ZvL: Efficacy of Zylet vs. Lotemax for the Treatment of Ocular Surface Inflammation/MGD/Blepharitis

• Sponsor: Massachusetts Eye and Ear Infirmary (Other)
• Overall Status: Completed
• CT.gov ID: NCT01456780
• Collaborator: Bausch & Lomb Incorporated (Industry)
• Enrollment: 60
• Location: 1
• Arms: 3
• Actual Duration (Months): 70
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

This is a Phase IV, single site, randomized, double masked, parallel control clinical trial of 60 subjects to investigate the variance of efficacy between Lotemax® and Zylet® for treatment of ocular surface inflammation due to meibomian gland dysfunction (MGD). Efficacy will be measured by in-vivo confocal microscopy, corneal fluorescein staining, grading of meibomian gland dysfunction and validated ocular symptom assessment questionnaire.

Condition or Disease	Intervention/Treatment	Phase
Meibomian Gland Dysfunction; Posterior Blepharitis	Drug: Loteprednol/tobramycin; Drug: Loteprednol; Drug: B+L Advanced Eye Relief Lubricant Drop	Phase 4

Detailed Description

Posterior blepharitis is a common chronic eyelid condition that is described as generalized inflammation of the posterior lid margin and associated with inflammation of the ocular surface and with symptoms of burning, irritation, and discomfort. Posterior blepharitis is associated with various disorders of the meibomian glands, known collectively as meibomian gland dysfunction (MGD). It is associated either with obstruction and inflammation of the meibomian glands or, less commonly, atrophy of the meibomian glands.

Clinically, MGD often presents with inspissated meibomian glands, oily tear film, as well as inflammation and vascularization of the meibomian gland orifices. Papillary hypertrophy of the tarsal conjunctiva and corneal punctate epitheliopathy are often present, and there are prominent associations with dermatoses, such as acne rosacea, seborrhoeic dermatitis, and atopic dermatitis. Evidence from several sources suggests that MGD of sufficient extent and degree is associated with a deficient tear lipid layer, an increase in tear evaporation, and the occurrence of an evaporative dry eye. In fact MGD is considered to be the most common cause of evaporative dry eye. Individuals with MGD often complain of significant discomfort, including burning, itching, irritation, and photophobia. They may also have other associated symptoms of dry eye and may be plagued by blurred vision, gradual contact lens intolerance. Furthermore, these patients may become functionally handicapped by the negative impact of dry eye on their crucial daily activities such as working, reading, using computer, and driving.

Despite the high incidence of posterior blepharitis, there is currently no consistently effective treatment for this condition and it still remains a therapeutic challenge. Posterior blepharitis has traditionally been managed with eyelid hygiene, topical antibiotics (erythromycin or bacitracin ointments), oral tetracyclines (tetracycline, doxycycline, or minocycline) and corticosteroids which are often time consuming, frustrating, and frequently ineffective or variably effective.

The purpose of this study is to compare the effectiveness of topical loteprednol (corticosteroid) vs. the combination of loteprednol and tobramycin (corticosteroid and antibiotic) against an artificial tear. It is critical to determine to what extent the addition of an antibiotic to a topical steroid can enhance the therapeutic efficacy of the treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Relative Efficacy of Loteprednol (Lotemax®) vs. Loteprednol/Tobramycin (Zylet®) in Treatment of Chronic Ocular Surface Inflammation Associated With Meibomian Gland Dysfunction (MGD)/Posterior Blepharitis
• Actual Study Start Date: Aug 1, 2011
• Actual Primary Completion Date: Mar 1, 2013
• Actual Study Completion Date: Jun 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Zylet Subject randomized to this arm will be treated with Zylet (Loteprednol/tobramycin), twice a day, for 4 weeks. Zylet is a combination of loteprednol and tobramycin. Loteprednol is in a class of drugs called corticosteroids. Loteprednol inhibits processes in the body that cause inflammation. Tobramycin is an antibiotic.	Drug: Loteprednol/tobramycin; Zylet (loteprednol/tobramycin) drops, 1 drop twice a day for 4 weeks.; Other Names: Zylet
Active Comparator: Lotemax Subject randomized to this arm will be treated with Lotemax, twice a day, for 4 weeks. Lotemax is also known as loteprednol. Loteprednol is in a class of drugs called corticosteroids. Loteprednol inhibits processes in the body that cause inflammation.	Drug: Loteprednol; Eye drops, 1 drop twice a day for 4 weeks; Other Names: Lotemax
Placebo Comparator: B+L Advanced Eye Relief Lubricant Drop Subject randomized to this arm will be treated with B+L Advanced Eye Relief Lubricant Eye Drops (Artificial Tears), twice a day, for 4 weeks.	Drug: B+L Advanced Eye Relief Lubricant Drop; Bausch + Lomb (B+L) Advanced Eye Relief Lubricant Drop (Artificial Tears), 1 drop twice a day for 4 weeks.; Other Names: artificial tears

Outcome Measures

Primary Outcome Measures

1. Ocular Surface Disease Index [Week 4 Time Point]

   OSDI is a 12-question survey used to measure the symptoms of dry eye disease. Each of the 12 individual questions rate one symptom on a 0-4 scale, with 4 meaning that the symptom is present all of the time and 0 meaning the symptom is present none of the time. The overall ODSI score is calculated by adding all of the values from the 12 questions, multiplying that value by 25, and dividing the resulting value by the number of questions answered. This results in an overall scale that ranges from 0-100, with 100 being severe dry eye symptoms and 0 being no dry eye symptoms.

2. Symptom Assessment iN Dry Eye (SANDE) Frequency Score [Week 4 Time Point]

   Questionnaire given to patients to assess the frequency of dry eye symptoms. The questionnaire utilizes a 100 mm horizontal Visual Analogue Scale technique to quantify the frequency of the patient's dry eye symptoms. Change is quantified from baseline to week 4. The range of the SANDE frequency scale is 0-100, with 0 being the minimum level of frequency of dry eye symptoms and 100 being the maximum level of frequency of dry eye symptoms.

3. Symptom Assessment iN Dry Eye (SANDE) Severity Score [Week 4 Time Point]

   Questionnaire given to patients to assess the severity of dry eye symptoms. The questionnaire utilizes a 100 mm horizontal Visual Analogue Scale technique to quantify the severity of the patient's dry eye symptoms. Change is quantified from baseline to week 4. The range of the SANDE severity scale is 0-100, with minimum level of severity of dry eye symptoms and 100 being the maximum level of severity of dry eye symptoms.

4. Corneal Fluorescein Staining Score [Week 4 Time Point]

   Corneal Fluorescein Staining is used to assess the level of corneal epitheliopathy that is related to dry eye disease. The CFS scale ranges from 0 to 15 scale, with 0 representing the minimum level of corneal epitheliopathy and 15 representing the maximum level of corneal epitheliopathy.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Male or female

• At least 18 years of age

• Has not worn contact lenses, except for bandage contact lens or rigid gas permeable lens, for at least 2 weeks prior to the study and agrees to not wear contact lenses during study

• Patient is in generally good & stable overall health

• Minimum corneal fluorescein staining of 4 in at least one eye

• OSDI score >22

• The patient must have a diagnosis of posterior blepharitis

• A negative urine pregnancy test result for women of childbearing potential

• Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation.

• Normal lid position and closure

• Ability to understand and provide informed consent to participate in this study

• Willingness to follow study instructions and likely to complete all required visits

Exclusion Criteria:

• History of Stevens-Johnson syndrome or ocular pemphigoid

• History of eyelid surgery

• Intra-ocular surgery or ocular laser surgery within 3 months

• History of microbial keratitis, including herpes

• Active ocular allergies

• Corneal epithelial defect > 1mm2

• Any change in use of topical anti-inflammatories, such as steroids, Restasis, or NSAID within the past 2 weeks

• Any change in dosage of tetracycline compounds (tetracycline, doxycycline, and minocycline) within the past two weeks

• Use of isotretinoin (Accutane) within the past 6 months

• Pregnant or lactating women

• Signs of current infection, including fever and current treatment with antibiotics

• Active liver, renal, or hematologic disease

• The use of any other investigational drug

• Individuals with a known history of glaucoma, individuals with IOP >22 Hg in either eye and individuals with a known family history of glaucoma in primary (first degree) relatives (ie. mother, father, sibling or child)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts Eye & Ear Infirmary	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Massachusetts Eye and Ear Infirmary
• Bausch & Lomb Incorporated

Investigators

• Principal Investigator: Reza Dana, MD, MPH, MSc, Massachusetts Eye and Ear Infirmary

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Reza Dana, MD, Principal Investigator, Massachusetts Eye and Ear Infirmary
• ClinicalTrials.gov Identifier: NCT01456780
• Other Study ID Numbers: 11-048H
• First Posted: Oct 21, 2011
• Last Update Posted: Aug 1, 2017
• Last Verified: Jul 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Reza Dana, MD, Principal Investigator, Massachusetts Eye and Ear Infirmary: Meibomian gland dysfunction; Blepharitis; Dry Eye; Ocular Inflammation; MGD; Zylet; Lotemax; Artificial Tear
• Additional relevant MeSH terms: Meibomian Gland Dysfunction; Blepharitis; Inflammation; Loteprednol Etabonate; Tobramycin; Lubricant Eye Drops

Study Results

Participant Flow

Arm/Group Title	Zylet	Lotemax	Bausch & Lomb Lubricant Drops
Arm/Group Description	Subject randomized to this arm will be treated with Zylet, twice a day, for 4 weeks. Zylet is a combination of loteprednol and tobramycin. Loteprednol is in a class of drugs called corticosteroids. Loteprednol inhibits processes in the body that cause inflammation. Tobramycin is an antibiotic. Loteprednol/tobramycin: Zylet (loteprednol/tobramycin) drops, 1 drop twice a day for 4 weeks.	Subject randomized to this arm will be treated with Lotemax, twice a day, for 4 weeks. Lotemax is also known as loteprednol. Loteprednol is in a class of drugs called corticosteroids. Loteprednol inhibits processes in the body that cause inflammation. Loteprednol: Eye drops, 1 drop twice a day for 4 weeks	Subject randomized to this arm will be treated with artificial tears, twice a day, for 4 weeks. Bausch + Lomb Advanced Eye Relief Lubricant Eye Drops: Bausch + Lomb Advanced Eye Relief Lubricant Eye Drops (Artificial Tears), 1 drop twice a day for 4 weeks.
Period Title: Overall Study
STARTED	20	20	20
COMPLETED	17	17	20
NOT COMPLETED	3	3	0

Baseline Characteristics

Arm/Group Title	Zylet	Lotemax	Bausch & Lomb Lubricant Drops	Total
Arm/Group Description	Subject randomized to this arm will be treated with Zylet, twice a day, for 4 weeks. Zylet is a combination of loteprednol and tobramycin. Loteprednol is in a class of drugs called corticosteroids. Loteprednol inhibits processes in the body that cause inflammation. Tobramycin is an antibiotic. Loteprednol/tobramycin: Zylet (loteprednol/tobramycin) drops, 1 drop twice a day for 4 weeks.	Subject randomized to this arm will be treated with Lotemax, twice a day, for 4 weeks. Lotemax is also known as loteprednol. Loteprednol is in a class of drugs called corticosteroids. Loteprednol inhibits processes in the body that cause inflammation. Loteprednol: Eye drops, 1 drop twice a day for 4 weeks	Subject randomized to this arm will be treated with artificial tears, twice a day, for 4 weeks. Bausch + Lomb Advanced Eye Relief Lubricant Eye Drops: Bausch + Lomb Advanced Eye Relief Lubricant Eye Drops (Artificial Tears), 1 drop twice a day for 4 weeks.	Total of all reporting groups
Overall Participants	17	17	20	54
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55 (13)	52 (12)	57 (12)	55 (13)
Sex: Female, Male (Count of Participants)
Female	8 47.1%	9 52.9%	15 75%	32 59.3%
Male	9 52.9%	8 47.1%	5 25%	22 40.7%
Ocular Surface Disease Index (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	59.7 (18.0)	52.0 (22.6)	57.0 (21.3)	56.3 (20.6)
Symptom Assessment in Dry Eye (SANDE) Frequency Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	77.8 (14.2)	60.9 (19.4)	68.1 (17.8)	68.9 (18.3)
Symptom Assessment in Dry Eye (SANDE) Severity Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	67.0 (19.8)	58.1 (19.6)	64.2 (19.5)	63.2 (19.6)
Corneal Fluorescein Staining (CFS) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	6.8 (2.6)	6.6 (2.5)	6.1 (2.0)	6.5 (2.3)

Outcome Measures

1. Primary Outcome

Title	Ocular Surface Disease Index
Description	OSDI is a 12-question survey used to measure the symptoms of dry eye disease. Each of the 12 individual questions rate one symptom on a 0-4 scale, with 4 meaning that the symptom is present all of the time and 0 meaning the symptom is present none of the time. The overall ODSI score is calculated by adding all of the values from the 12 questions, multiplying that value by 25, and dividing the resulting value by the number of questions answered. This results in an overall scale that ranges from 0-100, with 100 being severe dry eye symptoms and 0 being no dry eye symptoms.
Time Frame	Week 4 Time Point

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zylet	Lotemax	Bausch & Lomb Lubricant Drops
Arm/Group Description	Subject randomized to this arm will be treated with Zylet, twice a day, for 4 weeks. Zylet is a combination of loteprednol and tobramycin. Loteprednol is in a class of drugs called corticosteroids. Loteprednol inhibits processes in the body that cause inflammation. Tobramycin is an antibiotic. Loteprednol/tobramycin: Zylet (loteprednol/tobramycin) drops, 1 drop twice a day for 4 weeks.	Subject randomized to this arm will be treated with Lotemax, twice a day, for 4 weeks. Lotemax is also known as loteprednol. Loteprednol is in a class of drugs called corticosteroids. Loteprednol inhibits processes in the body that cause inflammation. Loteprednol: Eye drops, 1 drop twice a day for 4 weeks	Subject randomized to this arm will be treated with artificial tears, twice a day, for 4 weeks. Bausch + Lomb Advanced Eye Relief Lubricant Eye Drops: Bausch + Lomb Advanced Eye Relief Lubricant Eye Drops (Artificial Tears), 1 drop twice a day for 4 weeks.
Measure Participants	17	17	20
Mean (Standard Deviation) [units on a scale]	56.6 (22.4)	46.4 (24.8)	48.4 (18.9)

2. Primary Outcome

Title	Symptom Assessment iN Dry Eye (SANDE) Frequency Score
Description	Questionnaire given to patients to assess the frequency of dry eye symptoms. The questionnaire utilizes a 100 mm horizontal Visual Analogue Scale technique to quantify the frequency of the patient's dry eye symptoms. Change is quantified from baseline to week 4. The range of the SANDE frequency scale is 0-100, with 0 being the minimum level of frequency of dry eye symptoms and 100 being the maximum level of frequency of dry eye symptoms.
Time Frame	Week 4 Time Point

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zylet	Lotemax	Bausch & Lomb Lubricant Drops
Arm/Group Description	Subject randomized to this arm will be treated with Zylet, twice a day, for 4 weeks. Zylet is a combination of loteprednol and tobramycin. Loteprednol is in a class of drugs called corticosteroids. Loteprednol inhibits processes in the body that cause inflammation. Tobramycin is an antibiotic. Loteprednol/tobramycin: Zylet (loteprednol/tobramycin) drops, 1 drop twice a day for 4 weeks.	Subject randomized to this arm will be treated with Lotemax, twice a day, for 4 weeks. Lotemax is also known as loteprednol. Loteprednol is in a class of drugs called corticosteroids. Loteprednol inhibits processes in the body that cause inflammation. Loteprednol: Eye drops, 1 drop twice a day for 4 weeks	Subject randomized to this arm will be treated with artificial tears, twice a day, for 4 weeks. Bausch + Lomb Advanced Eye Relief Lubricant Eye Drops: Bausch + Lomb Advanced Eye Relief Lubricant Eye Drops (Artificial Tears), 1 drop twice a day for 4 weeks.
Measure Participants	17	17	20
Mean (Standard Deviation) [units on a scale]	65.9 (28.9)	51.7 (23.3)	50.5 (24.3)

3. Primary Outcome

Title	Symptom Assessment iN Dry Eye (SANDE) Severity Score
Description	Questionnaire given to patients to assess the severity of dry eye symptoms. The questionnaire utilizes a 100 mm horizontal Visual Analogue Scale technique to quantify the severity of the patient's dry eye symptoms. Change is quantified from baseline to week 4. The range of the SANDE severity scale is 0-100, with minimum level of severity of dry eye symptoms and 100 being the maximum level of severity of dry eye symptoms.
Time Frame	Week 4 Time Point

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zylet	Lotemax	Bausch & Lomb Lubricant Drops
Arm/Group Description	Subject randomized to this arm will be treated with Zylet, twice a day, for 4 weeks. Zylet is a combination of loteprednol and tobramycin. Loteprednol is in a class of drugs called corticosteroids. Loteprednol inhibits processes in the body that cause inflammation. Tobramycin is an antibiotic. Loteprednol/tobramycin: Zylet (loteprednol/tobramycin) drops, 1 drop twice a day for 4 weeks.	Subject randomized to this arm will be treated with Lotemax, twice a day, for 4 weeks. Lotemax is also known as loteprednol. Loteprednol is in a class of drugs called corticosteroids. Loteprednol inhibits processes in the body that cause inflammation. Loteprednol: Eye drops, 1 drop twice a day for 4 weeks	Subject randomized to this arm will be treated with artificial tears, twice a day, for 4 weeks. Bausch + Lomb Advanced Eye Relief Lubricant Eye Drops: Bausch + Lomb Advanced Eye Relief Lubricant Eye Drops (Artificial Tears), 1 drop twice a day for 4 weeks.
Measure Participants	17	17	20
Mean (Standard Deviation) [units on a scale]	64.5 (25.8)	54.4 (20.2)	51.2 (22.0)

4. Primary Outcome

Title	Corneal Fluorescein Staining Score
Description	Corneal Fluorescein Staining is used to assess the level of corneal epitheliopathy that is related to dry eye disease. The CFS scale ranges from 0 to 15 scale, with 0 representing the minimum level of corneal epitheliopathy and 15 representing the maximum level of corneal epitheliopathy.
Time Frame	Week 4 Time Point

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zylet	Lotemax	Bausch & Lomb Lubricant Drops
Arm/Group Description	Subject randomized to this arm will be treated with Zylet, twice a day, for 4 weeks. Zylet is a combination of loteprednol and tobramycin. Loteprednol is in a class of drugs called corticosteroids. Loteprednol inhibits processes in the body that cause inflammation. Tobramycin is an antibiotic. Loteprednol/tobramycin: Zylet (loteprednol/tobramycin) drops, 1 drop twice a day for 4 weeks.	Subject randomized to this arm will be treated with Lotemax, twice a day, for 4 weeks. Lotemax is also known as loteprednol. Loteprednol is in a class of drugs called corticosteroids. Loteprednol inhibits processes in the body that cause inflammation. Loteprednol: Eye drops, 1 drop twice a day for 4 weeks	Subject randomized to this arm will be treated with artificial tears, twice a day, for 4 weeks. Bausch + Lomb Advanced Eye Relief Lubricant Eye Drops: Bausch + Lomb Advanced Eye Relief Lubricant Eye Drops (Artificial Tears), 1 drop twice a day for 4 weeks.
Measure Participants	17	17	20
Mean (Standard Deviation) [units on a scale]	6.3 (4.2)	5.0 (3.3)	4.8 (3.2)

Adverse Events

Time Frame	4 Weeks
Arm/Group Title	Zylet		Lotemax		Bausch & Lomb Lubricant Drops
Arm/Group Description	Subject randomized to this arm will be treated with Zylet, twice a day, for 4 weeks. Zylet is a combination of loteprednol and tobramycin. Loteprednol is in a class of drugs called corticosteroids. Loteprednol inhibits processes in the body that cause inflammation (swelling). Tobramycin is an antibiotic. Loteprednol/tobramycin: Zylet (loteprednol/tobramycin) drops, 1 drop twice a day for 4 weeks.		Subject randomized to this arm will be treated with Lotemax, twice a day, for 4 weeks. Lotemax is also known as loteprednol. Loteprednol is in a class of drugs called corticosteroids. Loteprednol inhibits processes in the body that cause inflammation (swelling). Loteprednol: Eye drops, 1 drop twice a day for 4 weeks		Subject randomized to this arm will be treated with artificial tears, twice a day, for 4 weeks. Bausch + Lomb Advanced Eye Relief Lubricant Eye Drops: Bausch + Lomb Advanced Eye Relief Lubricant Eye Drops (Artificial Tears), 1 drop twice a day for 4 weeks.
All Cause Mortality
	Zylet		Lotemax		Bausch & Lomb Lubricant Drops
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)		0/20 (0%)
Serious Adverse Events
	Zylet		Lotemax		Bausch & Lomb Lubricant Drops
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Zylet		Lotemax		Bausch & Lomb Lubricant Drops
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/20 (10%)		1/20 (5%)		2/20 (10%)
Eye disorders
Eye Pain	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Blurriness	1/20 (5%)	2	1/20 (5%)	1	0/20 (0%)	0
Excess Tearing	1/20 (5%)	2	0/20 (0%)	0	0/20 (0%)	0
Redness	1/20 (5%)	2	0/20 (0%)	0	0/20 (0%)	0
Headache	0/20 (0%)	0	0/20 (0%)	0	1/20 (5%)	1
Shingles	0/20 (0%)	0	0/20 (0%)	0	1/20 (5%)	1
Dryness	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.