A Safety and Efficacy Study of a New Eye Drop Formulation in Patients With Dry Eye Disease.

• Sponsor: Allergan (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02553772
• Collaborator: (none)
• Enrollment: 242
• Locations: 13
• Arms: 2
• Actual Duration (Months): 8.1
• Patients Per Site: 18.6
• Patients Per Site Per Month: 2.3

Study Details

Study Description

Brief Summary

This study will evaluate the safety and efficacy of a new eye drop formulation in patients with dry eye disease.

Condition or Disease	Intervention/Treatment	Phase
Dry Eye Syndromes	Drug: Carboxymethylcellulose Based Eye Drop; Drug: Carboxymethylcellulose Sodium 0.5%	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 242 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Double-masked, Randomized Study to Compare the Safety and Efficacy of the OM3 Tear Formulation With REFRESH OPTIVE® ADVANCED Unit Dose for 3 Months in Patients With Dry Eye Disease
• Actual Study Start Date: Jan 6, 2016
• Actual Primary Completion Date: Sep 9, 2016
• Actual Study Completion Date: Sep 9, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: OM3 Tear Carboxymethylcellulose based eye drop [Omega-3 (OM3) Tear] administered as 1-2 drops in each eye, as needed, at least 2 times daily for 90 days.	Drug: Carboxymethylcellulose Based Eye Drop; Carboxymethylcellulose based eye drop (OM3 Tear) administered as 1-2 drops in each eye, as needed, at least 2 times daily for 90 days.
Active Comparator: REFRESH OPTIVE® ADVANCED Carboxymethylcellulose sodium 0.5% (REFRESH OPTIVE® ADVANCED) administered as 1-2 drops in each eye, as needed, at least 2 times daily for 90 days.	Drug: Carboxymethylcellulose Sodium 0.5%; Carboxymethylcellulose sodium 0.5% (REFRESH OPTIVE® ADVANCED) administered as 1-2 drops in each eye, as needed, at least 2 times daily for 90 days.; Other Names: REFRESH OPTIVE® ADVANCED

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the Ocular Surface Disease Index© (OSDI©) Score [Baseline, Day 90]

   The OSDI© consists of 12 questions the patient is asked measuring the presence of ocular symptoms. Each of the 12 questions was assessed using a 5-point scale where 0=none of the time and 4=all of the time. The score is converted to a 0 to 100-point score where 0 is no symptoms and 100 is most symptoms. A negative change from Baseline indicates improvement.

Secondary Outcome Measures

1. Change From Baseline in Tear Break-up Time (TBUT) [Baseline, Day 90]

   TBUT is defined as the time required for dry spots to appear on the surface of the eye after blinking. The longer it takes, the more stable the tear film. The worse eye is used for the calculations and is defined as the eye with the shortest average TBUT at Baseline. A positive number change from Baseline indicates improvement and a negative number change from Baseline indicates a worsening.

2. Change From Baseline in Corneal Staining Score [Baseline, Day 90]

   Total corneal staining with fluorescein was measured in the worse eye using a 6-point scale where 0= none, no staining (best) to 5=severe staining (worst). The total score is calculated as the sum of 5 regions of the cornea, resulting in a possible minimum score of 0 and a maximum possible score of 25 (severe staining score of 5 in all 5 regions). The worse eye is defined as the eye with the highest score at Baseline. A negative change from Baseline represents a decrease in staining (improvement).

3. Change From Baseline in Conjunctival Staining Score [Baseline, Day 90]

   Total conjunctival staining with lissamine green was measured in the worse eye using a 6-point scale where 0= none (best), no staining to 5=severe staining (worst). The total score is calculated as the sum of the 6 regions of the conjunctiva, resulting in a minimum possible score of 0 maximum possible score of 30 (severe staining score of 5 in 6 regions). The worse eye is defined as eye with the highest score at Baseline. A negative change from Baseline represents a decrease in staining (improvement).

4. Change From Baseline in the Schirmer Test [Baseline, Day 90]

   The Schirmer Test measures tears produced by the eye over 5 minutes using a paper strip inserted into the eye. The results indicate the presence of dry eye (Normal = greater than 10 millimeters (mm) of tears, Dry Eye = less than 10 mm of tears). The smaller the number, the more severe the dry eye. The worse eye defined as the eye with the lowest score at baseline is used to calculate the change at Day 90. A positive number change from baseline indicates an increase in tears (improvement).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Used artificial tears for dry eye

• Visual acuity of at least 20/32 (while wearing glasses, if necessary).

Exclusion Criteria:

• Use of contact lenses in the last 3 months, or anticipated use of contact lenses during the study

• Herpes keratitis in the last 6 months

• Cataract surgery, laser-assisted in situ keratomileusis [LASIK], or photorefractive keratectomy, within the last 6 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Private Practice of Milton Hom, OD	Azusa	California	United States	91702
2	Havana Research Institute LLC	Burbank	California	United States	91506
3	Lugene Eye Institute	Glendale	California	United States	91204
4	Eric M. White, OD, INC	San Diego	California	United States	92123
5	Moyes Eye Center, PC	Kansas City	Missouri	United States	64154
6	Ophthalmology Associates	Saint Louis	Missouri	United States	63131
7	Rochester Ophthalmological Group, PC	Rochester	New York	United States	14618
8	Charlotte Eye Ear Nose	Charlotte	North Carolina	United States	28210
9	Scott and Christie and Associate	Cranberry Township	Pennsylvania	United States	16066
10	Texan Eye	Austin	Texas	United States	78731
11	Department of Optometry & Vision Sciences, The University of Melbourne	Parkville		Australia	VIC 3010
12	Prof. M.T. Coroneo Pty. Ltd.	Randwick		Australia	NSW 2031
13	The University of New South Wales School of Optometry and Vision Science	Sydney		Australia	NSW 2052

Sponsors and Collaborators

• Allergan

Investigators

• Study Director: Medical Director, Allergan

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• More Information

Publications

None provided.

• Responsible Party: Allergan
• ClinicalTrials.gov Identifier: NCT02553772
• Other Study ID Numbers: 11182X-001
• First Posted: Sep 18, 2015
• Last Update Posted: Nov 17, 2017
• Last Verified: Oct 1, 2017

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Dry Eye Syndromes; Keratoconjunctivitis Sicca; Eye Diseases; Carboxymethylcellulose Sodium; Ophthalmic Solutions

Study Results

Participant Flow

Arm/Group Title	OM3 Tear	REFRESH OPTIVE® ADVANCED
Arm/Group Description	Carboxymethylcellulose based eye drop [Omega-3 (OM3) Tear] administered as 1-2 drops in each eye, as needed, at least 2 times daily for 90 days.	Carboxymethylcellulose sodium 0.5% (REFRESH OPTIVE® ADVANCED) administered as 1-2 drops in each eye, as needed, at least 2 times daily for 90 days.
Period Title: Overall Study
STARTED	120	122
COMPLETED	114	116
NOT COMPLETED	6	6

Baseline Characteristics

Arm/Group Title	OM3 Tear	REFRESH OPTIVE® ADVANCED	Total
Arm/Group Description	Carboxymethylcellulose based eye drop [Omega-3 (OM3) Tear] administered as 1-2 drops in each eye, as needed, at least 2 times daily for 90 days.	Carboxymethylcellulose sodium 0.5% (REFRESH OPTIVE® ADVANCED) administered as 1-2 drops in each eye, as needed, at least 2 times daily for 90 days.	Total of all reporting groups
Overall Participants	120	122	242
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.3 (17.3)	52.8 (16.7)	53.5 (17.0)
Age, Customized (participants) [Number]
< 30 years	16 13.3%	14 11.5%	30 12.4%
30 to 40 years	11 9.2%	18 14.8%	29 12%
> 40 years	93 77.5%	90 73.8%	183 75.6%
Sex: Female, Male (Count of Participants)
Female	84 70%	95 77.9%	179 74%
Male	36 30%	27 22.1%	63 26%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Ocular Surface Disease Index© (OSDI©) Score
Description	The OSDI© consists of 12 questions the patient is asked measuring the presence of ocular symptoms. Each of the 12 questions was assessed using a 5-point scale where 0=none of the time and 4=all of the time. The score is converted to a 0 to 100-point score where 0 is no symptoms and 100 is most symptoms. A negative change from Baseline indicates improvement.
Time Frame	Baseline, Day 90

Outcome Measure Data

Analysis Population Description

Intent-to-treat population included all randomized participants.

Arm/Group Title	OM3 Tear	REFRESH OPTIVE® ADVANCED
Arm/Group Description	Carboxymethylcellulose based eye drop [Omega-3 (OM3) Tear] administered as 1-2 drops in each eye, as needed, at least 2 times daily for 90 days.	Carboxymethylcellulose sodium 0.5% (REFRESH OPTIVE® ADVANCED) administered as 1-2 drops in each eye, as needed, at least 2 times daily for 90 days.
Measure Participants	120	122
Baseline	41.12 (12.68)	39.63 (11.33)
Change at Day 90	-15.61 (16.52)	-13.16 (17.71)

2. Secondary Outcome

Title	Change From Baseline in Tear Break-up Time (TBUT)
Description	TBUT is defined as the time required for dry spots to appear on the surface of the eye after blinking. The longer it takes, the more stable the tear film. The worse eye is used for the calculations and is defined as the eye with the shortest average TBUT at Baseline. A positive number change from Baseline indicates improvement and a negative number change from Baseline indicates a worsening.
Time Frame	Baseline, Day 90

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants. "n" in the category is the number of participants with data available at the given time-point.

Arm/Group Title	OM3 Tear	REFRESH OPTIVE® ADVANCED
Arm/Group Description	Carboxymethylcellulose based eye drop [Omega-3 (OM3) Tear] administered as 1-2 drops in each eye, as needed, at least 2 times daily for 90 days.	Carboxymethylcellulose sodium 0.5% (REFRESH OPTIVE® ADVANCED) administered as 1-2 drops in each eye, as needed, at least 2 times daily for 90 days.
Measure Participants	120	122
Baseline	4.77 (1.68)	4.93 (1.74)
Change at Day 90	1.12 (1.93)	1.34 (2.62)

3. Secondary Outcome

Title	Change From Baseline in Corneal Staining Score
Description	Total corneal staining with fluorescein was measured in the worse eye using a 6-point scale where 0= none, no staining (best) to 5=severe staining (worst). The total score is calculated as the sum of 5 regions of the cornea, resulting in a possible minimum score of 0 and a maximum possible score of 25 (severe staining score of 5 in all 5 regions). The worse eye is defined as the eye with the highest score at Baseline. A negative change from Baseline represents a decrease in staining (improvement).
Time Frame	Baseline, Day 90

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants. "n" in the category is the number of participants with data available at the given time-point.

Arm/Group Title	OM3 Tear	REFRESH OPTIVE® ADVANCED
Arm/Group Description	Carboxymethylcellulose based eye drop [Omega-3 (OM3) Tear] administered as 1-2 drops in each eye, as needed, at least 2 times daily for 90 days.	Carboxymethylcellulose sodium 0.5% (REFRESH OPTIVE® ADVANCED) administered as 1-2 drops in each eye, as needed, at least 2 times daily for 90 days.
Measure Participants	120	122
Baseline	4.49 (3.39)	4.51 (3.29)
Change at Day 90	-1.49 (2.37)	-0.58 (2.70)

4. Secondary Outcome

Title	Change From Baseline in Conjunctival Staining Score
Description	Total conjunctival staining with lissamine green was measured in the worse eye using a 6-point scale where 0= none (best), no staining to 5=severe staining (worst). The total score is calculated as the sum of the 6 regions of the conjunctiva, resulting in a minimum possible score of 0 maximum possible score of 30 (severe staining score of 5 in 6 regions). The worse eye is defined as eye with the highest score at Baseline. A negative change from Baseline represents a decrease in staining (improvement).
Time Frame	Baseline, Day 90

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants. "n" in the category is the number of participants with data available at the given time-point.

Arm/Group Title	OM3 Tear	REFRESH OPTIVE® ADVANCED
Arm/Group Description	Carboxymethylcellulose based eye drop [Omega-3 (OM3) Tear] administered as 1-2 drops in each eye, as needed, at least 2 times daily for 90 days.	Carboxymethylcellulose sodium 0.5% (REFRESH OPTIVE® ADVANCED) administered as 1-2 drops in each eye, as needed, at least 2 times daily for 90 days.
Measure Participants	120	122
Baseline	6.73 (5.65)	5.87 (4.46)
Change at Day 90	-1.76 (4.42)	-1.18 (4.03)

5. Secondary Outcome

Title	Change From Baseline in the Schirmer Test
Description	The Schirmer Test measures tears produced by the eye over 5 minutes using a paper strip inserted into the eye. The results indicate the presence of dry eye (Normal = greater than 10 millimeters (mm) of tears, Dry Eye = less than 10 mm of tears). The smaller the number, the more severe the dry eye. The worse eye defined as the eye with the lowest score at baseline is used to calculate the change at Day 90. A positive number change from baseline indicates an increase in tears (improvement).
Time Frame	Baseline, Day 90

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants. "n" is the number of participants in the category with data available at the given time-point.

Arm/Group Title	OM3 Tear	REFRESH OPTIVE® ADVANCED
Arm/Group Description	Carboxymethylcellulose based eye drop [Omega-3 (OM3) Tear] administered as 1-2 drops in each eye, as needed, at least 2 times daily for 90 days.	Carboxymethylcellulose sodium 0.5% (REFRESH OPTIVE® ADVANCED) administered as 1-2 drops in each eye, as needed, at least 2 times daily for 90 days.
Measure Participants	120	122
Baseline	9.91 (7.10)	9.85 (6.82)
Change at Day 90	1.40 (7.13)	1.38 (7.21)

Adverse Events

Time Frame	120 Days
Arm/Group Title	OM3 Tear		REFRESH OPTIVE® ADVANCED
Arm/Group Description	Carboxymethylcellulose based eye drop [Omega-3 (OM3) Tear] administered as 1-2 drops in each eye, as needed, at least 2 times daily for 90 days.		Carboxymethylcellulose sodium 0.5% (REFRESH OPTIVE® ADVANCED) administered as 1-2 drops in each eye, as needed, at least 2 times daily for 90 days.
All Cause Mortality
	OM3 Tear		REFRESH OPTIVE® ADVANCED
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	OM3 Tear		REFRESH OPTIVE® ADVANCED
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/120 (0.8%)		1/122 (0.8%)
Gastrointestinal disorders
Colitis ischaemic	1/120 (0.8%)		0/122 (0%)
Diverticulum	1/120 (0.8%)		0/122 (0%)
Injury, poisoning and procedural complications
Facial bones fracture	0/120 (0%)		1/122 (0.8%)
Fall	0/120 (0%)		1/122 (0.8%)
Other (Not Including Serious) Adverse Events
	OM3 Tear		REFRESH OPTIVE® ADVANCED
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/120 (0%)		0/122 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.