Dry Eye Disease
Conditions
Keywords
Keratoconjunctivitis Sicca, KCS, Dry eye
Brief summary
This is a Phase 4, multicenter, single arm, 12 week study in subjects with dry eye disease, which is inadequately controlled by cyclosporine 0.05% ophthalmic emulsion.
Detailed description
This is a phase 4, multicenter, open-label, single-arm, 12-week study of subjects with dry eye disease that is inadequately controlled by cyclosporine (CsA) 0.05% ophthalmic emulsion. Subject enrollment will be classified by evidence of dry eye disease (ie, signs, symptoms, or both signs and symptoms). Treatment will be one drop of CsA 0.09% ophthalmic solution (Cequa) in each eye twice daily (BID) for 12 weeks. The study hypothesis is that CsA 0.09% ophthalmic solution will show improved clinical benefit in subjects whose dry eye signs and/or symptoms are inadequately controlled while on CsA.
Interventions
DRUGCequaTM (Cyclosporine 0.09%) ophthalmic solution
One drop CequaTM (Cyclosporine 0.09%) ophthalmic solution in each eye twice daily, approximately 12 hours apart.
Sponsors
Sun Pharmaceutical Industries Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female subjects with a history of bilateral dry eye disease for a period of at least 3 months. 2. Aged of at least 18 years. 3. Subjects with total corneal fluorescein staining ≥6 or corneal fluorescein staining in an individual zone ≥2 as per National Eye Institute Grading Scale. 4. Subjects with modified symptom assessment in dry eye global symptom score, ≥40 using visual analogue scale. 5. Subjects with best-corrected visual acuity 20/200 or better in both eyes at the Screening/Baseline visit
Exclusion criteria
1. Subjects who have used cyclosporin 0.05% ophthalmic emulsion in both eyes for less than 3 months prior to the Screening/Baseline visit. 2. Subjects with history of treatment failure with cyclosporin 0.05% ophthalmic emulsion. 3. Subjects who have active seasonal and/or perennial allergic conjunctivitis in either eye. 4. Subjects who had already Use initiated any systemic or topical ocular medication.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Baseline in Total Corneal Fluoroscein Staining Score | Week12 | Scale for Corneal Staining as defined by the FDA/NEI: 0-4 (0-no staining, 4-severe staining). The higher number indicates more severe. The lower the number indicates less severe staining on the cornea |
| Change From Baseline in Modified Dry Eye Scoring. | Week12 | Based on questionnaire asked to subjects (sign and symptoms), modified symptom of dry eye score (range 0 to 100) will be assessed. Increase in score will indicate severity in the symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Baseline for Tear Osmolarity Score for Both Eyes | Week 12 | Tear osmolarity of both the eyes will be assessed and score (mOsm/L) will be allotted to each eye. Higher score will indicate severity of the disease (dry eye). Tear osmolarity OU was assessed using the TearLab Osmolarity System Test by collecting nanoliter volumes of tear fluid at each visit from each eyelid margin using the Osmolarity Test Pen and Test Card. Results were interpreted according to the provided instructions and scores (mOsm/L) for each eye were recorded. Normal, mild/moderate, and severe dry eyes had average tear osmolarity values of approximately 302+/-8 mOsm/L, 315+/-10 mOsm/L and 336+/022 mOsm/L, respectively. |
| Mean Change From Baseline in Frequency of Artificial Tear Product Use. | Week 12 | Based on entries in the subject diaries, frequency of artificial tear product use will be assessed. Frequency for artificial tear: This is number of times per day recorded in a daily diary log assessed at baseline and week 12. The higher the number the worse the outcome. The lower the number the better the outcome |
| Mean Change in Baseline for Conjunctival Staining Assessment | Week 12 | Based on Investigator's judgement, 6 areas of the conjunctiva will be evaluated in a low to moderate intensity. Scale for Conjunctival Staining defined: 0-6 (0 no staining, 6-severe staining). The higher the number indicates more severe. The lower the number indicates less severe staining on the conjunctival |
| Percentage of Subjects Who Prefer Study Treatments Over Prior Treatment. | Week 12 | Subjects will be asked, which treatment they prefer for the management of the dry eye (prior treatment or study treatment). Note- For this outcome measure, participants were provided the option to not choose either treatment as the preferred treatment. |
| Schirmer's Test Score | Week 12 | An unanesthetized Schirmer's test was performed in each eye at least 5 minutes after the lissamine green conjunctival staining to allow for any reflex tearing to subside. At each visit, strips were placed OU at the same time and timed for 5 min. Strips were removed after 5 min and the amount of wetting was recorded in mm and also marked with a line on the strip. The Investigator recorded a score for each eye. A score of greater than 10 mm in 5 minutes is accepted as normal. A score of less than 5 mm in 5 minutes indicates a tear deficiency. A score less than 10 mm in 5 minutes indicates a change from normal in tear production. |
| Changes From Baseline in Central Corneal Staining Score | Week 12 | Five areas of cornea will be evaluated on a 0 to 4 scale and value from 0 (absent) to 4 (severe) to each section will be allotted based on NEI grading scale |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CequaTM (Cyclosporine 0.09%) Ophthalmic Solution CequaTM (Cyclosporine 0.09%) ophthalmic solution: One drop CequaTM (Cyclosporine 0.09%) ophthalmic solution in each eye twice daily, approximately 12 hours apart. | 125 |
| Total | 125 |
Baseline characteristics
| Characteristic | CequaTM (Cyclosporine 0.09%) Ophthalmic Solution |
|---|---|
| Age, Continuous | 65.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 107 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Sex: Female, Male Female | 110 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 134 |
| other Total, other adverse events | 20 / 134 |
| serious Total, serious adverse events | 0 / 134 |
Outcome results
Primary
Change From Baseline in Modified Dry Eye Scoring.
Based on questionnaire asked to subjects (sign and symptoms), modified symptom of dry eye score (range 0 to 100) will be assessed. Increase in score will indicate severity in the symptoms.
Time frame: Week12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CequaTM (Cyclosporine 0.09%) Ophthalmic Solution | Change From Baseline in Modified Dry Eye Scoring. | -29.14 score on a scale | Standard Deviation 26.22 |
p-value: <0.0001Paired t-test
Primary
Mean Change in Baseline in Total Corneal Fluoroscein Staining Score
Scale for Corneal Staining as defined by the FDA/NEI: 0-4 (0-no staining, 4-severe staining). The higher number indicates more severe. The lower the number indicates less severe staining on the cornea
Time frame: Week12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CequaTM (Cyclosporine 0.09%) Ophthalmic Solution | Mean Change in Baseline in Total Corneal Fluoroscein Staining Score | -3.1 score on a scale | Standard Deviation 2.88 |
p-value: <0.0001Paired t-test
Secondary
Changes From Baseline in Central Corneal Staining Score
Five areas of cornea will be evaluated on a 0 to 4 scale and value from 0 (absent) to 4 (severe) to each section will be allotted based on NEI grading scale
Time frame: Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CequaTM (Cyclosporine 0.09%) Ophthalmic Solution | Changes From Baseline in Central Corneal Staining Score | -0.5 score on a scale | Standard Deviation 0.87 |
p-value: <0.0001Paired t-test
Secondary
Mean Change From Baseline in Frequency of Artificial Tear Product Use.
Based on entries in the subject diaries, frequency of artificial tear product use will be assessed. Frequency for artificial tear: This is number of times per day recorded in a daily diary log assessed at baseline and week 12. The higher the number the worse the outcome. The lower the number the better the outcome
Time frame: Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CequaTM (Cyclosporine 0.09%) Ophthalmic Solution | Mean Change From Baseline in Frequency of Artificial Tear Product Use. | -1.5 times product used/day | Standard Deviation 2.39 |
p-value: <0.0001Paired t-test
Secondary
Mean Change in Baseline for Conjunctival Staining Assessment
Based on Investigator's judgement, 6 areas of the conjunctiva will be evaluated in a low to moderate intensity. Scale for Conjunctival Staining defined: 0-6 (0 no staining, 6-severe staining). The higher the number indicates more severe. The lower the number indicates less severe staining on the conjunctival
Time frame: Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CequaTM (Cyclosporine 0.09%) Ophthalmic Solution | Mean Change in Baseline for Conjunctival Staining Assessment | -2.35 score on a scale | Standard Deviation 2.918 |
p-value: <0.0001Paired t-test
Secondary
Mean Change in Baseline for Tear Osmolarity Score for Both Eyes
Tear osmolarity of both the eyes will be assessed and score (mOsm/L) will be allotted to each eye. Higher score will indicate severity of the disease (dry eye). Tear osmolarity OU was assessed using the TearLab Osmolarity System Test by collecting nanoliter volumes of tear fluid at each visit from each eyelid margin using the Osmolarity Test Pen and Test Card. Results were interpreted according to the provided instructions and scores (mOsm/L) for each eye were recorded. Normal, mild/moderate, and severe dry eyes had average tear osmolarity values of approximately 302+/-8 mOsm/L, 315+/-10 mOsm/L and 336+/022 mOsm/L, respectively.
Time frame: Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CequaTM (Cyclosporine 0.09%) Ophthalmic Solution | Mean Change in Baseline for Tear Osmolarity Score for Both Eyes | OD- Right eye | -4.0 mOsm/L | Standard Deviation 19.44 |
| CequaTM (Cyclosporine 0.09%) Ophthalmic Solution | Mean Change in Baseline for Tear Osmolarity Score for Both Eyes | OS- left eye | -11.7 mOsm/L | Standard Deviation 18.54 |
p-value: 0.0323Paired t-test
p-value: 0.3447Paired t-test
Secondary
Percentage of Subjects Who Prefer Study Treatments Over Prior Treatment.
Subjects will be asked, which treatment they prefer for the management of the dry eye (prior treatment or study treatment). Note- For this outcome measure, participants were provided the option to not choose either treatment as the preferred treatment.
Time frame: Week 12
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CequaTM (Cyclosporine 0.09%) Ophthalmic Solution | Percentage of Subjects Who Prefer Study Treatments Over Prior Treatment. | Prefer study treatment | 69.4 percentage of participants |
| CequaTM (Cyclosporine 0.09%) Ophthalmic Solution | Percentage of Subjects Who Prefer Study Treatments Over Prior Treatment. | Prefer prior treatment | 21.8 percentage of participants |
Secondary
Schirmer's Test Score
An unanesthetized Schirmer's test was performed in each eye at least 5 minutes after the lissamine green conjunctival staining to allow for any reflex tearing to subside. At each visit, strips were placed OU at the same time and timed for 5 min. Strips were removed after 5 min and the amount of wetting was recorded in mm and also marked with a line on the strip. The Investigator recorded a score for each eye. A score of greater than 10 mm in 5 minutes is accepted as normal. A score of less than 5 mm in 5 minutes indicates a tear deficiency. A score less than 10 mm in 5 minutes indicates a change from normal in tear production.
Time frame: Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CequaTM (Cyclosporine 0.09%) Ophthalmic Solution | Schirmer's Test Score | 2.4 mm | Standard Deviation 8.61 |
p-value: 0.0029Paired t-test