Safety and Efficacy Study of New Eye Drop Formulations With Refresh Tears® in Patients With Dry Eye Disease

• Sponsor: Allergan (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01294384
• Collaborator: (none)
• Enrollment: 305
• Locations: 2
• Arms: 3
• Actual Duration (Months): 16.9
• Patients Per Site: 152.5
• Patients Per Site Per Month: 9

Study Details

Study Description

Brief Summary

This study will investigate the safety, efficacy and acceptability of two new eye drop formulations compared with Refresh Tears® in patients with dry eye disease.

Condition or Disease	Intervention/Treatment	Phase
Dry Eye Syndromes	Drug: carboxymethylcellulose sodium based New Eye Drop Formulation 1; Drug: carboxymethylcellulose sodium based New Eye Drop Formulation 2; Drug: carboxymethylcellulose sodium based Eye Drops	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 305 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Actual Study Start Date: May 1, 2011
• Actual Primary Completion Date: Sep 25, 2012
• Actual Study Completion Date: Sep 25, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: New Eye Drop Formulation 1 1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 1 in each eye at least twice daily for 90 days.	Drug: carboxymethylcellulose sodium based New Eye Drop Formulation 1; 1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 1 in each eye at least twice daily for 90 days.
Experimental: New Eye Drop Formulation 2 1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 2 in each eye at least twice daily for 90 days.	Drug: carboxymethylcellulose sodium based New Eye Drop Formulation 2; 1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 2 in each eye at least twice daily for 90 days.
Active Comparator: Refresh Tears® 1 to 2 drops of carboxymethylcellulose sodium based Eye Drops (Refresh Tears®) in each eye at least twice daily for 90 days.	Drug: carboxymethylcellulose sodium based Eye Drops; 1 to 2 drops of carboxymethylcellulose sodium based Eye Drops (Refresh Tears®) in each eye at least twice daily for 90 days.; Other Names: Refresh Tears®

Outcome Measures

Primary Outcome Measures

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

   The OSDI is a questionnaire consisting of 12 questions assessing severity of dry eye using a 5-point scale where 0=none of the time to 4=all of the time. The total score is the sum of the individual scores normalized (standardized) to a severity scale of 0=no symptoms (best score) to 100=maximum severity (worst score). A negative change from Baseline indicated improvement.

Secondary Outcome Measures

1. Change From Baseline in Visual Analog (VAS) Symptom Scale: Dryness [Baseline, Day 90]

   The participant rated the severity of their dry eye symptom: dryness using a VAS scale. Participants put a mark on a 100 millimeter line where 0 (far left on the line)=no symptoms to 100 (far right on the line)=most severe symptoms.

2. Percentage of Participants Much Better or Better in Near Visual Acuity (Low Contrast) [Baseline, Day 90]

   Near Visual Acuity was determined using the number of letters read correctly on a low contrast eye chart (gray letters on a white background). An increase in the number of letters read correctly indicated improvement. Much Better is defined as an increase of 10 or more letters read correctly at Day 90 compared to the worse eye at Baseline. Better is defined as an increase of 5 to 9 letters read correctly at Day 90 compared to the worse eye at Baseline.

3. Percentage of Participants Much Better or Better in Near Visual Acuity (High Contrast) [Baseline, Day 90]

   Near Visual Acuity was determined using the number of letters read correctly on a high contrast eye chart (black letters on a white background). An increase in the number of letters read correctly indicated improvement. Much Better is defined as an increase of 10 or more letters read correctly at Day 90 compared to the worse eye at Baseline. Better is defined as an increase of 5 to 9 letters read correctly at Day 90 compared to the worse eye at Baseline.

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

   TBUT is defined as the time (seconds) required for dry spots to appear on the surface of the eye after blinking. The longer it takes, the more stable the tear film. A positive number change from Baseline indicated improvement.

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

   The cornea is the transparent front part of the eye which covers the iris and pupil. Corneal staining following administration of fluorescein dye in the eye is graded using a 6-point scale where 0=no staining to 5=severe staining over 5 areas of the clear central part of the eye for a minimum score of 0 and maximum score of 25. The higher the grade score, the worse the dry eye condition. A negative number change from baseline represented a decrease in corneal staining (improvement).

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

   The conjunctiva is the clear membrane covering the white surface of the eye. Conjunctival staining following ocular administration of lissamine green dye was graded using a 6-point scale where 0=no staining to 5=severe staining over 6 areas of the white part of the eye for a minimum score of 0 and a maximum score of 30. The higher the score, the worse the dry eye condition. A negative number change from baseline represented a decrease in the severity of conjunctival staining (improvement).

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

   The Schirmer Test measures the rate of the secretion of tears produced by the eye over 5 minutes. The results indicate the presence of dry eye where Normal=greater than or equal to 10 millimeters (mm) of tears and Dry Eye=less than 10 mm of tears). The smaller the number, the more severe the dry eye. A positive number change from baseline indicated 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:

• Current use of an artificial tear product at least twice daily for at least 3 months, on average

• Ability/agreement to continue wearing existing spectacle correction (glasses) during study

Exclusion Criteria:

• Anticipated contact lens wear during study or contact lens use within 6 months

• Active ocular infection or allergy

• Use of any topical ophthalmic medications (eg, topical ophthalmic steroids, glaucoma drops) within 2 weeks

• Use of any topical cyclosporine products within 3 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Randwick	New South Wales	Australia
2		St. John's	Newfoundland and Labrador	Canada

Sponsors and Collaborators

• Allergan

Investigators

• Study Director: Medical Director, Allergan

Study Documents (Full-Text)

None provided.

More Information

Publications

• Simmons PA, Liu H, Carlisle-Wilcox C, Vehige JG. Efficacy and safety of two new formulations of artificial tears in subjects with dry eye disease: a 3-month, multicenter, active-controlled, randomized trial. Clin Ophthalmol. 2015 Apr 15;9:665-75. doi: 10.2147/OPTH.S78184. eCollection 2015.

• Responsible Party: Allergan
• ClinicalTrials.gov Identifier: NCT01294384
• Other Study ID Numbers: 10078X-001
• First Posted: Feb 11, 2011
• Last Update Posted: Apr 16, 2019
• Last Verified: Apr 1, 2019

• Additional relevant MeSH terms: Dry Eye Syndromes; Keratoconjunctivitis Sicca; Carboxymethylcellulose Sodium; Ophthalmic Solutions

Study Results

Participant Flow

Arm/Group Title	New Eye Drop Formulation 1	New Eye Drop Formulation 2	Refresh Tears®
Arm/Group Description	1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 1 in each eye at least twice daily for 90 days.	1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 2 in each eye at least twice daily for 90 days.	1 to 2 drops of carboxymethylcellulose sodium based Eye Drops (Refresh Tears®) in each eye at least twice daily for 90 days.
Period Title: Overall Study
STARTED	101	100	104
COMPLETED	97	94	95
NOT COMPLETED	4	6	9

Baseline Characteristics

Arm/Group Title	New Eye Drop Formulation 1	New Eye Drop Formulation 2	Refresh Tears®	Total
Arm/Group Description	1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 1 in each eye at least twice daily for 90 days.	1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 2 in each eye at least twice daily for 90 days.	1 to 2 drops of carboxymethylcellulose sodium based Eye Drops (Refresh Tears®) in each eye at least twice daily for 90 days.	Total of all reporting groups
Overall Participants	101	100	104	305
Age, Customized (Number) [Number]
< 40 years	9 8.9%	13 13%	7 6.7%	29 9.5%
40 to 60 years	42 41.6%	33 33%	43 41.3%	118 38.7%
> 60 years	50 49.5%	54 54%	54 51.9%	158 51.8%
Sex: Female, Male (Count of Participants)
Female	78 77.2%	80 80%	90 86.5%	248 81.3%
Male	23 22.8%	20 20%	14 13.5%	57 18.7%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Ocular Surface Disease Index© (OSDI) Score
Description	The OSDI is a questionnaire consisting of 12 questions assessing severity of dry eye using a 5-point scale where 0=none of the time to 4=all of the time. The total score is the sum of the individual scores normalized (standardized) to a severity scale of 0=no symptoms (best score) to 100=maximum severity (worst score). A negative change from Baseline indicated improvement.
Time Frame	Baseline, Day 90

Outcome Measure Data

Analysis Population Description

Participants from the Intent-to-Treat population, that included all randomized participants.

Arm/Group Title	New Eye Drop Formulation 1	New Eye Drop Formulation 2	Refresh Tears®
Arm/Group Description	1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 1 in each eye at least twice daily for 90 days.	1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 2 in each eye at least twice daily for 90 days.	1 to 2 drops of carboxymethylcellulose sodium based Eye Drops (Refresh Tears®) in each eye at least twice daily for 90 days.
Measure Participants	101	100	104
Baseline	36.83 (13.350)	38.51 (12.512)	38.86 (11.880)
Change from Baseline at Day 90	-14.72 (16.319)	-12.75 (17.612)	-14.49 (16.443)

2. Secondary Outcome

Title	Change From Baseline in Visual Analog (VAS) Symptom Scale: Dryness
Description	The participant rated the severity of their dry eye symptom: dryness using a VAS scale. Participants put a mark on a 100 millimeter line where 0 (far left on the line)=no symptoms to 100 (far right on the line)=most severe symptoms.
Time Frame	Baseline, Day 90

Outcome Measure Data

Analysis Population Description

Participants from the Intent-to-Treat population, that included all randomized participants.

Arm/Group Title	New Eye Drop Formulation 1	New Eye Drop Formulation 2	Refresh Tears®
Arm/Group Description	1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 1 in each eye at least twice daily for 90 days.	1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 2 in each eye at least twice daily for 90 days.	1 to 2 drops of carboxymethylcellulose sodium based Eye Drops (Refresh Tears®) in each eye at least twice daily for 90 days.
Measure Participants	101	100	104
Baseline	61.1 (22.10)	64.0 (19.05)	60.9 (18.98)
Change from Baseline at Day 90	-24.2 (30.78)	-19.2 (29.44)	-20.9 (29.20)

3. Secondary Outcome

Title	Percentage of Participants Much Better or Better in Near Visual Acuity (Low Contrast)
Description	Near Visual Acuity was determined using the number of letters read correctly on a low contrast eye chart (gray letters on a white background). An increase in the number of letters read correctly indicated improvement. Much Better is defined as an increase of 10 or more letters read correctly at Day 90 compared to the worse eye at Baseline. Better is defined as an increase of 5 to 9 letters read correctly at Day 90 compared to the worse eye at Baseline.
Time Frame	Baseline, Day 90

Outcome Measure Data

Analysis Population Description

Participants from the Intent-to-Treat population, that included all randomized participants.

Arm/Group Title	New Eye Drop Formulation 1	New Eye Drop Formulation 2	Refresh Tears®
Arm/Group Description	1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 1 in each eye at least twice daily for 90 days.	1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 2 in each eye at least twice daily for 90 days.	1 to 2 drops of carboxymethylcellulose sodium based Eye Drops (Refresh Tears®) in each eye at least twice daily for 90 days.
Measure Participants	101	100	104
Much better	5.0 5%	8.0 8%	5.8 5.6%
Better	22.0 21.8%	21.0 21%	30.8 29.6%

4. Secondary Outcome

Title	Percentage of Participants Much Better or Better in Near Visual Acuity (High Contrast)
Description	Near Visual Acuity was determined using the number of letters read correctly on a high contrast eye chart (black letters on a white background). An increase in the number of letters read correctly indicated improvement. Much Better is defined as an increase of 10 or more letters read correctly at Day 90 compared to the worse eye at Baseline. Better is defined as an increase of 5 to 9 letters read correctly at Day 90 compared to the worse eye at Baseline.
Time Frame	Baseline, Day 90

Outcome Measure Data

Analysis Population Description

Participants from the Intent-to-Treat population, that included all randomized participants.

Arm/Group Title	New Eye Drop Formulation 1	New Eye Drop Formulation 2	Refresh Tears®
Arm/Group Description	1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 1 in each eye at least twice daily for 90 days.	1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 2 in each eye at least twice daily for 90 days.	1 to 2 drops of carboxymethylcellulose sodium based Eye Drops (Refresh Tears®) in each eye at least twice daily for 90 days.
Measure Participants	101	100	104
Much Better	7.0 6.9%	6.0 6%	4.8 4.6%
Better	15.0 14.9%	20.0 20%	22.1 21.3%

5. Secondary Outcome

Title	Change From Baseline in Tear Break-Up Time (TBUT)
Description	TBUT is defined as the time (seconds) required for dry spots to appear on the surface of the eye after blinking. The longer it takes, the more stable the tear film. A positive number change from Baseline indicated improvement.
Time Frame	Baseline, Day 90

Outcome Measure Data

Analysis Population Description

Participants from the Intent-to-Treat population, that included all randomized participants.

Arm/Group Title	New Eye Drop Formulation 1	New Eye Drop Formulation 2	Refresh Tears®
Arm/Group Description	1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 1 in each eye at least twice daily for 90 days.	1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 2 in each eye at least twice daily for 90 days.	1 to 2 drops of carboxymethylcellulose sodium based Eye Drops (Refresh Tears®) in each eye at least twice daily for 90 days.
Measure Participants	101	100	104
Baseline	5.24 (2.007)	5.22 (1.870)	5.05 (1.894)
Change from Baseline at Day 90	1.65 (4.268)	1.97 (3.294)	1.27 (2.837)

6. Secondary Outcome

Title	Change From Baseline in Corneal Staining
Description	The cornea is the transparent front part of the eye which covers the iris and pupil. Corneal staining following administration of fluorescein dye in the eye is graded using a 6-point scale where 0=no staining to 5=severe staining over 5 areas of the clear central part of the eye for a minimum score of 0 and maximum score of 25. The higher the grade score, the worse the dry eye condition. A negative number change from baseline represented a decrease in corneal staining (improvement).
Time Frame	Baseline, Day 90

Outcome Measure Data

Analysis Population Description

Participants from the Intent-to-Treat population, that included all randomized participants.

Arm/Group Title	New Eye Drop Formulation 1	New Eye Drop Formulation 2	Refresh Tears®
Arm/Group Description	1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 1 in each eye at least twice daily for 90 days.	1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 2 in each eye at least twice daily for 90 days.	1 to 2 drops of carboxymethylcellulose sodium based Eye Drops (Refresh Tears®) in each eye at least twice daily for 90 days.
Measure Participants	101	100	104
Baseline	6.4 (4.97)	6.1 (4.25)	5.8 (4.29)
Change from Baseline at Day 90	-2.3 (3.75)	-2.0 (3.36)	-1.2 (3.13)

7. Secondary Outcome

Title	Change From Baseline in Conjunctival Staining
Description	The conjunctiva is the clear membrane covering the white surface of the eye. Conjunctival staining following ocular administration of lissamine green dye was graded using a 6-point scale where 0=no staining to 5=severe staining over 6 areas of the white part of the eye for a minimum score of 0 and a maximum score of 30. The higher the score, the worse the dry eye condition. A negative number change from baseline represented a decrease in the severity of conjunctival staining (improvement).
Time Frame	Baseline, Day 90

Outcome Measure Data

Analysis Population Description

Participants from the Intent-to-Treat population, that included all randomized participants.

Arm/Group Title	New Eye Drop Formulation 1	New Eye Drop Formulation 2	Refresh Tears®
Arm/Group Description	1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 1 in each eye at least twice daily for 90 days.	1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 2 in each eye at least twice daily for 90 days.	1 to 2 drops of carboxymethylcellulose sodium based Eye Drops (Refresh Tears®) in each eye at least twice daily for 90 days.
Measure Participants	101	100	104
Baseline	8.0 (5.34)	7.8 (5.45)	8.2 (5.44)
Change from Baseline at Day 90	-2.7 (4.72)	-2.4 (4.06)	-2.7 (4.36)

8. Secondary Outcome

Title	Change From Baseline in Schirmer Test
Description	The Schirmer Test measures the rate of the secretion of tears produced by the eye over 5 minutes. The results indicate the presence of dry eye where Normal=greater than or equal to 10 millimeters (mm) of tears and Dry Eye=less than 10 mm of tears). The smaller the number, the more severe the dry eye. A positive number change from baseline indicated an increase in tears (improvement).
Time Frame	Baseline, Day 90

Outcome Measure Data

Analysis Population Description

Participants from the Intent-to-Treat population, that included all randomized participants.

Arm/Group Title	New Eye Drop Formulation 1	New Eye Drop Formulation 2	Refresh Tears®
Arm/Group Description	1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 1 in each eye at least twice daily for 90 days.	1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 2 in each eye at least twice daily for 90 days.	1 to 2 drops of carboxymethylcellulose sodium based Eye Drops (Refresh Tears®) in each eye at least twice daily for 90 days.
Measure Participants	101	100	104
Baseline	8.7 (6.96)	10.3 (7.17)	8.9 (6.16)
Change from Baseline at Day 90	1.2 (7.07)	1.5 (6.12)	1.1 (7.07)

Adverse Events

Adverse Event Reporting Description	The safety population, that included all participants who received at least one dose of study treatment, was used to calculate the number of participants at risk for Adverse Events. (One randomized patient did not receive treatment and two patients received treatment but were not randomized.)
Arm/Group Title	New Eye Drop Formulation 1		New Eye Drop Formulation 2		Refresh Tears®
Arm/Group Description	1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 1 in each eye at least twice daily for 90 days.		1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 2 in each eye at least twice daily for 90 days.		1 to 2 drops of carboxymethylcellulose sodium based Eye Drops (Refresh Tears®) in each eye at least twice daily for 90 days.
All Cause Mortality
	New Eye Drop Formulation 1		New Eye Drop Formulation 2		Refresh Tears®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	New Eye Drop Formulation 1		New Eye Drop Formulation 2		Refresh Tears®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/102 (2%)		2/101 (2%)		1/103 (1%)
Ear and labyrinth disorders
Meniere's disease	1/102 (1%)		0/101 (0%)		0/103 (0%)
Infections and infestations
Pelvic inflammatory disease	0/102 (0%)		1/101 (1%)		0/103 (0%)
Injury, poisoning and procedural complications
Ligament rupture	1/102 (1%)		0/101 (0%)		0/103 (0%)
Nervous system disorders
Neuropathy peripheral	0/102 (0%)		0/101 (0%)		1/103 (1%)
Vascular disorders
Hypertension	0/102 (0%)		1/101 (1%)		0/103 (0%)
Other (Not Including Serious) Adverse Events
	New Eye Drop Formulation 1		New Eye Drop Formulation 2		Refresh Tears®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/102 (0%)		0/101 (0%)		0/103 (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.