Inflammation and Pain Associated With Cataract Surgery
Conditions
Brief summary
The purpose of this study is to evaluate the ocular safety, tolerability, and efficacy of ISV-305 (dexamethasone in DuraSite® 2) compared with Vehicle in the treatment of inflammation and pain associated with cataract surgery.
Detailed description
The purpose of this study is to evaluate the ocular safety, tolerability, and efficacy of topical administration of ISV-305 (0.1% dexamethasone in DuraSite® 2) compared with Vehicle when dosed twice daily for 1 day prior to surgery, the day of surgery and 14 days post cataract surgery.
Interventions
DRUGISV-305
Dexamethasone in DuraSite® 2 twice daily for 16 days
OTHERVehicle
Vehicle twice daily for 16 days
Sponsors
Sun Pharmaceutical Industries Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
17 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Are at least 17 years of age * Are scheduled for uncomplicated unilateral cataract surgery * Signature of the subject or parent(s) or legally authorized representative on the Informed Consent Form, and when appropriate the minor's assent in accordance with local regulations * Are willing and able to follow all instructions and attend all study visits * Are willing to avoid disallowed medication for the duration of the study * If female is of childbearing potential, agree to and submit a urine sample for pregnancy testing (prior to enrollment and at the end of the study) and use effective contraception for the duration of the study * Male subjects whose female partners are not post-menopausal must agree to one of the following: 1) completely abstain from sexual intercourse, 2) use a barrier method (condoms) with spermicide during sexual intercourse for the duration of the study, 3) provide documentation for having had a vasectomy (with documented infertility) * Additional inclusion criteria also apply
Exclusion criteria
* Have known sensitivity or poor tolerance to any component of the study drugs * Have any sign of iritis or scleritis in the study eye * Have an acute ocular infection (bacterial, viral or fungal) or active ocular inflammation in the study eye * Have any active or chronic/recurrent ocular or systemic disease that is uncontrolled and likely to affect wound healing (e.g., diabetes mellitus, systemic connective tissue disease, severe atopic disease) * Have known blood dyscrasia or bone marrow suppression * Have any active corneal pathology in the study eye * Have had radial keratotomy, corneal transplant, or LASIK in the study eye within the last 2 years * Be currently pregnant, nursing, or planning a pregnancy; or have a positive urine pregnancy test * Have prior (within 30 days of beginning study treatment) or anticipated concurrent use of an investigational drug or device * Have a condition or a situation which, in the investigator's opinion, may put the subject at increased risk, confound study data, or interfere significantly with the subject's study participation * Use of any medication the investigator feels may interfere with the study parameters * Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With Anterior Chamber Cell (ACC) Grade 0 in Study Eye at Day 15 (Last Observation Carried Forward) in the Modified Intent to Treat (mITT) Population | Day 15 | Biomicroscopic measurement of anterior chamber cells was conducted in the surgery eye (study eye) by the same examiner from visit to visit whenever possible. A slit-lamp biomicroscope was used at x16 magnification with a 1 x 1 mm oblique high-intensity beam. Two cell counts were summed and divided by 2 to determine an average final anterior chamber cell count. This final cell count was converted to a grade: Grades 0, 1, 2, 3, 4 were assigned for cell counts of 0, 1 to 10, 11 to 20, 21 to 50, and \> 50, respectively. If the averaged count fell between two grades, the higher grade was selected (e.g., if the two counts were 10 and 11, the average of 10.5 fell into Grade 2). Missing anterior chamber cell grade at Day 15 was imputed by last non-missing scheduled post-baseline anterior chamber cell grade assessed prior to Day 15 (last observation carried forward). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Who Achieved a Pain Score of 0 on the Visual Analog Scale (VAS) for Each Post-surgical Assessment | Day 1 to Day 29 | Eye pain/discomfort in the study eye was evaluated at every visit except Visit 2 (Surgery; Day 0) using a VAS, scoring from 0 to 100 using a mark on a 100 mm line (0 = absent; 100 = maximum). Participants were asked to rate the feeling of the symptom in the study eye from absent to extreme by moving a slide on the side of the scale to align with images of descriptive faces. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ISV-305 ISV-305 was administered as a topical ophthalmic formulation of 0.1% dexamethasone in DuraSite® 2 vehicle (InSite Vision's drug delivery system) twice daily (one drop in the morning and one drop in the evening) for 16 days. | 158 |
| Vehicle Vehicle (DuraSite® 2 vehicle) was administered as a matching topical ophthalmic formulation without dexamethasone twice daily (one drop in the morning and one drop in the evening) for 16 days. | 80 |
| Total | 238 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 11 |
| Overall Study | Lack of Efficacy | 20 | 37 |
| Overall Study | Other - Various Administrative Reasons | 8 | 3 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Protocol Violation | 4 | 3 |
| Overall Study | Surgery Cancelled | 4 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 3 |
Baseline characteristics
| Characteristic | Vehicle | Total | ISV-305 |
|---|---|---|---|
| Age, Continuous | 68.5 Years STANDARD_DEVIATION 9.37 | 68.2 Years STANDARD_DEVIATION 7.95 | 68.0 Years STANDARD_DEVIATION 7.15 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 6 Participants | 4 Participants |
| Race/Ethnicity, Customized Black or African American | 5 Participants | 15 Participants | 10 Participants |
| Race/Ethnicity, Customized Mixed | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 72 Participants | 213 Participants | 141 Participants |
| Sex: Female, Male Female | 43 Participants | 137 Participants | 94 Participants |
| Sex: Female, Male Male | 37 Participants | 101 Participants | 64 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 158 | 0 / 80 |
| other Total, other adverse events | 31 / 158 | 21 / 80 |
| serious Total, serious adverse events | 3 / 158 | 0 / 80 |
Outcome results
Primary
Proportion of Participants With Anterior Chamber Cell (ACC) Grade 0 in Study Eye at Day 15 (Last Observation Carried Forward) in the Modified Intent to Treat (mITT) Population
Biomicroscopic measurement of anterior chamber cells was conducted in the surgery eye (study eye) by the same examiner from visit to visit whenever possible. A slit-lamp biomicroscope was used at x16 magnification with a 1 x 1 mm oblique high-intensity beam. Two cell counts were summed and divided by 2 to determine an average final anterior chamber cell count. This final cell count was converted to a grade: Grades 0, 1, 2, 3, 4 were assigned for cell counts of 0, 1 to 10, 11 to 20, 21 to 50, and \> 50, respectively. If the averaged count fell between two grades, the higher grade was selected (e.g., if the two counts were 10 and 11, the average of 10.5 fell into Grade 2). Missing anterior chamber cell grade at Day 15 was imputed by last non-missing scheduled post-baseline anterior chamber cell grade assessed prior to Day 15 (last observation carried forward).
Time frame: Day 15
Population: mITT Population - included randomized participants who underwent cataract surgery, received at least one dose of ISV-305 or vehicle, and had at least one post-surgery efficacy assessment (ACC or VAS). Participants who received rescue medications were included in the mITT Population, but were treated as failures.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ISV-305 | Proportion of Participants With Anterior Chamber Cell (ACC) Grade 0 in Study Eye at Day 15 (Last Observation Carried Forward) in the Modified Intent to Treat (mITT) Population | 0 (did not receive rescue therapy) | 69 participants |
| ISV-305 | Proportion of Participants With Anterior Chamber Cell (ACC) Grade 0 in Study Eye at Day 15 (Last Observation Carried Forward) in the Modified Intent to Treat (mITT) Population | 0 (received rescue therapy) | 0 participants |
| ISV-305 | Proportion of Participants With Anterior Chamber Cell (ACC) Grade 0 in Study Eye at Day 15 (Last Observation Carried Forward) in the Modified Intent to Treat (mITT) Population | 1 | 64 participants |
| ISV-305 | Proportion of Participants With Anterior Chamber Cell (ACC) Grade 0 in Study Eye at Day 15 (Last Observation Carried Forward) in the Modified Intent to Treat (mITT) Population | 2 | 5 participants |
| ISV-305 | Proportion of Participants With Anterior Chamber Cell (ACC) Grade 0 in Study Eye at Day 15 (Last Observation Carried Forward) in the Modified Intent to Treat (mITT) Population | 3 | 6 participants |
| ISV-305 | Proportion of Participants With Anterior Chamber Cell (ACC) Grade 0 in Study Eye at Day 15 (Last Observation Carried Forward) in the Modified Intent to Treat (mITT) Population | 4 | 0 participants |
| Vehicle | Proportion of Participants With Anterior Chamber Cell (ACC) Grade 0 in Study Eye at Day 15 (Last Observation Carried Forward) in the Modified Intent to Treat (mITT) Population | 3 | 12 participants |
| Vehicle | Proportion of Participants With Anterior Chamber Cell (ACC) Grade 0 in Study Eye at Day 15 (Last Observation Carried Forward) in the Modified Intent to Treat (mITT) Population | 0 (did not receive rescue therapy) | 16 participants |
| Vehicle | Proportion of Participants With Anterior Chamber Cell (ACC) Grade 0 in Study Eye at Day 15 (Last Observation Carried Forward) in the Modified Intent to Treat (mITT) Population | 2 | 10 participants |
| Vehicle | Proportion of Participants With Anterior Chamber Cell (ACC) Grade 0 in Study Eye at Day 15 (Last Observation Carried Forward) in the Modified Intent to Treat (mITT) Population | 0 (received rescue therapy) | 0 participants |
| Vehicle | Proportion of Participants With Anterior Chamber Cell (ACC) Grade 0 in Study Eye at Day 15 (Last Observation Carried Forward) in the Modified Intent to Treat (mITT) Population | 4 | 4 participants |
| Vehicle | Proportion of Participants With Anterior Chamber Cell (ACC) Grade 0 in Study Eye at Day 15 (Last Observation Carried Forward) in the Modified Intent to Treat (mITT) Population | 1 | 30 participants |
p-value: 0.0005Chi-squared, Corrected
Secondary
Proportion of Participants Who Achieved a Pain Score of 0 on the Visual Analog Scale (VAS) for Each Post-surgical Assessment
Eye pain/discomfort in the study eye was evaluated at every visit except Visit 2 (Surgery; Day 0) using a VAS, scoring from 0 to 100 using a mark on a 100 mm line (0 = absent; 100 = maximum). Participants were asked to rate the feeling of the symptom in the study eye from absent to extreme by moving a slide on the side of the scale to align with images of descriptive faces.
Time frame: Day 1 to Day 29
Population: mITT Population - included randomized participants who underwent cataract surgery, received at least one dose of ISV-305 or vehicle, and had at least one post-surgery efficacy assessment (ACC or VAS). Participants who received rescue medications were included in the mITT Population but were treated as failures.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ISV-305 | Proportion of Participants Who Achieved a Pain Score of 0 on the Visual Analog Scale (VAS) for Each Post-surgical Assessment | Pain Score of 0 on Day 8 | 133 Participants |
| ISV-305 | Proportion of Participants Who Achieved a Pain Score of 0 on the Visual Analog Scale (VAS) for Each Post-surgical Assessment | Pain Score of 0 on Day 18 | 129 Participants |
| ISV-305 | Proportion of Participants Who Achieved a Pain Score of 0 on the Visual Analog Scale (VAS) for Each Post-surgical Assessment | Pain Score of 0 on Day 15 | 137 Participants |
| ISV-305 | Proportion of Participants Who Achieved a Pain Score of 0 on the Visual Analog Scale (VAS) for Each Post-surgical Assessment | Pain Score of 0 on Day 29 | 135 Participants |
| ISV-305 | Proportion of Participants Who Achieved a Pain Score of 0 on the Visual Analog Scale (VAS) for Each Post-surgical Assessment | Pain Score of 0 on Day 1 | 103 Participants |
| Vehicle | Proportion of Participants Who Achieved a Pain Score of 0 on the Visual Analog Scale (VAS) for Each Post-surgical Assessment | Pain Score of 0 on Day 29 | 51 Participants |
| Vehicle | Proportion of Participants Who Achieved a Pain Score of 0 on the Visual Analog Scale (VAS) for Each Post-surgical Assessment | Pain Score of 0 on Day 1 | 29 Participants |
| Vehicle | Proportion of Participants Who Achieved a Pain Score of 0 on the Visual Analog Scale (VAS) for Each Post-surgical Assessment | Pain Score of 0 on Day 8 | 44 Participants |
| Vehicle | Proportion of Participants Who Achieved a Pain Score of 0 on the Visual Analog Scale (VAS) for Each Post-surgical Assessment | Pain Score of 0 on Day 15 | 49 Participants |
| Vehicle | Proportion of Participants Who Achieved a Pain Score of 0 on the Visual Analog Scale (VAS) for Each Post-surgical Assessment | Pain Score of 0 on Day 18 | 50 Participants |
Comparison: Statistical analysis of proportion of participants who achieved a pain score of 0 on the VAS on Day 1p-value: <0.000195% CI: [1.823, 5.675]Chi-squared, Corrected
Comparison: Statistical analysis of proportion of participants who achieved a pain score of 0 on the VAS on Day 8p-value: <0.000195% CI: [2.305, 8.161]Chi-squared, Corrected
Comparison: Statistical analysis of proportion of participants who achieved a pain score of 0 on the VAS on Day 15p-value: <0.000195% CI: [2.113, 8.033]Chi-squared, Corrected
Comparison: Statistical analysis of proportion of participants who achieved a pain score of 0 on the VAS on Day 18p-value: 0.004395% CI: [1.38, 4.822]Chi-squared, Corrected
Comparison: Statistical analysis of proportion of participants who achieved a pain score of 0 on the VAS on Day 29p-value: 0.000595% CI: [1.695, 6.335]Chi-squared, Corrected