Cataract, Ocular Inflammation, Pain
Conditions
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.
Interventions
DRUGLoteprednol Etabonate Ophthalmic Gel dosed TID
Gel
DRUGLoteprednol Etabonate Ophthalmic Gel dosed BID
Gel
DRUGVehicle Gel
Gel
Sponsors
Bausch & Lomb Incorporated
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Vehicle BID and TID Vehicle Gel dosed BID and Vehicle Gel dosed TID, combined | 199 |
| LE Gel BID Loteprednol Etabonate Ophthalmic Gel dosed BID | 201 |
| LE Gel TID Loteprednol Etabonate Ophthalmic Gel dosed TID | 200 |
| Total | 600 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 2 |
| Overall Study | Disallowed medication | 1 | 1 | 0 |
| Overall Study | Physician Decision | 1 | 0 | 0 |
| Overall Study | Randomized in error | 2 | 0 | 1 |
| Overall Study | Rescue Therapy Use | 71 | 49 | 33 |
| Overall Study | Subject Request/Lost to Follow up | 1 | 5 | 5 |
Baseline characteristics
| Characteristic | Total | Vehicle BID and TID | LE Gel TID | LE Gel BID |
|---|---|---|---|---|
| Age, Continuous | 68.2 years STANDARD_DEVIATION 9.11 | 68.5 years STANDARD_DEVIATION 8.92 | 67.9 years STANDARD_DEVIATION 9.32 | 68.3 years STANDARD_DEVIATION 9.11 |
| Iris Color Blue | 146 Participants | 50 Participants | 49 Participants | 47 Participants |
| Iris Color Brown | 338 Participants | 111 Participants | 112 Participants | 115 Participants |
| Iris Color Green | 31 Participants | 17 Participants | 5 Participants | 9 Participants |
| Iris Color Hazel | 80 Participants | 20 Participants | 32 Participants | 28 Participants |
| Iris Color Other | 5 Participants | 1 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 29 Participants | 7 Participants | 9 Participants | 13 Participants |
| Race (NIH/OMB) Black or African American | 60 Participants | 14 Participants | 23 Participants | 23 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 16 Participants | 9 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) White | 490 Participants | 169 Participants | 163 Participants | 158 Participants |
| Sex: Female, Male Female | 363 Participants | 116 Participants | 130 Participants | 117 Participants |
| Sex: Female, Male Male | 237 Participants | 83 Participants | 70 Participants | 84 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 198 | 0 / 202 | 0 / 199 |
| other Total, other adverse events | 0 / 198 | 0 / 202 | 0 / 199 |
| serious Total, serious adverse events | 1 / 198 | 0 / 202 | 0 / 199 |
Outcome results
Primary
Number of Participants With Complete Resolution of Anterior Chamber (AC) Cells at Visit 5 (Postoperative Day 8)
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.
Time frame: 8 days
Population: Missing values and post rescue values imputed as failures.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vehicle BID and TID | Number of Participants With Complete Resolution of Anterior Chamber (AC) Cells at Visit 5 (Postoperative Day 8) | 40 Participants |
| LE Gel BID | Number of Participants With Complete Resolution of Anterior Chamber (AC) Cells at Visit 5 (Postoperative Day 8) | 52 Participants |
| LE Gel TID | Number of Participants With Complete Resolution of Anterior Chamber (AC) Cells at Visit 5 (Postoperative Day 8) | 61 Participants |
Primary
Number of Participants With Complete Resolution of Ocular Pain in Study Eye at Visit 5 (Postoperative Day 8)
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.
Time frame: 8 days
Population: Missing values and post rescue values imputed as failures.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vehicle BID and TID | Number of Participants With Complete Resolution of Ocular Pain in Study Eye at Visit 5 (Postoperative Day 8) | 99 Participants |
| LE Gel BID | Number of Participants With Complete Resolution of Ocular Pain in Study Eye at Visit 5 (Postoperative Day 8) | 151 Participants |
| LE Gel TID | Number of Participants With Complete Resolution of Ocular Pain in Study Eye at Visit 5 (Postoperative Day 8) | 151 Participants |
Secondary
Change From Baseline in Summed Anterior Chamber (AC) Cell and Flare Scores at Final On-Treatment Visit
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.
Time frame: 14 days
Population: Missing values and post-rescue values imputed using last observation carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vehicle BID and TID | Change From Baseline in Summed Anterior Chamber (AC) Cell and Flare Scores at Final On-Treatment Visit | -1.2 score on a scale | Standard Deviation 1.9 |
| LE Gel BID | Change From Baseline in Summed Anterior Chamber (AC) Cell and Flare Scores at Final On-Treatment Visit | -2.0 score on a scale | Standard Deviation 1.5 |
| LE Gel TID | Change From Baseline in Summed Anterior Chamber (AC) Cell and Flare Scores at Final On-Treatment Visit | -2.1 score on a scale | Standard Deviation 1.5 |
Secondary
Number of Participants With Complete Resolution of Anterior Chamber (AC) Cells in the Study Eye at Final On-treatment Visit.
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.
Time frame: 14 days
Population: Missing values and post rescue values imputed as failures.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vehicle BID and TID | Number of Participants With Complete Resolution of Anterior Chamber (AC) Cells in the Study Eye at Final On-treatment Visit. | 67 Participants |
| LE Gel BID | Number of Participants With Complete Resolution of Anterior Chamber (AC) Cells in the Study Eye at Final On-treatment Visit. | 82 Participants |
| LE Gel TID | Number of Participants With Complete Resolution of Anterior Chamber (AC) Cells in the Study Eye at Final On-treatment Visit. | 94 Participants |
Secondary
Number of Participants With Complete Resolution of Anterior Chamber (AC) Flare in the Study Eye at Final On-Treatment Visit
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 frame: 14 days
Population: Missing values and post rescue values imputed as failures.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vehicle BID and TID | Number of Participants With Complete Resolution of Anterior Chamber (AC) Flare in the Study Eye at Final On-Treatment Visit | 107 Participants |
| LE Gel BID | Number of Participants With Complete Resolution of Anterior Chamber (AC) Flare in the Study Eye at Final On-Treatment Visit | 143 Participants |
| LE Gel TID | Number of Participants With Complete Resolution of Anterior Chamber (AC) Flare in the Study Eye at Final On-Treatment Visit | 153 Participants |
Secondary
Number of Participants With Complete Resolution of Both Anterior Chamber (AC) Cells and AC Flare in the Study Eye at Final On-Treatment Visit
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.
Time frame: 14 days
Population: Missing values and post rescue values imputed as failures.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vehicle BID and TID | Number of Participants With Complete Resolution of Both Anterior Chamber (AC) Cells and AC Flare in the Study Eye at Final On-Treatment Visit | 66 Participants |
| LE Gel BID | Number of Participants With Complete Resolution of Both Anterior Chamber (AC) Cells and AC Flare in the Study Eye at Final On-Treatment Visit | 82 Participants |
| LE Gel TID | Number of Participants With Complete Resolution of Both Anterior Chamber (AC) Cells and AC Flare in the Study Eye at Final On-Treatment Visit | 92 Participants |
Secondary
Number of Participants With Complete Resolution of Ocular Pain in Study Eye at Final On-Treatment Visit
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.
Time frame: 14 days
Population: Missing values and post rescue values imputed as failures.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vehicle BID and TID | Number of Participants With Complete Resolution of Ocular Pain in Study Eye at Final On-Treatment Visit | 122 Participants |
| LE Gel BID | Number of Participants With Complete Resolution of Ocular Pain in Study Eye at Final On-Treatment Visit | 168 Participants |
| LE Gel TID | Number of Participants With Complete Resolution of Ocular Pain in Study Eye at Final On-Treatment Visit | 170 Participants |
Secondary
Number of Participants With Treatment Failure at Visit 5 (Postoperative Day 8)
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.
Time frame: 8 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vehicle BID and TID | Number of Participants With Treatment Failure at Visit 5 (Postoperative Day 8) | 62 Participants |
| LE Gel BID | Number of Participants With Treatment Failure at Visit 5 (Postoperative Day 8) | 23 Participants |
| LE Gel TID | Number of Participants With Treatment Failure at Visit 5 (Postoperative Day 8) | 20 Participants |