Loteprednol and Tobramycin Versus Tobramycin and Dexamethasone, in the Treatment of Blepharokeratoconjunctivitis

• Sponsor: Bausch & Lomb Incorporated (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01028027
• Collaborator: (none)
• Enrollment: 357
• Location: 1
• Arms: 2
• Duration (Months): 5
• Patients Per Site Per Month: 72

Study Details

Study Description

Brief Summary

This study is to evaluate the safety and efficacy of loteprednol etabonate [LE] and tobramycin ophthalmic suspension versus tobramycin and dexamethasone ophthalmic suspension in the treatment of ocular inflammation associated with blepharokeratoconjunctivitis (BKC).

Condition or Disease	Intervention/Treatment	Phase
Conjunctivitis; Keratitis; Blepharitis	Drug: Loteprednol and tobramycin; Drug: Tobramycin and dexamethasone	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 357 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Treatment
• Official Title: A Clinical Safety and Efficacy Evaluation of Zylet® Versus Tobradex in the Treatment of Blepharokeratoconjunctivitis
• Study Start Date: Oct 1, 2009
• Actual Primary Completion Date: Feb 1, 2010
• Actual Study Completion Date: Mar 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Loteprednol and tobramycin Loteprednol etabonate and tobramycin ophthalmic suspension	Drug: Loteprednol and tobramycin; Loteprednol etabonate and tobramycin ophthalmic suspension administered to study eye 4 times a day (QID) for 14 days.; Other Names: Zylet
Active Comparator: Tobramycin and dexamethasone Tobramycin and dexamethasone ophthalmic suspension	Drug: Tobramycin and dexamethasone; Tobramycin and dexamethasone ophthalmic suspension administered to study eye 4 times a day (QID) for 14 days.; Other Names: Tobradex

Outcome Measures

Primary Outcome Measures

1. Signs and Symptoms Composite Score - Change From Baseline to Day 15 - PP Population [Baseline, Day 15]

   The change from baseline (CFB) to Day 15 (Visit 4) in the ocular signs and symptoms composite score. Ocular signs and symptoms were collected for study eyes at each study visit using a 0-4 grading scale, assessed as 0 = none, 1 = minimal/trace, 2 = mild, 3 = moderate, and 4 = severe. The signs and symptoms composite score was the sum of each individual sign or symptom score. Per protocol population (PP).

Secondary Outcome Measures

1. Signs and Symptoms Composite Score - Change From Baseline to Day 15 - ITT Population [Baseline, Day 15]

   The CFB to Day 15 in the signs and symptoms composite score. Ocular signs and symptoms were collected for study eyes at each study visit using a 0-4 grading scale, assessed as 0 = none, 1 = minimal/trace, 2 = mild, 3 = moderate, and 4 = severe. The signs and symptoms composite score was the sum of each individual sign or symptom score. ITT population

2. Signs and Symptoms Composite Score - Change From Baseline to Day 8 - PP Population [Baseline, Day 8]

   The CFB to Day 8 (Visit 3) in the signs and symptoms composite score. Ocular signs and symptoms were collected for study eyes at each study visit using a 0-4 grading scale, assessed as 0 = none, 1 = minimal/trace, 2 = mild, 3 = moderate, and 4 = severe. The signs and symptoms composite score was the sum of each individual sign or symptom score.

3. Signs and Symptoms Composite Score - Change From Baseline to Day 8 - ITT Population [Baseline, Day 8]

   The CFB to Day 8 in the signs and symptoms composite score. Ocular signs and symptoms were collected for study eyes at each study visit using a 0-4 grading scale, assessed as 0 = none, 1 = minimal/trace, 2 = mild, 3 = moderate, and 4 = severe. The signs and symptoms composite score was the sum of each individual sign or symptom score. ITT population

4. Signs and Symptoms Composite Score Change From Baseline to Day 3 - PP Population [Baseline, Day 3]

   The CFB to Day 3 in the signs and symptoms composite score. Ocular signs and symptoms were collected for study eyes at each study visit using a 0-4 grading scale, assessed as 0 = none, 1 = minimal/trace, 2 = mild, 3 = moderate, and 4 = severe. The signs and symptoms composite score was the sum of each individual sign or symptom score. PP population.

5. Signs and Symptoms Composite Score Change From Baseline to Day 3 - ITT Population [Baseline, Day 3]

   The CFB to Day 3 in the signs and symptoms composite score. Ocular signs and symptoms were collected for study eyes at each study visit using a 0-4 grading scale, assessed as 0 = none, 1 = minimal/trace, 2 = mild, 3 = moderate, and 4 = severe. The signs and symptoms composite score was the sum of each individual sign or symptom score. ITT population.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Subjects must have a clinical diagnosis of BKC in at least one eye

• Subjects must be willing to discontinue contact lens use for the duration of the study

• Subjects who are able and willing to comply with all treatment and follow- up/study procedures.

Exclusion Criteria:

• Subjects participating in any drug or device clinical investigation within 30 days prior to entry into this study and/or during the period of study participation.

• Subjects who have any uncontrolled systemic disease or debilitating disease.

• Subjects who have a known hypersensitivity to the study drugs or their components (including benzalkonium chloride) or contraindications to tobramycin or ocular corticosteroids.

• Subjects who use any topical or systemic ophthalmic medications listed as disallowed in the study protocol, within the specified time frame prior to Visit 1.

• Subjects who have a disease or conditions which the Investigator determines could interfere with the safety and efficacy evaluations of the study drug.

• Subjects having ocular surgery (including laser surgery) in either eye within the past three months.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Bausch & Lomb Inc	Singapore		Singapore	556741

Sponsors and Collaborators

• Bausch & Lomb Incorporated

Investigators

• Study Director: Esther Chu, Bausch & Lomb Incorporated

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bausch & Lomb Incorporated
• ClinicalTrials.gov Identifier: NCT01028027
• Other Study ID Numbers: 617
• First Posted: Dec 9, 2009
• Last Update Posted: Feb 28, 2012
• Last Verified: Feb 1, 2012

• Keywords provided by Bausch & Lomb Incorporated: Blepharokeratoconjunctivitis
• Additional relevant MeSH terms: Conjunctivitis; Keratitis; Blepharitis; Loteprednol Etabonate; Tobramycin; Dexamethasone

Study Results

Participant Flow

Recruitment Details	This study was conducted at seven sites, by seven Investigators in the People's Republic of China. First participant was enrolled 10/21/2009 and last participant visit was 2/9/2010.
Pre-assignment Detail	A total of 357 participants with clinically diagnosed blepharokeratoconjunctivitis (BKC) in at least one eye were enrolled. 328 participants completed the study.

Arm/Group Title	Loteprednol and Tobramycin	Tobramycin and Dexamethasone
Arm/Group Description	Loteprednol etabonate 0.5% and tobramycin 0.3% ophthalmic suspension. Participants will instill one or two drops of study drug topically in the affected eye(s), at approximately four hour intervals, QID, for 14 days.	Tobramycin 0.3% and dexamethasone 0.1% ophthalmic suspension. Participants will instill one or two drops of study drug topically in the affected eye(s), at approximately four hour intervals, QID, for 14 days.
Period Title: Overall Study
STARTED	180	177
COMPLETED	164	164
NOT COMPLETED	16	13

Baseline Characteristics

Arm/Group Title	Loteprednol and Tobramycin	Tobramycin and Dexamethasone	Total
Arm/Group Description	Loteprednol etabonate 0.5% and tobramycin 0.3% ophthalmic suspension. Participants will instill one or two drops of study drug topically in the affected eye(s), at approximately four hour intervals, QID, for 14 days.	Tobramycin 0.3% and dexamethasone 0.1% ophthalmic suspension. Participants will instill one or two drops of study drug topically in the affected eye(s), at approximately four hour intervals, QID, for 14 days.	Total of all reporting groups
Overall Participants	180	177	357
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	40.8 (13.63)	41.72 (13.54)	41.26 (13.57)
Sex: Female, Male (Count of Participants)
Female	123 68.3%	113 63.8%	236 66.1%
Male	57 31.7%	64 36.2%	121 33.9%
Region of Enrollment (participants) [Number]
Singapore	180 100%	177 100%	357 100%

Outcome Measures

1. Primary Outcome

Title	Signs and Symptoms Composite Score - Change From Baseline to Day 15 - PP Population
Description	The change from baseline (CFB) to Day 15 (Visit 4) in the ocular signs and symptoms composite score. Ocular signs and symptoms were collected for study eyes at each study visit using a 0-4 grading scale, assessed as 0 = none, 1 = minimal/trace, 2 = mild, 3 = moderate, and 4 = severe. The signs and symptoms composite score was the sum of each individual sign or symptom score. Per protocol population (PP).
Time Frame	Baseline, Day 15

Outcome Measure Data

Analysis Population Description

The PP population was the population used for the primary efficacy analysis.

Arm/Group Title	Loteprednol and Tobramycin	Tobramycin and Dexamethasone
Arm/Group Description	Loteprednol etabonate 0.5% and tobramycin 0.3% ophthalmic suspension. Participants will instill one or two drops of study drug topically in the affected eye(s), at approximately four hour intervals, QID, for 14 days.	Tobramycin 0.3% and dexamethasone 0.1% ophthalmic suspension. Participants will instill one or two drops of study drug topically in the affected eye(s), at approximately four hour intervals, QID, for 14 days.
Measure Participants	156	152
Mean (Standard Deviation) [Scores on a scale]	-11.63 (4.56)	-12.41 (4.71)

2. Secondary Outcome

Title	Signs and Symptoms Composite Score - Change From Baseline to Day 15 - ITT Population
Description	The CFB to Day 15 in the signs and symptoms composite score. Ocular signs and symptoms were collected for study eyes at each study visit using a 0-4 grading scale, assessed as 0 = none, 1 = minimal/trace, 2 = mild, 3 = moderate, and 4 = severe. The signs and symptoms composite score was the sum of each individual sign or symptom score. ITT population
Time Frame	Baseline, Day 15

Outcome Measure Data

Analysis Population Description

The ITT population was used in this secondary efficacy parameter.

Arm/Group Title	Loteprednol and Tobramycin	Tobramycin and Dexamethasone
Arm/Group Description	Loteprednol etabonate 0.5% and tobramycin 0.3% ophthalmic suspension. Participants will instill one or two drops of study drug topically in the affected eye(s), at approximately four hour intervals, QID, for 14 days.	Tobramycin 0.3% and dexamethasone 0.1% ophthalmic suspension. Participants will instill one or two drops of study drug topically in the affected eye(s), at approximately four hour intervals, QID, for 14 days.
Measure Participants	164	165
Mean (Standard Deviation) [Score on a scale]	-11.64 (4.55)	-11.98 (4.95)

3. Secondary Outcome

Title	Signs and Symptoms Composite Score - Change From Baseline to Day 8 - PP Population
Description	The CFB to Day 8 (Visit 3) in the signs and symptoms composite score. Ocular signs and symptoms were collected for study eyes at each study visit using a 0-4 grading scale, assessed as 0 = none, 1 = minimal/trace, 2 = mild, 3 = moderate, and 4 = severe. The signs and symptoms composite score was the sum of each individual sign or symptom score.
Time Frame	Baseline, Day 8

Outcome Measure Data

Analysis Population Description

The PP population was used for this secondary efficacy parameters.

Arm/Group Title	Loteprednol and Tobramycin	Tobramycin and Dexamethasone
Arm/Group Description	Loteprednol etabonate 0.5% and tobramycin 0.3% ophthalmic suspension. Participants will instill one or two drops of study drug topically in the affected eye(s), at approximately four hour intervals, QID, for 14 days.	Tobramycin 0.3% and dexamethasone 0.1% ophthalmic suspension. Participants will instill one or two drops of study drug topically in the affected eye(s), at approximately four hour intervals, QID, for 14 days.
Measure Participants	155	150
Mean (Standard Deviation) [Score on a scale]	-9.20 (3.94)	-10.21 (4.23)

4. Secondary Outcome

Title	Signs and Symptoms Composite Score - Change From Baseline to Day 8 - ITT Population
Description	The CFB to Day 8 in the signs and symptoms composite score. Ocular signs and symptoms were collected for study eyes at each study visit using a 0-4 grading scale, assessed as 0 = none, 1 = minimal/trace, 2 = mild, 3 = moderate, and 4 = severe. The signs and symptoms composite score was the sum of each individual sign or symptom score. ITT population
Time Frame	Baseline, Day 8

Outcome Measure Data

Analysis Population Description

The ITT population was used in this secondary efficacy parameter.

Arm/Group Title	Loteprednol and Tobramycin	Tobramycin and Dexamethasone
Arm/Group Description	Loteprednol etabonate 0.5% and tobramycin 0.3% ophthalmic suspension. Participants will instill one or two drops of study drug topically in the affected eye(s), at approximately four hour intervals, QID, for 14 days.	Tobramycin 0.3% and dexamethasone 0.1% ophthalmic suspension. Participants will instill one or two drops of study drug topically in the affected eye(s), at approximately four hour intervals, QID, for 14 days.
Measure Participants	172	171
Mean (Standard Deviation) [Score on a scale]	-8.91 (4.24)	-9.96 (4.27)

5. Secondary Outcome

Title	Signs and Symptoms Composite Score Change From Baseline to Day 3 - PP Population
Description	The CFB to Day 3 in the signs and symptoms composite score. Ocular signs and symptoms were collected for study eyes at each study visit using a 0-4 grading scale, assessed as 0 = none, 1 = minimal/trace, 2 = mild, 3 = moderate, and 4 = severe. The signs and symptoms composite score was the sum of each individual sign or symptom score. PP population.
Time Frame	Baseline, Day 3

Outcome Measure Data

Analysis Population Description

The PP population was used for this secondary efficacy parameters.

Arm/Group Title	Loteprednol and Tobramycin	Tobramycin and Dexamethasone
Arm/Group Description	Loteprednol etabonate 0.5% and tobramycin 0.3% ophthalmic suspension. Participants will instill one or two drops of study drug topically in the affected eye(s), at approximately four hour intervals, QID, for 14 days.	Tobramycin 0.3% and dexamethasone 0.1% ophthalmic suspension. Participants will instill one or two drops of study drug topically in the affected eye(s), at approximately four hour intervals, QID, for 14 days.
Measure Participants	155	152
Mean (Standard Deviation) [Score on a scale]	-5.66 (3.46)	-5.98 (3.68)

6. Secondary Outcome

Title	Signs and Symptoms Composite Score Change From Baseline to Day 3 - ITT Population
Description	The CFB to Day 3 in the signs and symptoms composite score. Ocular signs and symptoms were collected for study eyes at each study visit using a 0-4 grading scale, assessed as 0 = none, 1 = minimal/trace, 2 = mild, 3 = moderate, and 4 = severe. The signs and symptoms composite score was the sum of each individual sign or symptom score. ITT population.
Time Frame	Baseline, Day 3

Outcome Measure Data

Analysis Population Description

The ITT population was used for this secondary efficacy parameters.

Arm/Group Title	Loteprednol and Tobramycin	Tobramycin and Dexamethasone
Arm/Group Description	Loteprednol etabonate 0.5% and tobramycin 0.3% ophthalmic suspension. Participants will instill one or two drops of study drug topically in the affected eye(s), at approximately four hour intervals, QID, for 14 days.	Tobramycin 0.3% and dexamethasone 0.1% ophthalmic suspension. Participants will instill one or two drops of study drug topically in the affected eye(s), at approximately four hour intervals, QID, for 14 days.
Measure Participants	177	176
Mean (Standard Deviation) [Score on a scale]	-5.54 (3.48)	-5.92 (3.69)

Adverse Events

Time Frame	14 days
Arm/Group Title	Loteprednol and Tobramycin		Tobramycin and Dexamethasone
Arm/Group Description	Loteprednol etabonate 0.5% and tobramycin 0.3% ophthalmic suspension. Participants will instill one or two drops of study drug topically in the affected eye(s), at approximately four hour intervals, QID, for 14 days.		Tobramycin 0.3% and dexamethasone 0.1% ophthalmic suspension. Participants will instill one or two drops of study drug topically in the affected eye(s), at approximately four hour intervals, QID, for 14 days.
All Cause Mortality
	Loteprednol and Tobramycin		Tobramycin and Dexamethasone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Loteprednol and Tobramycin		Tobramycin and Dexamethasone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/177 (0%)		0/177 (0%)
Other (Not Including Serious) Adverse Events
	Loteprednol and Tobramycin		Tobramycin and Dexamethasone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/177 (9%)		36/177 (20.3%)
Eye disorders
Increased IOP	16/177 (9%)	52	36/177 (20.3%)	52

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

All study data generated as a result of this study will be regarded as confidential, until appropriate analysis and review by the Sponsor or its designee and the Investigator(s) are completed. 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.