Dry Eye
Conditions
Brief summary
The purpose of this study is to evaluate the clinical effectiveness of SYSTANE® BALANCE compared to REFRESH OPTIVE® Advanced in subjects with lipid-deficient dry eye.
Interventions
Sponsors
Alcon Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Willing and able to attend all study visits; * Must sign an informed consent form; * Best-corrected visual acuity (BCVA) of 55 letters or better in each eye as assessed using an early treatment diabetic retinopathy study (ETDRS) chart; * Willing to take study products as directed for entire study; * Other protocol-specified inclusion criteria may apply.
Exclusion criteria
* Women of childbearing potential who are pregnant, plan to become pregnant during the study, breast feeding, or not using adequate birth control methods; * Contact lens use within 30 days prior to Screening Visit, or unwilling to avoid contact lens use during the course of the study; * Use of medication excluded by the protocol; * Diseases, illnesses, infections, or ocular abnormalities excluded by the protocol; * Ocular surgeries or procedures excluded by the protocol; * Other protocol-specified
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Tear Film Break-Up Time (TFBUT) at Day 35 | Baseline (Day 0), Day 35 | TFBUT (the time required for dry spots to appear on the surface of the eye after blinking) was assessed with a fluorescein strip and measured in seconds. Using a stopwatch, the investigator measured the time from the last blink until one or more black (dry) spots appeared in the precorneal tear film. The longer it takes, the more stable the tear film. A positive number change from baseline indicates improvement. Only one eye (analysis eye) contributed to the analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in TFBUT at Day 35 | Baseline (Day 0), Day 35 | TFBUT (the time required for dry spots to appear on the surface of the eye after blinking) was assessed with a fluorescein strip and measured in seconds. Using a stopwatch, the investigator measured the time from the last blink until one or more black (dry) spots appeared in the precorneal tear film. The longer it takes, the more stable the tear film. A positive number change from baseline indicates improvement. Only one eye (analysis eye) contributed to the analysis. |
| Lipid Layer Thickness (LLT) Area Under the Curve (AUC120) at Day 35 | Day 35 | LLT was measured using the LipiView® Ocular Surface Interferometer, an ophthalmic imaging device intended for use in adult patients to capture, archive, manipulate and store digital images of specular (interferometric) observations of the tear film, which can be visually monitored and photographically documented. Using these images, the LipiView® Interferometer measures the absolute thickness of the tear film lipid layer. |
| Mean Change From Baseline in Global Ocular Discomfort Visual Analog Scale (VAS) Score at Day 35 | Baseline (Day 0), Day 35 | Ocular discomfort frequency and severity (each graded on a separate 100-units scale) were assessed using a visual analog scale (VAS). Frequency score was in response to the question 'how often your eyes felt uncomfortable during the past week' ranging from 'Rarely' to 'All the time.' Severity score was in response to the question 'how uncomfortable your eyes felt during the past week' ranging from 'Very mildly uncomfortable' to 'Very severely uncomfortable.' The Global Ocular Discomfort Score, ranging from 0 to 100, was calculated for the given visit, as the square root of the product of the ocular discomfort frequency score multiplied by the ocular discomfort severity score. Improvement results in a reduction of the ocular discomfort frequency or severity, or both, translating into a reduction of the resulting Global Ocular Discomfort score as compared to baseline. A negative change from baseline indicates improvement. |
Participant flow
Recruitment details
Subjects were recruited from 14 study centers located in Australia (2), Taiwan (1), Singapore (1), United Kingdom (1) and the US (9).
Pre-assignment details
Of the 308 enrolled, 77 were exited as screen failures prior to randomization. This reporting group includes all randomized and treated subjects (231).
Participants by arm
| Arm | Count |
|---|---|
| SYSTANE BALANCE Propylene glycol, 0.6% eye drops, 1 drop in each eye 4 times per day for 35 days | 117 |
| REFRESH OPTIVE Lubricant eye drops, 1 drop in each eye 4 times per day for 35 days | 114 |
| Total | 231 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Other - Reason not given | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | SYSTANE BALANCE | REFRESH OPTIVE | Total |
|---|---|---|---|
| Age, Continuous | 56.7 years STANDARD_DEVIATION 14.7 | 55.6 years STANDARD_DEVIATION 16.35 | 56.2 years STANDARD_DEVIATION 15.51 |
| Race/Ethnicity, Customized Asian | 25 Participants | 27 Participants | 52 Participants |
| Race/Ethnicity, Customized Black or African American | 6 Participants | 7 Participants | 13 Participants |
| Race/Ethnicity, Customized Multiracial | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 4 Participants | 3 Participants | 7 Participants |
| Race/Ethnicity, Customized White | 81 Participants | 76 Participants | 157 Participants |
| Sex: Female, Male Female | 90 Participants | 92 Participants | 182 Participants |
| Sex: Female, Male Male | 27 Participants | 22 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 117 | 0 / 114 |
| other Total, other adverse events | 6 / 117 | 13 / 114 |
| serious Total, serious adverse events | 0 / 117 | 1 / 114 |
Outcome results
Primary
Mean Change From Baseline in Tear Film Break-Up Time (TFBUT) at Day 35
TFBUT (the time required for dry spots to appear on the surface of the eye after blinking) was assessed with a fluorescein strip and measured in seconds. Using a stopwatch, the investigator measured the time from the last blink until one or more black (dry) spots appeared in the precorneal tear film. The longer it takes, the more stable the tear film. A positive number change from baseline indicates improvement. Only one eye (analysis eye) contributed to the analysis.
Time frame: Baseline (Day 0), Day 35
Population: Per Protocol Analysis Set. At each time point, only subjects with a value at both Baseline and that time point are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SYSTANE BALANCE | Mean Change From Baseline in Tear Film Break-Up Time (TFBUT) at Day 35 | 0.999 seconds | Standard Deviation 1.9439 |
| REFRESH OPTIVE | Mean Change From Baseline in Tear Film Break-Up Time (TFBUT) at Day 35 | 0.864 seconds | Standard Deviation 1.6198 |
p-value: <0.000195% CI: [-0.341, 0.601]Mixed model repeated measures (MMRM)
Secondary
Change From Baseline in TFBUT at Day 35
TFBUT (the time required for dry spots to appear on the surface of the eye after blinking) was assessed with a fluorescein strip and measured in seconds. Using a stopwatch, the investigator measured the time from the last blink until one or more black (dry) spots appeared in the precorneal tear film. The longer it takes, the more stable the tear film. A positive number change from baseline indicates improvement. Only one eye (analysis eye) contributed to the analysis.
Time frame: Baseline (Day 0), Day 35
Population: Full Analysis Set. At each time point, only subjects with a value at both Baseline and that time point are included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SYSTANE BALANCE | Change From Baseline in TFBUT at Day 35 | 0.985 seconds | Standard Error 0.1651 |
| REFRESH OPTIVE | Change From Baseline in TFBUT at Day 35 | 0.867 seconds | Standard Error 0.1702 |
p-value: 0.3195% CI: [-0.349, 0.585]MMRM
Secondary
Lipid Layer Thickness (LLT) Area Under the Curve (AUC120) at Day 35
LLT was measured using the LipiView® Ocular Surface Interferometer, an ophthalmic imaging device intended for use in adult patients to capture, archive, manipulate and store digital images of specular (interferometric) observations of the tear film, which can be visually monitored and photographically documented. Using these images, the LipiView® Interferometer measures the absolute thickness of the tear film lipid layer.
Time frame: Day 35
Population: Area under the curve (AUC) lipid layer thickness (LLT) was removed from formal analysis as a secondary endpoint via amendment of the standalone Statistical Analysis Plan (SAP) due to a large proportion of data that were above the limit of detection.
Secondary
Mean Change From Baseline in Global Ocular Discomfort Visual Analog Scale (VAS) Score at Day 35
Ocular discomfort frequency and severity (each graded on a separate 100-units scale) were assessed using a visual analog scale (VAS). Frequency score was in response to the question 'how often your eyes felt uncomfortable during the past week' ranging from 'Rarely' to 'All the time.' Severity score was in response to the question 'how uncomfortable your eyes felt during the past week' ranging from 'Very mildly uncomfortable' to 'Very severely uncomfortable.' The Global Ocular Discomfort Score, ranging from 0 to 100, was calculated for the given visit, as the square root of the product of the ocular discomfort frequency score multiplied by the ocular discomfort severity score. Improvement results in a reduction of the ocular discomfort frequency or severity, or both, translating into a reduction of the resulting Global Ocular Discomfort score as compared to baseline. A negative change from baseline indicates improvement.
Time frame: Baseline (Day 0), Day 35
Population: Full Analysis Set. At each time point, only subjects with a value at both Baseline and that time point are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SYSTANE BALANCE | Mean Change From Baseline in Global Ocular Discomfort Visual Analog Scale (VAS) Score at Day 35 | -9.9 units on a scale | Standard Deviation 25.26 |
| REFRESH OPTIVE | Mean Change From Baseline in Global Ocular Discomfort Visual Analog Scale (VAS) Score at Day 35 | -8.8 units on a scale | Standard Deviation 26.11 |
p-value: 0.61895% CI: [-6.4, 4.7]MMRM