Dry Eye Disease
Conditions
Brief summary
The objective of the study is to assess the safety, efficacy, optimum dosage, and dosing regimen of K-161 in adult subjects with moderate to severe dry eye disease.
Interventions
DRUGK-161
K-161 alternate dosage
OTHERPlacebo (Vehicle)
Placebo 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 visit. * Have a reported history of dry eye disease in both eyes and a history of eye drop use for dry eye symptoms. * Meet all 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. * Must not meet any other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Inferior Corneal Fluorescein Staining Score Post Controlled Adverse Environment (Post-Controlled Adverse Environment (CAE)) | Baseline to Day 29 | Fluorescein Staining is measured with the Ora Calibra® Corneal and Conjunctival Staining Scale which is a 0 to 4 scale with increasing half-units and where higher numbers indicating more severe staining. K-161 compared to Vehicle. When study patients are exposed to Controlled Adverse Environment (CAE) in terms of relative humidity, temperature, airflow, and visual tasking, the ocular surface is stressed to react. This controlled environmental stress creates a consistent response that's reproducible over time. |
| Change in Ocular Discomfort Scale Post-CAE | Baseline to Day 29 | Ocular discomfort scores were subjectively graded by the subjects using the Ora Calibra® Ocular Discomfort Scale from 0 to 4 where 0 = No Discomfort and 4 = Constant Discomfort. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Fluorescein Staining Scores (Pre-CAE®) | Baseline to Day 29 | Fluorescein Staining is measured with the Ora Calibra® Corneal and Conjunctival Staining Scale which is a 0 to 4 scale with increasing half-units and where higher numbers indicating more severe staining. |
| Change in Lissamine Green Staining (Pre-CAE) Using the Ora Calibra® Scale (Conjunctival Sum) | Baseline to Day 29 | Ora Calibra Scale which is 0 to 4 scale with increasing half-units and where higher numbers indicating more severe staining. |
| Change in Conjunctival Redness (Pre-CAE) | Baseline to Day 29 | Conjunctival Redness Scale ranges from 0 to 4, where 0 = normal, without vasodilation and 4 = Broad Ciliary and Prominent, Horizontal Conjunctival Vasodilation. Higher scores indicate worsening conjunctival redness. |
| Change in Tear Film Break-Up Time (Pre CAE) | Baseline to Day 29 | — |
| Change in Tear Osmolarity (Pre CAE) | Baseline to Day 29 | — |
| Change in Schirmer's Test Value (Unanesthetized) Pre-CAE | Baseline to Day 29 | Measured with Schirmer's test strip with the length of the moistened area recorded in mm. Lower values indicate less tears produced in the eye. |
| Change in Blink Rate (Pre CAE) | Baseline to Day 29 | Blinks per 60 seconds. |
| Change in Ocular Discomfort Scale (Pre CAE) | Baseline to Day 29 | Ora Calibra® Ocular Discomfort Scale ranging from 0 to 4 |
| Change in Ocular Discomfort and 4-Symptom Questionnaire (Pre CAE) | Baseline to Day 29 | Scores ranging from 0 to 5. A score of 0 indicates no discomfort/symptoms and a score of 5 indicates worst discomfort/symptoms. |
| Change in Visual Analog Scale (Pre CAE) | Baseline to Day 29 | The length of the assessment line was 100 mm; a measure of 0 mm corresponded to no discomfort and 100 mm corresponds to maximal discomfort. |
| Change in Ocular Surface Disease Index Score (Pre-CAE) - Total OSDI | Baseline to Day 29 | The OSDI© is comprised of 12 questions, with each question assessed on a scale ranging from 0 to 4 where 0 = none of the time, 1 = some of the time, 2 = half of the time, 3 = most of the time, and 4 = all of the time. The range of total score is 0 to 100. Subscale scores are not reported. Higher score represents a worsen outcome. The total score is the sum of subscales. |
| Change in Unanesthetized Schirmer's Test (Pre CAE) | Baseline to Day 29 | Measured with Schirmer's test strip with the length of the moistened area recorded in mm. Lower values indicate less tears produced in the eye. |
| Change in Tear Film Break-up Time (TFBUT) Post-CAE | Baseline to Day 29 | — |
Countries
United States
Participant flow
Pre-assignment details
During the screening period, two 90-minute exposures to the CAE® were conducted to ascertain eligibility to enter the study. Participants who qualified after the initial screening visit entered the run-in phase, where they self-administered Vehicle for approximately 14 days. Those who qualified at Visit 2 (Day 1) were randomized to receive study drug in a double-masked fashion for 28 days.
Participants by arm
| Arm | Count |
|---|---|
| Placebo (BID) (Vehicle) 1 drop Ophthalmic Solution | 59 |
| 0.025% K-161 (BID) 1 drop Ophthalmic Solution | 59 |
| 0.1% K-161 (BID) 1 drop Ophthalmic Solution | 61 |
| 0.1% K-161 (QID) 1 drop Ophthalmic Solution | 59 |
| Total | 238 |
Baseline characteristics
| Characteristic | Placebo (BID) (Vehicle) | 0.025% K-161 (BID) | 0.1% K-161 (BID) | 0.1% K-161 (QID) | Total |
|---|---|---|---|---|---|
| Age, Customized < 65 years | 34 Participants | 37 Participants | 38 Participants | 38 Participants | 147 Participants |
| Age, Customized ≥ 65 years | 25 Participants | 22 Participants | 23 Participants | 21 Participants | 91 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 58 Participants | 58 Participants | 60 Participants | 58 Participants | 234 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Inferior Corneal Fluorescein Staining Score Post Controlled Adverse Environment (Post-CAE) | 3.30 scores on a scale STANDARD_DEVIATION 0.361 | 3.36 scores on a scale STANDARD_DEVIATION 0.405 | 3.35 scores on a scale STANDARD_DEVIATION 0.412 | 3.33 scores on a scale STANDARD_DEVIATION 0.378 | 3.33 scores on a scale STANDARD_DEVIATION 0.388 |
| Ocular Discomfort Scale Post-CAE | 3.8 scores on a scale STANDARD_DEVIATION 0.49 | 3.7 scores on a scale STANDARD_DEVIATION 0.48 | 3.7 scores on a scale STANDARD_DEVIATION 0.61 | 3.6 scores on a scale STANDARD_DEVIATION 0.72 | 3.7 scores on a scale STANDARD_DEVIATION 0.58 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 13 Participants | 16 Participants | 12 Participants | 15 Participants | 56 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants | 11 Participants | 10 Participants | 9 Participants | 45 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 29 Participants | 32 Participants | 37 Participants | 35 Participants | 133 Participants |
| Sex: Female, Male Female | 41 Participants | 43 Participants | 44 Participants | 43 Participants | 171 Participants |
| Sex: Female, Male Male | 18 Participants | 16 Participants | 17 Participants | 16 Participants | 67 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 / 59 | 0 / 59 | 0 / 61 | 0 / 59 |
| other Total, other adverse events | 2 / 59 | 7 / 59 | 25 / 61 | 24 / 59 |
| serious Total, serious adverse events | 3 / 59 | 0 / 59 | 0 / 61 | 0 / 59 |
Outcome results
Primary
Change in Inferior Corneal Fluorescein Staining Score Post Controlled Adverse Environment (Post-Controlled Adverse Environment (CAE))
Fluorescein Staining is measured with the Ora Calibra® Corneal and Conjunctival Staining Scale which is a 0 to 4 scale with increasing half-units and where higher numbers indicating more severe staining. K-161 compared to Vehicle. When study patients are exposed to Controlled Adverse Environment (CAE) in terms of relative humidity, temperature, airflow, and visual tasking, the ocular surface is stressed to react. This controlled environmental stress creates a consistent response that's reproducible over time.
Time frame: Baseline to Day 29
Population: Endpoints analysis was determined by comparing 0.1% K-161 BID to its Vehicle BID
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (BID) (Vehicle) | Change in Inferior Corneal Fluorescein Staining Score Post Controlled Adverse Environment (Post-Controlled Adverse Environment (CAE)) | -0.57 scores on a scale | Standard Error 0.075 |
| 0.1% K-161 (BID) | Change in Inferior Corneal Fluorescein Staining Score Post Controlled Adverse Environment (Post-Controlled Adverse Environment (CAE)) | -0.44 scores on a scale | Standard Error 0.073 |
p-value: 0.2175ANCOVA
Primary
Change in Ocular Discomfort Scale Post-CAE
Ocular discomfort scores were subjectively graded by the subjects using the Ora Calibra® Ocular Discomfort Scale from 0 to 4 where 0 = No Discomfort and 4 = Constant Discomfort.
Time frame: Baseline to Day 29
Population: Endpoints analysis was determined by comparing 0.1% K-161 BID to its Vehicle BID
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (BID) (Vehicle) | Change in Ocular Discomfort Scale Post-CAE | 0.0 score on a scale | Standard Error 0.06 |
| 0.1% K-161 (BID) | Change in Ocular Discomfort Scale Post-CAE | 0.0 score on a scale | Standard Error 0.06 |
p-value: 0.3852ANCOVA
Secondary
Change in Blink Rate (Pre CAE)
Blinks per 60 seconds.
Time frame: Baseline to Day 29
Population: Endpoints analysis was determined by comparing Vehicle BID to 0.1% K-161 BID and 0.025% K-161 BID
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (BID) (Vehicle) | Change in Blink Rate (Pre CAE) | 0.1 Blinks per 60 seconds | Standard Error 1.41 |
| 0.1% K-161 (BID) | Change in Blink Rate (Pre CAE) | 0.1 Blinks per 60 seconds | Standard Error 1.39 |
| 0.1% K-161 (BID) | Change in Blink Rate (Pre CAE) | -0.2 Blinks per 60 seconds | Standard Error 1.36 |
p-value: 0.9829ANCOVA
p-value: 0.8675ANCOVA
Secondary
Change in Conjunctival Redness (Pre-CAE)
Conjunctival Redness Scale ranges from 0 to 4, where 0 = normal, without vasodilation and 4 = Broad Ciliary and Prominent, Horizontal Conjunctival Vasodilation. Higher scores indicate worsening conjunctival redness.
Time frame: Baseline to Day 29
Population: Endpoints analysis was determined by comparing Vehicle BID to 0.1% K-161 BID and 0.025% K-161 BID
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (BID) (Vehicle) | Change in Conjunctival Redness (Pre-CAE) | -0.21 Point | Standard Error 0.061 |
| 0.1% K-161 (BID) | Change in Conjunctival Redness (Pre-CAE) | -0.20 Point | Standard Error 0.06 |
| 0.1% K-161 (BID) | Change in Conjunctival Redness (Pre-CAE) | -0.22 Point | Standard Error 0.059 |
p-value: 0.9146ANCOVA
p-value: 0.8494ANCOVA
Secondary
Change in Fluorescein Staining Scores (Pre-CAE®)
Fluorescein Staining is measured with the Ora Calibra® Corneal and Conjunctival Staining Scale which is a 0 to 4 scale with increasing half-units and where higher numbers indicating more severe staining.
Time frame: Baseline to Day 29
Population: Endpoints analysis was determined by comparing Vehicle BID to 0.1% K-161 BID and 0.025% K-161 BID
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (BID) (Vehicle) | Change in Fluorescein Staining Scores (Pre-CAE®) | Conjunctival Sum | -0.03 score on a scale | Standard Error 0.138 |
| Placebo (BID) (Vehicle) | Change in Fluorescein Staining Scores (Pre-CAE®) | Corneal Sum | -0.28 score on a scale | Standard Error 0.184 |
| Placebo (BID) (Vehicle) | Change in Fluorescein Staining Scores (Pre-CAE®) | Total Eye Sum | -0.30 score on a scale | Standard Error 0.292 |
| 0.1% K-161 (BID) | Change in Fluorescein Staining Scores (Pre-CAE®) | Conjunctival Sum | -0.22 score on a scale | Standard Error 0.136 |
| 0.1% K-161 (BID) | Change in Fluorescein Staining Scores (Pre-CAE®) | Corneal Sum | -0.36 score on a scale | Standard Error 0.182 |
| 0.1% K-161 (BID) | Change in Fluorescein Staining Scores (Pre-CAE®) | Total Eye Sum | -0.59 score on a scale | Standard Error 0.29 |
| 0.1% K-161 (BID) | Change in Fluorescein Staining Scores (Pre-CAE®) | Corneal Sum | -0.50 score on a scale | Standard Error 0.178 |
| 0.1% K-161 (BID) | Change in Fluorescein Staining Scores (Pre-CAE®) | Total Eye Sum | -0.80 score on a scale | Standard Error 0.283 |
| 0.1% K-161 (BID) | Change in Fluorescein Staining Scores (Pre-CAE®) | Conjunctival Sum | -0.28 score on a scale | Standard Error 0.133 |
Comparison: Corneal Sump-value: 0.7388ANCOVA
Comparison: Corneal Sump-value: 0.3717ANCOVA
Comparison: Conjunctival Sump-value: 0.3164ANCOVA
Comparison: Conjunctival Sump-value: 0.1953ANCOVA
Comparison: Total Eye Sump-value: 0.4645ANCOVA
Comparison: Total Eye Sump-value: 0.2135ANCOVA
Secondary
Change in Lissamine Green Staining (Pre-CAE) Using the Ora Calibra® Scale (Conjunctival Sum)
Ora Calibra Scale which is 0 to 4 scale with increasing half-units and where higher numbers indicating more severe staining.
Time frame: Baseline to Day 29
Population: Endpoints analysis was determined by comparing Vehicle BID to 0.1% K-161 BID and 0.025% K-161 BID
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (BID) (Vehicle) | Change in Lissamine Green Staining (Pre-CAE) Using the Ora Calibra® Scale (Conjunctival Sum) | -0.16 score on a scale | Standard Error 0.132 |
| 0.1% K-161 (BID) | Change in Lissamine Green Staining (Pre-CAE) Using the Ora Calibra® Scale (Conjunctival Sum) | -0.25 score on a scale | Standard Error 0.131 |
| 0.1% K-161 (BID) | Change in Lissamine Green Staining (Pre-CAE) Using the Ora Calibra® Scale (Conjunctival Sum) | -0.39 score on a scale | Standard Error 0.127 |
p-value: 0.599ANCOVA
p-value: 0.2122ANCOVA
Secondary
Change in Ocular Discomfort and 4-Symptom Questionnaire (Pre CAE)
Scores ranging from 0 to 5. A score of 0 indicates no discomfort/symptoms and a score of 5 indicates worst discomfort/symptoms.
Time frame: Baseline to Day 29
Population: Endpoints analysis was determined by comparing Vehicle BID to 0.1% K-161 BID and 0.025% K-161 BID
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (BID) (Vehicle) | Change in Ocular Discomfort and 4-Symptom Questionnaire (Pre CAE) | Grittiness | -0.1 Point | Standard Error 0.15 |
| Placebo (BID) (Vehicle) | Change in Ocular Discomfort and 4-Symptom Questionnaire (Pre CAE) | Dryness | -0.1 Point | Standard Error 0.14 |
| Placebo (BID) (Vehicle) | Change in Ocular Discomfort and 4-Symptom Questionnaire (Pre CAE) | Ocular Discomfort | -0.2 Point | Standard Error 0.13 |
| Placebo (BID) (Vehicle) | Change in Ocular Discomfort and 4-Symptom Questionnaire (Pre CAE) | Burning | 0.1 Point | Standard Error 0.13 |
| Placebo (BID) (Vehicle) | Change in Ocular Discomfort and 4-Symptom Questionnaire (Pre CAE) | Stinging | -0.1 Point | Standard Error 0.15 |
| 0.1% K-161 (BID) | Change in Ocular Discomfort and 4-Symptom Questionnaire (Pre CAE) | Dryness | -0.2 Point | Standard Error 0.14 |
| 0.1% K-161 (BID) | Change in Ocular Discomfort and 4-Symptom Questionnaire (Pre CAE) | Ocular Discomfort | -0.2 Point | Standard Error 0.13 |
| 0.1% K-161 (BID) | Change in Ocular Discomfort and 4-Symptom Questionnaire (Pre CAE) | Burning | 0.0 Point | Standard Error 0.13 |
| 0.1% K-161 (BID) | Change in Ocular Discomfort and 4-Symptom Questionnaire (Pre CAE) | Grittiness | -0.3 Point | Standard Error 0.15 |
| 0.1% K-161 (BID) | Change in Ocular Discomfort and 4-Symptom Questionnaire (Pre CAE) | Stinging | -0.1 Point | Standard Error 0.15 |
| 0.1% K-161 (BID) | Change in Ocular Discomfort and 4-Symptom Questionnaire (Pre CAE) | Stinging | -0.2 Point | Standard Error 0.14 |
| 0.1% K-161 (BID) | Change in Ocular Discomfort and 4-Symptom Questionnaire (Pre CAE) | Grittiness | -0.1 Point | Standard Error 0.15 |
| 0.1% K-161 (BID) | Change in Ocular Discomfort and 4-Symptom Questionnaire (Pre CAE) | Ocular Discomfort | -0.4 Point | Standard Error 0.13 |
| 0.1% K-161 (BID) | Change in Ocular Discomfort and 4-Symptom Questionnaire (Pre CAE) | Dryness | -0.3 Point | Standard Error 0.13 |
| 0.1% K-161 (BID) | Change in Ocular Discomfort and 4-Symptom Questionnaire (Pre CAE) | Burning | -0.1 Point | Standard Error 0.13 |
Comparison: Ocular Discomfortp-value: 0.7367ANCOVA
Comparison: Ocular Discomfortp-value: 0.3865ANCOVA
Comparison: Burningp-value: 0.8796ANCOVA
Comparison: Burningp-value: 0.3515ANCOVA
Comparison: Drynessp-value: 0.6338ANCOVA
Comparison: Drynessp-value: 0.4685ANCOVA
Comparison: Grittinessp-value: 0.4757ANCOVA
Comparison: Grittinessp-value: 0.8803ANCOVA
Comparison: Stingingp-value: 0.8529ANCOVA
Comparison: Stingingp-value: 0.7713ANCOVA
Secondary
Change in Ocular Discomfort Scale (Pre CAE)
Ora Calibra® Ocular Discomfort Scale ranging from 0 to 4
Time frame: Baseline to Day 29
Population: Endpoints analysis was determined by comparing Vehicle BID to 0.1% K-161 BID and 0.025% K-161 BID
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (BID) (Vehicle) | Change in Ocular Discomfort Scale (Pre CAE) | -0.3 Score | Standard Error 0.13 |
| 0.1% K-161 (BID) | Change in Ocular Discomfort Scale (Pre CAE) | -0.2 Score | Standard Error 0.13 |
| 0.1% K-161 (BID) | Change in Ocular Discomfort Scale (Pre CAE) | -0.5 Score | Standard Error 0.12 |
p-value: 0.2352ANCOVA
p-value: 0.5836ANCOVA
Secondary
Change in Ocular Surface Disease Index Score (Pre-CAE) - Total OSDI
The OSDI© is comprised of 12 questions, with each question assessed on a scale ranging from 0 to 4 where 0 = none of the time, 1 = some of the time, 2 = half of the time, 3 = most of the time, and 4 = all of the time. The range of total score is 0 to 100. Subscale scores are not reported. Higher score represents a worsen outcome. The total score is the sum of subscales.
Time frame: Baseline to Day 29
Population: Endpoints analysis was determined by comparing Vehicle BID to 0.1% K-161 BID and 0.025% K-161 BID
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (BID) (Vehicle) | Change in Ocular Surface Disease Index Score (Pre-CAE) - Total OSDI | -3.2 scores on a scale | Standard Error 2.03 |
| 0.1% K-161 (BID) | Change in Ocular Surface Disease Index Score (Pre-CAE) - Total OSDI | -2.9 scores on a scale | Standard Error 2 |
| 0.1% K-161 (BID) | Change in Ocular Surface Disease Index Score (Pre-CAE) - Total OSDI | -7.8 scores on a scale | Standard Error 1.95 |
p-value: 0.9274ANCOVA
p-value: 0.0888ANCOVA
Secondary
Change in Schirmer's Test Value (Unanesthetized) Pre-CAE
Measured with Schirmer's test strip with the length of the moistened area recorded in mm. Lower values indicate less tears produced in the eye.
Time frame: Baseline to Day 29
Population: Endpoints analysis was determined by comparing 0.1% K-161 BID to its Vehicle BID
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (BID) (Vehicle) | Change in Schirmer's Test Value (Unanesthetized) Pre-CAE | 3.4 mm | Standard Error 0.85 |
| 0.1% K-161 (BID) | Change in Schirmer's Test Value (Unanesthetized) Pre-CAE | 2.2 mm | Standard Error 0.8 |
p-value: 0.298ANCOVA
Secondary
Change in Tear Film Break-Up Time (Pre CAE)
Time frame: Baseline to Day 29
Population: Endpoints analysis was determined by comparing Vehicle BID to 0.1% K-161 BID and 0.025% K-161 BID
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (BID) (Vehicle) | Change in Tear Film Break-Up Time (Pre CAE) | 0.312 Seconds | Standard Error 0.088 |
| 0.1% K-161 (BID) | Change in Tear Film Break-Up Time (Pre CAE) | 0.398 Seconds | Standard Error 0.0863 |
| 0.1% K-161 (BID) | Change in Tear Film Break-Up Time (Pre CAE) | 0.242 Seconds | Standard Error 0.0848 |
p-value: 0.4747ANCOVA
p-value: 0.5619ANCOVA
Secondary
Change in Tear Film Break-up Time (TFBUT) Post-CAE
Time frame: Baseline to Day 29
Population: Endpoints analysis was determined by comparing 0.1% K-161 BID to its Vehicle BID
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (BID) (Vehicle) | Change in Tear Film Break-up Time (TFBUT) Post-CAE | 0.402 Seconds | Standard Error 0.109 |
| 0.1% K-161 (BID) | Change in Tear Film Break-up Time (TFBUT) Post-CAE | 0.132 Seconds | Standard Error 0.1049 |
p-value: 0.0634ANCOVA
Secondary
Change in Tear Osmolarity (Pre CAE)
Time frame: Baseline to Day 29
Population: Endpoints analysis was determined by comparing Vehicle BID to 0.1% K-161 BID and 0.025% K-161 BID
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (BID) (Vehicle) | Change in Tear Osmolarity (Pre CAE) | -0.5 mOsm/L | Standard Error 2.17 |
| 0.1% K-161 (BID) | Change in Tear Osmolarity (Pre CAE) | 1.0 mOsm/L | Standard Error 2.09 |
| 0.1% K-161 (BID) | Change in Tear Osmolarity (Pre CAE) | 0.4 mOsm/L | Standard Error 2.03 |
p-value: 0.5985ANCOVA
p-value: 0.7626ANCOVA
Secondary
Change in Unanesthetized Schirmer's Test (Pre CAE)
Measured with Schirmer's test strip with the length of the moistened area recorded in mm. Lower values indicate less tears produced in the eye.
Time frame: Baseline to Day 29
Population: Endpoints analysis was determined by comparing Vehicle BID to 0.1% K-161 BID and 0.025% K-161 BID
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (BID) (Vehicle) | Change in Unanesthetized Schirmer's Test (Pre CAE) | 3.3 mm | Standard Error 0.82 |
| 0.1% K-161 (BID) | Change in Unanesthetized Schirmer's Test (Pre CAE) | 3.1 mm | Standard Error 0.8 |
| 0.1% K-161 (BID) | Change in Unanesthetized Schirmer's Test (Pre CAE) | 2.1 mm | Standard Error 0.78 |
p-value: 0.833ANCOVA
p-value: 0.2777ANCOVA
Secondary
Change in Visual Analog Scale (Pre CAE)
The length of the assessment line was 100 mm; a measure of 0 mm corresponded to no discomfort and 100 mm corresponds to maximal discomfort.
Time frame: Baseline to Day 29
Population: Endpoints analysis was determined by comparing Vehicle BID to 0.1% K-161 BID and 0.025% K-161 BID
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (BID) (Vehicle) | Change in Visual Analog Scale (Pre CAE) | Itching | -3.1 mm | Standard Error 2.92 |
| Placebo (BID) (Vehicle) | Change in Visual Analog Scale (Pre CAE) | Eye Dryness | -4.1 mm | Standard Error 2.71 |
| Placebo (BID) (Vehicle) | Change in Visual Analog Scale (Pre CAE) | Blurry Vision | -0.2 mm | Standard Error 2.69 |
| Placebo (BID) (Vehicle) | Change in Visual Analog Scale (Pre CAE) | Burning/Stinging | -1.9 mm | Standard Error 2.78 |
| Placebo (BID) (Vehicle) | Change in Visual Analog Scale (Pre CAE) | Pain | 0.0 mm | Standard Error 2.37 |
| Placebo (BID) (Vehicle) | Change in Visual Analog Scale (Pre CAE) | Photophobia | -2.8 mm | Standard Error 2.78 |
| Placebo (BID) (Vehicle) | Change in Visual Analog Scale (Pre CAE) | Foreign Body Sensation | -1.1 mm | Standard Error 2.96 |
| 0.1% K-161 (BID) | Change in Visual Analog Scale (Pre CAE) | Blurry Vision | -5.5 mm | Standard Error 2.67 |
| 0.1% K-161 (BID) | Change in Visual Analog Scale (Pre CAE) | Burning/Stinging | -7.6 mm | Standard Error 2.76 |
| 0.1% K-161 (BID) | Change in Visual Analog Scale (Pre CAE) | Itching | -9.7 mm | Standard Error 2.92 |
| 0.1% K-161 (BID) | Change in Visual Analog Scale (Pre CAE) | Foreign Body Sensation | -6.9 mm | Standard Error 2.94 |
| 0.1% K-161 (BID) | Change in Visual Analog Scale (Pre CAE) | Eye Dryness | -6.1 mm | Standard Error 2.68 |
| 0.1% K-161 (BID) | Change in Visual Analog Scale (Pre CAE) | Photophobia | -6.2 mm | Standard Error 2.75 |
| 0.1% K-161 (BID) | Change in Visual Analog Scale (Pre CAE) | Pain | -6.0 mm | Standard Error 2.37 |
| 0.1% K-161 (BID) | Change in Visual Analog Scale (Pre CAE) | Eye Dryness | -10.7 mm | Standard Error 2.6 |
| 0.1% K-161 (BID) | Change in Visual Analog Scale (Pre CAE) | Itching | -6.1 mm | Standard Error 2.84 |
| 0.1% K-161 (BID) | Change in Visual Analog Scale (Pre CAE) | Pain | -4.2 mm | Standard Error 2.28 |
| 0.1% K-161 (BID) | Change in Visual Analog Scale (Pre CAE) | Photophobia | -10.7 mm | Standard Error 2.67 |
| 0.1% K-161 (BID) | Change in Visual Analog Scale (Pre CAE) | Blurry Vision | -7.5 mm | Standard Error 2.6 |
| 0.1% K-161 (BID) | Change in Visual Analog Scale (Pre CAE) | Foreign Body Sensation | -5.6 mm | Standard Error 2.82 |
| 0.1% K-161 (BID) | Change in Visual Analog Scale (Pre CAE) | Burning/Stinging | -5.6 mm | Standard Error 2.68 |
Comparison: Burning/Stingingp-value: 0.138ANCOVA
Comparison: Burning/Stingingp-value: 0.3334ANCOVA
Comparison: Itchingp-value: 0.1008ANCOVA
Comparison: Itchingp-value: 0.4582ANCOVA
Comparison: Foreign Body Sensationp-value: 0.1511ANCOVA
Comparison: Foreign Body Sensationp-value: 0.2555ANCOVA
Comparison: Blurry Visionp-value: 0.1546ANCOVA
Comparison: Blurry Visionp-value: 0.0495ANCOVA
Comparison: Eye Drynessp-value: 0.5791ANCOVA
Comparison: Eye Drynessp-value: 0.0736ANCOVA
Comparison: Photophobiap-value: 0.3666ANCOVA
Comparison: Photophobiap-value: 0.039ANCOVA
Comparison: Painp-value: 0.0655ANCOVA
Comparison: Painp-value: 0.1947ANCOVA