Conditions: Macular Edema
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 284
Healthy volunteers: no

Brief summary:
This study will evaluate the safety and efficacy of 700 μg dexamethasone versus laser photocoagulation in participants with diabetic macular edema (DME).

Detailed description:

Arms:
arm 1: Laser photocoagulation was administered in the study eye on Day 1, and on Months 3, 6, and 9, if retreatment indicated. arm 2: Dexamethasone 700 μg was administered as intravitreal injection in the study eye on Day 1, Months 5, and 10.

Interventions: intervention 1: Dexamethasone intervention 2: Laser Photocoagulation
Intervention descriptions: intervention 1: Dexamethasone 700 μg intravitreal injection in the study eye on Day 1, Months 5, and 10. intervention 2: Laser photocoagulation on Day 1, and on Months 3, 6, and 9, if retreatment indicated.

Protocol document:
Prot_001.pdf: 
NCT02121262 
 
Study ID: 206207‐026 
 
 
Title:  Dexamethasone Posterior Segment Drug Delivery System Versus Laser Photocoagulation in 
Patients With Diabetic Macular Edema 
 
 
Protocol Amendment 1 Date: 25Apr2013 
 
 
 


Allergan Confidential 
Protocol 206207-026 Amendment 1 
700 µg DEX PS DDS 
 
 
 
1 
 
 
  
 
ALLERGAN – CONFIDENTIAL 
The following contains confidential, proprietary information  
which is the property of Allergan 
 
STUDY TITLE 
Dexamethasone Posterior Segment Drug Delivery System Versus Laser Photocoagulation in 
Patients with Diabetic Macular Edema 
Protocol Number:   
206207-026 
Phase: 
3 
Name of Investigational Product:  
Dexamethasone Posterior Segment Drug Delivery System 
Sponsor: 
 
Allergan (North America) 
2525 Dupont Drive 
Irvine, California USA 
92612 
 
 
Emergency Telephone Number: 
Serious Adverse Event Reporting 
Fax Numbers: 
Allergan Medical Safety Physician 
Contact Information: 
Allergan Signatory: 
Refer to the final page of this protocol for electronic signature 
and date of approval. 
 
 


Allergan Confidential 
Protocol 206207-026 Amendment 1 
700 µg DEX PS DDS 
 
 
 
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INVESTIGATOR SIGNATURE PAGE 
INVESTIGATOR: 
 
STUDY LOCATION: 
 
 
I agree to: 
• Implement and conduct this study diligently and in strict compliance with the protocol, 
good clinical practices and all applicable laws and regulations. 
• Maintain all information supplied by Allergan in confidence and, when this information 
is submitted to an Institutional Review Board (IRB), Independent Ethics Committee 
(IEC) or another group, it will be submitted with a designation that the material is 
confidential. 
I have read this protocol in its entirety and I agree to all aspects. 
 
  
  
Investigator Printed Name  
  Signature 
  Date 
 
  
  
Investigator Printed Name  
  Signature 
  Date 
 
  
  
Investigator Printed Name  
  Signature 
  Date 
 
RETURN
 TO
 ALLERGAN
 WITH
 ATTACHED
 PROTOCOL
 
 
 


Allergan Confidential 
Protocol 206207-026 Amendment 1 
700 µg DEX PS DDS 
 
 
 
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Table of Contents 
Table of Contents 
...................................................................................................................... 3
 
List of Tables 
............................................................................................................................. 7
 
List of Figures 
........................................................................................................................... 7
 
Protocol Summary .................................................................................................................... 8
 
1. Background and Clinical Rationale 
................................................................................. 13 
2. Study Objectives and Clinical Hypotheses 
...................................................................... 16 
2.1  Study Objectives .................................................................................................... 16 
2.2  Clinical Hypotheses ............................................................................................... 17 
3. Study Design 
.................................................................................................................... 17
 
4. Study Population and Entry Criteria 
................................................................................ 17 
4.1  Number of Patients 
................................................................................................. 17 
4.2  Study Population Characteristics ........................................................................... 18 
4.3  Inclusion Criteria 
.................................................................................................... 18 
4.4  Exclusion Criteria................................................................................................... 19 
4.5  Permissible and Prohibited Medications/Treatments 
............................................. 21 
4.5.1 Permissible Medications/Treatments ......................................................... 21 
4.5.2 Acceptable Contraceptive Methods 
........................................................... 22 
4.5.3 Prohibited Medications/Treatments ........................................................... 22 
5. Study Treatments 
............................................................................................................. 23 
5.1  Study Treatments and Formulations 
....................................................................... 23 
5.2  Control Treatment 
.................................................................................................. 23 
5.3  Escape Therapy 
...................................................................................................... 23 
5.4  Methods for Masking/Blinding 
.............................................................................. 23 
5.5  Treatment Allocation Ratio and Stratification........................................................ 24 
5.6  Method for Assignment to Treatment Groups/Randomization 
.............................. 24 
5.7  Treatment Regimen and Dosing 
............................................................................. 24 
5.7.1 DEX PS DDS 
............................................................................................. 24 
5.7.2 Laser Photocoagulation 
.............................................................................. 25 
5.8  Storage of Study Medication 
.................................................................................. 25 
5.9  Study Drug Administration 
.................................................................................... 25 


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5.9.1 Peri-operative Anti-infective Treatment 
..................................................... 25 
5.9.2 Product Dispensing 
.................................................................................... 25 
5.9.3 Final Product Disposition 
........................................................................... 26 
5.9.4 Operative Procedure 
................................................................................... 26 
6. Response Measures and Summary of Data Collection Methods 
..................................... 27
 
6.1  Efficacy Measures 
.................................................................................................. 27 
6.1.1 Primary Efficacy Measure 
.......................................................................... 27 
6.1.2 Secondary Efficacy Measures 
.................................................................... 27 
 
 
 
 
6.4  Examination Procedures, Tests, Equipment, and Techniques 
................................ 28 
6.4.1 Best-corrected Visual Acuity 
...................................................................... 28 
6.4.2 Optical Coherence Tomography 
................................................................. 28 
6.4.3 Fluorescein Angiography 
........................................................................... 28 
6.4.4 Intraocular Pressure Measurement 
............................................................. 28 
6.5  Other Study Supplies 
.............................................................................................. 28 
6.6  Summary of Methods of Data Collection 
.............................................................. 29 
7. Statistical Procedures 
....................................................................................................... 29 
7.1  Analysis Populations 
.............................................................................................. 29 
7.2  Collection and Derivation of Primary and Secondary  Efficacy Assessments 
....... 29 
7.2.1 Primary Efficacy Variables 
......................................................................... 30 
7.2.2 Secondary Efficacy Variables 
..................................................................... 30 
7.3  Hypothesis and Methods of Analysis 
..................................................................... 31 
7.3.1 Primary Efficacy Analyses 
......................................................................... 31 
7.3.2 Secondary Efficacy Analyses 
..................................................................... 31 
 
 
 
 
 
 
 
 
7.5  Interim Analyses..................................................................................................... 33 
8. Study Visit Schedule and Procedures .............................................................................. 33 
8.1  Patient Entry Procedures 
........................................................................................ 34 
8.1.1 Overview of Entry Procedures 
................................................................... 34 
8.1.2 Informed Consent 
....................................................................................... 34 


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8.3  Instructions for Patients.......................................................................................... 40 
8.4  Unscheduled Visits 
................................................................................................. 40 
8.5  Compliance with Protocol 
...................................................................................... 41 
8.6  Early Discontinuation of Patients .......................................................................... 41 
8.7  Study Termination 
.................................................................................................. 41 
9. Adverse Events 
................................................................................................................ 41
 
9.1  Definitions 
.............................................................................................................. 41 
9.1.1 Adverse Event 
............................................................................................ 41 
9.1.2 Serious Adverse Event 
............................................................................... 42 
9.1.3 Severity ...................................................................................................... 42 
9.1.4 Relationship to Study Drug or Study Procedure 
........................................ 42 
9.2  Procedures for Reporting Adverse Events 
............................................................. 43 
9.3  Procedures for Reporting a Serious Adverse Event 
............................................... 43 
9.4  Procedures for Unmasking of Study Medication 
................................................... 44 
10. Administrative Items ....................................................................................................... 44 
10.1 Protection of Patients 
............................................................................................. 44 
10.1.1 Compliance with Informed Consent Regulations and  Relevant Country 
Regulations 
................................................................................................. 44 
10.1.2 Compliance With IEC Regulations 
............................................................ 44 
10.1.3 Compliance With Good Clinical Practice 
.................................................. 44 
10.1.4 Compliance With Electronic Records; Electronic Signatures  Regulations45 
10.2 Changes to the Protocol ......................................................................................... 45 
10.3 Patient Confidentiality ........................................................................................... 45 


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10.3.1 Patient Privacy ........................................................................................... 45 
10.4 Documentation 
....................................................................................................... 45 
10.4.1 Source Documents ..................................................................................... 45 
10.4.2 Electronic Case Report Form Completion 
................................................. 47 
10.4.3 Study Summary 
.......................................................................................... 47 
10.4.4 Retention of Documentation 
...................................................................... 48 
10.5 Labeling, Packaging, and Return or Disposal of Study Medications/Treatments 
.. 48 
10.5.1 Labeling/Packaging 
.................................................................................... 48 
10.5.2 Clinical Supply Inventory 
.......................................................................... 48 
10.5.3 Return or Disposal of Study Medications/Treatments and /or Supplies 
.... 49 
10.6 Monitoring by Allergan 
.......................................................................................... 49 
10.7 Handling of Biological Specimens......................................................................... 49 
10.8 Publications 
............................................................................................................ 49 
10.9 Coordinating Investigator ...................................................................................... 50 
11. References 
........................................................................................................................ 50
 
12. Attachments 
..................................................................................................................... 52
 
12.1 Examination Procedures, Tests, Equipment, and Techniques 
................................ 52 
 
 
12.1.2  Pregnancy Test 
......................................................................................... 52 
12.1.3  Handling of Biological Specimens 
.......................................................... 52 
12.1.4  Visual Acuity Assessment ....................................................................... 53 
12.1.5  Intraocular Pressure 
................................................................................. 53 
12.1.6  Optical Coherence Tomography 
.............................................................. 53 
12.1.7  Biomicroscopic Examination 
.................................................................. 53 
12.1.8  Fundus Ophthalmoscopic Examination 
................................................... 58 
12.1.9  Fluorescein Angiography ........................................................................ 61 
 
12.1.11 Modified-ETDRS Focal Photocoagulation Technique 
............................ 61 
12.2 Glossary of Abbreviations 
...................................................................................... 63 
12.3 Protocol Amendment Summary 
............................................................................. 65 


Allergan Confidential 
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List of Tables 
 
 
  
List of Figures 
 
 
Figure 2 
Dexamethasone Posterior Segment Drug Delivery System 
............................ 15 
  
 


Allergan Confidential 
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Protocol Summary 
Study Compound:  700 µg dexamethasone posterior segment drug delivery system (DEX PS DDS) 
Phase:  3 
Study Objectives:  
• To evaluate the safety and efficacy of the 700 µg DEX PS DDS compared with laser photocoagulation 
in patients with diabetic macular edema (DME) 
Clinical Hypotheses:  
• Treatment with 700 µg DEX PS DDS every 5 months is superior to laser photocoagulation according 
to the modified Early Treatment Diabetic Retinopathy Study (ETDRS) protocol with respect to the 
average change from baseline of best-corrected visual acuity (BCVA) during 12 months of treatment 
for DME 
• 700 µg DEX PS DDS administered every 5 months has an acceptable safety profile 
Study Design: 
Structure:  multicenter, randomized, comparative study 
Duration:  12 months 
Study Treatment Group:  700 µg DEX PS DDS  
Control:  laser photocoagulation according to the modified ETDRS protocol 
Dosage/Dose Regimen:   
• 700 µg DEX PS DDS every 5 months 
• Laser photocoagulation as needed according to ETDRS protocol every 3 months if  
o Optical coherence tomography (OCT) central subfield ≥ 250 µm with Stratus III (Zeiss), 
≥ 275 µm with Cirrus (Zeiss) or  
≥ 300 µm with Spectralis (Heidelberg)  
AND 
o Patient might benefit from retreatment in the opinion of the investigator 
Randomization/Stratification:  1:1 randomization, stratification by BCVA score (≥ 34 to ≤ 49 and  ≥ 50 to ≤ 70) 
at baseline within each study site 
 
 
 
 
 
 
 
 
 
Study Population Characteristics: 
Number of Patients:  Approximately 356 patients will be enrolled at 20 sites to ensure that at least 151 patients 
in each treatment group complete the study. 
Condition/Disease:  DME 
Key Inclusion Criteria:   
• male or female, at least 18 years of age 
• prior diagnosis of diabetes mellitus (type 1 or type 2)  
• presence of macular edema associated with diabetic retinopathy, defined as macular thickening by OCT as 
assessed by the investigator in the study eye involving the center of the macula (fovea) and with visual 
acuity (VA) decrease attributable to macular edema 


Allergan Confidential 
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700 µg DEX PS DDS 
 
 
 
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Key Exclusion Criteria:   
 
  
 
 
 
 
 
 
 
 
 
 
 
• laser photocoagulation to the retina of the study eye within 3 months prior to screening   
 
 
   
 
 
 
 
 
 
 
 
 
 
Response Measures 
Efficacy:  BCVA measured by ETDRS, central retinal thickness measured by OCT, area of macular leakage 
measured with fluorescein angiography (FA) 
 
 
  
  
 
General Statistical Methods and Types of Analyses:   
Analysis Populations:  Three populations will be used for statistical analyses:  modified intent-to-treat (mITT),  
per-protocol (PP), and safety. 
Primary Efficacy Analysis:  The primary efficacy endpoint is the average change from baseline in BCVA over 
12 months.  The primary analysis will be an analysis of covariance (ANCOVA) comparing the treatment 
difference in the mean average BCVA change from baseline in a 12-month study period.  The ANCOVA model 
will include the treatment group as the main effect and baseline BCVA score as the covariate.  The average 
change will be computed by subtracting the baseline BCVA from the area under the BCVA curve (AUC) 
divided by the total follow-up time for each patient.  Calculations for AUC will be based on observed data using 


Allergan Confidential 
Protocol 206207-026 Amendment 1 
700 µg DEX PS DDS 
 
 
 
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the trapezoidal method and will include all postbaseline BCVA data for the patient from the study treatment to 
the last VA measurement, regardless of scheduled or unscheduled visits.   
Secondary Efficacy Analyses:  Secondary efficacy analyses include a Cochran–Mantel-Haenszel (CMH) test 
stratified within each study site by baseline BCVA categories (≥ 34 to ≤ 49 and  ≥ 50 to ≤ 70) for treatment 
difference in proportion of patients with ≥ 15 letters improvement from baseline of BCVA at month 12; and 
ANCOVA on retinal thickness and total leakage area at month 12. 
 
 
 
 
 
   






Allergan Confidential 
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700 µg DEX PS DDS 
 
 
 
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1. 
 Background and Clinical Rationale  
Diabetes affects more than 220 million people worldwide (World Health Organization, 
WHO Diabetes Fact Sheet, 2011) and its prevalence is expected to grow to 366 million by 
2030 (Wild et al, 2004).  Diabetic macular edema (DME) is 1 of the major causes of vision 
loss in patients with diabetic retinopathy (Resnikoff et al, 2004).  Diabetic retinopathy (DR) 
and DME are common microvascular complications in patients with diabetes and may have 
sudden and debilitating impact on VA, eventually leading to blindness.  DME is a frequent 
manifestation of DR and is a major cause of vision loss in patients with DR.  DME results 
from retinal microvascular changes.  Thickening of the basement membrane and reduction in 
the number of pericytes are believed to lead to increased permeability and incompetence of 
the retinal vasculature.  This compromise of the blood-retinal barrier (BRB) leads to the 
leakage of plasma constituents into the surrounding retina, with subsequent retinal edema 
(Albert and Jakobiec, 2000).  Increase of vascular permeability and breakdown of the BRB in 
DME is thought to be caused by vascular epithelial growth factor (VEGF) effects, such as 
phosphorylation of tight junctional protein occludin and Fas-mediated endothelial cell 
apoptosis, and also by inflammatory effects like leukostasis, possibly due to increased 
expression of leukocyte adhesion molecules (Aiello et al, 1997). 
Laser photocoagulation has been shown to be efficacious in the prevention of mild to 
moderate vision loss from DME (ETDRS Report #1, 1985).  In the ETDRS protocol, laser 
photocoagulation reduced the risk of moderate visual loss from DME by 50% (from 24% to 
12% 3 years after initiation of treatment (ETDRS Report #2, 1987).  However, few patients 
experience improvement in vision following laser alone for DME, and persistent and 
recurrent macular edema is common (ETDRS Report #9, 1991).  DME due to DR may come 
from discrete points of leakage (focal edema) or from geographic areas of diffuse retinal 
vascular hyperpermeability (diffuse edema).  Diffuse diabetic macular edema is particularly 
refractory to laser treatment  (Bresnick, 1983).  The present study will use a modified 
EDTRS protocol (Modified-ETDRS Focal Photocoagulation Technique [Internet], 2006) 
commonly used in clinical practice (See Section 12.1.11). 
Ranibizumab has been approved for the treatment of DME in Europe and more recently 
(August 2012) in the USA. However, in China, for example, ranibizumab is approved only 
for treatment of age-related macular degeneration (AMD) and laser photocoagulation 
remains the current standard of care for DME. 
 


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Corticosteroids modulate vascular permeability through anti-inflammatory effects, in 
addition to suppressing production of VEGF and other permeability factors.   
Dexamethasone, a potent corticosteroid, has been shown to suppress inflammation by 
inhibiting edema, fibrin deposition, capillary leakage, and phagocytic migration of the 
inflammatory response.  In the past, the use of dexamethasone has yielded limited success in 
treating retinal disorders including macular edema, largely due to the inability to deliver and 
maintain adequate quantities of the drug to the posterior segment (Ahmed and Ai, 1999).  The 
dexamethasone Posterior Segment Drug Delivery System (DEX PS DDS) delivers a 700 µg 
total dose of dexamethasone to the vitreous with gradual release over time (Investigators 
Brochure) allowing for sustained drug levels to the target areas.  DEX PS DDS is composed 
of dexamethasone homogeneously dispersed into a biodegradable matrix composed of 
copolymers of lactic acid and glycolic acid, PLGA
 (poly [lactic-glycolic] acid), a material 
commonly used in medical devices such as absorbable sutures (Moritera et al, 1991; Singhal 
et al, 1988; Vicryl
® package insert, 1997; Visscher et al, 1985).  The DEX PS DDS does not 
need to be removed since the copolymer dissolves and absorbs over time.  An applicator (see 
Figure 2) was designed to facilitate intravitreal placement of the extruded DEX PS DDS.  By 
effectively delivering dexamethasone into the vitreous, DEX PS DDS offers a valuable new 
therapeutic option in the treatment of macular edema. 




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One of the most frequently reported adverse events associated with ophthalmic corticosteroid 
use is elevated intraocular pressure (IOP).  Although elevations of IOP were significantly 
more prevalent with DEX PS DDS than with sham, the increases either did not require 
treatment or were managed with topical IOP-lowering medications.  Like all injectable 
steroids, there was a higher incidence of cataracts with DEX PS DDS (7.4%) compared to 
sham (4.5%).  However, only 2 cataract surgeries were performed in the study eye (SE) 
during the 6-month study period. 
In the pivotal studies for patients with macular edema secondary to RVO, 98% of patients 
received a second injection of DEX PS DDS between 5 and 7 months after the initial 
treatment.  Post hoc analysis of these previous studies suggest that patients dosed between 
months 5 and 6 have better outcomes than the overall study population. 
Allergan has completed 1 phase 2 study with 700 µg DEX PS DDS in patients with DME.  
Study 206207-012 (PLACID study) was a 52-week, masked, multicenter, randomized, 
controlled trial (with up to 13 weeks additional follow up) to assess the safety and efficacy of 
700 µg DEX PS DDS in combination with laser photocoagulation in the treatment of patients 
with diffuse DME.  A
 total of 253 patients were randomized and enrolled in the study:   
126 in the Combination Therapy group and 127 in the Laser Alone group.  Intravitreal 
injection with 700 µg DEX PS DDS in combination with laser treatment was shown to 
provide more prolonged reduction in macular thickening and better VA
 overall than laser 
alone in patients with diffuse DME.  Treatment with combination therapy led to better 
outcomes than laser alone in improving vision at month 1 (31.7% versus 11.0%; p < 0.001) 
and at month 4 (26.2% versus 16.5%; p = 0.060) in the ITT population.  There was no 
statistically significant difference between the treatment groups at month 6. 
The aim of this study is to demonstrate that DEX PS DDS administered every 5 months will 
lead to greater improvement of VA
 than laser photocoagulation over 1 year of treatment.   
2. 
 Study Objectives and Clinical Hypotheses  
2.1 
 Study
  Objective
 
The objective of this study is to evaluate the safety and efficacy of the 700 µg DEX PS DDS 
compared with laser photocoagulation in patients with DME. 


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2.2 
 Clinical
  Hypotheses
 
• Treatment with 700 µg DEX PS DDS every 5 months is superior to laser 
photocoagulation according to the modified ETDRS protocol (with respect to the average 
change from baseline of BCVA
 during 12 months of treatment for DME) 
• 700 µg DEX PS DDS administered every 5 months has an acceptable safety profile 
3. 
 Study
  Design
 
This study is a multicenter, randomized, 12-month comparative study to evaluate if 700 µg 
DEX PS DDS administered every 5 months is safe and can achieve improvement of BCVA
  
superior to laser photocoagulation administered according to the modified ETDRS protocol 
(Section 12.1.11). 
Consenting patients will participate in a screening period lasting 2 to 14 days to evaluate 
patient eligibility
.  After eligibility has been determined by the investigator, patients will be 
randomized in a 1:1 ratio to receive: 
• 700 µg DEX PS DDS every 5 months  
or 
• laser photocoagulation according to the modified ETDRS protocol  
The randomization will be stratified by BCVA
 score at baseline (≥ 34 to ≤ 49 and 
 ≥ 50 to ≤ 70) within each investigator site.  The primary efficacy measure is average change 
of BCVA
 over a period of 12 months.  The total duration of study participation for each 
patient is approximately 12.5 months including screening and randomization/retreatment 
period.  Patients will attend the following 11 visits:  screening visit, randomization visit, 
8 assessment/retreatment visits, and study exit visit. 
4. 
 Study Population and Entry Criteria 
4.1 
 Number of Patients  
Approximately 356 patients will be enrolled at approximately 20 sites to ensure that at least 
151 patients in each treatment group complete the study
.  Of those, approximate10 patients 
assigned to DEX PS DDS at selected sites will participate in therapeutic drug monitoring. 


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4.2 
 Study Population Characteristics 
Patients with DME in at least 1 eye will be enrolled.  If both eyes are eligible for the study
, 
the eligible eye with worse VA
 should be selected as the SE.  The SE will be identified at the 
Screening visit and confirmed at the randomization visit and will remain the same throughout 
the entire study duration. 
4.3 
 Inclusion
  Criteria
 
The following are requirements for entry into the study:  
1. male or female, at least 18 years of age 
2. prior diagnosis of diabetes mellitus (type 1 or type 2)  
3. presence of macular edema 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 


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4.4 
 Exclusion
  Criteria
 
The following are criteria for exclusion from participating in the study: 
Systemic conditions or treatments: 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  


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10. anticipated need for ocular surgery in the SE during the 1-year study participation 
 
 
 
13. laser photocoagulation to the retina of the SE within 3 months prior to screening 
 
   
 
 
 
 
  
 
18. history of cataract surgery within the 3 months prior to screening  
 
 
 
 
 
 
  
 
 


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4.5 
 Permissible and Prohibited Medications/Treatments 
4.5.1 
 Permissible
  Medications/Treatments
 
Therapy considered necessary for the patients
' welfare may be given at the discretion of the 
investigator
.  If concurrent medications may have an effect on study outcomes, these 
medications should be administered in dosages that remain constant throughout the course of 
the trial.  If the permissibility of a specific medication or treatment is in question, please 
contact Allergan. 
Treatment of elevated IOP:  The need for treatment for elevated IOP will be at the discretion 
of the investigator
.  Consultation with glaucoma specialists should be considered when 
necessary
. 
Cataract surgery:  If a patient develops visually significant cataracts during the study period, 
the decision to perform cataract surgery is left to the discretion of the investigator and the 
patient.  Cataract surgery should be considered under the following conditions: 
• visual function no longer meets the patient’s needs and cataract surgery provides a 
reasonable likelihood of improvement 
• lens opacity inhibits optimal management of posterior segment disease 
• the lens causes inflammation (phacolysis, phacoanaphylaxis), angle closure, or medically 
unmanageable open-angle glaucoma 
Topical steroids, periocular, or intravitreal steroid injections:  allowed to treat inflammatory 
conditions in nonstudy eye 
Intravitreal anti-VEGF treatment:  allowed in the nonstudy eye   


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Use of systemic nonsteroidal anti-inflammatory drugs (NSAIDs):  systemic NSAIDs 
regularly used prior to enrollment will be allowed to continue during the study
, and should be 
administered at a dosage that remains constant throughtout the course of the trial. 
Nonocular steroids:  low-dose creams and ointments; intraarticular, inhaled, intranasal and 
ear drops allowed 
Panretinal photocoagulation:  if needed to treat neovascularization 
For patients who are assigned to DEX PS DDS drug monitoring, no corticosteroids (except 
the study medication) are allowed during the first 6 months. 
4.5.2 
 Acceptable Contraceptive Methods 
Women of childbearing potential must use reliable contraception.  The investigator and each 
patient will determine the appropriate method of contraception for the patient during the 
participation in the study
. 
If a female of childbearing potential becomes pregnant during the study
, the investigator will 
notify Allergan immediately after the pregnancy is confirmed, and the patient will be exited 
from the study after appropriate safety follow up.  The investigator will (1) notify the 
patient’s physician that the patient was being treated with an investigational drug (if 
applicable), 700 µg DEX PS DDS, and (2) follow the progress of the pregnancy
.  The 
investigator should discontinue study treatment, document the outcome of the pregnancy
, and 
provide a copy of the documentation to Allergan. 
4.5.3 
 Prohibited
  Medications/Treatments
 
The decision to administer a prohibited medication/treatment is done with the safety of the 
study participant as the primary consideration.  When possible, Allergan should be notified 
before the prohibited medication/treatment is administered. 
The following medications should be avoided during the study: 
• SE-intravitreal injections of any sort other than the study medication 
• SE-sub-tenon, subconjunctival or topical corticosteroids 


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• systemic corticosteroids (oral, inhaled, intranasal, intravenous, intramuscular, epidural, 
rectal, or extensive dermal); for patients who are assigned to DEX PS DDS drug 
monitoring any form of dexamethasone should be avoided during the first 6 months. 
• systemic anti-VEGF therapies 
• systemic immunosuppressants, immunomodulators, antimetabolites or alkylating agents 
• systemic carbonic anhydrase inhibitors (eg Diamox) 
•  SE-additional invasive nonstudy procedures or surgery 
If the permissibility of a specific medication/treatment is in question, please contact Allergan. 
5. 
 Study
  Treatments
 
 
5.1 
 Study Treatments and Formulations 
The study treatment will be dexamethasone intravitreal implant containing 700 µg 
dexamethasone in a solid polymer delivery system. 
5.2 
 Control
  Treatment
 
 
The control treatment will be laser photocoagulation according to modified ETDRS protocol. 
 
5.3 
 Escape
  Therapy
 
Treatment according to standard of care (SOC) should be considered for patients with a 
decrease of BCVA
  > 10 ETDRS letters from baseline, which is confirmed at 2 consecutive 
visits.  Patients who receive escape therapy will no longer eligible to receive study treatment, 
but will continue in the study for safety assessments.   
5.4 
 Methods for Masking/Blinding 
Study personnel collecting primary efficacy (BCVA) data and evaluators at the reading center 
will be blinded to study treatment assignment for the duration of the trial.  The BCVA
 
technician may not assist nor be present during the treatment procedure, as they need to 
remain unaware of patient treatment assignments. 


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5.5 
 Treatment Allocation Ratio and Stratification  
Patients will be randomized in a 1:1 ratio to either 700 µg DEX PS DDS or laser 
photocoagulation. 
The randomization will be stratified by BCVA
 score at baseline (≥ 34 to ≤ 49 and ≥ 50 to 
≤ 70) within each study site. 
5.6 
Method for Assignment to Treatment Groups/Randomization 
Prior to initiation of study treatment, each patient who provides informed consent and/or 
assent will be assigned a patient number that will serve as the patient identification number 
on all study documents. 
An automated interactive voice response system (IVRS) or interactive web response system 
(IWRS) will be used to manage the randomization and treatment assignment based on a 
randomization scheme prepared by Allergan Biostatistics. 
Study medication will be labeled with medication kit numbers.  The IVRS/IWRS system will 
provide the site with the specific medication kit number(s) for each randomized subject at the 
time of randomization.  Sites will dispense study medication/treatment according to the 
IVRS/IWRS instructions.  Sites will also call the IVRS or log onto the IWRS at subsequent 
visits to obtain a study medication kit number for dispensing study medication.  Sites will 
receive the IVRS/IWRS confirmation notifications for each transaction.  All notifications are 
to be maintained with the study source documents. 
5.7 
 Treatment Regimen and Dosing 
5.7.1 
 DEX PS DDS  
Patients assigned to the DEX PS DDS treatment group will receive 700 µg dexamethasone in 
a solid polymer delivery system at day 1, months 5, and 10.  
 


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5.7.2 
 Laser
  Photocoagulation
 
Patients assigned to the laser photocoagulation treatment group will receive laser treatment 
on day 1.  
Repeat laser photocoagulation at months 3, 6, and 9 will be administered if both of the 
following conditions are met: 
• OCT central subfield ≥ 250 µm with Stratus III (Zeiss), ≥ 275 with Cirrus (Zeiss)  or  
≥ 300 µm with Spectralis (Heidelberg)  
• patient might benefit from retreatment in the opinion of the investigator 
Laser treatment will be given according to the modified ETDRS treatment protocol 
(Section 12.1.11).  
5.8 
 Storage of Study Medication 
The study medication must be stored in a secure area and administered only to patients 
entered into the clinical study
, at no cost to the patient, in accordance with the conditions 
specified in this protocol. 
DEX PS DDS:   
 
    
      
5.9 
 Study Drug Administration  
5.9.1 
 Peri-operative
 Anti-infective
  Treatment
 
At the visit preceding each study drug administration, the patient will be given antibiotic 
ophthalmic solution (as applicable according to local practice) and instructed to instill a drop 
in the SE 4 times per day (QID) for 3 days prior to the study treatment procedure and up to 
QID (depending on the time of the study treatment procedure) on the day of the procedure, 
and QID for 3 days postoperatively
.  Patients should be instructed not to wear contact lenses 
while using antibiotics.  See the Procedure Manual for further details. 
5.9.2 
 Product
  Dispensing
 
 
Only qualified patients will receive study treatment.  The assigned staff member will access 
the IVRS/IWRS after patient randomization has been completed approximately 30 minutes 


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prior to the study treatment procedure to receive study treatment kit numbers that can be used 
for each patient (see the Procedure Manual for the IVRS/IWRS details).  Upon initial access 
to the IVRS/IWRS, a study treatment kit will be dispensed.  In the unlikely event that the 
initial applicator fails, the assigned staff member will access the IVRS/IWRS again to receive 
a second study treatment kit number to use.  Although it is not expected that further kits will 
be required, should further study treatment kits fail, up to a fourth kit may be obtained by 
accessing the IVRS/IWRS again.  If the fourth study treatment kit fails, the study treatment 
procedure should be aborted, and Allergan should be notified immediately
. 
The DEX PS DDS must only be handled at the time of the procedure and only under sterile 
conditions.  The study medication must be placed in enrolled patients’
 eyes by an investigator 
who possesses acceptable experience as determined by Allergan. 
5.9.3 
 Final Product Disposition 
The used applicators will be destroyed by the site.  For unused malfunctioning applicators, 
the assigned site personnel will record the nature of the malfunction on the appropriate form.  
The malfunctioning applicators will be destroyed by the site.  All unused applicators will be 
returned for destruction according to Allergan instructions. 
5.9.4 
 Operative
  Procedure
 
The study treatment procedure must be performed only in an operating room, surgical suite, 
or in an office setting using a sterile technique, as described in the Procedure Manual.  The 
study treatment kit(s) should be readily available during the procedure. 
Prior to study treatment, the SE of each patient will be anesthetized with topical and/or 
subconjunctival anesthetic and prepared according to the investigator’s standard of practice.  
Patients randomized to active treatment will have the study drug placed into the vitreous 
through the pars plana using the DEX PS DDS.  See the Procedure Manual for further details. 
Once the DEX PS DDS is deployed, the lever becomes locked to indicate that the applicator 
has been used and prevents reuse. 


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6. 
 Response Measures and Summary of Data Collection Methods 
6.1 
 Efficacy
  Measures
 
6.1.1 
 Primary Efficacy Measure 
The primary efficacy measure will be BCVA measured by ETDRS. 
6.1.2 
 Secondary Efficacy Measures 
Secondary efficacy measures will be: 
• central retinal thickness measured by OCT  
• total area of macular leakage measured on FA 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
   
 
 
 
  
 
 


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6.4 
 Examination
  Procedures,
  Tests,
 Equipment, and Techniques  
6.4.1 
 Best-corrected
  Visual
 Acuity
 
BCVA
 in the SE and in the nonstudy eye will be measured using the ETDRS VA
 protocol 
following manifest refraction.  All BCVA
 data will be used to assess safety as well as 
efficacy
. 
6.4.2 
 Optical
  Coherence
  Tomography
 
OCT is a laser-based, noninvasive, diagnostic system providing high-resolution imaging 
optical sections of the retina.  The mean retinal thickness in the 1-mm central subfield of the 
SE will be captured using time-domain OCT (Stratus III, Zeiss) or spectral-domain OCT 
(Cirrus, Zeiss or Spectralis, Heidelberg).  Electronic OCT images will be collected for 
evaluation by a reading center
.  Once an OCT instrument has been selected for a patient, that 
instrument must be used for all the study assessments for that patient for the duration of the 
study
. 
6.4.3 
 Fluorescein
 Angiography
 
Early and transit images will be taken of the SE.  Mid- and late-phase images will be taken of 
the study and nonstudy eye.  Electronic FA
 images will be collected for evaluation by a 
reading center
. 
6.4.4 
 Intraocular Pressure Measurement 
IOP will be measured using a Goldmann applanation tonometer instrument or a hand held 
tonometer
.  Once an instrument for IOP measurement has been selected for a patient, that 
instrument must be used for all the study assessments for that patient for the duration of the 
study
. 
6.5 
 Other Study Supplies 
Laboratory kits for the collection and shipment of hematology
, biochemistry
, and urine 
samples, including pregnancy test kits, will be provided by the central laboratory contracted 
by Allergan. 


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6.6 
 Summary of Methods of Data Collection 
An IVRS/IWRS will be used to screen, randomize, and manage study medication inventory
. 
Data will be collected using electronic case report form (eCRF) via a validated electronic 
data capture (EDC) system.  Source documents will be used and stored at sites, and may 
include a patient’s medical records, hospital charts, clinical charts, patient chart, copy of the 
EDC file, as well as the results of diagnostic tests, such as laboratory tests and ophthalmic 
examinations or tests.  A
 central lab will be used for the analysis of all blood samples.  A
 
central reading facility will be used for FA
 and OCT evaluations.  
7. 
 Statistical
  Procedures
 
One database lock will occur when all patients have either completed the study or 
discontinued from the study prematurely
.  The study will be unmasked for statistical analysis 
following the database lock.  A
 detailed analysis plan will be approved prior to database lock. 
7.1 
 Analysis
  Populations
 
Three analysis populations will be used for statistical analyses:  modified intent-to-treat 
(mITT), per-protocol (PP), and safety
. 
The mITT population will include all randomized and treated patients with at least 1 
postbaseline BCVA
 measurement.  The mITT population will be used for analysis of efficacy 
variables and baseline characteristics based on the randomized treatment group.   
The PP population will include all randomized and treated patients without any significant 
protocol violations.  The PP population will be used to analyze the primary efficacy variable 
as a secondary efficacy analysis.  The PP analysis will be based on the actual treatment that 
the patients received.   
The safety population will include all treated patients.  This population will be used for the 
safety analysis that will be based on the actual treatment that the patients received. 
7.2 
 Collection and Derivation of Primary and Secondary  Efficacy 
Assessments 
BCVA
 measured in the SE using the ETDRS method will be the primary efficacy assessment.  
For each patient, BCVA
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screening, day 1/randomization day (prior to the study treatment), and months 1, 2, 3, 5, 6, 7, 
9, 10, and 12/exit (or early exit) visits.  Analysis of BCVA
 obtained from the SE will be 
performed for efficacy
.  BCVA
 data from the nonstudy eye will be used only for safety 
evaluations. 
VA
 will be recorded on the CRF as the number of letters correctly read.  For a given eye, the 
4-meter distance (standard) of VA
 will be tested first.  If the patient correctly reads at least 
20 letters at 4 meters, the VA
 score will be set as the sum of 30, and the number of letters 
read correctly
.  If the patient correctly reads less than 20 letters at 4 meters, the VA
 will be 
measured again at 1 meter
.  The VA
 score will be set to the number of letters read correctly at 
1 meter plus the number of letters read correctly at 4 meters. 
BCVA
 measured at the randomization visit on day 1 prior to the study treatment will be 
considered as baseline for change from baseline.  BCVA
 data measured at the screening visit 
will be used for baseline only in the absence of BCVA
 data at the randomization visit on 
day 1.   
7.2.1 
 Primary
  Efficacy
  Variables
 
 
The primary efficacy variable is the average change from baseline in BCVA
 over the 
12-month study period.  The average change will be computed by subtracting the baseline 
BCVA
 from the area under the BCVA
 curve (AUC) divided by the total follow-up time for 
each patient.  Calculations for AUC will be based on observed data using the trapezoidal 
method and will include all postbaseline BCVA
 data for the patient from the study treatment 
to the last VA measurement, regardless of scheduled or unscheduled visits.   
7.2.2 
 Secondary
  Efficacy
  Variables
 
Secondary efficacy variables include:   ≥ 15 letters improvement from baseline in BCVA
 at 
month 12; change from baseline in the retinal thickness based on OCT at month 12; and 
change from baseline in total leakage area based on FA
 at month 12. 
Change From Baseline in Retinal Thickness Based on OCT 
OCT is a laser-based diagnostic system providing high-resolution optical sections of the 
retina.  OCT will be performed at the investigators’
 sites.  The OCT images will be 
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for the SE.  The retinal thickness (microns) in the central 1-mm macular subfield based on 
OCT will be assessed and analyzed as the secondary efficacy variable. 
Change From Baseline in Total Leakage Area Based on FA 
FA
 is a technique to examine the circulation of the retina using the dye tracing method.  It 
involves injection of sodium fluorescein into the systemic circulation, and then an angiogram 
is obtained by photographing the fluorescence emitted after illumination of the retina.  The 
focal and diffuse leakage area based on FA
 will be assessed.  The total leakage area defined 
as the sum of focal and diffuse leakage area will be computed and analyzed as the secondary 
efficacy variable. 
7.3 
 Hypothesis and Methods of Analysis 
Unless stated otherwise, analyses for efficacy will be performed using the mITT population 
based on the 2-sided hypothesis test with a nominal significance level of 0.05. 
7.3.1 
 Primary
  Efficacy
 Analyses
 
The primary efficacy endpoint is the average change from baseline in BCVA
 in 12 months.  
The primary analysis will be an analysis of covariance (ANCOVA) comparing the treatment 
difference in the mean average BCVA
 change from baseline over a 12-month study period.  
The ANCOVA
 model will include the treatment group as the main effect and baseline BCVA
 
score as the covariate.  
The null hypothesis is that there is no difference between 700-µg DEX PS DDS and laser in 
the average BCVA
 change from baseline in a 12-month period.  The alternative hypothesis is 
that there exists a difference between the 2 treatment groups.  The hypothesis test will be 
based on a 2-sided test at 0.05 significance level.  In addition, a 2-sided 95% confidence 
interval (CI) will be constructed for the difference between the treatment groups in 
least-square means using the same ANCOVA
 model.  Data collected after receiving any 
prohibited or standard of care treatments will be excluded from all the efficacy analysis. 
7.3.2 
 Secondary
  Efficacy
 Analyses
 
Analysis for proportion of patients with 15 or more letters improvement from baseline in 
BCVA
 at month 12 will be done using a Cochran–Mantel-Haenszel (CMH) test stratified by 
baseline BCVA
 categories (≥ 34 to ≤ 49 and ≥ 50 to ≤ 70) within each study site.   


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Analysis for change from baseline in retinal thickness at month 12 will be performed using 
an ANCOVA
 model with treatment and baseline BCVA
 score (≥ 34 to ≤ 49 and  ≥ 50 to ≤ 70) 
as the main effects and baseline retinal thickness as the covariate.  The between-group 
difference and the corresponding 2-sided 95% CI in least-square means will be computed 
using the ANCOVA
 model.  The within-group change from baseline will be analyzed using 
the paired t-test at the follow-up visits. 
Analysis for change from baseline in total leakage area at month 12 will be performed using 
an ANCOVA
 model with treatment and baseline BCVA
 score (≥ 34 to ≤ 49 and ≥ 50 to ≤ 70) 
as the main effects and baseline total leakage area as the covariate.  The between-group 
difference and the corresponding 2-sided 95% CI in least-square means will be computed 
using the ANCOVA
 model.  The within-group change from baseline will be analyzed using 
the paired t-test at the follow-up visits. 
 
 
 
 
 
 
 
  
 
7.3.4 
 Safety
 Analyses
 
The Medical Dictionary for Regulatory Activities (MedDRA) nomenclature will be used to 
code adverse events and biomicroscopy data.  
The number and percent of patients reporting adverse events will be tabulated by primary 
system organ class, preferred term, and severity for adverse event summarization.  The 
summary tables will be generated separately for adverse events reported during the screening 
to baseline period (pre-adverse event) and treatment emergent period.  Summaries for 
treatment-emergent adverse events will be organized into the following:  all adverse events 
regardless of causality; treatment-related adverse events; ocular adverse events in the SE; and 
treatment-related ocular adverse events in the SE.   
 
 


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7.5 
 Interim
 Analyses
 
No interim analysis is planned for this study
. 
8. 
 Study Visit Schedule and Procedures 
The total duration of study participation for each patient is approximately 12.5 months, 
including screening and randomization/retreatment period.  Patients will attend the following 


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11 visits:  screening visit, randomization visit, 8 assessment/retreatment visits, and study exit 
visit.  Please see Table 1 and Figure 1 for a schematic of the schedule of visits and 
procedures.  
8.1 
 Patient Entry Procedures  
8.1.1 
 Overview of Entry Procedures 
Prospective subjects as defined by the criteria in Sections 4.3 and 4.4 (inclusion/exclusion 
criteria) will be considered for entry into this study
.  Prior to patient randomization, patient 
eligibility must be reviewed and confirmed. 
8.1.2 
 Informed
  Consent
 
The study will be discussed with the patient, and a patient wishing to participate must give 
informed consent prior to any study-related procedures or change in treatment. Each patient 
that provides informed consent will be assigned a patient number that will be used on patient 
documentation throughout the study
.   
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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8.3 
 Instructions for Patients 
Patients are instructed to strictly follow the study visit schedule and to report all changes in 
condition to the investigative site. 
8.4 
 Unscheduled
  Visits
 
Additional examinations may be performed as necessary to ensure the safety and well being 
of patients during the study period.  Unscheduled visit eCRFs should be completed for each 
unscheduled visit.  For all parameters not measured, “Not Done” should be indicated and the 
forms should be signed and dated as appropriate. 


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8.5 
 Compliance
  with
  Protocol
 
Patients who are inadvertently enrolled, despite significant deviation from protocol-specified 
inclusion/exclusion criteria, will be followed to monitor patient safety
. 
Patients will be scheduled for follow-up visits, and these should occur as close as possible to 
the day specified in the visit schedule. 
At each visit after day 1, the investigator will ask patients if they have used any concomitant 
medications, and have had a procedure performed since the previous visit. 
8.6 
 Early Discontinuation of Patients 
Patients may voluntarily withdraw from the study at any time. 
Notification of early patient discontinuation from the study and the reason for discontinuation 
will be made to Allergan and will be clearly documented on the appropriate eCRF
. 
8.7 
 Study
  Termination
 
The study may be stopped at his/her study site at any time by the site investigator
.  Allergan 
may stop the study (and/or the study site) for any reason with appropriate notification. 
9. 
 Adverse
  Events
 
 
Adverse events occurring during the study will be recorded on an adverse event eCRF
.  If 
adverse events occur, the first concern will be the safety of the study participants.  
9.1 
 Definitions
 
9.1.1 
 Adverse
  Event
 
An adverse event is defined as any untoward medical occurrence in a patient or clinical 
investigation subject administered a pharmaceutical product and that does not necessarily 
have a causal relationship with this treatment.  An adverse event can therefore be any 
unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or 
disease temporally associated with the use of a medicinal (investigational) product, whether 
or not related to the medicinal (investigational) product.  In addition, during the screening 
period, adverse events will be assessed regardless of the administration of a pharmaceutical 
product.   


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Adverse events will be assessed and documented, as appropriate, throughout the study (ie, 
after informed consent has been obtained).  At each visit, the investigator will begin by 
querying for adverse events by asking each patient a general, nondirected question, such as 
“How have you been feeling since the last visit?”  Directed questioning and examination will 
then be done as appropriate.  All reported adverse events will be documented on the 
appropriate eCRF
.   
9.1.2 
 Serious
 Adverse
  Event
 
A
 serious adverse event is any adverse event occurring at any dose that results in any of the 
following outcomes:  death, a life-threatening adverse event, inpatient hospitalization or 
prolongation of existing hospitalization, a persistent or significant disability/incapacity
, or a 
congenital anomaly/birth defect.  Important medical events that may not result in death, be 
life-threatening, or require hospitalization may be considered a serious adverse event when, 
based upon appropriate medical judgment, they may jeopardize the patient and may require 
medical or surgical intervention to prevent 1 of the outcomes listed in this definition.  (See 
Section 9.3 for procedures for reporting a serious adverse event.) 
Note:  Allergan considers all cancer adverse events as serious adverse events.  In addition, 
Allergan considers any abortion (spontaneous or nonspontaneous) as a serious adverse event. 
9.1.3 
 Severity
 
A
 clinical determination will be made of the intensity of an adverse event.  The severity 
assessment for a clinical adverse event should be completed using the following definitions 
as guidelines: 
Mild 
Awareness of sign or symptom, but easily tolerated 
Moderate  
Discomfort enough to cause interference with usual activity 
Severe  
Incapacitating with inability to work or do usual activity 
Not applicable  
In some cases, an adverse event may be an ‘all or nothing’
 finding that 
cannot be graded 
9.1.4 
 Relationship to Study Drug or Study Procedure 
A
 determination will be made of the relationship (if any) between an adverse event and the 
study drug or study procedure, as applicable.  A
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determination is made that there is a reasonable possibility that the adverse event may have 
been caused by the drug or study procedure.   
9.2 
 Procedures for Reporting Adverse Events 
Any adverse event should be recorded on the appropriate eCRF
. 
All adverse events that are drug-related and unexpected (not listed as treatment-related in the 
current Investigators Brochure) are to be reported to the governing Institutional Review 
Board/Independent Ethics Committee (IRB/IEC) as required by the IRB/IEC, local 
regulations, and the governing health authorities. 
9.3 
 Procedures for Reporting a Serious Adverse Event 
Any serious adverse event occurring during the study period (beginning with informed 
consent) and for at least 2 months after the last dose of study drug should be immediately 
reported to an Allergan representative listed on the Allergan personnel page and recorded on 
the appropriate eCRFs.  All patients with a serious adverse event must be followed up, and 
the outcomes reported.  The investigator should supply Allergan and the IRB/IEC with any 
additional requested information (eg, autopsy reports and terminal medical reports).  
In the event of a serious adverse event, the investigator must: 
1. Notify Allergan immediately by fax using the serious adverse event reporting forms 
(for serious adverse event fax number, see page 1 of the protocol).  Emergency phone 
numbers and relevant Allergan personnel contacts are also on the front page of 
protocol. 
2. 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. 
3. Provide Allergan with a complete, written case history (adverse event report form) that 
includes a statement as to whether the event was or was not related to the use of the 
investigational drug. 
4. Promptly inform the governing IRB/IEC of the serious adverse event as required by 
the IRB/IEC, local regulations, and the governing health authorities. 


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9.4 
 Procedures for Unmasking of Study Medication 
Investigators will be aware of the treatment assignment. 
10. 
 Administrative
  Items
 
This protocol is to be conducted in accordance with the applicable Good Clinical Practice 
(GCP) regulations and guidelines, eg, the International Conference on Harmonisation (ICH) 
Guideline on GCP
. 
10.1 
 Protection of Patients 
10.1.1 
 Compliance with Informed Consent Regulations and Relevant 
Country Regulations 
Written informed consent is to be obtained from each patient prior to enrollment into the 
study
, and/or from the patient
's legally authorized representative in accordance with local 
regulatory requirements.   
There are special situations in which oral informed consent may be taken.  Approval to utilize 
oral consent procedures and instructions on how to properly obtain oral informed consent 
must be obtained from Allergan personnel. 
10.1.2 
 Compliance
  With
  IRB/IEC
  Regulations
 
This study is to be conducted in accordance with applicable IRB/IEC regulations.  The 
investigator must obtain approval from a properly constituted IRB/IEC prior to initiating the 
study and re-approval or review at least annually
.  Allergan is to be notified immediately if 
the responsible IRB/IEC has been disqualified or if proceedings leading to disqualification 
have begun.  Copies of all IRB/IEC correspondence with the investigator should be provided 
to Allergan. 
10.1.3 
 Compliance With Good Clinical Practice 
This protocol is to be conducted in accordance with the applicable local GCP regulations and 
guidelines.  


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10.1.4 
 Compliance With Electronic Records; Electronic Signatures 
Regulations  
This study is to be conducted in compliance with the regulations on electronic records and 
electronic signature. 
10.2 
 Changes to the Protocol 
The investigator should not implement any deviation from or changes of the protocol without 
approval by Allergan and prior review and documented approval/favorable opinion from the 
IRB/IEC of a protocol amendment, except where necessary to eliminate immediate hazards 
to study patients, or when the changes involve only logistical or administrative aspects of the 
study (eg, change in monitors, change of telephone numbers). 
10.3 
 Patient
  Confidentiality
 
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 name will not be disclosed in these documents.  The patient
's name may be 
disclosed to Allergan, the governing health authorities if they inspect the study records.  
Appropriate precautions will be taken to maintain confidentiality of medical records and 
personal information. 
10.3.1 
 Patient
  Privacy
 
Documentation in accordance with the relevant local privacy requirements (where 
applicable) is to be obtained from each patient prior to enrollment into the study
, and/or from 
the patient
's legally authorized representative in accordance with the applicable privacy
. 
10.4 
 Documentation
 
10.4.1 
 Source
  Documents
 
Source documents may include a patient
's medical records, hospital charts, clinic charts, the 
investigator
's patient study 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 part 
of the investigator
's record of a patient
's study-related data. 
The following information should be entered into the patient
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• patient’s name 
• patient’s contact information 
• the date that the patient entered the study
, patient number, and patient randomization (or 
medication kit) number 
• the study title and/or the protocol number of the study and the name of Allergan 
• the statement that informed consent has been obtained (including the date) prior to any 
study procedures being performed.  A
 statement that privacy required documentation for 
this study has been obtained (including the date). 
• dates of all patient visits 
• medical history
, including childbearing potential (if female), height, and weight 
• ophthalmic history 
• all concurrent medications (List all prescription and nonprescription medications being 
taken at the time of enrollment.  At each subsequent visit, changes to the list of 
medications should be recorded.) 
• vital signs (blood pressure and pulse rate) 
• manifest refraction and visual acuity worksheets 
• BCVA
 (source document information for these procedures must be captured and 
maintained in such a manner that the study personnel performing these examinations do 
not have access to the remaining study-related information or the source documents for 
any previous BCVA
 examinations) 
• IOP measurements 
• biomicroscopy results 
• indirect ophthalmoscopy results 
• FA
 duplicates, as well as backup copies of the electronic records if a digital system is 
used 


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• printouts of OCT
, as well as backup copies of the electronic records 
• occurrence and status of any adverse events 
• procedure notes of the study treatment procedure should include the following 
information: date and time of the procedure, evaluation of the injection site, location of 
injection to the nearest clock hour, and complications, if any 
• date the patient exited the study and a notation as to whether the patient completed the 
study or reason for discontinuation 
• the results of laboratory tests performed by the site (eg, results of urine pregnancy tests) 
• all concurrent procedures and concurrent medications (list all prescription and 
nonprescription medications being taken at the time of enrollment; at each subsequent 
visit, changes to the list of medications should be recorded) 
• any study personnel with knowledge of treatment assignment who shares this information 
with study personnel with no knowledge of a patient’s treatment assignment and/or 
shares this information with patients; the information shared is to be listed by parameter 
shared, whom the information was shared with, and the date it was shared 
 
 
 
10.4.2 
 Electronic Case Report Form Completion 
The investigator is responsible for ensuring that data are properly recorded on each patient
's 
eCRFs and related documents.  An investigator who has signed the protocol signature page 
should personally sign for the eCRFs (as indicated in the eCRFs) to ensure that the 
observations and findings are recorded on the eCRFs correctly and completely
.  The eCRFs 
are to be submitted to Allergan in a timely manner at the completion of the study
, or as 
otherwise specified by Allergan. 
10.4.3 
 Study
  Summary
 
An investigator
's summary will be provided to Allergan within a short time after the 
completion of the study
, or as designated by Allergan.  A
 summary is also to be provided to 
the responsible IRB/IEC. 


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10.4.4 
 Retention of Documentation 
All study-related correspondence, patient records, consent forms, patient privacy 
documentation, records of the distribution and use of all investigational products, and copies 
of eCRFs should be maintained on file. 
For countries falling within the scope of the ICH guidelines, the Allergan-specific essential 
documents should be retained until 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 at least 2 years have elapsed since the formal 
discontinuation of clinical development of the investigational product.  These documents 
should be retained for a longer period, however, if required by the applicable regulatory 
requirements or if needed by Allergan. 
In addition, for countries not falling within the scope of the ICH guidelines, local regulatory 
requirements should be followed regarding the retention of clinical study documentation. 
Allergan requires that it be notified in writing if the investigator wishes to relinquish 
ownership of the data so that mutually agreed-upon arrangements can be made for transfer of 
ownership to a suitably qualified, responsible person. 
10.5 
 Labeling, Packaging, and Return or Disposal of Study 
Medications/Treatments   
  
 
10.5.1 
 Labeling/Packaging
 
The study medications will be packaged, labeled, and supplied by Allergan.  All test articles 
will be identified as an investigational compound and will be labeled with the protocol study 
number and medication kit number.  The label will also specify the storage conditions and 
state that the study medication is limited to investigational use. 
10.5.2 
 Clinical Supply Inventory 
The investigator must keep an accurate accounting of the number of investigational units 
received from Allergan, dispensed to the patients, the number of units returned to the 
investigator by the patient, and the number of units returned to Allergan during and at the 
completion of the study
.  A
 detailed inventory must be completed for the study medication.  
The study medication must be dispensed only by an appropriately qualified person to patients 


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in the study
.  The medication is to be used in accordance with the protocol by patients who 
are under the direct supervision of an investigator
. 
10.5.3 
 Return or Disposal of Study Medications/Treatments and /or 
Supplies     
All clinical study medications/treatments and/or supplies will be returned to Allergan or 
Allergan designee for destruction. 
10.6 
 Monitoring
  by
 Allergan
 
A
 representative of Allergan will monitor the study on a periodic basis.  The determination of 
the extent and nature of monitoring will be based on considerations such as the objective, 
purpose, design, complexity
, blinding, size, and endpoints of the study
. 
Authorized representatives of Allergan or regulatory authority representatives will conduct 
on-site visits to review
, audit, and copy study-related documents.  These representatives will 
meet with the investigator(s) and appropriate staff at mutually convenient times to discuss 
study-related data and questions. 
10.7 
 Handling of Biological Specimens 
Samples of blood and urine for evaluation of hematology
, biochemistry
, and urinalysis will 
be analyzed at a facility meeting Good Laboratory Practice requirements and/or a validated 
method of quality assurance.  
Pharmacokinetic blood samples will be analyzed by a bioanalytical laboratory that meets 
Good Laboratory Practice requirements.  Details about collection and handling of the 
pharmacokinetic blood samples are provided in the Procedure Manual. 
10.8 
Publications 
Allergan as the sponsor, has proprietary interest in this study
.  Authorship and manuscript 
composition will reflect joint cooperation between multiple investigators and sites and 
Allergan personnel.  Authorship will be established prior to the writing of the manuscript.  As 
this study involves multiple centers, no individual publications will be allowed prior to 
completion of the final report of the multicenter study except as agreed with Allergan.   


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10.9 
 Coordinating
  Investigator
 
A
 signatory coordinating investigator will be designated prior to the writing of the clinical 
study report. 
11. 
 References
 
Age-Related Eye Disease Study Research Group.  A
 randomized, placebo-controlled, clinical 
trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-
related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol. 
2001;119:1417-1436. 
Ahmed I, Ai E. Macular disorders: cystoid macular edema. In: Yanoff M, Duker JS, eds.  
Ophthalmology
. London, United Kingdom: Mosby; 1999:34. 
Aiello LP
. Vascular endothelial growth factor and the eye: biochemical mechanisms of action 
and implications for novel therapies. Ophthalmic Res. 1997;29:354-362. 
Albert DM, Jakobiec FA.  Principles and Practice of Ophthalmology
. 2nd ed. Philadelphia: 
WB Saunders Co; 2000. 
Bresnick GH. Diabetic maculopathy
. A
 critical review highlighting diffuse macular edema. 
Ophthalmology
. 1983;90:1301-1317. 
Early Treatment Diabetic Retinopathy Study Research Group.  Photocoagulation for diabetic 
macular edema. ETDRS report number 1. Arch Ophthalmol. 1985;103:1796-1806. 
Early Treatment Diabetic Retinopathy Study Research Group.  Photocoagulation for diabetic 
macular edema. ETDRS report number 2. Ophtalmology
. 1987;94:761-774. 
Early Treatment Diabetic Retinopathy Study Research Group. Early photocoagulation for 
diabetic retinopathy
. ETDRS report number 9. Ophthalmology
. 1991;98(5 Suppl):766-785. 
Elashoff JD, Dixon WJ, Crede KM, Fotheringham NF
.  nQuery Advisor 6.01.  Saugus, 
Massachusetts:  Statistical Solutions; 2005. 
OZURDEX®, POSURDEX
® Investigator’s Brochure Version 13. Date: 30 April 2010 


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Jabs DA, Nussenblatt RB, Rosenbaum JT
, 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;140:509-516. 
Modified-ETDRS Focal Photocoagulation Technique [Internet] 2006 [cited 2011 Oct 31] 
Available from: 
http://publicfiles.jaeb.org/drcrnet/Misc/ModifiedETDRSFocalPhotoTech10.23.06.pdf. 
Moritera T
, Ogura Y
, Honda Y
, Wada R, Hyon SH, Ikada Y
. Microspheres of biodegradable 
polymers as a drug-delivery system in the vitreous. Invest Ophthalmol Vis Sci. 
1991;32:1785-1790. 
Nussenblatt RB, Palestine AG
, Chan C-C, Roberge F
. Standardization of vitreal inflammatory 
activity in intermediate and posterior uveitis. Ophthalmology 1985;92:467–471. 
Opremcak EM.  Uveitis:  A
 Clinical Manual for Ocular Inflammation.  Springer Verlag; New 
York:1995. 
Resnikoff S, Pascolini D, Etya’ale D, Kocur I, Pararajasegaram R, Pokharel GP et al. Global 
data on visual impairment in the year 2002. Bull World Health Organ 2004;82:844-851. 
Report of a WHO/IDF consultation. Definition and diagnosis of diabetes mellitus and 
intermediate hyperglycaemia [Internet] 2006 [cited 2011 Oct 31] 
Available from: 
http://www
.idf.org/webdata/docs/WHO_IDF_definition_diagnosis_of_diabetes.pdf.  
Singhal JP
, Singh H, Ray AR. Absorbable suture materials: preparation and properties.  JMS 
Rev Macromol Chem Phys 1988;C28(3&4):475-502. 
Vicryl® (polyglactin 910) sterile synthetic absorbable suture (package insert). Edinburgh, 
Great Britain: Ethicon Ltd; 1997. 
Visscher GE, Robison RL, Maulding HV
, Fong JW
, Pearson JE, Argentieri GJ.  
Biodegradation of and tissue reaction to 50:50 poly (DL-lactide-co-glycolide) microcapsules.  
J Biomed Mater Res. 1985;19:349-365. 
WHO, Diabetes Fact Sheet N°312 [Internet] August 2011 [cited 2011 Oct 31] 
Available from: 
http://www
.who.int/mediacentre/factsheets/fs312/en/.pdf 


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Wild S, Roglic G
, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for 
the year 2000 and projections for 2030. Diabetes Care. 2004;27:1047-1053. 
12. 
 Attachments
 
12.1 
 Examination
  Procedures,
  Test
s, Equipment, and Techniques 
 
  
 
 
 
 
 
 
 
 
 
12.1.2 
 Pregnancy
  Test
 
Females of childbearing potential will have urine pregnancy tests performed.  A
 female is 
considered to be of childbearing potential unless she is postmenopausal and without menses 
for 12 months or without a uterus and/or both ovaries.  Pregnancy test kits will be 
administered according to the instructions provided with the tests.  A
 negative pregnancy test 
result (required for female patients of childbearing potential only) must be obtained at 
screening and at the day 1 visit before study drug injection.  An additional test is required at 
the month 12/exit visit. 
12.1.3 
 Handling of Biological Specimens  
The 10-hour fasting blood and urine samples should be sent to the designated clinical 
laboratory for analysis on the same day that they are collected.   
Details on the collection and handling of pharmacokinetic blood samples are provided in the 
Procedure Manual.   


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12.1.4 
 Visual
 Acuity
 Assessment
 
BCVA
 will be measured using the ETDRS visual acuity protocol as modified by the Age-
related Eye Disease Study Research Group (AREDS report no. 8, 2001).  See the Procedure 
Manual for further details. 
12.1.5 
 Intraocular
  Pressure
 
IOP must be measured prior to pupil dilation.  Measurements will be taken using a Goldmann 
applanation tonometer or a hand held tonometer
.   
12.1.6 
 Optical
  Coherence
  Tomography
 
The approved equipment for this protocol include the following: the Stratus III (Carl Zeiss 
Meditec) with software version 4.0 or greater, or Cirrus (Zeiss) or Spectralis (Heidelberg). 
For sites using the Stratus OCT
, at least 6 consecutive radial scans through the macula, each 
approximately 6 mm in length, will be taken according to Table 1.  For sites using the Zeiss 
Cirrus spectral domain OCT instrument, a Cirrus Macular Cube 512 x 128 scan 
(128 horizontal scan lines comprised of 512 A-scans) will be required.  For sites using the 
Heidelberg Spectralis OCT instrument images must be acquired in the Volume Scan mode 
with ART set to 5 (512 by 97 A
 scans). 
Once the OCT instrument has been selected for a patient, that instrument must be used for all 
the study visits for that patient for the duration of the study
.    
12.1.7 
 Biomicroscopic
  Examination
 
12.1.7.1 Eyelids 
Eyelids will be evaluated for pathology
.  If pathology is present, it will be described. 


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12.1.7.2 Conjunctiva (Bulbar or Palpebral) 
Hyperemia 
None  
0  
=  
Normal, no flush or redness present 
Trace  
+0.5  =  
Minimal flush, reddish color 
Mild  
+1  
=  
Mild flush, reddish color 
Moderate  +2  
=  
Bright red color 
Severe  
+3  
=  
Deep, bright diffused redness 
Edema 
None  
0  
=  
Normal, no swelling of the conjunctiva 
Trace  
+0.5  =  
Minimal swelling of the conjunctiva, above normal, which 
is regional 
Mild  
+1  
=  
Mild swelling of the conjunctiva, above normal, which is 
regional 
Moderate  +2  
=  
General swelling of the conjunctiva 
Severe  
+3  
=  
Extensive swelling of the conjunctiva 
Subconjunctival Hemorrhage 
None  
0  
=  
No hemorrhage 
Trace  
+0.5  =   Flat and ≤ 1 quadrant 
Mild  
+1  
=  
Elevated and ≤ 1 quadrant, or flat and > 1 quadrant 
Moderate  +2  
=  
Elevated and > 1 but ≤ 2 quadrants 
Severe  
+3  
=  
Elevated and > 2 quadrants 
 


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12.1.7.3 Cornea 
Edema 
None  
0  
=  
Transparent and clear 
Trace  
+0.5  =  
Trace, localized epithelial haze 
Mild  
+1  
=  
Dull glass appearance that may include fine individual 
microcystic changes 
Moderate  +2  
=  
Dull glass appearance of epithelium with large number of 
vacuoles with or without stromal edema 
Severe  
+3  
=  
Epithelial bullae and/or stromal edema, localized or 
diffuse, with or without stromal striae 
Superficial Punctate Keratopathy 
 
0  
=  
None 
 
+0.5  =  
Trace 
 
+1  
=  
Mild 
 
+2  
=  
Moderate 
 
+3  
=  
Severe 


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12.1.7.4 Anterior Chamber 
For the measurements of cells and flare based on standardized uveitis nomenclature 
(Jabs et al, 2005), the following settings should be used: 
1 x 1 mm slit  
High magnification 
Highest slit lamp voltage  
Low ambient lighting 
Illumination angle of 45 degrees 
 
Same grader and slit lamp 
whenever possible 
Cells 
  
0  
=  
0 cells  
  
+0.5  =  
1to 5 cells (trace)  
  
+1  
=  
6 to15 cells 
  
+2  
=  
16 to 25 cells 
  
+3  
=  
26 to 50 cells 
  
+4  
=  
> 50 cells 
 
Hypopyon 
If hypopyon is present, it will be described and the level will be estimated in 
millimeters. 
Flare 
None  
0  
=  
No flare seen 
Faint  
+1  
=  
Faint flare seen 
Moderate  +2  
=  
Iris and lens details clear 
Marked  +3  
=  
Iris and lens details hazy 
Intense  
+4  
=  
Fibrin or plastic aqueous 
 
 


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12.1.7.5 Iris/Pupil 
The iris/pupil will be evaluated for pathology
.  If pathology is present, it will be described. 
Rubeosis Iridis  
  
0  
=  
No visible rubeosis iridis 
  
+0.5  =  
Trace visible rubeosis iridis 
  
+1  
=  
Obvious vessels in 1 quadrant (≤ 90 degrees) 
  
+2  
=  
Obvious vessels 2 to 3 quadrants (91to 270 degrees) 
  
+3  
=  
Obvious vessels 4 quadrants (271 to 360 degrees) 
 
Iris Color (screening only) 
Iris color will be recorded at screening using the following classification:  blue, green, hazel, 
brown, or other (specify).  
12.1.7.6 Lens 
Lens Status 
Lens status will be assessed as phakic, pseudophakic, or aphakic. 
Cataract Assessment (phakic eyes only) 
Presence and severity of nuclear, cortical, and posterior subcapsular cataract lens opacities 
will be evaluated by comparing biomicroscopic findings with standard photographs (refer to 
the Procedure Manual for further details).  Grades are assigned as follows for each type of 
opacity: 
Opacity is absent 
Opacity is present, but less than standard photo #2 
Opacity is present and as severe as or worse than standard photo #2 
 


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Assessment of Impact of Cataract on Visual Acuity 
Assuming that lens opacities were the only vision-limiting condition present in this eye, 
estimate what the best-corrected distance visual acuity would be based on lens opacities.  
Assume an undilated pupil and indoor lighting conditions. 
None 
20/25 ~ 20/40 
20/50 ~ 20/100 
> 20/100 
 
Posterior Capsule Assessment (aphakic or pseudophakic eyes only) 
For aphakic or pseudophakic eyes, the posterior capsule will be assessed and recorded as 
intact (yes or no). 
12.1.8 
 Fundus Ophthalmoscopic Examination 
When possible, for consistency purposes, the same lens(es) should be used for all 
assessments throughout the study
. 
12.1.8.1 Macula 
The macula will be evaluated for pathology
.  If pathology is present, it will be described.  
Note if the condition is not evaluable.  
12.1.8.2 Optic Nerve 
The optic nerve will be evaluated for pathology
.  If pathology is present, it will be described. 
Note if the condition is not evaluable. 
Cup/disc ratio will be reported using a 0.0 to 1.0 scale according to an Armaly chart provided 
by Allergan.  Note if the condition is not evaluable. 


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12.1.8.3 Vitreous  
(1 x 3 mm beam in anterior vitreous) (Opremcak, 1995) 
Cells 
0 
  =  
None 
+0.5 
  =  
1to10 cells 
+1 
  =  
11 to 20 cells 
+2 
  =  
21 to 30 cells 
+3 
  =  
31 to 100 cells 
+4 
  =  
> 100 cells 
Note if the condition is not evaluable. 
 
Vitreous Haze  
The ophthalmologist will grade vitreous haze by viewing the optic disc and posterior retina 
using the following settings and by comparing the haze against a photographic standardized 
scale (Nussenblatt et al, 1985) according to the chart provided by Allergan. 
Indirect ophthalmoscope and a 20-diopter lens 
Illumination set to mid-power 
Large beam 
Low ambient lighting 
Same grader and indirect ophthalmoscope whenever possible 
 
The scale is categorized as follows: 
0 
=  
No inflammation 
+0.5  
=  
Trace inflammation (slight blurring of the optic disc margins and/or 
loss of the nerve fiber layer [NFL] reflex)  
+1  
=  
Mild blurring of retinal vessels and optic nerve 
+2  
=  
Moderate blurring of optic nerve head 
+3  
=  
Marked blurring of optic nerve head 
+4  
=  
Optic nerve head not visible  
Note if the condition is not evaluable. 
 
 
 
 
 


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Vitreous Hemorrhage 
Vitreous hemorrhage will be evaluated for severity.  Indicate whether or not it is localized to 
the injection site. 
0 
=  
No visible evidence of hemorrhage on fundus ophthalmoscopic exam 
+0.5  
=  
Retinal detail is visible; trace hemorrhage is present  
+1  
=  
Retinal detail is visible; mild hemorrhage is present 
+2  
=  
Large retinal vessels are visible; central retinal detail is not visible  
+3  
=  
Red reflex is visible; no central retinal detail is seen posterior to the 
equator  
+4  
=  
No red reflex 
 
Posterior Vitreous Detachment 
The presence or absence of a posterior vitreous detachment will be evaluated. Note if the 
condition is not evaluable. 
12.1.8.4 Retina 
Retinal Hemorrhage  
The presence or absence of a retinal hemorrhage will be evaluated.  Note if the condition is 
not evaluable. 
Retinal Tear 
The presence or absence of a retinal tear will be evaluated.  Note if the condition is not 
evaluable. 
Retinal Detachment 
The presence or absence of a retinal detachment will be evaluated. It will be noted if the 
center of the macula is detached.  Note if the condition is not evaluable.  
Lattice Degeneration  
The presence or absence of lattice degeneration will be evaluated at screening and exit.  If 
present, the condition will be described.  Note if the condition is not evaluable. 
Round (Atrophic) Retinal Holes  


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The presence or absence of round retinal holes will be evaluated at screening and exit.  If 
present, the condition will be described.  Note if the condition is not evaluable. 
12.1.9 
 Fluorescein
 Angiography
 
Early and transit images will be taken of the study eye.  Mid- and late-phase images will be 
taken of the study and nonstudy eye.  Angiograms will be read by the study investigator to 
determine eligibility
.  
Electronic FA
 images will be collected for efficacy evaluation by a reading center
.   
 
 
 
 
 
12.1.11 
Modified-ETDRS Focal Photocoagulation Technique 
The laser treatment “session” should generally be completed in a single “sitting.”  The 
photocoagulation treatment technique, as described below
, is a modification of the ETDRS 
technique and is the treatment approach that is commonly used in clinical practice 
(Modified ETDRS Focal Photocoagulation Technique [Internet], 2006). 


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Burn characteristic 
Direct/grid photocoagulation (modified-ETDRS technique) 
Direct treatment 
Directly treat all leaking microaneurysms (MA) in areas of 
retinal thickening between 500 and 3000 microns from the 
center of the macula (although may treat between 300 and 
500 microns of macula if center-involved edema persists 
after initial focal photocoagulation, but generally not if the 
visual acuity is better than 20/40) 
Change in MA
 Color with 
Direct Treatment 
Not required, but at least a mild gray-white burn should be 
evident beneath all MAs 
Burn size for direct treatment  50 microns 
Burn duration for direct 
treatment 
0.05 to 0.1 sec 
Grid treatment 
Applied to all areas with edema not associated with MAs. If 
FA
 is obtained, grid is applied to areas of edema with 
angiographic nonperfusion when judged indicated by the 
investigator 
Area considered for grid 
treatment 
500 to 3000 microns superiorly
, nasally and inferiorly from 
center of macula 500 to 3500 microns temporally from 
macular center; no burns are placed within 500 microns of 
disc 
Burn size for grid treatment  50 microns 
Burn duration for grid 
treatment 
0.05 to 0.1 sec 
Burn intensity for grid 
treatment 
Barely visible (light gray) 
Burn separation for grid 
treatment 
2 visible burn widths apart 
Wavelength (grid and focal 
treatment) 
Green to yellow wavelengths 
 


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12.2 
 Glossary
  of
 Abbreviations
 
Term/Abbreviation  Definition 
ANCOVA  
analysis of covariance 
AREDS 
Age-Related Eye Disease Study Research Group 
BCVA 
best-corrected visual acuity 
BRB 
blood-retinal barrier  
CI 
confidence interval 
CMH 
Cochran-Mantel-Haenszel 
DEX PS DDS  
700-µg extruded dexamethasone posterior segment drug delivery 
system (extruded drug outside the applicator) 
DME 
diabetic macular edema 
DR 
diabetic retinopathy 
eCRF 
electronic case report form 
EDC 
electronic data capture system 
ETDRS 
Early Treatment Diabetic Retinopathy Study 
FA 
fluorescein angiography 
GCP 
Good Clinical Practice 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 
IOP 
intraocular pressure 
ITT 
intent-to-treat (population) 
IVRS/IWRS  
interactive voice/web response system  
MA 
microaneurysms  
MedDRA  
Medical Dictionary for Regulatory Activities 
NSAIDs 
nonsteroidal anti-inflammatory drugs  
OCT 
optical coherence tomography 
OU 
both eyes 
PK 
pharmacokinetic 
PLGA 
poly (lactic-glycolic) acid 
PP 
per-protocol (population) 
QID 
4 times per day 
RVO 
retinal vein occlusion 
SE 
study eye 
VA 
visual acuity 


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Term/Abbreviation  Definition 
VEGF 
vascular endothelial growth factor 
 
 
WHO 
World Health Organization 
 


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12.3 
Protocol
 Amendment
 Summary
 
Title:  Dexamethasone Posterior Segment Drug Delivery System Versus Laser 
Photocoagulation in Patients with Diabetic Macular Edema 
Protocol 206207-026 Amendment 1 
Date of Amendment:  April 2013 
Amendment Summary  
This summary includes changes made to Protocol 206207-026 (approved 01 September 
2012). The following key changes were made 1) adding pharmacokinetic analysis; 2) 
modification of the study sample size. 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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ALLERGAN
ALLERGAN 
 
 
 
 
 
 
 
 
 
Date (DD/MMM/YYYY)/Time (PT) Signed by: 
Justification 
  
 
 
            
 
           
 
            
 
           
 
            
 
           
 
     
 
           
 
            
 
           
 
            
 
           
 
            
 
           
 
            
 
           
 
            
 
           
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
 
Protocol 206207-026 amendment 1

SAP_000.pdf: 
NCT02121262 
 
Study ID: 206207‐026 
 
 
Title:  Dexamethasone Posterior Segment Drug Delivery System Versus Laser Photocoagulation in 
Patients With Diabetic Macular Edema  
 
Statistical Analysis Plan Date: 13Jan2020 
 
 
 


 
Title Page 
STATISTICAL ANALYSIS PLAN 
Dexamethasone Posterior Segment Drug Delivery System Versus Laser Photocoagulation 
in Participants with Diabetic Macular Edema 
 
Study Number: 
206207-026 
Development Phase: 
3 
Product Name: 
Dexamethasone Posterior Segment Drug Delivery 
System 
Sponsor: 
Allergan PLC 
2525 Dupont Drive, Irvine, California USA 92612 
 
 
This document is the property of Allergan PLC and may not, in full or part, be passed on, 
reproduced, published, distributed to any person, or submitted to any regulatory authority 
without the express written permission of Allergan PLC.16.1.9 Statistical Methods 
 


Allerg
700 µg
 
Title 
Table
List o
List o
1. 
I
1
2. 
A
2
2
2
3. 
D
3
3
3
4. 
D
4
4
4
4
4
5. 
E
5
5
gan Confidentia
g DEX PS DD
Page ..........
e of Contents
of Tables .....
of Abbreviat
Introduction 
1.1 
Primar
Analysis Pop
2.1 
Analys
2.2 
Analys
2.3 
Data C
Disposition a
3.1 
Dispos
3.2 
Protoc
3.3 
Analys
Demographi
4.1 
Demog
4.2 
Baselin
4.3 
Prior M
4.4 
Conco
4.5 
Medic
Efficacy Ana
5.1 
Primar
 
5.1.1
 
5.1.2
 
5.1.3
5.2 
Second
 
5.2.1
 
5.2.2
 
5.2.3
al                     
S 
...................
s .................
...................
tions and De
...................
ry Study Obj
pulations and
sis Populatio
sis Visit Win
Conventions 
and Exit Stat
sition and Ex
ol Deviation
sis Populatio
cs and Other
graphics .....
ne Character
Medications 
mitant Medi
al and Surgi
alyses .........
ry Efficacy A
Collection 
Efficacy Va
Primary Ef
Other Anal
dary Efficacy
BCVA Imp
Change fro
Change fro
                       
Tabl
....................
....................
....................
efinitions of T
....................
jectives and 
d Data Conv
ons ...............
ndows ..........
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fficacy Analy
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07-026 
...... 1 
...... 2 
...... 3 
...... 4 
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...... 7 
...... 7 
...... 7 
...... 9 
.... 10 
.... 10 
.... 10 
.... 10 
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.... 11 
.... 11 
.... 12 
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ary 
.... 13 
.... 14 
.... 14 
.... 14 
.... 14 
.... 14 
.... 15 


Allerg
700 µg
 
6. 
S
6
6
6
8. 
I
10. R
11. A
 
Table
Table
Table
gan Confidentia
g DEX PS DD
Safety Analy
6.1 
Exposu
6.2 
Treatm
6.3 
Seriou
Interim Anal
References ..
Amendments
e 2-1 
An
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Allergan Confidential                                                                                      Statistical Analysis Plan 206207-026 
700 µg DEX PS DDS 
4 
 
List of Abbreviations and Definitions of Terms 
Abbreviation/Term 
Definition 
AE 
Adverse event 
ANCOVA 
Analysis of covariance 
ANOVA 
Analysis of variance 
ATC 
Anatomical Therapeutic Chemical 
AUC 
Area under the curve 
BCVA 
Best corrected visual acuity 
CFB 
Change from baseline 
CI 
Confidence interval 
CMH 
CRT 
Cochran-Mantel-Haenszel 
Central retinal thickness 
D 
Day 
DEX PS DDS 
Extruded dexamethasone posterior segment drug delivery system 
DME 
Diabetic macular edema 
ETDRS 
Early treatment diabetic retinopathy study 
Ecrf 
FA 
Electronic case report form 
Fluorescein angiography 
IOP 
Intraocular pressure 
LS 
Least squares 
M 
Month 
MedDRA 
Medication Dictionary for Regulatory Activities 
mITT 
Modified intent-to-treat 
OCT 
Optical coherence tomography 
OU 
Both eyes 
PE 
Physical examination 
PP 
Per-protocol 
PT 
Preferred term 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SD 
Standard deviation 
SE 
Standard error 
SE 
Study eye 
SOC 
System organ class 
TEAE 
Treatment-emergent adverse event 
VA 
Visual acuity 
VFQ 
Visual functioning questionnaire  
WHO 
World Health Organization 
 


Allergan Confidential                                                                                      Statistical Analysis Plan 206207-026 
700 µg DEX PS DDS 
5 
 
1. 
Introduction 
This statistical analysis plan (SAP) details comprehensive, technical specifications of the 
statistical analyses of the efficacy, safety data and health outcomes outlined or specified in 
the final protocol of Study 206207-026 amendment 1. Specifications of tables, figures, and 
data listings are contained in a separate document. 
Study 206207-026 is a Phase 3, multicenter, randomized, 12-month comparative study. This 
study is conducted to evaluate the safety and efficacy of the 700 µg DEX PS DDS compared 
with laser photocoagulation in participants with diabetic macular edema (DME). This is a 
regional multicenter Phase 3 registration trial and is conducted exclusively in China and The 
Philippines. 
1.1 
Primary Study Objectives and Design 
The objective of the study is to evaluate the safety and efficacy of 700µg DEX PS DDS 
administered every 5 months. 
Consenting participants will participate in a screening period lasting 2 to 14 days to evaluate 
participant eligibility. After eligibility has been determined by the investigator, participants 
will be randomized in a 1:1 ratio to receive: 
• 700 µg DEX PS DDS every 5 months 
      or 
• laser photocoagulation according to the modified ETDRS protocol 
The randomization will be stratified by BCVA categories at baseline (≥ 34 to ≤ 49 and ≥ 50 
to ≤ 70) within each investigator site. The primary efficacy variable is average change of 
BCVA over a period of 12 months. The total duration of study participation for each 
participant is approximately 12.5 months including screening and randomization/retreatment 
period. Participants will attend the following 11 visits: screening visit, randomization visit, 8 
assessment/retreatment visits, and study exit visit, as listed in Table 1-1.


Allergan Confidential                                                                                      Statistical Analysis Plan 206207-026 
700 µg DEX PS DDS 
6 
 


Allergan Confidential                                                                                      Statistical Analysis Plan 206207-026 
700 µg DEX PS DDS 
7 
 
2. 
Analysis Populations and Data Conventions 
2.1 
Analysis Populations 
Approximately 356 participants will be enrolled at approximately 20 sites to ensure that at 
least 151 participants in each treatment group complete the study. Of those, approximately 10 
participants assigned to DEX PS DDS at selected sites will participate in therapeutic drug 
monitoring. 
The following 3 populations will be used for statistical analyses: modified intent-to-treat 
(mITT), per protocol (PP), and safety populations.    
The mITT population consists of randomized and treated participants with at least one 
postbaseline BCVA measurement. The mITT population will be used for all analyses except 
per-protocol and safety analyses. Analysis for mITT will be based on the randomized 
treatment regardless of the actual treatment that the participant received. 
The PP population is a subset of mITT population. 
 
 
 
 
 
 
 
 
 
 
The safety population consists of all participants who received the study medication or had 
the study procedure performed on the study eye. All safety analyses will be based on the 
safety population using the actual treatment that the participant received. 
2.2 
Analysis Visit Windows 
Visit windows are defined according to study days. 
The analysis visit windows for efficacy and safety endpoints except total leakage area are 
defined as follows: 


Allergan Confidential                                                                                      Statistical Analysis Plan 206207-026 
700 µg DEX PS DDS 
8 
 
Table 2-1 
Analysis Visit Definitions for Safety and Efficacy (BCVA, OCT and IOP) 
Study Visit 
(eCRF) 
Analysis Visit 
(Derived) 
Target Day 
(Number of Days from Day 1) 
Window 
(Study Days) 
Day 1(Baseline) 
Baseline 
1 
≤ 1 
Month 1 
Month 1 
30 
 [2, 45] 
Month 2 
Month 2 
60 
 [46, 75] 
Month 3 
Month 3 
90 
 [76, 120] 
Month 5 
Month 5 
150 
 [121, 165] 
Month 6 
Month 6 
180 
 [166, 195] 
Month 7 
Month 7 
210 
 [196, 240] 
Month 9 
Month 9 
270 
 [241, 285] 
Month 10 
Month 10 
300 
 [286, 330] 
Month 12/Exit 
Month 12 
360 
[331, 450] 
Month is defined as 30 days. 
 
The analysis visit windows for total leakage area are defined as follows: 
Table 2-2 
Efficacy Analysis Visit Definitions for Total Leakage Area 
Study Visit 
(eCRF) 
Analysis Visit 
(Derived) 
Target Day 
(Number of Days from Day 1) 
Window 
(Study Days) 
Day 1(Baseline) 
Baseline 
1 
≤ 1 
Month 3 
Month 3 
90 
 [2, 135] 
Month 6 
Month 6 
180 
 [136, 225] 
Month 9 
Month 9 
270 
 [226, 315] 
Month 12/Exit 
Month 12 
360 
 [316, 450] 
Month is defined as 30 days. 
 
 
In cases where multiple visits occurred within a single visit window, the last visit with non-
missing data will be used. 


Allergan Confidential                                                                                      Statistical Analysis Plan 206207-026 
700 µg DEX PS DDS 
9 
 
2.3 
Data Conventions 
• Unless stated otherwise in specific subsequent sections, data conventions and definitions 
listed below will be applied to all analyses. Study duration will be calculated for each 
participant as: 
Study duration = date of the last visit – date of the 1st study treatment + 1 
• In general, study day of a visit/assessment/treatment/event/procedure (i.e., BCVA 
assessment, escape therapy) will be calculated as below. 
If the visit date is on or after the 1st study treatment, study day will be calculated as: 
Study Day = visit date – date of the 1st study treatment + 1 
Day 1 is the day of the 1st study treatment 
If visit date is before the 1st study treatment, study day will be calculated as: 
Study Day = visit date – date of the 1st study treatment 
Day -1 is the day before the 1st study treatment 
• Unless otherwise specified, baseline data refer to assessments performed at the Baseline 
(Day 1) visit prior to the first treatment. Screening or unscheduled but prior to Day 1 
visits can be used for baseline in the absence of pertinent data at the baseline visit. 
• For continuous variables, descriptive statistics will include mean, median, standard 
deviation, 25-percentile, 75-percentile, minimum and maximum. Descriptive summary 
for the categorical data will be count and percentage for each category.  
• The Medical Dictionary for Regulatory Activities (MedDRA) nomenclature will be used 
to code adverse events, biomicroscopy, and ophthalmoscopy findings.  
• The Anatomical-Therapeutic-Chemical classification text from World Health 
Organization (WHO) Drug Dictionary will be used to code all medications for drug class 
and for drug name. 
• All data will be listed. 


Allergan Confidential                                                                                      Statistical Analysis Plan 206207-026 
700 µg DEX PS DDS 
10 
 
• Data after the escape therapy will be excluded from efficacy analyses and will be 
included in safety analyses. Since assessments (e.g., BCVA, CRT) are usually performed 
before any treatments (e.g., study treatment, escape therapy), data collected on the same 
day but prior to the escape therapy will be included in analysis.  
• Due to IP recall during the study, a small number of participants have delayed Ozurdex 
treatment at Month 12. It is recommended that these participants can come back 2 months 
after the last treatment for a follow-up visit. Therefore, data collected up to day 450 will 
be used in efficacy analysis. However, all data during the study will be included in safety 
analysis. 
3. 
Disposition and Exit Status 
Disposition and exit status of enrolled participants will be summarized. 
3.1 
Disposition and Exit Status 
Participant disposition will be summarized as a frequency distribution by treatment groups. 
Participant disposition encompasses the distribution of participants who screened, 
randomized, complete, and discontinue, along with eCRF-reported discontinuation reasons.  
3.2 
Protocol Deviation 
Protocol deviations will be captured and classified by categories in a separate document. 
Significant protocol deviations will be summarized for the mITT Population by treatment 
group. 
3.3 
Analysis Population 
Number of participants included for mITT, PP and Safety population will be summarized for 
all participants in total and by treatment group. Listing of participants excluded from PP 
population will be provided with reasons for exclusions. 
4. 
Demographics and Other Baseline Characteristics 
4.1 
Demographics 
Demographic data including age, age group (<45, 45-65, >65), sex, and race will be 
summarized with descriptive statistics and frequency distribution in total and by treatment 
group.    


Allergan Confidential                                                                                      Statistical Analysis Plan 206207-026 
700 µg DEX PS DDS 
11 
 
4.2 
Baseline Characteristics 
The following baseline characteristics will be summarized in total and by treatment group.  
• Height (meters) and Weight (kilograms) 
• Iris color (Blue, Green, Hazel, Brown, Other)  
• Iris color groups, defined as Dark (brown, black, other which contains black in 
comments), Light (blue, green, hazel, other which doesn’t contain black in comments) 
• Duration of diabetic macular edema (DME) (months) in the study eye, calculated as 
(randomization date - DME onset date)/30.4 
• BCVA score as a continuous variable and BCVA by randomization strata 
• Central retinal thickness (CRT) (microns) 
• Total area of macular leakage (mm2) 
• lens status assessment: Phakic, Pseudophakic or Ahakic 
4.3 
Prior Medications 
Prior medications include medications taken prior to the first study treatment. A medication 
or ophthalmic medication will be considered as a prior medication if it satisfies at least one of 
the following:   
• The start date is prior to day 1, regardless of the stop date;   
• The start date is unknown but marked as > 1 year; or 
• The stop date is prior to or on day 1, regardless of the start date 
For medications with a partial start or stop date where “> 1 year” is not marked for the start 
date or “ongoing” is not marked for the stop date and the day and/or the month is unknown, 
comparison to the study treatment date (Day 1) will start with the year followed by the month, 
if applicable, for determination of prior medications. In cases where a full determination 
cannot be made based on the partial information, the start date will be assigned to the 1st day 
of the month if the day of the month is missing or to January if the month of the year is 
missing; conversely, the stop date will be assigned to the last day of the month if the day of 
the month is missing or to December if the month is missing. This missing data imputation 
will be done for tabulation purposes.  All partial dates will be listed as recorded in the 
medication listing. 
Number and percentage of participants who reported prior medications will be summarized 
by Anatomical Therapeutic Chemical (ATC) 4 class and PT in total and by treatment group. 
ATC4 classes will be sorted alphabetically; PTs will be sorted in descending frequency in the 


Allergan Confidential                                                                                      Statistical Analysis Plan 206207-026 
700 µg DEX PS DDS 
12 
 
highest dose group. A separate analysis for prior ophthalmic medications used in the study 
eye will be performed.   
4.4 
Concomitant Medications 
Concomitant medications include medications taken after the first study treatment. A 
medication will be considered as a concomitant medication or concurrent procedure if it 
satisfies at least one of the following: 
• The start date is on or after the Day 1 treatment date regardless of the stop date;   
• The stop date is after the Day 1 treatment date, regardless of the start date; or 
• The stop date is unknown but marked as ongoing  
For medications with a partial start or stop date, the same conventions and algorithms as 
described for prior medications will be used for determination of concomitant medications  
Medications and procedures will be coded the same way as prior medications. Concomitant 
medications will be summarized in the same way as that for prior medications. A separate 
summary for concomitant ophthalmic medications used in the study eye will be done.  
Further, concurrent procedures will be summarized for each treatment group.  Similarly, 
concurrent ocular procedures used for the study eye will be summarized for each treatment 
group.   
4.5 
Medical and Surgical History 
Medical history including those ocular and non-ocular history, encompassing abnormalities 
and surgeries reported as occurring before the Screening Visit, will be coded using the 
Medical Dictionary for Regulatory Activities (MedDRA), version 19.1 or newer.  
Number and percentage of participants who reported medical history events will be 
summarized by MedDRA system organ class (SOC) and preferred term (PT) in total and by 
treatment group for the mITT Population. SOCs will be sorted alphabetically; PTs will be 
sorted in descending frequency in the highest dose group. The similar summaries or listings 
will be done for the following events as appropriate: 
• Medical history 
• Medical conditions at the trial initiation 
• Ophthalmic history in the study eye 
• Ophthalmic condition in the study eye at trial initiation 
• Surgical history 


Allerg
700 µg
 
• 
5. 
Unles
for th
0.05. 
5.1 
5.1.1
BCVA
The n
The p
mont
under
eye o
        
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curve
with 
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Ophthalm
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average BCV
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where
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ITT populat
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07-026 
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Allerg
700 µg
 
5.1.2
The p
differ
The A
score
The n
the av
that t
based
interv
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5.1.3
As a 
5.2 
Data 
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5.2.1
Analy
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and th
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g DEX PS DD
 Primary
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14 
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model.  
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yses will be d
ses 
set to missing
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The alternativ
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be calculate
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easured by O
baseline BC
The between-
l be compute
ysis Plan 20620
ng the treatm
h study perio
d baseline BC
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ve hypothesi
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confidence 
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on.  
receive esca
using LOCF
e therapy or 
an incorrect
tical analysi
onth 12 
from baselin
nszel (CMH)
95% confide
ed using norm
Month 12
OCT at month
CVA category
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ed using the 
07-026 
ment 
od. 
CVA 
r in 
is is 
-
ape 
F 
at 
t 
s.  
ne in 
) test 
ence 
mal 
h 12 
y as 
rence 
 


Allerg
700 µg
 
5.2.3
The t
leaka
perfo
main 
and th
ANC
gan Confidentia
g DEX PS DD
 Change
3
total area of 
age area. Ana
ormed using 
effects and 
he correspon
COVA model
al                     
S 
 from Bas
macular leak
alysis for cha
an ANCOVA
baseline tota
nding 2-side
l.  
                       
seline in To
kage measur
ange from b
A model wit
al leakage ar
d 95% CI in
                       
15 
otal Leaka
red by FA is 
aseline in to
h treatment 
rea as the co
n least-square
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age Area a
defined as t
otal leakage a
and baseline
variate. The
e means will
tatistical Analy
at Month 1
the sum of fo
area at mont
e BCVA cate
e between-gr
l be compute
ysis Plan 20620
12 
ocal and diff
th 12 will be
egories as th
roup differen
ed using the 
07-026 
fuse 
e 
e 
nce 
 


Allergan Confidential                                                                                      Statistical Analysis Plan 206207-026 
700 µg DEX PS DDS 
16 
 
6. 
Safety Analyses 
The safety analysis will be based on safety population using observed data. 
6.1 
Exposure to Study Treatment(s) 
Exposure to study treatment will be summarized by the number and percentage of 
participants receiving 0, 1, 2, or 3 injections for the DEX PS DDS treated group, or 0, 1, 2, 3, 
or 4 treatments for the laser photocoagulation treated group.  The mean number of study 
treatments and the numbers of total study days will be calculated for each treatment group.  
6.2 
Treatment-Emergent Adverse Events 
A treatment-emergent adverse event (TEAE) is an adverse event that occurs after the 
initiation of the study treatment (ie, the onset date is the same as or after the study treatment 
date), or an adverse event with onset prior to the study treatment that worsened in severity or 
became serious after the initiation of the study treatment.  
The incidence of TEAEs will be calculated by treatment groups and presented as the number 
and percent of participants experiencing the TEAE during the study period. Summaries for 
TEAE data will be organized into the following: all TEAEs regardless of causality; 
treatment-related TEAEs; ocular TEAEs; and treatment-related ocular TEAEs. The number 
and percent of participants with TEAEs will be presented as follows: 
• By primary system organ class in alphabetical order, and preferred term 
• By primary system organ class in alphabetical order and by the severity (maximum 
severity)  
Within each system organ class name, TEAEs will be tabulated by preferred term and sorted 
in descending order of frequency in the DEX PS DDS treated group and then by the laser 
photocoagulation treated group.  A participant with multiple occurrences of the same 
preferred term within the reporting period will be counted only once for that preferred term.  
In addition, TEAEs leading to discontinuation will be tabulated similarly. 
Analysis for adverse events of special interest will be done for cataract and elevated IOP. 
Summary for cataract will be based on participants with phakic lens at baseline. MedDRA 
terms for AE of cataract and elevated IOP are listed in Table 6-1. Additional terms may be 
added before database lock when applicable. 


Allergan Confidential                                                                                      Statistical Analysis Plan 206207-026 
700 µg DEX PS DDS 
17 
 
Table 6-1 
AE of Special Interest Terms  
System Organ Class 
Preferred Terms 
Group 
Eye Disorders 
Cataract 
Cataract AEs 
 
Cataract cortical 
Cataract AEs 
 
Cataract diabetic 
Cataract AEs 
 
Cataract nuclear 
Cataract AEs 
 
Cataract subcapsular 
Cataract AEs 
 
Lenticular opacities 
Cataract AEs 
 
Ocular hypertension 
Elevated IOP AE 
 
Angle closure glaucoma 
Elevated IOP AE 
 
Borderline glaucoma 
Elevated IOP AE 
 
Diabetic glaucoma 
Elevated IOP AE 
 
Glaucoma 
Elevated IOP AE 
 
Glaucoma Traumatic 
Elevated IOP AE 
 
Gaucomatous optic disc atrophy 
Elevated IOP AE 
 
Open angle glaucoma 
Elevated IOP AE 
 
Pigmentary glaucoma 
Elevated IOP AE 
 
Normal tension glaucoma 
Elevated IOP AE 
Investigations 
Intraocular pressure increased 
Elevated IOP AE 
 
Intraocular pressure fluctuation 
Elevated IOP AE 
Cataract AEs are limited to eyes classified as phakic at baseline. 
 
 
The AE start/end day referring to initial treatment date will be presented in listings. The 
calculation is the same as study day described in section 2.2.  
For each TEAE of a subject, the most recent treatment is defined as the most recent treatment 
prior to TEAE start. Most recent treatment date/day and TEAE start/end day referring to the 
most recent treatment will be presented in listings. 
• Most recent treatment day = most recent treatment date – initial treatment date + 1.  
• TEAE start/end day referring to the most recent treatment = TEAE start/end date - 
most recent treatment date +1.   
The following imputation rules only apply to cases in which the start date for AEs is 
incomplete (ie, partly missing). The imputation is done in order to determine TEAE. The data 
collected on CRF (ie, partly missing) will be presented in listings.  
Missing Month and Day 
• If the year of the incomplete start date is the same as the year of the first dose of study 
treatment, the month and day of the first dose of study treatment will be assigned to the 
missing fields. 
• If the year of the incomplete start date is before the year of the first dose of study 
treatment, December 31 will be assigned to the missing fields. 
• If the year of the incomplete start date is after the year of the first dose of study treatment, 
January 1 will be assigned to the missing fields. 


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18 
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Allerg
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                   Statistical Analysis Plan 206207-026 


Allergan Confidential                                                                                      Statistical Analysis Plan 206207-026 
700 µg DEX PS DDS 
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Allergan Confidential                                                                                      Statistical Analysis Plan 206207-026 
700 µg DEX PS DDS 
21 
 
8. 
Other Analyses 
8.1 
Subgroup Analyses 
China subgroup is defined as all China participants. All analyses will be performed for China 
subgroup.  
8.2 
Interim Analyses  
No interim analysis will be performed for this study. 
 
 
 
 
 
 
 
 
 
 
   
10. 
References 
Kenward, M.G., Roger, J.H. Small sample inference for fixed effects from restricted 
maximum likelihood. Biometrics 1997;53:983-97. 
11. 
Amendments 
To be added when occurred. 
 


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Ozurdex China 206207-026 SAP