Conditions: Cataract Pain Ocular Inflammation
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 600
Healthy volunteers: no

Brief summary:
Loteprednol Etabonate Ophthalmic Gel, (BID and TID) versus Vehicle Group for the Treatment of Ocular Inflammation and Pain Following Cataract Surgery.

Detailed description:
A Phase 3, Multi-Center, Double-Masked, Vehicle Controlled, Randomized, Parallel-Group Study to Assess Loteprednol Etabonate Ophthalmic Gel, (BID and TID) versus Vehicle Group for the Treatment of Ocular Inflammation and Pain Following Cataract Surgery.

Arms:
arm 1: Gel arm 2: Gel arm 3: Vehicle

Interventions: intervention 1: Loteprednol Etabonate Ophthalmic Gel dosed TID intervention 2: Loteprednol Etabonate Ophthalmic Gel dosed BID intervention 3: Vehicle Gel
Intervention descriptions: intervention 1: Gel intervention 2: Gel intervention 3: Gel

Protocol document:
Prot_SAP_000.pdf: 
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A Phase 3, Multi-Center, Double-Masked, Vehicle-Controlled, Randomized, Parallel-
Group Study to Assess Loteprednol Etabonate Ophthalmic Gel, 0.38% (BID and TID) 
versus Vehicle Gel for the Treatment of Ocular Inflammation and Pain Following Cataract 
Surgery
PROTOCOL
STUDY #875
IND #102654
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INVESTIGATOR STATEMENT OF APPROVAL
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A Phase 3, Multi-Center, Double-Masked, Vehicle-Controlled, Randomized, Parallel-
Group Study to Assess Loteprednol Etabonate Ophthalmic Gel, 0.38% (BID and TID) 
versus Vehicle Gel for the Treatment of Ocular Inflammation and Pain Following Cataract 
Surgery
PROTOCOL
STUDY #875
IND #102654
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PERSONNEL AND FACILITIES
NOTE: The information on this page is subject to change. All changes will be provided under separate cover.
Sponsor 
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Contact for Reporting Serious Adverse Events 
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TABLE OF CONTENTS
 
 
 
 
 
 
 
 
 
 
 
PAGE
SPONSOR APPROVAL PAGE ................................................................................................................................. 2 
INVESTIGATOR STATEMENT OF APPROVAL................................................................................................. 3 
PERSONNEL AND FACILITIES ............................................................................................................................. 4 
TABLE OF CONTENTS ............................................................................................................................................ 5 
LIST OF ABBREVIATIONS ..................................................................................................................................... 8 
SYNOPSIS..................................................................................................................................................................10 
PRIMARY ENDPOINTS..........................................................................................................................................18 
SAFETY ENDPOINTS .............................................................................................................................................19 
TOLERABILITY ENDPOINTS ..............................................................................................................................19 
ANALYSIS OF SECONDARY EFFICACY ENDPOINTS...................................................................................20 
1.0 
INTRODUCTION............................................................................................................................................23 
2.0 
OBJECTIVE ....................................................................................................................................................24 
3.0 
STUDY DESIGN..............................................................................................................................................25 
3.1 
DESCRIPTION OF STUDY DESIGN INCLUDING CHOICE OF CONTROL GROUPS ..........................................25 
3.2 
STUDY POPULATION.....................................................................................................................................25 
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3.3 
INVESTIGATORS............................................................................................................................................28 
3.4 
STUDY DURATION.........................................................................................................................................29 
3.5 
TREATMENTS................................................................................................................................................29 
3.6 
SELECTION OF DOSE ....................................................................................................................................29 
4.0 
STUDY MATERIALS.....................................................................................................................................29 
4.1 
DESCRIPTION OF INVESTIGATIONAL PRODUCT ..........................................................................................29 
4.2 
DESCRIPTION OF COMPARATOR PRODUCT................................................................................................. 29 
4.3 
INSTRUCTIONS FOR USE AND ADMINISTRATION .........................................................................................30 
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4.4 
PACKAGING AND LABELING.........................................................................................................................30 
4.5 
ACCOUNTABILITY.........................................................................................................................................31 
4.6 
MASKING/UNMASKING................................................................................................................................. 31 
4.7 
METHODS OF ASSIGNING SUBJECTS TO TREATMENT GROUPS ..................................................................32 
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4.8 
OTHER STUDY MATERIALS..........................................................................................................................33 
5.0 
EFFICACY AND SAFETY VARIABLES.....................................................................................................33 
5.1 
EFFICACY VARIABLES..................................................................................................................................33 
5.2 
SAFETY VARIABLES......................................................................................................................................33 
5.3 
TOLERABILITY VARIABLES..........................................................................................................................34 
5.4 
APPROPRIATENESS OF VARIABLES..............................................................................................................34 
5.5 
RISK ASSESSMENT........................................................................................................................................34 
6.0 
STUDY METHODS.........................................................................................................................................34 
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6.1 
STUDY VISITS................................................................................................................................................35 
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STUDY COMPLETION....................................................................................................................................40 
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CONCOMITANT MEDICATIONS/THERAPY ...................................................................................................41 
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6.4 
TREATMENT COMPLIANCE ..........................................................................................................................46 
6.5 
PROTOCOL DEVIATIONS...............................................................................................................................46 
7.0 
ADVERSE EVENTS........................................................................................................................................46 
7.1 
DEFINITION OF ADVERSE EVENTS...............................................................................................................46 
7.2 
DEFINITION OF SERIOUS ADVERSE EVENTS................................................................................................47 
7.3 
REPORTING ADVERSE EVENTS AND FOLLOW-UP .......................................................................................48 
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7.4 
REPORTING SERIOUS ADVERSE EVENTS AND FOLLOW-UP ........................................................................49 
7.5 
REPORTING PREGNANCIES AND FOLLOW-UP..............................................................................................50 
7.6 
SUBMITTING AN EXPEDITED SAFETY REPORT TO THE IRB (CENTRAL OR LOCAL) ..................................50 
8.0 
STATISTICAL METHODS ...........................................................................................................................51 
8.1 
STUDY ENDPOINTS........................................................................................................................................51 
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8.2 
HYPOTHESES.................................................................................................................................................52 
8.3 
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8.4 
STUDY POPULATIONS ...................................................................................................................................54 
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9.0 
DATA QUALITY ASSURANCE ...................................................................................................................59 
9.1 
STUDY MONITORING....................................................................................................................................59 
9.2 
SOURCE DOCUMENTATION ..........................................................................................................................60 
9.3 
CASE REPORT FORMS AND DATA VERIFICATION.......................................................................................60 
9.4 
RECORDING OF DATA AND RETENTION OF DOCUMENTS ...........................................................................60 
9.5 
AUDITING PROCEDURES...............................................................................................................................61 
9.6 
INSTITUTIONAL REVIEW BOARD/ETHICS COMMITTEE APPROVAL...........................................................61 
9.7 
PUBLICATION OF RESULTS...........................................................................................................................62 
10.0 
REFERENCES............................................................................................................................................63 

APPENDICES
APPENDIX A: 
SCHEDULE OF VISITS AND PARAMETERS.................................................. A-1 
APPENDIX B: 
METHODS OF CLINICAL EVALUATION ....................................................... B-1 
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SYNOPSIS
Bausch & Lomb Incorporated Study #875
Title:
A Phase 3, Multi-Center, Double-Masked, Vehicle-Controlled, Randomized, 
Parallel-Group Study to Assess Loteprednol Etabonate Ophthalmic Gel, 0.38% 
(BID and TID) versus Vehicle Gel for the Treatment of Ocular Inflammation 
and Pain Following Cataract Surgery
Phase of study: 

Number of subjects:
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Planned study 
period and duration 
of treatment:
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ZLOOEHDSSUR[LPDWHO\GD\V
Objective(s):
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RSKWKDOPLF JHO  %,' DQG 7,' IRU WKH WUHDWPHQW RI SRVWRSHUDWLYH
LQIODPPDWLRQDQGSDLQIROORZLQJFDWDUDFWVXUJHU\
Study design:
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7KHVWXG\GXUDWLRQZLOOEHDSSUR[LPDWHO\ZHHNVIURPWKHVFUHHQLQJDVVHVVPHQW
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VXUJHU\7KH9LVLWGDWHZLOOEHWKHGDWHRQZKLFKWKHILUVWVFUHHQLQJDVVHVVPHQWLV
SHUIRUPHG 7KH LQIRUPHG FRQVHQW GDWH PD\ EH WKH VDPH DV RU SULRU WR YLVLW
 VFUHHQLQJ DV VHVVHQW GDWH 9LVLW  ZLOO EH RQ WKH GD\ RI VXUJHU\ $W 9LVLW 
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DQG3RVWRSHUDWLYH'D\VDQGUHVSHFWLYHO\(IILFDF\ZLOOEH
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Study endpoints:
Primary Efficacy Endpoints
7KHSULPDU\HIILFDF\HQGSRLQWVIRUWKLVVWXG\DUH
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Secondary Efficacy Endpoints
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Safety Endpoints:
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Tolerability Endpoints:
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Criteria for 
inclusion:
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Visit 1 (Screening) Criteria
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Study procedures:
Visit 1: Screening Assessments  
NOTE: Visit 1 shall occur no earlier than 14 days prior to surgery. The
                  Visit 1 date will be the date on which the first screening assessment
                        is performed. The informed consent date may be the same as or prior
                        to visit 1( screening  assessent date). 
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NOTE: Surgery will be scheduled to occur ≤14 days from the Screening 
Assessment. Screening and surgery cannot take place on the same day.
Visit 2: Surgery (≤14 days from the Screening Assessment) 
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NOTE: Following surgery, subjects may only receive antibiotics and will be 
scheduled to return in 18 to 34 hours to determine if they have 
sufficient ocular inflammation to be included in the study (see 
Inclusion Criteria #12). Subjects who do not receive a posterior 
chamber IOL or who, in the Investigator's opinion, have complications 
such that it is not in the subject’s best interests to continue in the study 
are considered screen failures.
NOTE: If during the surgery it is determined that additional manipulations, 
such as pupil stretching or the use of iris hooks or peripheral relaxing 
corneal incisions are required, the subject is not eligible to participate 
in the trial. 
Visit 3: Postoperative Day 1 (Randomization [18 to 34 hours post-surgery]) 
NOTE: Post-surgery visits should be scheduled so that IOP can be assessed 
within ±2 hours of the time of IOP assessment on Visit 1.
NOTE: Unmasked study staff personnel will be designated for study drug 
handling, including dispensing to subjects, training subjects on dosing 
administration, and collection/review of study diaries at each visit 
(Section 4.6).
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Visit 4: Postoperative Day 3 (±1 Day)
NOTE: Post-surgery visits should be scheduled so that IOP can be assessed 
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NOTE: Subjects will be assessed at Visits 4 through 7 (Postoperative Days 3, 8, 
15, and 18) for treatment rescue. Subjects with worsening or no change 
in the grade of inflammation in the study eye compared with the 
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previous visit are eligible and may be considered for rescue medication
at the discretion of the Investigator.  The choice of rescue medication
and dosing shall be determined by the Investigator. See Section 6.2.3.1 
for more details. 
Visit 5: Postoperative Day 8 (±1 Day)
NOTE:  Post-surgery visits should be scheduled so that IOP can be assessed 
within ±2 hours of the time of IOP assessment on Visit 1.
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Visit 6: Postoperative Day 15 (±1 Day), (End of treatment)
NOTE: Post-surgery visits should be scheduled so that IOP can be assessed 
within ±2 hours of the time of IOP assessment on Visit 1.
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Visit 7: Postoperative Day 18 (±1 Day), (Post-treatment exam)
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Hypotheses 
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Family 1 of Hypotheses: Complete Resolution of AC Cells in the Study Eye at 
Visit 5
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Family 2 of Hypotheses: Complete Resolution of Pain in the Study Eye at Visit 5
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2.0
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3.0
STUDY DESIGN
3.1
Description of Study Design Including Choice of Control Groups 
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3.2
Study Population 
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3.2.1.1
Inclusion Criteria
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Visit 1 (Screening) Criteria
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Visit 3 (Postoperative Day 1) Criteria 
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3.2.1.2
Exclusion Criteria
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3.3
Investigators 
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3.4
Study Duration
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3.5
Treatments
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4.0
STUDY MATERIALS
4.1
Description of Investigational Product  
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4.2
Description of Comparator Product  
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Instructions for Use and Administration
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Packaging and Labeling  
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Accountability
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Masking/Unmasking 
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4.7
Methods of Assigning Subjects to Treatment Groups
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EFFICACY AND SAFETY VARIABLES
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6.1
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NOTE: Visit 1 shall occur no earlier than 14 das prior to surgery.  The Visit 1 date will be the 
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screen failures.
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treatment rescue. Subjects with worsening or no change in the grade of inflammation 
in the study eye compared with the previous visit are eligible and may be considered 
for rescue medication at the discretion of the Investigator.  The choice of rescue 
medication and dosing shall be determined by the Investigator. See Section 6.2.3.1 for 
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Table 2: 
Disallowed Therapies
Medication/Class of Drug
Status
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GD\VDIWHUVXUJHU\
%LRORJLF$JHQWV
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DIWHUVXUJHU\
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Additionally, any medication the subject uses that the Investigator and/or Medical Monitor 
feels may interfere with subject safety or study parameters should be considered a 
disallowed medication.
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6.4
Treatment Compliance 
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6.5
Protocol Deviations 
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7.0
ADVERSE EVENTS
7.1
Definition of Adverse Events
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7.2
Definition of Serious Adverse Events 
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7.3
Reporting Adverse Events and Follow-up
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7.4
Reporting Serious Adverse Events and Follow-up
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7.5
Reporting Pregnancies and Follow-up
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7.6
Submitting an Expedited Safety Report to the IRB (Central or Local)
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8.0
STATISTICAL METHODS
8.1
Study Endpoints
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8.2
Hypotheses
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Family 2 of Hypotheses: Complete Resolution of Pain in the Study Eye at Visit 5
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8.3
Sample Size
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8.4
Study Populations 
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8.5
Statistical Analysis
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8.5.1.1
Efficacy Endpoint Analyses 
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Table 3: Bonferroni-based tree gatekeeping hypothesis structure
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Safety Endpoint Analyses 
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8.5.1.3
Tolerability Endpoint Analyses 
Ocular Symptoms and Study Drug Sensation
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DATA QUALITY ASSURANCE 
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10.0
REFERENCES 
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-DDQXV 6' /HVKHU *$ $QWLLQIODPPDWRU\ GUXJV ,Q Clinical Ocular Pharmacology
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%HFNHU%,QWUDRFXODUSUHVVXUHUHVSRQVHWRWRSLFDOFRUWLFRVWHURLGVInvest Ophthalmol.
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HIIHFWRIGH[DPHWKDVRQHLQWKHQRUPDOH\HArch Ophthalmol
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APPENDIX A:
SCHEDULE OF VISITS AND PARAMETERS 
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APPENDIX B:
METHODS OF CLINICAL EVALUATION 
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NOTE:
Sites should use the same instrument and the same examiner when possible 
throughout the study. All ophthalmic assessments will be performed bilaterally.
1.0
OCULAR SYMPTOMS
The ocular symptoms of ocular pain, photophobia, itching, tearing, and ocular discharge are 
all to be graded by subjects using the following ordinal scales: 
Ocular Pain: A positive sensation of the eye, including foreign body sensation, stabbing, 
throbbing, or aching. 
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FRQVWDQWVKDUSVWDEELQJSDLQWKUREELQJRUDFKLQJHWFUHTXLULQJ
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Photophobia:
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Itching:
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Tearing:
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Ocular Discharge:
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ORZHUFXOGHVDF)UDQNPDWWLQJWRJHWKHURIH\HOLGVLQWKHPRUQLQJXSRQ
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2.0
STUDY DRUG SENSATION ASSESSMENT
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GUXJVHQVDWLRQZLOOEHJUDGHGRQWKHIROORZLQJRUGLQDOVFDOH
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3.0
VISUAL ACUITY 
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WKURXJKDSLQKROHGKDELWXDOXQDLGHGRUKLVWRULFDOFRUUHFWLRQXVLQJD6QHOOHQFKDUW
4.0
OCULAR SIGNS
A.
BIOMICROSCOPY
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The methodology described below must be used by all investigators for evaluation and grading 
of anterior chamber ocular inflammation.  A subject cannot be enrolled into the study if there 
is presence of any cells at the screening visit in either eye. 
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Cells:Assess accumulation of white blood cells in anterior aqueous humor; pigmented cells 
and red blood cells are to be ignored.
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Flare:  Assess scattering of a slit lamp light beam when directed into the anterior chamber 
(Tyndall effect).
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External Adnexa (Lids/Lashes): Assess erythema or edema of the external adnexa. In 
addition to erythema or edema, any other abnormality of the lid and lashes
that is observed will also be noted and graded according to the same 4-point 
grading scale. 
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Ciliary Flush:  Assess external congestion of blood vessels surrounding the limbus. 
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Conjunctival Chemosis:Assess swelling of the conjunctiva. 
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Bulbar and Palpebral Conjunctival Injection: Assess redness and swelling from dilated 
blood vessels in the bulbar and palpebral conjunctiva. It is at the Investigator’s 
discretion whether the superior lid is inverted for assessing palpebral conjunctival 
injection; the same technique should be used for a given subject at each visit. 
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Corneal Staining:  Assess after the instillation of fluorescein; fluorescein can be instilled 
either from a strip or as a 2% solution. A Wratten gel barrier filter will 
be provided by Bausch + Lomb for evaluation of corneal staining within 
2-3 minutes after fluorescein instillation. The Wratten gel barrier filter 
must be used in the observation pathway when grading corneal staining,
in combination with a cobalt blue exciter filter.
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Corneal Edema:  Assess degree of corneal edema.
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Lens Status:  Assess condition of the lens in the study eye 
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Hyphema:   Assess presence or absence of hyphema.
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Posterior Synechiae:  Assess for presence of adhesions between the iris and the lens. 
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Anterior Vitreous Haze:  Assess degree of vitreous haze by slit lamp examination of the 
anterior face of vitreous body. 
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Precipitates:  Assess for presence of precipitates on implant and cornea. 
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Hypopyon:  Assess for presence of hypopyon. 
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B. DILATED FUNDUS EXAMINATION
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Retina, Macula, and Choroid:  Assess for abnormalities in the retina, macula and choroid. 
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Optic Nerve:  Assess for abnormalities in the optic nerve.
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Cup/Disc Ratio: Assess the cup/disc ratio according to the following scale. Additionally, 
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5.0
INTRAOCULAR PRESSURE
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