Dry Eye Disease
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy and safety of SI-614 ophthalmic solution compared with placebo in patients with dry eye
Detailed description
This is a Phase 3, multicenter, randomized, double-masked study designed to evaluate the efficacy and safety of SI-614 ophthalmic solution compared to placebo in patients with dry eye. Approximately 230 male and female patients at least 18 years of age with dry eye in both eyes will be randomized to receive treatment with SI-614 or placebo in a 1:1 ratio. Randomized subjects received assigned study drug bilaterally four times daily. For efficacy endpoints, one "study eye" were defined for each patient based on the criteria at baseline and used for analysis.
Interventions
DRUGSI-614
One drop of study drug was instilled in each eye 4 times daily for 84 days
DRUGPlacebo
One drop of study drug was instilled in each eye 4 times daily for 84 days
Sponsors
Seikagaku Corporation
ORA, Inc.
Statistics & Data Corporation
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
* Have history of dry eye in both eyes for at least 6 months prior to Visit 1. * Have used and/or desired to use an artificial tear substitute for dry eye symptoms within 6 months prior to Visit 1. * If a female of childbearing potential, have a negative urine pregnancy test at Visit 1 and will be using an adequate method of birth control throughout the study period.
Exclusion criteria
* Have any clinically significant slit lamp findings at Visit 1 or Visit 2, including active blepharitis, meibomian gland dysfunction, lid margin inflammation or ocular allergies that requires therapeutic treatment and/or, in the opinion of the investigator, may interfere with the study parameters. * Be diagnosed with an ongoing ocular infection (bacterial, viral or fungal), or active ocular inflammation (eg, follicular conjunctivitis) at Visit 1 or Visit 2. * Have had any ocular surgical procedure within 12 months prior to Visit 1, or have any scheduled ocular surgical procedure during the study period. * Be a female who is pregnant, nursing an infant, or planning a pregnancy. * Have a known allergy and/or sensitivity to the study drug or its components. * Have a condition or is in a situation that, in the opinion of the investigator, may put the patient at significant risk, may confound the study results, or may interfere significantly with the patients' participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Day 29 in Corneal Fluorescein Staining Score in the Study Eye | 29 days | The examiner instilled sodium fluorescein solution into the inferior conjunctival cul-de-sac of each eye. After 3-5 minutes after instillation, the staining was graded with a scale, which was a 0 to 4 scale and where grade 0 = No Staining and 4 = Confluent Staining. Higher numbers indicate worse outcome. The total score was derived using the sum of the 3 regions such that possible scores range from 0 to 12. For efficacy endpoints, one "study eye" were defined for each patient based on the criteria at baseline and used for analysis. Analyses were for the study eye only. Efficacy was analyzed on all randomized subjects (232 subjects: 114 subjects in SI-614 and 118 subjects in Placebo). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Average Score of Ocular Discomfort and Dryness at the Bedtime Assessment From the Patient Daily Diary During Day 1 Through Day 14 | 14 days | Subjects graded the severity of their dry eye disease symptoms in their diary with rating the severity of 5 symptoms. Each symptom rating ranged from 0 to 5 using whole numbers, where 0 = None and 5 = Worst. Higher numbers indicate worse symptomology. The average score of the two symptoms of ocular discomfort (where 0 = None and 5 = Worst) and dryness (where 0 = None and 5 = Worst) was measured. |
Countries
United States
Contacts
STUDY_DIRECTORGeorge Ousler
ORA, Inc.
Participant flow
Recruitment details
This study is a study in which whole participants, not eyes were assigned to Arms/Groups. Patients were randomized to receive treatment with SI-614 or placebo in a 1:1 ratio, and the randomized subjects received assigned study drug bilaterally four times daily. For efficacy endpoints, one "study eye" was defined for each patient at baseline and used for analysis. Therefore, whole patients are assigned to Arms/Groups
Pre-assignment details
Of the screened 470 subjects, 238 subjects were screen failed, and 232 subjects were randomized (114 subjects in SI-614 and 118 subjects in Placebo). From the 232 subjects, 231 subjects (114 subjects in SI-614, and 117 subjects in Placebo) received at least one dose of study drug and 1 subject did not receive study drug. Efficacy was analyzed on all randomized subjects (232 subjects). Safety was analyzed on all subjects who receive at least 1 dose of randomized study drug (231 subjects).
Participants by arm
| Arm | Count |
|---|---|
| SI-614 SI-614: One drop of study drug was instilled in each eye 4 times daily for 84 days | 114 |
| Placebo Placebo: One drop of study drug was instilled in each eye 4 times daily for 84 days | 118 |
| Total | 232 |
Baseline characteristics
| Characteristic | SI-614 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 63.6 years STANDARD_DEVIATION 12.81 | 64.4 years STANDARD_DEVIATION 12.08 | 64.0 years STANDARD_DEVIATION 12.43 |
| Corneal Fluorescein Staining Score | 4.54 units on a scale STANDARD_DEVIATION 1.26 | 4.22 units on a scale STANDARD_DEVIATION 1.124 | 4.38 units on a scale STANDARD_DEVIATION 1.201 |
| Race/Ethnicity, Customized Ethnicity : Hispanic or Latino | 10 participants | 7 participants | 17 participants |
| Race/Ethnicity, Customized Ethnicity : Not Hispanic or Latino | 104 participants | 111 participants | 215 participants |
| Race/Ethnicity, Customized Race : American Indian or Alaska Native | 0 participants | 2 participants | 2 participants |
| Race/Ethnicity, Customized Race : Asian | 4 participants | 5 participants | 9 participants |
| Race/Ethnicity, Customized Race : Black or African American | 17 participants | 26 participants | 43 participants |
| Race/Ethnicity, Customized Race : Native Hawaiian or Other Pacific Islander | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Race : Other | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Race : White | 92 participants | 85 participants | 177 participants |
| Sex: Female, Male Female | 82 Participants | 84 Participants | 166 Participants |
| Sex: Female, Male Male | 32 Participants | 34 Participants | 66 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 114 | 0 / 117 |
| other Total, other adverse events | 31 / 114 | 23 / 117 |
| serious Total, serious adverse events | 4 / 114 | 3 / 117 |
Outcome results
Primary
Change From Baseline to Day 29 in Corneal Fluorescein Staining Score in the Study Eye
The examiner instilled sodium fluorescein solution into the inferior conjunctival cul-de-sac of each eye. After 3-5 minutes after instillation, the staining was graded with a scale, which was a 0 to 4 scale and where grade 0 = No Staining and 4 = Confluent Staining. Higher numbers indicate worse outcome. The total score was derived using the sum of the 3 regions such that possible scores range from 0 to 12. For efficacy endpoints, one study eye were defined for each patient based on the criteria at baseline and used for analysis. Analyses were for the study eye only. Efficacy was analyzed on all randomized subjects (232 subjects: 114 subjects in SI-614 and 118 subjects in Placebo).
Time frame: 29 days
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SI-614 | Change From Baseline to Day 29 in Corneal Fluorescein Staining Score in the Study Eye | 2.19 score on a scale | Standard Error 0.182 |
| Placebo | Change From Baseline to Day 29 in Corneal Fluorescein Staining Score in the Study Eye | 2.31 score on a scale | Standard Error 0.177 |
p-value: 0.31595% CI: [-0.62, 0.38]ANCOVA
Secondary
Change From Baseline in the Average Score of Ocular Discomfort and Dryness at the Bedtime Assessment From the Patient Daily Diary During Day 1 Through Day 14
Subjects graded the severity of their dry eye disease symptoms in their diary with rating the severity of 5 symptoms. Each symptom rating ranged from 0 to 5 using whole numbers, where 0 = None and 5 = Worst. Higher numbers indicate worse symptomology. The average score of the two symptoms of ocular discomfort (where 0 = None and 5 = Worst) and dryness (where 0 = None and 5 = Worst) was measured.
Time frame: 14 days
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SI-614 | Change From Baseline in the Average Score of Ocular Discomfort and Dryness at the Bedtime Assessment From the Patient Daily Diary During Day 1 Through Day 14 | -0.04 score on a scale | Standard Error 0.039 |
| Placebo | Change From Baseline in the Average Score of Ocular Discomfort and Dryness at the Bedtime Assessment From the Patient Daily Diary During Day 1 Through Day 14 | -0.04 score on a scale | Standard Error 0.039 |
p-value: 0.48795% CI: [-0.11, 0.11]Mixed Models Analysis