Dry Eye Disease
Conditions
Keywords
SAR 1118
Brief summary
The purpose of the study is to evaluate the safety and efficacy of lifitegrast ophthalmic solution compared to placebo in the treatment of dry eye.
Interventions
DRUGLifitegrast
Lifitegrast Ophthalmic Solution 5.0%
DRUGPlacebo
Placebo for Lifitegrast Ophthalmic Solution 5.0%
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Willing and able to read, sign and date the informed consent and HIPAA documents * Willing and able to comply with all study procedures * Be at least 18 years of age * Patient-reported history of dry eye in both eyes * A negative urine pregnancy test if female of childbearing potential and must use adequate birth control throughout the study period * Artificial tear use within the past 30 days
Exclusion criteria
* Any ocular condition that, in the opinion of the Investigator, could affect study parameters including, but not limited to, active ocular infection, ocular inflammation, glaucoma, and/or diabetic retinopathy * Unwilling to avoid wearing contact lenses for 7 days prior to first visit and for the duration of the study * Any blood donation or significant loss of blood within 56 days of Visit 1 * Any history of immunodeficiency disorder, positive HIV, hepatitis B, C, or evidence of acute active hepatitis A (anti-HAV IgM), or organ or bone marrow transplant. * Use of any prohibited medications at any time during the study unless otherwise specified * Any significant illness that could interfere with study parameters * History of laser assisted in situ keratomileusis (LASIK) or similar type of corneal refractive surgery within 12 months prior to first visit, and/or any other ocular surgical procedure within 12 months prior to first visit; or any scheduled ocular surgical procedure during the study period. * Known history of alcohol and/or drug abuse * Subjects with Dry eye secondary to scarring or destruction of conjunctival goblet cells (as with Vitamin A deficiency)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Inferior Corneal Fluorescein Staining Score to Day 84 | Baseline to Day 84 | Corneal staining was performed to grade the degree of corneal epithelial cell injury as measured by fluorescence using slit-lamp examination. The corneal surface is divided into three regions: superior, central and inferior. The scores for each of these 3 regions ranged from 0 to 4 (0=no staining; 1=few/rare punctate lesions; 2=discrete and countable lesions; 3=lesions too numerous to count, but not coalescent; 4=coalescent) with 0.5 point increments, and lower scores indicate improvement. Inferior corneal fluorescein staining scores from the study eye only were reported. Study eye is the 'worse eye', defined as the eye with worse (higher) score at baseline. |
| Change From Baseline in Eye Dryness Score (Visual Analogue Scale) to Day 84 | Baseline to Day 84 | Eye dryness score was assessed on a visual analogue scale (a 7-item \[burning/stinging, itching, foreign body sensation, eye discomfort, eye dryness, photophobia, and pain\], participant-reported, symptom index) with scores ranging from 0 to 100 (0=no discomfort; 100=maximal discomfort) and lower scores indicate a better outcome. |
Countries
United States
Participant flow
Pre-assignment details
Two of 720 participants were excluded from data analysis due to duplication. Therefore, 718 participants were randomized and treated. One participant from placebo arm (N=360) has taken study drug by mistake and considered for Lifitegrast arm (N=358). Therefore, Placebo (N=359), Lifitegrast (N=359) were considered for safety analysis.
Participants by arm
| Arm | Count |
|---|---|
| Lifitegrast | 358 |
| Placebo | 360 |
| Total | 718 |
Baseline characteristics
| Characteristic | Lifitegrast | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 58.7 years STANDARD_DEVIATION 13.93 | 58.9 years STANDARD_DEVIATION 14.26 | 58.8 years STANDARD_DEVIATION 14.09 |
| Sex: Female, Male Female | 285 Participants | 265 Participants | 550 Participants |
| Sex: Female, Male Male | 73 Participants | 95 Participants | 168 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 102 / 359 | 30 / 359 |
| serious Total, serious adverse events | 3 / 359 | 4 / 359 |
Outcome results
Primary
Change From Baseline in Eye Dryness Score (Visual Analogue Scale) to Day 84
Eye dryness score was assessed on a visual analogue scale (a 7-item \[burning/stinging, itching, foreign body sensation, eye discomfort, eye dryness, photophobia, and pain\], participant-reported, symptom index) with scores ranging from 0 to 100 (0=no discomfort; 100=maximal discomfort) and lower scores indicate a better outcome.
Time frame: Baseline to Day 84
Population: ITT population with last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lifitegrast | Change From Baseline in Eye Dryness Score (Visual Analogue Scale) to Day 84 | Change from Baseline to Day 84 | -35.30 units on a scale | Standard Deviation 28.4 |
| Lifitegrast | Change From Baseline in Eye Dryness Score (Visual Analogue Scale) to Day 84 | Baseline | 69.68 units on a scale | Standard Deviation 16.954 |
| Placebo | Change From Baseline in Eye Dryness Score (Visual Analogue Scale) to Day 84 | Change from Baseline to Day 84 | -22.75 units on a scale | Standard Deviation 28.6 |
| Placebo | Change From Baseline in Eye Dryness Score (Visual Analogue Scale) to Day 84 | Baseline | 69.22 units on a scale | Standard Deviation 16.761 |
p-value: <0.000195% CI: [8.51, 16.7]ANCOVA
Primary
Change From Baseline in Inferior Corneal Fluorescein Staining Score to Day 84
Corneal staining was performed to grade the degree of corneal epithelial cell injury as measured by fluorescence using slit-lamp examination. The corneal surface is divided into three regions: superior, central and inferior. The scores for each of these 3 regions ranged from 0 to 4 (0=no staining; 1=few/rare punctate lesions; 2=discrete and countable lesions; 3=lesions too numerous to count, but not coalescent; 4=coalescent) with 0.5 point increments, and lower scores indicate improvement. Inferior corneal fluorescein staining scores from the study eye only were reported. Study eye is the 'worse eye', defined as the eye with worse (higher) score at baseline.
Time frame: Baseline to Day 84
Population: Intent-to-treat (ITT) set included all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lifitegrast | Change From Baseline in Inferior Corneal Fluorescein Staining Score to Day 84 | Baseline | 2.39 units on a scale | Standard Deviation 0.763 |
| Lifitegrast | Change From Baseline in Inferior Corneal Fluorescein Staining Score to Day 84 | Change from Baseline to Day 84 | -0.73 units on a scale | Standard Deviation 0.926 |
| Placebo | Change From Baseline in Inferior Corneal Fluorescein Staining Score to Day 84 | Baseline | 2.40 units on a scale | Standard Deviation 0.722 |
| Placebo | Change From Baseline in Inferior Corneal Fluorescein Staining Score to Day 84 | Change from Baseline to Day 84 | -0.71 units on a scale | Standard Deviation 0.943 |
p-value: 0.618695% CI: [-0.1, 0.17]ANCOVA