
outcome of the pregnancy. The Investigator will retain these reports together with the subject’s 
source documents and will provide a copy of all documentation to the site’s monitor. 


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9.4 Schedule of Visits, Measurements and Dosing 
9.4.1   Scheduled Visits 
Refer to Appendix 1:  Schedule of Visits and Measurements for a schedule of visits and 
measurements. 
9.4.2   Unscheduled Visits 
In the case of an AE, an unscheduled visit may occur. The Investigator may perform additional 
assessments at their discretion. All additional assessments will be documented in the subject’s 
source document and eCRF. 
9.5 Compliance with Protocol 
This study will be conducted in compliance with the protocol, the ethical principles that have 
their origin in the Declaration of Helsinki, and the ICH consolidated Guideline E6 for Good 
Clinical Practice (GCP) (European Medicines Agency/ Committee for Medicinal Products for 
Human Use/ICH/135/1995). 
9.6 Subject Disposition 
9.6.1   Completed Subjects 
A completed subject is defined as having completed all 7 visits. Subjects who have discontinued 
from the study or withdrawn consent/assent will not be considered completed subjects.  
9.6.2   Discontinued subjects 
Subjects may be discontinued prior to their completion of the study due to the following: 
• AEs 
• Protocol violations 
• Subject’s decision (e.g. withdrawal of consent) 
• Administrative reasons (e.g. inability to continue, lost to follow up) 
• Sponsor termination of study 
• Principal Investigator’s (PI) decision 
• other 
Note: In addition, any subject may be discontinued for any sound medical reason. 
If at any time during the study the Investigator deems that the subject’s safety has been 
compromised or the subject has been non-compliant, the subject may be withdrawn from the 
study. 


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Any subject who wishes to withdraw from the study for any reason is entitled to do so at any 
time without obligation. 
Notification of a subject’s discontinuation and the reason for discontinuation will be made to Ora 
and/or the Sponsor and will be clearly documented on the eCRF. 
Any subject who discontinues study drug or who is administered rescue therapy will remain 
enrolled in the study and continue to participate in all subsequent visits for safety and efficacy 
assessments. If a subject discontinues participation in the study early, every attempt will be made 
to complete the exit procedures required at the final study visit (Visit 7). 
9.7 Study Termination 
The study may be stopped at any time by the Investigator (at their respective site), the Sponsor, 
and/or Ora with appropriate notification. 
9.8 Study Duration 
Subjects may be screened from Day -28 to Day -1 prior to surgery. The study will involve 7 
visits including a follow-up visit at Visit 7 (Day 22). Overall study duration will be 20-52 days, 
including the screening visit and a follow-up visit. 
9.9 Monitoring and Quality Assurance 
During the course of the study an Ora monitor, or designee, will make routine site visits to 
review protocol compliance, assess test article accountability, and ensure the study is being 
conducted according to the pertinent regulatory requirements. The review of the subjects’ 
medical records will be performed in a manner to ensure that data protection and subject 
confidentiality rights are adequately maintained. Further details of the study monitoring will be 
outlined in a Monitoring Plan. 
Regulatory authorities of domestic and foreign agencies, Ora Quality Assurance, and/or its 
designees may carry out on-site inspections and/or audits that may include source data checks. 
Therefore direct access to the original source data will be required for inspections and/or audits. 
All inspections and/or audits will be carried out giving consideration to data protection as well as 
subject confidentiality to the extent that local, national, and international laws apply. 
10 ADVERSE EVENTS 
10.1 Adverse Event 
An AE is defined as any untoward medical occurrence associated with the use of a drug in 
humans, whether or not the event is considered drug-related. An AE can therefore be any 
unfavorable and unintended sign (e.g. an abnormal laboratory finding), symptom, or disease 
occurring after the subject started dosing with the study drug, without any judgment about 
causality. Any pre-existing medical condition that worsens after administration of the study drug 
will also be considered a new AE. Study drug includes the study drug under evaluation (OCS-01) 


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and any comparator drug, placebo (vehicle), or any other medications required by the protocol 
given during any stage of the study. 
Documentation regarding the AE should be made as to the nature, date of onset, end date, 
severity, relationship to study drug, action(s) taken, seriousness, and outcome of any sign or 
symptom observed by the physician or reported by the subject upon indirect questioning. 
10.1.1   Severity 
Severity of an AE is defined as a qualitative assessment of the degree of intensity of an AE as 
determined by the Investigator or reported to him/her by the subject. The assessment of severity 
is made irrespective of the relationship to study drug or the seriousness of the event and should 
be evaluated according to the following scale: 
• Mild: AE is noticeable to the subject, but is easily tolerated and does not interfere with 
the subject’s daily activities. 
• Moderate: AE is bothersome, possibly requiring additional therapy, and may interfere 
with the subject’s daily activities. 
• Severe: AE is intolerable, necessitates additional therapy or alteration of therapy, and 
interferes with the subject’s daily activities. 
10.1.2   Relationship to Study Drug 
The relationship of each AE to the study drug should be determined by the Investigator using 
these explanations: 
• Suspected: A reasonable possibility exists that the study drug caused the AE. 
• Not Suspected: A reasonable possibility does not exist that the study drug caused the AE. 
“Suspected adverse reaction” means any AE for which there is a reasonable possibility that the 
study drug caused the AE.  “Reasonable possibility” means there is evidence to suggest a causal 
relationship between the study drug and the AE. Types of evidence that would suggest a causal 
relationship between the study drug and the AE include: a single occurrence of an event that is 
uncommon and known to be strongly associated with drug exposure (e.g. angioedema, hepatic 
injury, Stevens-Johnson Syndrome); one or more occurrences of an event that is not commonly 
associated with drug exposure, but is otherwise uncommon in the population exposed to the drug 
(e.g. tendon rupture); an aggregate analysis of specific events observed in a clinical trial (such as 
known consequences of the underlying disease or condition under investigation or other events 
that commonly occur in the study population independent of drug therapy) that indicates those 
events occur more frequently in the drug treatment group than in a concurrent or historical 
control group. 
10.1.3   Expectedness 
The expectedness of an AE should be determined based upon existing safety information about 
the study drug using these explanations: 


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• 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. 
• Expected: an AE that is listed in the IB at the specificity and severity that has been 
observed. 
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. 
Preliminary determination of classification of an AE as unexpected is the responsibility of the 
Investigator and subject to the Medical Monitor’s final determination. 
10.2 Serious Adverse Events 
An AE is considered serious if, in the view of either the Investigator or Sponsor, it results in any 
of the following outcomes: 
• Death; 
• 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 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. 
• 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 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. 
• A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions; 
Note: A SAEs 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). 
• 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 


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may jeopardize the patient or subject and may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition. 
10.3 Procedures for Reporting Adverse Events 
All AEs and their outcomes must be reported to Ora, the study Sponsor, and the IRB as required 
by the IRB, federal, state, or local regulations and governing health authorities and recorded on 
the appropriate eCRF. 
10.3.1   Reporting a Suspected Unexpected Adverse Reaction 
All AEs that are ‘suspected’ and ‘unexpected’ are to be reported to Ora, the study Sponsor, and 
the IRB as required by the IRB, regional and local regulations, and governing health authorities. 
10.3.2   Reporting a Serious Adverse Event 
To ensure subject safety, all SAEs, regardless of their relationship to the study drug, must be 
immediately reported. All information relevant to the SAE must be recorded on the appropriate 
case report forms. The Investigator is obligated to pursue and obtain information requested by 
Ora and/or the Sponsor in addition to that information reported on the case report form. All 
subjects experiencing an SAE must be followed-up with and the outcome reported. 
In the event of an SAE, the Investigator must notify Ora and the Sponsor upon becoming aware 
of a SAE; obtain and maintain in his/her files including all pertinent medical records, 
information, and medical judgments from colleagues who assisted in the treatment and follow-up 
of the subject; provide Ora and the study 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 of the AE within their guidelines for reporting SAEs. 
Investigators are to contact the study’s Medical Monitor or designee upon becoming aware of a 
SAE. 
10.4 Procedures for Unmasking of Study Drug 
The randomization code should be broken only in the event of a medical emergency, or when 
knowing the treatment assignment is absolutely necessary for the medical management of the 
study subject. When possible (i.e. in non-emergency situations), the study Sponsor or 
representative should be notified prior to unmasking study drug. In emergency situations, the 
Investigator must notify the Sponsor within 24 hours after determining that it is necessary to 
unmask the treatment assignment. The Investigator must also indicate in source documents and 
in the eCRF that the mask was broken and provide the date, time, and reason for breaking the 
mask. Any AE or SAE associated with breaking the mask must be recorded and reported as 
specified in this protocol. 
10.5 Type and Duration of the Follow-up of Subjects after Adverse Events 
AEs will be followed until the condition is resolved or stabilized. 


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11 STATISTICAL METHODS 
A complete detailed description of the statistical methods will be provided in the SAP.  
11.1 Statistical Hypotheses 
The hierarchical statistical hypotheses for evaluating the objectives of the study are as follows: 
Primary Endpoint:  
H011: The difference, between study eyes treated with OCS-01 BID and study eyes 
treated with placebo (vehicle), in the proportion of study eyes with absence of anterior 
chamber cells (score of ‘0’) at Visit 6 (Day 15) = 0. 
H111: The difference, between study eyes treated with OCS-01 BID and study eyes 
treated with placebo (vehicle), in the proportion of study eyes with absence of anterior 
chamber cells (score of ‘0’) at Visit 6 (Day 15) ≠ 0, with superiority claimed if the 
difference is greater than 0 (OCS-01 BID – placebo [vehicle]). 
H012: The difference, between study eyes treated with OCS-01 QD and study eyes 
treated with placebo (vehicle), in the proportion of study eyes with absence of anterior 
chamber cells (score of ‘0’) at Visit 6 (Day 15) = 0. 
H112: The difference, between study eyes treated with OCS-01 QD and study eyes 
treated with placebo (vehicle), in the proportion of study eyes with absence of anterior 
chamber cells (score of ‘0’) at Visit 6 (Day 15) ≠ 0, with superiority claimed if the 
difference is greater than 0 (OCS-01 QD – placebo [vehicle]). 
Hierarchical Primary Endpoint:  
H021: The difference, between study eyes treated with OCS-01 BID and study eyes 
treated with placebo (vehicle), in the proportion of study eyes with absence of pain 
(score of ‘0’) at Visit 4 (Day 4) = 0. 
H121: The difference, between study eyes treated with OCS-01 BID and study eyes 
treated with placebo (vehicle), in the proportion of study eyes with absence of pain 
(score of ‘0’) at Visit 4 (Day 4) ≠ 0, with superiority claimed if the difference is greater 
than 0 (OCS-01 BID – placebo [vehicle]). 
H022: The difference, between study eyes treated with OCS-01 QD and study eyes 
treated with placebo (vehicle), in the proportion of study eyes with absence of pain 
(score of ‘0’) at Visit 4 (Day 4) = 0. 
H122: The difference, between study eyes treated with OCS-01 QD and study eyes 
treated with placebo (vehicle), in the proportion of study eyes with absence of pain 
(score of ‘0’) at Visit 4 (Day 4) ≠ 0, with superiority claimed if the difference is greater 
than 0 (OCS-01 QD – placebo [vehicle]). 


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Multiple comparison adjustments for testing OCS-01 BID and OCS-01 QD versus placebo 
(vehicle) in the absence of anterior chamber cells will not be made (i.e. the testing of H011 versus 
H111 and H012 versus H112 will both be completed at a 2-sided alpha = 0.10). A hierarchical 
testing strategy will be employed for testing absence of pain; statistical inference will only be 
made on the absence of pain endpoint if the corresponding OCS-01 dose (BID or QD) 
demonstrated statistical superiority over placebo (vehicle) in the absence of anterior chamber 
cells. 
11.2 Analysis Populations 
The following analysis populations will be defined, although additional populations and further 
refinement of the below populations may be specified in the SAP, prior to unmasking study data: 
• Full Analysis Set: The full analysis set (FAS) will consist of all randomized subjects, 
analyzing subjects under the treatment to which they were randomized. 
• Per Protocol Population: The per protocol (PP) population is a subset of the FAS and 
includes subjects who remain in the study through Visit 6 (Day 15) (or who discontinue 
due to lack of efficacy or receive rescue medication prior to Visit 6 [Day 15]) with no 
major protocol violations that would affect the assessment of the primary efficacy 
endpoints of the study, analyzing subjects under the treatment received. Major protocol 
violations related to study inclusion or exclusion criteria, conduct of the trial, subject 
management, or subject assessment will be identified prior to unmasking treatment. 
• Safety Population: The safety population includes all randomized subjects who receive at 
least 1 dose of study medication. The safety population will be analyzed as treated and 
will be used for the safety analyses. No data will be excluded for any reason. 
11.3 Sample Size Determination 
With a total of 150 subjects (50 subjects per treatment group: OCS-01 BID, OCS-01 QD, and 
placebo [vehicle] in the FAS [i.e. 1:1:1 randomization]), the study has 85% power to detect a 
statistically significant treatment difference between OCS-01 BID and placebo and between 
OCS-01 QD and placebo for the proportion of subjects with absence of cells on post-operative 
Visit 6 (Day 15), assuming a 2-sided alpha level of 0.10 and the proportion of subjects with 
absence of cells is 0.45 (active) and 0.20 (placebo [vehicle]).   
Additionally, with this sample size, the study has 83% power to detect a statistically significant 
treatment difference between OCS-01 (BID or QD) and placebo for the proportion of subjects 
with absence of ocular pain on post-operative Visit 4 (Day 4), assuming a 2-sided alpha level of 
0.10, and the proportion of subjects with absence of ocular pain is 0.50 (active) and 0.25 
(placebo [vehicle]). 
11.4 Interim Analysis 
Interim analyses will not be performed. 


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11.5 Efficacy Analysis 
11.5.1   General Statistical Considerations 
Summaries for continuous variables will include the sample size, mean, standard deviation, 
median, minimum, and maximum. Summaries for discrete variables will include frequencies and 
percentages. Differences between treatment groups will be calculated as OCS-01 – placebo 
(vehicle), and change from baseline will be calculated as follow-up visit – baseline. Baseline 
values will be defined as the last non-missing measure prior to initiation of study treatment. All 
efficacy analyses will use a 2-sided alpha = 0.10 test unless otherwise stated and corresponding 
2-sided 90% and 95% confidence intervals (CIs) will be presented as applicable. 
The unit of analysis in this study will be the study eye for all ocular efficacy and safety 
summaries and the subject for all non-ocular summaries. 
11.5.2   Primary Efficacy Analysis 
Primary Efficacy Measure: The hierarchical primary efficacy measures are the absence of 
anterior chamber cells (i.e. score of ‘0’) at Visit 6 (Day 15) and the absence of pain (i.e. score of 
‘0’) at Visit 4 (Day 4). 
Primary Efficacy Analysis: The primary efficacy variables, the absence of anterior chamber cells 
at Visit 6 (Day 15) and the absence of pain at Visit 4 (Day 4), will be summarized using discrete 
summary statistics, including 2-sided 95% CIs for each treatment group.   
For each OCS-01 dose (BID and QD), the primary efficacy analyses will first test the difference 
in the proportion of study eyes with absence of anterior chamber cells (score of ‘0’) between 
OCS-01 and placebo (vehicle) at Visit 6 (Day 15) using the Pearson chi-squared statistic 
(Fisher’s exact test will be used if any expected cell count is less than 5). 
If the proportion of study eyes with absence of anterior chamber cells (score of ‘0’) is 
statistically significantly higher for OCS-01 versus placebo (vehicle) at a 2-sided alpha = 0.10 at 
Visit 6 (Day 15), for either dose of OCS-01 (BID or QD), then the study will be considered a 
success. The hierarchical hypothesis testing the proportion of study eyes with absence of pain 
(score of ‘0’) at Visit 4 (Day 4) between the corresponding OCS-01 dose and placebo (vehicle) 
will be performed using the Pearson chi-squared statistic at a 2-sided alpha=0.10 (Fisher’s exact 
test will be used if any expected cell count is less than 5).   
Analyses will be completed primarily on the FAS and secondarily on the PP population. 
11.5.3   Secondary Efficacy Analyses 
Secondary Efficacy Measure: The secondary efficacy measures include: 
1. Absence of anterior chamber cells at Visits 4, 5, and 7 (Days 4, 8, and 22);  
2. Absence of pain at Visits 5, 6, and 7 (Days 8, 15, and 22);  
3. Absence of flare at Visits 4, 5, 6, and 7 (Days 4, 8, 15, and 22). 


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4. Absence of both anterior chamber cells and flare at Visits 4, 5, 6, and 7 (Days 4, 8, 15, 
and 22);  
5. Use of rescue medication on or prior to each visit and overall.  
Secondary Efficacy Analysis:  The secondary efficacy variables, the differences in proportions 
of: study eyes with absence of anterior chamber cells (Visits 4, ,5 and 7 [Days 4, 8, and 22]), 
study eyes with absence of pain (Visits 5, 6, and 6 [Days 8, 15, and 22]), study eyes with absence 
of flare (Visits 4, 5, 6, and 7 [Days 4, 8, 15, and 22]), and study eyes with absence of both 
anterior chamber cells and anterior chamber flare (Visits 4, 5, 6, and 7 [Days 4, 8, 15, and 22]) 
will be summarized and analyzed similarly to the primary efficacy summaries and analyses. 
Use of rescue medication on or prior to each visit will be summarized by visit and overall using 
discrete summary statistics. 
Analyses will be completed primarily on the FAS and secondarily on the PP population. 
11.6 Safety Analysis 
The primary safety analyses will summarize VA, IOP, and AEs, as described below. 
VA data will be summarized at each visit, using discrete summaries including mean change from 
baseline in the number of letters and the proportion of subjects with worsening from previous 
visit of ≥ 2 lines using the ETDRS scale. The pin-hole VA procedure is detailed in Appendix 2:  
Examination Procedures, Tests, Equipment, and Techniques. 
IOP will be summarized for each visit, using continuous and discrete summary statistics, 
including mean change from baseline and the proportion of study eyes with an increase from 
baseline in IOP of 10 mmHg or more and the proportion of study eyes with IOP of 30 mmHg or 
more. The IOP procedure is summarized in Appendix 2:  Examination Procedures, Tests, 
Equipment, and Techniques. 
Ocular treatment-emergent AEs (TEAEs) in the study eye for all treated subjects will be 
summarized using discrete variables at the subject and event level by system organ class (SOC) 
and preferred term (PT) for each treatment group. A TEAE will be defined as any AE that occurs 
after the treatment is initiated. An additional analysis will examine ocular AEs for the non-study 
eye. Non-ocular TEAEs will be summarized using discrete summaries at the subject and event 
level by SOC and PT for each treatment group. Treatment related ocular and non-ocular TEAEs 
will be summarized similarly. Ocular and non-ocular TEAEs will also be summarized by 
severity. 
Slit lamp biomicroscopy and dilated indirect ophthalmoscopy measures will be summarized at 
each visit including shift from baseline (as appropriate) using discrete summary statistics.  
11.7 Handling of Missing Data 
The primary analyses of all efficacy data will use last observation carried forward (LOCF) to 
impute missing data; data for visits after a subject is discontinued for lack of efficacy or receives 


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rescue medication will be imputed as failures for success/failure endpoints and will be imputed 
using LOCF for other endpoints. To check robustness of results, sensitivity analyses of the 
primary efficacy endpoints will include analyses of observed data only, imputing data from 
subject visits after discontinuation for lack of efficacy or receipt of rescue medication as failures. 
Tipping point analysis and multiple imputation methods using monotone methodology will also 
be used to impute missing data as additional sensitivity analyses. PP analyses will use observed 
data only, with the exception of subjects who have missing data due to discontinuation for lack 
of efficacy or for subjects who receive rescue medication; for these subjects, missing data after 
discontinuation or data after receiving rescue medication will be imputed as failures for 
success/failure endpoints and will be imputed using LOCF for other endpoints.  
11.8 Demographics and Medical History 
Subject demographics comprising age, gender, race, and ethnicity will be presented using 
discrete or continuous summary statistics as appropriate. 
12 COMPLIANCE WITH GOOD CLINICAL PRACTICES, ETHICAL 
CONSIDERATIONS, AND ADMINISTRATIVE ISSUES 
This study will be conducted in compliance with the protocol, with GCPs including 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. 
12.1 Protection of Human Subjects 
12.1.1 Subject Informed Consent 
Informed consent must take place before any study specific procedures are initiated. Signed and 
dated written informed consent must be obtained from each subject prior to enrollment into the 
study.  
All ICFs must be approved for use by the Sponsor and receive approval/favorable opinion from 
an IRB 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 Ora prior to submission to the 
governing IRB 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. 
12.1.2   Institutional Review Board Approval 
This study is to be conducted in accordance with IRB regulations (U.S. 21 Code of Federal 
Regulations [CFR] Part 56.103). The Investigator must obtain appropriate IRB approval before 
initiating the study and re-approval at least annually. 
Only an IRB approved version of the ICF will be used. 


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12.1.3   Ethical Conduct of the Study 
This study will be conducted in accordance with the ethical principles that originated with the 
Declaration of Helsinki. 
12.2 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. 
Monitors, auditors and other authorized representatives of Ora, the Sponsor, the IRB approving 
this study, the 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. 
12.3 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 eCRF serves as the 
Investigator’s record of a subject’s study-related data. 
12.3.1   Retention of Documentation 
All study related correspondence, subject records, consent forms, record of the distribution and 
use of all study drug and copies of case report forms 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 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 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. 


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12.4 Labeling, Packaging, Storage, Accountability, and Return or Disposal of 
Study Drug 
12.4.1   Labeling/Packaging 
Study drug will be packed in single-use vials, with 10 per aluminum pouch and 2 pouches per 
box.  All study drugs will be labeled according to applicable regulatory requirements. 
12.4.2   Storage of Study Drug 
The study drug must be stored in a secure area accessible only to the Investigator and his/her 
designees. The study drug will be dispensed only to subjects entered into the clinical study, in 
accordance with the conditions specified in this protocol. 
Undispensed study drug should be stored at room temperature (15-25ºC). 
Once dispensed to subjects, study drug should be stored at ambient temperature.  
12.4.3   Accountability of Study Drug 
The study drug is to only be prescribed by the PI or his/her named sub Investigator(s), and is to 
only be used in accordance with this protocol.  The study drug must only be distributed to 
subjects eligible under this protocol to receive study drug. 
The Investigator or his/her designee must keep an accurate accounting of the study drug received 
from the supplier.  This includes the amount of study drug dispensed to subjects, amount of study 
drug returned to the Investigator by the subjects, and the amount returned or disposed upon the 
completion of the study. A detailed inventory must be completed for the study drug. 
12.4.4   Return or Disposal of Study Drug 
At the end of the study, all study drugs will be returned to the Sponsor or their designee or 
destroyed at the study site. The return or disposal of study drug will be specified in writing. 
12.5 Recording of Data on Source Documents and Case Report 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 


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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, compact discs (CDs) containing copies of 
all applicable subjects’ eCRFs will be provided to each Investigator Site to be maintained on file 
by the Investigator. 
12.6 Handling of Biological Specimens 
Not applicable 
12.7 Publications 
Authorship and manuscript composition will reflect joint cooperation among all parties involved 
in the study. Authorship will be established prior to the writing of the manuscript. The study 
Sponsor will have the final decision regarding the manuscript and publication. 


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REFERENCES 
Alcon Laboratories, I. (2000). PAZEO (olopatadine hydrochloride ophthalmic solution) 0.7%. 
Alcon Laboratories, I. (2002). Maxidex 0.1 % (dexamethasone ophthalmic suspension). 
CIOMS (2016). International Ethical Guidelines for Health-related Research Involving Humans. 
Geneva. 
Fong, R., B. E. Silverstein, J. H. Peace, J. I. Williams and J. L. Vittitow (2018). "Submicron 
loteprednol etabonate ophthalmic gel 0.38% for the treatment of inflammation and pain after 
cataract surgery." J Cataract Refract Surg 44(10): 1220-1229. 
Jabs, D. A., R. B. Nussenblatt, J. T. Rosenbaum and G. Standardization of Uveitis Nomenclature 
Working (2005). "Standardization of uveitis nomenclature for reporting clinical data. Results of 
the First International Workshop." Am J Ophthalmol 140(3): 509-516. 
Johannesson, G., P. Hallberg, A. Eklund, A. Behndig and C. Linden (2014). "Effects of topical 
anaesthetics and repeated tonometry on intraocular pressure." Acta Ophthalmol 92(2): 111-115. 
Johannesson, G., M. D. Moya-Ortega, G. M. Asgrimsdottir, S. H. Lund, M. Thorsteinsdottir, T. 
Loftsson and E. Stefansson (2014). "Kinetics of gamma-cyclodextrin nanoparticle suspension 
eye drops in tear fluid." Acta Ophthalmol 92(6): 550-556. 
Krag, S. and A. Hessellund (2014). "Topical dexamethasone-cyclodextrin microparticle eye 
drops for uveitic macular oedema." Acta Ophthalmol 92(8): e689-690. 
Kristinsson, J. K., H. Fridriksdottir, S. Thorisdottir, A. M. Sigurdardottir, E. Stefansson and T. 
Loftsson (1996). "Dexamethasone-cyclodextrin-polymer co-complexes in aqueous eye drops. 
Aqueous humor pharmacokinetics in humans." Invest Ophthalmol Vis Sci 37(6): 1199-1203. 
Liu, Y. C., M. Wilkins, T. Kim, B. Malyugin and J. S. Mehta (2017). "Cataracts." Lancet 
390(10094): 600-612. 
Loftsson, T. and E. Stefansson (2017). "Cyclodextrins and topical drug delivery to the anterior 
and posterior segments of the eye." Int J Pharm 531(2): 413-423. 
McCaffery, M. and A. Beebe (1994). "Pain: clinical manual for nursing practice." Nurs Stand 
9(11): 55. 
Ohira, A., K. Hara, G. Johannesson, M. Tanito, G. M. Asgrimsdottir, S. H. Lund, T. Loftsson 
and E. Stefansson (2015). "Topical dexamethasone gamma-cyclodextrin nanoparticle eye drops 
increase visual acuity and decrease macular thickness in diabetic macular oedema." Acta 
Ophthalmol 93(7): 610-615. 


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Rajpal, R. K., R. Fong and T. L. Comstock (2013). "Loteprednol etabonate ophthalmic gel 0.5% 
following cataract surgery: integrated analysis of two clinical studies." Adv Ther 30(10): 907-
923. 
Saari, K. M., L. Nelimarkka, V. Ahola, T. Loftsson and E. Stefansson (2006). "Comparison of 
topical 0.7% dexamethasone-cyclodextrin with 0.1% dexamethasone sodium phosphate for 
postcataract inflammation." Graefes Arch Clin Exp Ophthalmol 244(5): 620-626. 
Samudre, S. S., F. A. Lattanzio, Jr., P. B. Williams and J. D. Sheppard, Jr. (2004). "Comparison 
of topical steroids for acute anterior uveitis." J Ocul Pharmacol Ther 20(6): 533-547. 
Shulman, S., G. Johannesson, E. Stefansson, A. Loewenstein, A. Rosenblatt and Z. Habot-
Wilner (2015). "Topical dexamethasone-cyclodextrin nanoparticle eye drops for non-infectious 
Uveitic macular oedema and vitritis - a pilot study." Acta Ophthalmol 93(5): 411-415. 
Sigurdsson, H. H., F. Konraethsdottir, T. Loftsson and E. Stefansson (2007). "Topical and 
systemic absorption in delivery of dexamethasone to the anterior and posterior segments of the 
eye." Acta Ophthalmol Scand 85(6): 598-602. 
Tanito, M., K. Hara, Y. Takai, Y. Matsuoka, N. Nishimura, P. Jansook, T. Loftsson, E. 
Stefansson and A. Ohira (2011). "Topical dexamethasone-cyclodextrin microparticle eye drops 
for diabetic macular edema." Invest Ophthalmol Vis Sci 52(11): 7944-7948. 
Usayapant, A., A. H. Karara and M. M. Narurkar (1991). "Effect of 2-hydroxypropyl-beta-
cyclodextrin on the ocular absorption of dexamethasone and dexamethasone acetate." Pharm Res 
8(12): 1495-1499. 
Weber, M., L. Kodjikian, F. E. Kruse, Z. Zagorski and C. M. Allaire (2013). "Efficacy and safety 
of indomethacin 0.1% eye drops compared with ketorolac 0.5% eye drops in the management of 
ocular inflammation after cataract surgery." Acta Ophthalmol 91(1): e15-21. 


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Appendix 1:  Schedule of Visits and Measurements 
AE = adverse event; HIPPA =  
 
Study Parameter 
Visit 1 
( -28 to -1 Day(s) 
Prior to Surgery) 
Visit 2 
(Day 1, 18-30 h 
Post-Surgery) 
Treatment Period 
Follow-up 
Visit 3 
(Day 2, telephone 
call) 
Visit 4 
(Day 4 ± 
1) 
Visit 5 
(Day 8 ± 1) 
Visit 6 
(Day 15 ± 2) 
Visit 7 
(Day 22 ± 2) 
Informed Consent / HIPAA 
X 
 
 
 
 
 
 
Demographic Data 
X 
 
 
 
 
 
 
Medical and Medication History 
X 
 
 
 
 
 
 
Urine pregnancy Test 
X 
 
 
X 
Review Inclusion / Exclusion Criteria 
X 
X 
 
 
 
 
 
Medical and Medications Update 
X 
 
X 
X 
X 
X 
Ocular Pain (Study Eye Only) 
X 
X 
X 
X 
X 
X 
X 
Pin-hole Visual Acuity 
X 
X 
 
X 
X 
X 
X 
Slit lamp Biomicroscopy 
X 
X 
 
X 
X 
X 
X 
Ocular Inflammation Assessment of 
the Anterior Chamber Cell and Flare 
(Study Eye Only) 
X 
X 
 
X 
X 
X 
X 
Intraocular Pressure 
X 
 
 
X 
X 
X 
X 
Randomization 
 
X 
 
 
 
 
 
Dilated Indirect Ophthalmoscopy 
X 
 
 
 
 
 
X 
Dispense Study Medication and 
Dosing Diary 
 
X 
 
 
 
 
 
AE Query 
X 
 
X 
X 
X 
X 
Exit from Study 
 
 
 
 
 
X 


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Appendix 2:  Examination Procedures, Tests, Equipment, and Techniques 
 
Pin-hole Visual Acuity .................................................................................................................. 50 
Slit-lamp Evaluation ..................................................................................................................... 52 
During Slit Lamp Biomicroscopy: Ocular Inflammation Assessment of the Anterior Chamber 
Cell and Flare (Study Eye Only) ................................................................................................... 53 
Ocular Pain Grading Scale (Study Eye Only)............................................................................... 54 
Intraocular Pressure Procedures .................................................................................................... 55 
Dilated Indirect Ophthalmoscopy ................................................................................................. 56 
 
 


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Pin-hole Visual Acuity 
Pin-hole, logarithm of the minimum angle of resolution (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. Pin-hole visual acuity should be 
evaluated at the beginning of each visit in the study (i.e. prior to slit lamp examination). Pin-hole 
visual acuity testing should be done with a pin-hole occluder.  
Equipment 
The visual acuity chart to be used is the ETDRS chart. The patient viewing distance should be 4 
meters. If less than 20 letters are read at 4 meters the patient should be moved to a viewing 
distance of 1 meter and the visual acuity test re-started. 
In ALL cases, for purposes of standardizing the testing conditions during the study, all sites must 
use Chart 1 for the right eye (Weber, Kodjikian et al. 2013) and Chart 2 for the left eye (OS). 
The right eye (Weber, Kodjikian et al. 2013) should be tested first.  
Measurement Technique 
The chart should be at a comfortable viewing angle. A pin-hole occluder should be applied to the 
right eye which should be tested first. The patient should attempt to read each letter, line-by-line, 
left to right, beginning with line 1 at the top of the chart. The patient should be told that the chart 
has letters only, no numbers. If the patient reads a number, he or she should be reminded that the 
chart contains no numbers, and the examiner should then request a letter in lieu of the number. 
The patient should be asked to read slowly, so as to achieve the best identification of each letter. 
He/she is not to proceed to the next letter until he/she has given a definite response. 
If the patient changes a response (e.g., “that was a ‘C’ not an ‘O’”) before he has read aloud the 
next letter, then the change must be accepted. If the patient 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 patient says he 
or she cannot read a letter, he or she should be encouraged to guess. If the patient identifies a 
letter as one of two letters, he or she 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.  
Visual Acuity Calculations 
• The examiner records each letter identified correctly by circling the corresponding letter 
on the pin-hole VA Worksheet (Example worksheet for Chart 1 is below). 
• Letters read incorrectly or not read at all are NOT marked on the form. Each letter read 
correctly is scored as one point.  


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• For each row, write the total number of letters read correctly in the column to the right.  
• If line is attempted, but NO letters are read correctly–please enter the number zero (0).    
• If line is NOT attempted, please enter a dash (–). 
 
 
 
Letters read correctly at 4.0 meters 
Letters read correctly at 1.0 meter 
(Subject must be sitting for 1 meter test) 
Acuity 
Equivalent 
Chart 1 letters 
Number 
Correct 
Acuity 
Equivalent 
Chart 1 letters 
Number 
Correct 
20/200 
N 
C 
K 
Z 
O 
 
20/800 
N 
C 
K 
Z 
O  
20/160 
R 
H 
S 
D 
K 
 
20/640 
R 
H 
S 
D 
K  
20/125 
D 
O 
V 
H 
R 
 
20/500 
D 
O 
V 
H R 
 
20/100 
C 
Z 
R 
H 
S 
 
20/400 
C 
Z 
R 
H S 
 
20/80 
O 
N 
H 
R 
C 
 
20/320 
O 
N 
H 
R 
C 
 
20/63 
D 
K 
S 
N 
V 
 
20/250 
D 
K 
S 
N 
V 
 
20/50 
Z 
S 
O 
K 
N 
 
Total Number Correct at 1 meter: 
 
20/40 
C 
K 
D 
N 
R 
 
If less than 20 letters at 4 meters, add total 
number correct at 4 meters plus total number 
correct at 1 meter to calculate pin-hole VA. 
 
 
(If ≥ 20 at 4 meters add 30)             +______ 
 
Total number correct at 1 meter    +______ 
 
Calculated pin-hole VA Score:       =______ 
 
                                                 
20/32 
S 
R 
Z 
K 
D 
 
20/25 
H 
Z 
O 
V 
C 
 
20/20 
N 
V 
D 
O 
K 
 
20/16 
V 
H 
C 
N 
O 
 
20/12.5 
S 
V 
H 
C 
Z 
 
20/10 
O 
Z 
D 
V 
K 
 
Total Number Correct at 4 meters: 
 
 
Is total number correct at 4 meters 20 letters or 
more?              
 
□ Yes      □ No 
• 
If Yes, add 30 to total number correct at 4 
meters to calculate pin-hole VA 
• 
If No, test at 1 meter 
 


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Slit-lamp Evaluation 
Slit lamp biomicroscopy will be performed at each visit during the study. Magnification, slit 
beam and examination procedure will be consistent with Investigator’s standard practice. The 
Investigator will note any findings present and whether the findings are clinically significant or 
not clinically significant. Findings which are clinically significant will be described. All findings 
will be documented on each subject’s source document and corresponding electronic case report 
form. The following ocular structures will be examined: 
• Eyelid 
• Cornea 
• Conjunctiva 
• Anterior Chamber 
• Iris 
• Lens 
 
 


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During Slit Lamp Biomicroscopy: Ocular Inflammation Assessment of the Anterior 
Chamber Cell and Flare (Study Eye Only) 
The slit beam observations should be assessed in a dark room using a slit beam of 1.0 mm height 
and 1.0 mm width with maximum luminance, with 16x magnification, 1x1mm oblique high 
intensity beam fluorescein dye is to be instilled into the ocular cul-de-sac, or alternatively, 
fluorescein strips may be used to facilitate this examination.  
Anterior Chamber Cells and Flare  
The anterior chamber cell count will be recorded as the actual number of cells observed if ≤10 
cells are seen (only white blood cells should be counted; red blood cells and pigment cells should 
not be counted).  
Anterior Chamber Cells 
Anterior Chamber Flare 
Grade 
Cell Count 
Grade 
Flare Count 
0 
0 
0 
None 
1 
1-10 
1 
Faint 
2 
11-25 
2 
Moderate (iris and lens details clear) 
3 
26-50 
3 
Marked (iris and lens details hazy) 
4 
>50 
4 
Intense (fibrin or plasmoid aqueous) 
Scale based on (Jabs, Nussenblatt et al. 2005). 
 
 


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0
2
3
4
5
6
1
7
8
9
10
None
Mild
Moderate
Severe
Ocular Pain Grading Scale (Study Eye Only) 
Ocular pain will be assessed by the patient at screening and at each follow-up visit, utilizing a 
numerical pain rating scale graded from 0 to 10 (McCaffery and Beebe 1994). Subjects will 
assess the level of pain they are experiencing in the study eye at the time of the assessment. 
The examiner will ask the patient the following question: 
On a scale of 0 to 10, in which 0 is no pain and 10 is the worst possible or unbearable pain, 
please mark on the scale the number that best describes the pain or discomfort you are feeling in 
the operated* eye at this time. The middle of the scale (around 5) can be used to describe 
“moderate pain”. Only whole number scores are allowed.  
 
 
 
 
 
 
 
 
 
 
*At the screening assessment visit, the patient will be asked about the eye scheduled for surgery. 
The examiner will record the number selected by the patient on the appropriate eCRF. 
 
 


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Intraocular Pressure Procedures  
Intraocular pressure will be taken by qualified study site personnel (Investigator or his/her 
designee, technician) using a calibrated Goldmann application tonometer affixed to a slit lamp. 
The same instrument should be used at every study visit, if possible. 
The subject and slit lamp should be adjusted so that the subject’s head is firmly positioned on the 
chin rest and against the forehead rest. Both eyes will be tested, with the right eye preceding the 
left eye. The tension knob is pre-set at a low pressure value (4-6 mmHg) before and after each 
measurement.  
The technician will look through the binocular viewer of the slit lamp at low power and follow 
the image of the fluorescein-stained semicircles while he/she slowly rotates the tension knob 
until the inner borders of the fluorescein rings touch each other at the midpoint of their pulsation 
in response to the cardiac cycle. When this image is reached, the technician then takes his/her 
fingers off the tension knob and records the IOP reading in the source document. The procedure 
will be repeated on the same eye twice consecutively.  
If the measurements are within 2 mmHg or less of each other, the mean of the 2 readings will be 
calculated and recorded. If the 2 readings differ by more than 2 mmHg, a third (consecutive) 
reading will be taken and the median (middle) IOP will be recorded.  
Rounding of the mean IOP result is not allowed (i.e. a mean of 25.5 mmHg does not qualify as 
26 mmHg for meeting eligibility criteria, or a mean of 35.5 mmHg does not qualify as 36 
mmHg). 
 
 


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Dilated Indirect Ophthalmoscopy 
Dilated indirect ophthalmoscopic examination will be performed as indicated in the study 
flowchart in Appendix 1 after the patient informed consent/authorization, medical 
history/demographics, urine pregnancy test (if applicable), pin-hole visual acuity, slit lamp 
biomicroscopy, and tonometry. The examination will not be performed until the patient’s eyes 
are deemed sufficiently dilated in the opinion of the Investigator. The Investigator will note any 
findings present and whether the findings are clinically significant or not clinically significant. 
Findings which are clinically significant will be described. All findings will be documented on 
each patient’s source document and corresponding electronic case report form.  
The following will be examined: 
• Vitreous 
• Retina 
• Macula 
• Choroid 
• Optic Nerve  
 


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APPENDIX 3: PROTOCOL AMENDMENT SUMMARY 
AMENDMENT 1 
BACKGROUND AND RATIONALE FOR AMENDMENT 
The purpose of Protocol Amendment 1 is to revise the exclusion/inclusion criteria, revise 
the naming conventions for the treatment arms and clarify the IP storage condition 
requirements.  
SUMMARY OF CHANGES 
 
In the table below, the protocol text was amended by the following conventions: 
• Deletions to the original text are indicated by strike through letters. 
• Additions to amended text are indicated by bold letters. 
• Replacements of wording in the amended text are indicated by bold and 
italicized letters. 
Section 
Reason for Amendment 
Protocol Currently Reads 
Amended Text 
Throughout document 
Administrative corrections 
made throughout document 
N/A 
N/A 
1 SYNOPSIS 
Dosage/Dose 
Regimen/ 
Instillation/ 
Application/Use: 
Treatment arm naming 
conventions revised 
[…] Each subject will receive 
a master kit containing an AM 
dosing box and a PM dosing 
box. Each dosing box will 
contain 2 aluminum pouches 
with 10 single-use vials each. 
The master kit’s contents will 
be as follows for subjects 
randomized to each of the 
respective treatment arms:  
1. OCS-01 QD – 1 OCS-01 
box for AM dosing and 1 
placebo (vehicle) box for 
PM dosing 
2. OCS-01 BID – 2 OCS-01 
boxes (1 for AM and 1 
for PM) 
3. Placebo (vehicle) – 2 
placebo (vehicle) boxes 
(1 for AM and 1 for PM). 
[…]  
 
[…] Each subject will 
receive a master kit 
containing an AM dosing 
box and a PM dosing box. 
Each dosing box will 
contain 2 aluminum 
pouches with 10 single-use 
vials each. The master kit’s 
contents will be as follows 
for subjects randomized to 
each of the respective 
treatment arms:  
1. OCS-01 QD + Placebo 
(vehicle) QD  
2. OCS-01 BID  
3. Placebo (vehicle) BID 
[…] 
 
1  SYNOPSIS 
Exclusion Criteria 
Revision to inclusion/ 
exclusion criteria 
[…] 5.  Use anti-
inflammatory agents, 
analgesics/pain relievers 
(including opioids, narcotics, 
and other pain medications), 
[…] 5.  Use anti-
inflammatory agents, 
analgesics/pain relievers 
(including opioids, 
narcotics, and other pain 


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or immunomodulating 
agents, systemically or in 
either eye, and/or use 
medications for benign 
prostatic hyperplasia (BPH), 
from the washout period 
through the duration of the 
study. Washout periods for 
medications prior to the day 
of cataract surgery are as 
follows: […] 
 
[…] h.  Medications for BPH 
(e.g. alpha adrenergic 
blocking agents including 
tamsulosin, silodosin, 
alfuzosin, and finasteride): 
28 days; […] 
 
medications), or 
immunomodulating agents, 
systemically or in either 
eye, and/or currently using 
or have any historic use of 
medications for benign 
prostatic hyperplasia 
(BPH) from the washout 
period through the duration 
of the study. Washout 
periods for medications 
prior to the day of cataract 
surgery are as follows: [...] 
[...] h. Medications for 
BPH (e.g. alpha 
adrenergic blocking agents 
including tamsulosin, 
silodosin, alfuzosin, and 
finasteride): all current or 
previous use of BPH 
medications excludes 
participation in this study. 
[…] 
1  SYNOPSIS 
Exclusion Criteria 
Revision to inclusion/ 
exclusion criteria 
[…] 8.  Have an IOP ≤ 5 
mmHg or ≥ 22 mmHg in 
either eye at Visit 1 (Day -1 
to Day -28 [prior to 
surgery]). Subjects taking 
IOP-lowering medication 
must be on ≤ 2 IOP-lowering 
medications. Prostaglandin 
analogs are not allowed 
within 4 weeks of Visit 2 
(Day 1 [18 to 30 hours post-
surgery]). […] 
 
[…] 8.  Have an IOP ≤ 5 
mmHg or ≥ 22 mmHg in 
either eye at Visit 1 (Day -1 
to Day -28 [prior to 
surgery]). Subjects taking 
IOP-lowering medication 
must not be on more than 
1 IOP-lowering 
medication. Prostaglandin 
analogs are not allowed 
within 4 weeks of Visit 2 
(Day 1 [18 to 30 hours 
post-surgery]). […] 
 
1  SYNOPSIS 
Exclusion Criteria 
Revision to inclusion/ 
exclusion criteria 
13. Have active or a history 
of chronic or recurrent 
inflammatory eye disease 
(e.g. iritis, scleritis, uveitis, 
iridocyclitis, or rubeosis 
iritis) in the study eye; 
 
13. Have active or a 
history of chronic or 
recurrent inflammatory 
eye disease (e.g. iritis, 
scleritis, uveitis, 
iridocyclitis, or rubeosis 
iritis) in either the fellow 
eye or the study eye; 


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6  STUDY 
POPULATION 
6.4  Exclusion 
Criteria 
 
Revision to inclusion/ 
exclusion criteria 
[…] 5. Use anti-
inflammatory agents, 
analgesics/pain relievers 
(including opioids, narcotics, 
and other pain medications), 
or immunomodulating 
agents, systemically or in 
either eye, and/or use 
medications for benign 
prostatic hyperplasia (BPH), 
from the washout period 
through the duration of the 
study. Washout periods for 
medications prior to the day 
of cataract surgery are as 
follows: […] 
[…] h. Medications for BPH 
(e.g. alpha adrenergic 
blocking agents including 
tamsulosin, silodosin, 
alfuzosin, and finasteride): 
28 days; […] 
 
[…] 5. Use anti-
inflammatory agents, 
analgesics/pain relievers 
(including opioids, 
narcotics, and other pain 
medications), or 
immunomodulating 
agents, systemically or in 
either eye, and/or 
currently using or have 
any history of use of 
medications for benign 
prostatic hyperplasia 
(BPH) from the washout 
period through the 
duration of the study. 
Washout periods for 
medications prior to the 
day of cataract surgery are 
as follows: […] 
[…] h.  Medications for 
BPH (e.g. alpha 
adrenergic blocking agents 
including tamsulosin, 
silodosin, alfuzosin, and 
finasteride): all current or 
previous use of BPH 
medications excludes 
participation in this study.  
[…] 
 
6  STUDY 
POPULATION 
6.4  Exclusion 
Criteria 
 
Revision to inclusion/ 
exclusion criteria 
[…] 8. Have an IOP ≤ 5 
mmHg or ≥ 22 mmHg in 
either eye at Visit 1 (Day -1 
to Day -28 [prior to 
surgery]). Subjects taking 
IOP-lowering medication 
must be on ≤ 2 IOP-lowering 
medications. Prostaglandin 
analogs are not allowed 
within 4 weeks of Visit 2 
(Day 1 [18 to 30 hours post-
surgery]). […] 
 
[…] 8. Have an IOP ≤ 5 
mmHg or ≥ 22 mmHg in 
either eye at Visit 1 (Day -1 
to Day -28 [prior to 
surgery]). Subjects taking 
IOP-lowering medication 
must not be on more than 
1 IOP-lowering 
medication. Prostaglandin 
analogs are not allowed 
within 4 weeks of Visit 2 
(Day 1 [18 to 30 hours 
post-surgery]). […] 


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6  STUDY 
POPULATION 
6.4  Exclusion 
Criteria 
 
Revision to inclusion/ 
exclusion criteria 
[…] 13. Have active or a 
history of chronic or 
recurrent inflammatory eye 
disease (e.g. iritis, scleritis, 
uveitis, iridocyclitis, or 
rubeosis iritis) in the study 
eye; […] 
 
[…] 13. Have active or a 
history of chronic or 
recurrent inflammatory 
eye disease (e.g. iritis, 
scleritis, uveitis, 
iridocyclitis, or rubeosis 
iritis) in either the fellow 
eye or the study eye; […] 
8  STUDY 
MATERIALS 
8.1.2  Instructions for 
Use and 
Administration 
 
Treatment arm naming 
conventions revised 
[…] Each subject will receive 
a master kit containing an AM 
dosing box and a PM dosing 
box. Each dosing box will 
contain 2 aluminum pouches 
with 10 single-use vials each. 
The master kit’s contents will 
be as follows for subjects 
randomized to each of the 
respective treatment arms:  
• OCS-01 QD – 1 OCS-01 
box for AM dosing and 1 
placebo (vehicle) box for 
PM dosing 
• OCS-01 BID – 2 OCS-01 
boxes (1 for AM and 1 for 
PM) 
• Placebo (vehicle) – 2 
placebo (vehicle) boxes (1 
for AM and 1 for PM) […] 
[…] For Visit 1, the first dose 
will be instilled at the study 
visit under the supervision of 
the study staff (this dosing 
may be out of the 8 AM [± 2 
hours] dosing window). […]  
 
[…] Each subject will 
receive a master kit 
containing an AM dosing 
box and a PM dosing box. 
Each dosing box will 
contain 2 aluminum 
pouches with 10 single-use 
vials each. The master kit’s 
contents will be as follows 
for subjects randomized to 
each of the respective 
treatment arms:  
• OCS-01 QD + Placebo 
(vehicle) QD  
• OCS-01 BID  
• Placebo (vehicle) BID 
[…] 
[…] For Visit 2, the first 
dose will be instilled at the 
study visit under the 
supervision of the study 
staff (this dosing may be 
out of the 8 AM [± 2 hours] 
dosing window). […]  
 
9  STUDY 
METHODS AND 
PROCEDURES 
9.1.5  Methods for 
Clarification regarding 
use of randomization 
number instead of subject 
number 
 […] Each subject who 
qualifies for entry will be 
assigned a subject number and 
corresponding treatment 
according to the 
[…] Each subject who 
qualifies for entry will be 
assigned a randomization 
number and corresponding 
treatment according to the 


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Assignment to 
Treatment Groups: 
 
randomization code. Study 
drug will be randomly 
assigned using a 1:1:1 
assignment ratio, stratified by 
site, via an interactive 
response system. […] 
 
randomization code. Study 
drug will be randomly 
assigned using a 1:1:1 
assignment ratio, stratified 
by site, via an interactive 
response system. […] 
9  STUDY 
METHODS AND 
PROCEDURES 
9.2.1  Prohibited 
Medications/ 
Treatments 
 
Revision to inclusion/ 
exclusion criteria 
• […] Anti-inflammatory 
agents, analgesics/pain 
relievers (including 
opioids, narcotics, and 
other pain medications), or 
immunomodulating agents, 
systemically or in either 
eye, and/or the use of 
medications for BPH, from 
the washout period through 
the duration of the study; 
[…] 
[…] Table 2: Non-allowed 
Medications and Washout 
Periods 
Medication 
Washout 
Period 
Topical ocular 
steroids 
14 days 
Periocular 
injection of any 
corticosteroid 
solution 
28 days 
Intraocular 
treatment with a 
corticosteroid 
56 days 
after 
implantation 
Fluocinolone 
acetonide drug 
delivery systems 
48 months 
after 
implantation 
Intravitreal 
injection 
95 days 
after 
injection 
Systemic 
treatment with a 
corticosteroid 
including oral 
14 days 
Systemic or 
parenteral 
sustained/extende
180 days 
• […] Use anti-
inflammatory agents, 
analgesics/pain relievers 
(including opioids, 
narcotics, and other pain 
medications), or 
immunomodulating 
agents, systemically or in 
either eye, and/or 
currently using or have 
any historic use of 
medications for benign 
prostatic hyperplasia 
(BPH), from the 
washout period through 
the duration of the study; 
[…] 
[…] Table 3: Non-
allowed Medications 
and Washout Periods 
Medication 
Washout 
Period 
Topical ocular 
steroids 
14 days 
Periocular 
injection of any 
corticosteroid 
solution 
28 days 
Intraocular 
treatment with 
a corticosteroid 
56 days 
after 
implantation 
Fluocinolone 
acetonide drug 
delivery 
systems 
48 months 
after 
implantation 
Intravitreal 
injection 
95 days 
after 
injection 
Systemic 
treatment with 
14 days 


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Page 62 of 65 
d release 
corticosteroid 
Topical ocular 
NSAIDs 
7 days 
Systemic 
analgesics/pain 
relievers (e.g. 
gabapentin, 
pregabalin, and 
opioids) 
14 days 
Systemic 
acetaminophen, 
NSAIDs, 
acetylsalicylic 
acid, or other 
anti-inflammatory 
agents 
7 days 
BPH medication 
(e.g. alpha 
adrenergic 
blocking agents 
including 
tamsulosin, 
silodosin, 
alfuzosin, and 
finasteride) 
28 days 
Immunomodulati
ng or 
immunosuppressi
ve agents (e.g. 
cyclosporine, 
calcineurin 
inhibitors, 
antiproliferative 
agents, mTOR 
inhibitors, etc.) 
56 days 
Mast cell 
stabilizers or anti-
histamines (e.g. 
β2-adrenergic 
agonists. 
cromoglicic acid, 
ketotifen, 
brompheniramine
, cetirizine, 
diphenhydramine) 
7 days 
 
 
a corticosteroid 
including oral 
Systemic or 
parenteral 
sustained/exten
ded release 
corticosteroid 
180 days 
Topical ocular 
NSAIDs 
7 days 
Systemic 
analgesics/pain 
relievers (e.g. 
gabapentin, 
pregabalin, and 
opioids) 
14 days 
Systemic 
acetaminophen, 
NSAIDs, 
acetylsalicylic 
acid, or other 
anti-
inflammatory 
agents 
7 days 
BPH 
medication 
(e.g. alpha 
adrenergic 
blocking agents 
including 
tamsulosin, 
silodosin, 
alfuzosin, and 
finasteride) 
no current 
or historic 
use 
Immunomodula
ting or 
immunosuppres
sive agents (e.g. 
cyclosporine, 
calcineurin 
inhibitors, 
antiproliferative 
agents, mTOR 
inhibitors, etc.) 
56 days 
Mast cell 
stabilizers or 
anti-histamines 
(e.g. β2-
adrenergic 
agonists. 
cromoglicic 
acid, ketotifen, 
bromphenirami
ne, cetirizine, 
diphenhydrami
7 days 


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ne) 
 
12.4  Labeling, 
Packaging, Storage, 
Accountability, and 
Return or Disposal 
of Study Drug 
12.4.2  Storage of 
Study Drug 
 
Clarification on the IP 
storage condition 
requirements 
The study drug must be stored 
in a secure area accessible 
only to the Investigator and 
his/her designees. The study 
drug will be dispensed only to 
subjects entered into the 
clinical study, in accordance 
with the conditions specified 
in this protocol. […] 
[…] Once dispensed to 
subjects, study drug should be 
stored at room temperature.  
 
The study drug must be 
stored in a secure area 
accessible only to the 
Investigator and his/her 
designees. The study drug 
will be dispensed only to 
subjects entered into the 
clinical study, in accordance 
with the conditions 
specified in this protocol. 
[…] 
[…] Once dispensed to 
subjects, study drug should 
be stored at ambient 
temperature.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Oculis 
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Appendix 4: Ora Approvals 
Protocol Title: 
A Randomized, Double-masked, Vehicle-Controlled Study 
Evaluating the Efficacy and Safety of Two Doses ofOCS-01 
compared to Vehicle in the Treatment Inflammation and Pain 
Following Cataract Surgery 
Protocol Number: 
DX216 
Protocol Date: 
08Aug2019 
This clinical study protocol was subject to critical review and has been approved by the Sponsor. 
The following personnel contributed to writing and/or approving this protocol. 
,oocuSigned by Dr. David Hollander 
0 0 
· I 11...II . . I. .. 
j ' approve this document 
Signed: 
r. ±Iv t\ou..®\,IM,r 
8/9/2019 9:27:42 AM PDT
Name: 
vid Hollander, M.D., M.B.A. 
Title: c1u'er{lctf8|i}Bf¥ACABD19D58AD442 
Company: Ora, Inc. 
,DocuSigned by Aron Shapiro 
. a A 
- \
I ' approve this document 
Signed: 
#;, c, 
t\ 4 
a1912019 9-02·23 AM eor 
Nam . ron Shapiro 
Title: Sr.Vt'tfe!V²ii.³´1tµina¶tl2·1'&0 
Company: Ora, Inc. 
,oocuSigned by Dale USNER 
Signed:_--1¸'-¹--U.._£._º_a_---'-"''""""" ......... .......,.,=......_-
Name: 
le Usner, Ph.D.
Title: Bi»lf fficRuf EC424CA 7 40A308EOA4DB77 
Company: SDC 
,oocuSigned by Robert Rapoza 
l approve this document 
Signed: 
8/912019 9:41:56 AM PDT 
Name: obert Rapoza
Title: D1rett8P,1 eil¥i¥t\'f()\%t&ir8tl~E6EA94F 
Company: Ora, Inc. 
,oocuSigned by Amy Baggeroer 
. 
 
R 
-/1.... 
11 approve this document 
Signed: 
f.l U¼bU" 
aro120rn a·sz·rn AM eor 
Nam . my Baggeroer 
Title: Ctirli'ea1fflJelel4½ft98¾0o 
Company: Ora, Inc. 
,oocuSigned by Michelle Olsen 
S. 
d a 
'4A: ., •• dll_ 0". __ I' approve this document 
igne : 
"¿ 
À 
Á111i;zo•P 1?···0• AJ,' i;io-
Name:chelle Olsen, Ph.D. 
Title: Rftit6ilyAWflite1'916B4C757Eo1os95c71
Company: Ora, Inc. 
Confidential 
8/9/2019
Date: _____ _ 
8/9/2019
Date: _____ _ 
8/9/2019 
Date: _____ _ 
8/9/2019 
Date: -------
8/9/2019 
Date: _____ _ 
8/9/2019 
Date: -------
Page 64 of65 


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Appendix 5:  Investigator’s Signature 
Protocol Title: 
A Randomized, Double-masked, Vehicle-Controlled Study Evaluating 
the Efficacy and Safety of Two Doses of OCS-01 compared to Vehicle 
in the Treatment Inflammation and Pain Following Cataract Surgery 
Protocol Number: 
DX216 
Protocol Date: 
08Aug2019 
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 the Sponsor and its agents in confidence and, when this information is 
submitted to an Institutional Review Board (IRB), Ethical Review Committee (ERC) 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: 
Affiliation: 
Address: 
Telephone number: 

SAP_001.pdf: 
 
STATISTICAL ANALYSIS PLAN  
A Randomized, Double-masked, Vehicle-controlled Study Evaluating 
the Efficacy and Safety of Two Doses of OCS-01 compared to Vehicle 
in the Treatment of Inflammation and Pain Following Cataract Surgery 
 
 
 
Sponsor:   
 
Oculis ehf. 
 
 
 
 
 
 
Protocol Number: 
DX216 
 
Author:   
 
Brian Kilgallen, M.S. 
 
 
 
Senior Principal Biostatistician 
Statistics & Data Corporation 
 
SAP Version:   
1.0 Final 
SAP Date:   
 
08-Nov-2019 
 




Protocol DX216 SAP, Version 1.0 Final 
08-Nov-2019 
Confidential & Proprietary 
Page 3 of 33 
 
Table of Contents 
1. 
Introduction............................................................................................................................... 6 
2. 
Study Objectives ...................................................................................................................... 6 
2.1 Study Variables ........................................................................................................................ 6 
2.2 Primary Variables ..................................................................................................................... 6 
2.3 Secondary Variables ................................................................................................................ 6 
2.4 Safety Variables ....................................................................................................................... 6 
2.5 Statistical Hypotheses .............................................................................................................. 7 
3. 
Study Design and Procedures ................................................................................................. 8 
3.1 General Study Design .............................................................................................................. 8 
3.2 Schedule of Visits and Assessments ....................................................................................... 8 
4. 
Study Treatments ................................................................................................................... 10 
4.1 Method of Assigning Subjects to Treatment Groups ............................................................. 10 
4.2 Masking and Unmasking ........................................................................................................ 10 
5. 
Sample Size and Power Considerations ................................................................................ 10 
6. 
Data Preparation .................................................................................................................... 11 
6.1 Input Data ............................................................................................................................... 11 
6.2 Output Data ............................................................................................................................ 11 
7. 
Analysis Populations .............................................................................................................. 12 
7.1 Enrolled Subjects Population ................................................................................................. 12 
7.2 Full Analysis Set ..................................................................................................................... 12 
7.3 Per Protocol Population ......................................................................................................... 12 
7.4 Safety Population ................................................................................................................... 12 
8. 
General Statistical Considerations ......................................................................................... 12 
8.1 Unit of Analysis....................................................................................................................... 12 
8.2 Missing or Inconclusive Data Handling .................................................................................. 13 
8.2.1 
Partial Dates ................................................................................................................... 13 
8.2.2 
Missing Efficacy Data ..................................................................................................... 13 
8.2.3 
Missing Safety Data ....................................................................................................... 13 
8.3 Definition of Baseline ............................................................................................................. 14 
8.4 Data Analysis Conventions .................................................................................................... 14 
8.5 Adjustments for Multiplicity ..................................................................................................... 15 
9. 
Disposition of Subjects ........................................................................................................... 15 
10. 
Demographic and Pretreatment Variables ............................................................................. 16 
11. 
Medical History and Concomitant Medications ...................................................................... 16 
11.1 Medical History ....................................................................................................................... 16 
11.2 Prior and Concomitant Medications ....................................................................................... 17 


Protocol DX216 SAP, Version 1.0 Final 
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Confidential & Proprietary 
Page 4 of 33 
12. 
Dosing Compliance and Treatment Exposure ....................................................................... 18 
12.1 Dosing Compliance ................................................................................................................ 18 
12.2 Treatment Exposure ............................................................................................................... 18 
13. 
Efficacy Analyses ................................................................................................................... 19 
13.1 Primary Analysis .................................................................................................................... 19 
13.1.1 
Sensitivity Analyses of the Primary Efficacy Measures ............................................. 21 
13.1.2 
Subgroup Analyses of the Primary Efficacy Analysis ................................................ 23 
13.2 Secondary Analyses .............................................................................................................. 23 
13.2.1 
Anterior Chamber Cells .............................................................................................. 23 
13.2.2 
Ocular Pain ................................................................................................................. 24 
13.2.3 
Anterior Chamber Flare .............................................................................................. 24 
13.2.4 
Absence of Both Anterior Chamber Cells and Flare .................................................. 24 
13.2.5 
Rescue Medication Usage ......................................................................................... 24 
14. 
Safety Analyses ..................................................................................................................... 25 
14.1 Adverse Events ...................................................................................................................... 25 
14.2 Pin-hole Visual Acuity ............................................................................................................ 27 
14.3 Slit-Lamp Biomicroscopy Examination ................................................................................... 27 
14.4 Dilated Indirect Ophthalmoscopy ........................................................................................... 27 
14.5 Intraocular Pressure (IOP) ..................................................................................................... 28 
14.6 Clinical Laboratory Data ......................................................................................................... 28 
15. 
Interim Analyses ..................................................................................................................... 28 
16. 
Changes from Protocol-Stated Analyses ............................................................................... 28 
17. 
References ............................................................................................................................. 28 
18. 
Revision History ..................................................................................................................... 29 
19. 
Tables ..................................................................................................................................... 29 
20. 
Listings ................................................................................................................................... 31 
21. 
Figures ................................................................................................................................... 33 
 
 
 


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List of Abbreviations 
ADaM 
Analysis Data Model 
AE 
Adverse Event 
ATC 
Anatomical Therapeutic Chemical 
BID 
Bis in die (Twice Daily) 
CI 
Confidence Interval 
CS 
Clinically Significant 
eCRF 
Electronic Case Report Form 
ETDRS 
Early Treatment of Diabetic Retinopathy Study 
FAS 
Full Analysis Set 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IOP 
Intraocular Pressure 
LOCF 
Last Observation Carried Forward 
logMAR 
Logarithm of the Minimum Angle of Resolution 
MedDRA 
Medical Dictionary for Regulatory Activities 
MNAR 
Missing Not at Random 
NCS 
Not Clinically Significant 
OD 
Oculus Dexter (Right Eye) 
OS 
Oculus Sinister (Left Eye) 
OU 
Oculus Uterque (Both Eyes) 
PDF 
Portable Document Format 
PP 
Per Protocol 
PT 
Preferred Term 
QD 
Quaque die (Once Daily) 
RTF 
Rich Text Format 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SDC 
Statistics & Data Corporation 
SDTM 
Study Data Tabulation Model 
SOC 
System Organ Class 
TEAE 
Treatment-Emergent Adverse Event 
TLF 
Tables, Listings, and Figures 
WHO 
World Health Organization  
 
 


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1. Introduction 
The purpose of this statistical analysis plan (SAP) is to describe the planned analyses and reporting for 
protocol DX216, Amendment 1 dated 08-August-2019. 
This SAP is being written with due consideration of the recommendations outlined in the most recent 
International Conference on Harmonisation (ICH) E9 Guideline entitled Guidance for Industry: Statistical 
Principles for Clinical Trials and the most recent ICH E3 Guideline entitled Guidance for Industry: Structure 
and Content of Clinical Study Reports. 
This SAP describes the data that will be analyzed and the subject characteristics, efficacy, and safety 
assessments that will be evaluated. This SAP provides details of the specific statistical methods that will 
be used. The statistical analysis methods presented in this document will supersede the statistical analysis 
methods described in the clinical protocol. If additional analyses are required to supplement the planned 
analyses described in this SAP, they may be completed and will be identified in the clinical study report. 
2. Study Objectives 
The primary objective of this study is to evaluate the efficacy and safety of OCS-01 once daily (QD) and 
twice daily (BID) compared to placebo (vehicle) BID in the treatment of inflammation and pain following 
cataract surgery. 
The secondary objective of this study is to evaluate the optimal dosing frequency of OCS-01 (QD versus 
BID) in the treatment of inflammation and pain following cataract surgery. 
2.1 
Study Variables 
2.2 
Primary Variables 
The hierarchical primary efficacy measures are the absence of anterior chamber cells (i.e. score of ‘0’) at 
Visit 6 (Day 15) and the absence of pain (i.e. score of ‘0’) at Visit 4 (Day 4). 
2.3 
Secondary Variables 
The secondary efficacy measures include: 
• 
Absence of anterior chamber cells at Visits 4, 5, and 7 (Days 4, 8, and 22);  
• 
Absence of pain at Visits 3, 5, 6, and 7 (Days 8, 15, and 22);  
• 
Absence of flare at Visits 4, 5, 6, and 7 (Days 4, 8, 15, and 22). 
• 
Absence of both anterior chamber cells and flare at Visits 4, 5, 6, and 7 (Days 4, 8, 15, and 22); 
and 
• 
Use of rescue medication on or prior to each visit and overall. 
2.4 
Safety Variables 
Safety variables to be summarized will include visual acuity, intraocular pressure (IOP), occurrence of 
adverse events (AE), and measurements from slit lamp biomicroscopy and dilated indirect ophthalmoscopy. 


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2.5 
Statistical Hypotheses 
The hierarchical statistical hypotheses for evaluating the objectives of the study are as follows: 
Primary Endpoint:  
H011: 
The difference, between study eyes treated with OCS-01 BID and study eyes treated with 
placebo (vehicle), in the proportion of study eyes with absence of anterior chamber cells (score of 
‘0’) at Visit 6 (Day 15) = 0. 
H111: 
The difference, between study eyes treated with OCS-01 BID and study eyes treated with 
placebo (vehicle), in the proportion of study eyes with absence of anterior chamber cells (score of 
‘0’) at Visit 6 (Day 15) ≠ 0, with superiority claimed if the difference is greater than 0 (OCS-01 BID 
– placebo [vehicle]). 
H012: 
The difference, between study eyes treated with OCS-01 QD and study eyes treated with 
placebo (vehicle), in the proportion of study eyes with absence of anterior chamber cells (score of 
‘0’) at Visit 6 (Day 15) = 0. 
H112: 
The difference, between study eyes treated with OCS-01 QD and study eyes treated with 
placebo (vehicle), in the proportion of study eyes with absence of anterior chamber cells (score of 
‘0’) at Visit 6 (Day 15) ≠ 0, with superiority claimed if the difference is greater than 0 (OCS-01 QD 
– placebo [vehicle]). 
Hierarchical Primary Endpoint:  
H021: 
The difference, between study eyes treated with OCS-01 BID and study eyes treated with 
placebo (vehicle), in the proportion of study eyes with absence of pain (score of ‘0’) at Visit 4 (Day 
4) = 0. 
H121: 
The difference, between study eyes treated with OCS-01 BID and study eyes treated with 
placebo (vehicle), in the proportion of study eyes with absence of pain (score of ‘0’) at Visit 4 (Day 
4) ≠ 0, with superiority claimed if the difference is greater than 0 (OCS-01 BID – placebo 
[vehicle]). 
H022: 
The difference, between study eyes treated with OCS-01 QD and study eyes treated with 
placebo (vehicle), in the proportion of study eyes with absence of pain (score of ‘0’) at Visit 4 (Day 
4) = 0. 
H122: 
The difference, between study eyes treated with OCS-01 QD and study eyes treated with 
placebo (vehicle), in the proportion of study eyes with absence of pain (score of ‘0’) at Visit 4 (Day 
4) ≠ 0, with superiority claimed if the difference is greater than 0 (OCS-01 QD – placebo 
[vehicle]). 
Multiple comparison adjustments for testing OCS-01 BID and OCS-01 QD versus placebo (vehicle) in the 
absence of anterior chamber cells will not be made (i.e. the testing of H011 versus H111 and H012 versus H112 
will both be completed at a 2-sided alpha = 0.10). A hierarchical testing strategy will be employed for testing 
absence of pain; statistical inference will only be made on the absence of pain endpoint if the corresponding 
OCS-01 dose (BID or QD) demonstrated statistical superiority over placebo (vehicle) in the absence of 
anterior chamber cells.  


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3. Study Design and Procedures 
3.1 
General Study Design 
This study is a multi-center, randomized, double-masked, placebo (vehicle)-controlled study, designed to 
evaluate the efficacy and safety of OCS-01 ophthalmic suspension (QD versus BID) compared to placebo 
in treating inflammation and pain following cataract surgery.  
Eligible subjects will be randomized 1:1:1 to receive OCS-01 QD, OCS-01 BID, or placebo BID. Subjects 
will dose 1 drop in the study eye BID for 14 days, beginning 1 day post-surgery in the operated eye. The 
study will last 20-52 days, including screening and a follow-up visit at Visit 7 (Day 22 ± 2). 
3.2 
Schedule of Visits and Assessments 
The schedule of visits and assessments is provided in Table 1. 


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Table 1: Scheduled of Visits and Measurements 
 
Study Parameter 
Visit 1 
(-28 to -1 Day(s) 
Prior to 
Surgery) 
Visit 2 
(Day 1, 18-30 h 
Post-Surgery) 
Treatment Period 
Follow-up 
Visit 3 
(Day 2, 
telephone call) 
Visit 4 
(Day 4 ± 1) 
Visit 5 
(Day 8 ± 1) 
Visit 6 
(Day 15 ± 2) 
Visit 7 
(Day 22 ± 2) 
Informed Consent / HIPAA 
X 
 
 
 
 
 
 
Demographic Data 
X 
 
 
 
 
 
 
Medical and Medication History 
X 
 
 
 
 
 
 
Urine pregnancy Test 
X 
 
 
 
 
 
X 
Review Inclusion / Exclusion 
Criteria 
X 
X 
 
 
 
 
 
Medical and Medications Update 
 
X 
 
X 
X 
X 
X 
Ocular Pain (Study Eye Only) 
X 
X 
X 
X 
X 
X 
X 
Pin-hole Visual Acuity 
X 
X 
 
X 
X 
X 
X 
Slit lamp Biomicroscopy 
X 
X 
 
X 
X 
X 
X 
Ocular Inflammation Assessment of 
the Anterior Chamber Cell and Flare 
(Study Eye Only) 
X 
X 
 
X 
X 
X 
X 
Intraocular Pressure 
X 
 
 
X 
X 
X 
X 
Randomization 
 
X 
 
 
 
 
 
Dilated Indirect Ophthalmoscopy 
X 
 
 
 
 
 
X 
Dispense Study Medication and 
Dosing Diary 
 
X 
 
 
 
 
 
AE Query 
 
X 
 
X 
X 
X 
X 
Exit from Study 
 
 
 
 
 
 
X 


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4. Study Treatments 
Subjects will be assigned to 1 of 3 possible study treatments in this study. The study treatments to be 
evaluated in this study are: 
• 
OCS-01 ophthalmic suspension (QD) + Placebo (vehicle) (QD) 
• 
OCS-01 ophthalmic suspension (BID) 
• 
Placebo (vehicle) ophthalmic suspension (BID) 
Each subject will receive a master kit containing an AM dosing box and a PM dosing box. Each dosing box 
will contain 2 aluminum pouches with 10 single-use vials each. 
4.1 
Method of Assigning Subjects to Treatment Groups 
Each subject who signs an informed consent form (ICF) will be assigned a screening number. Screening 
numbers will be assigned in sequential order at each site beginning with 001 and will follow the two-digit 
site number (e.g. subject 077 at Site 99 will have Screening Number 99-077). Inclusion and exclusion 
criteria will be reviewed, and qualifying subjects will be enrolled into the study. The screening number will 
be used to identify subjects in all datasets and listings for this study. 
At the Visit 2 / Day 1 visit, eligible subjects will be randomized in a 1:1:1 ratio, stratified by site, to receive 
either OCS-01 ophthalmic suspension (QD) + Placebo (vehicle) (QD), OCS-01 ophthalmic suspension 
(BID), or Placebo (vehicle) ophthalmic suspension (BID). 
4.2 
Masking and Unmasking 
An independent biostatistician who is not otherwise involved in the study will generate the final, unmasked 
subject randomization as well as the final, unmasked kit list randomization. Interactive response technology 
will be used to provide randomization assignments. 
As described in Section 4, each subject will receive a master kit containing an AM dosing box and a PM 
dosing box. For masking purposes, each dosing box and the pouches within it will be labeled either “AM” 
or “PM.” Dosing boxes and pouches will be labeled this way regardless of whether the product within the 2 
boxes is the same (i.e. OCS-01 BID and placebo [vehicle] treatment arms) or different (i.e. OCS-01 QD).  
5. Sample Size and Power Considerations 
With a total of 150 subjects (50 subjects per treatment group: OCS-01 BID, OCS-01 QD, and placebo 
[vehicle] in the Full Analysis Set [FAS] [i.e. 1:1:1 randomization]), the study has 85% power to detect a 
statistically significant treatment difference between OCS-01 BID and placebo and between OCS-01 QD 
and placebo for the proportion of subjects with absence of cells on post-operative Visit 6 (Day 15), assuming 
a 2-sided alpha level of 0.10 and the proportion of subjects with absence of cells is 0.45 (active) and 0.20 
(placebo [vehicle]).   


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Additionally, with this sample size, the study has 83% power to detect a statistically significant treatment 
difference between OCS-01 (BID or QD) and placebo for the proportion of subjects with absence of ocular 
pain on post-operative Visit 4 (Day 4), assuming a 2-sided alpha level of 0.10, and the proportion of subjects 
with absence of ocular pain is 0.50 (active) and 0.25 (placebo [vehicle]). 
6. Data Preparation 
6.1 
Input Data 
All reported study data will be recorded on the electronic case report forms (eCRF) supplied by Statistics & 
Data Corporation (SDC). Only the Principal Investigator and authorized study staff according to the 
Delegation of Responsibilities log are entitled to make entries in the eCRF.  
After data are entered into the clinical study database, electronic edit checks and data review will be 
performed. All data validation specifications and procedures are detailed in the Data Validation Manual as 
a separate document. When the database has been declared to be complete and accurate, the database 
will be locked. Any changes to the database after data have been locked can only be made with the approval 
of the Sponsor and the clinical contract research organization (if applicable), in consultation with SDC.  
All analyses outlined in this document will be carried out after the following have occurred: 
• 
All data management requirements are met according to SDC standard operating procedures, 
including data entry, performance of edit and validation checks, documentation and resolution of 
data queries, and database lock with written authorization provided by appropriate SDC and 
Sponsor personnel. 
• 
Protocol deviations have been identified and status defined (major/minor deviations). 
• 
Analysis populations have been determined. 
• 
Randomized treatment codes have been unmasked. 
6.2 
Output Data 
Data from remote data capture and external data will be transferred to Biostatistics and incorporated into 
standard formats following the Study Data Tabulation Model (SDTM). Data will then be mapped to analysis 
datasets using the Analysis Data Model (ADaM). Both SDTM- and ADaM-formatted data will be used to 
create the subject listings, while all tables and figures will be based on the ADaM-formatted data. 
SDTM will follow the SDTM version 1.4 model and will be implemented using the SDTM Implementation 
Guide version 3.2 and the SDTM Controlled Terminology version 2016-06-24. ADaM data will follow the 
ADaM version 2.1 model and will be implemented using the ADaM Implementation Guide version 1.3. Both 


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SDTM and ADaM will be validated using Pinnacle 21 version 2.2. Any discrepancies in the validation will 
be noted in reviewer’s guides accompanying the final data transfers. 
Define.xml will be created for SDTM and ADaM using the Define-XML version 2.0 model 
7. Analysis Populations 
7.1 
Enrolled Subjects Population 
The enrolled subjects population will consist of all subjects who have provided informed consent and have 
data in the clinical database. 
7.2 
Full Analysis Set  
The full analysis set (FAS) will consist of all randomized subjects, analyzing subjects under the treatment 
to which they were randomized. 
7.3 
Per Protocol Population 
The per protocol (PP) population is a subset of the FAS and includes subjects who remain in the study 
through Visit 6 (Day 15) (or who discontinue due to lack of efficacy or receive rescue medication prior to 
Visit 6 [Day 15]) with no major protocol violations that would affect the assessment of the primary efficacy 
endpoints of the study, analyzing subjects under the treatment received. Major protocol violations related 
to study inclusion or exclusion criteria, conduct of the trial, subject management, or subject assessment will 
be identified prior to unmasking treatment. 
7.4 
Safety Population 
The Safety population includes all randomized subjects who receive at least 1 dose of study medication. 
The Safety population will be analyzed as treated and will be used for the safety analyses. No data will be 
excluded for any reason. 
8. General Statistical Considerations 
8.1 
Unit of Analysis 
For measurements taken at the subject level, the unit of analysis will be the individual subject and for 
measurements taken at the eye level, the unit of analysis will be the individual eye unless otherwise 
indicated. Where applicable, summaries by eye will present results separately for the study eye and for the 
non-study eye. Any outcomes (eg, adverse events) with reported location of OU will be counted as an event 
for both the study eye as well as the non-study eye. 
Non-ocular AEs, medical history, and concomitant medication usage will be presented at the subject level, 
but ocular AEs, medical history, and concomitant medication usage will be presented at the eye level as 
appropriate. 


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8.2 
Missing or Inconclusive Data Handling 
8.2.1 
PARTIAL DATES 
Imputation of partial or missing dates will be conducted in order to classify data as treatment-emergent or 
concomitant with treatment. Partial/missing start and end dates for AEs and concomitant medications will 
be imputed as follows: 
Partial/missing start date:  
• 
Dates with missing day only will be imputed as the 1st of the month unless the month and year are 
same as the month and year of first dose of study medication, in which case missing day will be 
imputed as the first dose day of study medication.  
• 
Dates with both day and month missing will be imputed as 01-Jan unless the year is same as the 
year of first dose of study medication, in which case missing day and month will be imputed as the 
first dose day and month of study medication. 
• 
Completely missing dates will be imputed as the first dose date of study medication unless the end 
date is on or before the first dose date of study medication, in which case missing date will be 
imputed as 1 Jan of the same year as the end date. 
Partial/missing end date:  
• 
Dates with missing day only will be imputed as the last day of the month unless the month and year 
are the same as the month and year of the last dose of study medication, in which case missing 
day will be imputed as the last dose day of study medication.  
• 
Dates with both day and month missing will be imputed as 31 Dec unless the year is same as the 
year of the last dose of study medication, in which case missing day and month will be imputed as 
the last dose day and month of study medication.  
• 
If the ongoing flag is missing or “Yes” then the date will not be imputed. If ongoing is “No” then the 
missing end date will be imputed as the last dose date. 
The original dates will be displayed in data listings and the imputed dates will be used in derivations only 
(study day, treatment-emergence status, etc). 
8.2.2 
MISSING EFFICACY DATA 
The primary analyses of all efficacy data will use last observation carried forward (LOCF) to impute missing 
data; data for visits after a subject is discontinued for lack of efficacy or receives rescue medication will be 
imputed as failures for success/failure endpoints and will be imputed using LOCF for other endpoints. 
Additional sensitivity analyses based on alternate handling of missing values will be conducted, and 
described in further detail in Section 13.1.1. 
8.2.3 
MISSING SAFETY DATA 
For all safety variables, missing data will not be imputed, observed values will be presented. 


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8.3 
Definition of Baseline 
Baseline is defined as the last non-missing measure prior to initiation of study treatment. Change from 
baseline will be calculated as follow-up visit value minus baseline value. 
8.4 
Data Analysis Conventions 
All data analysis will be performed by SDC after the study is completed and the database has been locked. 
After the study database has been locked and any other prerequisites for unmasking are met (e.g. all 
protocol deviations have been classified as major or minor), unmasking will be done for the purpose of the 
primary analysis, and all planned tables, listings, and figures (TLF) will be generated. 
Statistical programming and analyses will be performed using SAS® version 9.4 or higher. Output will be 
provided in rich text format (RTF) for tables and portable document format (PDF) for TLF using landscape 
orientation. All study data will be listed by subject, treatment, and visit (as applicable) based on all 
randomized subjects unless otherwise specified (e.g. demography data, which is also captured for screen 
failure subjects). 
Summaries for continuous and ordinal variables will include the number of observations (n), arithmetic 
mean, standard deviation (SD), median, minimum, and maximum. Minima and maxima will be reported with 
the same precision as the raw values; means and medians will be presented to one additional decimal 
place than reported in the raw values. Standard deviations will be presented to two additional decimal 
places than reported in the raw values. Summaries for discrete variables will include counts and 
percentages. All percentages will be rounded to one decimal place (i.e. XX.X%). Differences between active 
treatment groups and placebo (vehicle) will be calculated as active minus placebo and change from 
baseline will be calculated as follow-up visit minus baseline.  
Dates within subject data listings will be presented based on ISO 8601 standard, as DD-MMM-YYYY. 
All efficacy analyses will use a 2-sided alpha = 0.10 test unless otherwise stated and corresponding 2-sided 
90% and 95% confidence intervals (CI) will be presented as applicable. All p-values will be rounded to 4 
decimal places; p-values less than 0.0001 will be presented as “<0.0001”; p-values greater than 0.9999 will 
be presented as “>0.9999.” 
Unless otherwise specified, summaries will be presented by treatment group and (where applicable) eye 
and visit. Analysis by visit will be based on nominal visit identifier. Data from unscheduled visits, 
unscheduled time points, or unplanned repeat assessments will be included in the data listings. In general, 
these data will be excluded from the summary tables unless otherwise specified. 
Efficacy summaries by treatment group will include the 3 protocol defined treatment groups. Summaries of 
subject disposition and baseline characteristics will include additional subject groupings defined as: 
• 
OCS-01 Total, consisting of subjects in the OCS-01 QD + Placebo or OCS-01 BID treatment 
groups. 
• 
All Subjects, consisting of all subjects in the analysis population, regardless of treatment group. 


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Summaries of safety variables will also include the OCS-01 Total treatment group (but not All Subjects 
group). 
Subject data listings will be sorted by treatment group, subject number, visit/time point, and parameter as 
applicable. Subject data listings will use the largest applicable analysis population. In most cases this will 
be the Full Analysis Population (for assessments collected in randomized subjects) or the Safety Population 
(for assessments collected in randomized subjects where dosing is also relevant.  
For multiple imputation analyses where a seed may be specified, the seed will be set to 8-digit numeric 
value corresponding to the database lock date in YYYYMMDD format (eg, 20190901). If multiple seeds are 
needed within a program, the seed will be based on a 9-digit numeric consisting of the database lock date 
in YYYYMMDD format concatenated by an additional integer denoting the invocation number (eg, the first 
invocation would be 201909011, second would be 201909012). In addition, twenty imputations will be used 
as starting quantity, if the fraction of missing information is >30% then this will be increased to 40 
imputations (Graham 2007). 
8.5 
Adjustments for Multiplicity 
The hierarchy of statistical hypotheses for testing is described in Section 2.5.  
Multiple comparison adjustments for testing OCS-01 BID and OCS-01 QD versus placebo (vehicle) in the 
absence of anterior chamber cells will not be made (i.e. the testing of H011 versus H111 and H012 versus H112 
will both be completed at a 2-sided alpha = 0.10). A hierarchical testing strategy will be employed for testing 
absence of pain; statistical inference will only be made on the absence of pain endpoint if the corresponding 
OCS-01 dose (BID or QD) demonstrated statistical superiority over placebo (vehicle) in the absence of 
anterior chamber cells.  
Operationally, p-values from the predefined analyses within the SAP will be presented within all applicable 
tables,  however if one or both doses are not significantly different from placebo for the anterior chamber 
cell variable, then p-values generated for comparisons of the ocular pain variable should be considered 
exploratory / nominal in nature. 
9. Disposition of Subjects 
Disposition of subjects will be summarized for the Enrolled Subjects population. Among enrolled subjects, 
the total number of subjects randomized and number of subjects not randomized (i.e. screen failure) will be 
summarized. The primary reason for screen failure (among screen failure subjects) will also be tabulated.  
A subject listing will be provided which includes randomization status and reason for screen failure for 
subjects not randomized. 
Disposition of subjects will also be summarized among randomized subjects. The number of subjects in 
each of the analysis populations (FAS, PP, Safety population) as well as for each investigational site will 
be displayed by treatment group and overall. The number and percentage of subjects completing the study, 


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prematurely discontinuing from the study, and the reasons for study discontinuation will be summarized by 
treatment group and overall. A subject listing will be provided which includes the date and reason for 
premature study discontinuation. 
The number and percentage of subjects with major protocol deviations will be summarized by eCRF 
deviation code (e.g., Inclusion/Exclusion deviation), treatment group, and overall for the FAS. Protocol 
deviations will be reviewed and classified as major or minor prior to database lock and unmasking. Major 
deviations will be defined as those deviations that potentially impact the primary outcome of the study. A 
subject listing will be provided which includes the date of the deviation, the deviation code, the deviation 
description, and the classification of whether the deviation was judged to be major or minor in a blinded 
review. 
In addition, subject listings will be provided that include informed consent date, inclusion and exclusion 
criteria violations, and exclusions from the PP population.  
Details of the study randomization, including randomization date and time, randomized treatment and actual 
treatment, will also be included within a subject listing. 
10. Demographic and Pretreatment Variables 
The demographic variables collected in this study include age, sex, childbearing potential, ethnicity, race, 
and iris color. Subjects who record more than one race will be grouped into a single category denoted as 
Multi-Racial. Iris color will be summarized at the subject level, with a category for heterochromia. 
Demographic variables will be summarized for the FAS and Safety population, separately. 
Age (years) will be summarized, overall and by treatment, using continuous descriptive statistics. Age will 
also be categorized as follows: < 65 years and ≥ 65 years. Age will be reported in years and calculated 
using the following formula: 
Age = (Informed Consent Date – Date of Birth) / 365.25, truncated as an integer 
The number and percentage of subjects will be presented by treatment group and overall for age category, 
sex, childbearing potential status, race, ethnicity, and iris color.  
A subject listing that includes all demographic variables will be provided. 
11. Medical History and Concomitant Medications 
11.1 
Medical History 
Medical history and ocular history will be summarized separately for the Full Analysis Set. Ocular medical 
history is a subset of the overall medical history and will include those medical history items where an eye 
location (right eye [OD], left eye [OS], or both eyes [OU]) has been specified. 
Medical history and ocular history will be coded using Medical Dictionary for Regulatory Activities 
(MedDRA), version 22.0 (or higher).  


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Non-ocular medical history will be summarized using discrete summary statistics and presented by 
treatment group at the subject level by System Organ Class (SOC) and Preferred Term (PT). Ocular 
medical history will be summarized at the subject level by SOC and PT and separately for the study eye 
and non-study eye. If a subject reports the same PT multiple times within the same SOC, that PT will only 
be reported once within that SOC. As with the PT, if a subject reports multiple conditions within the same 
SOC, that SOC will only be reported once.  
Within table summaries, SOC will be listed in ascending alphabetical order; PTs will be listed in order of 
descending frequency for all subjects within each SOC. 
Listings of medical history will be generated separately for ocular and non-ocular data. The study eye will 
be identified within listings of ocular medical history. 
Details of each subject’s cataract surgery will also listed. 
11.2 
Prior and Concomitant Medications 
Prior and concomitant medication usage will be summarized with the Safety population. 
Prior and concomitant medications will be coded using World Health Organization (WHO) Drug Global (B3, 
March 2019 [or higher]) dictionary, and summarized to the therapeutic drug class (Anatomical Therapeutic 
Chemical [ATC] Level 4 classification) and preferred name. If the ATC Level 4 classification is not provided, 
the next lowest classification that is provided in the coding dictionary will be used. The preferred name will 
be defined as the active ingredient; if the active ingredient is not provided or includes more than two 
ingredients (e.g. multivitamins), then the drug name will be summarized as the preferred name. Any 
uncoded terms will be summarized under the ATC classification and preferred name of “Uncoded.” 
Prior medications are defined as those medications with an end date before first dose date of study 
administration. Concomitant medications are defined as those medications listed as having been taken (1) 
prior to initiation of study drug administration and continuing for any period of time following the first 
administration of study drug or (2) at any time following the first administration of study drug. With this 
definition, it should be noted it is possible for a medication to be both a prior and concomitant medication. 
Ocular medications are a subset of the overall medications and consist of those medication records where 
the location field on the eCRF is marked as OD, OS, or OU. In addition, medications which are classified 
as ‘non-ocular’ on the eCRF but which have potential to impact anterior chamber cell count or ocular pain 
will be reclassified as an ocular medication for analysis. These medications will be identified via manual 
review of coded medication classes as well as review of the indication fields. For purposes of analysis, the 
eye location value for analysis will be defined as OU. 
IOP lowering medications are a subset of medications where the investigator has indicated on the eCRF 
that the medication was used to lower IOP. Concomitant medications will be summarized separately for 
ocular and non-ocular medications. Concomitant ocular medications will be tabulated separately for study 


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eye and for non-study eye. Medications reported as OU will be summarized as a medication for both the 
study eye as well as the non-study eye. 
Medications will be tabulated for each treatment group using frequencies and percentages. Subjects may 
have more than one medication per ATC text. At each level of subject summarization, a subject will be 
counted once if he/she reports one or more medications. Percentages will be based on the number of 
subjects in each treatment group.  
The number and percent of subjects initiating IOP lowering medications will be summarized by treatment 
group at each post-BL visit as well as across all visits. 
Listings of prior and concomitant medications will be generated separately for ocular and non-ocular data. 
A separate listing will be generated for IOP lowering medications. 
Rescue medication usage is an efficacy measure for this study, analysis of rescue medication is described 
separately in Section 13.2.5. 
12. Dosing Compliance and Treatment Exposure 
12.1 
Dosing Compliance 
Details of individual administrations of study medication done at home by subjects are not captured within 
the clinical database, therefore dosing compliance will not be summarized. 
12.2 
Treatment Exposure  
The number and percent of subjects receiving at least one dose of study medication (i.e. Safety population) 
will be summarized as part of subject disposition.  
Although not captured directly on the CRF, additional variables related to study drug administration will also 
be derived for summarization: 
• 
Study drug interruption (yes/no), where interruptions will be identified via presence of a TEAE 
where action taken with study drug was marked as ‘drug interrupted’ or a protocol deviation 
indicating study drug was interrupted 
• 
Premature discontinuation of study drug (yes/no), where discontinuations will be idenfied via 
presence of a TEAE where action taken with study drug was marked as ‘drug withdrawn’ or a 
protocol deviation indicating study drug was prematurely discontinued. Subjects who discontinue 
the study prior to Visit 6 (Day 15) will also be reviewed to verify if study drug was prematurely 
discontinued or not. 
• 
Study drug completion, defined as those subjects where premature discontinuation of study drug 
is not equal to ‘yes’ 
A blinded data review will be conducted prior to database lock and unblinding to identify any other cases of 
study drug interruption or premature discontinuation of study drug which are known to have occurred, but 
are not identified through the criteria above. The classifications from this final review will be used for 
analysis. 


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The number and percent of subjects with study drug interruption, premature discontinuation of study drug, 
and study drug completion will be summarized by treatment group. 
Subject data listings will be generated to present details of study drug assignment, study drug replacement, 
as well as first instillation of study medication performed in-clinic on Day 1. Details from the study drug 
accountability assessment will also be listed. 
13. Efficacy Analyses 
13.1 
Primary Analysis 
The hierarchical primary efficacy measures are the absence of anterior chamber cells (i.e. score of ‘0’) in 
the study eye at Visit 6 (Day 15) and the absence of pain (i.e. score of ‘0’) at Visit 4 (Day 4). 
The anterior chamber cell count will be recorded as the actual number of cells observed if ≤10 cells are 
seen, otherwise a range is reported. Anterior chamber cell count is assessed for study eye only. Refer to 
Table 2 for details.  
Table 2. Anterior Chamber Cell Counts and Grade 
Anterior Chamber Cells 
Grade 
Cell Count 
0 
0 
1 
1-10 
2 
11-25 
3 
26-50 
4 
>50 
Ocular pain will be assessed by the patient at screening and at each follow-up visit, utilizing a numerical 
pain rating scale. Scores range from 0 to 10, where 0 = No Pain and 10 = Severe Pain, such that larger 
scores correspond to higher levels of pain. 
The observed anterior chamber cell count at Visit 6 will be used and categorized for analysis as follows: 
• 
Absence of anterior chamber cells: anterior chamber cells count of 0 / Grade 0 
• 
Presence of anterior chamber cells: anterior chamber cells count of 1 or more / Grade 1, 2, 3, or 4 
Within this analysis, missing values for visits after a subject is discontinued for lack of efficacy or values 
obtained after subject has received rescue medication will be imputed as failures (i.e. anterior chamber 
cells present) for analysis. For all other missing data, LOCF will be used to impute the missing anterior 
chamber cell count grade, and the LOCF value will then be categorized for analysis as “cells present” or 
“cells absent”.  


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Derivation of the pain score and absence of pain (i.e. score of ‘0’) variables at Visit 4 (Day 4) will follow the 
same approach for handling of missing data and handling of pain scores obtained following use of rescue 
medication. 
The primary efficacy variables, the absence of anterior chamber cells at Visit 6 (Day 15) and the absence 
of pain at Visit 4 (Day 4), will be summarized by treatment group using discrete summary statistics, including 
2-sided 90% CIs for the proportion in each treatment group based on Agresti-Coull method. 
For each OCS-01 dose (QD and BID ) separately, the primary efficacy analyses will first compare the 
proportion of study eyes with absence of anterior chamber cells (score of ‘0’) between OCS-01 and placebo 
(vehicle) at Visit 6 (Day 15) using the Pearson chi-squared statistic (Fisher’s exact test will be used if any 
expected cell count is less than 5). 
SAS® code used to generate the chi-squared test, Fisher’s exact test, and expected cell counts for 
comparison of OCS-01 BID with Placebo in anterior chamber cells response at Visit 6 is as follows:  
proc freq; 
  tables avalcat * trtp / chisq exact expected; 
  where avisitn=6 and trtp in (‘OCS-01 BID’ ‘Placebo (vehicle) BID’); 
run; 
where  
• 
trtp =Placebo (vehicle) BID; OCS-01 BID. 
• 
avalcat = ‘Absent’; ‘Present’. 
Comparison of OCS-01 QD versus placebo (vehicle) will be conducted in a similar manner, differing only 
by the treatment arms which are included within the comparison. Testing for each OCS-01 treatment group 
versus placebo (vehicle) for the absence of pain variable will use similar code. 
If the proportion of study eyes with absence of anterior chamber cells (score of ‘0’) is statistically significantly 
higher for OCS-01 versus placebo (vehicle) at a 2-sided alpha = 0.10 at Visit 6 (Day 15), for either dose of 
OCS-01 (BID or QD), then the study will be considered a success. The hierarchical hypothesis testing the 
proportion of study eyes with absence of pain (score of ‘0’) at Visit 4 (Day 4) between the corresponding 
OCS-01 dose and placebo (vehicle) will be performed using the Pearson chi-squared statistic at a 2-sided 
alpha = 0.10 (Fisher’s exact test will be used if any expected cell count is less than 5).   
Anterior chamber cell grade in the study eye at Visit 6 (Day 15) will be summarized by treatment group with 
descriptive statistics for discrete outcome, including shift from baseline. 
Ocular pain score at Visit 4 (Day 4) will be summarized by treatment group with descriptive statistics for 
continuous outcome, including change from baseline. 
The primary efficacy analysis will be conducted using the FAS.  


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13.1.1 SENSITIVITY ANALYSES OF THE PRIMARY EFFICACY MEASURES 
To check the robustness of primary efficacy analysis results, the previously described analyses of the 
primary efficacy measures will be repeated based on alternate handlings of missing data and major protocol 
deviations. 
An analysis based on observed data only will be conducted using FAS population. Data from subject visits 
after discontinuation for lack of efficacy or receipt of rescue medication will set to failure (i.e. non-respnose) 
for this analysis, all other missing values will not be imputed. The denominator will be based on the number 
of subjects in the treatment group with a non-missing value for analysis, which may be lower than total 
number of subjects in the treatment group. 
The analysis based on observed data using FAS described in previous paragraph will be repeated for PP 
population. 
Additional sensitivity analysis will also be conducted based on multiple imputation using the FAS population. 
The multiple imputation procedure will be done on the anterior chamber cell count grade, rather than the 
dichotomoized status variable (absent or present), and after imputation the fully imputed anterior chamber 
cell count grades will be dichotomized for analysis. The imputation procedure will be applied as follows: 
1. Values obtained after rescue medication usage (as well as those missing for other reasons such as 
study discontinuation, regardless of discontinuation reason), will initially be set to ‘missing’. 
2. For subjects with a non-monotone (intermittent) missing pattern, MCMC will be used to impute their 
missing intermittent anterior chamber cell count grades including treatment arm, baseline value, and 
anterior chamber cell count grade from previous visit(s) as explanatory variables in the model. This will 
be done 20 times limiting the imputation to in range results (i.e. imputed values will be constrained to 
be no less than 0.0, no more than 4.0, and will be rounded to nearest integer, consistent with values of 
Grade 0, 1, 2, 3, and 4 for anterior chamber cell grading). 
3. The remaining missing data for all subjects with a monotone missing data pattern will be imputed using 
regression with treatment arm, baseline value, and anterior chamber cell count grade from previous 
visit(s) as explanatory variables in the model. This model will be run once for each of the imputed 
datasets limiting imputation to in range results. 
4. In order to maintain consistency with other sensitivity analyses with respect to handling of values after 
rescue medication usage or values which were missing (prior to imputation) due to discontinuation for 
lack of efficacy, values for visits after a subject is discontinued for lack of efficacy or has received rescue 
medication which have an imputed value of ‘Grade 0 (Cells Absent)’ will be reclassified to ‘Grade 1 (1-
10 Cells)’. 
5. The anterior chamber cell counts (grades) will be categorized in the fully imputed data to cells present 
or cells absent. 
6. The estimated percentage of responders by treatment group will be presented based on the average 
proportion of responders in the multiply imputed datasets.  
7. Chi-square statistics will be generated separately for each of the imputations. Following the approach 
described by Ratitch et al (Ratich 2013), a Wilson-Hilferty transformation (Wilson 1931) will be applied 
to the individual chi-square statistics to obtain the equivalent standard normal values and standard error 
(1.0), and the values from the 20 individual imputations will then be combined using standard 
approaches within SAS Proc MIANALYZE. The two-sided p-value obtained fom SAS Proc MIANALYZE 
will then be divided by 2 to obtain the final p-value.  
SAS code for the multiple imputation is as follows: 
proc mi out=outmi nimpute=20 
   minimum=   0 0 0 0 


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   maximum=  4 4 4 4 
   round =  1 1 1 1 
   seed=<database lock date>1; 
   mcmc impute=monotone; 
   by trt01pn; 
   var base v4val v5val v6val; 
  run; 
 
proc mi data=outmi out=outmi2 nimpute=1 
   minimum= .   0 0 0 0 
   maximum= .4 4 4 4 
   round = . 1 1 1 1 
   seed=<database lock date>2; 
   class trt01pn; 
   monotone Reg(v4val = trt01pn base); 
   monotone Reg(v5val = trt01pn base v4val); 
   monotone Reg(v6val = trt01pn base v4val v5val); 
   var trt01pn base v4val v5val v6val; 
   by _imputation_; 
  run; 
As an additional sensitivity analysis, a tipping point analysis based on binomial outcome will also be 
conducted. Mirroring the primary analysis, anterior chamber cell counts obtained after rescue medication 
or due to discontinuation for lack of efficacy will again be set to non-response (cells present), all other 
remaining missing values will be imputed as part of this procedure. The goal of the tipping point analysis is 
to identify what proportion of the unknown missing values would need to be responders to cause the 
conclusions change, i.e., under which there is no longer evidence of a treatment effect. Then, the plausibility 
of such assumptions would be discussed. With this approach, also described as a “tipping point analysis 
via exhaustive scenarios analysis” (O’Kelly, 2014),  every possible combination of response (anterior 
chamber cells absent or present) is considered for all subjects with missing endpoint value, and the primary 
analysis is repeated for each of these scenarios. As an example, if we were to observe 3 missing endpoint 
values on the OCI-01 QD arm and 2 missing endpoint values on control arm, the primary analysis would 
be repeated assuming each of the following scenarios: 
• 
Three subjects with anterior chamber cells absent in the OCI-01 QD arm and two subjects with 
anterior chamber cells absent in PBO arm 
• 
Three subjects with anterior chamber cells absent in the OCI-01 QD arm and one subjects with 
anterior chamber cells absent in PBO arm and one subject with chamber cells present in PBO arm 
• 
Three subjects with anterior chamber cells absent in the OCI-01 QD arm and zero subjects with 
anterior chamber cells absent in PBO arm and two subjects with chamber cells present in PBO arm 
• 
Two subjects with anterior chamber cells absent and one subject with anterior chamber cells 
present in the OCI-01 QD arm, and two subjects with anterior chamber cells absent in PBO arm 
and so on, up to 
• 
Zero subjects with anterior chamber cells absent and three subjects with anterior chamber cells 
present in the OCI-01 QD arm, and zero subjects with anterior chamber cells absent and two 
subject with anterior chamber cells present in the PBO arm 
The primary analysis will be repeated based on all possible combinations with respect to the missing 
endpoint values, and the p-value generated for each scenario. A table will be produced to illustrate the 
p-values based on each combination of the potential outcomes among missing subjects for Placebo and 


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OCS treatment arms. Given that the nature of this analysis is to determine what conditions lead to reversal 
from a successful outcome to an unsuccessful outcome based on the unknown missing values, this 
summary will only be generated for the arm(s) that achieve statistical significance for the primary efficacy 
endpoint.  
The approaches described above for analysis based on observed case as well as multiple imputation and 
tipping point approaches will also be applied to the absence of pain score measure at Visit 4 (Day 4). For 
multiple imputation approach, the corresponding SAS code will be revised to align to maximum value of 
10.0 as well as the differing number of visits prior to endpoint. 
13.1.2 SUBGROUP ANALYSES OF THE PRIMARY EFFICACY ANALYSIS 
Descriptive summary of the number and proportions of responders, along with 90% CI, for both primary 
efficacy measurments will be tabulated separately in subgroups of subjects based on usage (yes/no) of any 
systemic anti-inflammatory drugs prior to Day 15 (Visit 6).  
A blinded review of all medications will be conducted prior to database lock and unblinding in order to 
properly classify each subject into the appropriate category. 
13.2 
Secondary Analyses 
The FAS population will be used for the secondary analyses.  
Unless otherwise noted, missing values for visits after a subject is discontinued for lack of efficacy or values 
obtained after subject has received rescue medication will be imputed as failures (e.g. anterior chamber 
cells present) for analysis. For all other missing data, LOCF will be used to impute the missing value. In the 
situation where anterior chamber cell count status is defined to be ‘present’ due to discontinuation for lack 
of efficacy or usage of rescue medication, but the LOCF value results in an imputed count of ‘0’, then the 
anterior chamber cell count value will be imputed as grade 1 (1 – 10 cells) instead to maintain consistency 
across analyses as to whether or not anterior chamber cell counts were present or absent for the subject 
at a given time point. A similar approach will be made for imputation of the ocular pain score, where imputed 
value of ‘0’ will be replaced by ‘1’ if subject is otherwise classified as having pain present due to 
discontinuation for lack of efficacy or usage of rescue medication. 
13.2.1 ANTERIOR CHAMBER CELLS 
The anterior chamber cell grade at each visit and change from baseline / shift from baseline will be 
summarized by treatment group at Visits 4, 5, and 7 (Days 4, 8, and 22) using continuous and discrete 
summary statistics. The anterior chamber cell count grade over time will also be displayed graphically with 
the mean and 90% CI at BL and each post-BL visit. 
The absence of presence of anterior chamber cells at each visit will be summarized with discrete summary 
statistics, along with 90% confidence interval for the proportion of subjects absent anterior chamber cells. 
For each OCS-01 dose (BID and QD) separately, the difference in the proportion of study eyes with absence 
of anterior chamber cells (score of ‘0’) between OCS-01 and placebo (vehicle) at each post-Baseline visit 


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will be conducted using the Pearson chi-squared statistic (Fisher’s exact test will be used if any expected 
cell count is less than 5). 
The observed anterior chamber cell grade values will be listed by subject and visit. 
13.2.2 OCULAR PAIN 
Absence of ocular pain at each visit will be summarized by treatment group with discrete summary statistics, 
along with 90% confidence interval for the proportion of subjects absent ocular pain. For each OCS-01 dose 
(BID and QD) separately, the difference in the proportion of study eyes with absence of anterior chamber 
cells (score of ‘0’) between OCS-01 and placebo (vehicle) at each post-Baseline visit will be conducted 
using the Pearson chi-squared statistic (Fisher’s exact test will be used if any expected cell count is less 
than 5). 
The ocular pain score, including change from Baseline, at each visit will be summarized by treatment group 
using continuous summary statistics. 
The observed ocular pain scores will be listed by subject and visit. 
13.2.3 ANTERIOR CHAMBER FLARE 
Anterior chamber flare is graded on a 5-unit scale where 0 = None, 1 = Faint, 2 = Moderate (iris and lens 
details clear), 3 = Marked (iris and lens details hazy), and 4 = Intense (fibrin or plastic aqueous).  
Anterior chamber flare grade, including absence of flare, will be be summarized by treatment group and 
analyzed at Visits 4, 5, 6, and 7 (Days 4, 8, 15, and 22) in the same fashion as described for the secondary 
analysis of anterior chamber cells. 
The observed anterior chamber flare grade values will be listed by subject and visit. 
13.2.4 ABSENCE OF BOTH ANTERIOR CHAMBER CELLS AND FLARE 
A composite variable based on absence of both anterior chamber cells and flare (i.e., anterior chamber cell 
grade = 0 and anterior chamber flare grade = 0) will also be summarized. 
Absence of both anterior chamber cells and flare at Visits 4, 5, 6, and 7 (Days 4, 8, 15, and 22) will be 
summarized by treatment group with discrete summary statistics along with 90% confidence interval for the 
proportion of subjects absent anterior chamber cells and flare. For each OCS-01 dose (BID and QD) 
separately, the difference in the proportion of study eyes with absence of anterior chamber cells (score of 
‘0’) between OCS-01 and placebo (vehicle) at each visit will be conducted using the Pearson chi-squared 
statistic (Fisher’s exact test will be used if any expected cell count is less than 5). 
13.2.5 RESCUE MEDICATION USAGE 
Rescue medications are defined for analysis as those concomitant medications where the eCRF question, 
“Was this concomitant medication utilized for Rescue” is answered “Yes,” and location is the study eye. 
Time to first rescue medication usage will be analyzed based on Kaplan-Meier approach by treatment 
group. Subjects will be considered to have an event at the date where rescue medication for study eye was 


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first initiated. Since rescue medication may be initiated at any time – at a scheduled visit or between 
scheduled visits – the timing of rescue medication usage will be based on the date in which rescue 
medication was started. Subjects who do not have any usage of rescue medication in the study eye will be 
censored at the date of the last visit. Subjects who discontinue prior to completing all treatment period visits 
will be evaluated based on the visits which are available. 
Rescue medication will be listed by subject and medication. 
14. Safety Analyses 
All safety analyses will be conducted using the Safety population. 
Analyses will be presented by treatment group. An additional “OCS-01 Total” group, consisting of all 
subjects in either OCS-01 treatment group, will also be included. 
14.1 
Adverse Events 
An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether 
or not the event is considered drug-related. Treatment-emergent adverse events (TEAE) are defined as 
any event that occurs or worsens on or after the day and time when first treatment is initiated.  
All AEs will be coded for analysis using MedDRA, version 22.0 (or higher). 
Ocular AEs are a subset of AEs and are identified as those AEs where the location field on the AE eCRF 
is marked as OD, OS, or OU.  
Severity of an AE is defined as a qualitative assessment of the degree of intensity of an AE as determined 
by the Investigator or reported to him/her by the subject. The assessment of severity is made irrespective 
of relationship to study drug or seriousness of the event and should be evaluated according to the following 
scale: 
• Mild: AE is noticeable to the subject, but is easily tolerated and does not interfere with the subject’s 
daily activities. 
• Moderate: AE is bothersome, possibly requiring additional therapy, and may interfere with the subject’s 
daily activities. 
• Severe: AE is intolerable, necessitates additional therapy or alteration of therapy, and interferes with 
the subject’s daily activities. 
The relationship of each AE to the study drug should be determined by the Investigator using these 
explanations: 
• Supected: A reasonable possibility exists that the study drug caused the AE. 
• Not Suspected: A reasonable possibility does not exist that the study drug caused the AE. 
The expectedness of an AE should be determined based upon existing safety information about the study 
drug using these explanations: 


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• 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. 
• Expected: an AE that is listed in the IB at the specificity and severity that has been observed. 
An AE is classified as expected or not based on Investigator’s assessment. 
An overall summary will be presented that includes the number of TEAEs and the number and percentage 
of subjects who experienced at least one TEAE, by treatment group. This summary will include similar 
summaries of serious TEAEs, suspected treatment-related TEAEs, expected TEAEs, unexpected TEAEs, 
TEAEs leading to study drug discontinuation, TEAEs leading to death, and TEAEs by maximum severity. 
Results will be presented for all events (ocular and non-ocular) as well as separately for ocular and non-
ocular events. Ocular events will be further separated into study eye versus non-study eye. 
A summarization of non-ocular TEAEs will include the overall number of TEAEs and overall number and 
percentage of subjects who experienced at least one TEAE. The number of TEAEs and the number and 
percentage of subjects will also be tabulated by (primary) SOC and PT. Ocular TEAEs will be summarized 
in a similar manner, but with results further subdivided into study eye and non-study eye. Including the two 
above described analyses, summaries by SOC and PT will be provided for the following categories of AEs: 
• 
Ocular TEAEs 
• 
Non-ocular TEAEs 
• 
Suspected treatment-related ocular TEAEs 
• 
Suspected treatment-related non-ocular TEAEs 
• 
Expected ocular TEAEs 
• 
Expected non-ocular TEAEs 
• 
Unexpected ocular TEAEs 
• 
Unexpected non-ocular TEAEs 
• 
Serious ocular TEAEs 
• 
Serious non-ocular TEAEs 
If a subject experiences the same PT multiple times within the same SOC, that subject will only be counted 
once for that PT witin that SOC. As with the PT, if a subject experiences multiple events within the same 
SOC, that subject will only be counted once for that SOC. In the summaries, SOC will be listed in ascending 
alphabetical order; PTs will be listed in order of descending frequency for all subjects within each SOC.  
Summaries of TEAEs by maximum severity will be presented for ocular AEs (separately for treated eye and 
non-study eye) and non-ocular AEs separately. The number of subjects with any TEAEs (along with 
percentages) will be tabulated by SOC and PT within each SOC by treatment group, along with maximum 
severity per subject for each PT. To count the number of subjects with any TEAEs, if a subject has multiple 


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TEAEs coded to the same PT within the same SOC, the subject will be counted once under the maximum 
severity. 
Separate listings of AEs will be produced to list all AEs, AEs leading to study drug discontinuation, and 
serious AEs. TEAEs will be identified within the listings.  
14.2 
Pin-hole Visual Acuity 
Pin-hole, logarithm of the minimum angle of resolution (logMAR) visual acuity is assessed at Visits 1, 2, 4, 
5, 6, and 7 (Days -28 to -1, 1, 4, 8, 15, and 22) using an Early Treatment Diabetic Retinography Study 
(ETDRS) chart.  
The observed and change from baseline in number of letters read correctly will be summarized for each 
eye (study eye, non-study eye) by visit and treatment group (including a group for all actively treated 
subjects) using continuous descriptive statistics.  
The number and proportion of subjects with worsening in visual acuity from previous visit of ≥2 lines 
(equivalent to reduction in 0.2 logMAR or 10 letters) will be tabulated by visit. 
A subject listing of visual acuity will also be produced. This listing will include a variable that indicates if an 
eye had a visual acuity worsening corresponding to ≥2 lines. 
14.3 
Slit-Lamp Biomicroscopy Examination  
A slit-lamp biomicroscopy examination of the eyelid, conjunctiva, cornea, anterior chamber, iris, and lens 
will be performed at Visits 1, 2, 4, 5, 6, and 7 (Days -28 to -1, 1, 4, 8, 15, and 22). The results will be graded 
as normal, abnormal not clinically significant (NCS), or abnormal clinically significant (CS). 
Shifts from baseline result to post-baseline result will be presented using counts and percentages in each 
shift category by visit and treatment group (including a group for all actively treated subjects). This summary 
will be produced by visit , separately for study eye and non-study eye. 
A subject listing of the slit-lamp biomicroscopy parameters will also be produced. 
14.4 
Dilated Indirect Ophthalmoscopy 
A dilated indirect ophthalmoscopy examination of the vitreous, retina, macula, choroid, and optic nerve will 
be performed at Visit 1 (Day -28 to -1) and Visit 7 (Day 22). The results will be graded as normal, abnormal 
NCS, or abnormal CS.  
Shifts from baseline result to post-baseline result will be presented using counts and percentages in each 
shift category by treatment group and for all actively treated subjects. This summary will be produced by 
visit, separately for study eye and non-study eye. 
A subject listing of the dilated indirect ophthalmoscopy results will also be produced.  


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14.5 
Intraocular Pressure (IOP) 
Subjects’ IOP will be assessed in each eye at Visits 1, 4, 5, 6, and 7 (Days -28 to -1, 4, 8, 15, and 22) using 
a calibrated Goldmann application tonometer affixed to a slit lamp. The measurement procedure will be 
repeated on the same eye twice consecutively. If the measurements are within 2 mmHg or less of each 
other, the mean of the 2 readings will be calculated and recorded. If the 2 readings differ by more than 2 
mmHg, a third (consecutive) reading will be taken and the median (middle) IOP will be recorded. All IOP 
measurements will be included within subject data listings, however the median value (i.e. the mean value 
when 2 measurements are made, or the median value when 3 measurements are available) will be used 
for descriptive summaries. 
The (median) IOP values and changes from baseline for each eye (study eye and non-study eye) will be 
summarized using continuous descriptive statistics by visit and eye for each treatment group and for all 
actively treated subjects. The maximum post-BL IOP value per subject, which refers to largest post-BL 
value per subject and eye regardless of which post-BL visit, will be included within this summary. The 
number and proportion of study eyes with IOP elevations based on the following cutoffs will be summarized: 
• 
An IOP value of 30 mmHg or more  
• 
An increase from baseline in IOP of 10 mmHg or more 
A subject listing of IOP will also be produced. Individual IOP values ≥ 30 mmHg or an increase from baseline 
value of ≥ 10 mmHg will be flagged within the listing. 
The number and percent of subjects with post-BLIOP lowering procedures will be summarized by treatment 
group at each post-BL visit as well as across all visits. 
A subject listing of any IOP lowering procedures will also be produced. 
Analyses of concomitant IOP lowering medications is described previously, within Section 11.2. 
14.6 
Clinical Laboratory Data 
Results from the urine pregnancy test at Visit 1 (Day -28 to -1) and Visit 7 (Day 22) will be listed by subject. 
15. Interim Analyses 
Interim analyses will not be performed. 
16. Changes from Protocol-Stated Analyses 
There are no changes from the protocol-stated analyses. 
17. References 
Allison, P. D. Missing Data. Sage University Paper Series: Quantitative Applications in the Social Sciences; 
no. 07-136: Sage Publications Ltd. 2001. 
Graham JW, Olchowski AE, Gilreath TD. How Many Imputations are Really Needed? Some Practical 
Clarifications of Multiple Imputation Theory. Prevention Science. 2007 Sep 1;8(3):206-13. 


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O’Kelly M, Ratitch B. Clinical trials with missing data: A guide for practitioners. (1st Ed). 2014 
Ratich, B., Lipkovich, I., Kelly, M., Combining Analysis Results from Mulitply Imputed Categorical Data. 
PharmaSUG 2013 – Paper SP03, 2013. 
Wilson, E. B., Hilferty, M. M. The distribution of chi-square. Proceedings of the National Academy of 
Sciences of the United States of America, 17, 684-688. 1931. 
18. Revision History 
Documentation of revision to the SAP will commence after approval of the final version 1.0. 
19. Tables 
Tables that will be included in the topline delivery are shown in boldface font.  
Table Number 
Title 
Population 
Table 14.1.1.1 
Subject Disposition 
Full Analysis Set 
Table 14.1.1.2 
Reasons for Screen Failure 
Enrolled Subjects 
Population 
Table 14.1.2 
Demographics 
Safety Population 
Table 14.1.3.1 
Ocular Medical History 
Full Analysis Set 
Table 14.1.3.2 
Non-Ocular Medical History 
Full Analysis Set 
Table 14.1.4.1 
Ocular Concomitant Medications 
Safety Population 
Table 14.1.4.2 
Non-Ocular Concomitant Medications 
Safety Population 
Table 14.1.4.3 
Post-BL IOP Lowering Medications by Visit 
Safety Population 
Table 14.2.1.1 
Absence of Anterior Chamber Cells at Visit 6 (Day 15): 
Missing Values Imputed via LOCF 
Full Analysis Set 
Table 14.2.1.2 
Absence of Anterior Chamber Cells at Visit 6 (Day 15): 
Observed Case with Limited Imputation 
Full Analysis Set 
Table 14.2.1.3 
Absence of Anterior Chamber Cells at Visit 6 (Day 15): 
Observed Case with Limited Imputation 
Per Protocol 
Population 
Table 14.2.1.4 
Absence of Anterior Chamber Cells at Visit 6 (Day 15): 
Missing Values Imputed via MI 
Full Analysis Set 
Table 14.2.1.5 
Absence of Anterior Chamber Cells at Day 15: Tipping 
Point Analysis 
Full Analysis Set 
Table 14.2.1.6 
Absence of Anterior Chamber Cells at Visit 6 (Day 15) by 
Subgroup: Missing Values Imputed via LOCF 
Full Analysis Set 


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Table 14.2.2.1 
Absence of Ocular Pain at Visit 4 (Day 4): Missing 
Values Imputed via LOCF 
Full Analysis Set 
Table 14.2.2.2 
Absence of Ocular Pain at Visit 4 (Day 4): Observed Case 
with Limited Imputation 
Full Analysis Set 
Table 14.2.2.3 
Absence of Ocular Pain at Visit 4 (Day 4): Observed Case 
with Limited Imputation 
Per Protocol 
Population 
Table 14.2.2.4 
Absence of Ocular Pain at Visit 4(Day 4): Missing Values 
Imputed via  MI 
Full Analysis Set 
Table 14.2.2.5 
Absence of Ocular Pain at Visit 4 (Day 4): Tipping Point 
Analysis 
Full Analysis Set 
Table 14.2.2.6 
Absence of Ocular Pain at Visit 4 (Day 4) by Subgroup: 
Missing Values Imputed via LOCF 
Full Analysis Set 
Table 14.2.3 
Absence of Anterior Chamber Cells by Visit 
Full Analysis Set 
Table 14.2.4.1 
Anterior Chamber Cell Count by Visit: Categorical 
Summary 
Full Analysis Set 
Table 14.2.4.2 
Anterior Chamber Cells Grade by Visit: Continuous 
Summary 
Full Analysis Set 
Table 14.2.5 
Absence of Ocular Pain by Visit 
Full Analysis Set 
Table 14.2.6 
Ocular Pain Score by Visit: Continuous Summary 
Full Analysis Set 
Table 14.2.7 
Absence of Anterior Chamber Flare by Visit 
Full Analysis Set 
Table 14.2.8.1 
Anterior Chamber Flare by Visit: Categorical Summary 
Full Analysis Set 
Table 14.2.8.2 
Anterior Chamber Flare by Visit: Continuous Summary 
Full Analysis Set 
Table 14.2.9 
Absence of Both Anterior Chamber Cells and Flare by 
Visit 
Full Analysis Set 
Table 14.2.10 
Rescue Medication Usage 
Full Analysis Set 
Table 14.3.1.1 
Overall Summary of TEAEs 
Safety Population 
Table 14.3.1.2.1 
Ocular TEAEs by System Organ Class and Preferred 
Term 
Safety Population 
Table 14.3.1.2.2 
Non-Ocular TEAEs by System Organ Class and Preferred 
Term 
Safety Population 
Table 14.3.1.3.1 
Suspected Treatment-Related Ocular TEAEs by System 
Organ Class and Preferred Term 
Safety Population 


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Table 14.3.1.3.2 
Suspected Treatment-Related Non-Ocular TEAEs by 
System Organ Class and Preferred Term 
Safety Population 
Table 14.3.1.4.1 
Expected Ocular TEAEs by System Organ Class and 
Preferred Term 
Safety Population 
Table 14.3.1.4.2 
Expected Non-Ocular TEAEs by System Organ Class and 
Preferred Term 
Safety Population 
Table 14.3.1.5.1 
Unexpected Ocular TEAEs by System Organ Class and 
Preferred Term 
Safety Population 
Table 14.3.1.5.2 
Unexpected Non-Ocular TEAEs by System Organ Class 
and Preferred Term 
Safety Population 
Table 14.3.1.6.1 
Serious Ocular TEAEs by System Organ Class and 
Preferred Term 
Safety Population 
Table 14.3.1.6.2 
Serious Non-Ocular TEAEs by System Organ Class and 
Preferred Term 
Safety Population 
Table 14.3.1.7.1 
Ocular TEAEs by System Organ Class, Preferred Term, 
and Maximum Severity 
Safety Population 
Table 14.3.1.7.2 
Non-Ocular TEAEs by System Organ Class, Preferred 
Term, and Maximum Severity 
Safety Population 
Table 14.3.2 
Pin-Hole Visual Acuity 
Safety Population 
Table 14.3.3 
Slit Lamp Biomicroscopy Shifts from Baseline to Post-
Baseline 
Safety Population 
Table 14.3.4 
Dilated Indirect Ophthalmoscopy Shifts from Baseline to 
Post-Baseline 
Safety Population 
Table 14.3.5.1 
Intraocular Pressure (mmHg) 
Safety Population 
Table 14.3.5.2 
Post-BL IOP Lowering Procedures by Visit 
Safety Population 
Table 14.3.6 
Treatment Exposure 
Safety Population 
20. Listings 
Listing Number 
Title 
Population 
Listing 16.1.7 
Randomization Schedule 
Full Analysis Set 
Listing 16.2.1 
Subject Disposition 
Full Analysis Set 
Listing 16.2.2.1 
Protocol Deviations 
Full Analysis Set 


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Listing 16.2.2.1 
Inclusion/Exclusion Criteria Violations 
Full Analysis Set 
Listing 16.2.3 
Study Population Inclusion 
Enrolled 
Subjects 
Population 
Listing 16.2.4.1 
Demographics 
Enrolled 
Subjects 
Population 
Listing 
16.2.4.2.1 
Ocular Medical History 
Full Analysis Set 
Listing 
16.2.4.2.2 
Non-Ocular Medical History 
Full Analysis Set 
Listing 
16.2.4.3.1 
Prior and Concomitant Ocular Medications 
Safety Population 
Listing 
16.2.4.3.2 
Prior and Concomitant IOP Lowering Medications 
Safety Population 
Listing 
16.2.4.3.3 
Prior and Concomitant Non-Ocular Medications 
Safety Population 
Listing 16.2.4.4 
IOP Lowering Procedures 
Safety Population 
Listing 16.2.4.5 
Cataract Surgery 
Full Analysis Set 
Listing 16.2.5.1 
Study Drug Administration 
Full Analysis Set 
Listing 16.2.5.2 
Study Drug Replacement 
Safety Population 
Listing 16.2.5.3 
Study Drug Accountability 
Full Analysis Set 
Listing 16.2.6.1 
 Ocular Pain 
Full Analysis Set 
Listing 16.2.6.2 
Anterior Chamber Cells and Flare 
Full Analysis Set 
Listing 16.2.7.1 
Adverse Events 
Full Analysis Set 
Listing 16.2.7.2 
Serious Adverse Events 
Full Analysis Set 
Listing 16.2.7.3 
Adverse Events Leading to Study Drug Discontinuation 
Safety Population 
Listing 16.2.8.1 
Urine Pregnancy Test 
Full Analysis Set 
Listing 16.2.9.1 
Pin-Hole Visual Acuity 
Full Analysis Set 
Listing 16.2.9.2 
Dilated Indirect Ophtalmoscopy 
Full Analysis Set 
Listing 16.2.9.3 
Slit Lamp Biomicroscopy 
Full Analysis Set 
Listing 16.2.9.4 
Intraocular Pressure 
Full Analysis Set 


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21. Figures 
Figure Number 
Title 
Population 
Figure 14.2.1 
Absence of Anterior Chamber Cells by Visit 
Full Analysis Set 
Figure 14.2.2 
Mean Anterior Cell Count Grade by Visit 
Full Analysis Set 
Figure 14.2.3 
Absence of Ocular Pain by Visit 
Full Analysis Set