Clinical trial NCT03012165
Conditions: Conjunctivitis, Allergic
Keywords: ADX-102 Allergic Conjunctivitis
Sponsor: Aldeyra Therapeutics, Inc.
Start date: 2016-12-01; Completion date: 2017-05-01
Enrollment: 154 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
A Multi-Center, Double-Masked, Randomized, Vehicle-Controlled, Phase 2b Evaluation of the Onset and Duration of ADX-102 Ophthalmic Drops (0.5% and 0.1%) Compared to Vehicle of ADX-102 Ophthalmic Drops in the Conjunctival Allergen Challenge (Ora-CAC®) Model of Acute Allergic Conjunctivitis.

Detailed description:

Arms: arm 1: ADX-102 Ophthalmic Drops (0.5%) administered twice in two weeks. arm 2: ADX-102 Ophthalmic Drops (0.1%) administered twice in two weeks. arm 3: Vehicle of ADX-102 Ophthalmic Drops
Interventions: intervention 1: ADX-102 Ophthalmic Drops (0.5%) intervention 2: ADX-102 Ophthalmic Drops (0.1%) intervention 3: Vehicle of ADX-102 Ophthalmic Drops
Intervention descriptions: intervention 1: ADX-102 Ophthalmic Drops (0.5%) administered twice in two weeks. intervention 2: ADX-102 Ophthalmic Drops (0.1%) administered twice in two weeks. intervention 3: Vehicle of ADX-102 Ophthalmic Drops administered twice in two weeks.

Protocol documents:
Prot_000.pdf: 
ADX-102 Ophthalmic Drops (0.5% and 0.1%) 
 Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-AC-004 
Final 1.0, 19 October 2016 
 
CONFIDENTIAL 
Page 1 of 56 
1 CLINICAL TRIAL PROTOCOL: ADX-102-AC-004 
Protocol Title: 
A Multi-Center, Double-Masked, Randomized, 
Vehicle-Controlled, Phase 2b Evaluation of the Onset 
and Duration of ADX-102 Ophthalmic Drops (0.5% 
and 0.1%) Compared to Vehicle of ADX-102 
Ophthalmic Drops in the Conjunctival Allergen 
Challenge (Ora-CAC®) Model of Acute Allergic 
Conjunctivitis  
Protocol Number: 
ADX-102-AC-004 
Name of Test Drug 
/Investigational Product: 
ADX-102 Ophthalmic Drops (0.5% and 0.1%) 
 
 
Indication Studied: 
Acute allergic conjunctivitis 
Development Phase: 
2b 
Brief Description: 
Multi-center, double-masked, randomized, vehicle-
controlled, phase 2b CAC study. 
Name of Sponsor: 
 
Aldeyra Therapeutics, Inc. 
131 Hartwell Ave. 
Lexington, MA 02421 
Contract Research 
Organization: 
 
Ora, Inc. 
300 Brickstone Square, Third Floor 
Andover, MA 01810 
IRB/IEC: 
 
 
 
 
 
Date 
Original Protocol: 
19 October 2016 
Statement of Compliance with Good Clinical Practice 
This study will be performed in compliance with the ethical principles of the Declaration of Helsinki and the 
International Conference on Harmonization (ICH) Harmonized Tripartite Guideline for Good Clinical Practice (GCP). 
Confidentiality Statement 
This protocol is confidential and the information available within it may not be reproduced or otherwise disseminated. 


ADX-102 Ophthalmic Drops (0.5% and 0.1%) 
 Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-AC-004 
Final 1.0, 19 October 2016 
 
CONFIDENTIAL 
Page 2 of 56 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 














ADX-102 Ophthalmic Drops (0.5% and 0.1%) 
 Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-AC-004 
Final 1.0, 19 October 2016 
 
CONFIDENTIAL 
Page 9 of 56 
TABLE OF CONTENTS 
1 CLINICAL TRIAL PROTOCOL: ADX-102-AC-004 .............................................1 
2 SYNOPSIS ....................................................................................................................3 
TABLE OF CONTENTS ..................................................................................................9 
List of Abbreviations .......................................................................................................12 
3 INTRODUCTION .......................................................................................................14 
4 STUDY OBJECTIVES..............................................................................................15 
5 CLINICAL HYPOTHESES ......................................................................................15 
6 OVERALL STUDY DESIGN ...................................................................................15 
7 STUDY POPULATION .............................................................................................15 
7.1 
Number of Subjects (approximate) ............................................................15 
7.2 
Study Population Characteristics ...............................................................16 
7.3 
inclusion Criteria .............................................................................................16 
7.4 
Exclusion Criteria ............................................................................................17 
7.5 
Withdrawal Criteria (if applicable)...............................................................18 
8 STUDY MEASURES ................................................................................................19 
8.1 
Efficacy Measures ...........................................................................................19 
8.1.1 Primary Efficacy Measure(s) ..........................................................................19 
 
8.1.3 Criteria for Effectiveness ................................................................................19 
8.2 
Safety Measures ..............................................................................................19 
9 STUDY MATERIALS................................................................................................20 
9.1 
Study Treatment(s) .........................................................................................20 
9.1.1 Study Treatment(s)/ Formulation(s) ...............................................................20 
9.1.2 Instructions for Use and Administration ........................................................20 
9.2 
Other Study Supplies .....................................................................................20 
10 STUDY METHODS AND PROCEDURES ............................................................21 
10.1 Subject Entry Procedures .............................................................................21 
10.1.1 Overview ........................................................................................................21 
10.1.2 Informed Consent ...........................................................................................21 
10.1.3 Washout Intervals ...........................................................................................21 
10.1.4 Procedures for Final Study Entry ...................................................................22 
10.1.5 Methods for Assignment to Treatment Groups: .............................................22 
10.2 Concurrent Therapies ....................................................................................22 
10.2.1 Prohibited Medications/Treatments ...............................................................23 
10.2.2 Escape Medications ........................................................................................23 
10.2.3 Special Diet or Activities ...............................................................................23 
10.3 Examination Procedures ...............................................................................23 
10.3.1 Procedures to be Performed at Each Study Visit with Regard to Study 
Objective(s) ....................................................................................................23 
10.4 Schedule of Visits, Measurements and Dosing ......................................28 
10.4.1 Scheduled Visits .............................................................................................28 
10.4.2 Unscheduled Visits .........................................................................................29 


ADX-102 Ophthalmic Drops (0.5% and 0.1%) 
 Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-AC-004 
Final 1.0, 19 October 2016 
 
CONFIDENTIAL 
Page 10 of 56 
10.5 Compliance with Protocol .............................................................................29 
10.6 Subject Disposition.........................................................................................29 
10.6.1 Completed Subjects ........................................................................................29 
10.6.2 Discontinued Subjects ....................................................................................29 
10.7 Study Termination ...........................................................................................30 
10.8 STUDY Duration ...............................................................................................30 
10.9 Monitoring and Quality Assurance .............................................................30 
11 ADVERSE EVENTS .................................................................................................30 
11.1.1 Severity ...........................................................................................................31 
11.1.2 Relationship to Investigational Product .........................................................31 
11.1.3 Expectedness ..................................................................................................32 
11.2 Serious Adverse Events ................................................................................32 
11.3 Procedures for Reporting Adverse Events ..............................................33 
11.3.1 Reporting a Suspected Unexpected Adverse Reaction ..................................33 
11.3.2 Reporting a Serious Adverse Event ................................................................34 
11.4 Procedures for Unmasking (if applicable) ................................................34 
11.5 Type and Duration of the Follow-up of Subjects after Adverse 
Events .................................................................................................................34 
12 STATISTICAL HYPOTHESES AND METHODS OF ANALYSES ...................35 
12.1 Study Populations ...........................................................................................35 
12.1.1 Intent-to-Treat Population ..............................................................................35 
12.1.2 Per-Protocol Population .................................................................................35 
12.1.3 Safety Population ...........................................................................................35 
12.2 General Imputation Methods ........................................................................35 
12.3 Primary Efficacy Variables ............................................................................36 
12.4 Criteria for Efficacy .........................................................................................36 
 
12.6 Statistical Hypotheses ...................................................................................37 
12.7 Sample Size ......................................................................................................37 
12.8 Demographic and Baseline Medical History ............................................37 
12.9 Primary Efficacy Analyses ............................................................................37 
 
12.11 Adjustment for Multiplicity ...........................................................................38 
12.12 Safety Analysis ................................................................................................38 
12.13 Interim Analysis ...............................................................................................39 
13 COMPLIANCE WITH GOOD CLINICAL PRACTICES, ETHICAL 
CONSIDERATIONS, AND ADMINISTRATIVE ISSUES....................................39 
13.1 Protection of Human Subjects .....................................................................39 
13.1.1 Subject Informed Consent ..............................................................................39 
13.1.2 Institutional Review Board (IRB) Approval ..................................................40 
13.2 Ethical Conduct of the Study .......................................................................40 
13.3 Subject Confidentiality ..................................................................................40 
13.4 Documentation .................................................................................................40 
13.4.1 Retention of Documentation ..........................................................................40 


ADX-102 Ophthalmic Drops (0.5% and 0.1%) 
 Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-AC-004 
Final 1.0, 19 October 2016 
 
CONFIDENTIAL 
Page 11 of 56 
13.5 Labeling, Packaging, Storage, Accountability, and Return or 
Disposal of Investigational Product ...........................................................41 
13.5.1 Labeling/Packaging ........................................................................................41 
13.5.2 Storage of Investigational Product .................................................................41 
13.5.3 Accountability of Investigational Product ......................................................42 
13.5.4 Final accountability and Disposal of Investigational Product ........................42 
13.6 Recording of Data on Source Documents and Case Reports Forms 
(CRFs) .................................................................................................................42 
13.7 Handling of Biological Specimens .............................................................42 
13.8 Publications ......................................................................................................42 
14 REFERENCES ..........................................................................................................43 
Appendix 1:  Schedule of Visits and Measurements ...........................................44 
Appendix 2: Examination Procedures, Tests, Equipment, and Techniques 45 
Appendix 3:  Investigational Product Composition/ Design .............................50 
Appendix 4:  Handling of Biological Specimens ..................................................52 
Appendix 5:  Protocol Amendment Summary .......................................................53 
Appendix 6:  Ora Approvals .......................................................................................54 
Appendix 6:  Sponsor (Aldeyra) Approvals ...........................................................55 
Appendix 7:  Investigator’s Signature .....................................................................56 


ADX-102 Ophthalmic Drops (0.5% and 0.1%) 
 Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-AC-004 
Final 1.0, 19 October 2016 
 
Confidential 
Page 12 of 56 
LIST OF ABBREVIATIONS 
AC 
allergic conjunctivitis  
ADE 
adverse device effect 
AE 
adverse event 
ANCOVA 
analysis of covariance  
BOCF 
baseline observation carried forward 
CAC 
conjunctival allergen challenge 
CFR 
Code of Federal Regulations 
CI 
confidence interval  
CRF 
case report form 
CRO 
contract research organization 
DHHS 
Department of Health and Human Services 
ECG 
electrocardiogram 
ERC 
ethical review committee 
ETDRS 
Early Treatment of Diabetic Retinopathy Study 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIPAA 
Health Information Portability and Accountability Act 
IB 
investigators’ brochure 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation 
IgE 
immunoglobulin-E 
IND 
investigational new drug application 
IOP 
intraocular pressure 
IP 
investigational product 
IRB 
institutional/independent review board 
ITT 
intent to treat 
LASIK 
laser in situ keratomileusis 
LOCF 
last observation carried forward 
logMAR 
logarithm of the minimum angle of resolution 


ADX-102 Ophthalmic Drops (0.5% and 0.1%) 
 Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-AC-004 
Final 1.0, 19 October 2016 
 
Confidential 
Page 13 of 56 
LS 
least squares 
MCMC 
Markov Chain Monte Carlo 
MedDRA 
Medical Dictionary for Regulatory Activities 
MI 
multiple imputation  
mmHg 
millimeters of mercury  
NCS 
not clinically significant 
NDA 
new drug application 
NSAID  
nonsteroidal anti-inflammatory drug 
OD 
right eye 
Ora-CAC® 
conjunctival allergen challenge 
OS 
left eye 
OU 
both eyes 
OTC 
over the counter 
PHI 
protected health information 
PP 
per protocol 
ROPI 
Report of Prior Investigations  
SAE 
serious adverse event 
SAP 
statistical analysis plan 
TEAE 
treatment emergent adverse event 
VA 
visual acuity 
 
 


ADX-102 Ophthalmic Drops (0.5% and 0.1%) 
 Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-AC-004 
Final 1.0, 19 October 2016 
 
Confidential 
Page 14 of 56 
3 INTRODUCTION 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 


ADX-102 Ophthalmic Drops (0.5% and 0.1%) 
 Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-AC-004 
Final 1.0, 19 October 2016 
 
Confidential 
Page 15 of 56 
 
 
 
 
 
4 STUDY OBJECTIVES 
To evaluate the efficacy of ADX-102 ophthalmic drops (0.5% and 0.1%) compared to 
vehicle of ADX-102 ophthalmic drops for the treatment of the signs and symptoms of 
acute allergic conjunctivitis.  
5 CLINICAL HYPOTHESES 
It is hypothesized that at least one concentration of ADX-102 ophthalmic drops will be 
more effective than vehicle of ADX-102 in the treatment of the signs and symptoms of 
acute allergic conjunctivitis.  
6 OVERALL STUDY DESIGN 
This is a multi-center, double-masked, randomized, vehicle-controlled, phase 2b study 
evaluating the efficacy of ADX-102 ophthalmic drops (0.5% and 0.1%) compared to 
vehicle of ADX-102 ophthalmic drops for the treatment of the signs and symptoms of 
acute allergic conjunctivitis.  
The trial will comprise of 4 office visits over a period of approximately 5 weeks.  Visits 1 
and 2 will be used to select a subject population that responds reproducibly to two CACs 
administered approximately 7 days apart.  Subjects who meet the entry criteria for itching 
and redness response to CAC at Visits 1 and 2 will be randomized (1:1:1) at Visit 3 (Day 
1, Enrollment/Randomization) to receive either ADX-102 ophthalmic drops (0.5%), 
ADX-102 ophthalmic drops (0.1%), or vehicle of ADX-102 ophthalmic drops bilaterally.  
Subjects will undergo the 1-hour (+5 minutes) duration of action CAC from the time of 
their instillation. Subjects will return approximately 14 days later for Visit 4 (Day 15± 3, 
10-Minutes Onset of Action CAC), at which time they will be treated with the same 
treatment they received at Visit 3 and challenged approximately 10 minutes after dosing.  
At Visit 4, final exit procedures will also be conducted and subjects will exit the study.   
7 STUDY POPULATION 
 NUMBER OF SUBJECTS (APPROXIMATE) 
7.1
Approximately 375 subjects will be screened in order to enroll approximately 150 
subjects at up to 5 sites.  




ADX-102 Ophthalmic Drops (0.5% and 0.1%) 
 Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-AC-004 
Final 1.0, 19 October 2016 
 
Confidential 
Page 17 of 56 
 EXCLUSION CRITERIA 
7.4
Each subject may not: 
1) have known contraindications or sensitivities to the use of the investigational 
product or any of its components;  
2) have any ocular condition that, in the opinion of the investigator, could affect the 
subject’s safety or trial parameters (including but not limited to narrow angle 
glaucoma, clinically significant blepharitis, follicular conjunctivitis, iritis, 
pterygium or a diagnosis of dry eye);   
3) have had ocular surgical intervention within three (3) months prior to Visit 1 or 
during the study and/or a history of refractive surgery within the past six (6) 
months; 
4) have a known history of retinal detachment, diabetic retinopathy, or active retinal 
disease; 
5) have the presence of an active ocular infection (bacterial, viral or fungal) or positive 
history of an ocular herpetic infection at any visit; 
6) use any of the following disallowed medications during the period indicated prior 
to Visit 1 and during the study:     
72 hours 
• systemic or ocular H1 antihistamine, H1 antihistamine/mast cell stabilizers, H1 
antihistamine- vasoconstrictor drug combinations 
7 days 
• decongestants 
• monoamine oxidase inhibitors 
• all other topical ophthalmic preparations (including artificial tears) 
• lid scrubs 
• topical prostaglandins or prostaglandin derivatives 
• ocular, topical, or systemic nonsteroidal anti-inflammatory drugs (NSAIDs) 
14 days 
• inhaled, ocular, topical, or systemic corticosteroids or mast cell stabilizers 
45 days 
• depo-corticosteroids 
2 months 
• immunotherapeutic agents: treatment must have been maintained steadily for at 
least 2 months; neither the immunotherapeutic agent nor its dosage may change 
during the clinical trial. 
Note: Currently marketed over-the-counter anti-allergy eye drops (i.e. anti-histamine/ vasoconstrictor 
combination products such as Visine®-A®) may be administered by trained study personnel to subjects 
at the end of Visits 1, 2, 3, and 4, after all evaluations are completed. 
7) have any significant illness (e.g. any autoimmune disease requiring therapy, severe 
cardiovascular disease [including arrhythmias] the investigator feels could be 
expected to interfere with the subject’s health or with the study parameters and/or put 




ADX-102 Ophthalmic Drops (0.5% and 0.1%) 
 Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-AC-004 
Final 1.0, 19 October 2016 
 
Confidential 
Page 19 of 56 
8 STUDY MEASURES 
 EFFICACY MEASURES  
8.1
 Primary Efficacy Measure(s) 
8.1.1
• Ocular itching evaluated by the subject at 10(±1), 15(±1), 20(±1) minutes post-
CAC at Visits 3 and 4 (0-4 scale, allowing half unit increments) 
 Criteria for Effectiveness 
8.1.3
To demonstrate the clinical effectiveness for ocular itching, ADX-102 Ophthalmic Drops 
will need to show clinical superiority over vehicle by at least 0.5 units of a 5 point scale 
for the 10(±1), 15(±1) and 20(±1) minutes post-CAC time points within a visit, and at 
least 1 unit for the majority
 of the same three post-CAC time points within a visit for 
each treatment comparison.  
 
 SAFETY MEASURES 
8.2
• Adverse Events (reported, elicited and observed) 
• Visual Acuity at Distance Utilizing an ETDRS chart  
• Slit-lamp Biomicroscopy  
• Intraocular Pressure  
• Dilated Fundoscopy 
 




ADX-102 Ophthalmic Drops (0.5% and 0.1%) 
 Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-AC-004 
Final 1.0, 19 October 2016 
 
Confidential 
Page 21 of 56 
10 STUDY METHODS AND PROCEDURES 
 SUBJECT ENTRY PROCEDURES 
10.1
 Overview 
10.1.1
Subjects as defined by the criteria in section 7.2, 7.3, and 7.4 will be considered for entry 
into this study. 
 Informed Consent 
10.1.2
Prior to a subject’s participation in the trial (i.e., changes in a subject’s medical treatment 
and/or study related procedures), the study will be discussed with each subject, and 
subjects wishing to participate must give written informed consent using an informed 
consent form (ICF).  The ICF must be the most recent version that has received 
approval/favorable review by a properly constituted Institutional Review Board. Failure 
to obtain a signed ICF renders the subject ineligible for the study.   
Informed consent may be obtained within 30 days prior to Visit 1; however, informed 
consent must be obtained prior to Visit 1 if any of the following criteria are determined 
during the telephone screening process: 
• Washout of certain medications is necessary 
• Sufficient time of discontinuation of contact lens wear is necessary 
• Post-operative period 
Medical/medication history, demographics, skin test and inclusion/exclusion review may 
be performed at the time of informed consent signing prior to Visit 1, but must be 
confirmed at Visit 1 (with the exception of demographics and skin test).   
 Washout Intervals 
10.1.3
Prior to performing other study procedures at Visit 1, study staff will confirm that the 
subject has not used any of the following restricted products: 
     
72 hours 
• Contact lenses 
• systemic or ocular H1 antihistamine, H1 antihistamine/mast cell stabilizers, 
H1 antihistamine- vasoconstrictor drug combinations 
7 days 
• decongestants 
• monoamine oxidase inhibitors 
• all other topical ophthalmic preparations (including artificial tears) 
• lid scrubs 
• topical prostaglandins or prostaglandin derivatives 
• ocular, topical, or systemic nonsteroidal anti-inflammatory drugs (NSAIDs) 
14 days 
• inhaled, ocular, topical, or systemic corticosteroids or mast cell stabilizers 


ADX-102 Ophthalmic Drops (0.5% and 0.1%) 
 Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-AC-004 
Final 1.0, 19 October 2016 
 
Confidential 
Page 22 of 56 
45 days 
• depo-corticosteroids 
2 months 
• immunotherapeutic agents: treatment must have been maintained steadily 
for at least 2 months; neither the immunotherapeutic agent nor its dosage 
may change during the clinical trial. 
Note: 
Currently 
marketed 
over-the-counter 
anti-allergy 
eye 
drops 
(ie, 
anti-
histamine/vasoconstrictor combination products such as  Visine®-A®) may be administered by 
trained study personnel to subjects at the end of Visits 1, 2, 3, and 4, after all evaluations are 
completed. 
 
 Procedures for Final Study Entry 
10.1.4
Subjects must continue to meet all of the inclusion criteria and none of the exclusion 
criteria prior to Visit 3 to be enrolled in the study. 
 Methods for Assignment to Treatment Groups: 
10.1.5
All subjects screened for the study who sign an ICF will be assigned a 3-digit screening 
number that will be entered in the Screening and Enrollment Log.  Screening numbers 
will be assigned in a sequential order beginning with 001.  Randomization will be used to 
avoid bias in the assignment of subjects to treatment and time point, to increase the 
likelihood that known and unknown subject attributes (e.g., demographics and baseline 
characteristics) are evenly balanced across treatment groups and across time points, and 
to enhance the validity of statistical comparisons.  
Once a subject meets all qualification criteria at Visit 3 (Day 1), they will be enrolled and 
randomly assigned to masked treatment using a 1:1:1 (ADX-102 ophthalmic drops 
[0.5%]: ADX-102 ophthalmic drops [0.1%]: vehicle of ADX-102 ophthalmic drops) 
assignment ratio.  Subjects will be assigned the lowest 4-digit randomization number 
available at the Investigative site within the appropriate stratum.  The randomization 
number will be stratified by the average post-CAC itching scores 
 at 
baseline (Visit 2) to ensure balance for the primary endpoint of ocular itching.  No 
randomization numbers will be skipped or omitted.  
 
 CONCURRENT THERAPIES 
10.2
 
 
 
 
 


ADX-102 Ophthalmic Drops (0.5% and 0.1%) 
 Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-AC-004 
Final 1.0, 19 October 2016 
 
Confidential 
Page 23 of 56 
 Prohibited Medications/Treatments 
10.2.1
• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Escape Medications 
10.2.2
 
 
 Special Diet or Activities 
10.2.3
Not Applicable. 
 EXAMINATION PROCEDURES 
10.3
The following procedures will be conducted as listed in Section 10.3.1. 
 Procedures to be Performed at Each Study Visit with Regard to Study 
10.3.1
Objective(s) 
10.3.1.1 
VISIT 1 (Day -21±3): Screening /Titration CAC 
• Informed Consent/HIPAA: Prior to any changes in a subject’s medical treatment 
and/or study visit procedures, the study will be discussed with each subject and 
subjects wishing to participate must give written informed consent and sign a HIPAA 
form. 












ADX-102 Ophthalmic Drops (0.5% and 0.1%) 
 Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-AC-004 
Final 1.0, 19 October 2016 
 
Confidential 
Page 29 of 56 
If a subject is discontinued at a scheduled study visit, the remaining assessments should 
be captured on the Unscheduled Visit/Early Exit Visit pages of the source document and 
corresponding eCRF. 
 Unscheduled Visits 
10.4.2
For Unscheduled Visits, the reason for the visit should be clearly documented on the 
appropriate eCRF, including findings from all evaluations that are completed.  
These visits may be performed to ensure subject safety.  All information gathered at 
unscheduled visits should be recorded on the Unscheduled Visit/Early Exit Visit pages of 
the source document and corresponding eCRF. 
Evaluations that may be conducted at an Unscheduled Visit (as appropriate, depending on 
the reason for the visit), include: 
• Update of Medical/Medication History 
• Urine Pregnancy Test 
• Visual Acuity at Distance Utilizing an ETDRS chart 
• Slit-lamp Biomicroscopy 
• Intraocular Pressure  
• Dilated Fundoscopy  
• Assessment of Adverse Events  
 COMPLIANCE WITH PROTOCOL 
10.5
Site staff will review concomitant medication use at each visit.  
Subjects who are inappropriately enrolled will be discontinued from the study. The 
reason for such discontinuation will be recorded as “protocol violation” in the source 
document and on the appropriate page in the eCRF.  
 SUBJECT DISPOSITION 
10.6
 Completed Subjects 
10.6.1
A completed subject is one who has not been discontinued from the study. 
 Discontinued Subjects 
10.6.2
Subjects may be discontinued prior to their completion of the study due to: 
• adverse events 
• protocol violations 
• lack of efficacy 
• administrative reasons (eg, inability to continue, lost to follow up) 


ADX-102 Ophthalmic Drops (0.5% and 0.1%) 
 Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-AC-004 
Final 1.0, 19 October 2016 
 
Confidential 
Page 30 of 56 
• manifest clinically active signs or symptoms of allergic conjunctivitis 
during the pre-CAC ocular allergic signs & symptoms assessment at 
Visit 4 
• Sponsor termination of study 
• other 
Note: In addition, any subject may be discontinued for any sound medical reason. 
Notification of a subject discontinuation and the reason for discontinuation will be made 
to Ora and/or study Sponsor and will be clearly documented on the eCRF. 
 STUDY TERMINATION 
10.7
The study may be stopped at any time by the investigator, the Sponsor, and/or Ora with 
appropriate notification. 
 STUDY DURATION 
10.8
Four office visits over a period of approximately 5 weeks. 
 MONITORING AND QUALITY ASSURANCE 
10.9
During the course of the study an Ora monitor, or designee, will make routine site visits 
to review protocol compliance, assess study drug accountability, and ensure the study is 
being conducted according to the pertinent regulatory requirements.  The review of the 
subjects’ medical records will be performed in a manner that adequately maintains 
subject confidentiality.  Further details of the study monitoring will be outlined in a 
monitoring plan. 
Regulatory authorities of domestic and foreign agencies, Ora quality assurance and/or its 
designees, as well as the Sponsor, may carry out on-site inspections and/or audits which 
may include source data checks.  Therefore, direct access to the original source data will 
be required for inspections and/or audits.  All inspections and audits will be carried out 
giving consideration to data protection as well as subject confidentiality to the extent that 
local, state, and federal laws apply. 
11 ADVERSE EVENTS 
An AE is defined as any untoward medical occurrence associated with the use of an 
investigational product (IP) in humans, whether or not considered IP-related. An AE can 
be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, 
or disease temporally associated with the use of an IP, without any judgment about 
causality. An AE can arise from any use of the IP (e.g., off-label use, use in combination 
with another drug or medical device) and from any route of administration, formulation, 
or dose, including an overdose. An AE can arise from any delivery, implantation, or use 
of a medical device, including medical device failure, subject characteristics that may 


ADX-102 Ophthalmic Drops (0.5% and 0.1%) 
 Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-AC-004 
Final 1.0, 19 October 2016 
 
Confidential 
Page 31 of 56 
impact medical device performance (e.g., anatomical limitations), and therapeutic 
parameters (e.g., energy applied, sizing, dose release) associated with medical device. 
All AEs spontaneously reported by the subject and/or in response to an open question 
from study personnel or revealed by observation, physical examination or other 
diagnostic procedures will be recorded in the source document and on the appropriate 
pages of the eCRF. Any clinically relevant deterioration in clinical finding is considered 
an AE and must be recorded. When possible, signs and symptoms indicating a common 
underlying pathology should be noted as 1 comprehensive event. Any pre-existing 
medical condition that worsens after administration of study medication will also be 
considered a new adverse event. Study medication includes the drug under evaluation or 
any other medications required by the protocol given during any stage of the study. 
Ocular complaints should not be addressed as AEs unless the complaint is outside the 
normal limits for allergic conjunctivitis symptoms after allergen exposure or is associated 
with clinical sequelae (i.e., adverse slit lamp examination finding). 
Documentation regarding the AE should be made as to the nature, date of onset, end date, 
severity, relationship to IP, action(s) taken, seriousness, and outcome of any sign or 
symptom observed by the physician or reported by the subject upon indirect questioning.  
 Severity 
11.1.1
Severity of an AE is defined as a qualitative assessment of the degree of intensity of an 
AE as determined by the investigator or reported to him/her by the subject.  The 
assessment of severity is made irrespective of relationship to IP or seriousness of the 
event and should be evaluated according to the following scale: 
• 
 
 
 
 
 
 
 
 
 Relationship to Investigational Product 
11.1.2
The relationship of each adverse event to the investigational product should be 
determined by the investigator using these explanations: 
• Suspected:  A reasonable possibility exists that the investigational product caused the 
adverse event. 
• Not Suspected: A reasonable possibility does not exist that the investigational product 
caused the adverse event. 


ADX-102 Ophthalmic Drops (0.5% and 0.1%) 
 Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-AC-004 
Final 1.0, 19 October 2016 
 
Confidential 
Page 32 of 56 
Suspected adverse reaction means any adverse event for which there is a reasonable 
possibility that the investigational product caused the adverse event.  “Reasonable 
possibility” means there is evidence to suggest a causal relationship between the 
investigational product and the adverse event.  Types of evidence that would suggest a 
causal relationship between the investigational product and the adverse event include:  a 
single occurrence of an event that is uncommon and known to be strongly associated with 
investigational product exposure (eg, angioedema, hepatic injury, Stevens-Johnson 
Syndrome); one or more occurrences of an event that is not commonly associated with 
investigational product exposure, but is otherwise uncommon in the population exposed 
to the investigational product (eg, 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 investigational product-treatment group than in a concurrent or 
historical control group. 
 Expectedness 
11.1.3
The expectedness of an AE should be determined based upon existing safety information 
about the IP using these explanations: 
• Unexpected:  an AE that is not listed in the Investigator’s Brochure (IB) or Report of 
Prior Investigations (ROPI) or is not listed at the specificity or severity that has been 
observed. 
• Expected:  an AE that is listed in the IB or ROPI at the specificity and severity that 
has been observed. 
• Not applicable: an AE unrelated to the IP. 
AEs that are mentioned in the IB or ROPI as occurring with a class of products or as 
anticipated from the pharmacological/ mechanical (or other) properties of the product, but 
are not specifically mentioned as occurring with the particular product under 
investigation are to be considered unexpected. 
The investigator should initially classify the expectedness of an AE, but the final 
classification is subject to the Medical Monitor and the Sponsor’s Medical Monitor’s 
determination. 
 SERIOUS ADVERSE EVENTS 
11.2
An AE is considered serious if, in the view of either the investigator or Sponsor/designee, 
it results in any of the following outcomes: 
• Death; 
• A life-threatening AE; 


ADX-102 Ophthalmic Drops (0.5% and 0.1%) 
 Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-AC-004 
Final 1.0, 19 October 2016 
 
Confidential 
Page 33 of 56 
Note:  An AE is considered “life-threatening” if, in the view of either the 
investigator or Sponsor/designee, its occurrence places the subject at immediate 
risk of death.  It does not include an AE that, had it occurred in a more severe 
form, might have caused death. 
• Inpatient hospitalization or prolongation of existing hospitalization; 
Note:  The term “inpatient hospitalization” refers to any inpatient admission (even 
if less than 24 hours).  For chronic or long-term inpatients, inpatient admission 
includes transfer within the hospital to an acute/intensive care inpatient unit.  
Inpatient hospitalization does not include:  emergency room visits; 
outpatient/same-day/ambulatory procedures; observation/short stay units; 
rehabilitation facilities; hospice facilities; nursing homes; or clinical 
research/phase 1 units. 
Note:  The term “prolongation of existing hospitalization” refers to any extension 
of an inpatient hospitalization beyond the stay anticipated or required for the 
reason for the initial admission as determined by the investigator or treating 
physician. 
• A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions; 
Note:  A serious adverse event (SAE) specifically related to visual threat would 
be interpreted as any potential impairment or damage to the subject’s eyes (e.g., 
hemorrhage, retinal detachment, central corneal ulcer or damage to the optic 
nerve). 
• A congenital anomaly/birth defect. 
Important medical events that may not result in death, are life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical 
judgment, they may jeopardize the subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. 
 PROCEDURES FOR REPORTING ADVERSE EVENTS 
11.3
All AEs and their outcomes must be reported to Ora, the study Sponsor/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. 
 Reporting a Suspected Unexpected Adverse Reaction 
11.3.1
All AEs that are ‘suspected’ and ‘unexpected’ are to be reported to Ora, the study 
Sponsor/designee and the IRB/IEC as required by the IRB/IEC, federal, state, or local 
regulations and governing health authorities. 


ADX-102 Ophthalmic Drops (0.5% and 0.1%) 
 Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-AC-004 
Final 1.0, 19 October 2016 
 
Confidential 
Page 34 of 56 
 Reporting a Serious Adverse Event 
11.3.2
To ensure subject safety, all SAEs, regardless of relationship to the IP, must be 
immediately reported.  All information relevant to the SAE must be recorded on the 
appropriate case report form.  The investigator is obligated to pursue and obtain 
information requested by Ora and/or the Sponsor/designee in addition to that information 
reported on the case report form.  All subjects experiencing a SAE must be followed up 
and the outcome reported. 
In the event of a SAE, the investigator must immediately notify the appropriate contact 
in the Study Manual.  
In addition, the investigator must obtain and maintain in his/her files all pertinent medical 
records, information, and medical judgments from colleagues who assisted in the 
treatment and follow-up of the subject; provide a complete case history, which includes a 
statement as to whether the event was or was not suspected to be related to the use of the 
IP; and inform the IRB of the SAE within their guidelines for reporting SAEs.  
 PROCEDURES FOR UNMASKING (IF APPLICABLE) 
11.4
When medically necessary, the investigator may need to determine what treatment has 
been assigned to a subject.  The Investigator should make every effort to contact Ora to 
discuss the subject’s emergency situation and the need to unmask a study subject prior to 
unmasking IP.   
If the investigator determines that emergency unmasking is necessary, the investigator 
should identify the given subject’s study drug kit which contains a scratch off laminate 
under which the treatment is identified along with the associated lot number. In order to 
unmask, the investigator should scratch off the laminate, using a flat object and applying 
pressure, to reveal the treatment assigned for that subject. The emergency unmasking 
should be performed by the designated site personnel.  The investigator must also 
indicate in source documents and in the eCRF that the mask was broken and provide the 
date, time, and reason for breaking the mask.  Any AE or SAE associated with breaking 
the mask must be recorded and reported as specified in this protocol.  The investigator 
has the responsibility to contact Ora within 24 hours of breaking the blind.   
Subjects will have the IP treatment discontinued immediately if treatment assignment is 
unmasked and will be discontinued from the study.  
 
 TYPE AND DURATION OF THE FOLLOW-UP OF SUBJECTS 
11.5
AFTER ADVERSE EVENTS 
AEs will be followed until:  
• Resolution (return to baseline status or to ‘normal’) 


ADX-102 Ophthalmic Drops (0.5% and 0.1%) 
 Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-AC-004 
Final 1.0, 19 October 2016 
 
Confidential 
Page 35 of 56 
• Stabilization of the event has occurred (no worsening or improvement expected by 
the Investigator) 
• Event is otherwise explained, regardless of whether the subject is still participating in 
the study 
If the subject is lost to follow-up, the investigator should make 3 reasonable attempts to 
contact the subject via telephone, post, or certified mail. All follow-up will be 
documented in the subject’s source document. Non-serious adverse events identified on 
the last scheduled contact must be recorded on the AE CRF with the status noted.  
12 STATISTICAL HYPOTHESES AND METHODS OF ANALYSES 
 STUDY POPULATIONS 
12.1
 Intent-to-Treat Population 
12.1.1
The Intent-to-Treat (ITT) population consists of all subjects who are randomized.  All 
data will be included and no subjects will be excluded because of protocol violations.  
The ITT population will be analyzed as randomized and will be used for the efficacy 
analyses.  
 Per-Protocol Population 
12.1.2
The Per-Protocol (PP) population is a subset of the ITT population and includes the 
subjects who completed the study through Visit 4 (Day 15) with no major protocol 
violations. This population will be analyzed as treated using observed data only for 
confirmatory analyses. 
 Safety Population 
12.1.3
The safety population includes all randomized subjects who received the test article. The 
safety population will be analyzed as treated and will be used for the safety analyses. No 
data will be excluded for any reason. 
 GENERAL IMPUTATION METHODS 
12.2
 
 
 
 
   


ADX-102 Ophthalmic Drops (0.5% and 0.1%) 
 Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-AC-004 
Final 1.0, 19 October 2016 
 
Confidential 
Page 36 of 56 
 
 
 
 
 PRIMARY EFFICACY VARIABLES 
12.3
The primary efficacy variable is: 
• Ocular itching evaluated by the subject at 10(±1), 15(±1), and 20(±1) minutes post-
CAC at Visits 3 and 4 (0-4 scale, allowing half unit increments). 
 CRITERIA FOR EFFICACY  
12.4
This clinical study is designed to evaluate the efficacy of ADX-102 Ophthalmic Drops 
compared to vehicle in the prevention of ocular itching at each designated time point 
post-CAC at Visits 3 and 4.  
To demonstrate the clinical effectiveness for ocular itching, ADX-102 Ophthalmic Drops 
will need to show clinical superiority over vehicle by at least 0.5 units of a 5 point scale 
for the 10(±1), 15(±1) and 20(±1) minutes post-CAC time points within a visit, and at 
least 1 unit for the majority 
 of the same three post-CAC time points within a visit for 
each treatment comparison. ADX-102 Ophthalmic Drops will also need to show 
statistical superiority over vehicle at each of the three time points.  The treatments will be 
tested against vehicle hierarchically, with the higher dose (0.5% ADX-102 Ophthalmic 
Drops) tested first and the lower dose (0.1% ADX-102 Ophthalmic Drops) tested 
conditional upon the higher dose showing statistical significance over vehicle. 




ADX-102 Ophthalmic Drops (0.5% and 0.1%) 
 Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-AC-004 
Final 1.0, 19 October 2016 
 
Confidential 
Page 38 of 56 
 ADJUSTMENT FOR MULTIPLICITY 
12.11
 
 
 
 
 
 
 
 
 
 
 
 
 
 SAFETY ANALYSIS 
12.12
The primary safety variable is the incidence of subjects with any adverse event during the 
entire study.  The percentage of subjects with specific treatment-emergent adverse events 
(TEAEs) will be summarized for each treatment group.  Incidence will be tabulated by 
MedDRA System Organ Class and preferred term within each system organ class.  
Adverse events will also be summarized for treatment-related AEs, SAEs, by maximal 
severity, and by day of onset relative to the start of treatment. 
The secondary safety variables of slit lamp biomicroscopy, dilated fundus examination, 
visual acuity, and IOP will be summarized descriptively using quantitative and qualitative 


ADX-102 Ophthalmic Drops (0.5% and 0.1%) 
 Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-AC-004 
Final 1.0, 19 October 2016 
 
Confidential 
Page 39 of 56 
summary statistics as appropriate.  Changes and shifts from baseline will also be 
summarized where applicable. 
 INTERIM ANALYSIS 
12.13
No interim analyses are planned. 
13 COMPLIANCE WITH GOOD CLINICAL PRACTICES, ETHICAL 
CONSIDERATIONS, AND ADMINISTRATIVE ISSUES 
This study will be conducted in compliance with the protocol, current 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 investigational 
products in the countries involved will be adhered to. 
 PROTECTION OF HUMAN SUBJECTS 
13.1
 Subject Informed Consent 
13.1.1
Informed consent must take place before any study specific procedures are initiated.  
Signed and dated written informed consent must be obtained from each subject and/or 
from the subject’s parent or legal guardian prior to enrollment into the study.   
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 Ora prior to submission to the governing IRB/IEC 
and that it is read, signed and dated by all subjects subsequently enrolled in the study as 
well as those currently enrolled in the study. 
Informed consent may be obtained within 30 days prior to Visit 1, however, informed 
consent must be obtained prior to Visit 1 if any of the following criteria are determined 
during the telephone screening process: 
• Proper washout of certain medications is necessary 
• Sufficient time of discontinuation of contact lens wear is necessary 
• Post-operative period 
Medical/medication history, demographics, skin test and inclusion/exclusion review may 
be performed at the time of informed consent signing prior to Visit 1, but must be 
confirmed at Visit 1 (with the exception of demographics and skin test).   


ADX-102 Ophthalmic Drops (0.5% and 0.1%) 
 Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-AC-004 
Final 1.0, 19 October 2016 
 
Confidential 
Page 40 of 56 
 Institutional Review Board (IRB) Approval 
13.1.2
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 ICF will be used. 
 ETHICAL CONDUCT OF THE STUDY 
13.2
This study will be conducted in accordance with the ethical principles that originated 
with the Declaration of Helsinki. 
 SUBJECT CONFIDENTIALITY 
13.3
All personal study subject data collected and processed for the purposes of this study 
should be maintained by the investigator and his/her staff with adequate precautions as to 
ensure that the confidentiality of the data in accordance with local, state, and federal laws 
and regulations. 
Monitors, auditors and other authorized representatives of Ora, the Sponsor, the IRB/IEC 
approving this study, the Food and Drug Administration, the Department of Health and 
Human Services, other domestic government agencies, and other foreign regulatory 
agencies will be granted direct access to the study subject’s original medical and study 
records for verification of the data and/or clinical trial procedures.  Access to this 
information will be permitted to the aforementioned individuals to the extent permitted 
by law. 
A report of the results of this study may be published or sent to the appropriate health 
authorities in any country in which the investigational product may ultimately be 
marketed, but the subject’s identity will not be disclosed in these documents. 
 DOCUMENTATION 
13.4
Source documents may include a subject’s medical records, hospital charts, clinic charts, 
the investigator’s study subject files, as well as the results of diagnostic tests such as X-
rays, laboratory tests, and electrocardiograms.  The investigator’s copy of the eCRFs 
serves as the investigator’s record of a subject’s study-related data. 
 Retention of Documentation 
13.4.1
All study related correspondence, subject records, ICFs, record of the distribution and use 
of all IPs and copies of eCRFs should be maintained on file for at least 2 years after the 
last approval of a marketing application in an ICH region and until there are no pending 
or contemplated marketing applications in an ICH region; or until at least 2 years have 
elapsed since the formal discontinuation of clinical development of the IP. 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 


ADX-102 Ophthalmic Drops (0.5% and 0.1%) 
 Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-AC-004 
Final 1.0, 19 October 2016 
 
Confidential 
Page 41 of 56 
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. 
 LABELING, PACKAGING, STORAGE, ACCOUNTABILITY, AND 
13.5
RETURN OR DISPOSAL OF INVESTIGATIONAL PRODUCT 
 Labeling/Packaging 
13.5.1
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 Storage of Investigational Product 
13.5.2
  
The IP must be stored in a secure area accessible only to the investigator and his/her 
designees. The IP will be administered only to subjects entered into the clinical study, in 
accordance with the conditions specified in this protocol. 


ADX-102 Ophthalmic Drops (0.5% and 0.1%) 
 Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-AC-004 
Final 1.0, 19 October 2016 
 
Confidential 
Page 42 of 56 
 Accountability of Investigational Product 
13.5.3
The IP 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 IP must only 
be distributed to subjects properly qualified under this protocol to receive IP. 
The investigator must keep an accurate accounting of the IP received from the supplier. 
This includes the amount of IP dispensed to subjects, amount of IP returned to the 
investigator by the subjects, and the amount returned or disposed upon the completion of 
the study.  A detailed inventory must be completed for the IP and available for Sponsor’s 
review during the course of the study. 
 Final accountability and Disposal of Investigational Product 
13.5.4
At the conclusion of the study, all IP reconciliation will be performed and all remaining 
IP will be destructed and disposed according to clinical site’s SOP. Sponsor will be 
provided with a final accounting of study drug for approval prior to destruction.  
 RECORDING OF DATA ON SOURCE DOCUMENTS AND CASE 
13.6
REPORTS FORMS (CRFS) 
The investigator is responsible for ensuring that study data is completely and accurately 
recorded on each subject’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 correction and when, by adding to the correction 
his/her initials as well as the date of the correction. 
 HANDLING OF BIOLOGICAL SPECIMENS 
13.7
Not Applicable. 
 PUBLICATIONS 
13.8
Authorship and manuscript composition will reflect cooperation among all parties 
involved in the study.  Authorship will be established before writing the manuscript.  Ora 
and the study Sponsor will have the final decision regarding the manuscript and 
publication. 
 
 


ADX-102 Ophthalmic Drops (0.5% and 0.1%) 
 Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-AC-004 
Final 1.0, 19 October 2016 
 
Confidential 
Page 43 of 56 
14 REFERENCES 
  
 
 
  
 
 
 
 
 
 
















ADX-102 Ophthalmic Drops (0.5% and 0.1%) 
 Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-AC-004 
Final 1.0, 19 October 2016 
 
Confidential 
Page 51 of 56 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 


ADX-102 Ophthalmic Drops (0.5% and 0.1%) 
 Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-AC-004 
Final 1.0, 19 October 2016 
 
Confidential 
Page 52 of 56 
APPENDIX 4:  HANDLING OF BIOLOGICAL SPECIMENS 
Not Applicable. 


ADX-102 Ophthalmic Drops (0.5% and 0.1%) 
 Aldeyra Therapeutics, Inc. 
Clinical Trial Protocol ADX-102-AC-004 
Final 1.0, 19 October 2016 
 
Confidential 
Page 53 of 56 
APPENDIX 5:  PROTOCOL AMENDMENT SUMMARY 
Not Applicable. 











SAP_001.pdf: 
67$7,67,&$/ $1$/<6,6 3/$1
$ 0XOWL&HQWHU 'RXEOH0DVNHG 5DQGRPL]HG 9HKLFOH&RQWUROOHG
3KDVH E (YDOXDWLRQ RI WKH 2QVHW DQG 'XUDWLRQ RI $';
2SKWKDOPLF 'URSV  DQG  &RPSDUHG WR 9HKLFOH RI $';
2SKWKDOPLF 'URSV LQ WKH &RQMXQFWLYDO $OOHUJHQ &KDOOHQJH 2UD
&$& 0RGHO RI $FXWH $OOHUJLF &RQMXQFWLYLWLV
6SRQVRU
$OGH\UD 7KHUDSHXWLFV ,QF
 +DUWZHOO $YH
/H[LQJWRQ 0$ 
3URWRFRO 1XPEHU
$';$&
$XWKRU
DQ
'DWH
0$<
9HUVLRQ





3URWRFRO $';$& 9HUVLRQ 
0$<
&RQILGHQWLDO 	 3URSULHWDU\
3DJH  RI 
7DEOH RI &RQWHQWV
 ,QWURGXFWLRQ   
 6WXG\ 2EMHFWLYHV   
 6WXG\ 9DULDEOHV  
 3ULPDU\ 9DULDEOHV  
 
 ([SORUDWRU\ 9DULDEOHV   
 6DIHW\ 9DULDEOHV  
 6WDWLVWLFDO +\SRWKHVHV  
 6WXG\ 'HVLJQ DQG 3URFHGXUHV   
 *HQHUDO 6WXG\ 'HVLJQ   
 6FKHGXOH RI 9LVLWV DQG $VVHVVPHQWV   
 6WXG\ 7UHDWPHQWV  
 0HWKRG RI $VVLJQLQJ 6XEMHFWV WR 7UHDWPHQW *URXSV   
 0DVNLQJ DQG 8QPDVNLQJ   
 6DPSOH 6L]H DQG 3RZHU &RQVLGHUDWLRQV   
 'DWD 3UHSDUDWLRQ   
 $QDO\VLV 3RSXODWLRQV   
 ,QWHQWWR7UHDW   
 3HU3URWRFRO  
 6DIHW\   
 *HQHUDO 6WDWLVWLFDO &RQVLGHUDWLRQV  
 8QLW RI $QDO\VLV   
 0LVVLQJ RU ,QFRQFOXVLYH 'DWD +DQGOLQJ   
 'HILQLWLRQ RI %DVHOLQH   
 'DWD $QDO\VLV &RQYHQWLRQV  
 $GMXVWPHQWV IRU 0XOWLSOLFLW\  
 'LVSRVLWLRQ RI 6XEMHFWV   
 'HPRJUDSKLF DQG 3UHWUHDWPHQW 9DULDEOHV   
 'HPRJUDSKLF 9DULDEOHV  
 3UHWUHDWPHQW 9DULDEOHV  
 0HGLFDO +LVWRU\ DQG &RQFRPLWDQW 0HGLFDWLRQV  
 0HGLFDO +LVWRU\   
 3ULRU DQG &RQFRPLWDQW 0HGLFDWLRQV   
 ([SRVXUH WR ,QYHVWLJDWLRQDO 3URGXFW  


3URWRFRO $';$& 9HUVLRQ 
0$<
&RQILGHQWLDO 	 3URSULHWDU\
3DJH  RI 
 (IILFDF\ $QDO\VHV   
 3ULPDU\ $QDO\VLV   
 
 
 
 
 
 
 ([SORUDWRU\ $QDO\VHV  
 6DIHW\ $QDO\VHV   
 $GYHUVH (YHQWV  
 9LVXDO $FXLW\ (7'56   
 6OLW/DPS %LRPLFURVFRS\ ([DPLQDWLRQ  
 ,QWUDRFXODU 3UHVVXUH ,23  
 'LODWHG )XQGRVFRS\ ([DPLQDWLRQ   
 ,QWHULP $QDO\VHV  
 &KDQJHV IURP 3URWRFRO6WDWHG $QDO\VHV  
 5HYLVLRQ +LVWRU\   
 7DEOHV  
 /LVWLQJV   
 )LJXUHV  


3URWRFRO $';$& 9HUVLRQ 
0$<
&RQILGHQWLDO 	 3URSULHWDU\
3DJH  RI 
/LVW RI $EEUHYLDWLRQV
$(
$GYHUVH (YHQW
$1&29$
$QDO\VLV RI &RYDULDQFH
$7&
$QDWRPLFDO 7KHUDSHXWLF &KHPLFDO &ODVVLILFDWLRQ
%2&)
%DVHOLQH 2EVHUYDWLRQ &DUULHG )RUZDUG
&$&
&RQMXQFWLYDO $OOHUJHQ &KDOOHQJH
&5)
&DVH 5HSRUW )RUP
&6
&OLQLFDOO\ 6LJQLILFDQW
&65
&OLQLFDO 6WXG\ 5HSRUW
H&5)
(OHFWURQLF &DVH 5HSRUW )RUP
(7'56
(DUO\ 7UHDWPHQW RI 'LDEHWLF 5HWLQRSDWK\ 6WXG\
+,3$$
+HDOWK ,QIRUPDWLRQ 3RUWDELOLW\ DQG $FFRXQWDELOLW\ $FW
,&)
,QIRUPHG &RQVHQW )RUP
,&+
,QWHUQDWLRQDO &RQIHUHQFH RQ +DUPRQLVDWLRQ
,23
,QWUDRFXODU 3UHVVXUH
,3
,QYHVWLJDWLRQDO 3URGXFW
,77
,QWHQWWR7UHDW
/2&)
/DVW 2EVHUYDWLRQ &DUULHG )RUZDUG
ORJ0$5
/RJDULWKP RI WKH 0LQLPXP $QJOH RI 5HVROXWLRQ
/6
/HDVW 6TXDUHV
0&0&
0DUNRY &KDLQ 0RQWH &DUOR
0HG'5$
0HGLFDO 'LFWLRQDU\ IRU 5HJXODWRU\ $FWLYLWLHV
1&6
1RW FOLQLFDOO\ VLJQLILFDQW
3')
3RUWDEOH 'RFXPHQW )RUPDW
33
3HU3URWRFRO
37
3UHIHUUHG 7HUP
57)
5LFK 7H[W )RUPDW
6$(
6HULRXV $GYHUVH (YHQW
6$3
6WDWLVWLFDO $QDO\VLV 3ODQ
6'
6WDQGDUG 'HYLDWLRQ
6'&
6WDWLVWLFV DQG 'DWD &RUSRUDWLRQ ,QFRUSRUDWHG
62&
6\VWHP 2UJDQ &ODVV
7($(
7UHDWPHQW(PHUJHQW $GYHUVH (YHQW
9$
9LVXDO $FXLW\
:+2 ''(
:RUOG +HDOWK 2UJDQL]DWLRQ 'UXJ 'LFWLRQDU\ (QKDQFHG


3URWRFRO $';$& 9HUVLRQ 
0$<
&RQILGHQWLDO 	 3URSULHWDU\
3DJH  RI 

,QWURGXFWLRQ
7KH SXUSRVH RI WKLV VWDWLVWLFDO DQDO\VLV SODQ 6$3 LV WR GHVFULEH WKH SODQQHG DQDO\VHV DQG UHSRUWLQJ IRU
SURWRFRO $';$& )LQDO  GDWHG 2&7
7KLV 6$3 LV EHLQJ ZULWWHQ ZLWK GXH FRQVLGHUDWLRQ RI WKH UHFRPPHQGDWLRQV RXWOLQHG LQ WKH PRVW UHFHQW
,QWHUQDWLRQDO &RQIHUHQFH RQ +DUPRQL]DWLRQ ,&+ ( *XLGHOLQH HQWLWOHG *XLGDQFH IRU ,QGXVWU\ 6WDWLVWLFDO
3ULQFLSOHV IRU &OLQLFDO 7ULDOV DQG WKH PRVW UHFHQW ,&+ ( *XLGHOLQH HQWLWOHG *XLGDQFH IRU ,QGXVWU\
6WUXFWXUH DQG &RQWHQW RI &OLQLFDO 6WXG\ 5HSRUWV &65
7KLV 6$3 GHVFULEHV WKH GDWD WKDW ZLOO EH DQDO\]HG DQG WKH VXEMHFW FKDUDFWHULVWLFV HIILFDF\ DQG VDIHW\
DVVHVVPHQWV WKDW ZLOO EH HYDOXDWHG 7KLV 6$3 SURYLGHV GHWDLOV RI WKH VSHFLILF VWDWLVWLFDO PHWKRGV WKDW ZLOO
EH XVHG 7KH VWDWLVWLFDO DQDO\VLV PHWKRGV SUHVHQWHG LQ WKLV GRFXPHQW ZLOO VXSHUVHGH WKH VWDWLVWLFDO
DQDO\VLV PHWKRGV GHVFULEHG LQ WKH FOLQLFDO SURWRFRO ,I DGGLWLRQDO DQDO\VHV DUH UHTXLUHG WR VXSSOHPHQW
WKH SODQQHG DQDO\VHV GHVFULEHG LQ WKLV 6$3 WKH\ PD\ EH FRPSOHWHG DQG ZLOO EH LGHQWLILHG LQ WKH &65

6WXG\ 2EMHFWLYHV
7KH REMHFWLYH RI WKLV VWXG\ LV WR HYDOXDWH WKH HIILFDF\ RI $'; RSKWKDOPLF GURSV  DQG 
FRPSDUHG WR YHKLFOH RI $'; RSKWKDOPLF GURSV IRU WKH WUHDWPHQW RI WKH VLJQV DQG V\PSWRPV RI DFXWH
DOOHUJLF FRQMXQFWLYLWLV

6WXG\ 9DULDEOHV

3ULPDU\ 9DULDEOHV
7KH SULPDU\ HIILFDF\ YDULDEOH LV WKH IROORZLQJ
x
2FXODU LWFKLQJ HYDOXDWHG E\ WKH VXEMHFW DW   DQG  PLQXWHV SRVWFRQMXQFWLYDO
DOOHUJHQ FKDOOHQJH &$& DW 9LVLWV  DQG   VFDOH DOORZLQJ KDOI XQLW LQFUHPHQWV


3URWRFRO $';$& 9HUVLRQ 
0$<
&RQILGHQWLDO 	 3URSULHWDU\
3DJH  RI 

([SORUDWRU\ 9DULDEOHV
7KHUH DUH QR H[SORUDWRU\ HIILFDF\ YDULDEOHV LQ WKLV VWXG\

6DIHW\ 9DULDEOHV
7KH VDIHW\ YDULDEOHV LQFOXGH WKH IROORZLQJ
x
$GYHUVH (YHQWV $( UHSRUWHG HOLFLWHG DQG REVHUYHG
x
9LVXDO $FXLW\ 9$ DW 'LVWDQFH 8WLOL]LQJ DQ (DUO\ 7UHDWPHQW 'LDEHWLF 5HWLQRSDWK\ 6WXG\ (7'56
FKDUW
x
6OLWODPS %LRPLFURVFRS\
x
,QWUDRFXODU 3UHVVXUH ,23
x
'LODWHG )XQGRVFRS\

6WDWLVWLFDO +\SRWKHVHV

6WXG\ 'HVLJQ DQG 3URFHGXUHV

*HQHUDO 6WXG\ 'HVLJQ
7KLV LV D PXOWLFHQWHU GRXEOHPDVNHG UDQGRPL]HG YHKLFOHFRQWUROOHG SKDVH E VWXG\ HYDOXDWLQJ WKH
HIILFDF\ RI $'; RSKWKDOPLF GURSV  DQG  FRPSDUHG WR YHKLFOH RI $'; RSKWKDOPLF
GURSV IRU WKH WUHDWPHQW RI WKH VLJQV DQG V\PSWRPV RI DFXWH DOOHUJLF FRQMXQFWLYLWLV
7KH WULDO ZLOO FRPSULVH  RIILFH YLVLWV RYHU D SHULRG RI DSSUR[LPDWHO\  ZHHNV 9LVLWV  DQG  ZLOO EH XVHG
WR VHOHFW D VXEMHFW SRSXODWLRQ WKDW UHVSRQGV UHSURGXFLEO\ WR WZR &$&V DGPLQLVWHUHG DSSUR[LPDWHO\ 
GD\V DSDUW 6XEMHFWV ZKR PHHW WKH HQWU\ FULWHULD IRU LWFKLQJ DQG UHGQHVV UHVSRQVH WR &$& DW 9LVLWV 
DQG  ZLOO EH UDQGRPL]HG  DW 9LVLW  'D\  (QUROOPHQW5DQGRPL]DWLRQ WR UHFHLYH HLWKHU $';






3URWRFRO $';$& 9HUVLRQ 
0$<
&RQILGHQWLDO 	 3URSULHWDU\
3DJH  RI 

0DVNLQJ DQG 8QPDVNLQJ
:KHQ PHGLFDOO\ QHFHVVDU\ WKH LQYHVWLJDWRU PD\ QHHG WR GHWHUPLQH ZKDW WUHDWPHQW KDV EHHQ DVVLJQHG
WR D VXEMHFW 7KH LQYHVWLJDWRU VKRXOG PDNH HYHU\ HIIRUW WR FRQWDFW 2UD WR GLVFXVV WKH VXEMHFW¶V HPHUJHQF\
VLWXDWLRQ DQG WKH QHHG WR XQPDVN D VWXG\ VXEMHFW SULRU WR XQPDVNLQJ WKH ,3
,I WKH LQYHVWLJDWRU GHWHUPLQHV WKDW HPHUJHQF\ XQPDVNLQJ LV QHFHVVDU\ WKH LQYHVWLJDWRU VKRXOG LGHQWLI\
WKH JLYHQ VXEMHFW¶V VWXG\ GUXJ NLW ZKLFK FRQWDLQV D VFUDWFK RII ODPLQDWH XQGHU ZKLFK WKH WUHDWPHQW LV
LGHQWLILHG DORQJ ZLWK WKH DVVRFLDWHG ORW QXPEHU ,Q RUGHU WR XQPDVN WKH LQYHVWLJDWRU VKRXOG VFUDWFK RII
WKH ODPLQDWH XVLQJ D IODW REMHFW DQG DSSO\LQJ SUHVVXUH WR UHYHDO WKH WUHDWPHQW DVVLJQHG IRU WKDW VXEMHFW
7KH HPHUJHQF\ XQPDVNLQJ VKRXOG EH SHUIRUPHG E\ WKH GHVLJQDWHG VLWH SHUVRQQHO 7KH LQYHVWLJDWRU
PXVW DOVR LQGLFDWH LQ VRXUFH GRFXPHQWV DQG LQ WKH HOHFWURQLF FDVH UHSRUW IRUP H&5) WKDW WKH PDVN
ZDV EURNHQ DQG SURYLGH WKH GDWH WLPH DQG UHDVRQ IRU EUHDNLQJ WKH PDVN $Q\ $( RU VHULRXV DGYHUVH
HYHQW 6$( DVVRFLDWHG ZLWK EUHDNLQJ WKH PDVN PXVW EH UHFRUGHG DQG UHSRUWHG DV VSHFLILHG LQ WKH VWXG\
SURWRFRO 7KH LQYHVWLJDWRU KDV WKH UHVSRQVLELOLW\ WR FRQWDFW 2UD ZLWKLQ  KRXUV RI EUHDNLQJ WKH EOLQG
6XEMHFWV ZLOO KDYH WKH ,3 WUHDWPHQW GLVFRQWLQXHG LPPHGLDWHO\ LI WUHDWPHQW DVVLJQPHQW LV XQPDVNHG DQG
ZLOO EH GLVFRQWLQXHG IURP WKH VWXG\

6DPSOH 6L]H DQG 3RZHU &RQVLGHUDWLRQV

'DWD 3UHSDUDWLRQ
$OO UHSRUWHG VWXG\ GDWD ZLOO EH UHFRUGHG RQ WKH H&5)V VXSSOLHG E\ 6WDWLVWLFV 	 'DWD &RUSRUDWLRQ 6'&
XVLQJ L0HG1HW 2QO\ WKH 3ULQFLSDO ,QYHVWLJDWRU DQG DXWKRUL]HG VWXG\ VWDII DFFRUGLQJ WR WKH 'HOHJDWLRQ
RI 5HVSRQVLELOLWLHV ORJ DUH HQWLWOHG WR PDNH HQWULHV LQ WKH H&5)
$IWHU GDWD DUH HQWHUHG LQWR WKH FOLQLFDO VWXG\ GDWDEDVH HOHFWURQLF HGLW FKHFNV DQG GDWD UHYLHZ ZLOO EH
SHUIRUPHG $OO GDWD YDOLGDWLRQ VSHFLILFDWLRQV DQG SURFHGXUHV DUH GHWDLOHG LQ WKH 'DWD 9DOLGDWLRQ 0DQXDO
DV D VHSDUDWH GRFXPHQW :KHQ WKH GDWDEDVH KDV EHHQ GHFODUHG WR EH FRPSOHWH DQG DFFXUDWH WKH
GDWDEDVH ZLOO EH ORFNHG $Q\ FKDQJHV WR WKH GDWDEDVH DIWHU GDWD KDYH EHHQ ORFNHG FDQ RQO\ EH PDGH
ZLWK WKH DSSURYDO RI WKH 6SRQVRU DQG 2UD LQ FRQVXOWDWLRQ ZLWK 6'&
$OO DQDO\VHV RXWOLQHG LQ WKLV GRFXPHQW ZLOO EH FDUULHG RXW DIWHU WKH IROORZLQJ KDYH RFFXUUHG


3URWRFRO $';$& 9HUVLRQ 
0$<
&RQILGHQWLDO 	 3URSULHWDU\
3DJH  RI 
x
$OO GDWD PDQDJHPHQW UHTXLUHPHQWV DUH PHW DFFRUGLQJ WR 6'& VWDQGDUG RSHUDWLQJ SURFHGXUHV
LQFOXGLQJ GDWD HQWU\ SHUIRUPDQFH RI HGLW DQG YDOLGDWLRQ FKHFNV GRFXPHQWDWLRQ DQG UHVROXWLRQ
RI GDWD TXHULHV DQG GDWDEDVH ORFN ZLWK ZULWWHQ DXWKRUL]DWLRQ SURYLGHG E\ DSSURSULDWH 6'& DQG
6SRQVRU SHUVRQQHO
x
3URWRFRO GHYLDWLRQV KDYH EHHQ LGHQWLILHG DQG VWDWXV GHILQHG PDMRUPLQRU GHYLDWLRQV
x
$QDO\VLV SRSXODWLRQV KDYH EHHQ GHWHUPLQHG DQG
x
5DQGRPL]HG WUHDWPHQW FRGHV KDYH EHHQ XQPDVNHG

$QDO\VLV 3RSXODWLRQV

,QWHQWWR7UHDW
7KH ,QWHQWWR7UHDW ,77 SRSXODWLRQ FRQVLVWV RI DOO VXEMHFWV ZKR DUH UDQGRPL]HG $OO GDWD ZLOO EH LQFOXGHG
DQG QR VXEMHFWV ZLOO EH H[FOXGHG EHFDXVH RI SURWRFRO YLRODWLRQV 7KH ,77 SRSXODWLRQ ZLOO EH DQDO\]HG DV
UDQGRPL]HG DQG ZLOO EH XVHG IRU WKH HIILFDF\ DQDO\VHV

3HU3URWRFRO
7KH 3HU3URWRFRO 33 SRSXODWLRQ LV D VXEVHW RI WKH ,77 SRSXODWLRQ DQG LQFOXGHV WKH VXEMHFWV ZKR
FRPSOHWHG WKH VWXG\ WKURXJK 9LVLW  'D\  ZLWK QR PDMRU SURWRFRO YLRODWLRQV 7KLV SRSXODWLRQ ZLOO EH
DQDO\]HG DV WUHDWHG XVLQJ REVHUYHG GDWD RQO\ IRU FRQILUPDWRU\ DQDO\VHV

6DIHW\
7KH VDIHW\ SRSXODWLRQ LQFOXGHV DOO UDQGRPL]HG VXEMHFWV ZKR UHFHLYHG WKH WHVW DUWLFOH 7KH VDIHW\
SRSXODWLRQ ZLOO EH DQDO\]HG DV WUHDWHG DQG ZLOO EH XVHG IRU WKH VDIHW\ DQDO\VHV 1R GDWD ZLOO EH H[FOXGHG
IRU DQ\ UHDVRQ

*HQHUDO 6WDWLVWLFDO &RQVLGHUDWLRQV

8QLW RI $QDO\VLV
7KH VXEMHFW ZLOO EH FRQVLGHUHG WKH XQLW RI DQDO\VLV IRU DOO YDULDEOHV ZLWK H[FHSWLRQV RI VOLWODPS
ELRPLFURVFRS\ DQG GLODWHG IXQGXV H[DPLQDWLRQ )RU WKH YDULDEOHV XVLQJ VXEMHFW DV WKH XQLW RI WKH
DQDO\VLV WKH DYHUDJH RI ERWK H\HV RI HDFK VXEMHFW ZLOO EH XVHG IRU VWDWLVWLFDO VXPPDULHV DQG DQDO\VHV
LQ FDVHV ZKHUH GDWD DUH FROOHFWHG IRU HDFK H\H )RU VOLWODPS ELRPLFURVFRS\ DQG GLODWHG IXQGXV
H[DPLQDWLRQ UHVXOWV WKH H\H ZLOO EH WKH XQLW RI DQDO\VLV DQG VXPPDULHV ZLOO EH SURYLGHG IRU DOO H\HV
FRPELQHG

0LVVLQJ RU ,QFRQFOXVLYH 'DWD +DQGOLQJ






3URWRFRO $';$& 9HUVLRQ 
0$<
&RQILGHQWLDO 	 3URSULHWDU\
3DJH  RI 

'HILQLWLRQ RI %DVHOLQH
)RU WKH SULPDU\ HIILFDF\ YDULDEOH RFXODU LWFKLQJ VFRUHV DW   DQG  PLQXWHV SRVW&$&
EDVHOLQH ZLOO UHIHU WR WKH WLPHUHOHYDQW PHDVXUH DW 9LVLW  HJ RFXODU LWFKLQJ DW  PLQXWHV SRVW&$& DW
9LVLW  ZLOO EH WKH EDVHOLQH IRU RFXODU LWFKLQJ DW  PLQXWHV SRVW&$& DW 9LVLWV  DQG 
)RU DOO VDIHW\ YDULDEOHV EDVHOLQH LV GHILQHG DV WKH ODVW PHDVXUHPHQW SULRU WR WKH ILUVW GRVH RI
VWXG\ PHGLFDWLRQ &KDQJH IURP EDVHOLQH ZLOO EH FDOFXODWHG DV IROORZXS YLVLW PLQXV EDVHOLQH YLVLW

'DWD $QDO\VLV &RQYHQWLRQV
$OO GDWD DQDO\VLV ZLOO EH SHUIRUPHG E\ 6'& DIWHU WKH VWXG\ LV FRPSOHWHG DQG WKH GDWDEDVH KDV EHHQ
ORFNHG DQG UHOHDVHG IRU XQPDVNLQJ 6WDWLVWLFDO SURJUDPPLQJ DQG DQDO\VHV ZLOO EH SHUIRUPHG XVLQJ 6$6
9HUVLRQ  RU KLJKHU 2XWSXW ZLOO EH SURYLGHG LQ ULFK WH[W IRUPDW 57) IRU WDEOHV DQG SRUWDEOH GRFXPHQW
IRUPDW 3') IRU WDEOHV OLVWLQJV DQG ILJXUHV XVLQJ ODQGVFDSH RULHQWDWLRQ $OO VWXG\ GDWD ZLOO EH OLVWHG E\
VXEMHFW WUHDWPHQW YLVLW DQG WLPH SRLQW DV DSSOLFDEOH EDVHG RQ DOO UDQGRPL]HG VXEMHFWV XQOHVV
RWKHUZLVH VSHFLILHG
6XPPDULHV IRU TXDQWLWDWLYH YDULDEOHV ZLOO LQFOXGH WKH QXPEHU RI REVHUYDWLRQV Q DULWKPHWLF PHDQ
VWDQGDUG GHYLDWLRQ 6' PHGLDQ PLQLPXP DQG PD[LPXP 0LQLPD DQG PD[LPD ZLOO EH UHSRUWHG ZLWK
WKH VDPH SUHFLVLRQ DV WKH UDZ YDOXHV PHDQV DQG PHGLDQV ZLOO EH SUHVHQWHG WR RQH DGGLWLRQDO GHFLPDO
SODFH WKDQ UHSRUWHG LQ WKH UDZ YDOXHV 6WDQGDUG GHYLDWLRQV ZLOO EH SUHVHQWHG WR WZR DGGLWLRQDO GHFLPDO
SODFHV WKDQ UHSRUWHG LQ WKH UDZ YDOXHV 6XPPDULHV IRU TXDOLWDWLYH YDULDEOHV ZLOO LQFOXGH IUHTXHQF\ FRXQWV
DQG SHUFHQWDJHV
$OO SHUFHQWDJHV ZLOO EH URXQGHG WR RQH GHFLPDO SODFH LH ;;;
'LIIHUHQFHV
EHWZHHQ DFWLYH WUHDWPHQW JURXSV DQG SODFHER ZLOO EH FDOFXODWHG DV DFWLYH PLQXV YHKLFOH DQG FKDQJH
IURP EDVHOLQH ZLOO EH FDOFXODWHG DV IROORZXS YLVLW PLQXV EDVHOLQH YLVLW
$OO VWDWLVWLFDO WHVWV ZLOO EH WZRVLGHG ZLWK D VLJQLILFDQFH OHYHO RI  Į   XQOHVV RWKHUZLVH VSHFLILHG
&RQILGHQFH LQWHUYDOV &, IRU GLIIHUHQFHV EHWZHHQ WUHDWPHQW JURXSV ZLOO EH WZRVLGHG DW  FRQILGHQFH
$OO SYDOXHV ZLOO EH URXQGHG WR IRXU GHFLPDO SODFHV SYDOXHV OHVV WKDQ  ZLOO EH SUHVHQWHG DV
³´ SYDOXHV JUHDWHU WKDQ  ZLOO EH SUHVHQWHG DV ³!´
8QOHVV RWKHUZLVH VSHFLILHG VXPPDULHV ZLOO EH SUHVHQWHG E\ WUHDWPHQW JURXS DQG ZKHUH DSSURSULDWH
YLVLW DQG WLPH SRLQW


3URWRFRO $';$& 9HUVLRQ 
0$<
&RQILGHQWLDO 	 3URSULHWDU\
3DJH  RI 

$GMXVWPHQWV IRU 0XOWLSOLFLW\
 'LVSRVLWLRQ RI 6XEMHFWV
6XEMHFW GLVSRVLWLRQ ZLOO EH SUHVHQWHG LQ WHUPV RI WKH QXPEHUV DQG SHUFHQWDJHV RI VXEMHFWV ZKR ZHUH
UDQGRPL]HG FRPSOHWHG WKH VWXG\ DQG GLVFRQWLQXHG IURP WKH VWXG\ 6XEMHFWV ZKR DUH QRW GLVFRQWLQXHG
IURP WKH VWXG\ ZLOO EH FRQVLGHUHG VWXG\ FRPSOHWHUV 'LVSRVLWLRQ ZLOO EH VXPPDUL]HG E\ WUHDWPHQW JURXS
DQG IRU DOO VXEMHFWV
7KH QXPEHU DQG SHUFHQWDJH RI VXEMHFWV SUHPDWXUHO\ GLVFRQWLQXHG IURP WKH VWXG\ DQG WKH UHDVRQV IRU
VWXG\ GLVFRQWLQXDWLRQ ZLOO EH VXPPDUL]HG E\ WUHDWPHQW JURXS IRU DOO UDQGRPL]HG VXEMHFWV 7KH UHDVRQV
IRU VWXG\ GLVFRQWLQXDWLRQ WKDW ZLOO EH VXPPDUL]HG LQFOXGH $( SURWRFRO YLRODWLRQ ODFN RI HIILFDF\
DGPLQLVWUDWLYH UHDVRQV PDQLIHVW FOLQLFDOO\ DFWLYH VLJQV RU V\PSWRPV RI DOOHUJLF FRQMXQFWLYLWLV GXULQJ WKH
SUH&$& RFXODU DOOHUJLF VLJQV 	 V\PSWRPV DVVHVVPHQW DW 9LVLW  VSRQVRU WHUPLQDWLRQ RI VWXG\
LQYHVWLJDWRU GHFLVLRQ DQG RWKHU $ VXEMHFW OLVWLQJ ZLOO EH SURYLGHG WKDW LQFOXGHV WKH GDWH RI DQG UHDVRQ
IRU SUHPDWXUH VWXG\ GLVFRQWLQXDWLRQ
6XEMHFW OLVWLQJV ZLOO EH SURYLGHG WKDW LQFOXGH LQIRUPHG FRQVHQW GDWH LQFOXVLRQ DQG H[FOXVLRQ FULWHULD
YLRODWLRQV DQG H[FOXVLRQV IURP WKH 33 SRSXODWLRQ
3URWRFRO YLRODWLRQV ZLOO EH VXPPDUL]HG E\ WUHDWPHQW JURXS IRU DOO UDQGRPL]HG VXEMHFWV IRU HDFK YLRODWLRQ
FDWHJRU\ LQIRUPHG FRQVHQW LQFOXVLRQH[FOXVLRQ UDQGRPL]DWLRQ VXEMHFW ZDV QRW WUHDWHG ZLWK DVVLJQHG
WUHDWPHQW DVVHVVPHQWSURFHGXUH QRW FRQGXFWHG SHU SURWRFRO UHTXLUHPHQWV PLVVHG YLVLW YLVLW FRQGXFWHG
RXW RI ZLQGRZ DVVHVVPHQW QRW GRQH VLWH IDLOXUH WR UHSRUW VXEMHFW XVH RI SURKLELWHG FRQFRPLWDQW
PHGLFDWLRQ LQYHVWLJDWLRQDO SURGXFW VWRUHG RXU RI FRUUHFW WHPSHUDWXUH FRQWURO ZDLYHU ZDV JUDQWHG RWKHU
DQG VHYHULW\ PLQ PDMRU XVLQJ FRXQWV DQG SHUFHQWDJHV 3HUFHQWDJHV ZLOO EH EDVHG RQ WKH WRWDO QXPEHU
RI VXEMHFWV UDQGRPL]HG LQ HDFK WUHDWPHQW JURXS $ VXEMHFW OLVWLQJ ZLOO EH SURYLGHG WKDW LQFOXGHV WKH GDWH


3URWRFRO $';$& 9HUVLRQ 
0$<
&RQILGHQWLDO 	 3URSULHWDU\
3DJH  RI 
RI WKH YLRODWLRQ WKH YLRODWLRQ GHVFULSWLRQ DQG WKH FODVVLILFDWLRQ RI ZKHWKHU WKH YLRODWLRQ ZDV MXGJHG WR EH
PDMRU RU PLQRU
 'HPRJUDSKLF DQG 3UHWUHDWPHQW 9DULDEOHV

'HPRJUDSKLF 9DULDEOHV
7KH GHPRJUDSKLF YDULDEOHV FROOHFWHG LQ WKLV VWXG\ LQFOXGH DJH VH[ UDFH HWKQLFLW\ DQG LULV FRORU
6XEMHFWV ZKR UHFRUG PRUH WKDQ RQH UDFH ZLOO EH JURXSHG LQWR D VLQJOH FDWHJRU\ GHQRWHG DV PXOWLUDFLDO
'HPRJUDSKLF YDULDEOHV ZLOO EH VXPPDUL]HG IRU WKH ,77 DQG 6DIHW\ SRSXODWLRQV VHSDUDWHO\
$JH \HDUV ZLOO EH VXPPDUL]HG RYHUDOO DQG E\ WUHDWPHQW XVLQJ FRQWLQXRXV GHVFULSWLYH VWDWLVWLFV $JH
ZLOO DOVR EH FDWHJRUL]HG DV IROORZV
 \HDUV DQG  \HDUV
$JH ZLOO EH UHSRUWHG LQ \HDUV DQG
FDOFXODWHG XVLQJ WKH IROORZLQJ IRUPXOD
$JH  LQIRUPHG FRQVHQW GDWH ± GDWH RI ELUWK   WUXQFDWHG DV DQ LQWHJHU
7KH QXPEHU DQG SHUFHQWDJH RI VXEMHFWV ZLOO EH SUHVHQWHG RYHUDOO DQG E\ WUHDWPHQW IRU DJH FDWHJRU\
VH[ UDFH HWKQLFLW\ DQG LULV FRORU IRU HDFK H\H VHSDUDWHO\
$ VXEMHFW OLVWLQJ WKDW LQFOXGHV DOO GHPRJUDSKLF YDULDEOHV ZLOO EH SURYLGHG

3UHWUHDWPHQW 9DULDEOHV
$W 9LVLW  VXEMHFWV VLJQLQJ WKH LQIRUPHG FRQVHQW DQG +HDOWK ,QVXUDQFH 3RUWDELOLW\ DQG $FFRXQWDELOLW\ $FW
+,3$$ IRUPV ZLOO EH JLYHQ D GLDJQRVWLF WHVW IRU DOOHUJLF GLVHDVH VNLQ WHVW 5HVXOWV IURP WKLV WHVW ZLOO
EH SURYLGHG LQ D VXEMHFW OLVWLQJ
 0HGLFDO +LVWRU\ DQG &RQFRPLWDQW 0HGLFDWLRQV

0HGLFDO +LVWRU\
0HGLFDO KLVWRU\ ZLOO EH FRGHG XVLQJ 0HGLFDO 'LFWLRQDU\ IRU 5HJXODWRU\ $FWLYLWLHV 0HG'5$ 
1RQRFXODU PHGLFDO KLVWRU\ ZLOO EH VXPPDUL]HG XVLQJ GLVFUHWH VXPPDU\ VWDWLVWLFV DQG SUHVHQWHG E\
WUHDWPHQW JURXS DW WKH VXEMHFW DQG HYHQW OHYHO E\ 6\VWHP 2UJDQ &ODVV 62& DQG 3UHIHUUHG 7HUP 37
XVLQJ WKH ,77 SRSXODWLRQ 2FXODU PHGLFDO KLVWRU\ ZLOO EH VLPLODUO\ VXPPDUL]HG DW WKH VXEMHFW OHYHO ,I D
VXEMHFW UHSRUWV WKH VDPH 37 PXOWLSOH WLPHV ZLWKLQ WKH VDPH 62& WKDW 37 ZLOO RQO\ EH UHSRUWHG RQFH
ZLWKLQ WKDW 62& $V ZLWK WKH 37 LI D VXEMHFW UHSRUWV PXOWLSOH FRQGLWLRQV ZLWKLQ WKH VDPH 62& WKDW 62&
ZLOO RQO\ EH UHSRUWHG RQFH
/LVWLQJV RI PHGLFDO KLVWRU\ ZLOO EH JHQHUDWHG VHSDUDWHO\ IRU RFXODU DQG QRQRFXODU GDWD

3ULRU DQG &RQFRPLWDQW 0HGLFDWLRQV


3URWRFRO $';$& 9HUVLRQ 
0$<
&RQILGHQWLDO 	 3URSULHWDU\
3DJH  RI 
 ([SRVXUH WR ,QYHVWLJDWLRQDO 3URGXFW
7KH QXPEHU DQG SHUFHQWDJH RI VXEMHFWV LQVWLOOHG ZLWK ,3 ZLOO EH VXPPDUL]HG E\ YLVLW DQG WUHDWPHQW JURXS
IRU WKH 6DIH\ SRSXODWLRQ 3HUFHQWDJHV ZLOO EH FDOFXODWHG EDVHG RQ WKH WRWDO QXPEHU RI VXEMHFWV LQ HDFK
WUHDWPHQW JURXS ZLWK UHVSRQVHV
$ OLVWLQJ RI ,3 LQVWLOODWLRQ IRU DOO VXEMHFWV ZLOO DOVR EH SURYLGHG
 (IILFDF\ $QDO\VHV

3ULPDU\ $QDO\VLV
7KH SULPDU\ HIILFDF\ YDULDEOH LV RFXODU LWFKLQJ HYDOXDWHG E\ WKH VXEMHFW DW   DQG 
PLQXWHV SRVW&$& PHDVXUHG DW 9LVLW   KRXU SRVW WUHDWPHQW DQG 9LVLW  PLQXWHV SRVW WUHDWPHQW
2FXODU LWFKLQJ ZLOO EH HYDOXDWHG XVLQJ WKH IROORZLQJ 2UD &DOLEUD70 &RQMXQFWLYDO $OOHUJHQ &KDOOHQJH
2FXODU ,WFKLQJ 6FDOH






3URWRFRO $';$& 9HUVLRQ 
0$<
&RQILGHQWLDO 	 3URSULHWDU\
3DJH  RI 


3URWRFRO $';$& 9HUVLRQ 
0$<
&RQILGHQWLDO 	 3URSULHWDU\
3DJH  RI 
 ([SORUDWRU\ $QDO\VHV
7KHUH LV QR SODQQHG H[SORUDWRU\ DQDO\VLV IRU WKLV VWXG\
 6DIHW\ $QDO\VHV
7KH SULPDU\ VDIHW\ YDULDEOH LV WKH LQFLGHQFH RI VXEMHFWV ZLWK DQ\ $( GXULQJ WKH HQWLUH VWXG\
7KH VHFRQGDU\ VDIHW\ YDULDEOHV RI YLVXDO DFXLW\ VOLWODPS ELRPLFURVFRS\ ,23 DQG GLODWHG IXQGXV
H[DPLQDWLRQ ZLOO EH VXPPDUL]HG GHVFULSWLYHO\ XVLQJ TXDQWLWDWLYH DQG TXDOLWDWLYH VXPPDU\ VWDWLVWLFV DV
DSSURSULDWH &KDQJHV DQG VKLIWV IURP EDVHOLQH ZLOO DOVR EH VXPPDUL]HG ZKHUH DSSOLFDEOH
$OO VDIHW\ DQDO\VHV ZLOO EH FRQGXFWHG XVLQJ WKH 6DIHW\ 3RSXODWLRQ 1R VWDWLVWLFDO LQIHUHQWLDO WHVWLQJ ZLOO EH
SHUIRUPHG IRU VDIHW\ YDULDEOHV

$GYHUVH (YHQWV
$Q $( LV GHILQHG DV DQ\ XQWRZDUG PHGLFDO RFFXUUHQFH DVVRFLDWHG ZLWK WKH XVH RI DQ ,3 LQ KXPDQV
ZKHWKHU RU QRW FRQVLGHUHG ,3UHODWHG $Q $( FDQ EH DQ\ XQIDYRUDEOH DQG XQLQWHQGHG VLJQ HJ DQ
DEQRUPDO ODERUDWRU\ ILQGLQJ V\PSWRP RU GLVHDVH WHPSRUDOO\ DVVRFLDWHG ZLWK WKH XVH RI DQ ,3 ZLWKRXW
DQ\ MXGJPHQW DERXW FDXVDOLW\ $Q $( FDQ DULVH IURP DQ\ XVH RI WKH ,3 HJ RIIODEHO XVH XVH LQ
FRPELQDWLRQ ZLWK DQRWKHU GUXJ RU PHGLFDO GHYLFH DQG IURP DQ\ URXWH RI DGPLQLVWUDWLRQ IRUPXODWLRQ RU
GRVH LQFOXGLQJ DQ RYHUGRVH $Q $( FDQ DULVH IURP DQ\ GHOLYHU\ LPSODQWDWLRQ RU XVH RI D PHGLFDO GHYLFH
LQFOXGLQJ PHGLFDO GHYLFH IDLOXUH VXEMHFW FKDUDFWHULVWLFV WKDW PD\ LPSDFW PHGLFDO GHYLFH SHUIRUPDQFH
HJ DQDWRPLFDO OLPLWDWLRQV DQG WKHUDSHXWLF SDUDPHWHUV HJ HQHUJ\ DSSOLHG VL]LQJ GRVH UHOHDVH
DVVRFLDWHG ZLWK PHGLFDO GHYLFH
$OO $(V VSRQWDQHRXVO\ UHSRUWHG E\ WKH VXEMHFW DQGRU LQ UHVSRQVH WR DQ RSHQ TXHVWLRQ IURP VWXG\
SHUVRQQHO RU UHYHDOHG E\ REVHUYDWLRQ SK\VLFDO H[DPLQDWLRQ RU RWKHU GLDJQRVWLF SURFHGXUHV ZLOO EH
UHFRUGHG LQ WKH VRXUFH GRFXPHQW DQG RQ WKH DSSURSULDWH SDJHV RI WKH H&5) $Q\ FOLQLFDOO\ UHOHYDQW
GHWHULRUDWLRQ LQ FOLQLFDO ILQGLQJ LV FRQVLGHUHG DQ $( DQG PXVW EH UHFRUGHG :KHQ SRVVLEOH VLJQV DQG
V\PSWRPV LQGLFDWLQJ D FRPPRQ XQGHUO\LQJ SDWKRORJ\ VKRXOG EH QRWHG DV RQH FRPSUHKHQVLYH HYHQW
$Q\ SUHH[LVWLQJ PHGLFDO FRQGLWLRQ WKDW ZRUVHQV DIWHU DGPLQLVWUDWLRQ RI VWXG\ PHGLFDWLRQ ZLOO DOVR EH
FRQVLGHUHG D QHZ $( 6WXG\ PHGLFDWLRQ LQFOXGHV WKH GUXJ XQGHU HYDOXDWLRQ RU DQ\ RWKHU PHGLFDWLRQV
UHTXLUHG E\ WKH SURWRFRO JLYHQ GXULQJ DQ\ VWDJH RI WKH VWXG\


3URWRFRO $';$& 9HUVLRQ 
0$<
&RQILGHQWLDO 	 3URSULHWDU\
3DJH  RI 
2FXODU FRPSODLQWV VKRXOG QRW EH DGGUHVVHG DV $(V XQOHVV WKH FRPSODLQW LV RXWVLGH WKH QRUPDO OLPLWV IRU
DOOHUJLF FRQMXQFWLYLWLV V\PSWRPV DIWHU DOOHUJHQ H[SRVXUH RU LV DVVRFLDWHG ZLWK FOLQLFDO VHTXHODH LH
DGYHUVH VOLWODPS H[DPLQDWLRQ ILQGLQJ
7UHDWPHQWHPHUJHQW DGYHUVH HYHQWV 7($(V DUH GHILQHG DV DQ\ HYHQW WKDW RFFXUV RU ZRUVHQV RQ RU
DIWHU WKH GD\ WKDW UDQGRPL]HG VWXG\ WUHDWPHQW LV LQLWLDWHG
$Q $( LV FRQVLGHUHG VHULRXV LI LQ WKH YLHZ RI HLWKHU WKH LQYHVWLJDWRU RU VSRQVRU LW UHVXOWV LQ DQ\ RI WKH
IROORZLQJ RXWFRPHV
x
'HDWK
x
$ OLIHWKUHDWHQLQJ $(
1RWH
$Q $( LV FRQVLGHUHG ³OLIHWKUHDWHQLQJ´ LI LQ WKH YLHZ RI HLWKHU WKH LQYHVWLJDWRU RU
6SRQVRUGHVLJQHH LWV RFFXUUHQFH SODFHV WKH VXEMHFW DW LPPHGLDWH ULVN RI GHDWK ,W GRHV QRW
LQFOXGH DQ $( WKDW KDG LW RFFXUUHG LQ D PRUH VHYHUH IRUP PLJKW KDYH FDXVHG GHDWK
x
,QSDWLHQW KRVSLWDOL]DWLRQ RU SURORQJDWLRQ RI H[LVWLQJ KRVSLWDOL]DWLRQ
1RWH 7KH WHUP ³LQSDWLHQW KRVSLWDOL]DWLRQ´ UHIHUV WR DQ\ LQSDWLHQW DGPLVVLRQ HYHQ LI OHVV
WKDQ  KRXUV )RU FKURQLF RU ORQJWHUP LQSDWLHQWV LQSDWLHQW DGPLVVLRQ LQFOXGHV WUDQVIHU
ZLWKLQ WKH KRVSLWDO WR DQ DFXWHLQWHQVLYH FDUH LQSDWLHQW XQLW ,QSDWLHQW KRVSLWDOL]DWLRQ GRHV
QRW
LQFOXGH
HPHUJHQF\
URRP
YLVLWV
RXWSDWLHQWVDPHGD\DPEXODWRU\
SURFHGXUHV
REVHUYDWLRQVKRUW VWD\ XQLWV UHKDELOLWDWLRQ IDFLOLWLHV KRVSLFH IDFLOLWLHV QXUVLQJ KRPHV RU
FOLQLFDO UHVHDUFKSKDVH  XQLWV
1RWH
7KH WHUP ³SURORQJDWLRQ RI H[LVWLQJ KRVSLWDOL]DWLRQ´ UHIHUV WR DQ\ H[WHQVLRQ RI DQ
LQSDWLHQW KRVSLWDOL]DWLRQ EH\RQG WKH VWD\ DQWLFLSDWHG RU UHTXLUHG IRU WKH UHDVRQ IRU WKH LQLWLDO
DGPLVVLRQ DV GHWHUPLQHG E\ WKH LQYHVWLJDWRU RU WUHDWLQJ SK\VLFLDQ
x
$ SHUVLVWHQW RU VLJQLILFDQW LQFDSDFLW\ RU VXEVWDQWLDO GLVUXSWLRQ RI WKH DELOLW\ WR FRQGXFW QRUPDO
OLIH IXQFWLRQV
1RWH
$ 6$( VSHFLILFDOO\ UHODWHG WR YLVXDO WKUHDW ZRXOG EH LQWHUSUHWHG DV DQ\ SRWHQWLDO
LPSDLUPHQW RU GDPDJH WR WKH VXEMHFW¶V H\HV HJ KHPRUUKDJH UHWLQDO GHWDFKPHQW FHQWUDO
FRUQHDO XOFHU RU GDPDJH WR WKH RSWLF QHUYH
x
$ FRQJHQLWDO DQRPDO\ELUWK GHIHFW
,PSRUWDQW PHGLFDO HYHQWV WKDW PD\ QRW UHVXOW LQ GHDWK DUH OLIHWKUHDWHQLQJ RU UHTXLUH KRVSLWDOL]DWLRQ PD\
EH FRQVLGHUHG VHULRXV ZKHQ EDVHG XSRQ DSSURSULDWH PHGLFDO MXGJPHQW WKH\ PD\ MHRSDUGL]H WKH
VXEMHFW DQG PD\ UHTXLUH PHGLFDO RU VXUJLFDO LQWHUYHQWLRQ WR SUHYHQW RQH RI WKH RXWFRPHV OLVWHG LQ WKLV
GHILQLWLRQ
7KH UHODWLRQVKLS RI HDFK $( WR WKH ,3 VKRXOG EH GHWHUPLQHG E\ WKH LQYHVWLJDWRU XVLQJ WKHVH H[SODQDWLRQV


3URWRFRO $';$& 9HUVLRQ 
0$<
&RQILGHQWLDO 	 3URSULHWDU\
3DJH  RI 
x
6XVSHFWHG $ UHDVRQDEOH SRVVLELOLW\ H[LVWV WKDW WKH ,3 FDXVHG WKH $(
x
1RW 6XVSHFWHG $ UHDVRQDEOH SRVVLELOLW\ GRHV QRW H[LVW WKDW WKH ,3 FDXVHG WKH $(
1RWH ³5HDVRQDEOH SRVVLELOLW\´ PHDQV WKHUH LV HYLGHQFH WR VXJJHVW D FDXVDO UHODWLRQVKLS
EHWZHHQ WKH LQYHVWLJDWLRQDO SURGXFW DQG WKH $( 7\SHV RI HYLGHQFH WKDW ZRXOG VXJJHVW D
FDXVDO UHODWLRQVKLS EHWZHHQ WKH LQYHVWLJDWLRQDO SURGXFW DQG WKH $( LQFOXGH D VLQJOH
RFFXUUHQFH RI DQ HYHQW WKDW LV XQFRPPRQ DQG NQRZQ WR EH VWURQJO\ DVVRFLDWHG ZLWK
LQYHVWLJDWLRQDO SURGXFW H[SRVXUH HJ DQJLRHGHPD KHSDWLF LQMXU\ 6WHYHQV-RKQVRQ
6\QGURPH RQH RU PRUH RFFXUUHQFHV RI DQ HYHQW WKDW LV QRW FRPPRQO\ DVVRFLDWHG ZLWK
LQYHVWLJDWLRQDO SURGXFW H[SRVXUH EXW LV RWKHUZLVH XQFRPPRQ LQ WKH SRSXODWLRQ H[SRVHG WR WKH
LQYHVWLJDWLRQDO SURGXFW HJ WHQGRQ UXSWXUH DQ DJJUHJDWH DQDO\VLV RI VSHFLILF HYHQWV
REVHUYHG LQ D FOLQLFDO WULDO VXFK DV NQRZQ FRQVHTXHQFHV RI WKH XQGHUO\LQJ GLVHDVH RU FRQGLWLRQ
XQGHU LQYHVWLJDWLRQ RU RWKHU HYHQWV WKDW FRPPRQO\ RFFXU LQ WKH VWXG\ SRSXODWLRQ LQGHSHQGHQW RI
GUXJ WKHUDS\ WKDW LQGLFDWHV WKRVH HYHQWV RFFXU PRUH IUHTXHQWO\ LQ WKH LQYHVWLJDWLRQDO SURGXFW
WUHDWPHQW JURXS WKDQ LQ D FRQFXUUHQW RU KLVWRULFDO FRQWURO JURXS
6HYHULW\ RI DQ $( LV GHILQHG DV D TXDOLWDWLYH DVVHVVPHQW RI WKH GHJUHH RI LQWHQVLW\ RI DQ $( DV
GHWHUPLQHG E\ WKH LQYHVWLJDWRU RU UHSRUWHG WR KLPKHU E\ WKH VXEMHFW 7KH DVVHVVPHQW RI VHYHULW\ LV
PDGH LUUHVSHFWLYH RI UHODWLRQVKLS WR ,3 RU VHULRXVQHVV RI WKH HYHQW DQG VKRXOG EH HYDOXDWHG DFFRUGLQJ
WR WKH IROORZLQJ VFDOH
x
0LOG (YHQW LV QRWLFHDEOH WR WKH VXEMHFW EXW LV HDVLO\ WROHUDWHG DQG GRHV QRW LQWHUIHUH ZLWK WKH
VXEMHFW¶V GDLO\ DFWLYLWLHV
x
0RGHUDWH (YHQW LV ERWKHUVRPH SRVVLEO\ UHTXLULQJ DGGLWLRQDO WKHUDS\ DQG PD\ LQWHUIHUH ZLWK WKH
VXEMHFW¶V GDLO\ DFWLYLWLHV
x
6HYHUH (YHQW LV LQWROHUDEOH QHFHVVLWDWHV DGGLWLRQDO WKHUDS\ RU DOWHUDWLRQ RI WKHUDS\ DQG
LQWHUIHUHV ZLWK WKH VXEMHFW¶V GDLO\ DFWLYLWLHV
$Q RYHUDOO VXPPDU\ ZLOO EH SUHVHQWHG WKDW LQFOXGHV WKH QXPEHU RI $(V DQG WKH QXPEHU DQG SHUFHQWDJH
RI VXEMHFWV ZKR H[SHULHQFHG DW OHDVW RQH $( E\ WUHDWPHQW JURXS DQG IRU DOO VXEMHFWV FRPELQHG 7KLV
VXPPDU\ ZLOO DOVR LQFOXGH EUHDNGRZQV RI $(V IXUWKHU FDWHJRUL]HG DV RFXODU RU QRQRFXODU 6$(V $(V
E\ PD[LPXP VHYHULW\ DQG UHODWLRQVKLS WR ,3 QXPEHU RI VXEMHFWV ZLWK $(V OHDGLQJ WR VXEMHFW ZLWKGUDZDO
DQG QXPEHU RI VXEMHFWV ZLWK $(V UHVXOWLQJ LQ GHDWK 7($(V VXPPDUL]HG IRU WKH VDPH FDWHJRULHV ZLOO
DOVR EH LQFOXGHG


3URWRFRO $';$& 9HUVLRQ 
0$<
&RQILGHQWLDO 	 3URSULHWDU\
3DJH  RI 
$GGLWLRQDO VXPPDULHV RI $(V ZLOO EH SURYLGHG VKRZLQJ WKH QXPEHU RI $(V DQG WKH QXPEHU DQG
SHUFHQWDJH RI VXEMHFWV ZKR H[SHULHQFHG DW OHDVW RQH $( 7KHVH VXPPDULHV ZLOO EH SUHVHQWHG DW WKH
VXEMHFW DQG HYHQW OHYHO E\ 62& DQG 37 ,I D VXEMHFW UHSRUWV WKH VDPH 37 PXOWLSOH WLPHV ZLWKLQ WKH VDPH
62& WKDW 37 ZLOO RQO\ EH UHSRUWHG RQFH ZLWKLQ WKDW 62& $V ZLWK WKH 37 LI D VXEMHFW UHSRUWV PXOWLSOH
FRQGLWLRQV ZLWKLQ WKH VDPH 62& WKDW 62& ZLOO RQO\ EH UHSRUWHG RQFH ,Q WKH VXPPDU\ 62& ZLOO EH
OLVWHG LQ DVFHQGLQJ DOSKDEHWLFDO RUGHU 37V ZLOO EH OLVWHG LQ RUGHU RI GHVFHQGLQJ IUHTXHQF\ IRU DOO VXEMHFWV
ZLWKLQ HDFK 62& 7KHVH VXPPDULHV ZLOO EH SUHVHQWHG IRU RFXODU DQG QRQRFXODU $(V VHSDUDWHO\ DQG
LQFOXGH WKH IROORZLQJ
x
$OO $(V
x
$OO 7($(V
x
$OO 7($(V VXVSHFWHG WR EH UHODWHG WR WKH ,3
x
$OO 6$(V
x
$OO 7($(V E\ PD[LPDO VHYHULW\ DQG
6XEMHFW OLVWLQJV ZLOO EH SURYLGHG IRU DOO DGYHUVH HYHQWV VHULRXV DGYHUVH HYHQWV DGYHUVH HYHQWV OHDGLQJ
WR GHDWK DQG DGYHUVH HYHQWV OHDGLQJ WR VWXG\ WUHDWPHQW GLVFRQWLQXDWLRQ

9LVXDO $FXLW\ (7'56
9$ ZLOO EH PHDVXUHG DW HYHU\ VWXG\ YLVLW SULRU WR WKH &$& )RU 9LVLW  LW ZLOO EH PHDVXUHG DJDLQ SRVW
&$& 9LVXDO DFXLW\ ORJ0$5 ZLOO EH VXPPDUL]HG E\ WUHDWPHQW XVLQJ WKH DYHUDJH RI ERWK H\HV IRU HDFK
VXEMHFW ZLWK TXDQWLWDWLYH VXPPDU\ VWDWLVWLFV 7KH QXPEHU RI VXEMHFWV ZLWK ZRUVHQLQJ RI DFXLW\ RI 
OHWWHUV RU PRUH IURP EDVHOLQH ZLOO DOVR EH VXPPDUL]HG ZLWK FRXQWV DQG ZLWK SHUFHQWDJHV EDVHG RQ WKH
WRWDO QXPEHU RI VXEMHFWV LQ HDFK WUHDWPHQW JURXS ZLWK UHVSRQVHV 5HVXOWV IRU 9$ ZLOO EH SUHVHQWHG LQ D
GDWD OLVWLQJ

6OLW/DPS %LRPLFURVFRS\ ([DPLQDWLRQ
$ VOLWODPS ELRPLFURVFRS\ H[DPLQDWLRQ ZLOO EH SHUIRUPHG DW HDFK YLVLW SULRU WR WKH &$& DQG DJDLQ SRVW
&$& IRU 9LVLW  DQG ZLOO FRQVLVW RI WKH H[DPLQDWLRQ RI WKH IROORZLQJ LWHPV
x
(\HOLG
x
&RQMXQFWLYD
x
&RUQHD
x
/HQV DQG
x
$QWHULRU &KDPEHU
7KH UHVXOWV ZLOO EH JUDGHG DV QRUPDO DEQRUPDO QRW FOLQLFDOO\ VLJQLILFDQW 1&6 RU DEQRUPDO FOLQLFDOO\
VLJQLILFDQW &6 7KH UHVXOWV ZLOO EH VXPPDUL]HG XVLQJ FRXQWV DQG SHUFHQWDJHV IRU HDFK WUHDWPHQW JURXS
IRU DOO H\HV FRPELQHG 3HUFHQWDJHV ZLOO EH EDVHG RQ WKH QXPEHU RI VXEMHFWV H\HV LQ HDFK WUHDWPHQW