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)
• Enrollment: 600
• Locations: 6
• Arms: 3
• Actual Duration (Months): 13
• Patients Per Site: 100
• Patients Per Site Per Month: 7.7

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 Disease	Intervention/Treatment	Phase
Cataract; Pain; Ocular Inflammation	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

Arm	Intervention/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

	Site	City	State	Country	Postal Code
1	Valeant Site 01	Phoenix	Arizona	United States	85032
2	Valeant Site 03	Oceanside	California	United States	92056
3	Valeant Site 05	Miami	Florida	United States	33143
4	Valeant Site 04	Quincy	Massachusetts	United States	02169
5	Valeant Site 06	Kansas City	Missouri	United States	64111
6	Valeant Site 02	Saint Louis	Missouri	United States	63131

Sponsors and Collaborators

• Bausch & Lomb Incorporated

Investigators

• Study Director: Denise Ramjit, Valeant Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 1, 2016

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: Cataract; Inflammation; Loteprednol Etabonate

Study Results

Participant Flow

Arm/Group Title	Vehicle BID and TID	LE Gel BID	LE Gel TID
Arm/Group Description	Vehicle Gel dosed BID and Vehicle Gel dosed TID, combined	Loteprednol Etabonate Ophthalmic Gel dosed BID	Loteprednol Etabonate Ophthalmic Gel dosed TID
Period Title: Overall Study
STARTED	199	201	200
COMPLETED	122	145	159
NOT COMPLETED	77	56	41

Baseline Characteristics

Arm/Group Title	Vehicle BID and TID	LE Gel BID	LE Gel TID	Total
Arm/Group Description	Vehicle Gel dosed BID and Vehicle Gel dosed TID, combined	Loteprednol Etabonate Ophthalmic Gel dosed BID	Loteprednol Etabonate Ophthalmic Gel dosed TID	Total of all reporting groups
Overall Participants	199	201	200	600
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

Title	Number of Participants With Complete Resolution of Anterior Chamber (AC) Cells at Visit 5 (Postoperative Day 8)
Description	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

Outcome Measure Data

Analysis Population Description

Missing values and post rescue values imputed as failures.

Arm/Group Title	Vehicle BID and TID	LE Gel BID	LE Gel TID
Arm/Group Description	Vehicle Gel dosed BID and Vehicle Gel dosed TID, combined	Loteprednol Etabonate Ophthalmic Gel dosed BID	Loteprednol Etabonate Ophthalmic Gel dosed TID
Measure Participants	199	201	200
Count of Participants [Participants]	40 20.1%	52 25.9%	61 30.5%

2. Primary Outcome

Title	Number of Participants With Complete Resolution of Ocular Pain in Study Eye at Visit 5 (Postoperative Day 8)
Description	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

Outcome Measure Data

Analysis Population Description

Missing values and post rescue values imputed as failures.

Arm/Group Title	Vehicle BID and TID	LE Gel BID	LE Gel TID
Arm/Group Description	Vehicle Gel dosed BID and Vehicle Gel dosed TID, combined	Loteprednol Etabonate Ophthalmic Gel dosed BID	Loteprednol Etabonate Ophthalmic Gel dosed TID
Measure Participants	199	201	200
Count of Participants [Participants]	99 49.7%	151 75.1%	151 75.5%

3. Secondary Outcome

Title	Number of Participants With Complete Resolution of Anterior Chamber (AC) Cells in the Study Eye at Final On-treatment Visit.
Description	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

Outcome Measure Data

Analysis Population Description

Missing values and post rescue values imputed as failures.

Arm/Group Title	Vehicle BID and TID	LE Gel BID	LE Gel TID
Arm/Group Description	Vehicle Gel dosed BID and Vehicle Gel dosed TID, combined	Loteprednol Etabonate Ophthalmic Gel dosed BID	Loteprednol Etabonate Ophthalmic Gel dosed TID
Measure Participants	190	201	198
Count of Participants [Participants]	67 33.7%	82 40.8%	94 47%

4. Secondary Outcome

Title	Number of Participants With Complete Resolution of Ocular Pain in Study Eye at Final On-Treatment Visit
Description	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

Outcome Measure Data

Analysis Population Description

Missing values and post rescue values imputed as failures.

Arm/Group Title	Vehicle BID and TID	LE Gel BID	LE Gel TID
Arm/Group Description	Vehicle Gel dosed BID and Vehicle Gel dosed TID, combined	Loteprednol Etabonate Ophthalmic Gel dosed BID	Loteprednol Etabonate Ophthalmic Gel dosed TID
Measure Participants	190	201	198
Count of Participants [Participants]	122 61.3%	168 83.6%	170 85%

5. Secondary Outcome

Title	Number of Participants With Complete Resolution of Anterior Chamber (AC) Flare in the Study Eye at Final On-Treatment Visit
Description	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

Outcome Measure Data

Analysis Population Description

Missing values and post rescue values imputed as failures.

Arm/Group Title	Vehicle BID and TID	LE Gel BID	LE Gel TID
Arm/Group Description	Vehicle Gel dosed BID and Vehicle Gel dosed TID, combined	Loteprednol Etabonate Ophthalmic Gel dosed BID	Loteprednol Etabonate Ophthalmic Gel dosed TID
Measure Participants	190	201	198
Count of Participants [Participants]	107 53.8%	143 71.1%	153 76.5%

6. Secondary Outcome

Title	Number of Participants With Complete Resolution of Both Anterior Chamber (AC) Cells and AC Flare in the Study Eye at Final On-Treatment Visit
Description	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

Outcome Measure Data

Analysis Population Description

Missing values and post rescue values imputed as failures.

Arm/Group Title	Vehicle BID and TID	LE Gel BID	LE Gel TID
Arm/Group Description	Vehicle Gel dosed BID and Vehicle Gel dosed TID, combined	Loteprednol Etabonate Ophthalmic Gel dosed BID	Loteprednol Etabonate Ophthalmic Gel dosed TID
Measure Participants	190	201	198
Count of Participants [Participants]	66 33.2%	82 40.8%	92 46%

7. Secondary Outcome

Title	Change From Baseline in Summed Anterior Chamber (AC) Cell and Flare Scores at Final On-Treatment Visit
Description	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

Outcome Measure Data

Analysis Population Description

Missing values and post-rescue values imputed using last observation carried forward.

Arm/Group Title	Vehicle BID and TID	LE Gel BID	LE Gel TID
Arm/Group Description	Vehicle Gel dosed BID and Vehicle Gel dosed TID, combined	Loteprednol Etabonate Ophthalmic Gel dosed BID	Loteprednol Etabonate Ophthalmic Gel dosed TID
Measure Participants	190	201	198
Mean (Standard Deviation) [score on a scale]	-1.2 (1.90)	-2.0 (1.50)	-2.1 (1.50)

8. Secondary Outcome

Title	Number of Participants With Treatment Failure at Visit 5 (Postoperative Day 8)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vehicle BID and TID	LE Gel BID	LE Gel TID
Arm/Group Description	Vehicle Gel dosed BID and Vehicle Gel dosed TID, combined	Loteprednol Etabonate Ophthalmic Gel dosed BID	Loteprednol Etabonate Ophthalmic Gel dosed TID
Measure Participants	199	201	200
Count of Participants [Participants]	62 31.2%	23 11.4%	20 10%

Adverse Events

Time Frame	14 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 Title	Vehicle BID and TID		LE Gel BID		LE Gel TID
Arm/Group Description	Vehicle Gel dosed BID and Vehicle Gel dosed TID, combined		Loteprednol Etabonate Ophthalmic Gel dosed BID		Loteprednol Etabonate Ophthalmic Gel dosed TID
All Cause Mortality
	Vehicle BID and TID		LE Gel BID		LE Gel TID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/198 (0%)		0/202 (0%)		0/199 (0%)
Serious Adverse Events
	Vehicle BID and TID		LE Gel BID		LE Gel TID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/198 (0.5%)		0/202 (0%)		0/199 (0%)
Metabolism and nutrition disorders
Hypokalemia	1/198 (0.5%)	1	0/202 (0%)	0	0/199 (0%)	0
Other (Not Including Serious) Adverse Events
	Vehicle BID and TID		LE Gel BID		LE Gel TID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/198 (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.