Loteprednol Etabonate Ophthalmic Ointment vs. Vehicle in the Treatment of Inflammation Following Cataract Surgery

• Sponsor: Bausch & Lomb Incorporated (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00645671
• Collaborator: (none)
• Enrollment: 400
• Location: 1
• Arms: 2
• Duration (Months): 12
• Patients Per Site Per Month: 33.4

Study Details

Study Description

Brief Summary

To evaluate the clinical safety and efficacy of Loteprednol Etabonate Ophthalmic Ointment, 0.5% vs. vehicle for the treatment of inflammation following cataract surgery

Condition or Disease	Intervention/Treatment	Phase
Ocular Inflammation	Drug: 0.5% Loteprednol Etabonate Ophthalmic Ointment; Drug: Vehicle of Loteprednol Etabonate Ophthalmic Ointment	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 400 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized Multicenter, Double-Masked, Parallel-Group Clinical Safety and Efficacy Evaluation of Loteprednol Etabonate Ophthalmic Ointment, 0.5% Versus Vehicle for the Treatment of Inflammation Following Cataract Surgery
• Study Start Date: Mar 1, 2008
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Loteprednol Etabonate Loteprednol etabonate 0.5% ophthalmic ointment	Drug: 0.5% Loteprednol Etabonate Ophthalmic Ointment; 1/2 inch ribbon four times a day for 14 days
Placebo Comparator: Vehicle Vehicle of loteprednol etabonate ointment	Drug: Vehicle of Loteprednol Etabonate Ophthalmic Ointment; 1/2 inch ribbon four times a day for 14 days

Outcome Measures

Primary Outcome Measures

1. Subjects With Complete Resolution of Anterior Chamber Cells and Flare. Grade=0. [Postoperative Day 8 (Visit 5)]

   A combination of the grades for inflammatory cells and flare in the anterior chamber. Cells: accumulation of white blood cells in aqueous. 0=No cells seen; 1=1-5 cells; 2=6-15 cells; 3=16-30 cells; 4= >30 cells. Flare: Scattering of a slit lamp light beam when directed into the anterior chamber (Tyndall effect). 0=None; 1=Mild; 2=Moderate; 3=Severe; 4=Very severe.

2. Grade 0 for Pain [Postoperative Day 8 (Visit 5)]

   Pain: A positive sensation of the eye, including foreign body sensation, stabbing, throbbing, or aching. Grade 0 = None; 1=Minimal; 2=Mild; 3=Moderate; 4=Moderately Severe; 5=Severe

Secondary Outcome Measures

1. Subjects With Complete Resolution of Anterior Chamber Cells and Flare. At Each Follow-up Visit. [At each follow-up visit through day18 (Visit 7)]

   A combination of the grades for inflammatory cells and flare in the anterior chamber. Cells: accumulation of white blood cells in aqueous. 0=No cells seen; 1=1-5 cells; 2=6-15 cells; 3=16-30 cells; 4= >30 cells. Flare: Scattering of a slit lamp light beam when directed into the anterior chamber (Tyndall effect). 0=None; 1=Mild; 2=Moderate; 3=Severe; 4=Very severe.

2. Change From Baseline to Each Follow-up Visit in Anterior Chamber Cells and Flare [Baseline and each follow-up visit through day18 (Visit 7)]

   A combination of the grades for inflammatory cells and flare in the anterior chamber. Cells: accumulation of white blood cells in aqueous. 0=No cells seen; 1=1-5 cells; 2=6-15 cells; 3=16-30 cells; 4= >30 cells. Flare: Scattering of a slit lamp light beam when directed into the anterior chamber (Tyndall effect). 0=None; 1=Mild; 2=Moderate; 3=Severe; 4=Very severe.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Subjects who are candidate for routine, uncomplicated cataract surgery

2. Subjects who, in the Investigator's opinion, have potential postoperative pinholed Snellen visual acuity (VA) of at least 20/200 in the study eye.

Exclusion Criteria:

1. Subjects who will require concurrent ocular therapy with NSAIDs, mast cell stabilizers, antihistamines, decongestants, or immunosuppressants (e.g., Restasis), or with ocular or systemic corticosteroids

2. Subjects who have known hypersensitivity or contraindication to the study drug(s) or their components

3. Subjects who are monocular or have pinholed Snellen VA 20/200 or worse in the non-study eye

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	John Hunkeler, MD	Overland Park	Kansas	United States	66210

Sponsors and Collaborators

• Bausch & Lomb Incorporated

Investigators

• Study Director: Alyson J Berliner, MD/PhD, Bausch & Lomb Incorporated

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bausch & Lomb Incorporated
• ClinicalTrials.gov Identifier: NCT00645671
• Other Study ID Numbers: 525
• First Posted: Mar 28, 2008
• Last Update Posted: Mar 24, 2015
• Last Verified: Mar 1, 2015

• Additional relevant MeSH terms: Cataract; Inflammation; Loteprednol Etabonate

Study Results

Participant Flow

Recruitment Details	A total of 400 subjects, 18 years old or older who were candidates for routine, uncomplicated cataract surgery, were enrolled at 17 investigative sites in the US. First subject was enrolled on 3/14/2008 and last subject visit was 3/23/2009.
Pre-assignment Detail	Following cataract surgery at visit 3 (post operative day 1), subjects were assessed for eligibility. 201 subjects were randomized to receive loteprednol etabonate ointment and 199 to receive its vehicle.

Arm/Group Title	Loteprednol Etabonate	Vehicle
Arm/Group Description	Loteprednol etabonate 0.5% ophthalmic ointment	Vehicle of loteprednol etabonate ointment
Period Title: Overall Study
STARTED	201	199
COMPLETED	200	193
NOT COMPLETED	1	6

Baseline Characteristics

Arm/Group Title	Loteprednol Etabonate	Vehicle	Total
Arm/Group Description	Loteprednol etabonate 0.5% ophthalmic ointment	Vehicle of loteprednol etabonate ointment	Total of all reporting groups
Overall Participants	201	199	400
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69.2 (9.39)	69.2 (8.77)	69.2 (9.08)
Sex: Female, Male (Count of Participants)
Female	118 58.7%	119 59.8%	237 59.3%
Male	83 41.3%	80 40.2%	163 40.8%
Race/Ethnicity, Customized (participants) [Number]
Asian	1 0.5%	6 3%	7 1.8%
Black or African American	17 8.5%	12 6%	29 7.3%
White	183 91%	179 89.9%	362 90.5%
Other	0 0%	2 1%	2 0.5%

Outcome Measures

1. Primary Outcome

Title	Subjects With Complete Resolution of Anterior Chamber Cells and Flare. Grade=0.
Description	A combination of the grades for inflammatory cells and flare in the anterior chamber. Cells: accumulation of white blood cells in aqueous. 0=No cells seen; 1=1-5 cells; 2=6-15 cells; 3=16-30 cells; 4= >30 cells. Flare: Scattering of a slit lamp light beam when directed into the anterior chamber (Tyndall effect). 0=None; 1=Mild; 2=Moderate; 3=Severe; 4=Very severe.
Time Frame	Postoperative Day 8 (Visit 5)

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	Loteprednol Etabonate	Vehicle
Arm/Group Description	Loteprednol etabonate 0.5% ophthalmic ointment	Vehicle of loteprednol etabonate ointment
Measure Participants	201	199
Yes	48 23.9%	27 13.6%
No	153 76.1%	172 86.4%

2. Secondary Outcome

Title	Subjects With Complete Resolution of Anterior Chamber Cells and Flare. At Each Follow-up Visit.
Description	A combination of the grades for inflammatory cells and flare in the anterior chamber. Cells: accumulation of white blood cells in aqueous. 0=No cells seen; 1=1-5 cells; 2=6-15 cells; 3=16-30 cells; 4= >30 cells. Flare: Scattering of a slit lamp light beam when directed into the anterior chamber (Tyndall effect). 0=None; 1=Mild; 2=Moderate; 3=Severe; 4=Very severe.
Time Frame	At each follow-up visit through day18 (Visit 7)

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	Loteprednol Etabonate	Vehicle
Arm/Group Description	Loteprednol etabonate 0.5% ophthalmic ointment	Vehicle of loteprednol etabonate ointment
Measure Participants	201	199
Visit 4 (postoperative day 3)	10 5%	9 4.5%
Visit 5 (postoperative day 8)	48 23.9%	27 13.6%
Visit 6 (postoperative day 15)	84 41.8%	30 15.1%
Visit 7 (postoperative day 18)	86 42.8%	39 19.6%

3. Secondary Outcome

Title	Change From Baseline to Each Follow-up Visit in Anterior Chamber Cells and Flare
Description	A combination of the grades for inflammatory cells and flare in the anterior chamber. Cells: accumulation of white blood cells in aqueous. 0=No cells seen; 1=1-5 cells; 2=6-15 cells; 3=16-30 cells; 4= >30 cells. Flare: Scattering of a slit lamp light beam when directed into the anterior chamber (Tyndall effect). 0=None; 1=Mild; 2=Moderate; 3=Severe; 4=Very severe.
Time Frame	Baseline and each follow-up visit through day18 (Visit 7)

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	Loteprednol Etabonate	Vehicle
Arm/Group Description	Loteprednol etabonate 0.5% ophthalmic ointment	Vehicle of loteprednol etabonate ointment
Measure Participants	201	199
Visit 4 (postoperative day 3)	-1.0 (1.08)	-0.4 (1.42)
Visit 5 (postoperative day 8)	-2.1 (1.31)	-0.7 (1.81)
Visit 6 (postoperative day 15)	-2.6 (1.37)	-0.9 (1.97)
Visit 7 (postoperative day 18)	-2.5 (1.45)	-1.1 (1.95)

4. Primary Outcome

Title	Grade 0 for Pain
Description	Pain: A positive sensation of the eye, including foreign body sensation, stabbing, throbbing, or aching. Grade 0 = None; 1=Minimal; 2=Mild; 3=Moderate; 4=Moderately Severe; 5=Severe
Time Frame	Postoperative Day 8 (Visit 5)

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	Loteprednol Etabonate	Vehicle
Arm/Group Description	Loteprednol etabonate 0.5% ophthalmic ointment	Vehicle of loteprednol etabonate ointment
Measure Participants	201	199
Yes	156 77.6%	90 45.2%
No	45 22.4%	109 54.8%

Adverse Events

Time Frame	The LE treatment group had a mean exposure of 13.2 days (+/-3.06), the vehicle treatment group mean exposure was 9.2 days (+/-5.10). Mean days of exposure was < 14 days due to the use of rescue medication, especially in the vehicle group.
Adverse Event Reporting Description	Ocular AE's in study eyes and were reported prior to rescue medication use - safety population.
Arm/Group Title	Loteprednol Etabonate		Vehicle
Arm/Group Description	Loteprednol etabonate 0.5% ophthalmic ointment		Vehicle of loteprednol etabonate ointment
All Cause Mortality
	Loteprednol Etabonate		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Loteprednol Etabonate		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/201 (1.5%)		2/199 (1%)
Cardiac disorders
Myocardial Infarction	1/201 (0.5%)	2	1/199 (0.5%)	2
Eye disorders
Endophthalmitis	1/201 (0.5%)	1	1/199 (0.5%)	1
Post-operative inflammation	1/201 (0.5%)	1	1/199 (0.5%)	1
Musculoskeletal and connective tissue disorders
Fracture	1/201 (0.5%)	1	1/199 (0.5%)	1
Other (Not Including Serious) Adverse Events
	Loteprednol Etabonate		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	110/201 (54.7%)		161/199 (80.9%)
Eye disorders
Anterior chamber cell	5/201 (2.5%)	15	10/199 (5%)	15
Anterior chamber inflammation	61/201 (30.3%)	167	106/199 (53.3%)	167
Ciliary hyperemia	5/201 (2.5%)	15	10/199 (5%)	15
Conjunctival hyperemia	10/201 (5%)	25	15/199 (7.5%)	25
Corneal edema	8/201 (4%)	19	11/199 (5.5%)	19
Eye pain	8/201 (4%)	34	26/199 (13.1%)	34
Iritis	11/201 (5.5%)	30	19/199 (9.5%)	30
Lacrimation increased	6/201 (3%)	20	14/199 (7%)	20
Ocular hyperemia	5/201 (2.5%)	15	10/199 (5%)	15
Ocular pruritis	5/201 (2.5%)	21	16/199 (8%)	21
Photophobia	17/201 (8.5%)	36	19/199 (9.5%)	36

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The results of the study may be published or presented by the Investigator(s) after the review by, and in consultation and agreement with, the Sponsor and such that confidential or proprietary information is not disclosed. Prior to publication or presentation, a copy of the final text should be forwarded by the Investigator(s) to the Sponsor or its designee for comment.