Trial Outcomes & Findings for Safety and Efficacy Study of New Eye Drop Formulations With Refresh Tears® in Patients With Dry Eye Disease (NCT NCT01294384)
NCT ID: NCT01294384
Last Updated: 2019-04-16
Results Overview
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.
COMPLETED
PHASE3
305 participants
Baseline, Day 90
2019-04-16
Participant Flow
Participant milestones
| Measure |
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.
|
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.
|
Refresh Tears®
1 to 2 drops of carboxymethylcellulose sodium based Eye Drops (Refresh Tears®) in each eye at least twice daily for 90 days.
|
|---|---|---|---|
|
Overall Study
STARTED
|
101
|
100
|
104
|
|
Overall Study
COMPLETED
|
97
|
94
|
95
|
|
Overall Study
NOT COMPLETED
|
4
|
6
|
9
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Safety and Efficacy Study of New Eye Drop Formulations With Refresh Tears® in Patients With Dry Eye Disease
Baseline characteristics by cohort
| Measure |
New Eye Drop Formulation 1
n=101 Participants
1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 1 in each eye at least twice daily for 90 days.
|
New Eye Drop Formulation 2
n=100 Participants
1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 2 in each eye at least twice daily for 90 days.
|
Refresh Tears®
n=104 Participants
1 to 2 drops of carboxymethylcellulose sodium based Eye Drops (Refresh Tears®) in each eye at least twice daily for 90 days.
|
Total
n=305 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Customized
< 40 years
|
9 Participants
n=93 Participants
|
13 Participants
n=4 Participants
|
7 Participants
n=27 Participants
|
29 Participants
n=483 Participants
|
|
Age, Customized
40 to 60 years
|
42 Participants
n=93 Participants
|
33 Participants
n=4 Participants
|
43 Participants
n=27 Participants
|
118 Participants
n=483 Participants
|
|
Age, Customized
> 60 years
|
50 Participants
n=93 Participants
|
54 Participants
n=4 Participants
|
54 Participants
n=27 Participants
|
158 Participants
n=483 Participants
|
|
Sex: Female, Male
Female
|
78 Participants
n=93 Participants
|
80 Participants
n=4 Participants
|
90 Participants
n=27 Participants
|
248 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
23 Participants
n=93 Participants
|
20 Participants
n=4 Participants
|
14 Participants
n=27 Participants
|
57 Participants
n=483 Participants
|
PRIMARY outcome
Timeframe: Baseline, Day 90Population: Participants from the Intent-to-Treat population, that included all randomized participants.
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.
Outcome measures
| Measure |
New Eye Drop Formulation 1
n=101 Participants
1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 1 in each eye at least twice daily for 90 days.
|
New Eye Drop Formulation 2
n=100 Participants
1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 2 in each eye at least twice daily for 90 days.
|
Refresh Tears®
n=104 Participants
1 to 2 drops of carboxymethylcellulose sodium based Eye Drops (Refresh Tears®) in each eye at least twice daily for 90 days.
|
|---|---|---|---|
|
Change From Baseline in Ocular Surface Disease Index© (OSDI) Score
Baseline
|
36.83 Score on a scale
Standard Deviation 13.350
|
38.51 Score on a scale
Standard Deviation 12.512
|
38.86 Score on a scale
Standard Deviation 11.880
|
|
Change From Baseline in Ocular Surface Disease Index© (OSDI) Score
Change from Baseline at Day 90
|
-14.72 Score on a scale
Standard Deviation 16.319
|
-12.75 Score on a scale
Standard Deviation 17.612
|
-14.49 Score on a scale
Standard Deviation 16.443
|
SECONDARY outcome
Timeframe: Baseline, Day 90Population: Participants from the Intent-to-Treat population, that included all randomized participants.
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.
Outcome measures
| Measure |
New Eye Drop Formulation 1
n=101 Participants
1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 1 in each eye at least twice daily for 90 days.
|
New Eye Drop Formulation 2
n=100 Participants
1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 2 in each eye at least twice daily for 90 days.
|
Refresh Tears®
n=104 Participants
1 to 2 drops of carboxymethylcellulose sodium based Eye Drops (Refresh Tears®) in each eye at least twice daily for 90 days.
|
|---|---|---|---|
|
Change From Baseline in Visual Analog (VAS) Symptom Scale: Dryness
Baseline
|
61.1 millimeters
Standard Deviation 22.10
|
64.0 millimeters
Standard Deviation 19.05
|
60.9 millimeters
Standard Deviation 18.98
|
|
Change From Baseline in Visual Analog (VAS) Symptom Scale: Dryness
Change from Baseline at Day 90
|
-24.2 millimeters
Standard Deviation 30.78
|
-19.2 millimeters
Standard Deviation 29.44
|
-20.9 millimeters
Standard Deviation 29.20
|
SECONDARY outcome
Timeframe: Baseline, Day 90Population: Participants from the Intent-to-Treat population, that included all randomized participants.
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.
Outcome measures
| Measure |
New Eye Drop Formulation 1
n=101 Participants
1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 1 in each eye at least twice daily for 90 days.
|
New Eye Drop Formulation 2
n=100 Participants
1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 2 in each eye at least twice daily for 90 days.
|
Refresh Tears®
n=104 Participants
1 to 2 drops of carboxymethylcellulose sodium based Eye Drops (Refresh Tears®) in each eye at least twice daily for 90 days.
|
|---|---|---|---|
|
Percentage of Participants Much Better or Better in Near Visual Acuity (Low Contrast)
Much better
|
5.0 Percentage of participants
|
8.0 Percentage of participants
|
5.8 Percentage of participants
|
|
Percentage of Participants Much Better or Better in Near Visual Acuity (Low Contrast)
Better
|
22.0 Percentage of participants
|
21.0 Percentage of participants
|
30.8 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, Day 90Population: Participants from the Intent-to-Treat population, that included all randomized participants.
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.
Outcome measures
| Measure |
New Eye Drop Formulation 1
n=101 Participants
1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 1 in each eye at least twice daily for 90 days.
|
New Eye Drop Formulation 2
n=100 Participants
1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 2 in each eye at least twice daily for 90 days.
|
Refresh Tears®
n=104 Participants
1 to 2 drops of carboxymethylcellulose sodium based Eye Drops (Refresh Tears®) in each eye at least twice daily for 90 days.
|
|---|---|---|---|
|
Percentage of Participants Much Better or Better in Near Visual Acuity (High Contrast)
Much Better
|
7.0 Percentage of participants
|
6.0 Percentage of participants
|
4.8 Percentage of participants
|
|
Percentage of Participants Much Better or Better in Near Visual Acuity (High Contrast)
Better
|
15.0 Percentage of participants
|
20.0 Percentage of participants
|
22.1 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, Day 90Population: Participants from the Intent-to-Treat population, that included all randomized participants.
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.
Outcome measures
| Measure |
New Eye Drop Formulation 1
n=101 Participants
1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 1 in each eye at least twice daily for 90 days.
|
New Eye Drop Formulation 2
n=100 Participants
1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 2 in each eye at least twice daily for 90 days.
|
Refresh Tears®
n=104 Participants
1 to 2 drops of carboxymethylcellulose sodium based Eye Drops (Refresh Tears®) in each eye at least twice daily for 90 days.
|
|---|---|---|---|
|
Change From Baseline in Tear Break-Up Time (TBUT)
Baseline
|
5.24 Seconds
Standard Deviation 2.007
|
5.22 Seconds
Standard Deviation 1.870
|
5.05 Seconds
Standard Deviation 1.894
|
|
Change From Baseline in Tear Break-Up Time (TBUT)
Change from Baseline at Day 90
|
1.65 Seconds
Standard Deviation 4.268
|
1.97 Seconds
Standard Deviation 3.294
|
1.27 Seconds
Standard Deviation 2.837
|
SECONDARY outcome
Timeframe: Baseline, Day 90Population: Participants from the Intent-to-Treat population, that included all randomized participants.
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).
Outcome measures
| Measure |
New Eye Drop Formulation 1
n=101 Participants
1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 1 in each eye at least twice daily for 90 days.
|
New Eye Drop Formulation 2
n=100 Participants
1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 2 in each eye at least twice daily for 90 days.
|
Refresh Tears®
n=104 Participants
1 to 2 drops of carboxymethylcellulose sodium based Eye Drops (Refresh Tears®) in each eye at least twice daily for 90 days.
|
|---|---|---|---|
|
Change From Baseline in Corneal Staining
Baseline
|
6.4 Score on a scale
Standard Deviation 4.97
|
6.1 Score on a scale
Standard Deviation 4.25
|
5.8 Score on a scale
Standard Deviation 4.29
|
|
Change From Baseline in Corneal Staining
Change from Baseline at Day 90
|
-2.3 Score on a scale
Standard Deviation 3.75
|
-2.0 Score on a scale
Standard Deviation 3.36
|
-1.2 Score on a scale
Standard Deviation 3.13
|
SECONDARY outcome
Timeframe: Baseline, Day 90Population: Participants from the Intent-to-Treat population, that included all randomized participants.
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).
Outcome measures
| Measure |
New Eye Drop Formulation 1
n=101 Participants
1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 1 in each eye at least twice daily for 90 days.
|
New Eye Drop Formulation 2
n=100 Participants
1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 2 in each eye at least twice daily for 90 days.
|
Refresh Tears®
n=104 Participants
1 to 2 drops of carboxymethylcellulose sodium based Eye Drops (Refresh Tears®) in each eye at least twice daily for 90 days.
|
|---|---|---|---|
|
Change From Baseline in Conjunctival Staining
Baseline
|
8.0 Score on a scale
Standard Deviation 5.34
|
7.8 Score on a scale
Standard Deviation 5.45
|
8.2 Score on a scale
Standard Deviation 5.44
|
|
Change From Baseline in Conjunctival Staining
Change from Baseline at Day 90
|
-2.7 Score on a scale
Standard Deviation 4.72
|
-2.4 Score on a scale
Standard Deviation 4.06
|
-2.7 Score on a scale
Standard Deviation 4.36
|
SECONDARY outcome
Timeframe: Baseline, Day 90Population: Participants from the Intent-to-Treat population, that included all randomized participants.
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).
Outcome measures
| Measure |
New Eye Drop Formulation 1
n=101 Participants
1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 1 in each eye at least twice daily for 90 days.
|
New Eye Drop Formulation 2
n=100 Participants
1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 2 in each eye at least twice daily for 90 days.
|
Refresh Tears®
n=104 Participants
1 to 2 drops of carboxymethylcellulose sodium based Eye Drops (Refresh Tears®) in each eye at least twice daily for 90 days.
|
|---|---|---|---|
|
Change From Baseline in Schirmer Test
Baseline
|
8.7 mm
Standard Deviation 6.96
|
10.3 mm
Standard Deviation 7.17
|
8.9 mm
Standard Deviation 6.16
|
|
Change From Baseline in Schirmer Test
Change from Baseline at Day 90
|
1.2 mm
Standard Deviation 7.07
|
1.5 mm
Standard Deviation 6.12
|
1.1 mm
Standard Deviation 7.07
|
Adverse Events
New Eye Drop Formulation 1
New Eye Drop Formulation 2
Refresh Tears®
Serious adverse events
| Measure |
New Eye Drop Formulation 1
n=102 participants at risk
1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 1 in each eye at least twice daily for 90 days.
|
New Eye Drop Formulation 2
n=101 participants at risk
1 to 2 drops of carboxymethylcellulose sodium based New Eye Drop Formulation 2 in each eye at least twice daily for 90 days.
|
Refresh Tears®
n=103 participants at risk
1 to 2 drops of carboxymethylcellulose sodium based Eye Drops (Refresh Tears®) in each eye at least twice daily for 90 days.
|
|---|---|---|---|
|
Ear and labyrinth disorders
Meniere's disease
|
0.98%
1/102
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.)
|
0.00%
0/101
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.)
|
0.00%
0/103
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.)
|
|
Injury, poisoning and procedural complications
Ligament rupture
|
0.98%
1/102
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.)
|
0.00%
0/101
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.)
|
0.00%
0/103
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.)
|
|
Infections and infestations
Pelvic inflammatory disease
|
0.00%
0/102
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.)
|
0.99%
1/101
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.)
|
0.00%
0/103
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.)
|
|
Vascular disorders
Hypertension
|
0.00%
0/102
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.)
|
0.99%
1/101
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.)
|
0.00%
0/103
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.)
|
|
Nervous system disorders
Neuropathy peripheral
|
0.00%
0/102
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.)
|
0.00%
0/101
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.)
|
0.97%
1/103
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.)
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER