Dry Eye Disease
Conditions
Brief summary
The purpose of this study is to assess the efficacy and safety of K-161 ophthalmic solution for the treatment of moderate to severe dry eye disease.
Interventions
DRUGK-161
K-161 Ophthalmic Solution
DRUGPlacebo
Vehicle Solution
Sponsors
Kowa Research Institute, Inc.
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
* Be at least 18 years of age at the time of Informed Consent * Have a reported history of dry eye disease in both eyes and a history of eye drop use for dry eye symptom * Meet all other inclusion criteria outlined in the clinical study protocol
Exclusion criteria
* Have any clinically significant ocular condition * Have a history of corneal refractive surgery and/or any other ocular surgical procedure within 12 months * Meet any other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in EDS (VAS) From Baseline to Day 85 | Baseline to Day 85 | * Eye Dryness Score (EDS) on Visual analog scale (VAS) * Participant self rated level of severity where, 0 mm corresponds to None and 100 mm corresponds to Worst Possible. |
| Change in Conjunctival Sum Fluorescein Staining Score From Baseline to Day 85 (Study Eye) | Baseline to Day 85 | * Assessed by expanded National Eye Institute (NEI) scale * Conjunctival sum will be assessed as the sum of points in 6 conjunctival zones, and each zone will be graded on a 5-point scale from 0 - no conjunctival staining to 4 - severe staining of the area (0.5 increments would be allowed) * Minimum is 0 and maximum is 24 for Conjunctival Sum Fluorescein Staining Score. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Day 85 in Ocular Surface Disease Index Score (OSDI©) | Baseline to Day 85 | OSDI is assessed on a scale of 0 to 100, with higher scores representing greater disability. |
| Change From Baseline to Day 85 in Total Eye Sum Fluorescein Staining Score (Study Eye) | Baseline to Day 85 | * Assessed by expanded National Eye Institute (NEI) scale. * Total eye sum will be assessed as the sum of Corneal sum fluorescein staining score and conjunctival sum fluorescein staining score. * Minimum is 0 and maximum is 44 for Total Eye Sum Fluorescein Staining Score. |
| Change From Baseline to Day 85 in Tear Film Break-up Time (TFBUT) (Study Eye) | Baseline to Day 85 | The time (in seconds) taken for the first dry spot to appear on the cornea after a complete blink (with the aid of a slit-lamp). |
| Change From Baseline to Day 85 in Schirmer's Test (Unanesthetized) (Study Eye) | Baseline to Day 85 | Length (mm) of the moistened area assessed by inserting a Schirmer test strip into the eye for 5 minutes to measure the production of tears. |
| Change From Baseline to Day 85 in Corneal Sum Fluorescein Staining Score (Study Eye) | Baseline to Day 85 | * Assessed by expanded National Eye Institute (NEI) scale. * Corneal sum will be assessed as the sum of points in 5 corneal zones, and each zone will be graded on a 5-point scale from 0 - no punctate stain in the area to 4 - Severe diffuse (coalescent) macropunctate stain of the area (0.5 increments would be allowed) * Minimum is 0 and maximum is 20 for Corneal Sum Fluorescein Staining Score |
Countries
United States
Participant flow
Pre-assignment details
At Visit 1 (Screening), eligible participants were provided single-masked run-in product (Vehicle) for self-administration in the morning and evening, for approximately 14 days. At Visit 2 (Baseline), participants who remained eligible for the study were randomized in a 1:1 ratio to double-masked IP (K-161 or Vehicle). Each participant provided voluntary informed consent before any study-specific assessments or procedures were performed.
Participants by arm
| Arm | Count |
|---|---|
| K-161 K-161 topical Ophthalmic solution for 12 weeks | 321 |
| Vehicle Vehicle K-161 identical topical ophthalmic solution without active drug for 12 weeks | 322 |
| Total | 643 |
Baseline characteristics
| Characteristic | K-161 | Vehicle | Total |
|---|---|---|---|
| Age, Continuous | 59.9 years STANDARD_DEVIATION 13.88 | 60.0 years STANDARD_DEVIATION 15.18 | 60.0 years STANDARD_DEVIATION 14.54 |
| Race/Ethnicity, Customized Asian | 39 Participants | 45 Participants | 84 Participants |
| Race/Ethnicity, Customized Black or African American | 42 Participants | 41 Participants | 83 Participants |
| Race/Ethnicity, Customized Multiple | 4 Participants | 4 Participants | 8 Participants |
| Race/Ethnicity, Customized Native Hawaiian | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 234 Participants | 230 Participants | 464 Participants |
| Sex: Female, Male Female | 233 Participants | 234 Participants | 467 Participants |
| Sex: Female, Male Male | 88 Participants | 88 Participants | 176 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 | 0 / 321 | 0 / 322 | 0 / 122 | 0 / 121 |
| other Total, other adverse events | 32 / 321 | 0 / 322 | 0 / 122 | 0 / 121 |
| serious Total, serious adverse events | 3 / 321 | 2 / 322 | 1 / 122 | 2 / 121 |
Outcome results
Primary
Change in Conjunctival Sum Fluorescein Staining Score From Baseline to Day 85 (Study Eye)
* Assessed by expanded National Eye Institute (NEI) scale * Conjunctival sum will be assessed as the sum of points in 6 conjunctival zones, and each zone will be graded on a 5-point scale from 0 - no conjunctival staining to 4 - severe staining of the area (0.5 increments would be allowed) * Minimum is 0 and maximum is 24 for Conjunctival Sum Fluorescein Staining Score.
Time frame: Baseline to Day 85
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| K-161 | Change in Conjunctival Sum Fluorescein Staining Score From Baseline to Day 85 (Study Eye) | -2.81 Score on a scale | Standard Deviation 3.661 |
| Vehicle | Change in Conjunctival Sum Fluorescein Staining Score From Baseline to Day 85 (Study Eye) | -3.25 Score on a scale | Standard Deviation 3.48 |
p-value: 0.2028Control-Based Mean Imputation
Primary
Change in EDS (VAS) From Baseline to Day 85
* Eye Dryness Score (EDS) on Visual analog scale (VAS) * Participant self rated level of severity where, 0 mm corresponds to None and 100 mm corresponds to Worst Possible.
Time frame: Baseline to Day 85
Population: The number of participants analyzed for the outcome measure may differ from the overall number of participants in each group. This discrepancy can be attributed to several factors, including:~• Missing data: Some participants may have incomplete data due to factors such as missed visits, early withdrawal, or loss to follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| K-161 | Change in EDS (VAS) From Baseline to Day 85 | -18.0 mm | Standard Deviation 25.1 |
| Vehicle | Change in EDS (VAS) From Baseline to Day 85 | -19.4 mm | Standard Deviation 25.34 |
p-value: 0.5019Control-Based Mean Imputation
Secondary
Change From Baseline to Day 85 in Corneal Sum Fluorescein Staining Score (Study Eye)
* Assessed by expanded National Eye Institute (NEI) scale. * Corneal sum will be assessed as the sum of points in 5 corneal zones, and each zone will be graded on a 5-point scale from 0 - no punctate stain in the area to 4 - Severe diffuse (coalescent) macropunctate stain of the area (0.5 increments would be allowed) * Minimum is 0 and maximum is 20 for Corneal Sum Fluorescein Staining Score
Time frame: Baseline to Day 85
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| K-161 | Change From Baseline to Day 85 in Corneal Sum Fluorescein Staining Score (Study Eye) | -1.92 Score on a scale | Standard Deviation 2.905 |
| Vehicle | Change From Baseline to Day 85 in Corneal Sum Fluorescein Staining Score (Study Eye) | -2.19 Score on a scale | Standard Deviation 2.841 |
p-value: 0.2512Control-Based Mean Imputation
Secondary
Change From Baseline to Day 85 in Ocular Surface Disease Index Score (OSDI©)
OSDI is assessed on a scale of 0 to 100, with higher scores representing greater disability.
Time frame: Baseline to Day 85
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| K-161 | Change From Baseline to Day 85 in Ocular Surface Disease Index Score (OSDI©) | -14.12 Score on a scale | Standard Deviation 17.099 |
| Vehicle | Change From Baseline to Day 85 in Ocular Surface Disease Index Score (OSDI©) | -14.17 Score on a scale | Standard Deviation 17.594 |
p-value: 0.7906Control-Based Mean Imputation
Secondary
Change From Baseline to Day 85 in Schirmer's Test (Unanesthetized) (Study Eye)
Length (mm) of the moistened area assessed by inserting a Schirmer test strip into the eye for 5 minutes to measure the production of tears.
Time frame: Baseline to Day 85
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| K-161 | Change From Baseline to Day 85 in Schirmer's Test (Unanesthetized) (Study Eye) | 2.4 mm | Standard Deviation 5.47 |
| Vehicle | Change From Baseline to Day 85 in Schirmer's Test (Unanesthetized) (Study Eye) | 2.6 mm | Standard Deviation 5.25 |
p-value: 0.5343Control-Based Mean Imputation
Secondary
Change From Baseline to Day 85 in Tear Film Break-up Time (TFBUT) (Study Eye)
The time (in seconds) taken for the first dry spot to appear on the cornea after a complete blink (with the aid of a slit-lamp).
Time frame: Baseline to Day 85
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| K-161 | Change From Baseline to Day 85 in Tear Film Break-up Time (TFBUT) (Study Eye) | 0.580 Seconds | Standard Deviation 1.2089 |
| Vehicle | Change From Baseline to Day 85 in Tear Film Break-up Time (TFBUT) (Study Eye) | 0.520 Seconds | Standard Deviation 1.1989 |
p-value: 0.3757Control-Based Mean Imputation
Secondary
Change From Baseline to Day 85 in Total Eye Sum Fluorescein Staining Score (Study Eye)
* Assessed by expanded National Eye Institute (NEI) scale. * Total eye sum will be assessed as the sum of Corneal sum fluorescein staining score and conjunctival sum fluorescein staining score. * Minimum is 0 and maximum is 44 for Total Eye Sum Fluorescein Staining Score.
Time frame: Baseline to Day 85
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| K-161 | Change From Baseline to Day 85 in Total Eye Sum Fluorescein Staining Score (Study Eye) | -4.73 Score on a scale | Standard Deviation 5.693 |
| Vehicle | Change From Baseline to Day 85 in Total Eye Sum Fluorescein Staining Score (Study Eye) | -5.44 Score on a scale | Standard Deviation 5.546 |
p-value: 0.1914Control-Based Mean Imputation