Post Surgical Ocular Inflammation and Pain
Conditions
Keywords
postsurgical, postoperative, ocular, cataract, inflammation, pain, corticosteroid
Brief summary
The primary objective of the study is to investigate the efficacy and safety of KPI-121 1.0% ophthalmic suspension compared to placebo in subjects who have undergone cataract surgery.
Detailed description
This is a Phase III, multicenter, double-masked, randomized, placebo-controlled, parallel-group study designed to evaluate the efficacy and safety of KPI-121 1.0% ophthalmic suspension versus placebo in subjects who require treatment of postoperative anterior ocular inflammation.
Interventions
DRUGKPI-121 1% Ophthalmic Suspension dosed BID
DRUGVehicle of KPI-121 Ophthalmic Suspension dosed BID
Sponsors
Kala Pharmaceuticals, 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
Candidates for routine, uncomplicated cataract surgery In Investigator's opinion, potential postoperative Snellen Distance VA by pinhole method of at least 20/200 in study eye.
Exclusion criteria
* Known hypersensitivity/contraindication to study product(s) or components. * History of glaucoma, intraocular pressure (IOP) \>21 mmHg at the screening or randomization visits, or being treated for glaucoma in either eye. * Diagnosis of: ongoing ocular infection; severe/serious ocular condition that in judgment of Investigator could confound study assessments or limit compliance; severe/serious systemic disease or uncontrolled medical condition that in judgment of Investigator could confound study assessments or limit compliance; or have been exposed to an investigational drug within the 30 days prior to screening or 18 days following surgery. * In the opinion of Investigator or study coordinator, be unwilling or unable to comply with study protocol or unable to successfully instill eye drops.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Resolution of Anterior Chamber (AC) Cells at Day 8 | Visit 5 (Day 8) maintained through Visit 6 (Day 15) | Number and percentage of subjects with complete resolution of AC cells in the surgical eye (study eye) at Day 8 maintained through Day 15, without receiving rescue medication prior to Day 15, for KPI-121 1% dosed twice daily (BID) compared with vehicle dosed BID. Investigators were asked to grade AC cell based on the following scale wherein higher scores indicate a higher degree of cells present and a decrease across time indicates the condition is getting better. Anterior Chamber Cells 0 = No cells seen 1. = 1 - 5 cells 2. = 6 - 15 cells 3. = 16 - 30 cells 4. = greater than 30 cells |
| Complete Resolution of Ocular Pain at Day 8 | Visit 5 (Day 8) maintained through Visit 6 (Day 15) | Number and percentage of subjects with complete resolution of ocular pain in the surgical eye (study eye) at Day 8 maintained through Day 15, without receiving rescue medication prior to Day 15, for KPI-121 1% dosed twice daily (BID) compared with vehicle dosed BID. Subjects were given the Subject-Rated Ocular Pain Assessment to subjectively rate their pain at Days 1, 4, 8, 15, and the follow-up visit between Days 17 and 19. Higher scores were worse outcomes. The following scoring scale was used for ocular pain: 0 = None 1. = Minimal 2. = Mild 3. = Moderate 4. = Moderately Severe 5. = Severe |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Resolution of Ocular Pain at Day 4 | Visit 4 (Day 4) maintained through Visit 6 (Day 15) | Number and percentage of subjects with complete resolution of ocular pain in the surgical eye (study eye) at Day 4 maintained through Day 15, without receiving rescue medication prior to Day 15, for KPI-121 1% dosed twice daily (BID) compared with vehicle dosed BID. Subjects were given the Subject-Rated Ocular Pain Assessment to subjectively rate their pain at Days 1, 4, 8, 15, and the follow-up visit between Days 17 and 19. Higher scores were worse outcomes. The following scoring scale was used for ocular pain: 0 = None 1. = Minimal 2. = Mild 3. = Moderate 4. = Moderately Severe 5. = Severe |
| Complete Resolution of Anterior Chamber (AC) Flare at Day 4 | Visit 4 (Day 4) maintained through Visit 6 (Day 15) | Number and percentage of subjects with complete resolution of AC flare in the surgical eye (study eye) at Day 4 maintained through Day 15, without receiving rescue medication prior to Day 15, for KPI-121 1% dosed twice daily (BID) compared with vehicle dosed BID. Investigators were asked to grade AC flare based on the following scale wherein higher scores indicate a higher degree of flare present and a decrease across time indicates the condition is getting better. Anterior Chamber Flare 0 = None 1. = Mild (trace to clearly noticeable, visible) 2. = Moderate (without plastic aqueous humor) 3. = Marked (with plastic aqueous humor) 4. = Severe (with fibrin deposits and/or clots) |
| Change From Baseline (BL) Anterior Chamber (AC) Cells at Day 4 | Visit 1 (Baseline) and Visit 4 (Day 4) | The difference in mean changes from BL in AC cell count grade at Day 4 for KPI-121 1% dosed twice daily (BID) compared with vehicle dosed BID. Investigators were asked to grade AC cell based on the following scale wherein higher scores indicate a higher degree of cells present and a decrease across time indicates the condition is getting better. Anterior Chamber Cells 0 = No cells seen 1. = 1 - 5 cells 2. = 6 - 15 cells 3. = 16 - 30 cells 4. = greater than 30 cells |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| KPI-121 1.0% Ophthalmic Suspension dosed BID
KPI-121 1% Ophthalmic Suspension dosed BID | 261 |
| Vehicle of KPI-121 Ophthalmic Suspension dosed BID
Vehicle of KPI-121 Ophthalmic Suspension dosed BID | 259 |
| Total | 520 |
Baseline characteristics
| Characteristic | KPI-121 1.0% Ophthalmic Suspension | Total | Vehicle of KPI-121 Ophthalmic Suspension |
|---|---|---|---|
| Age, Continuous | 67.5 years | 68.4 years | 69.3 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 38 Participants | 74 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 223 Participants | 446 Participants | 223 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 17 Participants | 36 Participants | 19 Participants |
| Race (NIH/OMB) Black or African American | 27 Participants | 51 Participants | 24 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 12 Participants | 6 Participants |
| Race (NIH/OMB) White | 206 Participants | 413 Participants | 207 Participants |
| Region of Enrollment United States | 261 participants | 520 participants | 259 participants |
| Sex: Female, Male Female | 144 Participants | 288 Participants | 144 Participants |
| Sex: Female, Male Male | 117 Participants | 232 Participants | 115 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 261 | 0 / 259 |
| other Total, other adverse events | 18 / 261 | 21 / 259 |
| serious Total, serious adverse events | 1 / 261 | 2 / 259 |
Outcome results
Primary
Complete Resolution of Anterior Chamber (AC) Cells at Day 8
Number and percentage of subjects with complete resolution of AC cells in the surgical eye (study eye) at Day 8 maintained through Day 15, without receiving rescue medication prior to Day 15, for KPI-121 1% dosed twice daily (BID) compared with vehicle dosed BID. Investigators were asked to grade AC cell based on the following scale wherein higher scores indicate a higher degree of cells present and a decrease across time indicates the condition is getting better. Anterior Chamber Cells 0 = No cells seen 1. = 1 - 5 cells 2. = 6 - 15 cells 3. = 16 - 30 cells 4. = greater than 30 cells
Time frame: Visit 5 (Day 8) maintained through Visit 6 (Day 15)
Population: Intent to Treat - All subjects randomized
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| KPI-121 1% Ophthalmic Suspension | Complete Resolution of Anterior Chamber (AC) Cells at Day 8 | 54 Participants |
| Vehicle of KPI-121 1% Ophthalmic Suspension | Complete Resolution of Anterior Chamber (AC) Cells at Day 8 | 32 Participants |
Comparison: P-values were based on 2-sided chi-squared tests (unadjusted) wherein the a priori significance level was 0.05.p-value: 0.010595% CI: [2, 14.7]Chi-squared
Primary
Complete Resolution of Ocular Pain at Day 8
Number and percentage of subjects with complete resolution of ocular pain in the surgical eye (study eye) at Day 8 maintained through Day 15, without receiving rescue medication prior to Day 15, for KPI-121 1% dosed twice daily (BID) compared with vehicle dosed BID. Subjects were given the Subject-Rated Ocular Pain Assessment to subjectively rate their pain at Days 1, 4, 8, 15, and the follow-up visit between Days 17 and 19. Higher scores were worse outcomes. The following scoring scale was used for ocular pain: 0 = None 1. = Minimal 2. = Mild 3. = Moderate 4. = Moderately Severe 5. = Severe
Time frame: Visit 5 (Day 8) maintained through Visit 6 (Day 15)
Population: Intent to Treat - All subjects randomized
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| KPI-121 1% Ophthalmic Suspension | Complete Resolution of Ocular Pain at Day 8 | 149 Participants |
| Vehicle of KPI-121 1% Ophthalmic Suspension | Complete Resolution of Ocular Pain at Day 8 | 96 Participants |
Comparison: P-values were based on 2-sided chi-squared test (unadjusted), wherein a priori significance level was 0.05p-value: <0.000195% CI: [11.6, 28.4]Chi-squared
Secondary
Change From Baseline (BL) Anterior Chamber (AC) Cells at Day 4
The difference in mean changes from BL in AC cell count grade at Day 4 for KPI-121 1% dosed twice daily (BID) compared with vehicle dosed BID. Investigators were asked to grade AC cell based on the following scale wherein higher scores indicate a higher degree of cells present and a decrease across time indicates the condition is getting better. Anterior Chamber Cells 0 = No cells seen 1. = 1 - 5 cells 2. = 6 - 15 cells 3. = 16 - 30 cells 4. = greater than 30 cells
Time frame: Visit 1 (Baseline) and Visit 4 (Day 4)
Population: Intent to Treat - All subjects randomized
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KPI-121 1% Ophthalmic Suspension | Change From Baseline (BL) Anterior Chamber (AC) Cells at Day 4 | -0.7 score on a scale | Standard Deviation 0.84 |
| Vehicle of KPI-121 1% Ophthalmic Suspension | Change From Baseline (BL) Anterior Chamber (AC) Cells at Day 4 | -0.5 score on a scale | Standard Deviation 0.91 |
Comparison: P-value was based on a 2-sided chi-squared test (unadjusted) wherein the a priori significance level was 0.0167 for each secondary endpoint. Overall alpha for all secondary endpoints was controlled at 0.05.p-value: 0.007895% CI: [-0.31, -0.05]Chi-squared
Secondary
Complete Resolution of Anterior Chamber (AC) Flare at Day 4
Number and percentage of subjects with complete resolution of AC flare in the surgical eye (study eye) at Day 4 maintained through Day 15, without receiving rescue medication prior to Day 15, for KPI-121 1% dosed twice daily (BID) compared with vehicle dosed BID. Investigators were asked to grade AC flare based on the following scale wherein higher scores indicate a higher degree of flare present and a decrease across time indicates the condition is getting better. Anterior Chamber Flare 0 = None 1. = Mild (trace to clearly noticeable, visible) 2. = Moderate (without plastic aqueous humor) 3. = Marked (with plastic aqueous humor) 4. = Severe (with fibrin deposits and/or clots)
Time frame: Visit 4 (Day 4) maintained through Visit 6 (Day 15)
Population: Intent to Treat - All subjects randomized
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| KPI-121 1% Ophthalmic Suspension | Complete Resolution of Anterior Chamber (AC) Flare at Day 4 | 113 Participants |
| Vehicle of KPI-121 1% Ophthalmic Suspension | Complete Resolution of Anterior Chamber (AC) Flare at Day 4 | 63 Participants |
p-value: <0.000195% CI: [11, 26.9]Chi-squared
Secondary
Complete Resolution of Ocular Pain at Day 4
Number and percentage of subjects with complete resolution of ocular pain in the surgical eye (study eye) at Day 4 maintained through Day 15, without receiving rescue medication prior to Day 15, for KPI-121 1% dosed twice daily (BID) compared with vehicle dosed BID. Subjects were given the Subject-Rated Ocular Pain Assessment to subjectively rate their pain at Days 1, 4, 8, 15, and the follow-up visit between Days 17 and 19. Higher scores were worse outcomes. The following scoring scale was used for ocular pain: 0 = None 1. = Minimal 2. = Mild 3. = Moderate 4. = Moderately Severe 5. = Severe
Time frame: Visit 4 (Day 4) maintained through Visit 6 (Day 15)
Population: Intent to Treat - All subjects randomized
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| KPI-121 1% Ophthalmic Suspension | Complete Resolution of Ocular Pain at Day 4 | 109 Participants |
| Vehicle of KPI-121 1% Ophthalmic Suspension | Complete Resolution of Ocular Pain at Day 4 | 64 Participants |
p-value: <0.000195% CI: [9.1, 25]Chi-squared
Post Hoc
Change From Baseline (BL) Anterior Chamber (AC) Cells at Day 15
The difference in mean changes from BL in AC cell count grade at Day 15 for KPI-121 1% dosed twice daily (BID) compared with vehicle dosed BID. Investigators were asked to grade AC cell based on the following scale wherein higher scores indicate a higher degree of cells present and a decrease across time indicates the condition is getting better. Anterior Chamber Cells 0 = No cells seen 1. = 1 - 5 cells 2. = 6 - 15 cells 3. = 16 - 30 cells 4. = greater than 30 cells
Time frame: Visit 1 (Baseline) and Visit 6 (Day 15)
Population: Intent to Treat - All subjects randomized
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KPI-121 1% Ophthalmic Suspension | Change From Baseline (BL) Anterior Chamber (AC) Cells at Day 15 | -1.8 score on a scale | Standard Deviation 0.84 |
| Vehicle of KPI-121 1% Ophthalmic Suspension | Change From Baseline (BL) Anterior Chamber (AC) Cells at Day 15 | -1.6 score on a scale | Standard Deviation 0.87 |
p-value: 0.016995% CI: [-0.28, -0.03]Chi-squared
Post Hoc
Change From Baseline (BL) Anterior Chamber (AC) Cells at Day 8
The difference in mean changes from BL in AC cell count grade at Day 8 for KPI-121 1% dosed twice daily (BID) compared with vehicle dosed BID. Investigators were asked to grade AC cell based on the following scale wherein higher scores indicate a higher degree of cells present and a decrease across time indicates the condition is getting better. Anterior Chamber Cells 0 = No cells seen 1. = 1 - 5 cells 2. = 6 - 15 cells 3. = 16 - 30 cells 4. = greater than 30 cells
Time frame: Visit 1 (Baseline) and Visit 5 (Day 8)
Population: Intent to Treat - All subjects randomized
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KPI-121 1% Ophthalmic Suspension | Change From Baseline (BL) Anterior Chamber (AC) Cells at Day 8 | -1.3 score on a scale | Standard Deviation 0.9 |
| Vehicle of KPI-121 1% Ophthalmic Suspension | Change From Baseline (BL) Anterior Chamber (AC) Cells at Day 8 | -1.0 score on a scale | Standard Deviation 0.94 |
p-value: 0.000595% CI: [-0.38, -0.11]Chi-squared