Dry Eye
Conditions
Keywords
Dry Eye, ophthalmic delivery
Brief summary
The purpose of this study is to evaluate the efficacy of three different concentrations (0.1%, 1.0%, 5.0%) of SAR 1118 Ophthalmic Solution compared to placebo in the treatment of dry eye.
Interventions
DRUGLifitegrast
Ophthalmic Solution
DRUGPlacebo
Ophthalmic Solution
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed Informed Consent Form and HIPAA document * 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 * Demonstrate a positive response when exposed to the Controlled Adverse Environment model * A negative urine pregnancy test if female of childbearing potential and must use adequate birth control throughout the study period
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 and for duration of the study period * 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 topical ophthalmic preparations (including tear substitutes) 72 hrs prior to screening assessments and through the entire study period * 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 Visit 1, and/or any other ocular surgical procedure within 12 months prior to Visit 1; or any scheduled ocular surgical procedure during the study period. * Known history of alcohol and/or drug abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Inferior Corneal Fluorescein Staining Score in Pre-Controlled Adverse Environment at Day 84 | Day 84 | Corneal staining was performed to grade the degree of corneal epithelial cell injury as measured by fluorescence using slit-lamp examination. The staining was graded with the Ophthalmic Research Associates, Inc. (ORA) scale. 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=occasional; 2=countable; 3=uncountable, but not confluent; 4=confluent) with 0.5 point increments, and lower score indicates a better outcome. 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Inferior Corneal Staining Score Change From Baseline (CFB) to Day 84 | Baseline (Day 0) and Day 84 | Corneal staining was performed to grade the degree of corneal epithelial cell injury as measured by fluorescence using slit-lamp examination. The staining was graded with the Ophthalmic Research Associates, Inc. (ORA) scale. 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=occasional; 2=countable; 3=uncountable, but not confluent; 4=confluent) with 0.5 point increments, and lower score indicates a better outcome. 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. |
Countries
United States
Participant flow
Pre-assignment details
The study was conducted in a Controlled Adverse Environment (CAE).
Participants by arm
| Arm | Count |
|---|---|
| Lifitegrast 0.1% | 57 |
| Lifitegrast 1.0% | 57 |
| Lifitegrast 5.0% | 58 |
| Placebo | 58 |
| Total | 230 |
Baseline characteristics
| Characteristic | Lifitegrast 0.1% | Lifitegrast 1.0% | Lifitegrast 5.0% | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 63.14 years STANDARD_DEVIATION 13.1 | 63.63 years STANDARD_DEVIATION 11.883 | 62.26 years STANDARD_DEVIATION 12.22 | 60.38 years STANDARD_DEVIATION 12.93 | 62.34 years STANDARD_DEVIATION 12.523 |
| Sex: Female, Male Female | 47 Participants | 40 Participants | 47 Participants | 45 Participants | 179 Participants |
| Sex: Female, Male Male | 10 Participants | 17 Participants | 11 Participants | 13 Participants | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 20 / 57 | 13 / 57 | 40 / 58 | 11 / 58 |
| serious Total, serious adverse events | 2 / 57 | 1 / 57 | 0 / 58 | 1 / 58 |
Outcome results
Primary
Inferior Corneal Fluorescein Staining Score in Pre-Controlled Adverse Environment at Day 84
Corneal staining was performed to grade the degree of corneal epithelial cell injury as measured by fluorescence using slit-lamp examination. The staining was graded with the Ophthalmic Research Associates, Inc. (ORA) scale. 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=occasional; 2=countable; 3=uncountable, but not confluent; 4=confluent) with 0.5 point increments, and lower score indicates a better outcome. 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: Day 84
Population: Intent-to-treat (ITT) population with LOCF defined as all randomized subjects. For the efficacy analysis, the Last Observation Carried Forward (LOCF) method will be used to impute missing values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lifitegrast 0.1% | Inferior Corneal Fluorescein Staining Score in Pre-Controlled Adverse Environment at Day 84 | 2.03 units on a scale | Standard Deviation 0.868 |
| Lifitegrast 1.0% | Inferior Corneal Fluorescein Staining Score in Pre-Controlled Adverse Environment at Day 84 | 1.92 units on a scale | Standard Deviation 0.768 |
| Lifitegrast 5.0% | Inferior Corneal Fluorescein Staining Score in Pre-Controlled Adverse Environment at Day 84 | 1.83 units on a scale | Standard Deviation 0.68 |
| Placebo | Inferior Corneal Fluorescein Staining Score in Pre-Controlled Adverse Environment at Day 84 | 2.05 units on a scale | Standard Deviation 0.715 |
p-value: 0.938195% CI: [-0.26, 0.39]Dunnett's test
p-value: 0.358595% CI: [-0.13, 0.53]Dunnett's test
p-value: 0.137595% CI: [-0.06, 0.6]Dunnett's test
Secondary
Inferior Corneal Staining Score Change From Baseline (CFB) 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 staining was graded with the Ophthalmic Research Associates, Inc. (ORA) scale. 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=occasional; 2=countable; 3=uncountable, but not confluent; 4=confluent) with 0.5 point increments, and lower score indicates a better outcome. 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 (Day 0) and Day 84
Population: ITT set with LOCF was used for analysis of this outcome. Here, n signifies the number of participants evaluable for the respective time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lifitegrast 0.1% | Inferior Corneal Staining Score Change From Baseline (CFB) to Day 84 | Pre-CAE: Baseline | 1.78 units on a scale | Standard Deviation 0.473 |
| Lifitegrast 0.1% | Inferior Corneal Staining Score Change From Baseline (CFB) to Day 84 | Pre-CAE: CFB to Day 84 | 0.25 units on a scale | Standard Deviation 0.841 |
| Lifitegrast 0.1% | Inferior Corneal Staining Score Change From Baseline (CFB) to Day 84 | Post-CAE: Baseline | 3.18 units on a scale | Standard Deviation 0.417 |
| Lifitegrast 0.1% | Inferior Corneal Staining Score Change From Baseline (CFB) to Day 84 | Post-CAE: Day 84 | 2.86 units on a scale | Standard Deviation 0.962 |
| Lifitegrast 1.0% | Inferior Corneal Staining Score Change From Baseline (CFB) to Day 84 | Pre-CAE: CFB to Day 84 | 0.10 units on a scale | Standard Deviation 0.735 |
| Lifitegrast 1.0% | Inferior Corneal Staining Score Change From Baseline (CFB) to Day 84 | Post-CAE: Baseline | 3.28 units on a scale | Standard Deviation 0.61 |
| Lifitegrast 1.0% | Inferior Corneal Staining Score Change From Baseline (CFB) to Day 84 | Post-CAE: Day 84 | 2.88 units on a scale | Standard Deviation 0.86 |
| Lifitegrast 1.0% | Inferior Corneal Staining Score Change From Baseline (CFB) to Day 84 | Pre-CAE: Baseline | 1.82 units on a scale | Standard Deviation 0.508 |
| Lifitegrast 5.0% | Inferior Corneal Staining Score Change From Baseline (CFB) to Day 84 | Post-CAE: Baseline | 3.16 units on a scale | Standard Deviation 0.523 |
| Lifitegrast 5.0% | Inferior Corneal Staining Score Change From Baseline (CFB) to Day 84 | Pre-CAE: CFB to Day 84 | 0.05 units on a scale | Standard Deviation 0.773 |
| Lifitegrast 5.0% | Inferior Corneal Staining Score Change From Baseline (CFB) to Day 84 | Post-CAE: Day 84 | 2.90 units on a scale | Standard Deviation 0.918 |
| Lifitegrast 5.0% | Inferior Corneal Staining Score Change From Baseline (CFB) to Day 84 | Pre-CAE: Baseline | 1.77 units on a scale | Standard Deviation 0.515 |
| Placebo | Inferior Corneal Staining Score Change From Baseline (CFB) to Day 84 | Post-CAE: Day 84 | 2.62 units on a scale | Standard Deviation 0.855 |
| Placebo | Inferior Corneal Staining Score Change From Baseline (CFB) to Day 84 | Pre-CAE: CFB to Day 84 | 0.40 units on a scale | Standard Deviation 0.802 |
| Placebo | Inferior Corneal Staining Score Change From Baseline (CFB) to Day 84 | Pre-CAE: Baseline | 1.65 units on a scale | Standard Deviation 0.513 |
| Placebo | Inferior Corneal Staining Score Change From Baseline (CFB) to Day 84 | Post-CAE: Baseline | 3.04 units on a scale | Standard Deviation 0.602 |