Clinical trial NCT03450629
Conditions: Open Angle Glaucoma Ocular Hypertension
Sponsor: Sun Pharma Advanced Research Company Limited
Start date: 2018-09-13; Completion date: 2020-12-01
Enrollment: 682 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The study will be conducted to evaluate the efficacy and safety of topical administration of PDP-716 compared with brimonidine tartrate ophthalmic solution.

Detailed description:

Arms: arm 1: None arm 2: None
Interventions: intervention 1: Brimonidine Tartrate Ophthalmic Suspension intervention 2: Brimonidine Tartrate Ophthalmic Solution
Intervention descriptions: intervention 1: PDP-716 intervention 2: Three Times Brimonidine Tartrate Ophthalmic Solution

Protocol documents:
Prot_000.pdf: 
IND# 123560 
 Brimonidine Tartrate Ophthalmic Suspension 0.35%  
Protocol No.: CLR_16_33                                                        
Amendment 03 
Sun Pharma Advanced Research Company Ltd.                         Confidential 
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Clinical Trial Protocol: CLR_16_33 
BRIMONIDINE TARTRATE OPHTHALMIC SUSPENSION   
 
Protocol Title: 
A Randomized, Multi-Center, Investigator-Masked, Parallel Group, 
Equivalence Study of Once Daily Brimonidine Tartrate Ophthalmic 
Suspension Compared with Three Times Daily Alphagan® P in Subjects 
with Open Angle Glaucoma or Ocular Hypertension. 
 
                                             
Protocol Number: 
CLR_16_33 
Study Phase: 
3  
Investigational 
Product Name: 
Brimonidine tartrate 0.35% ophthalmic suspension 
Indication: 
Reduction  in elevated intraocular pressure (IOP) in  subjects with open 
angle glaucoma or ocular hypertension 
Version/ 
amendment/Date 
Amendment  03,  20Sep  2018 
Previous Version/ 
amendment date: 
 Amendment 02,  08 Aug 2018 
Sponsor: 
Sun Pharma Advanced Research Company, Ltd. (SPARC) 
17 B Mahal Industrial Estate, 
Mahakali Caves Rd Andheri (E), 
Mumbai - 400 093 
India 
 
 
 
Confidentiality Statement 
This protocol contains confidential, proprietary information of Sun Pharma Advanced Research 
Company Ltd.  Further dissemination, distribution or copying of this protocol or its contents is 
strictly prohibited. 
 
 


IND# 123560 
 Brimonidine Tartrate Ophthalmic Suspension 0.35%  
Protocol No.: CLR_16_33                                                        
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 SPONSOR APPROVAL SIGNATURE 
 
 
 
 
 
 
 
 
 
 


IND# 123560 
 Brimonidine Tartrate Ophthalmic Suspension 0.35%  
Protocol No.: CLR_16_33                                                        
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SPONSOR’S CONTACT INFORMATION 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 


IND# 123560 
  Brimonidine Tartrate Ophthalmic Suspension 0.35%  
Protocol No.: CLR_16_33                                                                                 
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IND# 123560 
  Brimonidine Tartrate Ophthalmic Suspension 0.35%  
Protocol No.: CLR_16_33                                                                                 
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IND# 123560 
 Brimonidine Tartrate Ophthalmic Suspension 0.35%  
Protocol No.: CLR_16_33                                                       
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1.0 
TRIAL SYNOPSIS  
Title of the Study  
A Randomized, Multi-Center, Investigator-Masked, Parallel Group, 
Equivalence Study of Once Daily Brimonidine Tartrate Ophthalmic 
Suspension Compared with Three Times Daily Alphagan® P in Subjects 
with Open Angle Glaucoma or Ocular Hypertension. 
Protocol Number  
CLR_16_33 
Investigational 
Product  
Brimonidine tartrate 0.35% ophthalmic suspension 
Sponsor  
Sun Pharma Advanced Research Company (SPARC) Limited 
Trial Phase  
3 
Clinical Indication  
Open-angle glaucoma or ocular hypertension. 
Trail Design 
Multi-center, investigator-masked,  parallel group, stratified 
randomization 
Controls  
Brimonidine 0.1% ophthalmic solution  
(Alphagan P® 0.1%) 
Objectives:   
 
 
 
Primary Objectives:   
To evaluate the efficacy of once daily (QD) dosing of brimonidine 
tartrate ophthalmic suspension 0.35% compared with Alphagan® P 0.1% 
dosed 3 times a day (TID) in subjects with open-angle glaucoma or 
ocular hypertension. 
Secondary Objectives:   
To evaluate the safety of once daily (QD) dosing of brimonidine tartrate 
ophthalmic suspension 0.35% compared with Alphagan® -P, 0.1% dosed 
3 times a day (TID) in subjects with open-angle glaucoma or ocular 
hypertension. 
Study Population 
Characteristics 
Subjects 18 years age or older with open-angle glaucoma or ocular 
hypertension 
Number of Subjects Approximately 666 (333 per treatment arm); subjects will complete 12 


IND# 123560 
 Brimonidine Tartrate Ophthalmic Suspension 0.35%  
Protocol No.: CLR_16_33                                                       
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weeks of treatment. 
Route of 
Administration  
Topical ophthalmic instillation  
Dosage/Dose 
Regimen/ 
Instillation/Applica
tion/Use 
Subjects will receive one drop of either: 
• Brimonidine tartrate 0.35% ophthalmic suspension (SPARC) at 8:00 
AM ± 30 minutes 
 
• Brimonidine tartrate 0.1% ophthalmic solution (Alphagan® P 0.1%) 
at 8:00 AM ± 30 minutes, 2:00 PM ± 30 minutes, 8:00 PM ± 30 
minutes  
Duration of 
Participation in the 
Trial  
Efficacy and Safety: Up to 5 visits over 12 weeks 
Summary of Visit 
Schedule 
Visit 1: (Day -42 to Day -1): Screening 
Visit 2:  (Day 0): Baseline/Randomization 
Visit 3: (Week 2 ± 2 Days): Efficacy/Safety Evaluation 
Visit 4: (Week 6 ± 2 Days): Efficacy/Safety Evaluation 
Visit 5: (Week 12 ± 2 Days): Efficacy/Safety Evaluation and study exit 
Measures Taken to 
Reduce Bias  
Subjects will be randomized to treatment sequences in visit 2 to avoid 
bias in the assignment of subjects to treatment, to increase the likelihood 
that known and unknown subject attributes (eg, demographics and 
baseline characteristics) are evenly balanced across treatment groups, and 
to enhance the validity of statistical comparisons across treatment groups. 
Investigator-masked treatment will be used to reduce the potential of bias 
during data collection and evaluation of clinical endpoints. 
Eligibility Criteria 
           
 
 
 
 
 
 
Inclusion Criteria: 
Subjects MUST: 
1. Be male or female, of 18 years of age or older  
2. Provide signed and dated informed consent in accordance with good 
clinical practice (GCP) and local legislation prior to any study 
procedure. 
3. Have open angle glaucoma, (with or without pseudo exfoliation, 
pigment dispersion component) or ocular hypertension in both eyes 
and likely to be controlled on monotherapy. 
 
 
 


IND# 123560 
 Brimonidine Tartrate Ophthalmic Suspension 0.35%  
Protocol No.: CLR_16_33                                                       
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7. Females of childbearing potential must not be pregnant or lactating 
(as confirmed by a negative urine pregnancy test with a sensitivity of 
less than 50 mIU/mL or equivalent units of human chorionic 
gonadotropin). Women of childbearing potential must agree to the 
use of a reliable method of contraception (e.g., total abstinence, 
intrauterine device, a double-barrier method [such as condom plus 
diaphragm with spermicide], oral, transdermal, injected or implanted 
non- or hormonal contraceptive), throughout the study. A sterile 
sexual partner is not considered an adequate form of birth control. 
Subjects on hormonal contraceptives must have been on the same 
hormonal contraceptive for at least one month before the Screening 
and continue throughout the duration of the study. 
A female is considered of childbearing potential if she has had her 
first menses and she is either: 
a. not postmenopausal for at least 12 
consecutive months prior to enrollment; or 
b.  not surgically sterilized by bilateral tubal ligation, or bilateral 
oophorectomy, or hysterectomy 
c. Male subjects with partners of childbearing potential who are not 
using birth control as described above must use a barrier method 
of contraception (eg. Condom) if not surgically sterile (ie, 
vasectomy). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


IND# 123560 
 Brimonidine Tartrate Ophthalmic Suspension 0.35%  
Protocol No.: CLR_16_33                                                       
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9. Be able and willing to follow study instructions and complete all 
required visits. 
 
 
 
 
Exclusion Criteria:   
 
Subjects MUST NOT: 
1. Have angle closure glaucoma or a history of acute angle closure 
treated with a peripheral iridotomy 
2. Have uncontrolled systemic disease (eg, diabetes) which might 
interfere with the study 
3. Current or history of severe hepatic or renal impairment. Have 
severe cardiovascular disease unless his/her disease is controlled and 
clearance has been obtained  from the treating primary care 
physician or cardiologist 
4. Subjects with depression, cerebral or active coronary insufficiency or 
orthostatic hypotension. 
5. (If female of childbearing potential) Be pregnant, nursing, or 
planning a pregnancy during study entry and through the duration of 
the study. 
6. Have clinically relevant, abnormally low or high blood pressure or 


IND# 123560 
 Brimonidine Tartrate Ophthalmic Suspension 0.35%  
Protocol No.: CLR_16_33                                                       
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pulse rate  
7. 
 
8. Have any known allergy or sensitivity to the study medications or 
their components (brimonidine tartrate, amberlite IRP 69, 
hypromellose, povidone, carbopol, edetate disodium, n-lauroyl 
sarcosine, sodium, tromethamine, benzalkonium chloride, sodium 
carboxymethylcellulose, sodium borate, boric acid, sodium chloride, 
potassium chloride, calcium chloride, magnesium chloride, Purite® - 
preservative). 
 
 
 
 
 
 
11. Require the use of any ocular medications during the study other 
than the study medications; occasional use of artificial tears for mild 
dry eye or lid scrubs for mild blepharitis is allowed. 
 
 
12. Have any contraindications to brimonidine therapy 
13. Have known lack of ocular hypotensive response to alpha adrenergic 
receptor agonist. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 


IND# 123560 
 Brimonidine Tartrate Ophthalmic Suspension 0.35%  
Protocol No.: CLR_16_33                                                       
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. 
 
26. Have a condition or be in a situation which, in the investigator's 
opinion, may put the subject at a significant risk, may confound 
study results, or may interfere significantly with the subject's 
participation in the study. This criterion provides an opportunity 
for the investigator to exclude subject based on clinical judgment, 
even if other eligibility criteria are satisfied. 
Efficacy Measures  
Primary Efficacy Variable(s) 
The time-matched mean IOP (study eye) at each of the 3 time points 
(8:00 AM, 10:00 AM, 4:00 PM) on  
 week 12 
 
 
 
 
 
 
 
 
 
 
 
Safety Measures 
• Adverse events (AEs) 
 
 
 
 
 
 
 
 
 
 


IND# 123560 
 Brimonidine Tartrate Ophthalmic Suspension 0.35%  
Protocol No.: CLR_16_33                                                       
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Statistical methods 
and Analyses  
General Considerations:   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Efficacy Analyses:  
 
 
 


IND# 123560 
 Brimonidine Tartrate Ophthalmic Suspension 0.35%  
Protocol No.: CLR_16_33                                                       
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Summary of 
Known and 
Potential Risks and 
 
 


IND# 123560 
 Brimonidine Tartrate Ophthalmic Suspension 0.35%  
Protocol No.: CLR_16_33                                                       
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Benefits to Human 
Subjects 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 


IND# 123560 
 Brimonidine Tartrate Ophthalmic Suspension 0.35%  
Protocol No.: CLR_16_33                                                       
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IND# 123560 
 Brimonidine Tartrate Ophthalmic Suspension 0.35%  
Protocol No.: CLR_16_33                                                       
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IND# 123560 
 Brimonidine Tartrate Ophthalmic Suspension 0.35%  
Protocol No.: CLR_16_33                                                       
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IND# 123560 
 Brimonidine Tartrate Ophthalmic Suspension 0.35%  
Protocol No.: CLR_16_33                                                       
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IND# 123560 
 Brimonidine Tartrate Ophthalmic Suspension 0.35%  
Protocol No.: CLR_16_33                                                       
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IND# 123560 
 Brimonidine Tartrate Ophthalmic Suspension 0.35%  
Protocol No.: CLR_16_33                                                       
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IND# 123560 
 Brimonidine Tartrate Ophthalmic Suspension 0.35%  
Protocol No.: CLR_16_33                                                       
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LIST OF ABBREVIATIONS 
 
AE 
Adverse Event 
BSCVA 
Best-Spectacle Corrected Visual Acuity 
CI 
Confidence Interval 
CRO 
Contract research organization 
eCRF 
Electronic Case Report Form 
ETDRS 
Early Treatment Diabetic  Retinopathy Study 
FDA 
Food and Drug Administration 
GCP 
Good clinical practice  
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization of technical 
requirements for pharmaceuticals for human use 
IEC 
Independent Ethics Committee 
IMP  
Investigational medicinal product  
IOP 
Intraocular Pressure 
IP 
Investigational Product 
IRB 
Institutional Review Board 
ITT 
Intent-To-Treat 
LOCF 
Last Observation Carried Forward 
logMAR 
logarithm of the Minimum Angle of Resolution 
MAO 
Monamine Oxidase Inhibitor 
MedDRA 
Medical Dictionary of Regulatory Affairs 
MMRM 
Mixed Model Of Repeated Measures 
NCT 
Non contact tonometer 
OPD 
(in-)office physician dispensing 
OU 
Both eyes 
POC 
Proof-of-concept 
PP 
Per Protocol 
PT 
Preferred Term 
QD 
(Quaque Die) once daily 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SOC 
system organ class 


IND# 123560 
 Brimonidine Tartrate Ophthalmic Suspension 0.35%  
Protocol No.: CLR_16_33                                                       
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SPARC 
Sun Pharma Advanced Research Company, Ltd. 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
TOST 
Two one-sided tests 
TEAE 
Treatment-Emergent Adverse Event 
TID 
Three Times Daily 
 
 


IND# 123560 
 Brimonidine Tartrate Ophthalmic Suspension 0.35%  
Protocol No.: CLR_16_33                                                       
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2.0 
BACKGROUND INFORMATION  
Glaucoma is collection of disorders characterized by a slow and progressive degeneration of 
retinal ganglion cells and their axons, resulting in a distinct appearance of the optic disc and a 
concomitant pattern of visual field loss
 In 2010, 60.5 million people were estimated to be 
suffering from glaucoma worldwide, with a predicted increase to 79.6 million by 2020 
 It is a 
leading cause of blindness in the United States, affecting 1%-2% of individuals aged 60 and over 
   
There are several recognized risk factors of glaucoma including an increased intraocular pressure 
(IOP), aging, family history, high myopia, systemic hypertension, cardiovascular disease, 
migraine headaches, peripheral vasospasm and prior nerve damage 
Elevated IOP is the 
only proven treatable risk factor in multiple forms of glaucoma
  Increased IOP of greater 
than 21 mm Hg has traditionally been suspected to cause glaucoma 
the higher the IOP, the 
greater the likelihood of optic nerve damage and visual field loss. With IOP > 30 mmHg, the 
potential risk for vision loss is 40 times greater compared to an IOP of 15 mm Hg
  As IOP 
has been shown in several large-scale National Eye Institute-sponsored studies to be a major 
factor in the pathogenesis of the progression of glaucoma, pharmacologic reduction of IOP is 
today the mainstay of treatment for this condition 
  
Brimonidine is a highly selective and potent alpha2-adrenergic-receptor agonist that effectively 
lowers IOP and is useful as a monotherapy, adjunctive therapy, and replacement therapy in 
glaucoma and ocular hypertension. Brimonidine functions by dual mechanism, reducing inflow 
of aqueous humor production and increasing uveoscleral outflow. It has a greater selectivity for 
α2-ARs and lower lipid solubility than the first-generation compounds of this class, clonidine 
and apraclonidine.  After topical administration, brimonidine readily penetrates the cornea and 
results in reduction of IOP within one hour. Its peak effect is achieved within two hours post-
dosing and the trough effect occurs approximately 10 to 14 hours after administration 
  
Brimonidine tartrate is marketed and approved for use in the US only in topical ophthalmic 
formulations in concentrations between 0.1-0.2% (Alphagan, Alphagan® P, Combigan, and 
generic forms) and currently the only indication is for ocular hypertension and elevated IOP 
associated with open-angle glaucoma. Its pharmacology and toxicology profiles have been 
extensively characterized in previous US submissions. Due to its short half-life, brimonidine is 
dosed three times daily (TID) in the US. 
Brimonidine has been shown to be safe and well-tolerated ocularly and systemically in 
concentrations up to 0.5% when dosed twice daily for up to 1 month for IOP-lowering in 
glaucoma patients 
  The most common side effects included dry mouth, fatigue, blurring, 
burning, and stinging with frequency tending to be dose-dependent. 
Known barriers to compliance in glaucoma patients include adverse effects, multiple dosing, 
forgetfulness, age, physical disability, and complex multidrug regimens 
  Noncompliance 
with topical therapy has been identified as a critical factor associated with the development of 


IND# 123560 
 Brimonidine Tartrate Ophthalmic Suspension 0.35%  
Protocol No.: CLR_16_33                                                       
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blindness in glaucoma 
Studies on individual adherence with brimonidine tartrate 
ophthalmic solution for treatment of glaucoma have shown that adherence of patients was highly 
variable and pharmacologically insufficient for more than two third of the patients included in 
the study when patients were asked to take brimonidine eye drops twice daily and TID 
 
Due to the dose-intensive schedule, patient adherence to brimonidine therapy is low suggesting 
that there is a need for a longer acting drug or longer acting formulation to reduce dosing 
frequency. 
Sun Pharma Advanced Research Company Ltd. (SPARC; Sponsor) has developed a once daily 
(QD) long-acting ophthalmic product consisting of 0.35% brimonidine tartrate suspension in a 
nano-bound resin.  This product allows for the sustained release and activity of brimonidine over 
an extended period of time for the treatment of elevated IOP. This nano-size ion exchange resin 
technology is already in the marketed hypotensive ophthalmic suspension, Betoptic S® 
 
While lower concentrations of brimonidine are available (0.1, 0.15%, Alphagan® P, Allergan) for 
the treatment of glaucoma, the Sponsor’s drug-resin complex suspension product is expected 
provide a slow, consistent, and sustained release likely reducing the immediate exposure to drug.   
This feature has the potential for an improved safety profile over the higher concentrations of 
marketed drug and allowing for a reduced medication burden from TID to QD. 
 
 
 
 
    
 
 
 
 
 
 
 
 
  
  
  
 
 
 


IND# 123560 
 Brimonidine Tartrate Ophthalmic Suspension 0.35%  
Protocol No.: CLR_16_33                                                       
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allergic conjunctivitis, conjunctival hyperemia, and eye pruritus. Adverse reactions occurring in 
 
 
 
 
 
 
 
 
 
 
 
 
 


IND# 123560 
 Brimonidine Tartrate Ophthalmic Suspension 0.35%  
Protocol No.: CLR_16_33                                                       
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2.5 
Compliance Statement for Study Conduct in Accordance with Protocol, Good 
Clinical Practice and Applicable Regulatory Requirements 
The study protocol, amendments to the protocol (if applicable), Investigator’s brochure, subject 
recruitment procedures (e.g. advertisements) and the subject’s information and informed consent 
form as well as consent form updates (if applicable) will be submitted to the Institutional review 
board (IRB)/Independent ethics committee (IEC), which is constituted according to local law to 
obtain approval before initiation of the study and as applicable thereafter. 


IND# 123560 
 Brimonidine Tartrate Ophthalmic Suspension 0.35%  
Protocol No.: CLR_16_33                                                       
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The study will only be initiated after receipt of the approval from the IRB/IEC. The investigator 
will report promptly to the IRB/IEC new information that may adversely affect the safety of the 
subjects or the conduct of the study.  
The investigator will carry out the protocol in conformity with Good Clinical Practice (GCP) 
described in Guideline E6 of the ICH and applicable regulatory requirements. Before admission 
into the study, the written informed consent form must be personally signed and dated by the 
subject and by the investigator or designee who conducted the informed consent discussion.  
In obtaining and documenting informed consents, the investigator must comply with the 
applicable regulatory requirement(s), and must adhere to GCP. The investigator must inform the 
subject of all pertinent aspects of the study including the written information approved/favorably 
assessed by the IRB. 
3.0 
STUDY OBJECTIVES  
This study is designed to obtain estimates on the mean IOP at each of the 3 time points (8:00 
AM, 10:00 AM, 4:00 PM) on week 2, week 6 and week 12 in order to compare brimonidine 
tartrate 0.35% ophthalmic suspension, dosed QD at 8:00 AM and brimonidine tartrate 0.1%, 
dosed TID at approximately 8:00 AM, 2:00 PM, and 8:00 PM. 
The primary objective is to evaluate the efficacy of QD dosing with SPARC’s brimonidine 
tartrate ophthalmic suspension 0.35% compared with brimonidine tartrate ophthalmic solution 
0.1% dosed TID in subjects with open-angle glaucoma, or ocular hypertension. 
The secondary objective is to evaluate the safety of QD dosing with SPARC’s brimonidine 
tartrate ophthalmic suspension 0.35% compared with brimonidine tartrate ophthalmic solution 
0.1% dosed TID in subjects with open-angle glaucoma, or ocular hypertension. 
4.0 
STUDY DESIGN  
This is a multicenter, investigator-masked, randomized, parallel group, equivalence study. 
Treatment period will consist of QD and TID dosing for 12 weeks.  
Subjects who are chronically treated with ocular hypotensive medications are required to 
undergo appropriate washout periods prior to study entry to minimize any residual effects of 
other active ocular hypotensive medications.  
 
 
 


IND# 123560 
 Brimonidine Tartrate Ophthalmic Suspension 0.35%  
Protocol No.: CLR_16_33                                                       
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4.2 
Measures taken to avoid bias 
4.2.1 
Subject number 
At the screening visit after signing the informed consent form (ICF) form each subject will be 
allotted a subject number. The subject number will uniquely identify each subject in the study. 
The subject number will appear on all study documents relating to that subject. Subject 
numbering will be described separately in data management plan. 
4.2.2 
Randomization 
Subjects who qualify inclusion and exclusion criteria will be randomly assigned to study 
treatment using 
  
 
4.2.3 
Masking 
This is an evaluator-masked study. The investigator or designated evaluator, masked to treatment 
assignment, will perform all ophthalmic examinations. Unmasked study coordinator may 
perform all study procedures other than ophthalmic/clinical examination, or treatment of the 
subjects. The investigator (if different from the evaluator) will  be responsible for deciding the 
type of medical care a subject will get; identifying the kinds of work a subject can safely perform 
while in the study, and assessment of safety . In order to maintain masking, the unmasked study 


IND# 123560 
 Brimonidine Tartrate Ophthalmic Suspension 0.35%  
Protocol No.: CLR_16_33                                                       
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coordinator will dispense IP on visit 2,  3,and 4 in a room separate from the evaluating 
investigator and the subjects will be asked not to discuss the treatment received with the 
investigator or designated evaluator in order to maintain investigator/evaluator-masking. 
To minimize bias, Test and Reference bottles will be packed in an identical box with similar 
label. 
An unmasked site personnel will instill the in-office physician dispensing (OPD) doses in a room 
separate from the evaluating investigator in order to maintain investigator-masking. As a means 
to maintain investigator masking, subjects in the SPARC 0.35% treatment group will be brought 
into the dosing room at each dosing time point (ie, 8:00 AM and 2:00 PM but will only receive 
study medication at the 8:00 AM time point). 
In order to maintain masking, the Investigator will not personally retrieve/review the study 
medication diary; designated study personnel will collect and review the diary at each visit to 
ensure treatment compliance. 
Subjects will be instructed not to use the study medication on the morning of a study visit; 
 
 
   
 
 
 
 
 
 
5.0 
STUDY POPULATION 
5.1 
Number of Subjects (approximate) 
Efficacy and Safety: Approximately 666 subjects will be enrolled.  
5.2 
Inclusion Criteria 
Each subject must: 
1. Be male or female, of  18 years of age or older 
2. Provide signed and dated informed consent in accordance with GCP and local legislation 
prior to any study procedure. 


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 Brimonidine Tartrate Ophthalmic Suspension 0.35%  
Protocol No.: CLR_16_33                                                       
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3. Have open angle glaucoma, (with or without pseudo exfoliation, pigment dispersion 
component) or ocular hypertension in both eyes and likely to be controlled on 
monotherapy  
 
 
 
  
 
7. Females of childbearing potential must not be pregnant or lactating (as confirmed by a 
negative urine pregnancy test with a sensitivity of less than 50 mIU/mL or equivalent 
units of human chorionic gonadotropin). Women of childbearing potential must agree to 
the use of a reliable method of contraception (e.g., total abstinence, intrauterine device, a 
double-barrier method [such as condom plus diaphragm with spermicide], oral, 
transdermal, injected or implanted non- or hormonal contraceptive), throughout the study. 
A sterile sexual partner is not considered an adequate form of birth control. Subjects on 
hormonal contraceptives must have been on the same hormonal contraceptive for at least 
one month before the Screening and continue throughout the duration of the study. A 
female is considered of childbearing potential if she has had her first menses and she is 
either: not postmenopausal for at least 12 consecutive months prior to enrollment; or not 
surgically sterilized by bilateral tubal ligation, or bilateral oophorectomy, or 
hysterectomy.  Male subjects with female partners of childbearing potential who are not 
using birth control as described above must use a barrier method of contraception (eg, 
condom) if not surgically sterile (ie, vasectomy). 
 
 
 
 
 
 
 
 
 
 
 
 


IND# 123560 
 Brimonidine Tartrate Ophthalmic Suspension 0.35%  
Protocol No.: CLR_16_33                                                       
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 visits. 
 
 
 
 
5.3 
Exclusion Criteria  
Each subject must not: 
1. Have angle closure glaucoma or a history of acute angle closure treated with a peripheral 
iridotomy 
2. Have uncontrolled systemic disease (eg, diabetes) which might interfere with the study 
3. Current or history of severe hepatic or renal impairment. Have severe cardiovascular 
disease unless his/her disease is controlled and clearance has been obtained  from the 
treating primary care physician or cardiologist 
4. Subjects with depression, cerebral or active coronary insufficiency or orthostatic 
hypotension.  
5. (If female of childbearing potential) Be pregnant, nursing, or planning a pregnancy 
during study entry and through the duration of the study. 
6. Have clinically relevant, abnormally low or high blood pressure or pulse rate  
7. 
 
 
 
 


IND# 123560 
 Brimonidine Tartrate Ophthalmic Suspension 0.35%  
Protocol No.: CLR_16_33                                                       
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11. Require the use of any ocular medications during the study other than the study 
medications; occasional use of artificial tears for mild dry eye or lid scrubs for mild 
blepharitis is allowed. 
 
 
12. Have any contraindications to brimonidine therapy 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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26. Have a condition or be in a situation which, in the investigator's opinion, may put the 
subject at a significant risk, may confound study results, or may interfere significantly 
with the subject's participation in the study. This criterion provides an opportunity for 
the investigator to exclude subject based on clinical judgment, even if other eligibility 
criteria are satisfied. 
 
 
  
 
 
 
 
 
 
 
 
 
 
5.5 
Study Termination 
The study may be stopped at any time by the Sponsor, investigator and/or IEC with   appropriate 
notification. 
 If the study is prematurely terminated or suspended for any reason, the investigator/institution 
should promptly inform the subjects, should assure appropriate therapy and follow-up for the 
subjects, and, where required by the applicable regulatory requirement(s), should inform the 
regulatory authority(ies).  Additionally: 
1. If the investigator terminates or suspends the study without prior agreement of the 
sponsor, the investigator should inform the institution (where the study is conducted) 
where applicable, and the investigator/institution should promptly inform the sponsor and 
the EC, and should provide the sponsor and the IEC a detailed written explanation of the 
termination or suspension. 
2. The sponsor may discontinue entire study at any time, for ethical or scientific or business 
reasons. If the sponsor terminates or suspends a study, the investigator should promptly 
inform the institution where applicable and the investigator/institution should promptly 
inform the IEC and provide the IEC a detailed written explanation of the termination or 
suspension. 
3.  If the IEC terminates or suspends its approval/favorable opinion of a study, the 
investigator should inform the institution where applicable and the investigator/institution 
should promptly notify the sponsor and provide the sponsor with a detailed written 
explanation of the termination or suspension. 
 


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6.0 
STUDY PARAMETERS 
6.1 
Efficacy Measures  
6.1.1 
Primary Efficacy Variable(s) 
The time-matched mean IOP (study eye) at each of the 3 time points (8:00 AM, 10:00 AM, 4:00 
PM) on week 2, week 6 and week 12. 
 
 
 
 
 
 
 
 
 
 
 
 
6.2 
Safety Measures 
• AEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
7.0 
STUDY MATERIALS 
7.1 
Study Treatment(s) 
7.1.1 Study Treatments  
• Brimonidine tartrate 0.35% ophthalmic suspension (SPARC), QD 
• Brimonidine tartrate 0.1% ophthalmic solution (Alphagan P® 0.1%), TID 
 
 
 
 
 
 


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7.1.4 
Accountability and Retention of Investigational Product 
The investigational product is to only be used in accordance with this protocol.  The IP must only 
be distributed to subjects properly qualified under this protocol to receive IP. 
 
 
  


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8.0 
STUDY METHODS AND PROCEDURES 
8.1 
Subject Entry Procedures 
8.1.1 
Overview 
Subjects as defined by the criteria in Sections 5.1, 5.2 and 5.3 will be considered for entry into 
this study. 
8.1.2 
Informed Consent 
Prior to a subject’s participation in the study (i.e, changes in a subject’s medical treatment and/or 
study related procedures), the study will be discussed with each subject, and subjects wishing to 
participate must give written informed consent using an ICF forms.  The ICF form must be the 
most recent version that has received approval/favorable review by a properly constituted 
Institutional Review Board. 
 
 
 
 
 
  
 
  
  
 
 
  
 
 
 
 
 
 
 
 
 


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Protocol No.: CLR_16_33                                                       
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Protocol No.: CLR_16_33                                                       
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Protocol No.: CLR_16_33                                                       
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Protocol No.: CLR_16_33                                                       
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• In-OPD study medication instillation at 2:00 PM ± 30 minutes 
 
   
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 


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8.6 
Compliance with Protocol 
Subjects who are inappropriately enrolled will be discontinued from the study. 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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8.7 
Study Duration 
Study will comprise 5visits.  
     
                    Visit 1: (Day-42 to Day -1): Screening   
                 Visit 2: (Day 0) Baseline/Randomization 
                 Visit 3: (week 2 ± 2 Days) Efficacy/Safety Evaluation 
                 Visit 4: (Week 6 ± 2 Days) Efficacy/Safety Evaluation 
                 Visit 5: (Week 12 ± 2 Days) Efficacy/Safety Evaluation and study exit 
                     
8.8 
Monitoring and Quality Assurance 
During the course of the study CRO monitor, or designee, will make routine site visits to review 
protocol compliance, assess study drug accountability, and ensure the study is being conducted 
according to the pertinent regulatory requirements.  The review of the subjects’ medical records 
will be performed in a manner that adequately maintains subject confidentiality.  Further details 
of the study monitoring will be outlined in a monitoring plan. 
Regulatory authorities of domestic and foreign agencies, quality assurance and or its designees 
may carry out on-site inspections and/or audits which may include source data checks.  
Therefore direct access to the original source data will be required for inspections and/or audits.  
All inspections and audits will be carried out giving consideration to data protection as well as 
subject confidentiality to the extent that local, state, and federal laws apply. 
 
9.0 
SAFETY REPORTING  
9.1 
Reporting Adverse Events 
Any AE (clinical sign, symptom, or disease) temporally associated with the use of this 
investigational product, whether or not considered related to the investigational product, shall be 
reported and documented on the CRF. All AEs reported by the subject or observed by the 
Principal Investigator will be individually listed. All entries should contain an event term, date of 
onset, date of resolution, severity, action taken, outcome, relationship to study drug, and a 
seriousness assessment. The investigator will document all AEs in the subject’s source 
document. All AEs occurring during the study, including during the washout interval, will be 
reported and documented on the CRF. 
9.1.1 
Definitions 
Adverse Event – Any untoward medical occurrence in a clinical investigation subject 
administered a drug and does not necessarily have a causal relationship with this treatment. An 
AE can therefore, be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of an investigational product, 
whether or not related to the investigational product. 


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Serious Adverse Event (SAE) – Any experience that is fatal or life-threatening, requires or 
prolongs inpatient hospitalization, results in persistent or significant disability/ incapacity, is a 
congenital anomaly or birth defect or an important medical event or requires medical 
intervention.  
 
 
 
 
If death occurs, the primary cause of death or event leading to death should be recorded and 
reported as an SAE. “Fatal” will be recorded as the outcome of this specific event and death will 
not be recorded as separate event. Only, if no cause of death can be reported (eg, sudden death, 
unexplained death), the death per se might then be reported as an SAE. 
NOTE: The term "life-threatening" in the definition of "serious" refers to an event in which the 
subject was at risk of death at the time of the event; it does not refer to an event, which, 
hypothetically, might have caused death if it were more severe. 
A planned hospitalization for pre-existing condition, or a procedure required per protocol 
without a serious deterioration in health or clearly not associated with an AE is not to be 
considered as an AE. 
 
 
 
 
 
 
 
 
Additionally, the Principal Investigator will evaluate all AEs as follows: 
Seriousness: whether or not the AE is fatal or life threatening, persistent or permanently 
disabling, requires or prolongs inpatient hospitalization, is a congenital anomaly or an important 
medical event. 
Action taken:. Action taken is categorized as “none”, “study drug discontinued/withdrawn”, 
“study drug discontinued and restarted”, “required concomitant medication”, “required 
procedure”, or “other”. 
Event Outcome : Event outcome , or time last follow-up is recorded is categorized as “Fatal”, 
“Resolved”, “Resolved with sequelae”, “Resolving”, “Not Resolved”, “Unknown”. 
Intensity, to be graded as: 


IND# 123560 
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Protocol No.: CLR_16_33                                                       
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IND# 123560 
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Protocol No.: CLR_16_33                                                       
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Definition of the adverse event reporting period 
The AE/ SAE reporting period for safety surveillance begins when the subject sign’s ICF 
continues till end of study or early termination visit. 
Events that Do Not Meet the Definition of an SAE 
Elective hospitalizations to administer, or to simplify trial treatment or trial procedures are not 
considered SAEs. However, all events leading to unplanned hospitalizations or unplanned 
prolongation of an elective hospitalization (e.g., undesirable effects of any administered 
treatment) must be documented and reported as SAEs. 
 
 
 
 
9.2 
Procedures for Reporting Serious Adverse Events (SAE) and Suspected Unexpected 
Serious Adverse Reaction (SUSAR) 
Serious Adverse Events 
All SAEs must be reported according to ICH GCP or local regulations, applying the regulation 
with the stricter requirements. The report will contain as much available information concerning 
the SAE to enable the Sponsor’s safety physician/ CRO to file a report, which satisfies regulatory 
reporting requirements. The SAE report will be notified by Investigator within 24-hours of his/ 
her awareness to the Sponsor’s safety physician/CRO. These timelines apply to initial reports of 
SAEs and to all follow-up reports. 
All AEs/SAEs will be recorded on the AE Report Form and SAE report form in the eCRF and 
source documents.  
 
 
 
 
 
 
 
 
 
In the case of fatal or life-threatening events, please immediately telephone the Sponsor’s safety 
physician/CRO also. 


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Protocol No.: CLR_16_33                                                       
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Additional follow-up information should be completed on an SAE follow-up form with a copy 
sent to the Sponsor’s safety physician/CRO. 
 
 
 
 
 
 
 
 
 
 
 
 
Requests for follow-up will usually be made via the responsible Sponsor’s safety 
physician/CRO. 
 
Suspected Unexpected Serious Adverse Reactions (SUSARs):  
The applicable Regulatory Authorities shall be initially notified by Sponsor Safety Physician/ 
CRO of any SUSAR, no later than 15 calendar days from the “date learned” of the event. The 
applicable Regulatory Authorities will be initially notified as per regulation within 7 calendar 
days of any fatal or life-threatening SUSAR. If the safety report submitted within 7 calendar days 
is complete, an additional submission within 15 days from day 0 is not required.  
All participating Investigators and Ethics committee/ Institutional Review Board shall be notified 
of any SUSAR by CRO as per local regulatory requirement. 
 
 
 
 
 
 
  
 
 


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9.3 
Procedures for Unmasking (if applicable) 
When medically necessary, the investigator may need to determine what treatment has been 
assigned to a subject. Site will contact the designated personnel in SPARC or CRO in case the 
treatment code needs to be unmasked. When possible (ie, in non-emergent situations), CRO 
and/or the study sponsor should be notified before unmasking investigational product.      
Unmasking details will be provided to Sponsor’s designated safety physician in case of SUSAR 
for regulatory reporting purpose only.  
The code for all subjects will be broken when all subjects have completed the study, and all data 
for this period has been entered into the database and locked. 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
9.5 
Pregnancy 
A pregnancy test will be performed at screening and at visits specified in the protocol. Females 
of childbearing potential must not be pregnant or lactating (as confirmed by a negative urine 
pregnancy test with a sensitivity of less than 50 mIU/mL or equivalent units of human chorionic 
gonadotropin). Females of childbearing potential must agree to the use of a reliable method of 
contraception as described in Inclusion Criteria of this protocol and throughout the study. 
Subjects with a positive test at screening or during the study period will be excluded from study.  
Similarly, male subjects enrolled to the study will be instructed not father a child and avoid 
passage of semen to their partner by using an acceptable contraceptive method as discussed by 
the investigator during the enrollment to the study. However, if a female subject becomes 
pregnant during the study, the pregnancy will be recorded as a significant medical event and 
reported per SAE reporting procedure and the subject will be withdrawn from the study 
immediately. Similarly, if a female partner of a male subject becomes pregnant during the study, 
the medical event will be recorded appropriately. The ‘pregnancy reporting form’ will be 


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Protocol No.: CLR_16_33                                                       
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completed and submitted to Sponsor. The pregnancy shall be followed every three months till its 
outcome and up to one month post-delivery to assess the functional status of the child. If any 
SAE occurs during pregnancy than it will be reported using SAE forms as per timelines defined 
in section above. 
Any congenital abnormalities or birth defects in newborn will be followed three months post-
delivery. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
  
 
 
 
 
 
 
 
 
 
.  


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10.3 
Efficacy Variables 
The primary efficacy variable is: 
The time-matched mean IOP (study eye) at each of the 3 time points (8:00 AM, 10:00 AM, 4:00 
PM) on
 week 12.  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
10.4 
Safety Variables 
The safety variables are: 
• AEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 


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Protocol No.: CLR_16_33                                                       
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Protocol No.: CLR_16_33                                                       
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Protocol No.: CLR_16_33                                                       
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Protocol No.: CLR_16_33                                                       
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11.0 
COMPLIANCE WITH GOOD CLINICAL PRACTICES, ETHICAL 
CONSIDERATIONS, AND ADMINISTRATIVE ISSUES 
This study will be conducted in compliance with the protocol, current Good Clinical Practices, 
including the International Conference on Harmonization (ICH) Guidelines, and in general, 
consistent with the Declaration of Helsinki.  In addition, all applicable local, state, and federal 
requirements relevant to the use of IPs in the countries involved will be adhered to. 
11.1 
Protection of Human Subjects 
11.1.1 
Subject Informed Consent 
Informed consent must take place before any study specific procedures are initiated.  Signed and 
dated written informed consent  must be obtained from each subject prior to enrollment into the 
study.  If the subject is under the legal age of consent, the consent form must be signed by a legal 
guardian or as required by state and/or local laws and regulations. 
All informed consent forms must be approved for use by the sponsor and receive 
approval/favorable opinion from an IRB/IEC prior to their use.  If the consent form requires 
revision (eg, due to a protocol amendment or significant new safety information), it is the 
investigator’s responsibility to ensure that the amended informed consent is reviewed and 
approved by CRO prior to submission to the governing IRB/IEC and that it is read, signed and 


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Protocol No.: CLR_16_33                                                       
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dated by all subjects subsequently enrolled in the study as well as those currently enrolled in the 
study. 
If informed consent is taken under special circumstances (oral informed consent), then the 
procedures to be followed must be determined by CRO and/or study sponsor and provided in 
writing by CRO and/or study sponsor prior to the consent process. 
11.1.2 
Institutional Review Board Approval 
This study is to be conducted in accordance with Institutional Review Board regulations. The 
investigator must obtain appropriate IRB approval before initiating the study and re-approval at 
least annually. Only an IRB/ERC approved version of the ICF will be used. 
11.2 
Ethical Conduct of the Study 
This study will be conducted in accordance with the ethical principles that originated with the 
Declaration of Helsinki. 
11.3 
Subject Confidentiality 
All personal study subject data collected and processed for the purposes of this study should be 
maintained by the investigator and his/her staff with adequate precautions as to ensure that the 
confidentiality of the data in accordance with local, state, and federal laws and regulations. 
Monitors, auditors and other authorized representatives of CRO, the sponsor, the IRB/IEC 
approving this study, the Food and Drug Administration (FDA), the Department of Health and 
Human Services, other domestic government agencies, and other foreign regulatory agencies will 
be granted direct access to the study subject’s original medical and study records for verification 
of the data and/or clinical trial procedures.  Access to this information will be permitted to the 
aforementioned individuals to the extent permitted by law. 
A report of the results of this study may be published or sent to the appropriate health authorities 
in any country in which the IP may ultimately be marketed, but the subject’s identity will not be 
disclosed in these documents. 
11.4 
Documentation 
Source documents may include a subject’s medical records, hospital charts, clinic charts, the 
investigator’s study subject files, as well as the results of diagnostic tests.  The investigator’s 
copy of the electronic case report forms (eCRFs) serves as the investigator’s record of a subject’s 
study-related data. 


IND# 123560 
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Protocol No.: CLR_16_33                                                       
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Protocol No.: CLR_16_33                                                       
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Protocol No.: CLR_16_33                                                       
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Protocol No.: CLR_16_33                                                       
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Protocol No.: CLR_16_33                                                       
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Protocol No.: CLR_16_33                                                       
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Protocol No.: CLR_16_33                                                       
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Protocol No.: CLR_16_33                                                       
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ALPHAGAN® P has not been studied in patients with renal impairment. The effect of dialysis on brimonidine 
pharmacokinetics in patients with renal failure is not known. 


 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
  
 
  
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
   
 
 
 


 
 
 
   
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
  
  
 
  
 
 
 
 
 
 


 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 


IND# 123560 
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Protocol No.: CLR_16_33                                                       
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Protocol No.: CLR_16_33                                                       
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Protocol No.: CLR_16_33                                                       
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Protocol No.: CLR_16_33                                                       
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SAP_001.pdf: 
STATISTICAL ANALYSIS PLAN 
 
CLR-16-33 SAP V1 
22APR2021 
Page 1 of 30 
 
 
 
 
 
 
CLINICAL STUDY PROTOCOL 
 
A Randomized, Multi-Center, Investigator-Masked, Parallel Group, Equivalence Study of 
Once Daily Brimonidine Tartrate Ophthalmic Suspension Compared with Three Times Daily 
Alphagan® P in Subjects with Open Angle Glaucoma or Ocular Hypertension.  
 
Protocol No. 
 
: CLR_16_33 V1 Amendment 3 20Sep2018 
Plan Version No. 
: 1 
 
Plan Version Date 
: 22APR2021 
 


STATISTICAL ANALYSIS PLAN
CLR-16-33 SAP V1
22APR2021
Page 2 of 30


STATISTICAL ANALYSIS PLAN 
 
CLR-16-33 SAP V1 
22APR2021 
Page 3 of 30 
 
STATISTICAL ANALYSIS PLAN DETAILS 
 
TRIAL FULL TITLE 
A Randomized, Multi-Center, Investigator-Masked, Parallel 
Group, Equivalence Study of Once Daily Brimonidine Tartrate 
Ophthalmic Suspension Compared with Three Times Daily 
Alphagan® P in Subjects with Open Angle Glaucoma or Ocular 
Hypertension. 
PROTOCOL NUMBER 
CLR 16 33 
CT IDENTIFIER 
NCT03450629 
SAP VERSION 
2.0 
SAP VERSION DATE 
22APR2021 
 
 
 
 




STATISTICAL ANALYSIS PLAN 
 
CLR-16-33 SAP V1 
22APR2021 
Page 5 of 30 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


STATISTICAL ANALYSIS PLAN 
 
CLR-16-33 SAP V1 
22APR2021 
Page 6 of 30 
 
 
2  ABBREVIATIONS AND DEFINITIONS 
 
AE 
Adverse Event 
BSCVA 
Best-Spectacle Corrected Visual Acuity 
CI 
Confidence Interval 
CRO 
Contract research organization 
eCRF 
Electronic Case Report Form 
ETDRS 
Early Treatment Diabetic Retinopathy Study 
FDA 
Food and Drug Administration 
GAT 
Goldmann Applanation Tonometry 
GCP 
Good clinical practice 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization of technical 
requirements for pharmaceuticals for human use 
IEC 
Independent Ethics Committee 
IMP 
Investigational medicinal product 
IOP 
Intraocular Pressure 
IP 
Investigational Product 
IRB 
Institutional Review Board 
ITT 
Intent-To-Treat 
LOCF 
Last Observation Carried Forward 
logMAR 
logarithm of the Minimum Angle of Resolution 
MAO 
Monamine Oxidase Inhibitor 
MedDRA 
Medical Dictionary of Regulatory Affairs 
MMRM 
Mixed Model of Repeated Measures 
NCT 
Non-contact tonometer 
OPD 
(in-)Office physician dispensing 
OU 
Both eyes 
POC 
Proof-of-concept 
PP 
Per Protocol 
PT 
Preferred Term 
QD 
(Quaque Die) once daily 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SOC 
System Organ Class 
SPARC 
Sun Pharma Advanced Research Company, Ltd. 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
TOST 
Two one-sided tests 
TEAE 
Treatment-Emergent Adverse Event 
TID 
Three Times Daily 
 






STATISTICAL ANALYSIS PLAN 
 
CLR-16-33 SAP V1 
22APR2021 
Page 9 of 30 
 
 
 
 
 
 
 
6 STUDY METHODS 
6.1 
General Study Design and Plan 
 
x This is a multicenter, investigator/ evaluator -masked, randomized, parallel group, equivalence 
study. 
 
 
 
 
 
 
x The investigator or designated evaluator, masked to treatment assignment, will perform all 
ophthalmic examinations. Unmasked study coordinator may perform all study procedures other 
than ophthalmic/clinical examination, or treatment of the subjects. 
x Study Duration: 
o Visit 1: (Day-42 to Day -1): Screening 
o Visit 2: (Day 0) Baseline/Randomization 
o Visit 3: (Week 2 ± 2 Days) Efficacy/Safety Evaluation 
o Visit 4: (Week 6 ± 2 Days) Efficacy/Safety Evaluation 
o Visit 5: (Week 12 ± 2 Days) Efficacy/Safety Evaluation and study exit 
6.2 
Inclusion-Exclusion Criteria  
Inclusion Criteria: 
Each subject must: 
 
1. Be male or female, of 18 years of age or older 
2. Provide signed and dated informed consent in accordance with GCP and local legislation prior to 
any study procedure. 
3. Have open angle glaucoma, (with or without pseudo exfoliation, pigment dispersion component) 
or ocular hypertension in both eyes and likely to be controlled on monotherapy 
 
 
 
 








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required by the applicable regulatory requirement(s), should inform the regulatory authority(ies). 
Additionally: 
 
1. If the investigator terminates or suspends the study without prior agreement of the sponsor, the 
investigator should inform the institution (where the study is conducted) where applicable, and the 
investigator/institution should promptly inform the sponsor and the EC, and should provide the 
sponsor and the IEC a detailed written explanation of the termination or suspension. 
2. The sponsor may discontinue entire study at any time, for ethical or scientific or business reasons. 
If the sponsor terminates or suspends a study, the investigator should promptly inform the 
institution where applicable and the investigator/institution should promptly inform the IEC and 
provide the IEC a detailed written explanation of the termination or suspension. 
3. If the IEC terminates or suspends its approval/favourable opinion of a study, the investigator 
should inform the institution where applicable and the investigator/institution should promptly 
notify the sponsor and provide the sponsor with a detailed written explanation of the termination 
or suspension. 
6.5 
Randomization, Masking, and Unmasking 
x Subject Number 
At the screening visit after signing the informed consent form (ICF) each subject will be allotted 
a subject number. The subject number will uniquely identify each subject in the study. The subject 
number will appear on all study documents relating to that subject. Subject numbering is described 
separately in data management plan. 
 
x Randomization 
Subjects who qualify inclusion and exclusion criteria will be randomly assigned to study treatment 
using Interactive web response system. 
 
x Masking 
This is an evaluator-masked study. 
 
 
 
 
 
 
 
 
 
  
 
 
 




























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