A Comparison of Bimatoprost SR to Selective Laser Trabeculoplasty in Patients With Open-Angle Glaucoma or Ocular Hypertension
Phase: PHASE3
Conditions: Glaucoma, Open-Angle, Ocular Hypertension
Sponsor: AbbVie



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The following information can be found on FDA Form 1572 and/or study contacts page:  
Name and contact information of Allergan study personnel and Emergency Telephone 
Numbers; name, address, and statement of qualifications of each investigator; name of each 
subinvestigator working under the supervision of the investigator; name and address of the 
research facilities to be used; name and address of each reviewing IRB; US 21 CFR 312.23 
section 6(iii)b.

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INVESTIGATOR SIGNATURE PAGE
INVESTIGATOR:
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.

Ensure that all persons assisting with the trial are adequately informed about the protocol, 
the investigational product(s), and their trial-related duties and functions.
I have read this protocol in its entirety and I agree to all aspects.  
Investigator Printed Name
Signature
Date

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Table of Contents
Table of Contents ...................................................................................................................... 4
List of Tables............................................................................................................................. 7
Protocol Summary .................................................................................................................... 9
1.
Background and Clinical Rationale................................................................................. 25
1.1
Glaucoma and Treatment ....................................................................................... 25
1.2
Bimatoprost (LUMIGAN®) ................................................................................... 26
1.2.1
Nonclinical Studies with Bimatoprost SR.................................................. 27
1.2.2
Other Biodegradable Ocular Implants ....................................................... 29
1.2.3
Clinical Studies with Bimatoprost SR........................................................ 29
1.3
Study Rationale ...................................................................................................... 30
2.
Study Objectives and Clinical Hypotheses...................................................................... 31
2.1
Study Objectives .................................................................................................... 31
2.2
Clinical Hypotheses ............................................................................................... 31
3.
Study Design.................................................................................................................... 32
4.
Study Population and Entry Criteria................................................................................ 33
4.1
Number of Patients................................................................................................. 33
4.2
Study Population Characteristics ........................................................................... 33
4.2.1
Patients with Sickle Cell Trait/Disease or Other Hemoglobinopathies ..... 33
4.3
Inclusion Criteria.................................................................................................... 33
4.4
Exclusion Criteria................................................................................................... 35
4.5
Permissible and Prohibited Medications/Treatments............................................. 38
4.5.1
Permissible Medications/Treatments ......................................................... 38
4.5.2
Prohibited Medications/Treatments ........................................................... 40
4.5.3
Definition of Females of (Non-)Childbearing Potential and/or Acceptable 
Contraceptive Methods .............................................................................. 42
5.
Study Treatments ............................................................................................................. 43
5.1
Study Treatments and Formulations....................................................................... 43
5.2
Control Treatment .................................................................................................. 43
5.3
Methods for Masking............................................................................................. 43
5.4
Treatment Allocation Ratio and Stratification........................................................ 44
5.5
Method for Assignment to Treatment Groups/Randomization.............................. 44
5.6
Treatment Regimen................................................................................................ 44

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5.7
Storage of Study Medications ................................................................................ 45
5.8
Preparation of Study Medications/Treatments....................................................... 45
5.9
Study Treatment Administration ............................................................................ 46
5.9.1
Bimatoprost SR Administration................................................................. 46
5.9.2
SLT Administration.................................................................................... 49
6.
Response Measures and Summary of Data Collection Methods..................................... 50
6.1
Efficacy Measures.................................................................................................. 50
6.1.1
Primary Efficacy Measure.......................................................................... 50
6.2
Safety Measures ..................................................................................................... 51
6.3
Other Measures ...................................................................................................... 54
6.3.1
Medical History, Physical Examination, and Vital Signs........................... 54
6.3.2
Pregnancy Testing ...................................................................................... 55
6.3.3
Laboratory Procedures ............................................................................... 55
6.4
Other Study Supplies.............................................................................................. 56
6.5
Summary of Methods of Data Collection .............................................................. 57
7.
Statistical Procedures....................................................................................................... 57
7.1
Analysis Populations.............................................................................................. 58
7.2
Collection and Derivation of Primary and Secondary Efficacy Assessments........ 58
7.2.1
Primary Efficacy Variable.......................................................................... 59
7.2.2
Secondary Efficacy Variables..................................................................... 59
7.2.3
Other Efficacy Variables ............................................................................ 59
7.3
Hypothesis and Methods of Analysis..................................................................... 59
7.3.1
Primary Efficacy Analyses......................................................................... 60
7.3.2
Secondary Efficacy Analyses..................................................................... 61
7.3.3
Other Efficacy Analyses............................................................................. 62
7.3.4
Safety Analyses.......................................................................................... 62
7.4
Subgroup Analyses................................................................................................. 63
7.5
Sample Size Calculation ........................................................................................ 63
7.6
Interim Analyses..................................................................................................... 63
8.
Study Visit Schedule and Procedures .............................................................................. 63
8.1
Patient Entry Procedures........................................................................................ 65
8.1.1
Overview of Entry Procedures................................................................... 65
8.1.2
Informed Consent and Patient Privacy....................................................... 65
8.2
Washout Intervals................................................................................................... 65

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8.3
Procedures for Final Study Entry........................................................................... 66
8.4
Visits and Associated Procedures........................................................................... 67
8.4.1
Screening Visit ........................................................................................... 67
8.4.2
Baseline Visit ............................................................................................. 69
8.4.3
Treatment Period........................................................................................ 70
8.5
End of Study........................................................................................................... 78
8.6
Instructions for the Patients.................................................................................... 78
8.7
Unscheduled Visits................................................................................................. 79
8.8
Compliance with Protocol...................................................................................... 79
8.9
Early Discontinuation (Early Exit) of Patients....................................................... 79
8.10 Withdrawal Criteria................................................................................................ 80
8.11 Study Termination.................................................................................................. 80
9.
Adverse Events ................................................................................................................ 80
9.1
Definitions.............................................................................................................. 81
9.1.1
Adverse Event............................................................................................ 81
9.1.2
Serious Adverse Event ............................................................................... 81
9.1.3
Severity ...................................................................................................... 82
9.1.4
Relationship to Study Drug, Device, or Procedure.................................... 82
9.2
Procedures for Reporting Adverse Events ............................................................. 83
9.3
Procedures for Reporting a Serious Adverse Event............................................... 83
9.4
Procedures for Unmasking of Study Treatment..................................................... 84
10. Administrative Items ....................................................................................................... 84
10.1 Protection of Human Patients................................................................................. 84
10.1.1 Compliance With Informed Consent Regulations (US 21 CFR Part 50) and 
Relevant Country Regulations ................................................................... 84
10.1.2 Compliance With IRB or IEC Regulations ................................................ 85
10.1.3 Compliance With Good Clinical Practice .................................................. 85
10.1.4 Quality Assurance ...................................................................................... 85
10.1.5 Compliance With Electronic Records; Electronic Signatures Regulations 
(US 21 CFR Part 11).................................................................................. 85
10.2 Changes to the Protocol ......................................................................................... 85
10.3 Patient Confidentiality ........................................................................................... 86
10.3.1 Patient Privacy ........................................................................................... 86
10.4 Documentation....................................................................................................... 86
10.4.1 Source Documents ..................................................................................... 86

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Table 6
Schedule of Visits and Procedures:  Month 13 through Month 24/Exit ......... 23
Table 7
Minimum Washout Period by Ophthalmic Medication Class ........................ 66
Table 8
Administration Cycle 3 Schedule of Visits and Procedures (only for patients 
who reached Week 32 prior to implementation of Amendment 3)............... 157

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Protocol Summary
Study Compound:  Bimatoprost sustained release (SR) implants containing preservative-free bimatoprost 
(AGN-192024)
Phase:  3
Study Objective:  To evaluate the intraocular pressure (IOP)-lowering effect and safety of Bimatoprost SR 
compared with selective laser trabeculoplasty (SLT) in patients with open-angle glaucoma (OAG) or ocular 
hypertension (OHT) who are not adequately managed with topical IOP-lowering medication for reasons other 
than medication efficacy (eg, due to intolerance or nonadherence) 
Clinical Hypotheses:  
Bimatoprost SR will have an IOP-lowering effect that is noninferior to that of SLT in patients with OAG or 
OHT who are not adequately managed with topical IOP-lowering medication for reasons other than medication 
efficacy (eg, due to intolerance or nonadherence).
Bimatoprost SR administered intracamerally will have an acceptable safety profile in patients with OAG or 
OHT who are not adequately managed with topical IOP-lowering medication for reasons other than medication 
efficacy (eg, due to intolerance or nonadherence).
Study Design
Structure:  multicenter, paired eye, randomized, masked, conducted in 2 stages:

Stage 1:  Bimatoprost SR 15 µg vs SLT; 2 administration cycles for patients who had not received a 
third administration cycle before implementation of Amendment 3

Stage 2:  Bimatoprost SR 10 µg vs SLT; 2 administration cycles
Duration:  approximately 26 months, including screening period of up to 28 days before washout, washout 
period of up to 56 days before initial study treatment, plus 24 months of follow-up after initial Bimatoprost SR 
and SLT administration.
Study Treatment:  Bimatoprost SR 15 µg (Stage 1) or 10 µg (Stage 2)
Controls:  360° SLT administration 
Dosage/Dose Regimen:  
Patients will receive a 360° administration of SLT in 1 eye on Day 1 and an administration of Bimatoprost SR 
in the contralateral eye on Day 4, with a repeat administration of Bimatoprost SR at Week 16 if the patient 
meets the retreatment criteria.  For those patients not meeting retreatment criteria at Week 16, Cycle 2 may be 
performed at the investigator’s discretion during an unscheduled visit after Week 16 and prior to the Month 12
visit if the retreatment criteria are met.  (Note that for all patients who were enrolled and reached the Week 16 
visit prior to implementation of Amendment 6, retreatment with Bimatoprost SR was fixed at Week 16.) In 
order to mask the patient to the treatment assigned to each eye, on Day 1, a sham SLT procedure will be 
performed in the eye that will receive Bimatoprost SR administrations (hereafter referred to as the “Bimatoprost 
SR eye”).  Similarly, a sham needleless Bimatoprost SR administration (hereafter referred to as the “Sham
Bimatoprost SR administration”) that involves touching the eye at the area of insertion with a needleless 
applicator that does not deliver an implant into the anterior chamber, will be performed on the SLT-treated eye 
(hereafter referred to as the “SLT eye”) on Bimatoprost SR administration visits.  
Treatment schedule by eye is shown in 
Table 1.

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Table 1
Treatment Schedule by Eye
Treatment Visit
Bimatoprost SR Eye
SLT Eye
SLT administration
(Day 1)
Sham SLT
360° SLT
Bimatoprost SR Cycle 1 administration
(Day 4)
Bimatoprost SR
Sham Bimatoprost SR
Bimatoprost SR Cycle 2 administration
(Week 16)a
Bimatoprost SR
Sham Bimatoprost SR
SLT = selective laser trabeculoplasty; SR = sustained release
a
Cycle 2 administration of Bimatoprost SR is performed at Week 16 for all patients who meet retreatment criteria.  For 
those patients not meeting retreatment criteria at Week 16, Cycle 2 may be performed at the investigator’s discretion 
during an unscheduled visit after Week 16 and prior to the Month 12 visit if the retreatment criteria are met.  
Randomization/Stratification:  The eye with the higher IOP at Baseline will be assigned to be the primary eye.  
If baseline IOP is the same in both eyes, the right eye will be the primary eye.  The primary eye will be 
randomized to receive either Bimatoprost SR or SLT using a 1:1 ratio, stratified by primary eye baseline IOP 
(≤25 or > 25 mm Hg) 
  If the 
primary eye receives Bimatoprost SR, the contralateral eye will receive SLT.  If the primary eye receives SLT, 
the contralateral eye will receive Bimatoprost SR.
Visit Schedule:  Patients who complete all study treatments will have up to 28 visits and 5 phone calls.  The 
schedule includes the following:

Screening (up to 28 days); Washout period of up to 56 days for both eyes; and Baseline visit (up to 
3 days)

SLT treatment (Day 1) and phone call (Day 2) 

Bimatoprost SR Cycle 1 administration (Day 4); Cycle 1 Day 2 safety visit; Cycle 1 Day 4 and Week 2 
phone calls; and follow-up study visits at Weeks 4, 8, 12, and 15

Bimatoprost SR Cycle 2 administration (to occur at Week 16 for all patients who meet retreatment
criteria); Cycle 2 Day 2 safety visit; and Cycle 2 Day 4 and Week 2 phone calls
o
Patients who do not receive Cycle 2 administration at Week 16 will not attend the Cycle 2 
Administration Day visit on Week 16, or the Day 2 Safety or Day 4 and Week 2 phone calls 
associated with administration at Week 16.  For these patients, Cycle 2 may be performed at 
the investigator’s discretion during an unscheduled visit after Week 16 and prior to the 
Month 12 visit if the retreatment criteria are met; in this case, inadequate control of IOP 
should be confirmed at another scheduled or unscheduled visit prior to initiation of Cycle 2.  
All Cycle 2 visits will apply at the time of the Cycle 2 administration.

Follow-up visits at Weeks 20, 24, 28, 31, 36, 40, 44, 47, and 52; and Months 13, 14, 15, 16, 18, 20, 22, 
and 24/Exit
o
Regardless of the timing of Cycle 2 administration, all regularly scheduled visits should be 
completed.  Cycle 2 visits should be scheduled such that the Administration Day and the 
Day 2 Safety Visit do not occur on the day of a regularly scheduled study visit.  However, if 
the Cycle 2 Day 4 or Week 2 Phone Calls overlap with a regularly scheduled visit, perform
the regularly scheduled visit.  
o
Patients who receive the second administration of Bimatoprost SR at Week 16 and patients 
who never receive a second administration may, at the investigator’s discretion, skip the 

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visits at Months 13, 15 and 22 if the patient has received nonstudy IOP lowering medication 
in both eyes; has ≤ 25% of each implant remaining in the eye; and in the investigator’s 
clinical judgment, has no safety or other concern that would require the patient to attend these 
visits.  Please note: each eye should be evaluated on an individual basis when determining 
the need for additional nonstudy IOP-lowering treatments; initiation of treatment in one eye 
should not automatically lead to initiation of treatment in the contralateral eye.

Intraocular pressure evaluations will occur at Hour 0 (08:00 am ± 1 hour).  Selected patients at selected 
sites will have additional IOP measurements performed at Hour 2 (Hour 0 + 2 hours [± 30 minutes]) 
and Hour 8 (Hour 0 + 8 hours [± 30 minutes]).  
Study Population Characteristics
Number of Patients:  
Stage 1:  approximately 50 patients
Stage 2:  approximately 160 patients
Condition/Disease:  patients with OAG or OHT who require IOP-lowering medications in both eyes
Key Inclusion Criteria:  

Male or female, 18 years of age or older

Written informed consent and authorization for use and release of personal health information are 
obtained in accordance with the relevant country and local privacy requirements, where applicable (eg, 
Written Authorization for Use and Release of Health and Research Study Information [United States 
(US) sites] and written Data Protection consent [European Union (EU) sites])

In the investigator’s opinion, patient’s IOP is not adequately managed with topical medication for 
reasons other than medication efficacy (eg, due to intolerance or nonadherence)
Ocular

In the investigator’s opinion, both eyes can be treated adequately with topical prostamide, 
prostaglandin, or prostaglandin analog (eg, LUMIGAN, Xalatan®, Travatan®) eye drops as the sole 
therapy if medication was taken as directed

In the investigator’s opinion, patient’s IOP can be adequately managed with SLT monotherapy

In the investigator’s opinion, patient is a suitable candidate for SLT

Diagnosis of either OAG (ie, primary OAG,  pseudoexfoliation glaucoma, pigmentary glaucoma) or 
OHT in each eye, requiring bilateral IOP-lowering treatment (Note:  diagnosis does not have to be the 
same in both eyes)

Central endothelial cell density by specular microscopy confirmed as being qualified by Reading 
Center assessment prior to beginning Washout 

The iridocorneal angle must be independently confirmed as being qualified by 2 ophthalmologists 
using the following criteria:

Shaffer Grade ≥ 3 on clinical gonioscopy of the inferior angle

Peripheral anterior chamber depth by Van Herick  examination ≥ 1/2 corneal thickness 
Note:  The independent eligibility assessments must both agree that the Shaffer grade is ≥ 3 and the 
Van Herick grade is ≥ 1/2 corneal thickness.

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Regulatory Activities (MedDRA) nomenclature.  The number and percentage of patients reporting 
treatment-emergent adverse events will be tabulated based on the system organ class and preferred term.  
Ocular safety variables attributable to each eye will be tabulated by Bimatoprost SR or SLT eye. Nonocular 
safety variables will be summarized.
Sample Size Calculation:  The sample size calculation is based on paired-eye differences using a normal 
approximation with a 2-sided significance level of 0.05, assuming that there is no difference in mean IOP
change from baseline between Bimatoprost SR 10 µg eyes and SLT eyes and that change from baseline in IOP 
has a standard deviation of 4 mm Hg.  A sample size of 144 patients will provide approximately 98% power in 
showing noninferiority for 3 out of 3 timepoints with a noninferiority margin of 1.5 mm Hg, and 90% power in 
showing noninferiority for 2 out of 3 timepoints with a noninferiority margin of 1.0 mm Hg, assuming that both 
the between-eyes and the within-patient correlation coefficients are 0.5.  Assuming a premature discontinuation 
rate of 10%, approximately 160 patients are to be enrolled into this study and treated with 
Bimatoprost SR 10 µg.  Additionally, there are approximately 50 patients who were enrolled before 
implementation of Amendment 3.

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Table 2
Administration Cycle 1 Schedule of Visits and Procedures:  Screening through Day 2
Visit
Screening
Baselineb
Day 1 
(SLT 
Administration)
Day 2
Phone 
Callc
Visit Windows
Up to 28 days
Up to 3 days
Informed Consent/Authorization
X
Washouta
Up to 56 days
Demographic Data
X
Medical/Ophthalmic History
X
X
Adverse Events
X
X
X
X
Concomitant Medications/ Procedures
X
X
X
X
Visual Function Questionnaire-25
X
Physical Examination 
X
Vital Signs (at rest ≥5 minutes)
X
X
X
Pregnancy Testd
X
Blood and Urine Sample Collectione
Xe
Ocular Examinations in bold should be performed in the order shown
Pre-Hour 0 Exam (perform before Hour 0 IOP):
  Macroscopic Conjunctival Hyperemia Assessmentf
OU
Washouta
Up to 56 days
OU
Manifest Refractiong
OU
OU
Best-Corrected Visual Acuity
OU
OU
Intraocular Pressure Measurement Hour 0
OU
OU
Non-contact Exams (may perform in any order at any time before gonioscopy [before Hour 8 at
Baselineh])
  Macroscopic Iris Color Assessment 
OU
  Visual Fieldi
OU
OU
  Specular Microscopy
OU
  Anterior Segment Optical Coherence Tomography
OU

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1.
Background and Clinical Rationale
1.1
Glaucoma and Treatment
Glaucoma is a family of diseases commonly characterized by progressive optic neuropathy 
with associated visual field defects and is the leading cause of irreversible blindness in the 
world.  Glaucoma is classified by Becker-Shaffer into 3 broad types:  developmental, 
angle-closure, and open-angle glaucoma (OAG) (Stamper et al, 2009).  Open-angle glaucoma 
is further categorized into primary OAG (POAG, sometimes also referred to as chronic 
OAG) and secondary OAG (which includes pigmentary and pseudoexfoliation glaucoma), 
the former being the predominant form of OAG.  Primary OAG is characterized as a 
multifactorial optic neuropathy with a characteristic acquired atrophy of the optic nerve and 
loss of ganglion cells and their axons, developing in the presence of open anterior chamber 
(AC) angles, and manifesting characteristic visual field abnormalities 
(American Academy of Ophthalmology, 2010a).  Globally, over 60 million people are 
estimated to be affected by glaucoma (the majority of whom have OAG) and these numbers 
are expected to increase over time (Quigley and Broman, 2006; Varma et al, 2011; 
Cook and Foster, 2012).  Approximately 10% of eyes with elevated intraocular pressure 
(IOP) will progress to OAG over the course of a decade (Quigley et al, 1994).
Although many risk factors have been associated with OAG, elevated IOP remains the most
prominent factor and the only factor existing that ophthalmic intervention can reliably affect 
(Stamper et al, 2009).  A number of controlled trials have demonstrated that lowering IOP 
will slow or delay the appearance or progression of glaucomatous damage.  Large, 
randomized clinical trials such as the Ocular Hypertension Treatment Study 
(Kass et al, 2002) and the Early Manifest Glaucoma Trial (Heijl et al, 2002) addressed the 
value of early detection and lowering of elevated IOP in ocular hypertension (OHT) or 
POAG.  The effects and parameters of various interventions in eyes with established 
glaucomatous damage were addressed by the Collaborative Initial Glaucoma Treatment 
Study (Lichter et al, 2001) and the Advanced Glaucoma Intervention Study (AGIS) 
(AGIS, 2000).  The currently available approaches to lowering IOP include topical 
pharmacological therapy, laser trabeculoplasty (LT), incisional surgery, and cyclodestructive 
procedures.  Each of these approaches has its own risk-benefit ratio.  Because the risk-benefit 
ratio with drug therapy appears to be lower than that of surgical procedures, both historical
and contemporary practice has been to attempt pharmacological treatment before resorting to 
other more invasive alternatives.

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Although a variety of effective topical ocular antihypertensive medications (including 
bimatoprost) are available, patient nonadherence to topical therapy is one of the major 
challenges to preventing vision loss due to glaucoma, as consistent IOP reduction is 
associated with reduced risks of the development and progression of optic nerve damage 
(Friedman, 2009; Tsai, 2009).  One literature review found that up to 80% of patients 
deviated from their prescribed medication regimen (Olthoff et al, 2005).  In addition, most 
patients with OAG or OHT are elderly, and many have inherent difficulties applying daily 
antihypertensive eye drops due to physical and/or cognitive disabilities such as arthritis and 
poor memory (European Glaucoma Society guidelines, 2014; Tsai, 2009).  Guidelines have 
been developed and provided to clinicians for assisting patients with being adherent
(Budenz, 2009).  In addition, surgical interventions, both laser based (eg, LT) and incisional, 
are recommended as treatment options for patients with OAG and OHT who have challenges 
with topical medication adherence or tolerance (European Glaucoma Society guidelines, 
2014).  Laser trabeculoplasty is a safe and noninvasive procedure; however, repeatability of 
LT is controversial (Realini, 2008).  Patients will often require adjunctive therapy after LT, 
and may eventually require incisional surgery to control their IOP (Francis et al, 2005; 
Koucheki and Hashemi, 2012).  Incisional surgery presents the risk of significant 
sight-threatening complications, such as the globe perforation, suprachoroidal hemorrhage, 
hypotony maculopathy, corneal decompensation, and cataract formation or progression that 
may occur with filtering surgery (Mosaed et al, 2009).  As a result, Allergan has developed a 
sustained-release (SR) bimatoprost implant as an ocular antihypertensive therapy for patients 
with OAG and OHT who are not adequately managed by topical medication due to 
medication adherence or tolerability issues.
1.2
Bimatoprost (LUMIGAN®)
Bimatoprost is a member of a series of unique prostanoid compounds that are potent and 
efficacious ocular antihypertensive agents (Woodward et al, 1994, 2001, and 2004).  
Bimatoprost appears to mimic the activity of biologically active prostamides 
(Study BIO-99-308; Matias et al, 2004).  Chemically, prostamides differ from prostaglandin 
analogs by being neutral because they lack carboxylic acids (Krauss and Woodward, 2004).  
Prostamides can be biosynthetically derived from anandamide, an endogenous membrane 
lipid (Kozak et al, 2002; Weber et al, 2004; Woodward et al, 2001; Yu et al, 1997).  The
prostamide pathway leads to the biosynthesis of novel lipid amides that lower IOP.

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The IOP-lowering efficacy of LUMIGAN (bimatoprost ophthalmic solution) 0.03% is well 
established.  In phase 3 studies in patients with POAG or OHT, LUMIGAN administered 
once daily as monotherapy was superior to timolol at all timepoints 
(Higginbotham et al, 2002).  This was further substantiated in the extension studies which 
followed patients in a masked manner for up to 4 years (Cohen et al, 2004; 
Williams et al, 2008; Study 192024-014).  In clinical studies of patients with OAG or OHT 
with a mean baseline IOP of 26 mm Hg, the IOP-lowering effect of LUMIGAN administered 
once daily in the evening was 7 to 8 mm Hg (Cohen et al, 2004; 
LUMIGAN® Package Insert, 2012; Williams et al, 2008).  LUMIGAN was approved by the 
United States (US) Food and Drug Administration (FDA) in 2001.  Worldwide, LUMIGAN 
0.03% is currently licensed and marketed in more than 80 countries and LUMIGAN 0.01% is 
licensed and marketed in more than 40 countries.  Preservative-free bimatoprost ophthalmic 
solution 0.03% has been approved since November 2012 for lowering IOP, and is currently 
marketed in 10 countries.  
A sustained-release (SR) formulation of bimatoprost was developed at Allergan, Inc. to 
evaluate ocular antihypertensive therapies that do not require patient self-administration.  
Bimatoprost SR refers to the biodegradable, sustained-release, preservative-free bimatoprost 
implant which is preloaded in an applicator for administration; together they comprise the 
Bimatoprost SR product.  The Bimatoprost SR implant is injected into the AC via the corneal 
limbus using the prefilled applicator.  The biodegradable polymer matrix gradually degrades 
to carbon dioxide and water so that there is no need to remove the Bimatoprost SR implant 
once the drug has been released.  The Bimatoprost SR implant used in this study contains a 
total preservative-free bimatoprost load of 10 μg, and intracameral administration of this dose 
strength is expected to reduce the total daily drug exposure to the eye by approximately 
126-fold compared with topical LUMIGAN 0.03% application over 4 months, as well as 
possibly reducing the adverse effects observed with topical glaucoma medications.  The 
Bimatoprost SR implant is expected to release drug over approximately 4 months, and 
 
polymer matrix degradation is expected within approximately 12 months.  Although the 
biodegradation process of the Bimatoprost SR implant exceeds the drug release duration, 
experience from preclinical studies, the phase 1/2 (Study 192024-041D), and approved 
intravitreal implants composed of similar biodegradable polymers provide support for the
anticipated safety in a phase 3 clinical trial with repeated administration.  
1.2.1
Nonclinical Studies with Bimatoprost SR
Pharmacology, toxicology, and pharmacokinetic studies with multiple dose strengths, implant 
sizes, and formulations (Generation 1 and Generation 2) of Bimatoprost SR were completed 

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in 2 species (Beagle dogs and Cynomolgus monkeys) with a range of AC angle sizes in order 
to support the clinical program.  These studies build on the already considerable amount of 
nonclinical and clinical information available for topical bimatoprost (see Investigator’s 
Brochure [IB] for additional details).
Nonclinical studies with pharmacology endpoints (Reports BIO-09-803, BIO-11-920, 
PK09109-PK, BIO-09-785) showed dose-related reductions in IOP in normotensive 
Cynomolgus monkeys and Beagle dogs, as well as in laser-induced ocular hypertensive 
Cynomolgus monkeys following single doses.  Toxicology studies, of at least 6 to 12 months 
duration and including single and repeat Bimatoprost SR administration, were conducted in 
Cynomolgus monkeys and Beagle dogs (Studies TX09051-TX, TX09066-TX, TX10016-TX, 
TX11076-TX, TX12012-TX, TX12018-TX, and TX12102-TX).  Monkeys, which have a 
characteristically small AC angle compared to both dogs and humans, did not tolerate 
Bimatoprost SR dose strengths tested (≥ 10 μg Bimatoprost SR) due to chronic contact of the 
implant with corneal endothelium.  Single and repeat ocular toxicity studies with Generation 
2 Bimatoprost SR in dogs with varying AC angle sizes demonstrated acceptable safety and 
ocular tolerability with single doses ≤ 20 μg (Studies TX11076-TX, TX12012-TX, 
TX12018-TX) and with repeat doses of ≤ 15 μg (Studies TX12012-TX and TX12018-TX).  
Furthermore, no adverse drug- or implant-related ocular findings have been seen following 
3 intracameral injections of up to 20 μg (two 10 μg implants) Bimatoprost SR in the 
18-month repeat-dose Good Laboratory Practice (GLP) study in dogs (Study TX12102-TX).  
Pharmacokinetic studies of Bimatoprost SR (Studies PK09109-PK and PK11086-PK) in 
Beagle dogs demonstrated that systemic exposure of bimatoprost and bimatoprost acid was 
below the limit of quantitation (BLQ) with doses ≤ 60 μg.  Aqueous humor concentrations 
generally peaked by 10 weeks postdose for doses 
 μg (Generation 1 and Generation 2), 
then declined to low levels suggestive of near-complete drug release from the device at  
months for doses 
 μg.  By 14 weeks following a 20 μg (Generation 2) dose, ocular 
tissues samples were collected for analysis, which demonstrated that drug and metabolite 
concentrations were BLQ in aqueous humor, vitreous humor, retina, and the remnant 
implants, but detected in cornea, choroid, and iris-ciliary body.  A pharmacokinetic study 
(PK14025-PK) was conducted in Beagle dogs comparing the ocular distribution of topical 
bimatoprost 0.03% solution or a single Generation 2 Bimatoprost SR implant (15 µg).  
Following topical administration, bimatoprost and bimatoprost acid distributed into the 
iris-ciliary body as well as other (off target) tissues with concentrations in the bulbar 
conjunctiva, eyelid margin, and periorbital fat significantly higher than those observed in the 
iris-ciliary body.  In contrast, following administration of a single Generation 2 Bimatoprost 
SR implant at 15 μg, bimatoprost and bimatoprost acid concentrations were either below the 

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limit of quantitation (BLQ) or near the detection limit in bulbar conjunctiva, eyelid margin, 
and periorbital fat while the highest bimatoprost and bimatoprost acid concentrations were 
observed in the target tissue, the iris ciliary body.  Retinal concentrations were BLQ 
following both topical and Bimatoprost SR administration.
1.2.2
Other Biodegradable Ocular Implants
A number of SR drug delivery implants using the Allergan polylactic acid (PLA) and/or
polylactic-co-glycolic acid (PLGA) biodegradable platform preceded the development of the 
Bimatoprost SR implant.  The extensive clinical experience with previous intraocular 
implants demonstrates the safety and tolerability of an intraocular biodegradable implant 
administered into the eye via an applicator system.  For example, late phase clinical trials of 
SR implants have been completed for the OZURDEX®dexamethasone intravitreal implant 
using the NOVADUR® drug delivery system for intraocular injections.  Because Bimatoprost 
SR is similar to OZURDEX in a number of aspects and uses the NOVADUR drug delivery 
system for intraocular injections, these data may be supportive of the safety and tolerability 
of Bimatoprost SR in humans.
1.2.3
Clinical Studies with Bimatoprost SR
Study 192024-041D was a phase 1/2 paired-eye comparison study evaluating the safety and 
efficacy of 4 dose strengths of Bimatoprost SR (6, 10, 15, or 20 μg [2 x10 μg implants]), as 
single or repeat administrations in 1 eye (study eye), versus the use of topical LUMIGAN
0.03% once daily in the contralateral eye (nonstudy eye).  The objective of this study was to 
evaluate the safety and IOP-lowering efficacy of Bimatoprost SR in patients with OAG.  
A total of 109 patients received at least a single administration of Bimatoprost SR, and
24 patients received a repeat administration of Bimatoprost SR.  A trend in dose response 
was observed across the 4 dose strengths that were tested.
Data suggest that the implant may provide topical prostaglandin analog-like efficacy up to 
3 to 4 months post-implantation in the majority of patients.  Data following the second 
administration in the retreated patients showed similar IOP lowering efficacy to that observed 
following the first administration of Bimatoprost SR.  In addition, efficacy was maintained 
longer than the expected 3- to 4-month duration in many patients in this completed study.  By 
Month 6, most patients (> 66%) were still maintained on monotherapy with the initial 
Bimatoprost SR implant administered.  Among all Generation 2 dose strengths, at least 33% 
of patients had not received rescue or a second Bimatoprost SR treatment by Month 12.  At 
Month 24, at least 23% of patients had not received rescue or a second treatment.  

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Bimatoprost SR showed an acceptable safety profile with single and repeat administrations in 
study 192024-041D.  Most adverse events were ocular, mild or moderate in severity, 
occurred within the first 2 days after Bimatoprost SR administration, and were considered 
related to the study drug administration procedure.  There were no reports of serious study 
drug-related adverse events, and no new safety concerns were observed after the second 
treatment.  Please refer to the Investigator’s Brochure for details on reported safety findings.
Two identical global phase 3 studies (Studies 192024-091 and 192024-092) were initiated in 
late 2014.  These studies are assessing the safety and efficacy of Bimatoprost SR in 
multicenter, randomized, masked, parallel-group comparison studies of 2 dose strengths of 
Bimatoprost SR (10 and 15 µg) to an active control (timolol maleate 0.5%).
1.3
Study Rationale
Results of the completed phase 1/2 study, 192024-041D, showed that Bimatoprost SR 
provides a prostaglandin analog-like IOP-lowering efficacy when used at the dose strengths
being used in this phase 3 investigation.  Additionally, the safety profile of Bimatoprost SR 
at dose strengths of 20 μg (2 × 10 μg) or less in the phase 1/2 study was acceptable and 
supports additional clinical studies in humans.  Study 192024-093 was designed as a 
randomized, patient and efficacy evaluator-masked, paired-eye comparison evaluating the 
safety and IOP-lowering effects of repeated administrations of 15 μg Bimatoprost SR in 
patients with OAG or OHT who are not adequately managed with topical medication (eg, 
due to intolerance or nonadherence).  
Based on the interim data from phase 1/2 study 192024-041D, the higher of the two dose 
strengths being evaluated in the other global phase 3 studies, 15 µg, was selected for the 
2 phase 3 studies against an SLT comparator (192024-093 and 192024-095).  After
additional data from later-stage studies became available, the protocol in one of these studies 
(192024-093) was amended (Amendment 3) to reduce the dose strength for newly enrolled 
patients to 10 µg, in order to broaden the range of dose strengths evaluated in the 2 phase 3 
studies with the SLT comparator arm.  In addition, the number of administration cycles was 
reduced from 3 to 2 (eliminating Week 32 administration for newly enrolled patients and 
ongoing patients who had not yet received the Week 32 administration).  The number of 
administration cycles was reduced based on the duration of effect observed in completed 
24-month Study 192024-041D as well as the analysis of data from the first 3 months of 
treatment (primary analysis) in Study 192024-091, which suggested that the majority of 
patients do not require rescue treatment for an extended duration following their last 
Bimatoprost SR administration.  The results of both studies suggest that efficacy may be 

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maintained with fewer administration cycles.  In Amendment 6, an IOP-based retreatment 
criterion was added as a requirement for the second administration of Bimatoprost SR at 
Week 16 (patients not meeting retreatment criteria at Week 16 may receive the second 
administration of Bimatoprost SR at the investigator’s discretion during an unscheduled visit 
after Week 16 and prior to the Month 12 visit if the retreatment criteria are met).  The change 
from 3 to 2 administration cycles and the addition of the IOP-based retreatment criterion will 
not change the primary efficacy analysis, which is planned to occur after all patients treated 
with Bimatoprost SR 10 µg complete the Week 24 visit or discontinue the study and allows 
for assessment of the duration of effect of 2 Bimatoprost SR administration cycles 
throughout the study.
The comparator that is to be administered in the contralateral eye is selective laser 
trabeculoplasty (SLT), which is also indicated for this patient population.  SLT, one of the 
most frequently used LT modalities, is commonly used as an intermediate step between 
topical medications and incisional glaucoma surgery and is comparable in efficacy and 
durability to argon laser trabeculoplasty (ALT) (Damji et al, 1999; Damji et al, 2006; 
Martinez-de-la-casa et al, 2004; Rolim de Moura et al, 2007; Wang et al, 2013).  SLT causes
minimal tissue destruction compared with ALT and is increasingly being adopted as the LT 
standard of care (Realini, 2008).  SLT has been reported to reduce IOP effectively in eyes 
with OHT and OAG, as reports often suggest IOP reduction to be similar to topical 
prostaglandin analogues (Katz et al, 2012; Nagar et al, 2009; McAlinden 2014).  This study 
is 1 of 2 phase 3 studies that will compare the IOP-lowering effects and safety profiles of 
Bimatoprost SR and SLT.
2.
Study Objectives and Clinical Hypotheses 
2.1
Study Objectives
To evaluate the IOP-lowering effect and safety of Bimatoprost SR compared with SLT in 
patients with OAG or OHT, who are not adequately managed with topical IOP-lowering 
medication for reasons other than medication efficacy (eg, due to intolerance or 
nonadherence).
2.2
Clinical Hypotheses
Bimatoprost SR will have an IOP-lowering effect that is noninferior to that of SLT in patients 
with OAG or OHT who are not adequately managed with topical IOP-lowering medication 
for reasons other than medication efficacy (eg, due to intolerance or nonadherence).

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Bimatoprost SR administered intracamerally will have an acceptable safety profile in patients 
with OAG or OHT who are not adequately managed with topical IOP-lowering medication
for reasons other than medication efficacy (eg, due to intolerance or nonadherence).
3.
Study Design
This study is a multicenter, paired-eye, randomized, efficacy evaluator-masked 26-month 
study conducted in 2 stages and evaluating 2 different dose strengths of Bimatoprost SR 
(Stage 1:  15 µg; Stage 2:  10 µg).  The safety and IOP-lowering effect of Bimatoprost SR 
will be compared with SLT in OAG and OHT patients who are not adequately managed with 
topical medication for reasons other than medication efficacy (eg, due to intolerance or 
nonadherence).
The study is being conducted in 2 stages because the protocol was amended (Amendment 3)
to reduce the dose strength for newly enrolled patients to 10 µg in order to broaden the range 
of dose strengths evaluated in the 2 phase 3 studies with the SLT comparator arm.  The 
primary efficacy analysis will be performed for patients in Stage 2 only.
The eye with the higher IOP at Baseline will be assigned as the primary eye.  If baseline IOP 
is the same in both eyes, the right eye will be the primary eye.  The primary eye will be 
randomized to receive either Bimatoprost SR or SLT using a 1:1 ratio, stratified by primary 
eye baseline IOP (≤ 25 versus > 25 mm Hg) 
 
  If the primary eye receives Bimatoprost SR, the 
contralateral eye will receive SLT.  If the primary eye receives SLT, the contralateral eye 
will receive Bimatoprost SR.
Patients will receive a 360° administration of SLT in 1 eye on Day 1, and administration of 
Bimatoprost SR in the contralateral eye on Day 4, with a repeat administration of 
Bimatoprost SR at Week 16 for all patients who meet retreatment criteria.  For those patients 
not meeting retreatment criteria at Week 16, Cycle 2 may be performed at the investigator’s 
discretion during an unscheduled visit after Week 16 and prior to the Month 12 visit if the 
retreatment criteria are met.  (Note that for all patients who were enrolled and reached the 
Week 16 visit prior to implementation of Amendment 6, retreatment with Bimatoprost SR 
was fixed at Week 16.) In order to mask the patient to the treatment assigned to each eye, on 
Day 1 a Sham SLT procedure will be performed in the eye to be administered Bimatoprost 
SR (hereafter refer to as the “Bimatoprost SR eye”).  A Sham Bimatoprost SR administration 
will be performed in the eye that underwent SLT (hereafter referred to as the “SLT eye”) on 
each Bimatoprost SR administration visit (Day 4 and Week 16) (see 

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Table 1).
4.
Study Population and Entry Criteria
4.1
Number of Patients 
Approximately 160 patients will be enrolled and treated with Bimatoprost SR 10 µg at 
approximately 70 sites, in order to have an estimated 144 patients treated with Bimatoprost 
SR 10 µg complete the study based on a premature discontinuation rate of 10%.  
Approximately 50 patients enrolled before implementation of Amendment 3 and received 
Bimatoprost SR 15 µg.
4.2
Study Population Characteristics
The study population consists of patients with bilateral OAG or OHT who are not adequately 
managed with topical medication for reasons other than medication efficacy (eg, due to 
intolerance or nonadherence).  Both eyes must require IOP-lowering treatment, must be able 
to be adequately managed on SLT monotherapy, and must meet study entry criteria.
4.2.1
Patients with Sickle Cell Trait/Disease or Other 
Hemoglobinopathies
Patients with sickle cell trait or disease or other hemoglobinopathies may be enrolled at the 
discretion of the investigator based on an individual risk-benefit assessment.  Because of a 
slightly higher risk of IOP elevation and intraocular complications in the setting of a 
microhyphema, patients with these disorders may undergo optional additional safety 
monitoring (biomicroscopy and IOP measurement) after Bimatoprost SR administration at 
the investigator’s discretion.  Additional information about the previous experience with the 
use of Bimatoprost SR in patients with sickle cell trait is provided in the IB.  
4.3
Inclusion Criteria
The following are requirements for entry into the study:  
1. Male or female, 18 years of age or older 

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2. Written informed consent and authorization for use and release of personal health 
information are obtained in accordance with the relevant country and local privacy 
requirements, where applicable (eg, Written Authorization for Use and Release of 
Health and Research Study Information [Unites States (US) sites] and written Data 
Protection consent [European Union (EU) sites])
3. Patient is willing to withhold his/her IOP treatments according to the study 
requirements, and in the opinion of the investigator, can do so without significant 
risk.  Note: If patients cannot discontinue their currently prescribed therapy for up to 
8 weeks to meet the Washout period for study entry, the investigator may switch the 
patient’s medication to one that requires a shorter washout interval during the 
washout of the original medication (see Section 8.2 and Table 7)
4. Patient has the ability to understand and the willingness to follow study instructions 
and requirements and is likely to complete all required visits and procedures
5. In the investigator’s opinion, patient’s IOP is not adequately managed with topical 
medication for reasons other than medication efficacy (eg, due to intolerance or 
nonadherence)
6. Negative pregnancy test at Baseline for females of childbearing potential
Ocular Inclusion Criteria for Both Eyes:
7. In the investigator’s opinion, both eyes can be treated adequately with topical 
prostamide, prostaglandin, or prostaglandin analog (eg, LUMIGAN, Xalatan, 
Travatan) eye drops as the sole therapy if medication was taken as directed
8. In the investigator’s opinion, patient’s IOP can be adequately managed with SLT 
monotherapy
9. In the investigator’s opinion, patient is a suitable candidate for SLT
10. Diagnosis of either OAG (ie, primary OAG, pseudoexfoliation glaucoma, pigmentary 
glaucoma) or OHT in each eye, requiring bilateral IOP-lowering treatment.  (Note:  
diagnosis does not have to be the same in both eyes)
11. Central endothelial cell density by specular microscopy confirmed as being qualified 
by Reading Center assessment prior to beginning Washout 
12. The iridocorneal angle must be independently confirmed as being qualified by 2 
ophthalmologists using the following criteria:
a.
Shaffer Grade ≥ 3 on clinical gonioscopy of the inferior angle
b. Peripheral anterior chamber depth by Van Herick examination ≥ 1/2 corneal 
thickness 

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Note:  The independent eligibility assessments must both agree that the Shaffer grade 
is ≥3 and the Van Herick grade is ≥ 1/2 corneal thickness  
13. At the Baseline visit, patient has been appropriately washed out of all IOP-lowering 
medications
14. At the Baseline visit (8:00 am ± 1 hour), IOP of ≥22 and ≤34 mm Hg, with 
difference between eyes of ≤5 mm Hg  
15. At the Screening and Baseline (Day -3 to -1) visits, Best-Corrected Visual Acuity 
(Snellen equivalent, by manifest refraction) of 20/50 or better in each eye
4.4
Exclusion Criteria
The following are criteria for exclusion from participating in the study:
1. Uncontrolled systemic disease
2. Females who are pregnant, nursing, or planning a pregnancy, or who are of 
childbearing potential and not using a reliable means of contraception during the 
study (see Section 4.5.3)
3. Known allergy or sensitivity to the study medication or its components, any 
component of the delivery vehicle, or any diagnostic or surgical prep agents used 
during the study (eg, topical anesthetic, dilating drops, fluorescein, povidone-iodine)
4. Any condition which would preclude the patient’s ability to comply with study 
requirements (including completion of the study)
5. Patients who have a condition or are in a situation, which, in the investigator’s 
opinion, may put the patient at significant risk, may confound the study results, or 
may interfere significantly with the patient’s participation in the study
6. Concurrent or anticipated enrollment in an investigational drug or device study or 
participation in such a study from 2 months prior to the Baseline visit through the 
final study visit
7. Previous use of commercially available Bimatoprost SR; concurrent enrollment in 
another Allergan Bimatoprost SR study; or previous enrollment in which an implant 
was received.  Patients enrolled in the 192024-091/092 studies who were randomized 
to the control treatment and never received an implant may be considered for 
enrollment at the investigator’s discretion.  
8. Known history of bleeding disorder or prolonged bleeding after surgery (in the 
opinion of the investigator).  Note:  Patients receiving pharmacologic blood thinners 
(eg, aspirin, Coumadin) may be enrolled at the investigator’s discretion.

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Ocular Exclusion Criteria for Both Eyes:
9. History of previous laser trabeculoplasty
10. History or evidence of clinically relevant, substantial ocular trauma (eg, a traumatic 
cataract, traumatic angle recession, etc)
11. The following surgical history:
a.
History or evidence of complicated cataract surgery:  eg, surgery 
resulting in complicated lens placement (such as anterior chamber 
intraocular lens implant [IOL], sulcus IOL, aphakia, etc) or 
intraoperative complications (such as a posterior capsular tear [with or 
without vitreous loss], substantial iris trauma, etc).  
Note:  history of uncomplicated cataract surgery is not an exclusion.
b. History of phakic IOL insertion for refractive error correction 
12. Intraocular surgery (including cataract surgery) and/or any ocular laser surgery within 
the 6 months prior to treatment (Day 1) 
13. Any history of corneal graft, including partial grafts (eg, Descemet’s Stripping 
Endothelial Keratoplasty [DSEK], Descemet’s Membrane Endothelial Keratoplasty 
[DMEK]); or incisional refractive surgery (eg, radial keratotomy), other than 
astigmatic keratotomy or limbal relaxing incisions
14. Corneal or other ocular abnormalities that would preclude accurate readings with an 
applanation tonometer, anterior segment-optical coherence tomography, specular 
microscope, and/or a contact pachymeter, or could confound study results, eg, 
moderate to severe corneal dystrophy, including Anterior Basement Membrane 
Disease (ABMD; ie, Map-Dot-Fingerprint [MDF]) and guttata.  Mild ABMD or mild 
guttata are not exclusionary by clinical examination if, in the opinion of the 
investigator, the condition is stable and not likely to cause corneal changes during the 
course of the study.  
15. Active or recurrent ocular disease (eg, uveitis, ocular infection, chronic moderate to 
severe blepharitis or severe dry eye, severe ocular seasonal allergies) or sight 
threatening diseases (eg, neovascular age-related macular degeneration [ARMD], 
diabetic macular edema) that, in the opinion of the investigator, would put the patient 
at a significant risk or would interfere with the interpretation of the study data.  
Patients with slowly progressive eye diseases (ie, mild cataracts, nonneovascular 
ARMD) can be enrolled at the discretion of the investigator.

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16. Any history of external ocular or intraocular malignancy, and/or any history of benign 
ocular neoplasia that in the investigator’s opinion resulted in clinically significant 
ocular morbidity 
17. History of herpetic ocular diseases (including herpes simplex virus and varicella 
zoster virus)
18. The following ocular surface findings:
a.
Bulbar conjunctival hyperemia, on either macroscopic or slit-lamp 
examination, > +1 (mild) at baseline
b. Active ocular surface findings other than bulbar conjunctival 
hyperemia, on either macroscopic or slit-lamp examination, > +1
(mild) at Baseline
19. History of moderate or worse (≥ +2) bulbar conjunctival hyperemia due to marketed 
prostaglandin, prostamide, or prostaglandin analog use
20. The anticipated wearing of contact lenses during the study that deviates from the 
following (contact lens wear is allowed during the study, but is to be temporarily 
discontinued before study visits, and before and after an Administration Day 
according to the following):
a.
Use of soft lenses should be discontinued at least 3 days prior to 
Baseline, and use of rigid gas permeable or hard contact lenses should 
be discontinued at least 1 week prior to Baseline 
b. Use of soft lenses should be discontinued at least 3 days and use of 
rigid gas permeable or hard contact lenses should be discontinued at 
least 1 week prior to a scheduled study visit or Administration Day 
visit
c.
Use of contact lenses of any kind should be discontinued for 1 week 
following any Bimatoprost SR (or Sham) administration
21. Central corneal thickness of < 480 or > 620 micrometers 
22. Anticipated need for any incisional or laser ocular surgery during the study
23. History of anatomically narrow angle resulting in evidence of angle changes or any 
history of closed angle glaucoma.  Note:  historically narrow angled patients whose 
angle has been opened by cataract surgery or peripheral iridotomy may be eligible for 
enrollment if they have no evidence of angle abnormalities.
24. History or evidence of a peripheral iridotomy/iridectomy in the inferior iris 

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25. Any history of trabeculectomy or other types of glaucoma surgery, including a 
glaucoma seton or aqueous bypass stents
26. Peripheral anterior synechiae (PAS) in the inferior iridocorneal angle on gonioscopic 
examination at Screening
27. Visual field loss that, in the opinion of the investigator, is functionally significant (eg, 
split fixation, field defect within the central 10 degrees that is visually significant or 
likely to cause central visual impairment upon progression) or shows evidence of 
progressive visual field loss within the year prior to baseline (Note:  Two visual fields 
are required for qualification, 1 performed within the 10 months prior to or at 
Screening, and 1 performed at baseline or during the washout period using the 
protocol-required testing method [see Procedure Manual].  The same test 
methodology should be used for all historical and study-related examination for a 
given patient.)
28. Evidence of macular edema during screening or in patient’s medical history 
29. Anticipated use of corticosteroids in either eye (except as described in Section 4.5.1
[Permissible Medications/Treatments]) or systemically during the study, or historical 
use prior to Baseline within:
3 years:  intraocular fluocinolone acetonide
6 months:  intraocular corticosteroid(s) other than fluocinolone; any injectable 
periocular or sub-Tenon’s/subconjunctival corticosteroid
2 months:  systemic (eg, oral, intramuscular, intravenous) or topical ocular 
corticosteroids 
2 weeks:  dermal corticosteroids applied to skin of the eyelid(s), around the eye, 
or adnexa 
30. Anticipated use of other topical ocular medications except as described in 
Section 4.5.1 (Permissible Medications/Treatments)
4.5
Permissible and Prohibited Medications/Treatments
4.5.1
Permissible Medications/Treatments
Ophthalmic Medications/Treatments
Intermittent use of artificial tear products is allowed if they are taken > 15 minutes before any 
study procedure or if they are required for a study procedure.  Intermittent use of ocular 
decongestants or antihistamines is allowed if not taken within 2 days prior to a scheduled 
visit.  

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Use of artificial tear products and ocular decongestants or antihistamines may be restarted 
3 days after any study administration (Bimatoprost SR, Sham Bimatoprost SR, SLT, or Sham 
SLT) procedure.  
Note:  post-procedural use of artificial tear products following SLT/Sham SLT 
administration is allowed at the investigator’s discretion; patients should be instructed 
to wait at least 15-20 minutes after instilling required medication (eg, NSAID) drops 
before instilling artificial tear products.  Use of artificial tears is not allowed 
following Bimatoprost SR/Sham Bimatoprost SR administration except as described 
above (restart 3 days after).
Use of post-Bimatoprost SR administration topical ocular antibiotics for 3 days, and 
corticosteroids or nonsteroidal anti-inflammatory drugs (NSAIDs) for up to 7 days following 
the administration days is permissible.
Use of immediate pre- and post-SLT topical ocular antihypertensive medication (ie, 
brimonidine or apraclonidine) is permissible.  Post-SLT topical NSAIDS are also permissible 
for 3 days following the procedure.  The medications instructed for use pre- and post-SLT are 
described in detail in Section 5.9.2.
Systemic Medications
Systemic beta-blocker containing medications are permitted, provided that the dose/dosing 
regimen has remained stable for at least 2 months prior to screening and is not anticipated to 
change during the duration of the study.
The use of systemic NSAIDS is also permitted.
In addition, therapy considered necessary for the patient’s welfare may be given at the 
discretion of the investigator.  If possible, the concurrent therapy (ocular and systemic) 
administered should not have an effect on study outcomes.  However, if concurrent 
medications may have an effect on study outcomes, these medications should be 
administered in dosages that remain constant throughout the duration of the study.  If the 
permissibility of a specific medication/treatment is in question, please contact Allergan.      
In the unlikely event that the Bimatoprost SR implant requires removal for significant safety 
reasons, this may be performed at the discretion of the investigator following a discussion 
with the medical safety physician at Allergan as needed (see Procedure Manual for details).

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Note that in the event that the investigator performs an unanticipated incisional surgical 
procedure on the Bimatoprost SR implanted eye during which ocular fluid is to be removed, 
ocular fluid/implant samples may be collected for analysis at the investigator’s discretion 
(see Procedure Manual for details).
4.5.2
Prohibited Medications/Treatments
The decision to administer a prohibited medication/treatment is taken with the safety of the 
study participant as the primary consideration.  When possible, Allergan should be notified 
before the prohibited medication/treatment is administered.
During the study, patients must not participate in other investigational drug or device studies.
Nonstudy IOP-lowering Treatments
Any concurrent nonstudy IOP-lowering treatment (eg, topical ophthalmic medication 
containing an ocular antihypertensive, LT) is prohibited in either eye during the study 
(through Month 24), unless necessary for the safety of the patient due to inadequate control 
of IOP as determined by the investigator.  Inadequate control of IOP should be confirmed at a 
subsequent visit (scheduled or unscheduled visit).  Initiation of treatment in one eye should 
not automatically lead to initiation of treatment in the contralateral eye.  Each eye should be 
evaluated on an individual basis when determining the need for additional nonstudy IOP-
lowering treatments.  If nonstudy IOP-lowering treatment is initiated, the investigator will be 
expected to attest to the need for additional nonstudy IOP-lowering treatment for safety 
reasons for each eye individually. Use of any concurrent nonstudy IOP-lowering treatment 
with any known effect on study outcomes (eg, crossover effect on the contralateral eye) is 
prohibited during the study.  
In order to maintain patient masking to treatments assigned to each eye, patients who have 
received nonstudy topical IOP-lowering treatment in a Bimatoprost SR eye will receive 
Sham Bimatoprost SR administration in that eye on the Bimatoprost SR Cycle 2 
administration day(s).  If nonstudy topical IOP-lowering medication is initiated in an SLT 
eye, the patient will continue to receive Sham Bimatoprost SR administration in the SLT eye 
on the administration day(s).  In all cases, the contralateral eye that does not require nonstudy 
topical IOP-lowering medication will maintain the same treatment regimen assigned at 
randomization.  Patients who have received nonstudy IOP-lowering treatment in both eyes 
will not receive Bimatoprost SR administration or Sham Bimatoprost SR administration in 
either eye, and therefore do not need to attend the Bimatoprost SR (or Sham Bimatoprost SR) 
administration visits and immediate postadministration visits (ie, Bimatoprost SR Cycle 2 

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administration [Week 16], Cycle 2 Day 2 safety visit, and Cycle 2 Day 4 and Week 2 phone 
calls).
Contact Lenses
Use of soft contact lenses within 3 days and use of rigid gas permeable or hard contact lenses 
within 1 week prior to a scheduled study visit or Administration Day, or use of contact lenses 
of any kind within 1 week following any Bimatoprost SR (or Sham) administration in either 
eye is prohibited.  
Other Medications
The following medications (or classes of medications) and treatment procedures are not 
permitted as concurrent therapy during the study unless the patient has already received 
nonstudy IOP-lowering medication or treatment in both eyes:

Subconjunctival, sub-Tenon’s, intravitreal, or other ophthalmic injections of any 
medications in either eye

Use of any topical ophthalmic medications (except as described above and in 
Section 4.5.1) in either eye

Surgical (incisional and laser) procedures that are not related to study-specific 
Bimatoprost SR (or Sham) and SLT administration procedures in either eye; patients 
may exit the study early if an ophthalmic incisional procedure is required  

Oral, intramuscular, or intravenous corticosteroids from 2 months prior to the 
Baseline visit through study exit 

Use of bimatoprost for hypotrichosis during the study period in either eye

Use of cyclosporine ophthalmic solution during the study period in either eye

Systemic use of carbonic anhydrase inhibitor 

Any initiation of or alterations in systemic regimen of beta-blocker containing 
medications from 2 months prior to screening through the study exit

Use of corticosteroids in either eye (except as described in Section 4.5.1 for 
postoperative use) or systemically during the study or historical use prior to Baseline 
within:

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3 years:  intraocular fluocinolone acetonide
6 months:  intraocular corticosteroid(s) other than fluocinolone; any injectable 
periocular or sub-Tenon’s/subconjunctival corticosteroid
2 months:  systemic (eg, oral, intramuscular, intravenous) or topical ocular 
corticosteroids 
2 weeks:  dermal corticosteroid applied to skin of the eyelid(s), around the eye, or 
adnexa
4.5.3
Definition of Females of (Non-)Childbearing Potential and/or 
Acceptable Contraceptive Methods
For purposes of this study, females will be considered of childbearing potential unless they 
are naturally postmenopausal or permanently sterilized (ie, hysterectomy).  Natural 
menopause is defined as the permanent cessation of menstrual periods, determined 
retrospectively after a woman has experienced 12 months of amenorrhea without any other 
obvious pathological or physiological cause.  For women of childbearing potential who may 
participate in the study, the following methods of contraception, if properly used, are 
generally considered reliable:  hormonal contraceptives (ie, oral, patch, injection, implant), 
male condom with intravaginal spermicide, diaphragm or cervical cap with spermicide, 
vaginal contraceptive ring, intrauterine device, surgical sterilization (bilateral tubal ligation, 
bilateral salpingectomy), vasectomized partner, or true sexual abstinence (when this is in line 
with the preferred and usual lifestyle of the subject).
The investigator and each patient will determine the appropriate method of contraception for 
the patient during the participation in the study.
If a female 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 (and unmask the study treatment as 
needed for pregnancy monitoring), and (2) follow the progress of the pregnancy.  The 
investigator must document the outcome of the pregnancy and provide a copy of the 
documentation to Allergan.

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5.
Study Treatments 
5.1
Study Treatments and Formulations
The clinical formulation of Bimatoprost SR contains preservative-free bimatoprost dispersed 
in a biodegradable polymer matrix (including PLA and PLGA).  The biodegradable implants 
are preloaded in the applicator.  The formulations used in this study are Bimatoprost SR 
15 µg (11048X, for Stage 1) and 10 µg (11047X, for Stage 2).
5.2
Control Treatment 
The control treatment is a 360° administration of SLT.
5.3
Methods for Masking
A sham SLT procedure will be performed in the Bimatoprost SR eye and a sham Bimatoprost
SR administration will be performed in the SLT eye to ensure masking of the study 
treatments.  The Sham Bimatoprost SR administration involves touching of the eye at the 
area of insertion with an Allergan-provided needleless applicator that does not deliver an 
implant into the AC.  
The patient and the site staff will be masked to the treatment assignment for each eye.  Only 
the site coordinator and designated staff will be unmasked to the patient’s treatment 
assignment for each eye.  Efficacy IOP measurements will be masked using a 2-person 
reading method as described in Section 6.1.1.  
The site staff who perform IOP readings will be masked to the treatment assignment for each 
eye.  Site personnel and patients will be instructed and reminded throughout the study not to 
discuss study medication assignments to ensure masking is maintained.  
In the event that the patient requires postoperative topical eyedrops in only 1 eye following a 
Bimatoprost SR administration (eg, topical corticosteroids or anti-inflammatory eyedrops) or 
SLT administration (eg, treatment of acute post-SLT IOP spike), in order to maintain masking 
of the eye receiving study treatment, the investigator will be instructed to dispense the 
required medication without disclosing which eye is the Bimatoprost SR or SLT eye or the 
etiology of the signs/symptoms that require the medication.

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5.4
Treatment Allocation Ratio and Stratification 
The eye with the higher IOP at baseline will be assigned as primary eye and randomized to 
receive either Bimatoprost SR or SLT using a 1:1 ratio, stratified by the primary eye baseline 
IOP (≤ 25 or > 25 mm Hg) 
 
.  If the primary eye receives Bimatoprost SR, the contralateral eye will 
receive SLT.  If the primary eye receives SLT, the contralateral eye will receive 
Bimatoprost SR.  If baseline IOP is the same in both eyes, the right eye will be the primary 
eye.
5.5
Method for Assignment to Treatment Groups/Randomization
Prior to initiation of any study procedures, each patient who provides informed consent will 
be assigned a patient number that will serve as the patient’s identification number on all 
study documents.
For determination of stratification group assignment for the primary eye for each patient, 
sites will be required to enter Baseline IOP (at Hour 0) data for both eyes into an automated 
interactive response system.
At the time of randomization (Day 1 SLT Administration Day), an automated interactive 
response system will be used to manage the randomization and treatment assignment for the 
Bimatoprost SR and SLT.  A randomization number will be assigned to a patient according to 
the order of enrollment within each IOP stratum (Baseline primary eye Hour 0 IOP ≤ 25 or 
> 25 mm Hg)
 
across the study.  That is, the interactive response system will assign the next available 
randomization number to the patient at the time when the investigator requests 
randomization.  
The interactive response system will provide the site with the specific treatment assignment
for each randomized patient/eye at the time of randomization (Day 1 SLT Administration 
Day).  Sites will contact the interactive response system at subsequent visits to obtain a study 
medication kit number for dispensing study medication (Bimatoprost SR and Sham).  Study 
medication kits for Bimatoprost SR and Sham administration will be labeled with medication 
kit numbers.  Sites will receive interactive response system confirmation notifications for 
each transaction.  All notifications are to be maintained with the study source documents.
5.6
Treatment Regimen 
The treatment assignments are summarized in 

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Table 1.  The eye randomized to receive Bimatoprost SR will receive an intracameral 
administration of Bimatoprost SR on Day 4 and at Week 16 (if retreatment criteria are met),
plus Sham SLT administration on Day 1 only.  For those patients who do not meet 
retreatment criteria at Week 16, the second Bimatoprost SR administration may be performed 
at the investigator’s discretion during an unscheduled visit after Week 16 and prior to the 
Month 12 visit if the retreatment criteria are met.  The contralateral eye will receive one 360° 
SLT administration on Day 1 only, plus Sham Bimatoprost SR administration on Day 4 and
Week 16 (or at the time of the second Bimatoprost SR administration for patients who 
receive it later than Week 16).  Patients will receive the same dose strength throughout the 
study (ie, patients in Stage 1 received 15 µg and patients in Stage 2 will receive 10 µg).
For patients who still have any visible Bimatoprost SR implants or have not received 
nonstudy IOP-lowering medications by the time of study discontinuation or completion, 
poststudy evaluations including the need for IOP-lowering medications should be conducted 
according to the treating physician’s clinical opinion.  Further patient follow-up will be 
determined by the treating physician’s clinical opinion.
5.7
Storage of Study Medications
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.  Only assigned study personnel authorized by the investigator may 
have access to study medication.  Bimatoprost SR and Sham needleless applicators must be 
stored in the original sealed foil pouch.  Investigational medicinal product must be stored as 
described in the Investigator’s Brochure.  Sites must report any temperature excursions as 
described in the Procedure Manual or contact Allergan or its designee for further instructions.
For further details on storage, including requirements for study-provided eye drops, please 
refer to the Procedure Manual and/or contact Allergan.
5.8
Preparation of Study Medications/Treatments 
Bimatoprost SR is loaded into the single use applicator during manufacturing and is provided 
within the applicator as a sterile, finished product.  Study site personnel should notify 
Allergan or its designee immediately to advise of any situation in which the study medication 
is defective.

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5.9
Study Treatment Administration 
Study medication must only be administered to patients who meet the eligibility criteria in 
accordance with the conditions specified in this protocol.  Medication will be labeled with 
either a single panel label or booklet label.  Records of use of medication kit numbers for 
each patient will be maintained by the site and recorded in the electronic case report form 
(eCRF) as appropriate.
5.9.1
Bimatoprost SR Administration
5.9.1.1
Patient Preparation
Administration day assessments (including vital signs and query for concomitant medications 
and adverse events) should be completed.  At least 3 administrations of a broad spectrum 
topical ophthalmic antibiotic drop and topical anesthetic drop should be administered to each 
eye approximately every 5 minutes beginning approximately 15 minutes prior to the 
procedure.  With the patient in a supine position, the eye and conjunctival fornices should be 
irrigated with 5% ophthalmic povidone-iodine solution and the lids and surrounding orbital 
area should be prepped and draped according to the standard protocol detailed in the 
Procedure Manual.
5.9.1.2
Study Treatment Location
At the discretion of the investigator, Bimatoprost SR (or Sham) administration may be 
performed at an Ambulatory Surgical Center (ASC; free standing or hospital based) or in the 
office setting (eg, in a procedure room with an operating microscope).  As a standard ASC 
technique an intravenous catheter may be placed and intravenous sedatives may be used at 
the discretion of the investigator and/or anesthesiologist.  The ASC may have standard 
operating procedures (SOPs) that require an electrocardiogram and/or a chest radiograph 
performed prior to the procedure.  A separate standard consent to have the procedure at an 
ASC may be required per the SOPs at the facility.
Sterile technique should be practiced at all times.
5.9.1.3
Administration Technique
Intracameral administration of Bimatoprost SR must be performed by an ophthalmologist 
who has had adequate training and has been approved by Allergan to perform the procedure.  
The principal investigator at a site may designate a subinvestigator to perform the procedure, 

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subject to Allergan approval and training.  The study medication kit should be readily 
available during the procedure.
The procedure is described in detail in the Procedure Manual.  In brief, following the sterile 
preparation and sterile field setup, an appropriately sized sterile lid speculum should be 
placed between the eyelids of the patient.  The entrance site for the applicator needle is just 
anterior to the insertion of the conjunctiva through the clear cornea in the superior or 
temporal quadrant.  The trajectory of the needle should be parallel to the iris plane.  The eye 
is stabilized by either counter traction with a sterile toothed forceps or counter pressure with 
a cotton tipped applicator as the needle is advanced through the cornea.  The actuator button 
is depressed until an audible and/or palpable click is heard.  The Bimatoprost SR implant 
should be visible exiting the needle bevel into the aqueous humor.  The needle is then 
immediately removed from the AC, and the wound is checked for aqueous leakage.  
Following removal of the lid speculum and sterile drape, additional drops of broad spectrum 
antibiotics should be applied.
The procedure for the second administration of Bimatoprost SR is the same.
The preparation and procedure for all sham administrations is the same; however, the sham 
applicator will not have a needle and thus will not enter the AC (but should touch the eye at 
the area of recommended insertion).
5.9.1.4
Immediate Posttreatment Observation
Following Bimatoprost SR administration, the patient is allowed to sit upright and is kept for 
a minimum of 1 hour of observation.  The surgeon will examine each of the patient’s eyes to 
ensure that the AC is formed prior to the patient being released.
The patient will be supplied a bottle of topical ophthalmic antibiotic drops and instructions to 
use them for the next 3 days (including the day of the administration) in both eyes and to 
follow up as per protocol.
Prior to leaving the site, patients should be instructed to contact the study site immediately if 
they experience any adverse events after treatment.  If the patient reports having experienced 
adverse events, these must be recorded on the appropriate eCRF.
The same posttreatment observation and antibiotic requirements apply after the second 
administration of Bimatoprost SR or Sham.

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Note:  Patients with sickle cell disease or trait (or other hemoglobinopathies) may undergo 
optional biomicroscopy and IOP examination in both eyes 4 hours after each Bimatoprost SR 
administration (or Sham administration).  This optional IOP examination is for postoperative 
purposes only, and as such does not require use of the masked, 2-person reading method.  
The IOP should be taken only once to avoid excessive postadministration (or Sham 
administration) manipulation of the eye, and should be taken by the investigator (or other 
unmasked, qualified personnel).  This postadministration (or Sham administration) 
examination may be performed using a Goldmann applanation tonometer or a hand-held 
tonometer (see the Procedure Manual for details).
5.9.1.5
Retreatment with Bimatoprost SR
For all patients who meet retreatment criteria at Week 16, Cycle 2 Bimatoprost SR
administration will occur at Week 16.  
For patients who do not meet retreatment criteria at Week 16, Cycle 2 Bimatoprost SR
administration may occur at the investigator’s discretion during an unscheduled visit after 
Week 16 and prior to the Month 12 visit based on the investigator’s clinical judgment 
regarding the patient’s IOP control and if the retreatment criteria are met.  Note:  beyond 
Week 16, Cycle 2 administration is not mandatory even if the retreatment criteria are met.
Patients who have received nonstudy IOP-lowering treatment (prohibited during the study 
except for pre- and post-SLT administration, Section 4.5.1) in only 1 eye will still attend 
administration visits regardless of whether the eye receiving additional medication is the 
Bimatoprost SR eye or the SLT eye.  If the eye treated with additional nonstudy IOP lowering 
medication is the Bimatoprost SR eye, the eye will receive Sham Bimatoprost SR 
administrations at the administration visits.  If the eye treated with additional nonstudy IOP 
lowering medication is the SLT eye, that eye will continue to receive Sham Bimatoprost SR 
administrations.  Patients who have been treated with nonstudy IOP-lowering medication in 
both eyes will not attend the administration day visits, nor will they attend the Day 2, Day 4 
(phone call), and Week 2 (phone call) visits following an administration.  Patients who have 
received nonstudy IOP-lowering medication in one or both eyes will be followed for the 
duration of the study through the Month 24/Exit visit.  
Retreatment of an eligible implanted eye is permitted if the following criteria are met in that 
eye:

IOP > 17 mm Hg

There is no evidence of any of the following:

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o
Significant corneal findings related to presence of the implant (including corneal 
edema, peripherally adjacent to the implant location and/or central) at any visit
o
Endothelial cell density less than 1800 cells/mm2 by specular microscopy, 
confirmed at 2 consecutive visits on separate days
o
Persistent and progressive corneal endothelial cell density decrease ≥15% from 
baseline confirmed at 2 consecutive visits on separate days (scheduled or 
unscheduled)
o
Remaining implant size or position from prior administration that, based on the 
investigator’s evaluation, precludes placement of another implant (eg, may cause 
chronic contact of the implants with the corneal endothelium)
o
Clinically significant intraocular inflammatory findings (eg, PAS, uveitis, 
iridocyclitis, macular edema, etc) at any visit.  Note:  mild AC cells/iritis related 
to the administration procedure itself that resolves rapidly (with or without 
NSAIDs or steroids) is not prohibitive

In the investigator’s opinion, it is safe for the study eye to receive an additional 
administration of Bimatoprost SR
Signs or symptoms will be documented in the eCRF.
5.9.2
SLT Administration
5.9.2.1
Pre-SLT Patient Preparation
Measure the IOP in both eyes and record the result.  Because this is a preoperative 
measurement and not used for efficacy analyses, this measurement does not need to be 
masked and only 1 measurement needs to be performed.  
Instill 1 drop of apraclonidine or brimonidine (see Procedure Manual) into each eye 
30 minutes to 1 hour prior to SLT (or Sham SLT).  Topical anesthetic drop (eg, proparacaine 
hydrochloride or equivalent) should be administered to each eye approximately every 
5 minutes beginning approximately 15 minutes prior to the procedure.  
5.9.2.2
SLT and Sham SLT Procedure
SLT must be performed by an ophthalmologist who has had adequate training and has been 
approved by Allergan.  The investigator will perform 360 degrees of SLT using the 
standardized method that is detailed in the Procedure Manual.  Sham SLT will then be 
performed on the contralateral eye using the same method, with the exception that the laser is 
not switched to the active state.  

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5.9.2.3
Post-SLT
Administer 1 drop of apraclonidine or brimonidine into each eye and recheck the IOP 1 hour 
after SLT and Sham SLT administration; because this is a postoperative measurement and not 
used for efficacy analyses, this measurement does not need to be masked and only 
1 measurement needs to be performed.  If an IOP spike is observed, the investigator should 
treat using his/her standard of practice.
The patient will be supplied a bottle of topical NSAID eyedrops and instructions to use them 
as directed for the next 3 days (including the day of the administration) in both eyes and to 
follow up as per protocol.
Prior to leaving the site, patients should be instructed to contact the study site immediately if 
they experience any adverse events after treatment.  If the patient reports having experienced 
adverse events, these should be recorded on the appropriate eCRF.
6.
Response Measures and Summary of Data Collection Methods
Detailed information on equipment and methodology to be used is provided in the Procedure 
Manual.
Study evaluations should be performed by the same investigator/subinvestigator throughout 
the study whenever possible.  If it is not possible to use the same individual to follow the 
patient, then an attempt should be made to have investigators overlap (examine the patient 
together and discuss findings) for at least 1 visit.
6.1
Efficacy Measures
6.1.1
Primary Efficacy Measure
The primary efficacy measure, IOP, will be measured using a Goldmann applanation 
tonometer.  Examiners masked to the treatment assignment should perform all efficacy IOP 
measurements at approximately the same time of day for a given patient throughout the study 
whenever possible.
A 2-person reading method will be used for all efficacy IOP measurements, wherein 1 person 
adjusts the dial in a masked fashion and a second person reads and records the value.  The 
right eye is to be measured first and the left eye measured second.  Two consecutive 
measurements will be taken of each eye.  If the first 2 measurements differ by > 1 mm Hg, a 
third measurement will be taken.  If the first 2 measurements differ by ≤ 1 mm Hg, the IOP 

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for the given eye will be the average of the 2 readings.  If the difference between the first 
2 measurements is > 1 mm Hg, the IOP for the given eye will be the median of the 
3 readings.
All Hour 0 IOP examinations should be scheduled at 08:00 AM ± 1 hour.  As scheduling 
permits, the patient should have approximately the same Hour 0 time of day throughout the 
study.  At selected sites in consenting patients, additional IOP measurements will be 
performed at Hour 2 (Hour 0 + 2 hours [± 30 minutes]) and Hour 8 (Hour 0 + 8 hours 
[± 30 minutes]).  
6.2
Safety Measures
The following will be collected and recorded on the appropriate eCRF page(s):  
Adverse Events:  All adverse events, from the moment the patient signs the informed 
consent form, will be monitored and recorded in the patient’s source documents.  All events 
will be reported to Allergan on an adverse event eCRF, including seriousness, severity, action 
taken, and relationship to study drug.  If adverse events occur, the first concern will be the 
safety of the study patient.
Weight and Height:  Weight will be measured in pounds (lb) or kilograms (kg) using a 
scale.  Height will be measured in inches (in) or centimeters (cm).  Height and weight will be 
measured at Screening as part of the demographic data; historical patient information and/or 
patient reports should not be used for either measurement.
Vital signs:  Systolic and diastolic blood pressure and pulse rate will be measured after 
patients have been at rest (seated) for at least 5 minutes.  Body temperature will be measured 
orally (or with an infrared forehead thermometer) and recorded as °F or °C.
Blood and Urine Sample Collection:  Blood and urine samples will be collected for blood 
chemistry, hematology panels, and urinalysis by a central laboratory or designated regional 
facility.  
Pregnancy:  Females of childbearing potential will have pregnancy tests performed.  
Pregnancy test kits will be provided by Covance Central Laboratory Services or a designated 
regional laboratory and will be administered according to the instructions provided with the 
tests.  

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Measures of Ocular Safety:
Best Corrected Visual Acuity:  Visual acuity tests will be performed at all scheduled visits 
except on any of the Bimatoprost SR administration days or SLT Administration Day.  
Manifest refraction using Snellen equivalent with a logMar chart (see Procedure Manual) 
will be performed at Screening; Baseline; Weeks 12, 24, and 52; and Months 18 and 24/Exit.  
At all other visits, the visual acuity technician will use the last manifest refraction performed 
and determine the Snellen equivalent visual acuity using the logMar chart.  If there is a 2-line 
or more reduction in visual acuity from the last best-corrected visual acuity performed, a 
repeat manifest refraction in both eyes and best-corrected visual acuity will be performed.
Macroscopic Iris Color Assessment:  Iris color will be assessed visually at each designated 
visit using the appropriate assessment guide (see the Procedure Manual for further details).  
Macroscopic Conjunctival Hyperemia Assessment:  Macroscopic conjunctival hyperemia 
will be assessed using the appropriate assessment guide (see the Procedure Manual for 
further details).
Gonioscopy/Angle Assessment:  Gonioscopic examination for eligibility at Screening (only) 
will be independently performed by 2 ophthalmologists as described in the Protocol 
Procedure Manual.  The independent eligibility assessors should not share their assessments 
with each other until the assessment is recorded.  The 2 ophthalmologists’ independent 
eligibility assessments must confirm patient eligibility for participation in the study.  
Subsequent gonioscopic examinations will be performed by the study investigator.  Using 
gonioscopy, the investigator will evaluate the inferior iridocorneal angle and the Bimatoprost 
SR implant.
Biomicroscopy:  Biomicroscopic examinations will be performed using a slit lamp.  The 
examinations will include evaluation of the condition of the eyelids, conjunctiva, cornea, AC
(with Van Herick anterior chamber depth assessment at Screening only), iris/pupil, and lens 
(Lens assessment is performed using the modified AREDS procedure and is collected on 
dilated examination days through a dilated pupil, using the slit lamp biomicroscope.  Please
see the Procedure Manual for details).  
Lens Assessment:  Biomicroscopic findings will be evaluated for the presence and severity 
of nuclear, cortical, and posterior subcapsular lens opacities.  See the Procedure Manual for 
further details.

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Optic Disc Examination:  The cup/disc ratio and presence of optic disc pathology will be 
determined using stereoscopic evaluation.
Dilated Ophthalmoscopy:  The stereoscopic fundus assessments should be conducted 
through a dilated pupil.  The examinations will include evaluation of the macula, vitreous, 
and retina.
Specular Microscopy:  Endothelial cell density will be assessed using specular microscopy 
performed on the central cornea at all sites.  The determination of central endothelial cell 
density for study entry as well as study visit measures will be determined by the Reading 
Center.  See the Procedure Manual for further details.  The same instrument should be used 
throughout the study for a given patient.  Qualification will remain valid for 1 year after 
Screening in patients who are not enrolled at the time of Screening, if in the investigator’s 
opinion there have been no clinically significant changes occurring in the eyes (eg, ocular 
surgery) during that time.
Pachymetry:  Corneal thickness using ultrasound (contact) pachymetry will be performed on 
the central cornea.  The same instrument should be used throughout the study for a given 
patient.  Contact pachymetry may be performed any time after gonioscopy.  See the 
Procedure Manual for further details.
Anterior Segment-Optical Coherence Tomography:  Anterior segment-optical coherence 
tomography measurements will be performed at all sites and a Reading Center will be used to 
examine angle size for investigational purposes.  See the Anterior Segment Optical 
Coherence Tomography Image Acquisition manuals from the Reading Center for further 
details on the use of optical coherence tomography.  In the event that the anterior 
segment-optical coherence tomography type as specified in the manuals is not available, a 
suitable alternative may be approved by Allergan and the designated reading center for use.  
The same instrument should be used throughout the study for a given patient.
Visual Field:  Visual field examinations will be assessed using automated perimetry (using 
either Humphrey 24-2 full threshold program or 24-2 Swedish Interactive Thresholding 
Algorithm (SITA) Standard, or Octopus G1 or 24-2 and dynamic or normal strategy).  The 
same test methodology must be used throughout the entire study for a given patient. Visual
field data may also be submitted to an Allergan designated vendor for additional evaluation.

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6.3
Other Measures
 
 
 
 
 
 
 
 
 
 
 
  
6.3.1
Medical History, Physical Examination, and Vital Signs 
6.3.1.1
Medical History 
A standard medical history (including all relevant conditions that the patient has had in the 
past or currently has) will be captured in the patient source documents.  All surgical 
procedures should have an associated medical history entry.  Current medications as well as 
those stopped within 60 days prior to the Screening visit and procedures within 90 days prior 
to the Screening visit will be recorded.  In addition, all previous medications taken for OAG 
or OHT for at least 3 months prior to study entry will be recorded on the appropriate source 
document and/or eCRF page.
6.3.1.2
Physical Examination
The patient will be examined by qualified medical personnel for any physical abnormality of 
the following systems:  general appearance; head, eyes, ears, nose, and throat; 
heart/cardiovascular; lungs; abdomen; neurologic; extremities; back; musculoskeletal; 

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lymphatic; and skin. The patient’s height and weight will be recorded at the Screening visit 
only.
6.3.1.3
Vital Signs
The below vital signs will be measured at all patient visits and should be recorded prior to 
any invasive procedures.

Pulse rate (beats per minute [bpm]):  the patient should be resting in a seated position 
for a minimum of 5 minutes prior to measurement.  Pulse rate is then counted over 
30 seconds (and multiplied by 2 to obtain bpm).

Blood pressure (mm Hg):  the patient should be resting in a seated position for a 
minimum of 5 minutes prior to measurement.  Systolic/diastolic blood pressure will 
be measured with a sphygmomanometer (manual sphygmomanometer or automated 
blood pressure measuring device).

Temperature (°C/°F):  the patient should be seated and the body temperature taken 
orally (or with an infrared forehead thermometer).
6.3.2
Pregnancy Testing
Urine will be collected from females of childbearing potential for pregnancy testing (urine 
pregnancy test).  The urine test for pregnancy will be performed at the site utilizing the 
dipstick method at all specified timepoints.  Serum testing may be performed instead of urine 
testing if required by the local institution.  
Further, in countries/institutions where required by local institution or health authority, an 
additional serum test may be done any time between Baseline and Bimatoprost SR (or Sham)
administration.  Negative results for all pregnancy tests are required to be confirmed prior to 
the time of Bimatoprost SR (or Sham) administration.  
6.3.3
Laboratory Procedures
A central laboratory or designated regional facility will analyze blood and urine specimens 
for this study; including any repeat laboratory tests.  Blood and urine samples will be 
obtained for the analysis of blood chemistry, hematology, and urinalysis.
Refer to the Central Laboratory Manual for further details regarding central laboratory 
collection and shipment procedures.

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Laboratory test results will be forwarded from the central laboratory or designated regional 
facility to the study site and to Allergan or its designee.  The investigator or qualified site 
personnel must review all laboratory results for any adverse events.  Laboratory test results 
that represent adverse events should be reflected on an adverse event eCRF page.
Evaluation and management of abnormal laboratory results should be conducted according to 
local site practice.
6.3.3.1
Hematology 
Hematology will be measured and includes hematocrit, hemoglobin, glycated hemoglobin, 
mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, mean 
corpuscular volume, platelets, red blood cell (RBC) count, RBC morphology, total white 
blood cell (WBC) count and differential (neutrophils, bands, lymphocytes, monocytes, 
basophils, and eosinophils).  
6.3.3.2
Serum Chemistry 
Serum chemistry will include albumin, alkaline phosphatase, alanine transaminase, aspartate 
transaminase, bicarbonate, calcium, chloride, creatinine, creatine kinase, direct bilirubin, 
glucose, indirect bilirubin, magnesium, phosphorous, potassium, sodium, total bilirubin, total 
cholesterol, total protein, urea nitrogen, and uric acid.
6.3.3.3
Urinalysis 
Urine will be analyzed for clarity, color, bilirubin, blood, glucose, ketones, leukocyte 
esterase, nitrite, pH, protein, specific gravity, urobilinogen, and microscopic sediment 
(WBCs, RBCs, casts, bacteria, crystals, and epithelial cells).
6.4
Other Study Supplies
The following will be provided by Allergan or designated suppliers:

All supplies needed for central laboratory blood and urine sampling (urinalysis, blood 
chemistry, and hematology), urine pregnancy test kits, and ocular fluid collection kits

Shipping materials for shipment of laboratory samples to central laboratory 

 

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
As needed:  anterior segment-optical coherence tomography, anterior segment-optical 
coherence tomography software and/or module, Specular Microscope, contact 
(ultrasound) pachymetry equipment

 

Ancillary administration procedure supplies and postoperative topical ophthalmic 
antibiotics may be supplied
Sites that are not able to receive supplies from Allergan due to country regulations will need 
to provide their own supplies.
Allergan will not provide any nonstudy IOP-lowering medications.
6.5
Summary of Methods of Data Collection
This study will use eCRFs using remote electronic data capture through a qualified third 
party vendor.  The data will be entered on the eCRFs in a timely manner on an ongoing basis.  
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 case report forms (as indicated in the eCRFs) to ensure that the 
observations and findings are recorded on the eCRFs correctly and completely.  A certified 
electronic copy of the eCRF including data corrections will be provided to the site for 
archiving at the end of the study.
A central laboratory or designated regional facility will be used for analysis of blood 
chemistry and hematology, urinalysis, and ocular fluid sample analysis (if ocular fluid is 
obtained).  Laboratory data will be transferred to Allergan on a periodic basis throughout the 
study.
7.
Statistical Procedures
The study is being conducted in 2 stages.  In Stage 1, patients are treated with 
Bimatoprost SR 15 µg and SLT.  In Stage 2, patients are treated with Bimatoprost SR 10 µg 
and SLT.  
Three database locks will be performed:  1) when all patients treated with Bimatoprost SR 10
µg complete the Week 24 visit or have prematurely discontinued before the Week 24 visit, 
2) when all patients treated with Bimatoprost SR 10 µg have completed the Month 12 visit or 

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prematurely discontinued before the Month 12 visit, and 3) when all patients treated with 
Bimatoprost SR 10 µg have completed the Month 24 visit or prematurely discontinued before 
the Month 24 visit.  Analyses will be performed after each lock.  Prior to the first database 
lock a detailed analysis plan will be finalized.  To maintain the integrity of the ongoing study, 
Allergan study personnel who are directly involved in data handling and supporting the trial 
(such as the clinical study team) will remain masked to treatment assignment of individual 
patients during the study.  To avoid potential data unmasking between locks and to protect 
trial integrity, study statistical personnel who have been unmasked after each lock will no
longer be involved directly in any ongoing masked study conduct.  Another statistician, who 
is still masked to study treatment, will assume these responsibilities until the next lock.  
Unmasked data handling and appropriate data and results access will be specified prior to 
each lock.
7.1
Analysis Populations
The intent-to-treat (ITT) population is defined as all patients randomized to receive 
Bimatoprost SR 15 µg, Bimatoprost SR 10 µg, or SLT.  
The per-protocol (PP) population is defined as all patients in the Bimatoprost SR 10 µg ITT
population who have no protocol deviations affecting the data for primary efficacy analysis
for all visits (Week 4, Week 12, and Week 24).  The PP population will be used for selected 
efficacy analyses.  A list of patients with data excluded from the PP population will be 
finalized prior to database lock.
The Bimatoprost SR 15 µg, Bimatoprost SR 10 µg, and SLT safety populations are defined 
as all patients who received any study treatments and will be used for safety analyses.
7.2
Collection and Derivation of Primary and Secondary Efficacy 
Assessments
The primary efficacy measurement is IOP, which will be measured in each eye using the 
Goldmann applanation tonometer.  Two consecutive measurements will be taken for each 
eye.  If these 2 measurements differ by > 1 mm Hg, then a third measurement will be 
performed.  If the first 2 measurements differ by ≤ 1 mm Hg, or a third measurement is 
required but only 2 measurements are obtained, then the IOP value for a given eye is the 
average of the 2 measurements. If 3 measurements are required (ie, the first 2 measurements 
differ by > 1 mm Hg) and obtained, then the IOP value for the given eye is the median of the
3 measurements.  If, for any reason, only a single measurement is obtained, then this 
measurement will be used as the IOP value.

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To avoid confounding of efficacy data, IOP measurements obtained after initiating the use of 
nonstudy IOP-lowering medication in an eye will be included in the study database but will 
be excluded from efficacy analyses.
7.2.1
Primary Efficacy Variable 
The primary efficacy variable is IOP change from baseline (follow up value minus baseline 
value) and the primary time period is 24 weeks (measurements for the primary analysis are 
designated for the following timepoints:  Weeks 4, 12, and 24). 
7.2.2
Secondary Efficacy Variables
Secondary efficacy variables include:  

Time to initial use of nonstudy IOP-lowering treatment (as determined by the
investigator)

Percentage of Bimatoprost SR and SLT eyes achieving ≥ 20% reduction in IOP from 
baseline

IOP changes from baseline at Weeks 8, 15, and 20
7.2.3
Other Efficacy Variables
  
 
7.3
Hypothesis and Methods of Analysis
In general, continuous variables will be summarized by descriptive statistics including 
sample size, mean, standard deviation, median, minimum, and maximum.  Categorical 
variables will be summarized by frequency and percentage. 

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Data collected from patients treated with Bimatoprost SR 10 µg and Bimatoprost SR 15 µg
will be analyzed separately. Specifically, efficacy analysis for patients treated with 
Bimatoprost SR 15 µg will be limited to Hour 0 IOP descriptive summary statistics. Safety 
summaries will be generated for Bimatoprost SR 10 µg and Bimatoprost SR 15 µg using the 
same analysis methods, but will be presented separately.
7.3.1
Primary Efficacy Analyses
The primary efficacy analysis will be performed for patients treated with Bimatoprost SR 
10 µg in the ITT population.  The primary efficacy variable is IOP change from baseline and 
Weeks 4, 12, and 24 are the primary analysis timepoints.
The null and alternative hypotheses for the comparison between Bimatoprost SR 10 µg-
treated eyes and SLT-treated eyes at each visit of Weeks 4, 12, and 24 are:
Null hypothesis:  the difference in mean IOP change from baseline between the 
Bimatoprost SR 10 µg eye and SLT eye (Bimatoprost SR 10 µg minus SLT) is 
> 1.5 mm Hg.
Alternative hypothesis:  the difference in mean IOP change from baseline between the 
Bimatoprost SR 10 µg eye and SLT eye (Bimatoprost SR 10 µg minus SLT) is 
≤1.5 mm Hg.
IOP change from baseline will be analyzed using a mixed effect model for repeated measures 
(MMRM).  The model will include IOP change from baseline as the response variable and 
treatment, visit, eye, baseline IOP, treatment-by-visit, visit-by-baseline, and visit-by-eyes 
interactions as covariates.  Unstructured correlation for study visits and eyes will be used for
repeated measures on the same patient.  
The mean difference between the Bimatoprost SR 10 µg eyes and SLT eyes (Bimatoprost SR
10 µg minus SLT) and the corresponding 95% confidence interval (CI) will be constructed at 
each visit from MMRM analysis. The noninferiority comparison for Bimatoprost SR 10 µg
versus SLT at Weeks 4, 12, and 24 is the primary analysis.  If the upper limit of the 95% CI is 
≤1.5 mm Hg at all 3 visits, Bimatoprost SR 10 µg statistical noninferiority to SLT is 
demonstrated.  In addition, Bimatoprost SR 10 µg is considered clinically noninferior to SLT 
if the upper limit of the 95% CI is ≤ 1.0 mm Hg at 2 out of the 3 visits of Weeks 4, 12, and 
24.

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As part of the sensitivity analysis for the primary efficacy analysis, a PP analysis using the 
same MMRM model as the one used in the primary efficacy analysis will be performed.  The 
PP analysis will be based on the data from PP population.
Additionally, a by-visit analysis using an ANCOVA model will be conducted using the data 
from Bimatoprost SR 10 µg ITT population, where the between-eye correlation will be 
included in the same way as the MMRM model used for the primary analysis.
Finally, handling of missing data will be supplemented by sensitivity analyses using multiple 
imputation and tipping point (adding different penalties to the imputed values) approach.
7.3.2
Secondary Efficacy Analyses 
Secondary efficacy analyses will be performed for patients treated with Bimatoprost SR 
10 µg in the ITT populations.  
Superiority Test of Bimatoprost SR 10 μg Versus SLT
A superiority test of Bimatoprost SR 10 µg versus SLT will be performed once noninferiority 
is demonstrated in the primary efficacy analysis.  Superiority of Bimatoprost SR 10 µg
versus SLT is considered achieved if the upper limit of the 95% CI is < 0 mm Hg at Weeks 4, 
12, and 24.
Time to Initial Use of Nonstudy IOP-lowering Treatment (As Determined by the 
Investigator)
Time to initial use of nonstudy IOP-lowering treatment from the date of the first study 
treatment will be estimated separately for Bimatoprost SR 10 µg and SLT .
Additionally, time to initial use of nonstudy IOP-lowering treatment from the second
injection, will be analyzed similarly for Bimatoprost SR 10 µg.
Percentage of Bimatoprost SR and SLT Eyes Achieving ≥ 20% Reduction in IOP
Number and percent of Bimatoprost SR 10 µg and SLT eyes that have achieved a ≥ 20% 
reduction in IOP by visit in each eye will be summarized.
IOP Change from Baseline at Weeks 8, 15, and 20
Summary statistics for Bimatoprost SR 10 µg and SLT eyes will be tabulated for IOP change 
from baseline at Weeks 8, 15 and 20;

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7.3.3
Other Efficacy Analyses
 
 
 
 
 
 
7.3.4
Safety Analyses
Safety analyses will be performed separately for patients in the Bimatoprost SR 15 µg and 
Bimatoprost SR 10 µg safety populations.  The Medical Dictionary for Regulatory Activities 
(MedDRA) nomenclature will be used to code adverse events and medical history.  The 
number and percent of patients reporting treatment emergent adverse events will be tabulated 
based on the primary SOC and preferred terms.  Summary tables will be generated for all 
adverse events regardless of causality as well as treatment-related adverse events for the 
entire study and by treatment cycle.  Other safety variables include vital signs (blood 
pressure, pulse rate, and temperature) and pregnancy test results.  Ocular safety will be 
evaluated through assessment of visual acuity and visual field, evaluation of macroscopic 
bulbar conjunctival hyperemia and iris color, assessment of endothelial cell density and 
corneal thickness, IOP measurement, and biomicroscopic and ophthalmoscopic examinations 
(including gonioscopy with Bimatoprost SR implant assessment, optic disc examination, and 
dilated fundus examination).
Ocular adverse events and safety variables attributable to each eye will be summarized by 
Bimatoprost SR or SLT eye, and nonocular safety variables will be summarized by patient.

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7.4
Subgroup Analyses
A subgroup analysis will be conducted for patients who received Bimatoprost SR 10 µg
administration under the flexible dosing regimen as specified in the protocol. This will
include patients enrolled under Amendment 6 and patients who were reconsented to 
Amendment 6 before receiving the second Bimatoprost SR administration. 
The details of this subgroup analysis will be provided in the Statistical Analysis Plan.
7.5
Sample Size Calculation
The sample size calculation is based on paired-eye differences using a normal approximation 
with a 2-sided significance level of 0.05, assuming that there is no difference in mean IOP 
change from baseline between Bimatoprost SR 10 µg eyes and SLT eyes and that change 
from baseline in IOP has a standard deviation of 4 mm Hg.  A sample size of 144 patients 
treated with Bimatoprost SR 10 µg will provide approximately 98% power in showing 
noninferiority in 3 out of 3 timepoints with a noninferiority margin of 1.5 mm Hg, and 90% 
power in showing noninferiority in 2 out of 3 timepoints with a noninferiority margin of 1.0
mm Hg, assuming that both the between-eyes and the within-patient correlation coefficients 
are 0.5.
Assuming a premature discontinuation rate of 10%, approximately 160 patients are to be 
enrolled into this study and treated with Bimatoprost SR 10 µg.  Additionally, there are 
approximately 50 patients who were enrolled before implementation of Amendment 3.
7.6
Interim Analyses
No interim analyses are planned.  
8.
Study Visit Schedule and Procedures
Patients who complete all study treatments will have up to 28 visits and 5 phone calls.  The 
schedule includes the following:  

Screening (up to 28 days); Washout period of up to 56 days for both eyes; and 
Baseline visit (up to 3 days)

SLT treatment (Day 1) and phone call (Day 2) 

Bimatoprost SR Cycle 1 administration (Day 4); Cycle 1 Day 2 safety visit; Cycle 1 
Day 4 and Week 2 phone calls; and follow-up study visits at Weeks 4, 8, 12, and 15

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
Bimatoprost SR Cycle 2 administration (to occur at Week 16 for all patients who 
meet retreatment criteria); Cycle 2 Day 2 safety visit; and Cycle 2 Day 4 and Week 2 
phone calls
o Patients who do not receive Cycle 2 administration at Week 16 will not attend 
the Cycle 2 Administration Day visit on Week 16, or the Day 2 Safety or Day 
4 and Week 2 phone calls associated with administration at Week 16. For 
these patients, Cycle 2 may be performed at the investigator’s discretion 
during an unscheduled visit after Week 16 and prior to the Month 12 visit if 
the retreatment criteria are met; in this case, inadequate control of IOP should 
be confirmed at another scheduled or unscheduled visit prior to initiation of 
Cycle 2.  All Cycle 2 visits will apply at the time of the Cycle 2 
administration.

Follow-up visits at Weeks 20, 24, 28, 31, 36, 40, 44, 47, and 52; and Months 13, 14, 
15, 16, 18, 20, 22, and 24/Exit

Regardless of the timing of Cycle 2 administration, all regularly scheduled 
visits should be completed.  Cycle 2 visits should be scheduled such that the 
Administration Day and the Day 2 Safety Visit do not occur on the day of a 
regularly scheduled study visit.  However, if the Cycle 2 Day 4 or Week 2 
Phone Calls overlap with a regularly scheduled visit, perform the regularly 
scheduled visit.

Patients who receive the second administration of Bimatoprost SR at Week 16 
and patients who never receive a second administration may, at the 
investigator’s discretion, skip the visits at Months 13, 15 and 22 if the patient 
has received nonstudy IOP lowering medication in both eyes; has ≤25% of
each implant remaining in the eye; and in the investigator’s clinical judgment, 
has no safety or other concern that would require the patient to attend these 
visits.  Please note:  as described in Section 4.5.2, each eye should be 
evaluated on an individual basis when determining the need for additional
nonstudy IOP-lowering treatments; initiation of treatment in one eye should 
not automatically lead to initiation of treatment in the contralateral eye.
IOP evaluations will occur at Hour 0 (08:00 AM ± 1 hour) in all patients.  Selected patients at
selected sites will have additional IOP measurements performed at Hour 2 (Hour 0 + 2 hours 
[± 30 minutes]) and Hour 8 (Hour 0 + 8 hours [± 30 minutes]).

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The study visits should adhere as closely as possible to the schedule shown in Table 2,
Table 3, Table 4, Table 5, and Table 6.
8.1
Patient Entry Procedures 
8.1.1
Overview of Entry Procedures
Prospective patients as defined by the criteria in Section 4.3 and Section 4.4
(inclusion/exclusion criteria) will be considered for entry into this study.
8.1.2
Informed Consent and Patient Privacy
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.  The patient 
must also give authorization (US only), data protection consent (EU only), and other written 
documentation in accordance with the relevant country and local privacy requirements 
(where applicable) prior to any study-related procedures or change in treatment.  
Each patient who provides informed consent will be assigned a patient number that will be 
used on patient documentation throughout the study.  
8.2
Washout Intervals
All patients must provide informed consent prior to beginning any drug washout for the 
purposes of inclusion in this study.  Patients currently being treated with IOP-lowering
medication(s) in either eye will begin washout of these medication(s) following completion 
of the screening procedures and Reading Center confirmation of endothelial cell density by 
specular microscopy.  The screening and washout periods may not be concurrent.  The
washout period will be up to 56 days depending on the minimum washout period schedule 
below.
If patients cannot discontinue their prescribed therapy for up to 8 weeks to meet the washout 
period for study entry, the investigator may switch the patient’s medication to one that
requires a shorter washout interval during the washout of the original medication (Table 7).  
Nonetheless, the investigator should adhere to the minimum washout period for all 
IOP-lowering medications as indicated in Table 7.
If, after initial washout, the IOP does not meet entry criteria and the investigator believes this 
is due to inadequate washout, if time remains in the washout period he/she may perform
additional washout, as long as the total washout period does not exceed 56 days.

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Table 7
Minimum Washout Period by Ophthalmic Medication Class
Ophthalmic Medications
Minimum 
Washout Period
Parasympathomimetics (eg, PILAGAN®, Carbachol, Pilocar®)
4 days
Carbonic Anhydrase Inhibitors (topical or systemic) (eg, Diamox®, Trusopt®, 
Azopt®)
4 days
Sympathomimetics (eg, PROPINE®, Epifrin®)
14 days
Alpha-agonists (eg, ALPHAGAN P, Iopidine®)
14 days
Beta-adrenergic blocking agents (eg, Timoptic®, BETAGAN®, Betoptic®, Betoptic-
S®, Opti-Pranolol®, Ocupress®, Timoptic XE®)
28 days
Rho-kinase inhibitors (eg, Rhopressa®, Glanatec®)
28 days
Prostamides, prostaglandins and prostaglandin analogues, as well as combination 
products that include these medications (eg, LUMIGAN, Xalatan, Travatan, 
Rescula®, GANFORT®)
28 days
Combination therapy (for example, COMBIGAN® [28 days], Cosopt® [28 days], 
GANFORT® [28 days], Simbrinza® [14 days], Azarga® [28 days], etc)
longest minimum 
duration of any
component based 
on medication class
For patients undergoing a washout, interim safety evaluation(s) of IOP at some time during 
the washout period may be performed at the discretion of the investigator.
Note:  Medications should only be discontinued (washed out) if the investigator feels that it 
is safe and appropriate, and if the patient is willing to discontinue the medication for the 
duration of the study.  If the medication cannot be discontinued then the patient will not be 
eligible for study entry.
8.3
Procedures for Final Study Entry
The results from the screening ocular and physical examinations, and laboratory tests 
(hematology/blood chemistry/urinalysis) must be evaluated and determined to be acceptable 
to the investigator prior to the patient’s entry into the study.  If repeat laboratory tests are 
done, the results must be reviewed prior to study treatment initiation on Day 1. Reading
Center qualification of endothelial cell density must be confirmed prior to beginning 
Washout.  After confirmation of eligibility on Day 1, the interactive response system is
contacted for randomization.  However, this contact for randomization may take place at the 
end of the baseline day visit if needed.  See Section 5.5 for the method for assignment to 
treatment groups/randomization.  
A patient is considered to have enrolled in the study at the time of the first study treatment 
administration (SLT or Sham SLT).

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8.4
Visits and Associated Procedures
The following sections provide a list of procedures for each scheduled visit. Additional
information on the examination procedures, equipment, and techniques for the measures 
listed in this section is presented in the Procedure Manual.
Ocular examination procedures should be performed in the order listed at each visit.  
Flexibility in procedure order is allowed, as indicated in the tables (Table 2, Table 3, Table 4, 
Table 5, and Table 6).  Noncontact examinations may be performed at any time prior to 
gonioscopy (including before or after Hour 0 IOP). Intraocular pressure should be measured 
at approximately the same time of day at each visit.  Hour 0 is defined as 8:00 AM ± 1 hour.  
All IOP measurements for a given visit day must be completed prior to performing any 
examination procedures that require pupil dilation.
Examiners performing IOP measurements should be masked to the patient’s treatment group.  
Effort should be made to keep IOP examiners masked to the patient’s other evaluation 
results.
8.4.1
Screening Visit
After informed consent and other documentation have been obtained (as described in 
Section 8.1.2), the procedures listed below are carried out.  Intraocular pressure 
measurements must be performed in 1 day; however, other procedures (eg, postdilation and 
imaging procedures) may be performed on a different day as long as the screening 
procedures are completed within a 28-day period.  Perform pupil dilation/diagnostic 
procedures after the completion of the final IOP measurement of the day or on a different 
day.

Collection of demographic data

Collection of medical and ophthalmic history

Collection of adverse events

Collection of concomitant medications and procedures

Physical examination

Vital signs (at rest ≥ 5 minutes)

Collection of blood and urine samples

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The following procedures should be performed in both eyes in the order below (procedures in 
bold should be done in the order shown):

Pre-Hour 0 examination (perform before Hour 0 IOP):
o
Macroscopic conjunctival hyperemia assessment 

Manifest refraction (Manifest refraction will be used to provide a correction for 
best-corrected visual acuity testing.  At all study visits, if there is a 2-line or more 
reduction in visual acuity from the last best-corrected visual acuity performed, a 
repeat manifest refraction in both eyes and best-corrected visual acuity will be 
performed.)

Best-corrected visual acuity

Intraocular pressure measurement at Hour 0

Non-contact examinations:  The following may be performed in any order, at any 
time before gonioscopy (including prior to Hour 0 IOP):
o
Visual field (Two visual field tests are required prior to the administration 
procedure.  The first can be performed up to 10 months prior to or at 
Screening, and the second during the washout period or at the Baseline visit.  
For a given patient, the same test methodology must be used for fields that are 
historical as well as fields performed throughout the study.)
o
Specular microscopy
o
Anterior segment-optical coherence tomography 
o
  
  Assessment 
will be repeated at Week 52 and Month 24/Exit and may be performed at any 
interim study visit at the discretion of the investigator.)
o
Biomicroscopy 

Gonioscopy/angle assessment (The examination at Screening will be independently 
performed by 2 ophthalmologists for eligibility purposes.  Examination will also 
include, 
 

Pachymetry (may be performed at any time after gonioscopy)

Pupil dilation (Post-dilation examinations below may be performed in any order)
o
Dilated ophthalmoscopy
o
Optic disc examination
Eligibility is then determined and the interactive response system is contacted.

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Washout may begin after Screening visit procedures have been completed and the Reading 
Center has confirmed central endothelial cell density (see Section 8.2 for a description of 
washout).  
8.4.2
Baseline Visit
The Baseline visit occurs after the washout period has been completed.  Baseline visit 
procedures, excluding IOP measurements (which must be performed in 1 day), can be 
performed over a 3-day period; all must be completed by the day before the administration 
day.  Perform pupil dilation/diagnostic procedures after the completion of the final IOP 
measurement or on a different day.

Collection of medical and ophthalmic history (confirmation)

Collection of adverse events

Collection of concomitant medications and procedures

Completion of Visual Field Questionnaire-25 (VFQ-25)

Vital signs (at rest ≥ 5 minutes)

Pregnancy test for females of childbearing potential (as defined in Section 4.5.3)
The following procedures should be performed in both eyes (procedures in bold should be 
done in the order shown):

Pre-Hour 0 examination (perform before Hour 0 IOP):
o
Macroscopic conjunctival hyperemia assessment (The examination may also 
include, 
 

Manifest refraction (Manifest refraction will be used to provide a correction for 
best-corrected visual acuity testing.  At all study visits, if there is a 2-line or more 
reduction in visual acuity from the last best-corrected visual acuity performed, a 
repeat manifest refraction in both eyes and best-corrected visual acuity will be 
performed.)

Best-corrected visual acuity

Intraocular pressure measurement at Hour 0 

Non-contact examinations:  The following may be performed in any order, at any 
time before Hour 8 IOP (including prior to Hour 0 IOP):
o
Macroscopic iris color assessment
o
Visual field (If dilation is required to perform this test, then the visual field 
test should be performed after the last IOP measurement of the day.)

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o
Biomicroscopy (The examination may also include, 
 
)

Intraocular pressure measurements at Hours 2 and 8 (at selected sites in 
consenting patients)

Pupil dilation (post-dilation examinations below may be performed in any order)
o
Dilated ophthalmoscopy
o
Optic disc examination
Determine eligibility and enter Hour 0 IOP into the interactive response system.  
8.4.3
Treatment Period
8.4.3.1
Day 1 SLT Administration
The following procedures are performed on the day of SLT or Sham SLT administration:

Collection of adverse events

Collection of concomitant medications and procedures

Vital signs (at rest ≥ 5 minutes)

Confirm eligibility

Contact interactive response system for randomization (this contact may take place 
1 day prior to the administration day, if needed)  

Preoperative IOP measurement (measurement does not need to be masked and only 
1 measurement needs to be performed)

Administer assigned study treatment (360or Sham SLT; see details in Section 5.9.2)

Postoperative biomicroscopy

Postoperative IOP measurement (measurement does not need to be masked and only 
1 measurement needs to be performed)
All patients must remain at the surgical facility for at least 1 hour for bilateral eye 
examination after 360or Sham SLT administration.  
Each patient will be supplied a bottle of topical NSAID eyedrops and instructions to use 
them 4 times daily for the next 3 days (including the day of the administration) in both eyes 
and to follow up as per protocol.

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8.4.3.2
Day 2 (Phone Call)
On the day after study treatment administration, the patient will be contacted by telephone to 
collect the following:

Collection of adverse events

Collection of concomitant medications and procedures
If the patient reports symptoms or findings of concern in the Day 2 phone call (including but 
not limited to photophobia, blurred vision, eye pain, vitreous floaters), the investigator must 
bring the patient in for ophthalmic examination.
8.4.3.3
Day 4 (Bimatoprost SR Cycle 1 Administration)
The following procedures are performed on the day of Bimatoprost SR administration:

Collection of adverse events

Collection of concomitant medications and procedures

Vital signs (at rest ≥ 5 minutes)

Contact interactive response system for kit allocation (this contact may take place 
1 day prior to the administration day, if needed)    

Administer assigned study treatment (Bimatoprost SR or Sham Bimatoprost SR; see 
details in Section 5.9)

Contact interactive response system to confirm kit assignment if applicable
All patients must remain at the surgical facility for bilateral eye examination at least 1 hour 
after Bimatoprost SR administration or sham administration procedure.  For patients with 
sickle cell disease or trait (or other hemoglobinopathies), the investigator may perform 
optional biomicroscopy and measure IOP in both eyes 4 hours after the administration
procedure as desired.  This IOP examination is for postoperative purposes only, and as such 
does not require a masked, 2-person reading method.  The IOP should be taken only once to 
avoid excessive postadministration (or sham administration) manipulation of the eye, and 
should be taken by the investigator (or other unmasked, qualified personnel).  This 
postadministration (or sham administration) examination may be performed using a 
Goldmann applanation tonometer or a hand-held tonometer.  See full procedure instructions 
in the Procedure Manual.

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Each patient will be supplied a bottle of topical ophthalmic antibiotic drops and instructions 
to use them for the next 3 days (including the day of the administration) in both eyes and to 
follow up as per protocol.
8.4.3.4
Cycle 1:  Day 2 (Cycle 1 Safety Visit)
The following procedures are performed on Cycle 1 Day 2:

Collection of adverse events

Collection of concomitant medications and procedures

Vital signs (at rest ≥ 5 minutes)
The following procedures should be performed in both eyes (procedures in bold should be 
done in the order shown):

Pre-Hour 0 examinations (may perform in any order before Hour 0 IOP):  
o
Macroscopic conjunctival hyperemia assessment (The examination may also 
include, 
 
)
o
Best-corrected visual acuity

Intraocular pressure measurement at Hour 0

Non-contact examination:  The following may be performed at any time after the 
pre-Hour 0 examinations (including prior to Hour 0 IOP):  
o
Biomicroscopy (The examination may also include, 
 
 
.)
8.4.3.5
Cycle 1:  Day 4 and Week 2 (Cycle 1 Phone Calls)
On Cycle 1 Day 4 and Cycle 1 Week 2, the patient will be contacted by telephone to collect 
the following:

Collection of adverse events

Collection of concomitant medications and procedures
If the patient reports symptoms or findings of concern in the Day 4 or Week 2 phone call 
(including but not limited to photophobia, blurred vision, eye pain, vitreous floaters), the 
investigator must bring the patient in for ophthalmic examination.

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8.4.3.6
Cycle 1:  Weeks 4, 8, 12, and 15
The following procedures are performed at Weeks 4 (±4 days), 8 (± 4 days), 12 (±4 days), 
and 15 (±4 days):

Collection of adverse events

Collection of concomitant medications and procedures

Vital signs (at rest ≥ 5 minutes)
The following procedures should be performed in both eyes (procedures in bold should be 
done in the order shown):

Pre-Hour 0 examinations (may be performed in any order before Hour 0 IOP):
o
Macroscopic conjunctival hyperemia assessment (The examination may also 
include, 
 
.)
o
Best-corrected visual acuity

Intraocular pressure measurement at Hour 0 

Non-contact examinations:  The following may be performed in any order, at any 
time before gonioscopy (including prior to Hour 0 IOP):
o
Macroscopic iris color assessment (Weeks 4 and 12 only)
o
Manifest refraction (Week 12 only)
o
Specular microscopy (Weeks 4 and 12 only)
o
Biomicroscopy (The examination may also include, 
 
 
.)

Intraocular pressure measurement at Hours 2 and 8 (at selected sites in 
consenting patients; Week 12 only)

Gonioscopy/angle assessment (The examination will also include, 
 
.  Perform 
gonioscopy at least 2 hours prior to H8 IOP measurement at Week 12.)

Pachymetry (may be done any time after gonioscopy; Weeks 4 and 12 only)

Pupil dilation (Week 12 only) (post dilation examinations below may be performed 
in any order)
o
Dilated ophthalmoscopy (Week 12 only)
o
Optic disc examination (Week 12 only)

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8.4.3.7
Bimatoprost SR Cycle 2 Day 1 Administration
The following procedures are performed at Week 16 (-2/+4 days) for all patients who meet 
retreatment criteria.  
Patients who do not receive Cycle 2 administration at Week 16 will not attend the Cycle 2 
Administration Day visit on Week 16, or the Day 2 Safety or Day 4 and Week 2 phone calls 
associated with administration at Week 16.  For those patients not meeting retreatment 
criteria at Week 16, Cycle 2 may be performed at the investigator’s discretion during an 
unscheduled visit after Week 16 and prior to the Month 12 visit if the retreatment criteria are 
met; in this case, inadequate control of IOP should be confirmed at another scheduled or 
unscheduled visit prior to initiation of Cycle 2.  For patients who begin Cycle 2 after Week 
16 and before Month 12, the Cycle 2 visits (Administration Day, Day 2 Safety Visit, and Day 
4 and Week 2 Phone Calls) will apply at the time that Cycle 2 occurs.  Regardless of the 
timing of Cycle 2, all regularly scheduled visits should be completed.  Cycle 2 should be 
scheduled such that the Administration Day and the Day 2 Safety Visit do not occur on the 
day of a regularly scheduled study visit.  However, if the Cycle 2 Day 4 or Week 2 Phone 
Calls overlap with a regularly scheduled visit, perform the regularly scheduled visit.

Collection of adverse events

Collection of concomitant medications and procedures

Vital signs (at rest ≥ 5 minutes)

Contact interactive response system for kit allocation (this contact may take place 
1 day prior to the Cycle 2 administration day, if needed)

Administer assigned study treatment

Contact interactive response system to confirm kit assignment if applicable
All patients must remain at the surgical facility for bilateral eye examination at least 1 hour 
after Bimatoprost SR administration or sham administration procedure.  For patients with 
sickle cell disease or trait (or other hemoglobinopathies), the investigator may perform 
optional biomicroscopy and measure IOP in both eyes 4 hours after the administration 
procedure as desired.  This IOP examination is for postoperative purposes only, and as such 
does not require a masked, 2-person reading method.  The IOP should be taken only once to 
avoid excessive postadministration (or sham administration) manipulation of the eye, and 
should be taken by the investigator (or other unmasked, qualified personnel).  This 
postadministration (or sham administration) examination may be performed using a 
Goldmann applanation tonometer or a hand-held tonometer.  See full procedure instructions 
in the Procedure Manual.

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8.4.3.8
Cycle 2:  Day 2 (Cycle 2 Safety Visit)
The following procedures are performed on Cycle 2 Day 2:

Collection of adverse events

Collection of concomitant medications and procedures

Vital signs (at rest ≥ 5 minutes)
The following procedures should be performed in both eyes (procedures in bold should be 
done in the order shown):

Pre-Hour 0 examinations:
o
Macroscopic conjunctival hyperemia assessment (The examination may also 
include, 
 
)
o
Best-corrected visual acuity

Intraocular pressure measurement at Hour 0

Non-contact examination:  The following may be performed at any time after the 
pre-Hour 0 examinations (including prior to Hour 0 IOP):
o
Biomicroscopy (The examination may also include, 
 
 
)
8.4.3.9
Cycle 2:  Day 4 and Week 2 (Cycle 2 Phone Calls)
On Cycle 2 Day 4 and Cycle 2 Week 2, the patient will be contacted by telephone to collect 
the following:

Collection of adverse events

Collection of concomitant medications and procedures
If the patient reports symptoms or findings of concern in the Day 4 or Week 2 phone call 
(including but not limited to photophobia, blurred vision, eye pain, vitreous floaters), the 
investigator must bring the patient in for ophthalmic examination.
8.4.3.10
Weeks 20, 24, 28, and 31
The following procedures are performed at Weeks 20 (± 4 days), 24 (±4 days), 28 (± 4 days), 
and 31 (± 4 days):

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
Collection of adverse events

Collection of concomitant medications and procedures

Vital signs (at rest ≥ 5 minutes)
The following procedures should be performed in both eyes (procedures in bold should be 
done in the order shown):

Pre-Hour 0 examinations:
o
Macroscopic conjunctival hyperemia assessment (The examination may also 
include, 
 
)
o
Best-corrected visual acuity

Intraocular pressure measurement at Hour 0 

Non-contact examinations:  The following may be performed in any order, at any 
time before gonioscopy (including prior to Hour 0 IOP):
o
Macroscopic iris color assessment (Week 24 only)
o
Manifest refraction (Week 24 only)
o
Visual field (If dilation is required to perform this test, then the visual field 
test should be performed after the last IOP measurement of the day.) (Week 24 
only)
o
Specular microscopy (Week 24 only)
o
Biomicroscopy (The examination may also include, 
 
 
)

Intraocular pressure measurement at Hours 2 and 8 (at selected sites in 
consenting patients; Week 24 only)

Gonioscopy/angle assessment (The examination will also include, 
 
)

Pachymetry (Week 24 only) (may be done any time after gonioscopy)

Pupil dilation (may perform post-dilation eye exams in any order; Week 24 only)
o
Dilated ophthalmoscopy (Week 24 only)
o
Optic disc examination (Week 24 only)

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8.4.3.11
Weeks 36, 40, 44, 47, and 52; and Months 13, 14, 15, 16, 18, 20, 
22, and 24/Exit
The following procedures are performed at Weeks 36 (± 4 days), 40 (± 4 days), 44 (± 4 days), 
47 (± 4 days), and 52 (± 4 days) and Months 13 (± 4 days), 14 (± 4 days), 15 (± 4 days), 
16 (± 4 days), 18 (± 7 days), 20 (± 7 days)¸ 22 (± 7 days)¸ and 24/Exit (± 7 days).
Patients who receive the second administration of Bimatoprost SR at Week 16 and patients 
who never receive a second administration may, at the investigator’s discretion, skip the 
visits at Months 13, 15 and 22 if the patient has received nonstudy IOP lowering medication 
in both eyes; has ≤25% of each implant remaining in the eye; and in the investigator’s 
clinical judgment, has no safety or other concern that would require the patient to attend 
these visits.  Please note:  as described in Section 4.5.2, each eye should be evaluated on an 
individual basis when determining the need for additional nonstudy IOP-lowering treatments; 
initiation of treatment in one eye should not automatically lead to initiation of treatment in 
the contralateral eye.

Collection of adverse events

Collection of concomitant medications and procedures

Vital signs (at rest ≥ 5 minutes)

Pregnancy test for females of childbearing potential (as defined in Section 4.5.3) 
(Month 24/Exit only)
The following procedures should be performed in both eyes (procedures in bold should be 
done in the order shown):

Pre-Hour 0 examinations (may perform in any order before Hour 0 IOP):
o
Macroscopic conjunctival hyperemia assessment (The examination will also
include,
 
 
 may be performed at interim visits for appearance of or 
increase/decrease in hyperemia.)
o
Best-corrected visual acuity

Intraocular pressure measurement at Hour 0

Non-contact examinations:  The following may be performed in any order, at any 
time before gonioscopy (including prior to Hour 0 IOP):
o
Macroscopic iris color assessment (Week 52 and Months 18 and 24/Exit only)
o
Manifest refraction (Week 52 and Months 18 and 24/Exit only)

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o
Visual field  (If dilation is required to perform this test, then the visual field 
test should be performed after the last IOP measurement of the day.) (Week 52
and Months 18 and 24/Exit only)
o
Specular microscopy (Weeks 40 and 52 and Months 16, 20, and 24/Exit only)
o
(at Week 52 and Month 24/Exit at 
selected sites in both eyes of all consenting patients who underwent 
assessment at Screening; may be done at interim visits at the discretion of the 
investigator.  Perform any contact assessments following IOP measurements.)
o
Biomicroscopy (The examination will also include, 
 
 
 may be performed at 
interim visits for appearance of or increase/decrease in hyperemia.) 

Gonioscopy/angle assessment (The examination will also include,
 
) 

Pachymetry (Weeks 40 and 52 and Months 16, 20, and 24/Exit only) (may be done 
any time after gonioscopy)

Pupil dilation (Weeks 40 and 52 and Months 16, 20, and 24/Exit only) (post dilation 
exams below may be performed in any order)
o
Dilated ophthalmoscopy (Weeks 40 and 52 and Months 16, 20, and 24/Exit 
only)
o
Optic disc examination (Weeks 40 and 52 and Months 16, 20, and 24/Exit 
only)

Contact interactive response system at Month 24/Exit to report patient’s exit status
8.5
End of Study
The end of the clinical phase of the study will be considered achieved when last patient has 
completed his or her last study visit.
8.6
Instructions for the Patients
Patients should be instructed to strictly follow the study visit schedule and to report all 
changes in their condition to the investigative site.
Instruction should be given to the patient to maintain a stable dose of any concomitant 
medication used chronically, or any new medications initiated during the study whenever 
possible.  Patients should be instructed to communicate any changes to their medication at 

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their next study visit.  Patients should also be reminded to contact the study site if they are
experiencing any difficulties during their study participation.
Patients should be instructed to remove their contact lenses before instillation of any topical 
ophthalmic medication, and to keep contact lenses out for at least 15 minutes after instillation 
of eye drops.
8.7
Unscheduled Visits
Additional examinations may be performed as necessary to ensure the safety and wellbeing 
of patients during the study period.  Unscheduled visit eCRFs should be completed for each 
unscheduled visit.  An assessment of any adverse event should be completed.
8.8
Compliance with Protocol
Patients must be able to adhere to the study visit schedule; appropriate inclusion, exclusion, 
and treatment criteria; permitted and prohibited medication criteria; and testing parameters as 
described in the protocol.  At each study visit, patients will be asked if they have used their 
study-provided eye drops as instructed and whether they have used any concomitant 
medications/therapies or had any concurrent procedures since the previous visit.
Patients should be scheduled for study visits as closely to the day specified in the visit 
schedule as possible.
8.9
Early Discontinuation (Early Exit) of Patients
Patients may voluntarily withdraw from the study at any time.
Patients who have received nonstudy IOP-lowering medication in one or both eyes, or who 
do not undergo Cycle 2 administration, will be followed for the duration of the study through 
the Month 24/Exit visit.  If the implant has been removed, the patient may discontinue the 
study if based on investigator assessment the eye is in stable condition, at which time they 
should complete the Month 24/Exit visit procedures.
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 case report form.
When patients discontinue before Month 24/Exit, the site should complete all procedures for 
the Month 24/Exit visit at the patient’s last visit.

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8.10
Withdrawal Criteria
After the first administration (or Sham), failure to undergo an Administration Day visit does 
not indicate total withdrawal from the study.  Patients who have received nonstudy 
IOP-lowering treatment in one or both eyes, or who do not undergo Cycle 2 administration,
will continue through the duration of the study.  
The investigator should consider withdrawing a patient from the study early if any of the 
following criteria are met:

Patient develops (or has an exacerbation of) a medical condition that, in the opinion 
of the investigator, compromises the patient’s ability to participate in the study

Patient is unwilling or unable to continue to comply with study procedures

Patient is unwilling or unable to continue in the study
If a patient develops (or has an exacerbation of) a medical condition that, in the opinion of 
the investigator, would put the patient at an unacceptable medical risk by continuing study 
participation, the patient will be withdrawn from the study.
Whenever possible, the decision to withdraw a patient from the study or study treatment 
should be discussed with Allergan.
8.11
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.  In the 
event that the study is stopped, patients will be followed for 16 weeks after their last 
Bimatoprost SR (or Sham) administration, after which they will return to standard of care as 
per the investigator’s discretion.  
9.
Adverse Events 
Adverse events occurring during the study will be recorded on an adverse event case report 
form.  If adverse events occur, the first concern will be the safety of the study participants.  

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9.1
Definitions
9.1.1
Adverse Event
An adverse event is any untoward medical occurrence in a patient or clinical investigation 
patient administered a pharmaceutical product and that does not necessarily have a causal 
relationship with the 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.  This definition includes events related to the medical 
(investigational) product (Bimatoprost SR implant and applicator combination) or 
comparator medical device (SLT), and events related to the procedures involved, and also 
includes any malfunction or deterioration in the characteristics and/or performance of a 
device.  During the screening period, adverse events will be assessed regardless of the 
administration of a pharmaceutical product.  
Note:  Adverse events must be collected once informed consent has been obtained, regardless 
of whether or not the patient has been administered study treatment.
Progression of treatment indication including new or worsening of anticipated clinical signs 
or symptoms, which are collected as clinical efficacy variables and assessed as unequivocally 
associated with the disease progression and /or lack of efficacy, should NOT be reported as 
adverse events unless the disease progression is greater than anticipated in the natural course 
of the disease.
IOP return to baseline following the cessation of the Bimatoprost SR treatment effect should 
not be considered an adverse event.
Adverse events will be assessed, documented, and recorded in the eCRF 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 case report form.  
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 

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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 or subject and 
may require medical or surgical intervention to prevent one of the outcomes listed in this 
definition.  (See Section 9.3 for procedures for reporting a serious adverse event.)
Allergan considers all cancer adverse events as serious adverse events.  In addition, Allergan 
considers any abortion (spontaneous or nonspontaneous) as a serious adverse event.
Pre-planned surgeries or procedures for pre-existing, known medical conditions for which a 
patient requires hospitalization is not reportable as a serious adverse event.
Any pre-planned surgery or procedure should be clearly documented in the site source 
documents by the medically qualified investigator at the time of the patient’s entry into the 
study.  If it has not been documented at the time of the patient’s entry into the study, then it 
should be documented as a serious adverse event and reported to Allergan.
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 must 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 
which cannot be graded.
9.1.4
Relationship to Study Drug, Device, or Procedure
A determination will be made of the relationship (if any) between an adverse event and the 
study drug, device, or procedure, as applicable.  A causal relationship is present if a 
determination is made that there is a reasonable possibility that the adverse event may have 
been caused by the study drug, device, or procedure.  

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If an adverse event is deemed related to study drug or device, the investigator will be asked 
to further delineate whether the adverse event was related to the administration procedure 
(versus the study drug or device).
Note:  A study procedure occurring during the screening/baseline period can include a 
washout of medication or study required diagnostic procedure.
9.2
Procedures for Reporting Adverse Events
Any adverse event must be recorded on the appropriate case report form.
All adverse events that are study drug or device-related and unexpected (not listed as 
treatment-related in the current Investigator's Brochure) must 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.  Any adverse event that is 
marked “ongoing” at the exit visit must be followed-up as appropriate.
9.3
Procedures for Reporting a Serious Adverse Event
Any serious adverse event occurring during the study period (beginning with informed 
consent and continuing through the final study visit) and for at least 4 months after the last 
dose of study drug must be immediately reported but no later than 24 hours after learning of 
a serious adverse event.  Serious adverse events must be reported to Allergan (or Agent of 
Allergan) as listed on the Allergan Study Contacts Page and recorded on the serious adverse 
event form.  All patients with a serious adverse event must be followed up and the outcomes 
reported.  The investigator must supply the sponsor and the IRB/IEC with any additional 
requested information (eg, autopsy reports and discharge summaries).  
In the event of a serious adverse event, the investigator must:
1. Notify Allergan immediately by fax or email using the serious adverse event form 
(contact details can be found on page 1 of the serious adverse event form); phone 
numbers and relevant Allergan personnel contacts are also on the front page of 
protocol and Study Contacts Page.
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.

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3. Provide Allergan with a complete, written description of the adverse event(s) on the 
serious adverse event form describing the event chronologically, including any 
treatment given (eg, medications administered, procedures performed) for the adverse 
event(s).  Summarize relevant clinical information about the event:  signs, symptoms, 
diagnosis, clinical course and relevant clinical laboratory tests, etc.  Include any 
additional or alternative explanation(s) for the causality which includes a statement as 
to whether the event was or was not related to the use of the study drug, device, or 
procedure.
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.
9.4
Procedures for Unmasking of Study Treatment
The primary investigator and select site staff (eg, study coordinator) are unmasked.  When 
necessary for the safety and proper treatment of the patient, the investigator can unmask the 
patient and/or other site personnel.  
When possible, the sponsor (Allergan Medical Safety Physician) should be notified prior to 
unmasking the patient and/or other site personnel.  In instances where this is not possible, the 
sponsor should be notified as soon as possible thereafter.  
The reason for unmasking the patient and/or other site personnel must be recorded in the 
patient’s source documents.
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, Allergan SOPs, and the applicable regulatory requirements.
10.1
Protection of Human Patients
10.1.1
Compliance With Informed Consent Regulations (US 21 CFR 
Part 50) and Relevant Country Regulations
Written informed consent is to be obtained from each patient prior to any study-related 
activities or procedures in the study, and/or from the patient's legally authorized 
representative.  If the patient is under the legal age of consent, the consent form must be 

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signed by the legally authorized representative in accordance with the relevant country and 
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 or IEC Regulations
This study is to be conducted in accordance with IRB regulations (US 21 CFR Part 56.103) 
or applicable 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 GCP regulations and 
guidelines.  
10.1.4
Quality Assurance
Compliance with the ethical and scientific ICH GCP quality standard, along with Allergan 
SOPs, on the design, conduct, recording, and reporting of clinical trials provides protection 
for the wellbeing and rights of patients as well as assuring the quality and credibility of the 
clinical trial data.  Quality Control activities will be undertaken within the quality assurance 
system to verify that the requirements for the quality of trial-related activities have been 
fulfilled.
10.1.5
Compliance With Electronic Records; Electronic Signatures 
Regulations (US 21 CFR Part 11)
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 must not implement any deviation from or changes of the protocol without 
approval by Allergan and prior review and documented approval/favorable opinion from the 

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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 the Sponsor of the study, Allergan, or the governing health authorities or the 
FDA 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
Written authorization (US sites only), data protection consent (European sites only), and 
other documentation in accordance with the relevant country and 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 requirements (eg, the Health Insurance Portability and Accountability Act Standards 
for Privacy of Individually Identifiable Health Information (“HIPAA”), European Union Data 
Protection Directive 95/46/EC [“EU Directive”]).
In accordance with HIPAA requirements, additional purposes of this study may include 
publishing of anonymous patient data from the study.  
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 case report forms 
serves as part of the investigator's record of a patient's study-related data.  
The following information should be entered into the patient's medical record:

Patient’s name

Patient’s contact information

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
The date that the patient entered the study, patient number, and patient medication kit 
number.  

The study title and/or the protocol number of the study and the name of Allergan.

A statement that informed consent was obtained (including the date).  A statement that 
written authorization (US sites only), data protection consent (EU sites only), or other 
country and local patient privacy required documentation for this study has been 
obtained (including the date).

Dates of all patient visits

All concurrent medications (List all prescription and non-prescription medications 
being taken at the time of enrollment.  At each subsequent visit, changes to the list of 
medications should be recorded.)

Occurrence and status of any adverse events (including any procedure-related adverse 
events due to complications)

The 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, blood chemistry and 
hematology, urinalysis, and pregnancy tests)

Key study variables
Documentation of the patient's medical history
Vital signs, physical examination findings
IOP and ophthalmic examination findings
Dates of SLT or Sham SLT administration procedure
Dates of Bimatoprost SR or Sham administration procedure
Documentation of whether any procedure including study treatment
administration was performed according to the protocol, noting any deviations (if 
applicable)
 
 

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Source documentation practices must follow Section 4.0 of ICH E6, Good Clinical Practice:  
Consolidated Guidance and ALCOA, ie, records must be Attributable, Legible, 
Contemporaneous, Original, and Accurate.
10.4.2
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 and will be maintained in a central data repository.
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.
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 case report forms should be maintained on file.
For countries falling within the scope of the ICH guidelines, 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 
requirement(s) 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.

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10.5
Labeling, Packaging, and Return or Disposal of Study 
Medications/Treatments
10.5.1
Labeling/Packaging
Packaged and labeled study medication will be supplied by Allergan.
The assembled Bimatoprost SR (or Sham applicator) is individually packaged into a 
laminated foil pouch with desiccant and sealed.  The entire foil pouch package is terminally 
sterilized.  Each pouch will be placed into its own carton.  The medication will be identified 
as an investigational product.  The study number and medication kit number will be 
identified on the medication labels.
The study medication contents are described in Section 5.1 and Section 5.2.
10.5.2
Clinical Supply Inventory
The investigator must keep an accurate accounting of the number of investigational units 
received from Allergan, dispensed or administered 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 or administered only by an 
appropriately qualified person to patients 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.  Used applicators will be disposed of immediately in a 
sharps container.
Any malfunctioning applicators should be returned to Allergan or designee.  Written 
instructions provided by Allergan should be followed when returning a malfunctioning 
applicator to Allergan or its representative.

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10.6
Monitoring by the Sponsor
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
Laboratory specimens for blood chemistry panel, hematology including complete blood 
count with differential, and urinalysis will be sent to a centralized clinical laboratory or a 
designated regional facility with certification from a recognized accreditation agency (eg, 
College of American Pathology or Clinical Laboratory Improvement Amendments 
certification) to be assayed using validated methods.  All blood and urine samples will be 
stored at the centralized clinical laboratory following testing, and will be discarded after a 
time period indicated by Allergan.  Allergan shall have full ownership rights to any biological 
specimens/samples derived from the study.
See the Covance Laboratory Manual and the Procedure Manual for procedural details.
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.  
10.9
Coordinating Investigator
A signatory Coordinating Investigator will be designated prior to the writing of the Clinical 
Study Report.

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10.10
 
 
 
 
 
 
  
 
 
 
  
 

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11.
References
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Ophthalmology; 2010a.  27 p.
Budenz DL.  A clinician's guide to the assessment and management of nonadherence in 
glaucoma.  Ophthalmology.  2009;116:S43-S47.
Cohen JS, Gross RL, Cheetham JK, VanDenburgh AM, Bernstein P, Whitcup SM.  Two-year 
double-masked comparison of bimatoprost with timolol in patients with glaucoma or ocular 
hypertension.  Surv Ophthalmol.  2004;49 (Suppl 1):S45-S52.
Cook C, Foster P.  Epidemiology of glaucoma:  What’s new?  Can J Ophthalmol.  
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argon laser trabeculoplasty:  a prospective randomised clinical trial.  Br J Ophthalmol.  
1999;83(6):718-722.
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PubliComm:  Italy; 2014. 187p. 
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replacement for medical therapy in open-angle glaucoma.  Am J Ophthalmol.  
2005;140(3):524-525.
Friedman DS.  Introduction:  new insights on enhancing adherence to topical glaucoma 
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Heijl A, Leske MC, Bengtsson B, Hyman L, Bengtsson B, Hussein M.  Reduction of 
intraocular pressure and glaucoma progression:  results from the early manifest glaucoma 
trial.  Arch Ophthalmol.  2002;120:1268-1279.
Higginbotham EJ, Schuman JS, Goldberg I, Gross RL, VanDenburgh AM, Chen K, et al.  
One-year, randomized study comparing bimatoprost and timolol in glaucoma and ocular 
hypertension.  Arch Ophthalmol.  2002;120:1286-1293.
Kass MA, Heuer DK, Higginbotham EJ, Johnson CA, Keltner JL, Miller JP, et al.  The 
Ocular Hypertension Treatment Study:  a randomized trial determines that topical ocular 
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Katz LJ, Steinmann WC, Kabir A, Molineaux J, Wizov SS, Marcellino G, et al.  Selective 
laser trabeculoplasty versus medical therapy as initial treatment of glaucoma:  a prospective, 
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glaucoma.  J Glaucoma.  2012;21(1):65-70.
Kozak KR, Crews BC, Morrow JD, Wang L-H, Ma YH, Weinander R, et al.  Metabolism of 
the endocannabinoids, 2-arachidonylglycerol and anandamide, into prostaglandin, 
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2002;277:44877-44885.
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and discussion of new evidence.  Surv Ophthalmol.  2004;49(Suppl 1):S5-S11.
Lichter PR, Musch DC, Gillespie BW, Guire KE, Janz NK, Wren PA, et al.  Interim clinical 
outcomes in the Collaborative Initial Glaucoma Treatment Study comparing initial treatment 
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Matias I, Chen J, De Petrocellis L, Bisogno T, Ligresti A, Fezza F, et al.  Prostaglandin 
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surgeries for glaucoma.  Trans Am Ophthalmol Soc.  2009;107:127-133; discussion 134-135.
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hypotensive treatment in patients with glaucoma or ocular hypertension an evidence-based 
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2020.  Br J Ophthalmol.  2006;90(3):262-267.
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development of glaucomatous visual field loss in ocular hypertension.  Arch Ophthalmol.  
1994;112:644-649.
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In:  Becker-Shaffer’s Diagnosis and Therapy of the Glaucomas.  8th ed.  Amsterdam:  Mosby 
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Tsai JC.  A comprehensive perspective on patient adherence to topical glaucoma therapy.  
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Wang H, Cheng JW, Wei RL, Cai JP, Li Y, Ma XY.  Meta-analysis of selective laser 
trabeculoplasty with argon laser trabeculoplasty in the treatment of open-angle glaucoma.  
Can J Ophthalmol.  2013;48(3):186-192.
Weber A, Ni J, Ling KH, Acheampong A, Tang-Liu DD, Burk R, et al.  Formation of 
prostamides from anandamide in FAAH knockout mice analyzed by HPLC with tandem 
mass spectrometry.  J Lipid Res.  2004;45:757-763.
Williams RD, Cohen JS, Gross RL, Liu CC, Safyan E, Batoosingh AL.  Long-term efficacy 
and safety of bimatoprost for intraocular pressure lowering in glaucoma and ocular 
hypertension:  year 4.  Br J Ophthalmol.  2008;92:1387-1392.
Woodward DF, Chan MF, Burke JA, Cheng-Bennett A, Chen G, Fairbairn CE, et al.  Studies 
on the ocular hypotensive effects of prostaglandin F2 alpha ester prodrugs and receptor 
selective prostaglandin analogs.  J Ocul Pharmacol.  1994;10:177-193.
Woodward DF, Krauss AH, Chen J, Lai RK, Spada CS, Burk RM.  The pharmacology of 
bimatoprost (Lumigan).  Surv Ophthalmol.  2001;45(Suppl 4):S337-S345.
Woodward DF, Phelps RL, Krauss AH, Weber A, Short B, Chen J, et al.  Bimatoprost:  A 
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12.
Attachments
Not applicable
12.1
Glossary of Abbreviations
Term/Abbreviation
Definition
ABMD
Anterior Basement Membrane Disease
AC
anterior chamber
AGIS
Advanced Glaucoma Intervention Study
ALT
argon laser trabeculoplasty
ANCOVA
analysis of covariance
ARMD
Age-related macular degeneration
ASC
Ambulatory Surgical Center
BLQ
below the limit of quantitation
bpm
beats per minute
CFR
Code of Federal Regulations
CI
confidence interval
DMEK
Descemet’s Membrane Endothelial Keratoplasty
DSEK
Descemet’s Stripping Endothelial Keratoplasty
eCRF
electronic case report form
EU
European Union
FDA
Food and Drug Administration
GCP
Good Clinical Practice
GLP
Good Laboratory Practice
H
hour
HIPAA
Health Insurance Portability and Accountability Act
IB
Investigator’s Brochure
ICH
International Conference on Harmonisation
IEC
independent ethics committee
IOL
intraocular lens 
IOP
intraocular pressure
IRB
institutional review board
ITT
intent-to-treat
LOCF
last observation carried forward
LT
laser trabeculoplasty

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Term/Abbreviation
Definition
MDF
Map-Dot-Fingerprint
MedDRA
Medical Dictionary for Regulatory Activities
MI
Multiple imputation
MMRM
mixed effect model for repeated measures
NSAID
nonsteroidal anti-inflammatory drug
OAG
open-angle glaucoma
OHT
ocular hypertension
OU
both eyes
PAS
peripheral anterior synechiae
PLA
polylactic acid
PLGA
polylactic-co-glycolic acid
POAG
primary open-angle glaucoma
PP
per protocol
RBC
red blood cell
SC/T
patients with sickle cell disease or trait or other 
hemoglobinopathies
SLT
selective laser trabeculoplasty
SOC
system organ class
SOP
standard operating procedures
SR
sustained release
US
United States
WBC
white blood cell
WOCF
worst (postrandomization) observation carried forward
X 
perform procedure