Conditions: Inflammation and Pain Following Ocular Surgery
Keywords: RTA 408 Ocular surgery Cataract surgery Ocular inflammation Ocular pain Eye inflammation omaveloxolone
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 109
Healthy volunteers: no

Brief summary:
This study assesses the efficacy and safety of two concentrations of RTA 408 Ophthalmic Suspension in the treatment of patients who have inflammation and pain following ocular surgery.

Detailed description:
Following ophthalmic surgery, the current standard of care includes a topical ophthalmic corticosteroid or other anti-inflammatory agent to treat ocular inflammation and improve patient comfort. If left untreated, inflammation of the eye may result in further ocular complications including scarring, vision loss, or blindness. Although the exact dosing regimen is physician-dependent, patients are typically prescribed a topical corticosteroid for a period of 2-4 weeks following surgery, being tapered over the course of delivery as the inflammation subsides. Topical anti-inflammatory agents are usually administered multiple times per day, particularly in the early period following ophthalmic surgery. Continuing efforts in drug development aim to identify alternatives to ophthalmic corticosteroid use, due to their well-known local and systemic negative side effects.

Arms:
arm 1: Patients will receive a single drop of Omaveloxolone Ophthalmic suspension 1.0% instilled into the study eye twice daily (approximately 12 hours apart) for 14 days, beginning 24 ± 6 hours after surgery arm 2: Patients will receive a single drop of Omaveloxolone Ophthalmic suspension 0.5% instilled into the study eye twice daily (approximately 12 hours apart) for 14 days, beginning 24 ± 6 hours after surgery arm 3: Patients will receive a single drop of vehicle for Omaveloxolone Ophthalmic suspension was instilled into the study eye twice daily (approximately 12 hours apart) for 14 days, beginning 24 ± 6 hours after surgery

Interventions: intervention 1: Omaveloxolone Ophthalmic Suspension 1.0% intervention 2: Omaveloxolone Opthalmic Suspension 0.5% intervention 3: Placebo
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None

Protocol document:
Prot_000.pdf: 




RTA 408 Ophthalmic Suspension 
 
 
 
 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
 
 
 
 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 3 of 77 
SYNOPSIS 
Protocol Title: 
A Multicenter, Randomized, Dose-Ranging, 
Double-Masked, Placebo-Controlled Phase 2 Study 
Evaluating the Safety and Efficacy of RTA 408 
Ophthalmic Suspension for the Treatment of Ocular 
Inflammation and Pain following Ocular Surgery 
Protocol Number: 
408-C-1307 
Study Drug: 
1) RTA 408 Ophthalmic Suspension 0.5%  
2) RTA 408 Ophthalmic Suspension 1.0%  
3) Placebo for RTA 408 Ophthalmic Suspension  
Study Phase: 
Phase 2 
Primary Objective: 
To evaluate the clinical efficacy and safety of two 
concentrations of RTA 408 Ophthalmic Suspension 
against placebo in the treatment of patients with 
inflammation and pain following ocular surgery 
Secondary Objective: 
None 
Overall Study Design 
Structure: 
Multi-center, double-masked, randomized, placebo-
controlled, dose-ranging, efficacy study  
Duration: 
Approximately 21 to 49 days (6 study visits) 
Controls: 
Placebo for RTA 408 Ophthalmic Suspension  


57$2SKWKDOPLF6XVSHQVLRQ




5HDWD3KDUPDFHXWLFDOV
&OLQLFDO7ULDO3URWRFRO&




$PHQGPHQW)HE

&RQILGHQWLDO

3DJHRI
'RVDJH'RVH5HJLPHQ
3DWLHQWVZLOOEHUDQGRPL]HGLQDUDWLRWRRQHRI
WKHIROORZLQJJURXSVIRU%,'GRVLQJLQWKHVWXG\H\H
LQWKHPRUQLQJDQGHYHQLQJDSSUR[LPDWHO\KRXUV
DSDUWIRUGD\V
• 57$2SKWKDOPLF6XVSHQVLRQ
• 57$2SKWKDOPLF6XVSHQVLRQ
• 3ODFHERIRU57$2SKWKDOPLF6XVSHQVLRQ
6XPPDU\RI9LVLW6FKHGXOH
9LVLW'D\6FUHHQLQJ%DVHOLQH(YDOXDWLRQ
9LVLW'D\KRXUVSRVWVXUJHU\6WXG\
HQUROOPHQW5DQGRPL]DWLRQDQGVW6WXG\
'UXJ'RVH
9LVLW'D\2Q7UHDWPHQW)ROORZXS
,QIODPPDWLRQDQG3DLQ$VVHVVPHQWV
9LVLW'D\2Q7UHDWPHQW)ROORZXS
,QIODPPDWLRQDQG3DLQ$VVHVVPHQWV
9LVLW'D\,QIODPPDWLRQDQG3DLQ
$VVHVVPHQWVDIWHU(QGRI7UHDWPHQW
9LVLW'D\3RVW7UHDWPHQW)ROORZXS
([LW9LVLW
0HDVXUHV7DNHQWR5HGXFH
%LDV
5DQGRPL]DWLRQ ZLOO EH XVHG WR DYRLG ELDV LQ WKH
DVVLJQPHQWRISDWLHQWVWRWUHDWPHQWWRLQFUHDVHWKH
OLNHOLKRRG WKDW NQRZQ DQG XQNQRZQ SDWLHQW
DWWULEXWHV DUH HYHQO\ EDODQFHG DFURVV WUHDWPHQW
JURXSV DQG WR HQKDQFH WKH YDOLGLW\ RI VWDWLVWLFDO
FRPSDULVRQV DFURVV WUHDWPHQW JURXSV 0DVNHG
WUHDWPHQW ZLOO EH XVHG WR UHGXFH SRWHQWLDO ELDV
GXULQJ GDWD FROOHFWLRQ DQG HYDOXDWLRQ RI FOLQLFDO
HQGSRLQWV


RTA 408 Ophthalmic Suspension 
 
 
 
 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
 
 
 
 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 5 of 77 
Study Population Characteristics 
Number of Patients: 
Approximately 105 patients will be enrolled in this 
study to complete 93 patients: 31 per arm  
Condition/Disease: 
Inflammation and pain following ocular surgery  
Inclusion Criteria: 
Patients must:  
1. Have 
provided 
written 
informed 
consent, 
approved by the appropriate institutional review 
board; 
2. Be able to comply with study requirements and 
visit schedule; 
3. Be greater than or equal to 18 years of age of 
either sex or any race;  
4. Have undergone unilateral cataract extraction via 
phacoemulsification 
and 
posterior 
chamber 
intraocular lens (PCIOL) implantation in the 
study 
eye 
on 
the 
day 
prior 
to 
study 
enrollment/randomization; 
5. Have a grade of ≥ 2 in anterior chamber cell 
score on day after surgery (Day 1) in the study 
eye; 
6. Have a potential post-operative pin-hole visual 
acuity (VA) < 1.0 logarithm of the minimum 
angle of resolution (logMAR) in the operative 
eye and fellow eye as measured using an Early 
Treatment for Diabetic Retinopathy Study 
(ETDRS) chart; 
7. (For females of childbearing potential) agree to 
have urine pregnancy testing performed at 
screening (must be negative) and at exit visit; 
must not be lactating; and must agree to use a 
medically acceptable form of birth control1 
throughout the study duration. Women of 
childbearing potential include all females who 
have experienced menarche and have not 
experienced 
menopause 
(as 
defined 
by 
                                                 
1Acceptable forms of birth control are spermicide with barrier, oral contraceptive, injectable or implantable 
method of contraception, transdermal contraceptive, intrauterine device, or surgical sterilization of partner. 
For non-sexually active females, abstinence will be considered an acceptable form of birth control.  


RTA 408 Ophthalmic Suspension 
 
 
 
 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
 
 
 
 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 6 of 77 
amenorrhea for greater than 12 consecutive 
months) or have not undergone successful 
surgical sterilization (hysterectomy, bilateral 
tubal ligation, or bilateral oophorectomy).   
Exclusion Criteria: 
Patients must not: 
1. Have any intraocular inflammation present in the 
study eye during the screening slit lamp 
examination; 
2. Have a score greater than “0” on the Ocular Pain 
Assessment at Screening in the study eye; 
3. Have an immunosuppressive disease or an 
autoimmune disease that in the opinion of the 
Investigator could affect the quality of the ocular 
surface; 
4. Have active or chronic/recurrent ocular or 
systemic disease that is uncontrolled and will 
likely affect wound healing; 
5. Currently have suspected or known malignancy 
or is currently receiving antineoplastic therapy; 
6. 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 has a positive urine pregnancy 
test at screening; 
7. Use anti-inflammatory agents, analgesics/pain 
relievers (including opioids, narcotics and other 
pain medications) or immunomodulating agents, 
systemically, or in the study 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 surgery are as follows:  
a. Medications for BPH (tamsulosin, silodosin, 
alfuzosin, finasteride): 28 days  
b. Systemic corticosteroids: 14 days 
c. Systemic analgesics/pain relievers (e.g., 
gabapentin, pregabalin, NSAIDs and 
opioids): 14 days 
Note: Use of acetaminophen (up to 4,000 
mg/day) and ‘baby’ aspirin (up to 81 
mg/day) during the study are allowed. Use 
of an opioid during cataract surgery is 
allowed. 


RTA 408 Ophthalmic Suspension 
 
 
 
 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
 
 
 
 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 7 of 77 
d. Periocular injection of any corticosteroid 
solution: 28 days 
e. Corticosteroid depot in the study eye: 56 
days after implantation  
f. Cyclosporine: 56 days 
g. Topical ocular corticosteroid: 7 days  
h. Topical ocular NSAID: 7 days 
8. Have glaucoma or be taking medications to treat 
glaucoma in the study eye; 
9. Have an intraocular pressure (IOP)  ≤ 5 mmHg 
in either eye; 
10. Currently have or have a history of Herpes 
Simplex Keratitis in the study eye;  
11. Have active corneal abrasions or ulcers in the 
study eye; 
12. Have active or a history of chronic or recurrent 
inflammatory eye disease (e.g. iritis, scleritis, 
uveitis, iridocyclitis, rubeosis iritis) in the study 
eye; 
13. 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);  tuberculosis of the eye; 
corneal 
dystrophies; 
intraocular 
infections, 
dysthyroid ophthalmopathy, active chalazion, or 
uncontrolled blepharitis in the study eye; 
14. Have uncontrolled and clinically significant dry 
eye syndrome in the study eye (artificial tears are 
allowed); 
15. Have proliferative diabetic retinopathy (PDR), 
compromised 
macular 
function; 
significant 
macular diseases; clinically significant macular 
edema (CSME); or a history of cystoid macular 
edema in the study eye;  
16. Have had corneal or retinal surgery (laser or 
incisional) within the past 6 months, or be 
planning to have laser or incisional surgery 
during the study period in the study eye (other 
than cataract surgery);  
17. Have surgery planned or scheduled for the 
contralateral eye during the study; 
18. Have previous ocular trauma with visible 
scarring or any deformities due to the trauma in 
the study eye; 
19. Require the use of a contact lens or a collagen 
shield within 72 hours of investigational drug 




RTA 408 Ophthalmic Suspension 
 
 
 
 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
 
 
 
 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 9 of 77 
Efficacy Measures: 
Hierarchical Primary Efficacy Measures 
1. a. Absence of anterior chamber cells (i.e., score 
of ‘0’) at Visit 5 (Day 15) for the 1.0% 
concentration of RTA 408 Ophthalmic 
Suspension compared to Placebo 
 
b. Absence of anterior chamber cells (i.e., score 
of ‘0’) at Visit 5 (Day 15) for the 0.5% 
concentration of RTA 408 Ophthalmic 
Suspension compared to Placebo 
 
2. a. Absence of pain (i.e., score of ‘0’) at Visit 3 
(Day 4) for the 1.0% concentration of RTA 408 
Ophthalmic Suspension compared to Placebo 
 
b. Absence of pain (i.e., score of ‘0’) at Visit 3 
(Day 4) for the 0.5% concentration of RTA 408 
Ophthalmic Suspension compared to Placebo 
Secondary Efficacy Measures 
1. Absence of anterior chamber cells at Visits 3, 4 
or 6 (Days 4, 8 or 21 respectively) 
2. Absence of pain at Visits 4, 5 or 6 (Days 8, 15 or 
21 respectively) 
3. Absence of flare at Visits 3, 4, 5 or 6 (Days 4, 8, 
15 or 21 respectively) 
Safety Measures: 
• Slit lamp biomicroscopy  
• Pin-hole visual acuity  
• IOP  
• Dilated indirect ophthalmoscopic examination  
• AE monitoring  
Other: 
None 
General Statistical  
Methods and Types  
of Analyses: 
 
Efficacy Analysis: 
Primary efficacy analyses will first test the 
difference in proportion of study eyes with a grade 
of ‘0’ in anterior chamber cells between the 1.0% 
concentration of RTA 408 Ophthalmic Suspension 
and placebo and between the 0.5% concentration of 




RTA 408 Ophthalmic Suspension 
 
 
 
 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
 
 
 
 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 11 of 77 
General Considerations: 
The unit of analysis in this study will be the study 
eye for all efficacy and safety summaries.  
Additionally, non-ocular adverse events will be 
presented at the patient level. Non-study eye safety 
summaries will also be presented as appropriate. 
The primary analyses of all efficacy data will use 
last observation carried forward (LOCF) to impute 
missing data; data for visits after a patient is 
discontinued for lack of efficacy 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 data will include analyses of 
observed data only, imputing data from patient visits 
after discontinuation for lack of efficacy as failures.  
Other imputation methods may be applied as 
additional sensitivity analyses.  
Per protocol analyses will use observed data only, 
with the exception of patients who have missing data 
due to discontinuation for lack of efficacy; for these 
patients, missing data after discontinuation will be 
imputed as failures for success/failure endpoints and 
will be imputed using LOCF for other endpoints. 
Summaries for continuous variables will include the 
sample size (n), mean, standard deviation, median, 
minimum, and maximum. Summaries for discrete 
variables will include frequencies and percentages. 
Differences between treatment groups will be 
calculated as Test – Placebo and change from 
baseline will be calculated as follow-up visit – 
baseline. The baseline visit will be defined as the 
last non-missing measure prior to initiation of 
investigational treatment. All efficacy analyses will 
use a one-sided alpha=0.10 test unless otherwise 
stated.  
The secondary efficacy variables, study eyes with 
absence of anterior chamber cells (Visits 3, 4 or 6), 
study eyes with absence of pain (Visits 4, 5 or 6) and 
study eyes with absence of flare (Visits 3, 4, 5 or 6) 
will be summarized similarly to the primary efficacy 
summaries. Additionally, anterior chamber cells and 
flare as well as pain at each visit and change from 


RTA 408 Ophthalmic Suspension 
 
 
 
 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
 
 
 
 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 12 of 77 
baseline will be summarized using continuous and 
discrete summary statistics. 
The sum of anterior chamber cells and flare grade 
will be summarized similarly to anterior chamber 
cells and flare separately. 
Safety Analysis: 
The primary safety analysis will summarize ocular 
treatment emergent AEs (TEAEs) in the study eye 
for all treated patients using discrete summaries at 
the patient and event level by system organ class and 
preferred term 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 patient and event level by system 
organ class and preferred term 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. 
The IOP data will be summarized at each visit using 
both continuous summaries (including change from 
baseline) and discrete summaries (including the 
proportion of patients with change in IOP from 
baseline ≥ 10 mm Hg and the proportion of patients 
with an IOP ≥ 30 mm Hg that occurs at any time 
following initiation of study treatment) as well as 
shift tables. 
Slit lamp biomicroscopy and dilated indirect 
ophthalmoscopic examination measures will be 
summarized at each visit using discrete summary 
statistics. 
Visual Acuity data will be summarized at each visit, 
using discrete summaries including change from 
baseline in the number of lines and the proportion of 
patients with worsening from previous visit of ≥ 2 
lines. 
Summary of Known 
and Potential Risks and 
This study is the first clinical study to evaluate the 
safety and efficacy of RTA 408 Ophthalmic 
Suspension. 


RTA 408 Ophthalmic Suspension 
 
 
 
 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
 
 
 
 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 13 of 77 
Benefits to Human Patients 
 
The ocular tolerability of RTA 408 was evaluated in 
multiple nonclinical studies in rats, guinea pigs, 
rabbits, and monkeys. No ocular or systemic toxicity 
was observed and systemic exposure was very low 
in all species tested. Conjunctival irritation was 
observed in the rabbit ocular GLP toxicity study 
with frequent dosing (4x/day); however, this was 
reversible, was not observed in a non-GLP study in 
rabbits, was not observed in the monkey ocular GLP 
toxicity study, and is readily monitorable in the 
clinic. In vitro and in vivo studies conducted to date 
demonstrate that RTA 408 is a potent activator of 
the Nrf2 pathway and an inhibitor of the NF-κB 
pathway, and should thus be an effective anti-
inflammatory agent for ophthalmic indications of 
inflammation and pain.  


RTA 408 Ophthalmic Suspension 
 
 
 
 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
 
 
 
 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 14 of 77 
TABLE OF CONTENTS 
SYNOPSIS ..................................................................................................................................... 3 
List of Abbreviations .................................................................................................................. 17 
1 
INTRODUCTION.............................................................................................................. 19 
2 
STUDY OBJECTIVES ...................................................................................................... 20 
3 
CLINICAL HYPOTHESES ............................................................................................. 20 
4 
OVERALL STUDY DESIGN ........................................................................................... 20 
5 
STUDY POPULATION .................................................................................................... 21 
5.1 
Number of Patients .................................................................................................. 21 
5.2 
Study Population Characteristics .......................................................................... 21 
5.3 
Inclusion Criteria .................................................................................................... 21 
5.4 
Exclusion Criteria .................................................................................................... 22 
5.5 
Withdrawal Criteria ................................................................................................ 24 
6 
STUDY PARAMETERS ................................................................................................... 24 
6.1 
Efficacy Measures .................................................................................................... 24 
6.1.1 
Secondary Efficacy Variables ...................................................................... 24 
6.2 
Safety Measures ....................................................................................................... 24 
6.3 
Other Measures ....................................................................................................... 25 
7 
STUDY MATERIALS ....................................................................................................... 25 
7.1 
Study Treatments .................................................................................................... 25 
7.1.1 
Study Treatments/Formulations ................................................................... 25 
7.1.2 
Instructions for Use and Administration ...................................................... 25 
7.2 
Other Study Supplies .............................................................................................. 25 
8 
STUDY METHODS AND PROCEDURES .................................................................... 26 
8.1 
Patient Entry Procedures ....................................................................................... 26 
8.1.1 
Overview ...................................................................................................... 26 
8.1.2 
Informed Consent......................................................................................... 26 
8.1.3 
Washout Intervals ........................................................................................ 26 
8.1.4 
Procedures for Final Study Entry ................................................................. 27 
8.1.5 
Methods for Assignment to Treatment Groups ........................................... 27 
8.2 
Concurrent Therapies ............................................................................................. 27 
8.2.1 
Prohibited Medications/Treatments ............................................................. 27 
8.2.2 
Escape Medications ..................................................................................... 28 
8.2.3 
Special Diet or Activities ............................................................................. 29 
8.3 
Examination Procedures ......................................................................................... 29 
8.3.1 
Procedures to be Performed at Each Study Visit with Regard 
to Study Objectives ................................................................................................... 29 
8.4 
Schedule of Visits, Measurements and Dosing ..................................................... 32 
8.4.1 
Scheduled Visits........................................................................................... 32 
8.4.2 
Unscheduled Visits ...................................................................................... 32 
8.5 
Compliance with Dosing ......................................................................................... 33 
8.6 
Patient Disposition ................................................................................................... 33 
8.6.1 
Completed Patients ...................................................................................... 33 
8.6.2 
Discontinued Patients................................................................................... 33 
8.7 
Study Termination .................................................................................................. 34 


RTA 408 Ophthalmic Suspension 
 
 
 
 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
 
 
 
 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 15 of 77 
8.8 
Study Duration ........................................................................................................ 34 
8.9 
Monitoring and Quality Assurance ....................................................................... 34 
9 
ADVERSE EVENTS (AEs) ............................................................................................... 35 
9.1 
Adverse Event .......................................................................................................... 35 
9.1.1 
Severity ........................................................................................................ 35 
9.1.2 
Relationship to Study Drug .......................................................................... 35 
9.2 
Serious Adverse Events (SAEs) .............................................................................. 36 
9.3 
Procedures for Reporting AEs ............................................................................... 37 
9.3.1 
Reporting a Suspected Unexpected Adverse Reaction ................................ 37 
9.3.2 
Reporting an SAE ........................................................................................ 37 
9.4 
Procedures for Emergency Unmasking of Study Drug ....................................... 38 
9.5 
Type and Duration of the Follow-up of Patients after AEs ................................. 38 
10 
STATISTICAL HYPOTHESES AND METHODS OF ANALYSES........................... 39 
10.1 Study Populations .................................................................................................... 39 
10.1.1 Intent-to-Treat Population ............................................................................ 39 
10.1.2 Safety Population ......................................................................................... 39 
10.1.3 Per Protocol Population ............................................................................... 39 
10.2 Unit of Analysis ........................................................................................................ 39 
10.3 General Imputation Methods ................................................................................. 39 
10.4 Efficacy Variables .................................................................................................... 40 
10.5 Safety Variables ....................................................................................................... 40 
10.6 Statistical Hypotheses .............................................................................................. 40 
10.7 Sample Size .............................................................................................................. 42 
10.8 Methods of Analyses ................................................................................................ 42 
10.9 Demographics and Baseline Medical History ....................................................... 43 
10.10 Primary Efficacy Analyses ..................................................................................... 43 
10.11 Secondary Efficacy Analyses .................................................................................. 44 
10.12 Safety Analyses ........................................................................................................ 44 
10.13 Subgroup Analysis ................................................................................................... 44 
10.14 Interim Analysis ...................................................................................................... 44 
11 
COMPLIANCE WITH GOOD CLINICAL PRACTICES, ETHICAL 
CONSIDERATIONS, AND ADMINISTRATIVE ISSUES ........................................... 45 
11.1 Protection of Human Subjects................................................................................ 45 
11.1.1 Patient Informed Consent ............................................................................ 45 
11.1.2 Institutional Review Board (IRB) Approval ................................................ 45 
11.2 Ethical Conduct of the Study ................................................................................. 45 
11.3 Patient Confidentiality ............................................................................................ 46 
11.4 Documentation ......................................................................................................... 46 
11.4.1 Retention of Documentation ........................................................................ 46 
11.5 Labeling, Packaging, Storage, Accountability, and Return or 
Disposal of Study Drug ........................................................................................... 47 
11.5.1 Labeling/Packaging...................................................................................... 47 
11.5.2 Storage of Study Drug ................................................................................. 47 
11.5.3 Accountability of Study Drug ...................................................................... 47 
11.5.4 Return or Disposal of Study Drug ............................................................... 47 
11.6 Recording of Data on Source Documents and eCRFs .......................................... 47 


RTA 408 Ophthalmic Suspension 
 
 
 
 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
 
 
 
 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 16 of 77 
11.7 Handling of Biological Specimens .......................................................................... 48 
11.8 Publications .............................................................................................................. 48 
12 
REFERENCES ................................................................................................................... 49 
APPENDIX 1: EXAMINATION PROCEDURES .................................................................. 50 
APPENDIX 2:  SCHEDULE OF VISITS AND MEASUREMENTS .................................... 56 
APPENDIX 3: PROTOCOL AMENDMENTS ....................................................................... 57 
APPENDIX 4:  SPONSOR APPROVALS ............................................................................... 76 
APPENDIX 5:  INVESTIGATOR’S SIGNATURE ................................................................ 77 
 
 
 


57$2SKWKDOPLF6XVSHQVLRQ




5HDWD3KDUPDFHXWLFDOV
&OLQLFDO7ULDO3URWRFRO&




$PHQGPHQW)HE

&RQILGHQWLDO

3DJHRI
/LVWRI$EEUHYLDWLRQV
$(
$GYHUVH(YHQW
$8&
$UHDXQGHUWKHFXUYH
%,'
%LVLQGLHWZLFHGDLO\
%3+
%HQLJQSURVWDWLFK\SHUSODVLD
&)5
&RGHRI)HGHUDO5HJXODWLRQV
&5)
&DVH5HSRUW)RUP
&52
&RQWUDFW5HVHDUFK2UJDQL]DWLRQ
&60(
&OLQLFDOO\VLJQLILFDQWPDFXODUHGHPD
'++6
'HSDUWPHQWRI+HDOWKDQG+XPDQ6HUYLFHV
H&5)
(OHFWURQLF&DVH5HSRUW)RUP
(7'56
(DUO\7UHDWPHQWRI'LDEHWLF5HWLQRSDWK\6WXG\
)'$
)RRGDQG'UXJ$GPLQLVWUDWLRQ
*&3
*RRG&OLQLFDO3UDFWLFH
+(&
+\GUR[\HWK\OFHOOXORVH
+,3$$
+HDOWK,QIRUPDWLRQ3RUWDELOLW\DQG$FFRXQWDELOLW\$FW
+U
+RXU
,&)
,QIRUPHG&RQVHQW)RUP
,&+
,QWHUQDWLRQDO&RQIHUHQFHRQ+DUPRQLVDWLRQ
,(&
,QGHSHQGHQW(WKLFV&RPPLWWHH
,1'
,QYHVWLJDWLRQDO1HZ'UXJ$SSOLFDWLRQ
,1)•
,QWHUIHURQJDPPD
,23
,QWUDRFXODU3UHVVXUH
,5%
,QVWLWXWLRQDO,QGHSHQGHQW5HYLHZ%RDUG
,77
,QWHQWWR7UHDW
/2&)
/DVW2EVHUYDWLRQ&DUULHG)RUZDUG
ORJ0$5
/RJDULWKPRIWKH0LQLPXP$QJOHRI5HVROXWLRQ
P/
0LOOLOLWHU
• J
0LFURJUDP
1&6
1RWFOLQLFDOO\VLJQLILFDQW
1'$
1HZ'UXJ$SSOLFDWLRQ
1)• • 
1XFOHDUIDFWRUNDSSDOLJKWFKDLQHQKDQFHURIDFWLYDWHG%FHOOV
QJ
1DQRJUDP
12
1LWULFR[LGH
14
1$'+TXLQLQHR[LGRUHGXFWDVH
1UI
1XFOHDUIDFWRUHU\WKURLGGHULYHG
16$,'
1RQVWHURLGDODQWLLQIODPPDWRU\DJHQW
3&,2/
3RVWHULRUFKDPEHULQWUDRFXODUOHQV
3'5
3UROLIHUDWLYHGLDEHWLFUHWLQRSDWK\
3+,
3URWHFWHG+HDOWK,QIRUPDWLRQ
33
3HU3URWRFRO
393
3RO\YLQ\OS\UUROLGRQH
4'
4XDTXHGLH2QFHGDLO\


RTA 408 Ophthalmic Suspension 
 
 
 
 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
 
 
 
 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 18 of 77 
SAE 
Serious Adverse Event 
SAP 
Statistical analysis plan 
SUN 
Standardization of the Uveitis Nomenclature 
VA 
Visual acuity 
 
 


57$2SKWKDOPLF6XVSHQVLRQ




5HDWD3KDUPDFHXWLFDOV
&OLQLFDO7ULDO3URWRFRO&




$PHQGPHQW)HE

&RQILGHQWLDO

3DJHRI
 ,1752'8&7,21
)ROORZLQJRSKWKDOPLFVXUJHU\WKHFXUUHQWVWDQGDUGRIFDUHLQFOXGHVDWRSLFDORSKWKDOPLF
FRUWLFRVWHURLGRURWKHUDQWLLQIODPPDWRU\DJHQWWRWUHDWRFXODULQIODPPDWLRQDQGLPSURYH
SDWLHQWFRPIRUW ,IOHIWXQWUHDWHGLQIODPPDWLRQRIWKHH\HPD\UHVXOWLQ IXUWKHURFXODU
FRPSOLFDWLRQV LQFOXGLQJ VFDUULQJ YLVLRQ ORVV RU EOLQGQHVV $OWKRXJK WKH H[DFW GRVLQJ
UHJLPHQLVSK\VLFLDQGHSHQGHQWSDWLHQWVDUHW\SLFDOO\SUHVFULEHGDWRSLFDOFRUWLFRVWHURLG
IRUDSHULRGRIZHHNVIROORZLQJVXUJHU\EHLQJWDSHUHGRYHUWKHFRXUVHRIGHOLYHU\DV
WKH LQIODPPDWLRQ VXEVLGHV 7RSLFDO DQWLLQIODPPDWRU\ DJHQWV DUH XVXDOO\ DGPLQLVWHUHG
PXOWLSOH WLPHV SHU GD\ SDUWLFXODUO\ LQ WKH HDUO\ SHULRG IROORZLQJ RSKWKDOPLF VXUJHU\
&RQWLQXLQJ HIIRUWV LQ GUXJ GHYHORSPHQW DLP WR LGHQWLI\ DOWHUQDWLYHV WR RSKWKDOPLF
FRUWLFRVWHURLGXVHGXHWRWKHLUZHOONQRZQORFDODQGV\VWHPLFQHJDWLYHVLGHHIIHFWV
1DWXUDO WULWHUSHQRLGV VXFK DV ROHDQROLF DFLG DQG XUVROLF DFLG ZKLFK DUH GHULYHG IURP
SODQWH[WUDFWVKDYHEHHQXVHGH[WHQVLYHO\LQ$VLDQPHGLFLQHIRUWKHLUDQWLLQIODPPDWRU\
DQG DQWLFDQFHU SURSHUWLHV 5HIHUHQFH  /LX  $ VHULHV RI VHPLV\QWKHWLF
WULWHUSHQRLGVZDVSUHSDUHGEDVHGRQWKHVWUXFWXUHRIROHDQROLFDFLGDQGWHVWHGWRLGHQWLI\
FRPSRXQGV RSWLPL]HG IRU WKHLU DELOLW\ WR LQKLELW WKH LQGXFWLRQ RI QLWULF R[LGH 12 LQ
SULPDU\PRXVHPDFURSKDJHVWUHDWHGZLWKLQWHUIHURQJDPPD,)1• 5HIHUHQFH +RQGD

57$  LV D QRYHO ROHDQDQH WULWHUSHQRLG ZLWKLQWKLVFODVVRIFRPSRXQGV7KHUHVXOWV
IURPLQYLWURDQGLQYLYRSUHFOLQLFDOVWXGLHVFRQGXFWHGWRGDWHGHPRQVWUDWHWKDW57$
DVZHOODVRWKHUVHPLV\QWKHWLFWULWHUSHQRLGVDUHSRWHQWDFWLYDWRUVRIWKH1UIQXFOHDU
IDFWRUHU\WKURLGGHULYHGSDWKZD\DQGLQKLELWRUVRIWKH1)ț%QXFOHDUIDFWRUNDSSD
OLJKWFKDLQHQKDQFHURIDFWLYDWHG%FHOOVSDWKZD\DQGWKXVLQGXFHDQDQWLR[LGDQWDQG
DQWLLQIODPPDWRU\SKHQRW\SH
5HDWDKDVGHPRQVWUDWHGLQSUHFOLQLFDOPRGHOVWKDWWRSLFDORFXODUDGPLQLVWUDWLRQRI57$
LQFUHDVHVWKHH[SUHVVLRQRI142DSURWRW\SLFDO1UIWDUJHWJHQHLQWKHFRUQHDO
HSLWKHOLXPDQGWKHFRUQHDOHQGRWKHOLXPRIUDEELWVZLWKWKHJUHDWHVWHIIHFWREVHUYHGLQWKH
GRVHJURXS7RSLFDORFXODUDGPLQLVWUDWLRQRI57$[GD\DWFRQFHQWUDWLRQVDV
ORZDVLVHIILFDFLRXVLQYLYRDVDQDQWLLQIODPPDWRU\DJHQWLQDUDEELWPRGHORI
SDUDFHQWHVLVLQGXFHGRFXODULQIODPPDWLRQ
57$  LV UHDGLO\ DEVRUEHG DQG GLVWULEXWHG LQWR RFXODU WLVVXHV DIWHU WRSLFDO RFXODU
DGPLQLVWUDWLRQZLWKVXVWDLQHGFRQFHQWUDWLRQVREVHUYHGIRUDWOHDVWKRXUVDIWHUWKHODVW
GRVH7KLVRFXODUSKDUPDFRNLQHWLFSURILOHLVFRQVLVWHQWZLWKWKHHIILFDF\REVHUYHGZLWK
WZLFHGDLO\RFXODUGRVLQJLQUDEELWV
2FXODU*/3WR[LFLW\VWXGLHVKDYHEHHQFRPSOHWHGZLWK57$2SKWKDOPLF6XVSHQVLRQ
LQUDEELWVDQGPRQNH\VZLWKUHSHDWHG[GD\DGPLQLVWUDWLRQRI57$
DQG  IRU GD\V  $V H[SHFWHG V\VWHPLF H[SRVXUH WR 57$ ZDV YHU\ ORZ LQ
UDEELWVDQGPRQNH\VZLWKPD[LPXPFRQFHQWUDWLRQV&PD[RQ'D\RIDSSUR[LPDWHO\
DQGQJP/UHVSHFWLYHO\2YHUDOOWKHWRSLFDORFXODUDGPLQLVWUDWLRQRI57$
2SKWKDOPLF6XVSHQVLRQDWFRQFHQWUDWLRQVRIDQGIRXUWLPHVGDLO\ IRU
GD\V LQ UDEELWV EXW QRW PRQNH\V SURGXFHG RFXODU LUULWDWLRQ EXW GLG QRW FDXVH DQ\
RFXODURUV\VWHPLFWR[LFLW\LQUDEELWVRUPRQNH\V7KXVWKHQRREVHUYHGDGYHUVHHIIHFW
OHYHO 12$(/ ZDV GHWHUPLQHG WR EH DW OHDVW 57$ 2SKWKDOPLF 6XVSHQVLRQ


RTA 408 Ophthalmic Suspension 
 
 
 
 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
 
 
 
 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 20 of 77 
administered 4x/day for 28 days in rabbits and monkeys.  The conjunctival irritation 
observed in the rabbit ocular GLP toxicity study was reversible, was not observed in a 
non-GLP study in rabbits, was not observed in the monkey ocular GLP toxicity study, 
and is readily monitorable in the clinic. 
Although it is highly unlikely that meaningful systemic exposure will result following 
topical ocular administration in humans, the systemic toxicity potential of RTA 408 has 
been extensively investigated in rats and monkeys, with daily oral administration for up 
to 6 months in rats and 9 months in monkeys. 
Based on an integrated assessment of the nonclinical data, it is concluded that RTA 408 
has an acceptable safety profile for topical ophthalmic use as indicated in the proposed 
topical ocular study in patients following uncomplicated cataract surgery at 
concentrations of 0.5% and 1.0% with a BID dosage regimen.  
2 STUDY OBJECTIVES 
To evaluate the clinical efficacy and safety of RTA 408 Ophthalmic Suspension in two 
concentrations versus placebo in the treatment of patients with inflammation and pain 
following uncomplicated cataract surgery. 
3 CLINICAL HYPOTHESES 
It is hypothesized that RTA 408 Ophthalmic Suspension will be more effective than 
placebo in the alleviation of inflammation and pain following cataract surgery. 
4 OVERALL STUDY DESIGN 
This trial will be a multi-center, double-masked, randomized, dose-ranging, placebo-
controlled study consisting of 6 visits over approximately 7 weeks (49 days). 
Randomization will be used to avoid bias in the assignment of patients to treatment, to 
increase the likelihood that known and unknown patient attributes (e.g., demographics 
and baseline characteristics) are evenly balanced across treatment groups, and to enhance 
the validity of statistical comparisons across treatment groups. Masked treatment will be 
used to reduce potential of bias during data collection and evaluation of clinical 
endpoints.    
At Visit 1 (Day -1 to Day -28), patients will be screened to ensure that they meet all 
initial inclusion criteria and none of the exclusion criteria. Medical and medication 
histories will be taken, the patients will subjectively grade ocular pain using the scales 
provided, and pin-hole visual acuity will be assessed. The Investigator will then perform 
a slit lamp biomicroscopic examination with intraocular pressure (IOP) measurement, 
and grading of anterior chamber inflammation. A dilated indirect ophthalmoscopic 
examination will also be performed. Female patients of childbearing potential will be 
given a urine pregnancy test.  
At Visit 2 (Day 1, 24 ± 6 hours post-surgery), patients’ medical and medication histories 
will be updated, patients will be queried for ocular pain, pin-hole visual acuity will be 
assessed, and the Investigator will perform a slit lamp biomicroscopic evaluation, IOP 


RTA 408 Ophthalmic Suspension 
 
 
 
 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
 
 
 
 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 21 of 77 
measurement, and grading of anterior chamber inflammation. Qualifying patients  will 
then be randomized to one of the following treatment groups (in a 1:1:1 ratio): RTA 408 
Ophthalmic Suspension 0.5% (N=35), RTA 408 Ophthalmic Suspension 1.0% (N=35), or 
placebo for RTA 408 Ophthalmic Suspension (N=35). Study drug will be dispensed 
along with the Study Drug Compliance Diary.  A trained unmasked technician will 
instruct patients on how to instill the study drug twice daily in the morning and evening 
(approximately 12 hours apart) for 14 days on the eye that underwent surgery. The first 
dose of study drug will be instilled in-office.  
At Visits 3 (Day 4± 1), 4 (Day 8± 1), and 5 (Day 15+ 1), patients’ medical and 
medication histories will be updated, patients will be queried for ocular pain, pin-hole 
visual acuity will be assessed, and the Investigator will perform a slit lamp 
biomicroscopic evaluation, IOP measurement, and grading of anterior chamber 
inflammation. AEs will be noted, and the Study Drug Compliance Diary will be 
reviewed. Day 14 will be the last day of study drug treatment at home. On Visit 5 (Day 
15+ 1), the study drug and Study Drug Compliance Diary will be collected. 
At Visit 6 (Day 21± 1), patients’ medical and medication histories will be updated, 
patients will be queried for ocular pain, pin-hole visual acuity will be assessed, and the 
Investigator will perform a slit lamp biomicroscopic evaluation, IOP assessment, and 
grading of anterior chamber inflammation. A dilated indirect ophthalmoscopic 
examination will also be performed. AEs will be noted, and a urine pregnancy test will be 
given to females of childbearing potential. Patients will then exit the study.  
5 STUDY POPULATION 
5.1 
Number of Patients 
Approximately 105 patients will be enrolled in this multi-center study, 35 per arm, in 
order to complete 31 patients per arm.  
5.2 
Study Population Characteristics 
Patients age 18 and older who are scheduled to undergo ocular surgery, and who 
meet all inclusion criteria and none of the exclusion criteria.  
5.3 
Inclusion Criteria 
Each patient must meet the following criteria: 
1. Have provided written informed consent, approved by the appropriate institutional 
review board; 
2. Be able to comply with study requirements and visit schedule; 
3. Be greater than or equal to 18 years of age of either sex or any race;  
4. Have undergone unilateral cataract extraction via phacoemulsification and 
posterior chamber intraocular lens (PCIOL) implantation in the study eye on the 
day prior to study enrollment/randomization; 
5. Have a grade of ≥ 2 in anterior chamber cell score on day after surgery (Day 1) in 
the study eye; 


RTA 408 Ophthalmic Suspension 
 
 
 
 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
 
 
 
 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 22 of 77 
6. Have a potential post-operative pin-hole visual acuity (VA) < 1.0 logarithm of the 
minimum angle of resolution (logMAR) in the operative eye and fellow eye as 
measured using an Early Treatment for Diabetic Retinopathy Study (ETDRS) 
chart; 
7. (For females of childbearing potential) agree to have urine pregnancy testing 
performed at screening (must be negative) and at exit visit; must not be lactating; 
and must agree to use a medically acceptable form of birth control2 throughout 
the study duration. Women of childbearing potential include all females who have 
experienced menarche and have not experienced menopause (as defined by 
amenorrhea for greater than 12 consecutive months) or have not undergone 
successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral 
oophorectomy).   
5.4 
Exclusion Criteria 
Each patient may not meet any of the following: 
1. Have any intraocular inflammation present in the study eye during the screening 
slit lamp examination; 
2. Have a score greater than “0” on the Ocular Pain Assessment at Screening in the 
study eye; 
3. Have an immunosuppressive disease or an autoimmune disease that in the opinion 
of the Investigator could affect the quality of the ocular surface; 
4. Have active or chronic/recurrent ocular or systemic disease that is uncontrolled 
and will likely affect wound healing; 
5. Currently have suspected or known malignancy or is currently receiving 
antineoplastic therapy; 
6. 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 has 
a positive urine pregnancy test at screening; 
7. Use anti-inflammatory agents, analgesics/pain relievers (including opioids, 
narcotics and other pain medications) or immunomodulating agents systemically, 
or in the study 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 surgery are as follows: 
a. Medications for BPH (tamsulosin, silodosin, alfuzosin, finasteride): 28 days  
b. Systemic corticosteroids: 14 days 
c. Systemic analgesics/pain relievers (e.g., gabapentin, pregabalin, NSAIDs and 
opioids): 14 days 
Note: Use of acetaminophen (up to 4,000 mg/day) and ‘baby’ aspirin (up to 81 
mg/day) during the study are allowed. Use of an opioid during cataract 
surgery is allowed. 
d. Periocular injection of any corticosteroid solution: 28 days 
                                                 
2Acceptable forms of birth control are spermicide with barrier, oral contraceptive, injectable or implantable 
method of contraception, transdermal contraceptive, intrauterine device, or surgical sterilization of partner. 
For non-sexually active females, abstinence will be considered an acceptable form of birth control.  


RTA 408 Ophthalmic Suspension 
 
 
 
 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
 
 
 
 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 23 of 77 
e. Corticosteroid depot in the study eye: 56 days after implantation  
f. Cyclosporine: 56 days 
g. Topical ocular corticosteroid: 7 days  
h. Topical ocular NSAID: 7 days 
8. Have glaucoma or be taking medications to treat glaucoma in the study eye; 
9. Have an intraocular pressure (IOP)  ≤ 5 mmHg in either eye; 
10. Currently have or have a history of Herpes Simplex Keratitis in the study eye;  
11. Have active corneal abrasions or ulcers in the study eye; 
12. Have active or a history of chronic or recurrent inflammatory eye disease (e.g. 
iritis, scleritis, uveitis, iridocyclitis, rubeosis iritis) in the study eye; 
13. 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);  
tuberculosis of the eye; corneal dystrophies; intraocular infections, dysthyroid 
ophthalmopathy, active chalazion, or uncontrolled blepharitis in the study eye; 
14. Have uncontrolled and clinically significant dry eye syndrome in the study eye 
(artificial tears are allowed); 
15. Have proliferative diabetic retinopathy (PDR), compromised macular function; 
significant macular diseases; clinically significant macular edema (CSME); or a 
history of cystoid macular edema in the study eye;  
16. Have had corneal or retinal surgery (laser or incisional) within the past 6 months, 
or be planning to have laser or incisional surgery during the study period in the 
study eye (other than cataract surgery);  
17. Have  surgery planned or scheduled for the contralateral eye during the study; 
18. Have previous ocular trauma with visible scarring or any deformities due to the 
trauma in the study eye; 
19. Require the use of a contact lens or a collagen shield within 72 hours of 
investigational drug treatment or during the study period in the study eye; be 
unwilling to discontinue use of contact lenses during study period in the study 
eye; 
20. Require use of non-diagnostic topical ophthalmic solutions (other than 
perioperative mydriatics, anesthetics and antiseptics, prophylactic antibiotics, lid 
scrubs for mild blepharitis, or artificial tears for the management of dry eye) in 
the study eye for the duration of the study; 
21. Have known allergy or sensitivity to the investigational product or its 
components; 
22. Have ocular hemorrhage in the study eye that interferes with evaluation of post-
surgery inflammation; 
23. Have undergone any other ophthalmic surgical procedure (e.g., vitrectomy, 
relaxing incisions, iridectomy, conjunctival excisions, use of iris hooks or other 
iris dilators, etc.) in addition to the cataract extraction procedure and PCIOL 
implantation in the study eye; 
24. Have previously enrolled in this clinical study, or are planning to participate in 
another clinical trial during the follow-up period, that could confound the 
treatment or outcomes of this investigation; 
25. Be excluded if the Investigator determines that the patient should not be included 
for 
reasons 
not 
already 
specified 
(e.g., 
systemic 
or 
other 
ocular 


RTA 408 Ophthalmic Suspension 
 
 
 
 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
 
 
 
 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 24 of 77 
disease/abnormality), if the health of the patient or the validity of the study 
outcomes may be compromised by the patient’s enrollment. 
5.5 
Withdrawal Criteria  
If at any time during the study the investigator determines that a patient’s safety has 
been compromised, the patient may be withdrawn from the study. 
Patients may withdraw consent from the study at any time. 
Sponsor and/or investigator may discontinue any patient for non-compliance or any 
valid medical reason (see Section 8.6.2). 
6 STUDY PARAMETERS 
6.1 
Efficacy Measures  
The hierarchical primary efficacy variables are the following: 
1. Absence of anterior chamber cells (i.e., score of ‘0’) at Visit 5 (Day 15) for: 
a. The 1.0% concentration of RTA 408 Ophthalmic Suspension compared 
to Placebo 
b. The 0.5% concentration of RTA 408 Ophthalmic Suspension compared 
to Placebo. 
2. Absence of pain (i.e., score of ‘0’) at Visit 3 (Day 4) for: 
a. The 1.0% concentration of RTA 408 Ophthalmic Suspension compared to 
Placebo; to be tested if 1a. is statistically significant in favor of the active 
arm. 
b. The 0.5% concentration of RTA 408 Ophthalmic Suspension compared to 
Placebo; to be tested if 1b. is statistically significant in favor of the active 
arm. 
6.1.1 Secondary Efficacy Variables 
1. Absence of anterior chamber cells at Visits 3, 4, or 6 (Days 4±1, 8±1, or 
21±1, respectively) 
2. Absence of pain at Visits 4, 5 or 6 (Days 8±1, 15+1 or 21±1, respectively) 
3. Absence of flare at Visits 3, 4, 5 or 6 (Days 4±1, 8±1, 15+1 or 21±1, 
respectively) 
6.2 
Safety Measures 
• Slit lamp biomicroscopy  
• Pin-hole visual acuity  
• IOP  
• Dilated indirect ophthalmoscopic examination 
• AE monitoring 




57$2SKWKDOPLF6XVSHQVLRQ




5HDWD3KDUPDFHXWLFDOV
&OLQLFDO7ULDO3URWRFRO&




$PHQGPHQW)HE

&RQILGHQWLDO

3DJHRI
 678'<0(7+2'6$1'352&('85(6

3DWLHQW(QWU\3URFHGXUHV
 2YHUYLHZ
3DWLHQWV DV GHILQHG E\ WKH FULWHULD LQ VHFWLRQ   DQG  ZLOO EH
FRQVLGHUHGIRUHQWU\LQWRWKLVVWXG\6HH$SSHQGL[IRUDWDEXODUVXPPDU\RI
VWXG\YLVLWVDQGSURFHGXUHVUHTXLUHGIRUHDFKYLVLW
 ,QIRUPHG&RQVHQW
3ULRUWRDSDWLHQW¶VSDUWLFLSDWLRQLQWKHWULDOLHFKDQJHVLQDSDWLHQW¶VPHGLFDO
WUHDWPHQWDQGRUVWXG\UHODWHGSURFHGXUHVWKHVWXG\ZLOOEHGLVFXVVHGZLWK
HDFKSDWLHQWDQGSDWLHQWVZLVKLQJWRSDUWLFLSDWHPXVWJLYHZULWWHQLQIRUPHG
FRQVHQWXVLQJDQLQIRUPHGFRQVHQWIRUP7KHLQIRUPHGFRQVHQWIRUPPXVWEH
WKH PRVW UHFHQW YHUVLRQ WKDW KDV UHFHLYHG DSSURYDOIDYRUDEOH UHYLHZ E\ D
SURSHUO\FRQVWLWXWHG,QVWLWXWLRQDO5HYLHZ%RDUG
 :DVKRXW,QWHUYDOV
6WXG\VWDIIZLOOFRQILUPWKDWWKHSDWLHQWKDVQRWXVHGSULRUWR'D\IRUWKH
LQGLFDWHG ZDVKRXW LQWHUYDO DQ\ RI WKH IROORZLQJ GLVDOORZHG PHGLFDWLRQV
V\VWHPLFDOO\RULQWKHVWXG\H\HJURXSHGE\ZDVKRXWSHULRG
KRXUV
• &RQWDFWOHQVRUDFROODJHQVKLHOGLQWKHVWXG\H\H
GD\V
• 7RSLFDORFXODUFRUWLFRVWHURLG
• 7RSLFDORFXODU16$,'
GD\V
• 6\VWHPLFFRUWLFRVWHURLGV
• 6\VWHPLF DQDOJHVLFVSDLQ UHOLHYHUV HJ JDEDSHQWLQ SUHJDEDOLQ
16$,'VDQGRSLRLGV
1RWH8VHRIDFHWDPLQRSKHQXSWRPJGD\DQGµEDE\¶DVSLULQ
XS WR  PJGD\ GXULQJ WKH VWXG\ DUH DOORZHG 8VH RI DQ RSLRLG
GXULQJFDWDUDFWVXUJHU\LVDOORZHG
GD\V
• 3HULRFXODULQMHFWLRQRIDQ\FRUWLFRVWHURLGVROXWLRQ
• 6\VWHPLF PHGLFDWLRQV IRU %3+ WDPVXORVLQ VLORGRVLQ DOIX]RVLQ
ILQDVWHULGH
GD\V
• &RUWLFRVWHURLGGHSRWLQWKHVWXG\H\HDIWHULPSODQWDWLRQ


57$2SKWKDOPLF6XVSHQVLRQ




5HDWD3KDUPDFHXWLFDOV
&OLQLFDO7ULDO3URWRFRO&




$PHQGPHQW)HE

&RQILGHQWLDO

3DJHRI
• 7RSLFDORFXODUF\FORVSRULQH
 3URFHGXUHVIRU)LQDO6WXG\(QWU\
3DWLHQWVPXVWVDWLVI\DOOLQFOXVLRQDQGQRQHRIWKHH[FOXVLRQFULWHULDLQRUGHUWR
EHHQWHUHGLQWRWKHVWXG\RQ6WXG\9LVLW
 0HWKRGVIRU$VVLJQPHQWWR7UHDWPHQW*URXSV
$OOSDWLHQWVVFUHHQHGIRUWKHVWXG\ZKRVLJQDFRQVHQWIRUPZLOOEHDVVLJQHGD
GLJLW VFUHHQLQJ QXPEHU ZKLFK ZLOO EH HQWHUHG LQ WKH 6FUHHQLQJ DQG
(QUROOPHQW/RJ7KH3DWLHQW,'QXPEHUZLOOEHDGLJLWQXPEHUFRQVLVWLQJRI
WKHGLJLWVLWHQXPEHUFRPELQHGZLWKWKHGLJLWVFUHHQLQJQXPEHU
2QFHDSDWLHQWPHHWVDOOTXDOLILFDWLRQFULWHULDWKH\ZLOOEHUDQGRPO\DVVLJQHG
WRPDVNHGWUHDWPHQWXVLQJD57$57$SODFHER
DVVLJQPHQW UDWLR 3DWLHQWV ZLOO EH UDQGRPL]HG RQ WKH ILUVW GD\ SRVWVXUJHU\
'D\E\DVVLJQPHQWRIWKHORZHVWGLJLWVWXG\GUXJNLWQXPEHUDYDLODEOHDW
WKHLULQYHVWLJDWLYHVLWH1RVWXG\GUXJNLWQXPEHUVZLOOEHVNLSSHGRURPLWWHG
$WUDLQHGXQPDVNHGWHFKQLFLDQZLOODGPLQLVWHUVWXG\GUXJIURPWKHERWWOHRI
WKHVWXG\GUXJNLWDVVLJQHGWRWKHSDWLHQW(DFKVWXG\GUXJNLWZLOOEHODEHOHG
ZLWK WKH GLJLW VWXG\ GUXJ NLW QXPEHU  7KH ERWWOH RI VWXG\ GUXJ ZLOO EH
GLVSHQVHGWRWKHSDWLHQWIRUXVHRQVXEVHTXHQWGD\V

&RQFXUUHQW7KHUDSLHV
7KHXVHRIDQ\FRQFXUUHQWPHGLFDWLRQSUHVFULSWLRQRURYHUWKHFRXQWHUXVHGZLWKLQ
WKHODVWGD\VEHIRUH9LVLWDQGIRUWKHGXUDWLRQRIWKHVWXG\LVWREHUHFRUGHGRQ
WKH SDWLHQW¶V VRXUFH GRFXPHQW DQG FRUUHVSRQGLQJ FDVH UHSRUW IRUP H&5) DORQJ
ZLWKWKHUHDVRQWKHPHGLFDWLRQZDVWDNHQ
&RQFXUUHQW HQUROOPHQW LQ DQRWKHU LQYHVWLJDWLRQDO GUXJ RU GHYLFH VWXG\ LV QRW
SHUPLWWHG
 3URKLELWHG0HGLFDWLRQV7UHDWPHQWV
3URKLELWHGPHGLFDWLRQVWUHDWPHQWVIRUWKHGXUDWLRQRIWKHVWXG\DUH
• 7RSLFDORFXODUFRUWLFRVWHURLGLQWKHVWXG\H\H
• 7RSLFDORFXODU16$,'LQWKHVWXG\H\H
• 6\VWHPLFFRUWLFRVWHURLGV
• 3HULRFXODULQMHFWLRQRIDQ\FRUWLFRVWHURLGVROXWLRQLQWKHVWXG\H\H
• &RUWLFRVWHURLGGHSRWLQWKHVWXG\H\HDIWHULPSODQWDWLRQ
• 7RSLFDORFXODUF\FORVSRULQHLQWKHVWXG\H\H
• $QWLLQIODPPDWRU\ RU LPPXQRPRGXODWLQJ DJHQWV V\VWHPLFDOO\ RU LQ
WKHVWXG\H\H


57$2SKWKDOPLF6XVSHQVLRQ




5HDWD3KDUPDFHXWLFDOV
&OLQLFDO7ULDO3URWRFRO&




$PHQGPHQW)HE

&RQILGHQWLDO

3DJHRI
• 6\VWHPLF PHGLFDWLRQV IRU EHQLJQ SURVWDWLF K\SHUSODVLD %3+ HJ
WDPVXORVLQVLORGRVLQDOIX]RVLQILQDVWHULGH
• 6\VWHPLF $QDOJHVLFVSDLQ UHOLHYHUV LQFOXGLQJ RSLRLGV QDUFRWLFV DQG
RWKHU SDLQ PHGLFDWLRQV V\VWHPLFDOO\ HJ JDEDSHQWLQ SUHJDEDOLQ
16$,'VDQGRSLRLGV
1RWH8VHRIDFHWDPLQRSKHQXSWRPJGD\DQGµEDE\¶DVSLULQ
XS WR  PJGD\ GXULQJ WKH VWXG\ DUH DOORZHG 8VH RI DQ RSLRLG
GXULQJFDWDUDFWVXUJHU\LVDOORZHG
• *ODXFRPDPHGLFDWLRQVRURFXODUK\SHUWHQVLRQPHGLFDWLRQVLQWKHVWXG\
H\H
• &RQWDFWOHQVRUDFROODJHQVKLHOGLQWKHVWXG\H\H
• 1RQGLDJQRVWLFWRSLFDORSKWKDOPLFVROXWLRQVRWKHUWKDQSHULRSHUDWLYH
P\GULDWLFV DQHVWKHWLFV DQG DQWLVHSWLFV SURSK\ODFWLF DQWLELRWLFV OLG
VFUXEV IRUPLOGEOHSKDULWLVRUDUWLILFLDO WHDUV IRU WKH PDQDJHPHQW RI
GU\H\HLQWKHVWXG\H\H
• $QWLQHRSODVWLFWKHUDS\
• $Q\ RWKHU RSKWKDOPLF VXUJLFDO SURFHGXUH HJ YLWUHFWRP\ UHOD[LQJ
LQFLVLRQVLULGHFWRP\FRQMXQFWLYDOH[FLVLRQVXVHRILULVKRRNVRURWKHU
LULVGLODWRUVHWFLQDGGLWLRQWRWKHFDWDUDFWH[WUDFWLRQSURFHGXUHDQG
3&,2/LPSODQWDWLRQLQWKHVWXG\H\H
• 3ODQ WR KDYH ODVHURULQFLVLRQDOVXUJHU\LQWKHVWXG\H\H RWKHU WKDQ
FDWDUDFWVXUJHU\

• 6XUJHU\SODQQHGRUVFKHGXOHGIRUWKHFRQWUDODWHUDOH\H

,I D SDWLHQW XVHV D GLVDOORZHG PHGLFDWLRQ WKLV XVH ZLOO EH UHFRUGHG DV D
SURWRFRO YLRODWLRQ 3URWRFRO YLRODWLRQV PXVW EH UHSRUWHG WR WKH ,5% LQ
DFFRUGDQFHZLWKWKHLUVWDQGDUGRSHUDWLQJSURFHGXUHV
 (VFDSH0HGLFDWLRQV
8VH RI HVFDSH PHGLFDWLRQV VKRXOG EH DYRLGHG LI SRVVLEOH ,I LQ WKH
LQYHVWLJDWRU¶V DVVHVVPHQW HVFDSH PHGLFDWLRQ LV UHTXLUHG GXH WR ODFN RI
HIILFDF\WKHVWXG\GUXJVKRXOGEHGLVFRQWLQXHGSULRUWRDGPLQLVWUDWLRQRIWKH
ILUVWGRVHRIHVFDSHPHGLFDWLRQ7KHSDWLHQWVKRXOGUHPDLQLQWKHVWXG\DQG
FRQWLQXH WR EH IROORZHG SHU WKH SURWRFRO IRU DOO UHPDLQLQJ YLVLWV DQG
DVVHVVPHQWV WR WKH HQG RI WKH VWXG\ 7KHVH SDWLHQWV ZKR UHTXLUH HVFDSH
PHGLFDWLRQVKRXOGEHFRQVLGHUHGDVGLVFRQWLQXHGIURPVWXG\PHGLFDWLRQGXH
WRODFNRIHIILFDF\DQGWKHHVFDSHPHGLFDWLRQVXVHGPXVWEHGRFXPHQWHGLQ
WKHH&5)


57$2SKWKDOPLF6XVSHQVLRQ




5HDWD3KDUPDFHXWLFDOV
&OLQLFDO7ULDO3URWRFRO&




$PHQGPHQW)HE

&RQILGHQWLDO

3DJHRI
 6SHFLDO'LHWRU$FWLYLWLHV
1RWDSSOLFDEOH

([DPLQDWLRQ3URFHGXUHV
 3URFHGXUHVWREH3HUIRUPHGDW(DFK6WXG\9LVLWZLWK5HJDUGWR6WXG\
2EMHFWLYHV
 9,6,76FUHHQLQJ9LVLW'D\WR'D\
• ,QIRUPHG &RQVHQW+,3$$ 3ULRU WR DQ\ FKDQJHV LQ D SDWLHQW¶V PHGLFDO
WUHDWPHQW DQGRU SHUIRUPLQJ VWXG\ YLVLW SURFHGXUHV WKH VWXG\ ZLOO EH
GLVFXVVHGZLWKHDFKSDWLHQWDQGSDWLHQWVZLVKLQJWRSDUWLFLSDWHPXVWJLYH
ZULWWHQLQIRUPHGFRQVHQWDQGVLJQD+,3$$IRUP
• 5HYLHZ RI ,QFOXVLRQ DQG ([FOXVLRQ &ULWHULD ,I SDWLHQWV PHHW DOO LQLWLDO
LQFOXVLRQDQGQRQHRIWKHH[FOXVLRQFULWHULDWKH\PD\FRPSOHWHWKLVYLVLW
• 'HPRJUDSKLF GDWD DQG PHGLFDOPHGLFDWLRQRFXODU KLVWRU\ &ROOHFW DQG
UHFRUG DOO GHPRJUDSKLF GDWD PHGLFDO KLVWRU\ DQ\ PHGLFDWLRQV UHIHU WR
6HFWLRQ  DQG DQ\ XQGHUO\LQJ FRQGLWLRQV &XUUHQW XQGHUO\LQJ
FRQGLWLRQVLQFOXGLQJWKRVHWKDWEHJDQZLWKLQWKHODVWWKLUW\GD\VZKLFK
PD\KDYHEHHQUHVROYHGEHIRUHVFUHHQLQJPXVWEHUHFRUGHG5HFRUGDQ\
PHGLFDWLRQV WKH SDWLHQWLVWDNLQJDVZHOODVWKRVHWKHSDWLHQWPD\KDYH
WDNHQEXWGLVFRQWLQXHGZLWKLQGD\VSULRUWRVFUHHQLQJUHIHUWR6HFWLRQ

• 8ULQH3UHJQDQF\7HVWIRUIHPDOHVRIFKLOGEHDULQJSRWHQWLDO:RPHQRI
FKLOGEHDULQJ SRWHQWLDO PXVW KDYH D QHJDWLYH XULQH SUHJQDQF\ WHVW WR
FRQWLQXH LQ WKH VWXG\ DQG PXVW DJUHH WR XVH DQ DGHTXDWH PHWKRG RI
FRQWUDFHSWLRQ IRU WKH GXUDWLRQ RI WKH VWXG\ LQ RUGHU WR EH HQUROOHG
$FFHSWDEOH IRUPV RI ELUWK FRQWURO DUH VSHUPLFLGH ZLWK EDUULHU RUDO
FRQWUDFHSWLYH LQMHFWDEOH RU LPSODQWDEOH PHWKRG RI FRQWUDFHSWLRQ
WUDQVGHUPDOFRQWUDFHSWLYHLQWUDXWHULQHGHYLFHRUVXUJLFDOVWHULOL]DWLRQRI
SDUWQHU
R )RUQRQVH[XDOO\DFWLYHIHPDOHVDEVWLQHQFHZLOOEHFRQVLGHUHGDQ
DFFHSWDEOHIRUPRIELUWKFRQWURO
• $VVHVVPHQWRI2FXODU3DLQ3DWLHQWVZLOODVVHVVRFXODUSDLQLQWKHVWXG\
H\HVHH$SSHQGL[
• 3LQ+ROH9LVXDO$FXLW\8WLOL]LQJDQ(7'56&KDUW3DWLHQWVPXVWKDYHD
SRWHQWLDOSRVWRSHUDWLYHSLQKROH9$ORJ0$5LQWKHRSHUDWLYHH\H
DQGLQWKHIHOORZH\HDVPHDVXUHGXVLQJDQ(7'56FKDUW
• 6OLW /DPS %LRPLFURVFRS\ $ VOLW ODPS H[DP ZLOO EH SHUIRUPHG LQ ERWK
H\HVWRH[FOXGHSDWLHQWVZLWKGLVDOORZHGRFXODUFRQGLWLRQVVHH$SSHQGL[



57$2SKWKDOPLF6XVSHQVLRQ




5HDWD3KDUPDFHXWLFDOV
&OLQLFDO7ULDO3URWRFRO&




$PHQGPHQW)HE

&RQILGHQWLDO

3DJHRI
• $VVHVVPHQWRI2FXODU,QIODPPDWLRQ7KH,QYHVWLJDWRUZLOODVVHVVDQWHULRU
FKDPEHU FHOOV DQG IODUH LQ WKH VWXG\ H\H XVLQJ VOLW ODPS ELRPLFURVFRS\
VHH$SSHQGL[
• $VVHVVPHQW RI ,QWUDRFXODU 3UHVVXUH 7RQRPHWU\ ZLOO EH XVHG WR DVVHVV
LQWUDRFXODU SUHVVXUH LQ ERWK H\HV3DWLHQWVZKR KDYHRFXODUK\SRWHQVLRQ
,23
PP+J
RU
DUH
WDNLQJ
PHGLFDWLRQV
WR
WUHDW
RFXODU
K\SHUWHQVLRQJODXFRPDLQWKHVWXG\H\HZLOOEHH[FOXGHGIURPWKHVWXG\

• 'LODWHG
,QGLUHFW
2SKWKDOPRVFRSLF
([DPLQDWLRQ
'LODWHG
LQGLUHFW
RSKWKDOPRVFRSLF H[DPLQDWLRQ ZLOO EH SHUIRUPHG LQ ERWK H\HV IRU VDIHW\
SXUSRVHVVHH$SSHQGL[
• 6FKHGXOHIRU9LVLW
 9,6,7+RXUV3RVW6XUJHU\'D\
• 8SGDWHRI0HGLFDO0HGLFDWLRQ+LVWRU\
• $VVHVVPHQWRI2FXODU3DLQ
• 3LQ+ROH9LVXDO$FXLW\8WLOL]LQJDQ(7'56&KDUW
• 6OLW/DPS%LRPLFURVFRS\
• $VVHVVPHQW RI 2FXODU ,QIODPPDWLRQ 2QO\ SDWLHQWV ZLWK   VFRUH LQ
DQWHULRUFKDPEHUFHOOLQWKHVWXG\H\HZLOOEHLQFOXGHG
• $VVHVVPHQWRI,QWUDRFXODU3UHVVXUH3DWLHQWVZLOOEHH[FOXGHGZKRKDYH
PP+J,23RQWKHGD\DIWHUVXUJHU\LQHLWKHUH\H
• 5HYLHZRI,QFOXVLRQDQG([FOXVLRQ&ULWHULD,ISDWLHQWVPHHWDOOLQFOXVLRQ
DQGQRQHRIWKHH[FOXVLRQFULWHULDWKH\ZLOOEHHQUROOHGLQWKHVWXG\DQG
UDQGRPL]HGWRUHFHLYHGUXJ
• 5DQGRPL]DWLRQ3DWLHQWVZKRPHHWDOOLQFOXVLRQDQGQRQHRIWKHH[FOXVLRQ
FULWHULDDQGTXDOLI\WRFRQWLQXHLQWKHVWXG\ZLOOEHUDQGRPL]HGWRPDVNHG
WUHDWPHQWUHIHUWR6HFWLRQ
• 6WXG\ 'UXJ ,QVWLOODWLRQ $ WUDLQHG XQPDVNHG WHFKQLFLDQ QRW LQYROYHG LQ
DQ\RWKHUVWXG\DVVHVVPHQWVZLOOLQVWUXFWWKHSDWLHQWWRSHUIRUPVWXG\GUXJ
LQVWLOODWLRQRIRQHH\HGURSWRWKHVWXG\H\H7KHILUVWGRVHLQVWLOOHGGXULQJ
WKLV YLVLW ZLOO EH FRQVLGHUHG WKH PRUQLQJ GRVH UHJDUGOHVV RI WKH WLPH LQ
ZKLFKLWLVLQVWLOOHG7KHVHFRQGGRVHZLOOEHLQVWLOOHGLQWKHHYHQLQJDQG
PD\EHLQVWLOOHGOHVVWKDQDSSUR[LPDWHO\KRXUVDSDUW
• 6WXG\ 'UXJ DQG 6WXG\ 'UXJ &RPSOLDQFH 'LDU\ 'LVSHQVDWLRQ DQG
,QVWUXFWLRQV$WUDLQHGWHFKQLFLDQZLOOLQVWUXFWSDWLHQWVRQKRZWRLQVWLOO
WKHVWXG\GUXJUHIHUWR6HFWLRQDQGFRPSOHWHWKHSDWLHQWGLDU\DW
KRPH7KHVWXG\GUXJDQGVWXG\GUXJFRPSOLDQFHGLDU\ZLOOEHGLVSHQVHG
WRSDWLHQWVIRUKRPHXVH


57$2SKWKDOPLF6XVSHQVLRQ




5HDWD3KDUPDFHXWLFDOV
&OLQLFDO7ULDO3URWRFRO&




$PHQGPHQW)HE

&RQILGHQWLDO

3DJHRI
• $(4XHU\$(VERWKHOLFLWHGDQGREVHUYHGZLOOEHPRQLWRUHGWKURXJKRXW
WKHVWXG\$OO$(VERWKHOLFLWHGDQGREVHUYHGZLOOEHSURPSWO\UHYLHZHG
E\ WKH ,QYHVWLJDWRU IRU DFFXUDF\ DQG FRPSOHWHQHVV $OO $(V ZLOO EH
GRFXPHQWHGRQWKHDSSURSULDWHH&5)
• 6FKHGXOHIRU9LVLW
 9,6,7'D\
• 8SGDWHRI0HGLFDO0HGLFDWLRQ+LVWRU\
• 5HYLHZRI6WXG\'UXJ&RPSOLDQFH'LDU\
• $VVHVVPHQWRI2FXODU3DLQ
• 3LQ+ROH9LVXDO$FXLW\8WLOL]LQJDQ(7'56&KDUW
• 6OLW/DPS%LRPLFURVFRS\
• $VVHVVPHQWRI2FXODU,QIODPPDWLRQ
• $VVHVVPHQWRI,QWUDRFXODU3UHVVXUH
• $(4XHU\
• 6FKHGXOHIRU9LVLW
 9,6,7'D\
• 8SGDWHRI0HGLFDO0HGLFDWLRQ+LVWRU\
• 5HYLHZRI6WXG\'UXJ&RPSOLDQFH'LDU\
• $VVHVVPHQWRI2FXODU3DLQ
• 3LQ+ROH9LVXDO$FXLW\8WLOL]LQJDQ(7'56&KDUW
• 6OLW/DPS%LRPLFURVFRS\
• $VVHVVPHQWRI2FXODU,QIODPPDWLRQ
• $VVHVVPHQWRI,QWUDRFXODU3UHVVXUH
• $(4XHU\
• 6FKHGXOHIRU9LVLW
 9,6,7'D\
• 8SGDWHRI0HGLFDO0HGLFDWLRQ+LVWRU\
• 5HYLHZRI6WXG\'UXJ&RPSOLDQFH'LDU\
• &ROOHFWLRQRI6WXG\'UXJDQG6WXG\'UXJ&RPSOLDQFH'LDU\
• $VVHVVPHQWRI2FXODU3DLQ
• 3LQ+ROH9LVXDO$FXLW\8WLOL]LQJDQ(7'56&KDUW


57$2SKWKDOPLF6XVSHQVLRQ




5HDWD3KDUPDFHXWLFDOV
&OLQLFDO7ULDO3URWRFRO&




$PHQGPHQW)HE

&RQILGHQWLDO

3DJHRI
• 6OLW/DPS%LRPLFURVFRS\
• $VVHVVPHQWRI2FXODU,QIODPPDWLRQ
• $VVHVVPHQWRI,QWUDRFXODU3UHVVXUH
• $(4XHU\
• 6FKHGXOHIRU9LVLW
 9,6,7(;,79,6,7'D\RU(DUO\([LW
• 8SGDWHRI0HGLFDO0HGLFDWLRQ+LVWRU\
• 5HYLHZRI6WXG\'UXJ&RPSOLDQFH'LDU\
• &ROOHFWLRQRI6WXG\'UXJDQG6WXG\'UXJ&RPSOLDQFH'LDU\
• $VVHVVPHQWRI2FXODU3DLQ
• 3LQ+ROH9LVXDO$FXLW\8WLOL]LQJDQ(7'56&KDUW
• 6OLW/DPS%LRPLFURVFRS\
• $VVHVVPHQWRI2FXODU,QIODPPDWLRQ
• $VVHVVPHQWRI,QWUDRFXODU3UHVVXUH
• 'LODWHG,QGLUHFW2SKWKDOPRVFRSLF([DPLQDWLRQ
• $(4XHU\
• 8ULQH3UHJQDQF\7HVWIRU:RPHQRI&KLOGEHDULQJ3RWHQWLDO
• ([LW3DWLHQWVZLOOH[LWWKHVWXG\

6FKHGXOHRI9LVLWV0HDVXUHPHQWVDQG'RVLQJ
 6FKHGXOHG9LVLWV
5HIHUWR$SSHQGL[IRUDVFKHGXOHRIYLVLWVDQGPHDVXUHPHQWV
 8QVFKHGXOHG9LVLWV
7KHVH YLVLWV PD\ EH SHUIRUPHG LQ RUGHU WR HQVXUH SDWLHQW VDIHW\ $OO
LQIRUPDWLRQ JDWKHUHG DW XQVFKHGXOHG YLVLWV VKRXOG EH UHFRUGHG RQ WKH
8QVFKHGXOHG9LVLWSDJHVRIWKH6RXUFH'RFXPHQWDQGFRUUHVSRQGLQJH&5)
,IDUDQGRPL]HGSDWLHQWGRHVQRWDWWHQGWKHLUVFKHGXOHGYLVLWWKHH&5)SDJHV
IRUWKHPLVVHGYLVLWZLOOEHVNLSSHG

7KHVHSURFHGXUHVDUHWREHFRPSOHWHGRQ9LVLWRQO\LIQRWSHUIRUPHGDW9LVLW


57$2SKWKDOPLF6XVSHQVLRQ




5HDWD3KDUPDFHXWLFDOV
&OLQLFDO7ULDO3URWRFRO&




$PHQGPHQW)HE

&RQILGHQWLDO

3DJHRI
$OOHIIRUWVVKRXOGEHPDGHWRVFKHGXOHSDWLHQWVIRUDQ([LW9LVLWWRFRPSOHWH
([LW3URFHGXUHV,QIRUPDWLRQIURP(DUO\([LW9LVLWVVKRXOGEHUHFRUGHGRQWKH
9LVLW([LW9LVLWSDJHV
(YDOXDWLRQVWKDWPD\EHFRQGXFWHGDWDQ8QVFKHGXOHG9LVLWDVDSSURSULDWH
GHSHQGLQJRQWKHUHDVRQIRUWKHYLVLWLQFOXGH
• 8SGDWH0HGLFDO0HGLFDWLRQ+LVWRU\
• 5HYLHZ&ROOHFW6WXG\'UXJ&RPSOLDQFH'LDU\DQG6WXG\'UXJ
• $VVHVVPHQWRIRFXODUSDLQ
• 3LQKROHYLVXDODFXLW\
• 6OLWODPSELRPLFURVFRS\
• $VVHVVPHQWRI2FXODU,QIODPPDWLRQ
• ,QWUDRFXODUSUHVVXUHPHDVXUHPHQW
• 'LODWHGLQGLUHFWRSKWKDOPRVFRSLFH[DPLQDWLRQ
• $VVHVVPHQWRI$(V
• 8ULQHSUHJQDQF\WHVWIRUIHPDOHVRIFKLOGEHDULQJSRWHQWLDO

&RPSOLDQFHZLWK'RVLQJ
6LWHVWDIIZLOOUHYLHZFRQFRPLWDQWPHGLFDWLRQXVHDWHDFKYLVLW
3DWLHQWV ZLOO EH SURYLGHG ZLWK D VWXG\ GUXJ FRPSOLDQFH GLDU\ WR GRFXPHQW %,'
GRVLQJ IRU  GD\V 3DWLHQW FRPSOLDQFH ZLWK GRVLQJ ZLOO EH DVVHVVHG E\ LQRIILFH
UHYLHZRIVWXG\GUXJFRPSOLDQFHGLDU\3DWLHQWVZKRPLVVPRUHWKDQRIWKHLU
VWXG\GUXJGRVHVPRUHWKDQWRWDOGRVHVZLOOEHFRQVLGHUHGQRQFRPSOLDQWZLWK
GRVLQJDQGDSURWRFROGHYLDWLRQVKRXOGEHUHFRUGHG

3DWLHQW'LVSRVLWLRQ
 &RPSOHWHG3DWLHQWV
$FRPSOHWHGSDWLHQWLVRQHZKRKDVQRWEHHQGLVFRQWLQXHGIURPWKHVWXG\DQG
FRQWLQXHVVWXG\DVVHVVPHQWVWKURXJK9LVLW'D\
 'LVFRQWLQXHG3DWLHQWV
3DWLHQWVPD\EHGLVFRQWLQXHGIURPWKHVWXG\SULRUWRWKHLUFRPSOHWLRQRIWKH
VWXG\GXHWRDQ\RIWKHIROORZLQJUHDVRQV
• $(V
• 3URWRFROYLRODWLRQV
• /DFNRIHIILFDF\
• $GPLQLVWUDWLYHUHDVRQVHJLQDELOLW\WRFRQWLQXHORVWWRIROORZXS


57$2SKWKDOPLF6XVSHQVLRQ




5HDWD3KDUPDFHXWLFDOV
&OLQLFDO7ULDO3URWRFRO&




$PHQGPHQW)HE

&RQILGHQWLDO

3DJHRI
• 6SRQVRUWHUPLQDWLRQRIVWXG\
• 9ROXQWDU\ZLWKGUDZDO
• 3UHJQDQF\
,I D IHPDOH KDV D SRVLWLYH SUHJQDQF\ WHVW GXULQJ WKH VWXG\ WKH
SDWLHQWVKRXOGVWRSVWXG\WUHDWPHQWDQGWKH,QYHVWLJDWRUZLOOQRWLI\
WKHVSRQVRULPPHGLDWHO\7KH,QYHVWLJDWRUVKDOOUHTXHVWFRSLHVRIDOO
UHODWHG PHGLFDO UHSRUWV GXULQJ WKH SUHJQDQF\ DQG VKDOO GRFXPHQW
WKH RXWFRPH RI WKH SUHJQDQF\ IURP WKH SDWLHQW DQGRU SDWLHQW¶V
SK\VLFLDQ 7KH ,QYHVWLJDWRU ZLOO UHWDLQ WKHVH UHSRUWV WRJHWKHU ZLWK
WKH SDWLHQW¶V VRXUFH GRFXPHQWV DQG ZLOO SURYLGH D FRS\ RI DOO
GRFXPHQWDWLRQWRWKHVSRQVRU
• 2WKHU
1RWH ,Q DGGLWLRQ DQ\ SDWLHQW PD\ EH GLVFRQWLQXHG IRU DQ\ VRXQG PHGLFDO
UHDVRQ
1RWLILFDWLRQRIDSDWLHQW¶VGLVFRQWLQXDWLRQRIVWXG\GUXJDGPLQLVWUDWLRQDQGWKH
UHDVRQIRUGLVFRQWLQXDWLRQZLOOEHPDGHWR&52DQGVWXG\6SRQVRUDQGZLOO
EHFOHDUO\GRFXPHQWHGRQWKHH&5)3DWLHQWVZKRUHFHLYHHVFDSHPHGLFDWLRQ
DUHWRGLVFRQWLQXHVWXG\GUXJDGPLQLVWUDWLRQDQGDUHWRUHPDLQLQWKHVWXG\DQG
EHIROORZHGSHUWKHSURWRFROWRWKHHQGRIWKHVWXG\3DWLHQWVZKRGLVFRQWLQXH
VWXG\GUXJDGPLQLVWUDWLRQIRURWKHUUHDVRQVDUHHQFRXUDJHGWRUHPDLQLQWKH
VWXG\DQGFRQWLQXHZLWKVWXG\DVVHVVPHQWVWKURXJKWKHHQGRIWKHVWXG\
1RWLILFDWLRQ RI D SDWLHQW¶V GLVFRQWLQXDWLRQ RI VWXG\ SDUWLFLSDWLRQ DQG WKH
UHDVRQIRUGLVFRQWLQXDWLRQZLOOEHPDGHWR&52DQGVWXG\6SRQVRUDQGZLOO
EHFOHDUO\GRFXPHQWHGRQWKHH&5)

6WXG\7HUPLQDWLRQ
7KH VWXG\ PD\ EH VWRSSHG DW DQ\ WLPH E\ WKH ,QYHVWLJDWRU RU WKH 6SRQVRU ZLWK
DSSURSULDWHQRWLILFDWLRQ

6WXG\'XUDWLRQ
$QLQGLYLGXDOSDWLHQW¶VSDUWLFLSDWLRQLQWKHVWXG\LVH[SHFWHGWRODVWDSSUR[LPDWHO\
ZHHNVIURPVFUHHQLQJWRH[LW

0RQLWRULQJDQG4XDOLW\$VVXUDQFH
'XULQJWKHFRXUVHRIWKHVWXG\D&52PRQLWRURUGHVLJQHHZLOOPDNHURXWLQHVLWH
YLVLWV WR UHYLHZ SURWRFRO FRPSOLDQFH DVVHVV VWXG\ GUXJGHYLFH DFFRXQWDELOLW\ DQG
HQVXUH WKH VWXG\ LV EHLQJ FRQGXFWHG DFFRUGLQJ WR WKH SHUWLQHQW UHJXODWRU\
UHTXLUHPHQWV 7KH UHYLHZ RI WKH SDWLHQWV¶ PHGLFDO UHFRUGV ZLOO EH SHUIRUPHG LQ D
PDQQHUWKDWDGHTXDWHO\PDLQWDLQVSDWLHQWFRQILGHQWLDOLW\)XUWKHUGHWDLOVRIWKHVWXG\
PRQLWRULQJZLOOEHRXWOLQHGLQDPRQLWRULQJSODQ
5HJXODWRU\ DXWKRULWLHV RI GRPHVWLF DQG IRUHLJQ DJHQFLHV WKH 6SRQVRU DQGRU LWV
GHVLJQHHVPD\FDUU\RXWRQVLWHLQVSHFWLRQVDQGRUDXGLWVZKLFKPD\LQFOXGHVRXUFH


57$2SKWKDOPLF6XVSHQVLRQ




5HDWD3KDUPDFHXWLFDOV
&OLQLFDO7ULDO3URWRFRO&




$PHQGPHQW)HE

&RQILGHQWLDO

3DJHRI
GDWDFKHFNV7KHUHIRUHGLUHFWDFFHVVWRWKHRULJLQDOVRXUFHGDWDZLOOEHUHTXLUHGIRU
LQVSHFWLRQV DQGRU DXGLWV $OO LQVSHFWLRQV DQG DXGLWV ZLOO EH FDUULHG RXW JLYLQJ
FRQVLGHUDWLRQWRGDWDSURWHFWLRQDVZHOODVSDWLHQWFRQILGHQWLDOLW\WRWKHH[WHQWWKDW
ORFDOVWDWHDQGIHGHUDOODZVDSSO\
 $'9(56((9(176$(V

$GYHUVH(YHQW
$Q$(LVGHILQHGDVDQ\XQWRZDUGPHGLFDORFFXUUHQFHDVVRFLDWHGZLWKWKHXVHRID
GUXJ LQ KXPDQV ZKHWKHU RU QRW WKH HYHQW LV FRQVLGHUHG GUXJUHODWHG $Q $( FDQ
WKHUHIRUH EH DQ\ XQIDYRUDEOH DQG XQLQWHQGHG VLJQ HJ DQ DEQRUPDO ODERUDWRU\
ILQGLQJV\PSWRPRUGLVHDVHRFFXUULQJDIWHUWKHILUVWGRVHRIVWXG\GUXJZLWKRXW
DQ\MXGJPHQWDERXWFDXVDOLW\$Q\SUHH[LVWLQJPHGLFDOFRQGLWLRQWKDWZRUVHQVDIWHU
ILUVW DGPLQLVWUDWLRQ RI WKH VWXG\ GUXJ ZLOO DOVR EH FRQVLGHUHG D QHZ $( 7KH $(
UHSRUWLQJSHULRGHQGVXSRQVWXG\H[LW6WXG\GUXJLQFOXGHVWKHLQYHVWLJDWLRQDOGUXJ
XQGHUHYDOXDWLRQDQGSODFHERJLYHQGXULQJDQ\VWDJHRIWKHVWXG\
'RFXPHQWDWLRQUHJDUGLQJWKH$(VKRXOGEHPDGHDVWRWKHQDWXUHGDWHRIRQVHWHQG
GDWHVHYHULW\UHODWLRQVKLSWRVWXG\GUXJDFWLRQVWDNHQVHULRXVQHVVDQGRXWFRPH
RIDQ\VLJQRUV\PSWRPREVHUYHGE\WKHSK\VLFLDQRUUHSRUWHGE\WKHSDWLHQWXSRQ
LQGLUHFWTXHVWLRQLQJ
 6HYHULW\
6HYHULW\ RI DQ $( LV GHILQHG DV D TXDOLWDWLYH DVVHVVPHQW RI WKH GHJUHH RI
LQWHQVLW\RIDQ$(DVGHWHUPLQHGE\WKH,QYHVWLJDWRURUUHSRUWHGWRKLPKHUE\
WKHSDWLHQW7KHDVVHVVPHQWRIVHYHULW\LVPDGHLUUHVSHFWLYHRIUHODWLRQVKLSWR
VWXG\GUXJRUVHULRXVQHVVRIWKHHYHQWDQGVKRXOGEHHYDOXDWHGDFFRUGLQJWR
WKHIROORZLQJVFDOH
• 0LOG(YHQWLVQRWLFHDEOHWRWKHSDWLHQWEXWLVHDVLO\WROHUDWHGDQGGRHV
QRWLQWHUIHUHZLWKWKHSDWLHQW¶VGDLO\DFWLYLWLHV
• 0RGHUDWH(YHQWLVERWKHUVRPHSRVVLEO\UHTXLULQJDGGLWLRQDOWKHUDS\
DQGPD\LQWHUIHUHZLWKWKHSDWLHQW¶VGDLO\DFWLYLWLHV
• 6HYHUH(YHQWLVLQWROHUDEOHQHFHVVLWDWHVDGGLWLRQDOWKHUDS\RUDOWHUDWLRQ
RIWKHUDS\DQGLQWHUIHUHVZLWKWKHSDWLHQW¶VGDLO\DFWLYLWLHV
 5HODWLRQVKLSWR6WXG\'UXJ
7KHUHODWLRQVKLSRIHDFK$(WRWKHVWXG\GUXJVKRXOGEHGHWHUPLQHGE\WKH
,QYHVWLJDWRUXVLQJWKHVHH[SODQDWLRQV
• 6XVSHFWHG$UHDVRQDEOHSRVVLELOLW\H[LVWVWKDWWKHVWXG\GUXJFDXVHG
WKH$(
• 1RW6XVSHFWHG$UHDVRQDEOHSRVVLELOLW\GRHVQRWH[LVWWKDWWKHVWXG\
GUXJFDXVHGWKH$(


RTA 408 Ophthalmic Suspension 
 
 
 
 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
 
 
 
 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 36 of 77 
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: the event follows a reasonable temporal 
sequence from the time of study drug administration, and/or, follows a known 
response pattern to the study drug, but could have been produced by other 
factors; a reasonable temporal sequence of the event with study drug 
administration exists and, based upon the known pharmacologic action of the 
drug, known or previously reported adverse reactions to the drug or class of 
drugs, or judgment based on the investigator’s clinical experience, the 
association of the event with study drug administration seems likely; 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. 
9.2 
Serious Adverse Events (SAEs) 
An AE is considered serious if, in the view of either the Investigator or Sponsor, it 
results in any of the following regulatory outcome definitions: 
1. Death; 
2. A life-threatening AE; 
 Note:  An AE is considered “life-threatening” if, in the view of either 
the Investigator or Sponsor, its occurrence places the patient or patient 
at immediate risk of death. It does not include an AE that, had it 
occurred in a more severe form, might have caused death. 
3. 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 


RTA 408 Ophthalmic Suspension 
 
 
 
 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
 
 
 
 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 37 of 77 
required for the reason for the initial admission as determined by the 
Investigator or treating physician. 
4. A persistent or significant incapacity or substantial disruption of the ability 
to conduct normal life functions; 
 Note: An SAE specifically related to visual threat would be interpreted 
as any potential impairment or damage to the patient’s eyes (e.g., 
hemorrhage, retinal detachment, central corneal ulcer or damage to the 
optic nerve). 
5. A congenital anomaly/birth defect; 
6. Important medical event. 
 Note: Important medical events that may not result in death, are life-
threatening, or require hospitalization may be considered serious 
when, based upon appropriate medical judgment, they may jeopardize 
the patient or patient and may require medical or surgical intervention 
to prevent one of the outcomes listed in this definition. 
9.3 
Procedures for Reporting AEs 
All AEs and their outcomes must be reported to the study Sponsor or designee, and 
the IRB/IEC as required by the IRB/IEC, federal, state, or local regulations and 
governing health authorities and recorded on the appropriate eCRF. AEs should be 
reported from the first instillation of study drug until the final study visit. 
9.3.1 Reporting a Suspected Unexpected Adverse Reaction 
All AEs that are ‘suspected’ and ‘unexpected’ are to be reported to CRO, the 
study Sponsor and the IRB/IEC as required by the IRB/IEC, federal, state, or 
local regulations and governing health authorities. 
9.3.2 Reporting an SAE 
To ensure patient safety, all SAEs, regardless of relationship to the study drug, 
must be immediately reported (i.e. no later than 24 hours after the site’s 
awareness of the event).  All information relevant to the serious AE must be 
recorded on the appropriate CRFs. The Investigator is obligated to pursue and 
obtain information requested by CRO and the Sponsor in addition to that 
information reported on the eCRF. All patients experiencing an SAE must be 
followed up and the outcome reported. 
In the event of an SAE, the Investigator must notify the Sponsor or designee 
immediately (i.e. no later than 24 hours after the site’s awareness of the 
event); obtain and maintain in his/her files all pertinent medical records, 
information, and medical judgments from colleagues who assisted in the 
treatment and follow-up of the patient; provide CRO and the study Sponsor 
with a complete case history, which includes a statement as to whether the 




RTA 408 Ophthalmic Suspension 
 
 
 
 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
 
 
 
 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 39 of 77 
If the Investigator becomes aware of any new information regarding an SAE (i.e., 
resolution, change in condition, or new treatment), a new SAE/Unanticipated Report 
Form must be completed and faxed to the Sponsor or designee within 24 hours of 
the site’s awareness of the event. The original SAE form is not to be altered. The 
report should describe whether the event has resolved or continues and how the 
event was treated. 
10 STATISTICAL HYPOTHESES AND METHODS OF ANALYSES 
10.1 Study Populations 
10.1.1 Intent-to-Treat Population 
The Intent-to-Treat (ITT) population consists of all patients who are 
randomized. All data will be included and no patients will be excluded 
because of protocol violations. The ITT population will be analyzed as 
randomized and will be used for the efficacy analyses.   
10.1.2 Safety Population 
The Safety population includes all randomized patients who received at least 
one dose of investigational treatment. The Safety population will be analyzed 
as treated and will be used for the safety analyses.  No data will be excluded 
for any reason. 
10.1.3 Per Protocol Population 
The Per Protocol (PP) population is a subset of the ITT population and 
includes patients who remain in the study through Visit 5 (Day 15) with no 
major protocol violations that would affect the assessment of the primary 
efficacy endpoints of the study. Patients without major protocol violations 
thought to affect the primary efficacy outcome who discontinue the study due 
to lack of efficacy will be analyzed in the PP analysis with missing data after 
discontinuation imputed as failures for success/failure endpoints and will be 
imputed using last observation carried forward (LOCF) for other endpoints. 
Otherwise, this population will be analyzed as treated using observed data 
only for confirmatory analyses. 
10.2 Unit of Analysis 
The unit of analysis in this study will be the study eye for all efficacy and safety 
summaries. Additionally, non-ocular AEs will be presented at the patient level. Non-
study eye safety summaries will also be presented as appropriate.   
10.3 General Imputation Methods 
The primary analyses of all efficacy data will use LOCF to impute missing data; data 
for visits after a patient is discontinued for lack of efficacy will be imputed as 


57$2SKWKDOPLF6XVSHQVLRQ




5HDWD3KDUPDFHXWLFDOV
&OLQLFDO7ULDO3URWRFRO&




$PHQGPHQW)HE

&RQILGHQWLDO

3DJHRI
IDLOXUHV IRU VXFFHVVIDLOXUH HQGSRLQWV DQG ZLOO EH LPSXWHG XVLQJ /2&) IRU RWKHU
HQGSRLQWV 7R FKHFN UREXVWQHVV RI UHVXOWV VHQVLWLYLW\ DQDO\VHV RI WKH SULPDU\
HIILFDF\GDWDZLOOLQFOXGHDQDO\VHVRIREVHUYHGGDWDRQO\LPSXWLQJGDWDIURPSDWLHQW
YLVLWVDIWHUGLVFRQWLQXDWLRQIRUODFNRIHIILFDF\DVIDLOXUHV2WKHULPSXWDWLRQPHWKRGV
PD\EHDSSOLHGDVDGGLWLRQDOVHQVLWLYLW\DQDO\VHV
3HU3URWRFRODQDO\VHVZLOOXVHREVHUYHGGDWDRQO\ZLWKWKHH[FHSWLRQRISDWLHQWVZKR
KDYH PLVVLQJ GDWD GXH WR GLVFRQWLQXDWLRQ IRU ODFN RI HIILFDF\ IRU WKHVH SDWLHQWV
PLVVLQJGDWDDIWHUGLVFRQWLQXDWLRQZLOOEHLPSXWHGDVIDLOXUHV
 (IILFDF\9DULDEOHV
7KHSULPDU\HIILFDF\YDULDEOHVDUH
$EVHQFHRIDQWHULRUFKDPEHUFHOOVLHVFRUHRIµ¶DW9LVLW'D\IRU
D 7KHFRQFHQWUDWLRQRI57$2SKWKDOPLF6XVSHQVLRQFRPSDUHG
WRSODFHER
E 7KHFRQFHQWUDWLRQRI57$2SKWKDOPLF6XVSHQVLRQFRPSDUHG
WRSODFHER
$EVHQFHRISDLQLHVFRUHRIµ¶DW9LVLW'D\IRU
F 7KHFRQFHQWUDWLRQRI57$2SKWKDOPLF6XVSHQVLRQFRPSDUHGWR
SODFHERWREHWHVWHGLIDLVVWDWLVWLFDOO\VLJQLILFDQWLQIDYRURIWKHDFWLYH
DUP
G 7KHFRQFHQWUDWLRQRI57$2SKWKDOPLF6XVSHQVLRQFRPSDUHGWR
SODFHERWREHWHVWHGLIELVVWDWLVWLFDOO\VLJQLILFDQWLQIDYRURIWKHDFWLYH
DUP
6HFRQGDU\HIILFDF\YDULDEOHVLQFOXGH
 $EVHQFH RI DQWHULRU FKDPEHU FHOOV DW 9LVLWV   RU  'D\V   RU 
UHVSHFWLYHO\
 $EVHQFHRISDLQDW9LVLWVRU'D\VRUUHVSHFWLYHO\
 $EVHQFHRIIODUHDW9LVLWVRU'D\VRUUHVSHFWLYHO\
 6DIHW\9DULDEOHV
7KHVDIHW\YDULDEOHVDUH
•
6OLW/DPS([DPLQDWLRQ
•
3LQKROH9LVXDO$FXLW\
•
,QWUDRFXODU3UHVVXUH
•
'LODWHGLQGLUHFWRSKWKDOPRVFRSLFH[DPLQDWLRQ
•
$(V
 6WDWLVWLFDO+\SRWKHVHV
+ 7KHGLIIHUHQFHEHWZHHQVWXG\H\HVWUHDWHGZLWKWKHFRQFHQWUDWLRQRI
57$2SKWKDOPLF6XVSHQVLRQDQGVWXG\H\HVWUHDWHGZLWKSODFHERLQ


RTA 408 Ophthalmic Suspension 
 
 
 
 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
 
 
 
 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 41 of 77 
the proportion of study eyes with absence of anterior chamber cells (score 
of 0) at Visit 5 (Day 15) = 0. 
HA11: The difference, between study eyes treated with the 1.0% concentration of 
RTA 408 Ophthalmic Suspension and study eyes treated with placebo in 
the proportion of study eyes with absence of anterior chamber cells (score 
of 0) at Visit 5 (Day 15) ≠ 0, with superiority claimed if the difference is 
greater than 0 (RTA 408 Ophthalmic Suspension – Placebo). 
H012: The difference, between study eyes treated with the 0.5% concentration of 
RTA 408 Ophthalmic Suspension and study eyes treated with Placebo, in 
the proportion of study eyes with absence of anterior chamber cells (score 
of 0) at Visit 5 (Day 15) = 0. 
HA12: The difference, between study eyes treated with the 0.5% concentration of 
RTA 408 Ophthalmic Suspension and study eyes treated with placebo in 
the proportion of study eyes with absence of anterior chamber cells (score 
of 0) at Visit 5 (Day 15) ≠ 0, with superiority claimed if the difference is 
greater than 0 (RTA 408 Ophthalmic Suspension – Placebo). 
and 
H021: The difference, between study eyes treated with the 1.0% concentration of 
RTA 408 Ophthalmic Suspension and study eyes treated with placebo in 
the proportion of study eyes with absence of pain (score of 0) at Visit 3 
(Day 4) = 0. 
HA21: The difference, between study eyes treated with the 1.0% concentration of 
RTA 408 Ophthalmic Suspension and study eyes treated with placebo in 
the proportion of study eyes with absence of pain (score of 0) at Visit 3 
(Day 4) ≠ 0, with superiority claimed if the difference is greater than 0 
(RTA 408 Ophthalmic Suspension – Placebo). 
H022: The difference, between study eyes treated with the 0.5% concentration of 
RTA 408 Ophthalmic Suspension and study eyes treated with placebo in 
the proportion of study eyes with absence of pain (score of 0) at Visit 3 
(Day 4) = 0. 
HA22: The difference, between study eyes treated with the 0.5% concentration of 
RTA 408 Ophthalmic Suspension and study eyes treated with placebo in 
the proportion of study eyes with absence of pain (score of 0) at Visit 3 
(Day 4) ≠ 0, with superiority claimed if the difference is greater than 0 
(RTA 408 Ophthalmic Suspension – Placebo). 
The primary analyses will first test the difference in the proportion of patients with 
absence of anterior chamber cells in the study eye between the 1.0% concentration of 
RTA 408 Ophthalmic Suspension and placebo and between the 0.5% concentration 
of RTA 408 Ophthalmic Suspension and placebo at Visit 5 (Day 15) using the 
Pearson chi-squared statistic.  
If the proportion of patients with a grade of ‘0’ for anterior chamber cells is 
statistically significantly higher for the 1.0% concentration versus placebo at a 1-




RTA 408 Ophthalmic Suspension 
 
 
 
 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
 
 
 
 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 43 of 77 
10.9 Demographics and Baseline Medical History 
Patient demographics: gender, race, ethnicity, and age will be presented using 
discrete summary statistics. Age will also be presented using continuous summary 
statistics.  
Non-ocular and ocular (study eye and fellow eye) medical history will be 
summarized by treatment group using discrete summaries. 
10.10 Primary Efficacy Analyses 
The primary efficacy variables, study eyes with absence of anterior chamber cells at 
Visit 5 (Day 15) and study eyes with absence of pain at Visit 3 (Day 4), will be 
summarized using discrete summary statistics, including 90% asymptotic normal 
confidence intervals for each treatment group. The primary efficacy analyses will 
first test the difference in proportion of study eyes with a grade of ‘0’ in anterior 
chamber cells between the 1.0% concentration of RTA 408 Ophthalmic Suspension 
and placebo and between the 0.5% concentration of RTA 408 Ophthalmic 
Suspension and placebo at Visit 5 (Day 15) using the Pearson chi-squared statistic.  
If the proportion of patients with a grade of ‘0’ for anterior chamber cells is 
statistically significantly higher for the 1.0% concentration versus placebo at a 1-
sided alpha=0.10, then the hierarchical hypothesis testing will compare the 
proportion of patients with absence of ocular pain at Visit 3 (Day 4) between the 
1.0% concentration of RTA 408 Ophthalmic Suspension and placebo using the 
Pearson chi-squared statistic at a 1-sided alpha=0.10.   
If the proportion of patients with a grade of ‘0’ for anterior chamber cells is 
statistically significantly higher for the 0.5% concentration versus placebo at a 1-
sided alpha=0.10, then the hierarchical hypothesis will compare the proportion of 
patients with absence of ocular pain at Visit 3 (Day 4) between the 0.5% 
concentration of RTA 408 Ophthalmic Suspension and placebo using the Pearson 
chi-squared statistic at a one-sided alpha=0.10.   
Additionally, 95% confidence intervals will be constructed around the difference in 
proportions for each primary outcome using asymptotic normal approximations. 
Fisher’s exact tests will be employed in cases of expected counts less than five. 
If the test of the difference in the proportion of study eyes with absence of anterior 
chamber cells is statistically significant in favor of the 1.0% or 0.5% concentration 
of RTA 408 Ophthalmic Suspension versus placebo, then the study will be 
considered a success and the concentration(s) of RTA 408 Ophthalmic Suspension 
showing statistical significance will be declared to be superior to placebo in the 
proportion of study eyes with absence of anterior chamber cells at Visit 5 (Day 15). 
Additionally, a Cochran-Armitage test will be used to test for trend separately in the 
proportion of study eyes with absence of anterior chamber cells and the proportion 
of study eyes with absence of pain with increasing active concentration, using all 
three treatment groups. 


RTA 408 Ophthalmic Suspension 
 
 
 
 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
 
 
 
 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 44 of 77 
10.11 Secondary Efficacy Analyses 
The secondary efficacy variables will be summarized at Days 4, 8, and 21 for 
absence of anterior chamber cells and at Days 8, 15 and 21 for absence of ocular 
pain, similarly to the primary efficacy summaries. Additionally, anterior chamber 
cell grade and ocular pain score at each visit and change from baseline will be 
summarized using continuous and discrete summary statistics. 
Absence of anterior chamber flare and anterior chamber flare grade and the sum of 
anterior chamber cell and flare grade, including absence of both anterior chamber 
cell and flare will be summarized similarly to anterior chamber cells and pain at each 
visit. 
10.12 Safety Analyses 
The primary safety analysis will summarize ocular treatment-emergent AEs 
(TEAEs) in the study eye for all treated patients using discrete summaries at the 
patient- and event-level by system organ class and preferred term for each treatment 
group. A TEAE will be defined as occurring on or after the day that treatment is 
initiated.  An additional analysis will investigate ocular AEs for the non-study eye. 
Non-ocular TEAEs will be summarized using discrete summaries at the patient- and 
event-level by system organ class and preferred term 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. 
The IOP data will be summarized at each visit using both continuous summaries 
(including change from baseline) and discrete summaries (including the proportion 
of patients with change in IOP from baseline ≥ 10 mm Hg and the proportion of 
patients with an IOP ≥ 30 mm Hg that occurs at any time following instillation of 
study treatment) as well as shift tables. 
Slit lamp biomicroscopy and dilated indirect ophthalmoscopic examination measures 
will be summarized at each visit using discrete summary statistics. 
Visual acuity data will be summarized at each visit, using discrete summaries, 
including change from baseline in the number of lines and the proportion of patients 
with change from previous visit of ≥ 2 lines. 
10.13 Subgroup Analysis 
No subgroup analyses are planned. 
10.14 Interim Analysis 
No interim analyses are planned. 


RTA 408 Ophthalmic Suspension 
 
 
 
 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
 
 
 
 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 45 of 77 
11 COMPLIANCE WITH GOOD CLINICAL PRACTICES, 
ETHICAL CONSIDERATIONS, AND ADMINISTRATIVE 
ISSUES 
This study will be conducted in compliance with the protocol, Good Clinical 
Practices (GCPs), including the International Conference on Harmonization (ICH) 
Guidelines, and in general, consistent with the Declaration of Helsinki. In addition, 
all applicable local, state, and federal requirements relevant to the use of study drugs 
in the countries involved will be adhered to. 
11.1 Protection of Human Subjects 
11.1.1 Patient 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 patient and/or from the patient’s parent or legal guardian prior to 
enrollment into the study. If the patient is under the legal age of consent, the 
consent form must be signed by a legal guardian or as required by state and/or 
local laws and regulations. 
All informed consent forms must be approved for use by the Sponsor and 
receive approval/favorable opinion from an IRB/IEC prior to their use. If the 
consent form requires revision (e.g., due to a protocol amendment or 
significant new safety information), it is the Investigator’s responsibility to 
ensure that the amended informed consent is reviewed and approved by 
Sponsor prior to submission to the governing IRB/IEC and that it is read, 
signed and dated by all patients subsequently enrolled in the study as well as 
those currently enrolled in the study. 
If informed consent is taken under special circumstances (oral informed 
consent), then the procedures to be followed must be determined by CRO and 
study Sponsor and provided in writing by CRO and study Sponsor prior to the 
consent process. 
11.1.2 Institutional Review Board (IRB) Approval 
This study is to be conducted in accordance with Institutional Review Board 
regulations (U.S. 21 CFR Part 56.103). The Investigator must obtain 
appropriate IRB approval before initiating the study and re-approval at least 
annually. 
Only an IRB/ERC approved version of the informed consent form will be 
used. 
11.2 Ethical Conduct of the Study 
This study will be conducted in accordance with the ethical principles that originated 
with the Declaration of Helsinki. 


RTA 408 Ophthalmic Suspension 
 
 
 
 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
 
 
 
 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 46 of 77 
11.3 Patient Confidentiality 
All personal study patient 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 CRO, the Sponsor, the 
IRB/IEC approving this study, the FDA, the DHHS, other domestic government 
agencies, and other foreign regulatory agencies will be granted direct access to the 
study patient’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 patient’s identity will not be disclosed in these documents. 
11.4 Documentation 
Source documents may include a patient’s medical records, hospital charts, clinic 
charts, the Investigator’s study patient files, as well as the results of diagnostic tests 
such as X-rays, laboratory tests, and ECGs. The Investigator’s copy of the CRFs 
serves as the Investigator’s record of a patient’s study-related data. 
11.4.1 Retention of Documentation 
All study related correspondence, patient records, consent forms, record of the 
distribution and use of all study drug and copies of CRFs should be 
maintained on file for at least two years after the last approval of a marketing 
application in an ICH region and until there are no pending or contemplated 
marketing applications in an ICH region; or until at least two years have 
elapsed since the formal discontinuation of clinical development of the 
investigational product. 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. 


RTA 408 Ophthalmic Suspension 
 
 
 
 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
 
 
 
 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 47 of 77 
11.5 Labeling, Packaging, Storage, Accountability, and Return or 
Disposal of Study Drug 
11.5.1 Labeling/Packaging 
Each study drug kit will be labeled with a 5-digit study drug kit number and 
will contain one bottle of study drug. All bottles of active and placebo 
treatment will be identical in appearance and will be packaged in identical 
containers. The study drug kit and each bottle will have a label bearing 
information meeting applicable regulatory requirements. Study drug bottles 
will come with directions for use and other appropriate information on each 
part. Study drug will be packaged and labeled based on the randomization list 
generated prior to the start of the study.   
11.5.2 Storage of Study Drug 
The study drug product must be stored upright at 2° to 8°C (36° to 46° F), in a 
refrigerator, protected from freezing, protected from strong light, and stored in 
a secure area accessible only to the Investigator and his/her designees. The 
study drug product will be administered only to patients entered into the 
clinical study, in accordance with the conditions specified in this protocol. 
11.5.3 Accountability of Study Drug 
The study drug is to only be prescribed by the Principal Investigator or his/her 
named sub-Investigator(s), and is to only be used in accordance with this 
protocol. The study drug must only be distributed to patients properly 
qualified under this protocol to receive study drug. 
The Investigator must keep an accurate accounting of the study drug received 
from the supplier. This includes the amount of study drug dispensed to 
patients, amount of study drug returned to the Investigator by the patients, and 
the amount returned or disposed upon the completion of the study. A detailed 
inventory must be completed for the study drug. 
11.5.4 Return or Disposal of Study Drug 
All study drug 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. 
11.6 Recording of Data on Source Documents and eCRFs  
The Investigator is responsible for ensuring that study data is completely and 
accurately recorded on each patient’s eCRF, source document, and all study-related 
material. 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 


RTA 408 Ophthalmic Suspension 
 
 
 
 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
 
 
 
 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 48 of 77 
correction and when, by adding to the correction his/her initials as well as the date of 
the correction. 
11.7 Handling of Biological Specimens 
Not applicable. 
11.8 Publications 
Authorship and manuscript composition will reflect cooperation among all parties 
involved in the study. Authorship will be established before writing the manuscript. 
The Sponsor will have the final decision regarding the manuscript and publication. 
 
 


RTA 408 Ophthalmic Suspension 
 
 
 
 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
 
 
 
 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 49 of 77 
12 REFERENCES 
1. 
Liu J. Pharmacology of oleanolic acid and ursolic acid. J Ethnopharmacol 
1995;49:57-68. 
2. 
Honda T, Rounds BV, Gribble GW, Suh N, Wang Y, Sporn MB. Design and 
synthesis of 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid, a novel and highly 
active inhibitor of nitric oxide production in mouse macrophages. Bioorg Med 
Chem Lett 1998;8:2711-2714. 
3. 
Jabs, D.A., R.B. Nussenblatt, J. T. Rosenbaum. Standardization of Uveitis 
Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature 
for reporting clinical data. Results of the First International Workshop. Am J 
Ophthalmol 2005, 140(3):509-516. 
4. 
National Institutes of Health (NIH). Numeric Pain Rating Scale (NPRS). Warren 
Grant Magnuson Clinical Center. Pain Intensity Instruments. July 2003.  
 
 


RTA 408 Ophthalmic Suspension 
 
 
 
 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
 
 
 
 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 50 of 77 
0
2
3
4
5
6
1
7
8
9
10
None
Mild
Moderate
Severe
APPENDIX 1: EXAMINATION PROCEDURES 
OCULAR PAIN GRADING SCALE (STUDY EYE) 
Ocular Pain will be assessed by the patient at screening and at each follow-up visit, 
utilizing a Numerical Pain Rating Scale1 graded from 0 to 10. Patients will assess the 
level of pain they are experiencing in the study eye at the time of the assessment. Patients 
may only select whole numbers on the scale.  
The examiner will ask the patient the following question related to Figure 1: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 whole 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”.  
Figure 1 
Ocular Pain Grading Scale 
 
 
 
 
 
 
 
 
 
 
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. 
 
 
1 Reference 4. National Institutes of Health (NIH). Numeric Pain Rating Scale (NPRS). . Warren Grant Magnuson 
Clinical Center. Pain Intensity Instruments. July 2003.  
 
 


RTA 408 Ophthalmic Suspension 
 
 
 
 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
 
 
 
 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 51 of 77 
APPENDIX 1 (CONTINUED) 
PIN-HOLE VISUAL ACUITY PROCEDURES (EACH EYE) 
Pin-hole, 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. If smaller reproduction (18" by 
18", e.g., from Prevent Blindness) wall charts are used, the patient viewing distance 
should be exactly 10 feet (or as specified by the manufacturer). In ALL cases, for 
purposes of standardizing the testing conditions during the study, all sites must use only 
the 'R' charts, and the right eye should be tested first. For reflectance (wall) charts, the 
chart should be placed frontally and well-illuminated. 
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. 
 
 


RTA 408 Ophthalmic Suspension 
 
 
 
 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
 
 
 
 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 52 of 77 
APPENDIX 1 (CONTINUED) 
PIN-HOLE VISUAL ACUITY PROCEDURES (cont.) 
LogMAR Visual Acuity Calculations 
The last line in which a letter is read correctly will be taken as the base logMAR reading. 
To this value will be added the number "N x 0.02" where 'N' represents the total number 
of letters missed up to and included in the last line read. This total sum represents the 
logMAR visual acuity for that eye. 
For example: Patient correctly reads 4 of 5 letters on the 0.2 line, and 2 of 5 letters on the 
0.1 line. 
Base LogMAR 
= 0.1 
N (total number of letters incorrect on 
line 0.2 as well as 0.1) 
 
 
 
= 4 
N x T (T=0.02) 
= 0.08 
Base logMAR + (N x T) 
= 0.1 + 0.08 
logMAR VA 
= 0.18 
Repeat the procedure for the left eye. 
In order to provide standardized and well-controlled assessments of visual acuity during 
the study, all visual acuity assessments at a single site must be consistently done using the 
same lighting conditions and pin-hole during the entire study. If the same conditions and 
use of pin-hole cannot be used, the reason for the change in condition and pin hole should 
be documented. 
 
 


57$2SKWKDOPLF6XVSHQVLRQ




5HDWD3KDUPDFHXWLFDOV
&OLQLFDO7ULDO3URWRFRO&




$PHQGPHQW)HE

&RQILGHQWLDO

3DJHRI
$33(1',;&217,18('
6/,7/$03%,20,&526&23<($&+(<(
6OLWODPSELRPLFURVFRS\ZLOOEHSHUIRUPHGGXULQJWKHVWXG\2EVHUYDWLRQVZLOOEHJUDGHG
DV1RUPDORU$EQRUPDO$OODEQRUPDOILQGLQJVRWKHUWKDQWKHHQGSRLQWVEHLQJDVVHVVHG
E\ WKH VWXG\ VFDOHV DQWHULRU FKDPEHU FHOOV DQG IODUH ZLOO EH GRFXPHQWHG RQ HDFK
SDWLHQW¶V VRXUFH GRFXPHQW DQG FRUUHVSRQGLQJ HOHFWURQLF FDVH UHSRUW IRUP H&5) $OO
DEQRUPDOILQGLQJVZLOOEHFDWHJRUL]HGDVFOLQLFDOO\VLJQLILFDQWILQGLQJVWKDWPD\LQWHUIHUH
ZLWKVWXG\SDUDPHWHUVRURWKHUZLVHFRQIRXQGWKHGDWDDVGHWHUPLQHGE\WKHLQYHVWLJDWRU
DQGQRWFOLQLFDOO\VLJQLILFDQW
7KHIROORZLQJZLOOEHH[DPLQHGDWHDFKYLVLW
• (\HOLG
• &RQMXQFWLYD
• &RUQHD
• ,ULV
• /HQV
• $QWHULRUFKDPEHU
([WHUQDO H[DPLQDWLRQ DQG ELRPLFURVFRS\ ZLOO EH SHUIRUPHG XVLQJ D VOLW ODPS
0DJQLILFDWLRQ ZLOO EH FRQVLVWHQW ZLWK VWDQGDUG FOLQLFDO SUDFWLFH  7KH SDWLHQW ZLOO EH
VHDWHG




RTA 408 Ophthalmic Suspension 
 
 
 
 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
 
 
 
 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 54 of 77 
APPENDIX 1 (CONTINUED) 
DURING SLIT-LAMP BIOMICROSCOPY: ANTERIOR CHAMBER CELLS 
AND FLARE (STUDY EYE)  
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 
fewer than 10 cells are seen (only white blood cells should be counted; red blood cells 
and pigment cells should not be counted). Flare will be graded using the SUN* Working 
Group grading scheme. 
 
Anterior Chamber Cells 
Grade 
Number of Cells in Field 
0 
0 cells 
1 
1 to 10 cells 
2 
11 to 20 cells 
3 
21 to 50 cells 
4 
> 50 cells 
 
*Reference 3.  Standardization of the Uveitis Nomenclature (SUN): Jabs et al. 2005. 
 
INTRAOCULAR PRESSURE (IOP) PROCEDURES (EACH EYE) 
Applanation tonometry, Goldmann tonometer required. Do NOT use non-contact 
tonometry. 
 
 
Flare 
Grade 
Description 
0 
None 
1+ 
Faint 
2+ 
Moderate  
iris and lens details clear 
3+ 
Marked  
iris and lens details hazy 
4+ 
Intense 
fibrin or plastic aqueous 


57$2SKWKDOPLF6XVSHQVLRQ




5HDWD3KDUPDFHXWLFDOV
&OLQLFDO7ULDO3URWRFRO&




$PHQGPHQW)HE

&RQILGHQWLDO

3DJHRI
$33(1',;&217,18('
',/$7(',1',5(&723+7+$/026&23,&(;$0,1$7,21($&+(<(

'LODWHGLQGLUHFWRSKWKDOPRVFRSLFH[DPLQDWLRQZLOOEHSHUIRUPHGDVLQGLFDWHGLQWKHVWXG\
IORZFKDUW
LQ
$SSHQGL[

DIWHU
WKH
SDWLHQW
,&)DXWKRUL]DWLRQ
PHGLFDO
KLVWRU\GHPRJUDSKLFV XULQH SUHJQDQF\ WHVW LI DSSOLFDEOH SLQKROH YLVXDO DFXLW\ VOLW
ODPS ELRPLFURVFRS\ DQG WRQRPHWU\ 7KH H[DPLQDWLRQ ZLOO QRW EH SHUIRUPHG XQWLO WKH
SDWLHQW¶V H\HV DUH GHHPHG VXIILFLHQWO\ GLODWHG LQ WKH RSLQLRQ RI WKH LQYHVWLJDWRU 7KH
LQYHVWLJDWRUZLOOQRWHDQ\ILQGLQJVSUHVHQWDQGZKHWKHURUQRWWKHILQGLQJVDUHFOLQLFDOO\
VLJQLILFDQWRUQRWFOLQLFDOO\VLJQLILFDQW)LQGLQJVZKLFKDUHFOLQLFDOO\VLJQLILFDQWZLOOEH
GHVFULEHG

7KHIROORZLQJZLOOEHH[DPLQHG

• 9LWUHRXV
• 5HWLQD
• 0DFXOD
• &KRURLG
• 2SWLF1HUYH




RTA 408 Ophthalmic Suspension 
 
 
 
 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
 
 
 
 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 56 of 77 
APPENDIX 2:  SCHEDULE OF VISITS AND MEASUREMENTS 
Study Parameter 
Visit 1 
(≥ -28 Days 
Prior to 
Surgery) 
Visit 2 
(Day 1,  
24 ± 6 hrs 
Post-
Surgery) 
Visit 3 
(Day 42) 
Visit 4 
(Day 82) 
Visit 5 
(Day 153) 
Visit 6  
(Day 212, 
Exit or Early 
Exit Visit) 
Informed Consent/ 
HIPAA 
X 
 
 
 
 
 
Demographic Data 
X 
 
 
 
 
 
Medical and Medication 
History 
X 
 
 
 
 
 
Urine Pregnancy Test (for 
females of childbearing 
potential)  
X 
 
 
 
 
X 
Review of Inclusion and 
Exclusion Criteria 
X 
X 
 
 
 
 
Medical and Medication 
History Update 
 
X 
X 
X 
X 
X 
Ocular Pain Assessment 
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 Anterior 
Chamber Cell and Flare (at 
Slit-lamp Biomicroscopy) 
X 
X 
X 
X 
X 
X 
Intraocular Pressure 
Assessment  
X 
X 
X 
X 
X 
X 
Randomization of Study 
Patients 
 
X 
 
 
 
 
Dilated Indirect 
Ophthalmoscopic 
Examination 
X 
 
 
 
 
X 
Study Drug Instillation1 
 
X 
 
 
 
 
Study Drug and 
Compliance Diary 
Instructions and 
Dispensation 
 
X 
 
 
 
 
AE Query 
 
X 
X 
X 
X 
X 
Review of Study Drug 
Compliance Diary 
 
 
X 
X 
X 
X 
Collection of Study Drug 
and Compliance Diary 
 
 
 
 
X 
X4 
Exit from Study 
 
 
 
 
 
X 
1First study drug dose will be instilled in-office at Visit 2. Patients will instill study drug twice daily at-
home in the morning and evening (approximately 12 hrs apart) between study visits, from Day 1 through 
Day 14. 
2± 1 Day 
3 + 1 Day 
4 In case of early termination or if patient did not return study drug prior to Visit 5.  


57$2SKWKDOPLF6XVSHQVLRQ

5HDWD3KDUPDFHXWLFDOV
&OLQLFDO7ULDO3URWRFRO&
$PHQGPHQW)HE

&RQILGHQWLDO

3DJHRI
$33(1',;35272&2/$0(1'0(176
 5$7,21$/()25$0(1'0(17

7KHSXUSRVHRIWKHSURWRFRODPHQGPHQWLVWRPDNHDGPLQLVWUDWLYHXSGDWHVWKURXJKRXW([FOXVLRQFULWHULDDQGKDG
DGGLWLRQDOH[FOXVLRQDU\LWHPVVSHFLILHGDGGLWLRQDOVWXG\GUXJGRVLQJLQVWUXFWLRQVZHUHDGGHGWR6HFWLRQDGGLWLRQDOGHWDLOV
UHJDUGLQJHVFDSHPHGLFDWLRQVZHUHVSHFLILHGLQ6HFWLRQDQG6HFWLRQZDVGHOHWHGJLYHQ6SRQVRU3KDUPDFRYLJLODQFHZLOO
DVVHVVIRUDGYHUVHHYHQWH[SHFWHGQHVV

 6800$5<2)&+$1*(6

,QWKHWDEOHEHORZWKHSURWRFROWH[WZDVDPHQGHGE\WKHIROORZLQJFRQYHQWLRQV
• 'HOHWLRQVWRRULJLQDOWH[WDUHLQGLFDWHGE\VWULNHWKURXJKOHWWHUV
• $GGLWLRQVWRDPHQGHGWH[WDUHLQGLFDWHGE\EROGOHWWHUV
• 5HSODFHPHQWRIZRUGLQJLQWKHDPHQGHGWH[WDUHLQGLFDWHGE\EROGDQGLWDOLFL]HGOHWWHUV


RTA 408 Ophthalmic Suspension 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 58 of 77 
 
Section 
Reason for 
Amendment 
Protocol Currently Reads 
Amended Text 
Title Page 
Administrative 
update 
[blank] 
Amendment 1:  10-Feb-2014 
Header 
Administrative 
update 
RTA 408 Sterile Ophthalmic Suspension 
RTA 408 Sterile Ophthalmic Suspension 
Header 
Administrative 
update 
Original Protocol: 21-Nov-2013 
Amendment 1: 10-Feb-2014 
Synopsis  
pg 5 – Inclusion 
Criteria #4 
Administrative 
update 
Have undergone unilateral cataract extraction via 
phacoemulsification on the day prior to study 
enrollment/randomization; 
 
Have undergone unilateral cataract extraction via 
phacoemulsification and posterior chamber 
intraocular lens (PCIOL) implantation in the 
study eye on the day prior to study 
enrollment/randomization; 
Synopsis  
pg 5 – Inclusion 
Criteria #5 
Administrative 
update 
Have a grade of ≥2 in anterior chamber cell score 
on day after surgery (Day 1); 
Have a grade of ≥2 in anterior chamber cell score 
on day after surgery (Day 1) in the study eye; 
Synopsis  
pg 5 – Inclusion 
Criteria #6 
Administrative 
update 
Have a potential post-operative pin-hole visual 
acuity (VA) of greater than 1.0 logarithm of the 
minimum angle of resolution (logMAR) in the 
operative eye and fellow eye as measured using an 
Early Treatment for Diabetic Retinopathy Study 
(ETDRS) chart; 
Have a potential post-operative pin-hole visual 
acuity (VA) of greater than< 1.0 logarithm of the 
minimum angle of resolution (logMAR) in the 
operative eye and fellow eye as measured using 
an Early Treatment for Diabetic Retinopathy 
Study (ETDRS) chart; 
Synopsis  
pg 5 – Inclusion 
Criteria #7 
Administrative 
update 
(For females of childbearing potential) agree to 
have urine pregnancy testing performed at 
screening (must be negative) and at exit visit1; must 
not be lactating; and must agree to use a medically 
acceptable form of birth control2 throughout the 
study duration. 
________________________ 
(For females of childbearing potential) agree to 
have urine pregnancy testing performed at 
screening (must be negative) and at exit visit1; 
must not be lactating; and must agree to use a 
medically acceptable form of birth control1 
throughout the study duration. 
________________________ 


RTA 408 Ophthalmic Suspension 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 59 of 77 
1 The subject must choose an acceptable method of 
birth control as specified in inclusion criterion 7 in 
order to continue in the study. 
2 Acceptable forms of birth control are spermicide 
with barrier, oral contraceptive, injectable or 
implantable method of contraception, transdermal 
contraceptive, intrauterine device, or surgical 
sterilization of partner. For non-sexually active 
females, abstinence will be considered an 
acceptable form of birth control. 
1 The subject must choose an acceptable method 
of birth control as specified in inclusion criterion 
7 in order to continue in the study. 
1 Acceptable forms of birth control are spermicide 
with barrier, oral contraceptive, injectable or 
implantable method of contraception, transdermal 
contraceptive, intrauterine device, or surgical 
sterilization of partner. For non-sexually active 
females, abstinence will be considered an 
acceptable form of birth control. 
Synopsis  
pg 6 – Exclusion 
Criteria #7 
Additional 
exclusion criteria 
added 
Use the following anti-inflammatory or 
immunomodulating agents systemically, or in the 
study eye, for the duration of the study. Washout 
periods for medications prior to surgery are as 
follows:  
a. Systemic corticosteroids: 14 days 
b. Periocular injection of any corticosteroid 
solution: 28 days 
c. Corticosteroid depot in the study eye: 56 
days after implantation  
d. Cyclosporine: 56 days 
e. Topical ocular corticosteroid: 7 days  
f. Topical ocular NSAID: 7 days 
 
Use anti-inflammatory agents, analgesics/pain 
relievers (including opioids, narcotics and 
other pain medications) or immunomodulating 
agents systemically, or in the study eye, and/or 
use medications for benign prostatic 
hyperplasia (BPH), from the washout period 
through for the duration of the study. Washout 
periods for medications prior to surgery are as 
follows:  
a. Medications for BPH (tamsulosin, 
silodosin, alfuzosin, finasteride): 28 days  
b. Systemic corticosteroids: 14 days 
c. Systemic analgesics/pain relievers (e.g., 
gabapentin, pregabalin, NSAIDs and 
opioids): 14 days 
Note: Use of acetaminophen (up to 4,000 
mg/day) and ‘baby’ aspirin (up to 81 
mg/day) during the study are allowed. Use 
of an opioid during cataract surgery is 
allowed. 
d. Periocular injection of any corticosteroid 
solution: 28 days 


RTA 408 Ophthalmic Suspension 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 60 of 77 
e. Corticosteroid depot in the study eye: 56 
days after implantation  
f. Cyclosporine: 56 days 
g. Topical ocular corticosteroid: 7 days  
h. Topical ocular NSAID: 7 days 
Synopsis  
pg 7 – Exclusion 
Criteria #9 
Administrative 
update 
Have an IOP  ≤ 5 mmHg in either eye; 
Have an intraocular pressure (IOP)  ≤ 5 mmHg 
in either eye; 
Synopsis  
pg 7 – Exclusion 
Criteria #16 
Administrative 
update 
Have had corneal or retinal surgery (laser or 
incisional) within the past 6 months, or be planning 
to have laser or incisional surgery during the study 
period in the study eye;  
Have had corneal or retinal surgery (laser or 
incisional) within the past 6 months, or be 
planning to have laser or incisional surgery 
during the study period in the study eye (other 
than cataract surgery); 
Synopsis  
pg 7 – Exclusion 
Criteria #17 
Administrative 
update 
Have a scheduled surgery in the contralateral eye 
during the study;  
Have a surgery planned or scheduled surgery in 
for the contralateral eye during the study; 
Synopsis  
Pg 8 –  
Exclusion Criteria 
#23 
Additional 
exclusion criteria 
added 
Have undergone a vitrectomy procedure in addition 
to the cataract extraction procedure in the study 
eye; 
Have undergone any other ophthalmic surgical 
procedure (e.g., vitrectomy, relaxing incisions, 
iridectomy, conjunctival excisions, use of iris 
hooks or other iris dilators, etc.) a vitrectomy 
procedure in addition to the cataract extraction 
procedure and PCIOL implantation in the study 
eye; 
Synopsis  
Pg 8 –  
Exclusion Criteria 
#24 
Administrative 
update 
Have previously enrolled in this clinical study, or 
will be participating during the follow-up 
period in another clinical trial that could confound 
the treatment or outcomes of this investigation; 
Have previously enrolled in this clinical study, or 
will beare planning to participate in another 
clinical trial during the follow-up period, in 
another clinical trial that could confound the 
treatment or outcomes of this investigation; 
Synopsis Pg 10 –  
General Statistical 
Administrative 
update 
If in addition to a statistically significant test of the 
difference in the proportion of study eyes with 
If in addition to a statistically significant test of 
the difference in the proportion of study eyes with 


RTA 408 Ophthalmic Suspension 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 61 of 77 
Methods and 
Types of 
Analyses: 
Efficacy Analysis 
(5th Paragraph) 
 
 
absence of anterior chamber cells at Visit 5 (Day 
15) in favor of RTA 408 Ophthalmic Suspension, 
the test of the difference in the proportion of study 
eyes with absence of ocular pain at Visit 3 (Day 4) 
is statistically significant in favor of RTA 408 
Ophthalmic Suspension, then RTA 408 Ophthalmic 
Suspension will be declared to be superior to 
placebo in both the proportion of study eyes with 
absence of anterior chamber cells at Visit 5 (Day 
15) and the proportion of study eyes with absence 
of ocular pain at Visit 3 (Day 4). 
absence of anterior chamber cells at Visit 5 (Day 
15) in favor of RTA 408 Ophthalmic Suspension, 
the test of the difference in the proportion of 
study eyes with absence of ocular pain at Visit 3 
(Day 4) is statistically significant in favor of RTA 
408 Ophthalmic Suspension, then RTA 408 
Ophthalmic Suspension will be declared to be 
superior to placebo in both the proportion of 
study eyes with absence of anterior chamber cells 
at Visit 5 (Day 15) and the proportion of study 
eyes with absence of ocular pain at Visit 3 (Day 
4). 
Synopsis Pg 11 – 
General Statistical 
Methods and 
Types of 
Analyses: 
General 
Considerations 
(5th and 6th 
Paragraphs)  
 
Administrative 
update 
The secondary efficacy variables, study eyes with 
absence of anterior chamber cells (Visits 3, 4 or 6), 
study eyes with absence of pain (Visits 4, 5 or 6) 
and study eyes with absence of flare (Visits 3, 4, 5 
or 6) will be summarized and analyzed similarly to 
the primary efficacy summaries and analyses. 
Additionally, anterior chamber cells and flare as 
well as pain at each visit and change from baseline 
will be summarized using continuous and discrete 
summary statistics. 
The sum of anterior chamber cells and flare grade 
will be summarized and analyzed similarly to 
anterior chamber cells and flare separately. 
The secondary efficacy variables, study eyes with 
absence of anterior chamber cells (Visits 3, 4 or 
6), study eyes with absence of pain (Visits 4, 5 or 
6) and study eyes with absence of flare (Visits 3, 
4, 5 or 6) will be summarized and analyzed 
similarly to the primary efficacy summaries and 
analyses. Additionally, anterior chamber cells and 
flare as well as pain at each visit and change from 
baseline will be summarized using continuous 
and discrete summary statistics. 
The sum of anterior chamber cells and flare grade 
will be summarized and analyzed similarly to 
anterior chamber cells and flare separately. 
List of 
Abbreviations  
Administrative 
update 
… 
BID Bis in die (twice daily) 
CFR Code of Federal Regulations 
… 
… 
BID Bis in die (twice daily) 
BPH Benign prostatic hyperplasia  
CFR Code of Federal Regulations 


RTA 408 Ophthalmic Suspension 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 62 of 77 
NSAID Non-steroidal anti-inflammatory agent 
PDR Proliferative diabetic retinopathy 
… 
… 
NSAID Non-steroidal anti-inflammatory agent 
PCIOL Posterior chamber intraocular lens 
PDR Proliferative diabetic retinopathy 
... 
Section 4 
Paragraph 2 
Administrative 
update 
. . .The Investigator will then perform a slit lamp 
biomicroscopic examination with IOP 
measurement, and grading of anterior chamber 
inflammation. A dilated indirect ophthalmoscopic 
examination will also be performed. Female 
patients of childbearing potential will be given a 
urine pregnancy test.  
...The Investigator will then perform a slit lamp 
biomicroscopic examination with intraocular 
pressure (IOP) measurement, and grading of 
anterior chamber inflammation. A dilated indirect 
ophthalmoscopic examination will also be 
performed. Female patients of childbearing 
potential will be given a urine pregnancy test.  
Section 4 
Paragraph 3 
Administrative 
update 
…Qualifying patients (with ≥2 score in anterior 
chamber cell, IOP ≤22 mm Hg) will then be 
randomized to one of the following treatment 
groups (in a 1:1:1 ratio): RTA 408 Ophthalmic 
Suspension 0.5% (N=35), RTA 408 Ophthalmic 
Suspension 1.0% (N=35), or placebo for RTA 408 
Ophthalmic Suspension (N=35). 
…Qualifying patients (with ≥2 score in anterior 
chamber cell, IOP ≤22 mm Hg) will then be 
randomized to one of the following treatment 
groups (in a 1:1:1 ratio): RTA 408 Ophthalmic 
Suspension 0.5% (N=35), RTA 408 Ophthalmic 
Suspension 1.0% (N=35), or placebo for RTA 
408 Ophthalmic Suspension (N=35). 
Section 5.3 
Inclusion Criteria 
#4 
Administrative 
update 
Have undergone unilateral cataract extraction via 
phacoemulsification on the day prior to study 
enrollment/randomization; 
 
Have undergone unilateral cataract extraction via 
phacoemulsification and posterior chamber 
intraocular lens (PCIOL) implantation in the 
study eye on the day prior to study 
enrollment/randomization; 
Section 5.3 
Inclusion Criteria 
#5 
Administrative 
update 
Have a grade of ≥2 in anterior chamber cell score 
on day after surgery (Day 1); 
Have a grade of ≥2 in anterior chamber cell score 
on day after surgery (Day 1) in the study eye; 
Section 5.3 
Administrative 
Have a potential post-operative pin-hole visual 
Have a potential post-operative pin-hole visual 


RTA 408 Ophthalmic Suspension 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 63 of 77 
Inclusion Criteria 
#6 
update 
acuity (VA) of greater than 1.0 logarithm of the 
minimum angle of resolution (logMAR) in the 
operative eye and fellow eye as measured using an 
Early Treatment for Diabetic Retinopathy Study 
(ETDRS) chart; 
acuity (VA) of greater than< 1.0 logarithm of the 
minimum angle of resolution (logMAR) in the 
operative eye and fellow eye as measured using 
an Early Treatment for Diabetic Retinopathy 
Study (ETDRS) chart; 
Section 5.3 
Inclusion Criteria 
#7 
Administrative 
update 
(For females of childbearing potential) agree to 
have urine pregnancy testing performed at 
screening (must be negative) and at exit visit1; must 
not be lactating; and must agree to use a medically 
acceptable form of birth control2 throughout the 
study duration. 
________________________ 
1 The subject must choose an acceptable method of 
birth control as specified in inclusion criterion 7 in 
order to continue in the study. 
2 Acceptable forms of birth control are spermicide 
with barrier, oral contraceptive, injectable or 
implantable method of contraception, transdermal 
contraceptive, intrauterine device, or surgical 
sterilization of partner. For non-sexually active 
females, abstinence will be considered an 
acceptable form of birth control. 
(For females of childbearing potential) agree to 
have urine pregnancy testing performed at 
screening (must be negative) and at exit visit1; 
must not be lactating; and must agree to use a 
medically acceptable form of birth control1 
throughout the study duration. 
________________________ 
1 The subject must choose an acceptable method 
of birth control as specified in inclusion criterion 
7 in order to continue in the study. 
1 Acceptable forms of birth control are spermicide 
with barrier, oral contraceptive, injectable or 
implantable method of contraception, transdermal 
contraceptive, intrauterine device, or surgical 
sterilization of partner. For non-sexually active 
females, abstinence will be considered an 
acceptable form of birth control. 
Section 5.4 
Exclusion Criteria 
#7 
Additional 
exclusion criteria 
added 
Use the following anti-inflammatory or 
immunomodulating agents systemically, or in the 
study eye, for the duration of the study. Washout 
periods for medications prior to surgery are as 
follows:  
a. 
Systemic corticosteroids: 14 days 
b. 
Periocular injection of any corticosteroid 
solution: 28 days 
Use anti-inflammatory agents, analgesics/pain 
relievers (including opioids, narcotics and 
other pain medications) or immunomodulating 
agents systemically, or in the study eye, and/or 
use medications for benign prostatic 
hyperplasia (BPH), from the washout period 
through for the duration of the study. Washout 
periods for medications prior to surgery are as 


RTA 408 Ophthalmic Suspension 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 64 of 77 
c. 
Corticosteroid depot in the study eye: 56 
days after implantation  
d. 
Cyclosporine: 56 days 
e. 
Topical ocular corticosteroid: 7 days  
f. 
Topical ocular NSAID: 7 days 
 
follows:  
a. Medications for BPH (tamsulosin, 
silodosin, alfuzosin, finasteride): 28 days  
b. Systemic corticosteroids: 14 days 
c. Systemic analgesics/pain relievers (e.g., 
gabapentin, pregabalin, NSAIDs and 
opioids): 14 days 
Note: Use of acetaminophen (up to 4,000 
mg/day) and ‘baby’ aspirin (up to 81 
mg/day) during the study are allowed. Use 
of an opioid during cataract surgery is 
allowed. 
d. Periocular injection of any corticosteroid 
solution: 28 days 
e. Corticosteroid depot in the study eye: 56 
days after implantation  
f. Cyclosporine: 56 days 
g. Topical ocular corticosteroid: 7 days  
h. Topical ocular NSAID: 7 days 
Section 5.4 
Exclusion Criteria 
#9 
Administrative 
update 
Have an IOP  ≤ 5 mmHg in either eye; 
 
Have an intraocular pressure (IOP)  ≤ 5 mmHg 
in either eye; 
Section 5.4 
Exclusion Criteria 
#16 
Administrative 
update 
Have had corneal or retinal surgery (laser or 
incisional) within the past 6 months, or be planning 
to have laser or incisional surgery during the study 
period in the study eye;  
 
Have had corneal or retinal surgery (laser or 
incisional) within the past 6 months, or be 
planning to have laser or incisional surgery 
during the study period in the study eye (other 
than cataract surgery);  
 
Section 5.4 
Exclusion Criteria 
#17 
Administrative 
update 
Have a scheduled surgery in the contralateral eye 
during the study;  
Have a surgery planned or scheduled surgery in 
for the contralateral eye during the study; 


RTA 408 Ophthalmic Suspension 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 65 of 77 
Section 5.4 
Exclusion Criteria 
#23 
Additional 
exclusion criteria 
added 
Have undergone a vitrectomy procedure in addition 
to the cataract extraction procedure in the study 
eye; 
Have undergone any other ophthalmic surgical 
procedure (e.g., vitrectomy, relaxing incisions, 
iridectomy, conjunctival excisions, use of iris 
hooks or other iris dilators, etc.) a vitrectomy 
procedure in addition to the cataract extraction 
procedure and PCIOL implantation in the study 
eye; 
Section 5.4 
Exclusion Criteria 
#24 
Administrative 
update 
Have previously enrolled in this clinical study, or 
will be participating during the follow-up 
period in another clinical trial that could confound 
the treatment or outcomes of this investigation; 
Have previously enrolled in this clinical study, or 
will beare planning to participate in another 
clinical trial participating during the follow-up 
period, in another clinical trial that could 
confound the treatment or outcomes of this 
investigation; 
Section 6.1.2  
 
Administrative 
update 
This clinical study is designed to evaluate the 
efficacy and safety of two concentrations of RTA 
408 Ophthalmic Suspension compared to placebo 
in the treatment of inflammation and pain 
following ocular surgery. To demonstrate clinical 
efficacy, RTA 408 Ophthalmic Suspension must be 
effective in eliminating anterior chamber cells (i.e. 
score of ‘0’) at Visit 5 (Day 15) post-ocular 
surgery. If, in addition to absence of anterior 
chamber cells, RTA 408 Ophthalmic Suspension is 
also effective in elimination of ocular pain (i.e. 
score of ‘0’) at Visit 3 (Day 4) post-ocular surgery, 
then absence of pain will also be claimed. 
This clinical study is designed to evaluate the 
efficacy and safety of two concentrations of RTA 
408 Ophthalmic Suspension compared to placebo 
in the treatment of inflammation and pain 
following ocular surgery. To demonstrate clinical 
efficacy, RTA 408 Ophthalmic Suspension must 
be effective in eliminating anterior chamber cells 
(i.e. score of ‘0’) at Visit 5 (Day 15) post ocular 
surgery. If, in addition to absence of anterior 
chamber cells, RTA 408 Ophthalmic Suspension 
is also effective in elimination of ocular pain (i.e. 
score of ‘0’) at Visit 3 (Day 4) post ocular 
surgery, then absence of pain will also be 
claimed. 
Section 7.1.2 3rd 
Bullet Point 
Additional dosing 
instructions 
specified 
Instructions to patients on study drug 
administration will include: Remove from 
refrigerator.  SHAKE WELL BEFORE 
USE.  Instill one drop twice daily for 14 days in the 
Instructions to patients on study drug 
administration will include: Remove from 
refrigerator.  SHAKE WELL BEFORE 
USE.  Instill one drop twice daily for 14 days in 


57$2SKWKDOPLF6XVSHQVLRQ
5HDWD3KDUPDFHXWLFDOV
&OLQLFDO7ULDO3URWRFRO&
$PHQGPHQW)HE

&RQILGHQWLDO

3DJHRI
PRUQLQJDQGHYHQLQJDSSUR[LPDWHO\KRXUV
DSDUWLQWKHH\HWKDWXQGHUZHQWVXUJHU\5HWXUQ
GUXJWRUHIULJHUDWRUIRUVWRUDJHDIWHUHDFK
XVH'LVFRQWLQXHXVHRIWKHVWXG\GUXJDIWHU
FRPSOHWLQJVHFRQGGRVHRQ'D\.HHSRXWRI
UHDFKRIFKLOGUHQ
WKHPRUQLQJDQGHYHQLQJDSSUR[LPDWHO\KRXUV
DSDUWLQWKHH\HWKDWXQGHUZHQWVXUJHU\6WXG\
GUXJPXVWEHQRWEHLQVWLOOHGZLWKLQPLQXWHV
RIDIWHULQVWLOODWLRQRIDQ\RWKHURFXODU
PHGLFDWLRQVRUDUWLILFLDOWHDUV5HWXUQWKHVWXG\
GUXJWRUHIULJHUDWRUIRUVWRUDJHDIWHUHDFK
XVH'LVFRQWLQXHXVHRIWKHVWXG\GUXJDIWHU
LQVWLOOLQJFRPSOHWLQJWKHVHFRQGGRVHRQ'D\
.HHSRXWRIUHDFKRIFKLOGUHQ
6HFWLRQ

$GPLQLVWUDWLYH
XSGDWH
6WXG\VWDIIZLOOFRQILUPWKDWWKHSDWLHQWKDVQRW
XVHGSULRUWR'D\IRUWKHLQGLFDWHGZDVKRXW
LQWHUYDODQGIRUWKHGXUDWLRQRIWKHVWXG\DQ\RIWKH
IROORZLQJGLVDOORZHGPHGLFDWLRQVV\VWHPLFDOO\RU
LQWKHVWXG\H\HJURXSHGE\ZDVKRXWSHULRG
«
GD\V
•
6\VWHPLFFRUWLFRVWHURLGV

GD\V
•
3HULRFXODULQMHFWLRQRIDQ\FRUWLFRVWHURLG
VROXWLRQ

6WXG\VWDIIZLOOFRQILUPWKDWWKHSDWLHQWKDVQRW
XVHGSULRUWR'D\IRUWKHLQGLFDWHGZDVKRXW
LQWHUYDODQGIRUWKHGXUDWLRQRIWKHVWXG\DQ\RI
WKHIROORZLQJGLVDOORZHGPHGLFDWLRQV
V\VWHPLFDOO\RULQWKHVWXG\H\HJURXSHGE\
ZDVKRXWSHULRG
«
GD\V
•
6\VWHPLFFRUWLFRVWHURLGV
•
6\VWHPLFDQDOJHVLFVSDLQUHOLHYHUV
HJJDEDSHQWLQSUHJDEDOLQ
16$,'VDQGRSLRLGV
1RWH 8VH RI DFHWDPLQRSKHQ XS WR
 PJGD\ DQG µEDE\¶ DVSLULQ XS
WR  PJGD\ GXULQJ WKH VWXG\ DUH
DOORZHG 8VH RI DQ RSLRLG GXULQJ
FDWDUDFWVXUJHU\LVDOORZHG

GD\V
•
3HULRFXODULQMHFWLRQRIDQ\
FRUWLFRVWHURLGVROXWLRQ


57$2SKWKDOPLF6XVSHQVLRQ
5HDWD3KDUPDFHXWLFDOV
&OLQLFDO7ULDO3URWRFRO&
$PHQGPHQW)HE

&RQILGHQWLDO

3DJHRI
•
0HGLFDWLRQVIRU%3+WDPVXORVLQ
VLORGRVLQDOIX]RVLQILQDVWHULGH
6HFWLRQ
$GPLQLVWUDWLYH
XSGDWH
•
*ODXFRPDPHGLFDWLRQVRURFXODUK\SHUWHQVLRQ
PHGLFDWLRQVLQWKHVWXG\H\H
•
2FXODU K\SHUWHQVLRQ PHGLFDWLRQV LQ WKH VWXG\
H\H
«
•
9LWUHFWRP\ SURFHGXUH LQ DGGLWLRQ WR WKH
FDWDUDFWH[WUDFWLRQSURFHGXUHLQWKHVWXG\H\H
•
,IDSDWLHQWXVHVDGLVDOORZHGPHGLFDWLRQWKLV
ZLOOEHUHFRUGHGDVDSURWRFROYLRODWLRQ
•
6\VWHPLFPHGLFDWLRQVIRUEHQLJQSURVWDWLF
K\SHUSODVLD
%3+
HJ
WDPVXORVLQ
VLORGRVLQDOIX]RVLQILQDVWHULGH
•
6\VWHPLF
$QDOJHVLFVSDLQ
UHOLHYHUV
LQFOXGLQJRSLRLGVQDUFRWLFVDQGRWKHUSDLQ
PHGLFDWLRQVV\VWHPLFDOO\HJJDEDSHQWLQ
SUHJDEDOLQ16$,'VDQGRSLRLGV
•
1RWH 8VH RI DFHWDPLQRSKHQ XS WR 
PJGD\ DQG µEDE\¶ DVSLULQ XS WR 
PJGD\GXULQJWKHVWXG\DUHDOORZHG8VH
RI DQ RSLRLG GXULQJ FDWDUDFW VXUJHU\ LV
DOORZHG
•
*ODXFRPD
PHGLFDWLRQV
RU
RFXODU
K\SHUWHQVLRQPHGLFDWLRQVLQWKHVWXG\H\H
•
2FXODUK\SHUWHQVLRQPHGLFDWLRQVLQWKHVWXG\
H\H
«
•
$Q\ RWKHU RSKWKDOPLF VXUJLFDO SURFHGXUH
HJ
YLWUHFWRP\
UHOD[LQJ
LQFLVLRQV
LULGHFWRP\ FRQMXQFWLYDO H[FLVLRQV XVH RI
LULV KRRNV RU RWKHU LULV GLODWRUV HWF
9LWUHFWRP\ SURFHGXUH LQ DGGLWLRQ WR WKH
FDWDUDFW H[WUDFWLRQ SURFHGXUH DQG 3&,2/
LPSODQWDWLRQLQWKHVWXG\H\H
•
3ODQWRKDYHODVHURULQFLVLRQDOVXUJHU\LQ
WKH VWXG\ H\H RWKHU WKDQ FDWDUDFW
VXUJHU\


57$2SKWKDOPLF6XVSHQVLRQ
5HDWD3KDUPDFHXWLFDOV
&OLQLFDO7ULDO3URWRFRO&
$PHQGPHQW)HE

&RQILGHQWLDO

3DJHRI
•
6XUJHU\ SODQQHG RU VFKHGXOHG IRU WKH
FRQWUDODWHUDOH\H
,IDSDWLHQWXVHVDGLVDOORZHGPHGLFDWLRQWKLVXVH
ZLOOEHUHFRUGHGDVDSURWRFROYLRODWLRQ
6HFWLRQ
$GGLWLRQDOGHWDLOV
VSHFLILHGIRU
HVFDSH
PHGLFDWLRQV
8VHRIHVFDSHPHGLFDWLRQVVKRXOGEHDYRLGHGLI
SRVVLEOH,IHVFDSHPHGLFDWLRQLVJLYHQWKHVWXG\
GUXJVKRXOGEHGLVFRQWLQXHGDQGWKHSDWLHQWVKRXOG
UHPDLQLQWKHVWXG\DQGIROORZHGSHUWKHSURWRFRO
WRWKHHQGRIWKHVWXG\
8VHRIHVFDSHPHGLFDWLRQVVKRXOGEHDYRLGHGLI
SRVVLEOH,ILQWKHLQYHVWLJDWRU¶VDVVHVVPHQW
HVFDSHPHGLFDWLRQLVUHTXLUHGJLYHQGXHWRODFN
RIHIILFDF\WKHVWXG\GUXJVKRXOGEHGLVFRQWLQXHG
SULRUWRDGPLQLVWUDWLRQRIWKHILUVWGRVHRI
HVFDSHPHGLFDWLRQDQG7KHSDWLHQWVKRXOG
UHPDLQLQWKHVWXG\DQGFRQWLQXHWREHIROORZHG
SHUWKHSURWRFROIRUDOOUHPDLQLQJYLVLWVDQG
DVVHVVPHQWVWRWKHHQGRIWKHVWXG\7KHVH
SDWLHQWVZKRUHTXLUHHVFDSHPHGLFDWLRQVKRXOG
EHFRQVLGHUHGDVGLVFRQWLQXHGIURPVWXG\
PHGLFDWLRQGXHWRODFNRIHIILFDF\DQGWKH
HVFDSHPHGLFDWLRQVXVHGPXVWEHGRFXPHQWHG
LQWKHH&5)
6HFWLRQ
6XEEXOOHW3LQ
+ROH9LVXDO
$FXLW\8WLOL]LQJ
DQ(7'56&KDUW
$GPLQLVWUDWLYH
XSGDWH
3DWLHQWVPXVWKDYHDSRWHQWLDOSRVWRSHUDWLYHSLQ
KROH9$RIJUHDWHUWKDQORJ0$5LQWKH
RSHUDWLYHH\HDQGLQWKHIHOORZH\HDVPHDVXUHG
XVLQJDQ(7'56FKDUW
3DWLHQWVPXVWKDYHDSRWHQWLDOSRVWRSHUDWLYHSLQ
KROH9$RIJUHDWHUWKDQORJ0$5LQWKH
RSHUDWLYHH\HDQGLQWKHIHOORZH\HDVPHDVXUHG
XVLQJDQ(7'56FKDUW
6HFWLRQ
$GPLQLVWUDWLYH
XSGDWH
7KHVHYLVLWVPD\EHSHUIRUPHGLQRUGHUWRHQVXUH
SDWLHQWVDIHW\$OOLQIRUPDWLRQJDWKHUHGDW
XQVFKHGXOHGYLVLWVVKRXOGEHUHFRUGHGRQWKH
8QVFKHGXOHG9LVLW(DUO\([LW9LVLWSDJHVRIWKH
6RXUFH'RFXPHQWDQGFRUUHVSRQGLQJH&5)
,IDUDQGRPL]HGSDWLHQWGRHVQRWDWWHQGWKHLU
VFKHGXOHGYLVLWWKHH&5)SDJHVIRUWKHPLVVHGYLVLW
7KHVHYLVLWVPD\EHSHUIRUPHGLQRUGHUWRHQVXUH
SDWLHQWVDIHW\$OOLQIRUPDWLRQJDWKHUHGDW
XQVFKHGXOHGYLVLWVVKRXOGEHUHFRUGHGRQWKH
8QVFKHGXOHG9LVLW(DUO\([LW9LVLWSDJHVRIWKH
6RXUFH'RFXPHQWDQGFRUUHVSRQGLQJH&5)
,IDUDQGRPL]HGSDWLHQWGRHVQRWDWWHQGWKHLU
VFKHGXOHGYLVLWWKHH&5)SDJHVIRUWKHPLVVHG


RTA 408 Ophthalmic Suspension 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 69 of 77 
will be skipped.  
All efforts should be made to schedule patients for 
an Exit Visit to complete Exit Procedures.  
visit will be skipped.  
All efforts should be made to schedule patients 
for an Exit Visit to complete Exit Procedures. 
Information from Early Exit Visits should be 
recorded on the Visit 6/Exit Visit pages. 
Section 8.5 
Administrative 
update 
Patients will be provided with a study drug 
compliance diary to document BID dosing for 14 
days. Patient compliance with dosing will be 
assessed by in-office review of study drug 
compliance diary. Patients who miss more than 
25% of their study drug doses (more than 7 doses) 
will be considered non-compliant with dosing and 
a protocol deviation should be recorded. 
Patients will be provided with a study drug 
compliance diary to document BID dosing for 14 
days. Patient compliance with dosing will be 
assessed by in-office review of study drug 
compliance diary. Patients who miss more than 
25% of their study drug doses (more than 7 total 
doses) will be considered non-compliant with 
dosing and a protocol deviation should be 
recorded. 
Section 8.6.1 
Completed 
Patients 
Administrative 
update 
A completed patient is one who has not been 
discontinued from the study. 
A completed patient is one who has not been 
discontinued from the study and continues study 
assessments through Visit 6 (Day 21). 
Section 8.6.2 
Discontinued 
Patients 
Administrative 
update 
Patients may be discontinued prior to their 
completion of the study due to any of the following 
reasons: 
… 
Notification of a patient’s discontinuation and the 
reason for discontinuation will be made to CRO 
and study Sponsor and will be clearly documented 
on the eCRF. 
Patients may be discontinued from the study 
prior to their completion of the study due to any 
of the following reasons: 
… 
Notification of a patient’s discontinuation of 
study drug administration and the reason for 
discontinuation will be made to CRO and 
study Sponsor and will be clearly documented 
on the eCRF.  Patients who receive escape 
medication are to discontinue study drug 
administration and are to remain in the study 
and be followed per the protocol to the end of 


57$2SKWKDOPLF6XVSHQVLRQ
5HDWD3KDUPDFHXWLFDOV
&OLQLFDO7ULDO3URWRFRO&
$PHQGPHQW)HE

&RQILGHQWLDO

3DJHRI
WKHVWXG\3DWLHQWVZKRGLVFRQWLQXHVWXG\
GUXJDGPLQLVWUDWLRQIRURWKHUUHDVRQVDUH
HQFRXUDJHGWRUHPDLQLQWKHVWXG\DQG
FRQWLQXHZLWKVWXG\DVVHVVPHQWVWKURXJKWKH
HQGRIWKHVWXG\
1RWLILFDWLRQRIDSDWLHQW¶VGLVFRQWLQXDWLRQRI
VWXG\SDUWLFLSDWLRQDQGWKHUHDVRQIRU
GLVFRQWLQXDWLRQZLOOEHPDGHWR&52DQGVWXG\
6SRQVRUDQGZLOOEHFOHDUO\GRFXPHQWHGRQWKH
H&5)
6HFWLRQ
6SRQVRU
3KDUPDFRYLJLODQFH
ZLOODVVHVVIRU
H[SHFWHGQHVV

7KHH[SHFWHGQHVVRIDQ$(VKRXOGEHGHWHUPLQHG
EDVHGXSRQH[LVWLQJVDIHW\LQIRUPDWLRQDERXWWKH
VWXG\GUXJXVLQJWKHVHH[SODQDWLRQV
• 8QH[SHFWHGDQ$(WKDWLVQRWOLVWHGLQWKH
,%RULVQRWOLVWHGDWWKHVSHFLILFLW\RU
VHYHULW\WKDWKDVEHHQREVHUYHG
• ([SHFWHGDQ$(WKDWLVOLVWHGLQWKH,%DW
WKHVSHFLILFLW\DQGVHYHULW\WKDWKDVEHHQ
REVHUYHG
• 1RWDSSOLFDEOH$Q$(XQUHODWHGWRWKH
VWXG\GUXJ
$(VWKDWDUHPHQWLRQHGLQWKH,%DVRFFXUULQJZLWK
DFODVVRIGUXJVRUDVDQWLFLSDWHGIURPWKH
SKDUPDFRORJLFDOSURSHUWLHVRIWKHGUXJEXWDUHQRW
VSHFLILFDOO\PHQWLRQHGDVRFFXUULQJZLWKWKHWKH
SDUWLFXODUGUXJXQGHULQYHVWLJDWLRQDUHWREH
FRQVLGHUHGXQH[SHFWHG
7KHH[SHFWHGQHVVRIDQ$(VKRXOGEHGHWHUPLQHG
EDVHGXSRQH[LVWLQJVDIHW\LQIRUPDWLRQDERXWWKH
VWXG\GUXJXVLQJWKHVHH[SODQDWLRQV
• 8QH[SHFWHGDQ$(WKDWLVQRWOLVWHGLQ
WKH,%RULVQRWOLVWHGDWWKHVSHFLILFLW\RU
VHYHULW\WKDWKDVEHHQREVHUYHG
• ([SHFWHGDQ$(WKDWLVOLVWHGLQWKH,%DW
WKHVSHFLILFLW\DQGVHYHULW\WKDWKDVEHHQ
REVHUYHG
• 1RWDSSOLFDEOH$Q$(XQUHODWHGWRWKH
VWXG\GUXJ
$(V WKDW DUH PHQWLRQHG LQ WKH ,% DV RFFXUULQJ
ZLWK D FODVV RI GUXJV RU DV DQWLFLSDWHG IURP WKH
SKDUPDFRORJLFDO SURSHUWLHV RI WKH GUXJ EXW DUH
QRW VSHFLILFDOO\ PHQWLRQHG DV RFFXUULQJ ZLWK
WKHWKH SDUWLFXODU GUXJ XQGHU LQYHVWLJDWLRQ DUH WR
EHFRQVLGHUHGXQH[SHFWHG
6HFWLRQ
3DUDJUDSK
$GPLQLVWUDWLYH
XSGDWH
,IWKH,QYHVWLJDWRUEHFRPHVDZDUHRIDQ\QHZ
LQIRUPDWLRQUHJDUGLQJDQ6$(LHUHVROXWLRQ
,IWKH,QYHVWLJDWRUEHFRPHVDZDUHRIDQ\QHZ
LQIRUPDWLRQUHJDUGLQJDQ6$(LHUHVROXWLRQ


RTA 408 Ophthalmic Suspension 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 71 of 77 
change in condition, or new treatment), a new 
SAE/Unanticipated Report Form must be 
completed and faxed to CRO within 24 hours of 
the site’s awareness of the event. 
change in condition, or new treatment), a new 
SAE/Unanticipated Report Form must be 
completed and faxed to the Sponsor or designee 
CRO within 24 hours of the site’s awareness of 
the event. 
Section 10.6 
Administrative 
update 
If in addition to a statistically significant test of the 
difference in the proportion of study eyes with 
absence of anterior chamber cells at Visit 5 (Day 
15) in favor of the 1.0% concentration of RTA 408 
Ophthalmic Suspension, the test of the difference 
in the proportion of study eyes with absence of 
ocular pain at Visit 3 (Day 4) is statistically 
significant in favor of the 1.0% RTA 408 
Ophthalmic Suspension, then the 1.0% 
concentration of RTA 408 Ophthalmic Suspension 
will be declared to be superior to placebo in both 
the proportion of study eyes with absence of 
anterior chamber cells at Visit 5 (Day 15) and the 
proportion of study eyes with absence of ocular 
pain at Visit 3 (Day 4).   
OR 
If in addition to a statistically significant test of the 
difference in the proportion of study eyes with 
absence of anterior chamber cells at Visit 5 (Day 
15) in favor of the 0.5% concentration of RTA 408 
Ophthalmic Suspension, the test of the difference 
in the proportion of study eyes with absence of 
ocular pain at Visit 3 (Day 4) is statistically 
significant in favor of the 0.5% RTA 408 
Ophthalmic Suspension, then the 0.5% 
concentration of RTA 408 Ophthalmic Suspension 
will be declared to be superior to placebo in both 
If in addition to a statistically significant test of 
the difference in the proportion of study eyes with 
absence of anterior chamber cells at Visit 5 (Day 
15) in favor of the 1.0% concentration of RTA 
408 Ophthalmic Suspension, the test of the 
difference in the proportion of study eyes with 
absence of ocular pain at Visit 3 (Day 4) is 
statistically significant in favor of the 1.0% RTA 
408 Ophthalmic Suspension, then the 1.0% 
concentration of RTA 408 Ophthalmic 
Suspension will be declared to be superior to 
placebo in both the proportion of study eyes with 
absence of anterior chamber cells at Visit 5 (Day 
15) and the proportion of study eyes with absence 
of ocular pain at Visit 3 (Day 4).   
OR 
If in addition to a statistically significant test of 
the difference in the proportion of study eyes 
with absence of anterior chamber cells at Visit 5 
(Day 15) in favor of the 0.5% concentration of 
RTA 408 Ophthalmic Suspension, the test of the 
difference in the proportion of study eyes with 
absence of ocular pain at Visit 3 (Day 4) is 
statistically significant in favor of the 0.5% RTA 
408 Ophthalmic Suspension, then the 0.5% 
concentration of RTA 408 Ophthalmic 
Suspension will be declared to be superior to 


RTA 408 Ophthalmic Suspension 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 72 of 77 
the proportion of study eyes with absence of 
anterior chamber cells at Visit 5 (Day 15) and the 
proportion of study eyes with absence of ocular 
pain at Visit 3 (Day 4).   
placebo in both the proportion of study eyes with 
absence of anterior chamber cells at Visit 5 (Day 
15) and the proportion of study eyes with absence 
of ocular pain at Visit 3 (Day 4).   
Section 10.10 
Administrative 
update 
If in addition to a statistically significant test of the 
difference in the proportion of study eyes with 
absence of anterior chamber cells at Visit 5 (Day 
15) in favor of the 1.0% concentration of RTA 408 
Ophthalmic Suspension, the test of the difference 
in the proportion of study eyes with absence of 
ocular pain at Visit 3 (Day 4) is statistically 
significant in favor of the 1.0% RTA 408 
Ophthalmic Suspension, then the 1.0% 
concentration of RTA 408 Ophthalmic Suspension 
will be declared to be superior to placebo in both 
the proportion of study eyes with absence of 
anterior chamber cells at Visit 5 (Day 15) and the 
proportion of study eyes with absence of ocular 
pain at Visit 3 (Day 4).   
OR 
If in addition to a statistically significant test of the 
difference in the proportion of study eyes with 
absence of anterior chamber cells at Visit 5 (Day 
15) in favor of the 0.5% concentration of RTA 408 
Ophthalmic Suspension, the test of the difference 
in the proportion of study eyes with absence of 
ocular pain at Visit 3 (Day 4) is statistically 
significant in favor of the 0.5% RTA 408 
Ophthalmic Suspension, then the 0.5% 
concentration of RTA 408 Ophthalmic Suspension 
will be declared to be superior to placebo in both 
the proportion of study eyes with absence of 
If in addition to a statistically significant test of 
the difference in the proportion of study eyes with 
absence of anterior chamber cells at Visit 5 (Day 
15) in favor of the 1.0% concentration of RTA 
408 Ophthalmic Suspension, the test of the 
difference in the proportion of study eyes with 
absence of ocular pain at Visit 3 (Day 4) is 
statistically significant in favor of the 1.0% RTA 
408 Ophthalmic Suspension, then the 1.0% 
concentration of RTA 408 Ophthalmic 
Suspension will be declared to be superior to 
placebo in both the proportion of study eyes with 
absence of anterior chamber cells at Visit 5 (Day 
15) and the proportion of study eyes with absence 
of ocular pain at Visit 3 (Day 4).   
OR 
If in addition to a statistically significant test of 
the difference in the proportion of study eyes with 
absence of anterior chamber cells at Visit 5 (Day 
15) in favor of the 0.5% concentration of RTA 
408 Ophthalmic Suspension, the test of the 
difference in the proportion of study eyes with 
absence of ocular pain at Visit 3 (Day 4) is 
statistically significant in favor of the 0.5% RTA 
408 Ophthalmic Suspension, then the 0.5% 
concentration of RTA 408 Ophthalmic 
Suspension will be declared to be superior to 
placebo in both the proportion of study eyes with 


RTA 408 Ophthalmic Suspension 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 73 of 77 
anterior chamber cells at Visit 5 (Day 15) and the 
proportion of study eyes with absence of ocular 
pain at Visit 3 (Day 4).   
If in addition to a statistically significant test of the 
difference in the proportion of study eyes with 
absence of anterior chamber cells at Visit 5 (Day 
15) in favor of the 1.0% concentration of RTA 408 
Ophthalmic Suspension, the anterior chamber cells 
at Visit 5 (Day 15) is statistically significant in 
favor of the 0.5% concentration of RTA 408 
Ophthalmic Suspension, then both concentrations 
of RTA 408 Ophthalmic Suspension will be 
declared to be superior to placebo in the proportion 
of study eyes with absence of anterior chamber 
cells at Visit 5 (Day 15). 
Finally, if a statistically significant test of the 
difference in the proportion of study eyes with 
absence of anterior chamber cells at Visit 5 (Day 
15) in favor of the 0.5% concentration of RTA 408 
Ophthalmic Suspension, the test of the difference 
in the proportion of study eyes with absence of 
ocular pain at Visit 3 (Day 4) is statistically 
significant in favor of the 0.5% RTA 408 
Ophthalmic Suspension, then the 0.5% 
concentration of RTA 408 Ophthalmic Suspension 
will be declared to be superior to placebo in both 
the proportion of study eyes with absence of 
anterior chamber cells at Visit 5 (Day 15) and the 
proportion of study eyes with absence of ocular 
pain at Visit 3 (Day 4).   
absence of anterior chamber cells at Visit 5 (Day 
15) and the proportion of study eyes with absence 
of ocular pain at Visit 3 (Day 4).   
If in addition to a statistically significant test of 
the difference in the proportion of study eyes with 
absence of anterior chamber cells at Visit 5 (Day 
15) in favor of the 1.0% concentration of RTA 
408 Ophthalmic Suspension, the anterior chamber 
cells at Visit 5 (Day 15) is statistically significant 
in favor of the 0.5% concentration of RTA 408 
Ophthalmic Suspension, then both concentrations 
of RTA 408 Ophthalmic Suspension will be 
declared to be superior to placebo in the 
proportion of study eyes with absence of anterior 
chamber cells at Visit 5 (Day 15). 
Finally, if a statistically significant test of the 
difference in the proportion of study eyes with 
absence of anterior chamber cells at Visit 5 (Day 
15) in favor of the 0.5% concentration of RTA 
408 Ophthalmic Suspension, the test of the 
difference in the proportion of study eyes with 
absence of ocular pain at Visit 3 (Day 4) is 
statistically significant in favor of the 0.5% RTA 
408 Ophthalmic Suspension, then the 0.5% 
concentration of RTA 408 Ophthalmic 
Suspension will be declared to be superior to 
placebo in both the proportion of study eyes with 
absence of anterior chamber cells at Visit 5 (Day 
15) and the proportion of study eyes with absence 
of ocular pain at Visit 3 (Day 4).   
Section 10.11 
Administrative 
update 
The secondary efficacy variables will be 
summarized and analyzed at Days 4, 8, and 21 for 
The secondary efficacy variables will be 
summarized and analyzed at Days 4, 8, and 21 for 


RTA 408 Ophthalmic Suspension 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 74 of 77 
absence of anterior chamber cells and at Days 8, 15 
and 21 for absence of ocular pain, similarly to the 
primary efficacy summaries and analyses. 
Additionally, anterior chamber cell grade and 
ocular pain score at each visit and change from 
baseline will be summarized using continuous and 
discrete summary statistics. 
Absence of anterior chamber flare and anterior 
chamber flare grade and the sum of anterior 
chamber cell and flare grade, including absence of 
both anterior chamber cell and flare will be 
summarized and analyzed similarly to anterior 
chamber cells and pain at each visit. 
absence of anterior chamber cells and at Days 8, 
15 and 21 for absence of ocular pain, similarly to 
the primary efficacy summaries and analyses. 
Additionally, anterior chamber cell grade and 
ocular pain score at each visit and change from 
baseline will be summarized using continuous 
and discrete summary statistics. 
Absence of anterior chamber flare and anterior 
chamber flare grade and the sum of anterior 
chamber cell and flare grade, including absence 
of both anterior chamber cell and flare will be 
summarized and analyzed similarly to anterior 
chamber cells and pain at each visit. 
Appendix 1 
Ocular Pain 
Grading Scale 
(Study Eye) 
Administrative 
update  
Ocular Pain will be assessed by the patient at 
screening and at each follow-up visit, utilizing a 
Numerical Pain Rating Scale1 graded from 0 to 10. 
Patients 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”. 
*At the screening assessment visit, the patient will 
be asked about the eye scheduled for surgery. 
Ocular Pain will be assessed by the patient at 
screening and at each follow-up visit, utilizing a 
Numerical Pain Rating Scale1 graded from 0 to 
10. Patients will assess the level of pain they are 
experiencing in the study eye at the time of the 
assessment. Patients may only select whole 
numbers on the scale.  
The examiner will ask the patient the following 
question related to Figure 1: 
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 whole 
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”. 


RTA 408 Ophthalmic Suspension 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 75 of 77 
1 Reference 4. Numeric Pain Rating Scale (NPRS). 
National Institutes of Health (NIH), Warren Grant 
Magnuson Clinical Center. Pain Intensity 
Instruments. July 2003. 
Figure 1 
Ocular Pain Grading Scale 
… 
*At the screening assessment visit, the patient 
will be asked about the eye scheduled for surgery. 
1 Reference 4. National Institutes of 
Health (NIH). Numeric Pain Rating Scale 
(NPRS). National Institutes of Health 
(NIH),. Warren Grant Magnuson Clinical 
Center. Pain Intensity Instruments. July 
2003. 
Appendix 2 
Footnote #4 
Administrative 
update 
In case of early termination or if patient did not 
return study drug at prior to Visit 5. 
In case of early termination or if patient did not 
return study drug at prior to Visit 5. 
Appendix 3 
Rationale for 
Amendment 1 and 
the Table of 
Changes was 
inserted 
Not applicable. 
[Rationale for amendment 1 and the table of 
changes was inserted] 
Appendix 4 
Administrative 
update 
Protocol Number: 408-C-1307 
Protocol Number: 408-C-1307 Amendment 1 
Appendix 4 
Administrative 
update 
Final Date: 21-Nov-2013 
Final Date: 10-Feb-2014 
Appendix 5 
Administrative 
update 
Protocol Number: 408-C-1307 
Protocol Number: 408-C-1307 Amendment 1 
Appendix 5 
Administrative 
update 
Final Date: 21-Nov-2013 
Final Date: 10-Feb-2014 




RTA 408 Ophthalmic Suspension 
 
 
 
 
Reata Pharmaceuticals 
Clinical Trial Protocol: 408-C-1307 
 
 
 
 
Amendment 1: 10-Feb-2014 
 
Confidential 
 
Page 77 of 77 
APPENDIX 5:  INVESTIGATOR’S SIGNATURE 
Protocol Title: 
A Multicenter, Randomized, Dose-Ranging, Double-Masked, 
Placebo Controlled Phase 2 Study Evaluating the Safety and 
Efficacy of RTA 408 Ophthalmic Suspension  for the Treatment 
of Ocular Inflammation and Pain following Ocular Surgery 
Protocol Number: 
408-C-1307 Amendment 1 
Final Date: 
10-Feb-2014 
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 CRO and the Sponsor 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:  
 
<enter name and credentials> 
<enter title> 
<enter affiliation> 
<enter address> 
<enter phone number> 

SAP_001.pdf: