LE Gel for the Treatment of Ocular Inflammation and Pain Following Cataract Surgery

Sponsor
Bausch & Lomb Incorporated (Industry)
Overall Status
Completed
CT.gov ID
NCT02786901
Collaborator
(none)
600
Enrollment
6
Locations
3
Arms
13
Actual Duration (Months)
100
Patients Per Site
7.7
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or DiseaseIntervention/TreatmentPhase
  • Drug: Loteprednol Etabonate Ophthalmic Gel dosed TID
  • Drug: Loteprednol Etabonate Ophthalmic Gel dosed BID
  • Drug: Vehicle Gel
Phase 3

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
600 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Multi-Center, Double-Masked, Vehicle-Controlled, Randomized, Parallel-Group Study to Assess Loteprednol Etabonate Ophthalmic Gel, (BID and TID) Versus Vehicle Gel
Actual Study Start Date :
Jun 1, 2016
Actual Primary Completion Date :
Jun 13, 2017
Actual Study Completion Date :
Jul 1, 2017

Arms and Interventions

ArmIntervention/Treatment
Experimental: Loteprednol Etabonate Ophthalmic Gel dosed TID

Gel

Drug: Loteprednol Etabonate Ophthalmic Gel dosed TID
Gel
Other Names:
  • LE
  • Experimental: Loteprednol Etabonate Ophthalmic Gel dosed BID

    Gel

    Drug: Loteprednol Etabonate Ophthalmic Gel dosed BID
    Gel
    Other Names:
  • LE
  • Placebo Comparator: Vehicle Gel

    Vehicle

    Drug: Vehicle Gel
    Gel
    Other Names:
  • Vehicle
  • Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Complete Resolution of Anterior Chamber (AC) Cells at Visit 5 (Postoperative Day 8) [8 days]

      Slit lamp examination was performed. White blood cell accumulation in anterior aqueous humor was assessed by the Investigator during slit lamp examination and graded on a 5-point scale: Grade 0 = no cells seen; Grade 1 = 1 to 5 cells; Grade 2 = 6 to 15 cells; Grade 3 = 16 to 30 cells; Grade 4 = > 30 cells. Complete resolution of AC cells was defined as Cell score = 0 in the study eye.

    2. Number of Participants With Complete Resolution of Ocular Pain in Study Eye at Visit 5 (Postoperative Day 8) [8 days]

      Ocular pain, defined as a positive sensation of the eye, including foreign body sensation, stabbing, throbbing, or aching, was assessed and graded by subjects on a 6-point scale: 0 (None), 1 (Minimal), 2 (Mild), 3 (Moderate), 4 (Moderately Severe), and 5 (Severe). Complete Resolution of Ocular Pain was defined as Pain Score = 0.

    Secondary Outcome Measures

    1. Number of Participants With Complete Resolution of Anterior Chamber (AC) Cells in the Study Eye at Final On-treatment Visit. [14 days]

      Slit lamp examination was performed. White blood cell accumulation in anterior aqueous humor was assessed by the Investigator during slit lamp examination and graded on a 5-point scale: Grade 0 = no cells seen; Grade 1 = 1 to 5 cells; Grade 2 = 6 to 15 cells; Grade 3 = 16 to 30 cells; Grade 4 = > 30 cells. Complete resolution of AC cells was defined as Cell score = 0 in the study eye.

    2. Number of Participants With Complete Resolution of Ocular Pain in Study Eye at Final On-Treatment Visit [14 days]

      Ocular pain, defined as a positive sensation of the eye, including foreign body sensation, stabbing, throbbing, or aching, was assessed and graded by subjects on a 6-point scale: 0 (None), 1 (Minimal), 2 (Mild), 3 (Moderate), 4 (Moderately Severe), and 5 (Severe). Complete Resolution of Ocular Pain was defined as Pain Score = 0.

    3. Number of Participants With Complete Resolution of Anterior Chamber (AC) Flare in the Study Eye at Final On-Treatment Visit [14 days]

      Flare was evaluated by the Investigator by assessing the scattering of a slit lamp light beam directed into the anterior chamber (Tyndall effect). Flare was graded on a 5-point scale: 0 (None), 1 (Mild), 2 (Moderate), 3 (Severe), and 4 (Very Severe). An AC flare score of 0 in the study eye was considered complete resolution.

    4. Number of Participants With Complete Resolution of Both Anterior Chamber (AC) Cells and AC Flare in the Study Eye at Final On-Treatment Visit [14 days]

      Slit lamp examination was performed. White blood cell accumulation in anterior aqueous humor was assessed by the Investigator during slit lamp examination and graded on a 5-point scale: Grade 0 = no cells seen; Grade 1 = 1 to 5 cells; Grade 2 = 6 to 15 cells; Grade 3 = 16 to 30 cells; Grade 4 = > 30 cells. Complete resolution of AC cells was defined as Cell score = 0 in the study eye. Flare was evaluated by the Investigator by assessing the scattering of a slit lamp light beam directed into the anterior chamber (Tyndall effect). Flare was graded on a 5-point scale: 0 (None), 1 (Mild), 2 (Moderate), 3 (Severe), and 4 (Very Severe). An AC flare score of 0 in the study eye was considered complete resolution.

    5. Change From Baseline in Summed Anterior Chamber (AC) Cell and Flare Scores at Final On-Treatment Visit [14 days]

      Slit lamp examination was performed. White blood cell accumulation in anterior aqueous humor was assessed by the Investigator during slit lamp examination and graded on a 5-point scale: Grade 0 = no cells seen; Grade 1 = 1 to 5 cells; Grade 2 = 6 to 15 cells; Grade 3 = 16 to 30 cells; Grade 4 = > 30 cells. Flare was evaluated by the Investigator by assessing the scattering of a slit lamp light beam directed into the anterior chamber (Tyndall effect). Flare was graded on a 5-point scale: 0 (None), 1 (Mild), 2 (Moderate), 3 (Severe), and 4 (Very Severe). The combined endpoint was defined as the sum of the scores for AC cells and AC flare. Summed Anterior Chamber (AC) Cell and Flare Scores could range from 0 to 8.

    6. Number of Participants With Treatment Failure at Visit 5 (Postoperative Day 8) [8 days]

      A participant was considered a treatment failure at Visit 5 if they started any rescue medication prior to, or on the day of, Visit 5. If a subject did not have a Visit 5, due either to early discontinuation or to a missed visit, then treatment failure at Visit 5 was defined as starting rescue medication prior to, or on, Postoperative Day 8.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:
    1. Be 18 years or older on the date the Informed Consent Form (ICF) is signed and with the capacity to provide voluntary informed consent.

    2. Be able to read, understand, and provide written informed consent on the Institutional Review Board (IRB)/Ethics Committee (EC) approved ICF and provide Health Insurance Portability and Accountability Act (HIPAA) authorization.

    3. Be willing and able to comply with all treatment and follow-up/study procedures.

    4. Be a candidate for routine, uncomplicated cataract surgery (phaco-emulsification with posterior chamber intraocular lens [IOL] implantation, not combined with any other surgery).

    5. In the Investigator's opinion, have potential postoperative pin-holed Snellen visual acuity (VA) of at least 20/200 in the study eye at Visit 1 (Screening) and at least 20/200 in the fellow eye.

    Key Exclusion Criteria:
    1. Have a severe/serious ocular condition or history/presence of chronic generalized systemic disease that the Investigator feels might increase the risk to the subject or confound the result(s) of the study.

    2. Be a female subject who is pregnant or breastfeeding.

    3. Be monocular (fellow eye is nonfunctional or fellow eye's pinhole vision is worse than Snellen 20/200).

    4. Have had ocular surgery (including laser surgery) in the study eye within 3 months or in the fellow eye within 2 weeks prior to Visit 1 (Screening).

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Valeant Site 01PhoenixArizonaUnited States85032
    2Valeant Site 03OceansideCaliforniaUnited States92056
    3Valeant Site 05MiamiFloridaUnited States33143
    4Valeant Site 04QuincyMassachusettsUnited States02169
    5Valeant Site 06Kansas CityMissouriUnited States64111
    6Valeant Site 02Saint LouisMissouriUnited States63131

    Sponsors and Collaborators

    • Bausch & Lomb Incorporated

    Investigators

    • Study Director: Denise Ramjit, Valeant Pharmaceuticals

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Bausch & Lomb Incorporated
    ClinicalTrials.gov Identifier:
    NCT02786901
    Other Study ID Numbers:
    • 875
    First Posted:
    Jun 1, 2016
    Last Update Posted:
    Jan 8, 2021
    Last Verified:
    Jan 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group TitleVehicle BID and TIDLE Gel BIDLE Gel TID
    Arm/Group DescriptionVehicle Gel dosed BID and Vehicle Gel dosed TID, combinedLoteprednol Etabonate Ophthalmic Gel dosed BIDLoteprednol Etabonate Ophthalmic Gel dosed TID
    Period Title: Overall Study
    STARTED199201200
    COMPLETED122145159
    NOT COMPLETED775641

    Baseline Characteristics

    Arm/Group TitleVehicle BID and TIDLE Gel BIDLE Gel TIDTotal
    Arm/Group DescriptionVehicle Gel dosed BID and Vehicle Gel dosed TID, combinedLoteprednol Etabonate Ophthalmic Gel dosed BIDLoteprednol Etabonate Ophthalmic Gel dosed TIDTotal of all reporting groups
    Overall Participants199201200600
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    68.5
    (8.92)
    68.3
    (9.11)
    67.9
    (9.32)
    68.2
    (9.11)
    Sex: Female, Male (Count of Participants)
    Female
    116
    58.3%
    117
    58.2%
    130
    65%
    363
    60.5%
    Male
    83
    41.7%
    84
    41.8%
    70
    35%
    237
    39.5%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    1
    0.5%
    1
    0.5%
    2
    0.3%
    Asian
    7
    3.5%
    13
    6.5%
    9
    4.5%
    29
    4.8%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    1
    0.5%
    0
    0%
    1
    0.2%
    Black or African American
    14
    7%
    23
    11.4%
    23
    11.5%
    60
    10%
    White
    169
    84.9%
    158
    78.6%
    163
    81.5%
    490
    81.7%
    More than one race
    0
    0%
    1
    0.5%
    1
    0.5%
    2
    0.3%
    Unknown or Not Reported
    9
    4.5%
    4
    2%
    3
    1.5%
    16
    2.7%
    Iris Color (Count of Participants)
    Blue
    50
    25.1%
    47
    23.4%
    49
    24.5%
    146
    24.3%
    Brown
    111
    55.8%
    115
    57.2%
    112
    56%
    338
    56.3%
    Green
    17
    8.5%
    9
    4.5%
    5
    2.5%
    31
    5.2%
    Hazel
    20
    10.1%
    28
    13.9%
    32
    16%
    80
    13.3%
    Other
    1
    0.5%
    2
    1%
    2
    1%
    5
    0.8%

    Outcome Measures

    1. Primary Outcome
    TitleNumber of Participants With Complete Resolution of Anterior Chamber (AC) Cells at Visit 5 (Postoperative Day 8)
    DescriptionSlit lamp examination was performed. White blood cell accumulation in anterior aqueous humor was assessed by the Investigator during slit lamp examination and graded on a 5-point scale: Grade 0 = no cells seen; Grade 1 = 1 to 5 cells; Grade 2 = 6 to 15 cells; Grade 3 = 16 to 30 cells; Grade 4 = > 30 cells. Complete resolution of AC cells was defined as Cell score = 0 in the study eye.
    Time Frame8 days

    Outcome Measure Data

    Analysis Population Description
    Missing values and post rescue values imputed as failures.
    Arm/Group TitleVehicle BID and TIDLE Gel BIDLE Gel TID
    Arm/Group DescriptionVehicle Gel dosed BID and Vehicle Gel dosed TID, combinedLoteprednol Etabonate Ophthalmic Gel dosed BIDLoteprednol Etabonate Ophthalmic Gel dosed TID
    Measure Participants199201200
    Count of Participants [Participants]
    40
    20.1%
    52
    25.9%
    61
    30.5%
    2. Primary Outcome
    TitleNumber of Participants With Complete Resolution of Ocular Pain in Study Eye at Visit 5 (Postoperative Day 8)
    DescriptionOcular pain, defined as a positive sensation of the eye, including foreign body sensation, stabbing, throbbing, or aching, was assessed and graded by subjects on a 6-point scale: 0 (None), 1 (Minimal), 2 (Mild), 3 (Moderate), 4 (Moderately Severe), and 5 (Severe). Complete Resolution of Ocular Pain was defined as Pain Score = 0.
    Time Frame8 days

    Outcome Measure Data

    Analysis Population Description
    Missing values and post rescue values imputed as failures.
    Arm/Group TitleVehicle BID and TIDLE Gel BIDLE Gel TID
    Arm/Group DescriptionVehicle Gel dosed BID and Vehicle Gel dosed TID, combinedLoteprednol Etabonate Ophthalmic Gel dosed BIDLoteprednol Etabonate Ophthalmic Gel dosed TID
    Measure Participants199201200
    Count of Participants [Participants]
    99
    49.7%
    151
    75.1%
    151
    75.5%
    3. Secondary Outcome
    TitleNumber of Participants With Complete Resolution of Anterior Chamber (AC) Cells in the Study Eye at Final On-treatment Visit.
    DescriptionSlit lamp examination was performed. White blood cell accumulation in anterior aqueous humor was assessed by the Investigator during slit lamp examination and graded on a 5-point scale: Grade 0 = no cells seen; Grade 1 = 1 to 5 cells; Grade 2 = 6 to 15 cells; Grade 3 = 16 to 30 cells; Grade 4 = > 30 cells. Complete resolution of AC cells was defined as Cell score = 0 in the study eye.
    Time Frame14 days

    Outcome Measure Data

    Analysis Population Description
    Missing values and post rescue values imputed as failures.
    Arm/Group TitleVehicle BID and TIDLE Gel BIDLE Gel TID
    Arm/Group DescriptionVehicle Gel dosed BID and Vehicle Gel dosed TID, combinedLoteprednol Etabonate Ophthalmic Gel dosed BIDLoteprednol Etabonate Ophthalmic Gel dosed TID
    Measure Participants190201198
    Count of Participants [Participants]
    67
    33.7%
    82
    40.8%
    94
    47%
    4. Secondary Outcome
    TitleNumber of Participants With Complete Resolution of Ocular Pain in Study Eye at Final On-Treatment Visit
    DescriptionOcular pain, defined as a positive sensation of the eye, including foreign body sensation, stabbing, throbbing, or aching, was assessed and graded by subjects on a 6-point scale: 0 (None), 1 (Minimal), 2 (Mild), 3 (Moderate), 4 (Moderately Severe), and 5 (Severe). Complete Resolution of Ocular Pain was defined as Pain Score = 0.
    Time Frame14 days

    Outcome Measure Data

    Analysis Population Description
    Missing values and post rescue values imputed as failures.
    Arm/Group TitleVehicle BID and TIDLE Gel BIDLE Gel TID
    Arm/Group DescriptionVehicle Gel dosed BID and Vehicle Gel dosed TID, combinedLoteprednol Etabonate Ophthalmic Gel dosed BIDLoteprednol Etabonate Ophthalmic Gel dosed TID
    Measure Participants190201198
    Count of Participants [Participants]
    122
    61.3%
    168
    83.6%
    170
    85%
    5. Secondary Outcome
    TitleNumber of Participants With Complete Resolution of Anterior Chamber (AC) Flare in the Study Eye at Final On-Treatment Visit
    DescriptionFlare was evaluated by the Investigator by assessing the scattering of a slit lamp light beam directed into the anterior chamber (Tyndall effect). Flare was graded on a 5-point scale: 0 (None), 1 (Mild), 2 (Moderate), 3 (Severe), and 4 (Very Severe). An AC flare score of 0 in the study eye was considered complete resolution.
    Time Frame14 days

    Outcome Measure Data

    Analysis Population Description
    Missing values and post rescue values imputed as failures.
    Arm/Group TitleVehicle BID and TIDLE Gel BIDLE Gel TID
    Arm/Group DescriptionVehicle Gel dosed BID and Vehicle Gel dosed TID, combinedLoteprednol Etabonate Ophthalmic Gel dosed BIDLoteprednol Etabonate Ophthalmic Gel dosed TID
    Measure Participants190201198
    Count of Participants [Participants]
    107
    53.8%
    143
    71.1%
    153
    76.5%
    6. Secondary Outcome
    TitleNumber of Participants With Complete Resolution of Both Anterior Chamber (AC) Cells and AC Flare in the Study Eye at Final On-Treatment Visit
    DescriptionSlit lamp examination was performed. White blood cell accumulation in anterior aqueous humor was assessed by the Investigator during slit lamp examination and graded on a 5-point scale: Grade 0 = no cells seen; Grade 1 = 1 to 5 cells; Grade 2 = 6 to 15 cells; Grade 3 = 16 to 30 cells; Grade 4 = > 30 cells. Complete resolution of AC cells was defined as Cell score = 0 in the study eye. Flare was evaluated by the Investigator by assessing the scattering of a slit lamp light beam directed into the anterior chamber (Tyndall effect). Flare was graded on a 5-point scale: 0 (None), 1 (Mild), 2 (Moderate), 3 (Severe), and 4 (Very Severe). An AC flare score of 0 in the study eye was considered complete resolution.
    Time Frame14 days

    Outcome Measure Data

    Analysis Population Description
    Missing values and post rescue values imputed as failures.
    Arm/Group TitleVehicle BID and TIDLE Gel BIDLE Gel TID
    Arm/Group DescriptionVehicle Gel dosed BID and Vehicle Gel dosed TID, combinedLoteprednol Etabonate Ophthalmic Gel dosed BIDLoteprednol Etabonate Ophthalmic Gel dosed TID
    Measure Participants190201198
    Count of Participants [Participants]
    66
    33.2%
    82
    40.8%
    92
    46%
    7. Secondary Outcome
    TitleChange From Baseline in Summed Anterior Chamber (AC) Cell and Flare Scores at Final On-Treatment Visit
    DescriptionSlit lamp examination was performed. White blood cell accumulation in anterior aqueous humor was assessed by the Investigator during slit lamp examination and graded on a 5-point scale: Grade 0 = no cells seen; Grade 1 = 1 to 5 cells; Grade 2 = 6 to 15 cells; Grade 3 = 16 to 30 cells; Grade 4 = > 30 cells. Flare was evaluated by the Investigator by assessing the scattering of a slit lamp light beam directed into the anterior chamber (Tyndall effect). Flare was graded on a 5-point scale: 0 (None), 1 (Mild), 2 (Moderate), 3 (Severe), and 4 (Very Severe). The combined endpoint was defined as the sum of the scores for AC cells and AC flare. Summed Anterior Chamber (AC) Cell and Flare Scores could range from 0 to 8.
    Time Frame14 days

    Outcome Measure Data

    Analysis Population Description
    Missing values and post-rescue values imputed using last observation carried forward.
    Arm/Group TitleVehicle BID and TIDLE Gel BIDLE Gel TID
    Arm/Group DescriptionVehicle Gel dosed BID and Vehicle Gel dosed TID, combinedLoteprednol Etabonate Ophthalmic Gel dosed BIDLoteprednol Etabonate Ophthalmic Gel dosed TID
    Measure Participants190201198
    Mean (Standard Deviation) [score on a scale]
    -1.2
    (1.90)
    -2.0
    (1.50)
    -2.1
    (1.50)
    8. Secondary Outcome
    TitleNumber of Participants With Treatment Failure at Visit 5 (Postoperative Day 8)
    DescriptionA participant was considered a treatment failure at Visit 5 if they started any rescue medication prior to, or on the day of, Visit 5. If a subject did not have a Visit 5, due either to early discontinuation or to a missed visit, then treatment failure at Visit 5 was defined as starting rescue medication prior to, or on, Postoperative Day 8.
    Time Frame8 days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleVehicle BID and TIDLE Gel BIDLE Gel TID
    Arm/Group DescriptionVehicle Gel dosed BID and Vehicle Gel dosed TID, combinedLoteprednol Etabonate Ophthalmic Gel dosed BIDLoteprednol Etabonate Ophthalmic Gel dosed TID
    Measure Participants199201200
    Count of Participants [Participants]
    62
    31.2%
    23
    11.4%
    20
    10%

    Adverse Events

    Time Frame14 days
    Adverse Event Reporting Description The Safety population was used for reporting of adverse events. One participant was included in the vehicle group in the ITT (Intent to Treat) population but did not administer study drug, so this participant was excluded from the Safety population. Another participant, randomized to the LE gel TID group, and included in this treatment group in the ITT population, actually received LE gel BID and so was included in LE gel BID treatment group in the Safety population
    Arm/Group TitleVehicle BID and TIDLE Gel BIDLE Gel TID
    Arm/Group DescriptionVehicle Gel dosed BID and Vehicle Gel dosed TID, combinedLoteprednol Etabonate Ophthalmic Gel dosed BIDLoteprednol Etabonate Ophthalmic Gel dosed TID
    All Cause Mortality
    Vehicle BID and TIDLE Gel BIDLE Gel TID
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/198 (0%) 0/202 (0%) 0/199 (0%)
    Serious Adverse Events
    Vehicle BID and TIDLE Gel BIDLE Gel TID
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total1/198 (0.5%) 0/202 (0%) 0/199 (0%)
    Metabolism and nutrition disorders
    Hypokalemia1/198 (0.5%) 10/202 (0%) 00/199 (0%) 0
    Other (Not Including Serious) Adverse Events
    Vehicle BID and TIDLE Gel BIDLE Gel TID
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/198 (0%) 0/202 (0%) 0/199 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Please contact Sponsor directly for additional information.

    Results Point of Contact

    Name/TitleStudy Manager
    OrganizationBausch Health
    Phone(908) 242-8287
    Emailsandra.narain@bauschhealth.com
    Responsible Party:
    Bausch & Lomb Incorporated
    ClinicalTrials.gov Identifier:
    NCT02786901
    Other Study ID Numbers:
    • 875
    First Posted:
    Jun 1, 2016
    Last Update Posted:
    Jan 8, 2021
    Last Verified:
    Jan 1, 2021