Intraocular Lens Replacement
Conditions
Keywords
cataract, lens replacement
Brief summary
The purpose of this study is to determine the safety and efficacy of OMS302 (the study drug) for maintaining intraoperative mydriasis in individuals undergoing Intraocular Lens Replacement (ILR) surgery.
Interventions
DRUGOMS302
OMS302 drug product will be supplied as a sterile, clear colorless liquid, free from particulates of foreign matter. Each vial contains a nominal 4.5 mL solution containing 60.75 millimolar (mM) phenylephrine hydrochloride (HCl) and 11.25 mM ketorolac tromethamine formulated in a 20 mM sodium citrate buffer (pH 6.3 +/- 0.5). For administration to patients, 4.4 mL of the drug product is added to a 500 mL bottle of commercially available balanced salt solution (BSS) through a syringe filter. This will achieve 4.0 mL of the drug product in a 500 mL bottle of BSS.
DRUGPlacebo
Placebo drug product will be supplied as a sterile, clear colorless liquid, free from particulates of foreign matter. Each vial contains a nominal 4.5 mL solution containing 20 mM sodium citrate buffer (pH 6.3 +/- 0.5). For administration to patients, 4.4 mL of the drug product is added to a 500 mL bottle of commercially available BSS through a syringe filter. This will achieve 4.0 mL of the drug product in a 500 mL bottle of BSS.
Sponsors
Omeros Corporation
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
* Competent and willing to voluntarily provide informed consent * 18 years of age or older * In good general health needing to undergo cataract extraction or lens extraction with lens replacement surgery in one eye, under topical anesthesia
Exclusion criteria
* No allergies to the medications and/or the active ingredients of any of the study medications * No medications with the same activities of the active ingredients in OMS302 for defined time intervals prior to and after surgery * No other significant eye injuries, eye conditions or general medical conditions likely to interfere with the evaluation of the study medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Area-under-the-Curve (AUC) Analysis of Change From Baseline in Pupil Diameter (mm) During Surgery | from surgery baseline (pre-incision) through surgery end (time of cortical clean-up/wound closure) | Change in pupil diameter over time from surgical baseline (immediately prior to surgical incision) to the end of the surgical procedure (wound closure) was summarized using descriptive statistics by treatment arm and time-point (every minute). The primary analysis of the change in pupil diameter was based on the mean area-under-the-curve (AUC) pupil diameter change from baseline. First, the AUC of the pupil diameter from surgical baseline to wound closure was calculated using the trapezoidal rule. Second, the mean AUC was obtained by dividing the AUC by the total time of surgery. Third, the mean AUC of change from baseline was calculated by subtracting the baseline pupil diameter from the mean AUC. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Photophobia at 6 Hours After Surgery (Ocular Pain and Symptoms Numerical Ordinal Scale [Numerical Rating System - NRS] Scores) | Six hours postoperatively | Photophobia outcomes based on Ocular Pain and Symptoms Numerical Ordinal Scale (Numerical Rating System - NRS) at 6 hours postoperatively. |
| Photophobia at Day 1 After Surgery (Ocular Pain and Symptoms Numerical Ordinal Scale [Numerical Rating System - NRS] Scores) | One day | Photophobia outcomes based on Ocular Pain and Symptoms Numerical Ordinal Scale (Numerical Rating System - NRS) at Day 1 postoperatively |
| Mean Area-under-the-Curve Analysis of Ocular Pain Visual Analog Scale (VAS) Score Within 12 Hours Postoperatively | 12 hours | The primary analysis of the ocular pain VAS (where 0 = no pain and 100 = worst possible pain) was based on the mean area-under-the-curve (AUC). The AUC of the ocular pain VAS during 12 hours postoperatively was calculated by the trapezoidal rule in which the hour 11 was used to represent the time-point 10-12 hours. The mean AUC was defined as the AUC divided by the number of hours with ocular pain VAS results during the first 12 hours postoperatively. |
| Ocular Inflammation in Summed Ocular Inflammation Score (SOIS) Grade on Day 1 | One day | The mean SOIS summarized by treatment arm and time point on Day 1 postoperatively. Ocular inflammation was evaluated by measuring the anterior chamber cell count and flare using a slit lamp biomicroscope. SOIS was calculated by adding the average of subject's anterior chamber cells and flare grades. The minimum SOIS was 0 (indicating absence of inflammation), whereas the maximum SOIS was 8. Grading was as follows: Anterior Chamber Cells: Grade None = 0/no cells; Grade Mild = +1/1-5 cells; Grade Moderate = +2/6-15 cells; Grade Severe = +3/16-30 cells; Grade Very Severe = +4/\>30 cells. Anterior Chamber Flare: Grade None = 0/no Tyndall effect; Grade Mild = +1/barely discernable Tyndall effect; Grade Moderate = +2/moderately intense Tyndall beam in anterior chamber; Grade Severe = +3/severely intense Tyndall beam; Grade Very Severe = +4/very severely intense Tyndall beam with a white and milky appearance to the aqueous |
| Ocular Pain VAS Score After Day of Surgery - Day 1 | One day | Pain VAS scores (where 0 = no pain and 100 = worst possible pain) after the day of surgery summarized by treatment arm and time-point. |
| Best Corrected Visual Acuity (BVCA) Log Score on Day 1 | One day | Best-Corrected Visual Acuity (BCVA) summarized by the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity log score. For subjects without a score due to inability to read the ETDRS chart, the log score was imputed as 1.6 for the purpose of treatment comparisons. Subjects without a score because the manifest refraction was not completed were excluded from the analysis. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| OMS302 OMS302 diluted in Balanced Salt Solution and administered as irrigation solution during Intraocular Lens Replacement surgery.
OMS302: OMS302 drug product will be supplied as a sterile, clear colorless liquid, free from particulates of foreign matter. Each vial contains a nominal 4.5 mL of solution containing 60.75 mM phenylephrine hydrochloride (HCl) and 11.25 mM ketorolac tromethamine formulated in a 20 mM sodium citrate buffer (pH 6.3 +/- 0.5). For administration to patients, 4.4 mL of the drug product are added to a 500-mL bottle of commercially available BSS solution through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle. | 201 |
| Placebo Placebo diluted in Balanced Salt Solution and administered as irrigation solution during Intraocular Lens Replacement surgery.
Placebo: Placebo drug product will be supplied as a sterile, clear colorless liquid, free from particulates of foreign matter. Each vial contains a nominal 4.5 mL of solution containing 20 mM sodium citrate buffer (pH 6.3 +/- 0.5). For administration to patients, 4.4 mL of the drug product are added to a 500-mL bottle of commercially available BSS solution through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle. | 201 |
| Total | 402 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Randomized | Adverse Event | 1 | 1 |
| Randomized | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | OMS302 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 68.2 years STANDARD_DEVIATION 9.6 | 68.5 years STANDARD_DEVIATION 9.9 | 68.4 years STANDARD_DEVIATION 9.7 |
| Sex: Female, Male Female | 119 Participants | 111 Participants | 230 Participants |
| Sex: Female, Male Male | 82 Participants | 90 Participants | 172 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 156 / 201 | 154 / 201 |
| serious Total, serious adverse events | 1 / 201 | 0 / 201 |
Outcome results
Primary
Mean Area-under-the-Curve (AUC) Analysis of Change From Baseline in Pupil Diameter (mm) During Surgery
Change in pupil diameter over time from surgical baseline (immediately prior to surgical incision) to the end of the surgical procedure (wound closure) was summarized using descriptive statistics by treatment arm and time-point (every minute). The primary analysis of the change in pupil diameter was based on the mean area-under-the-curve (AUC) pupil diameter change from baseline. First, the AUC of the pupil diameter from surgical baseline to wound closure was calculated using the trapezoidal rule. Second, the mean AUC was obtained by dividing the AUC by the total time of surgery. Third, the mean AUC of change from baseline was calculated by subtracting the baseline pupil diameter from the mean AUC.
Time frame: from surgery baseline (pre-incision) through surgery end (time of cortical clean-up/wound closure)
Population: Subjects with interpretable video images obtained during intraocular lens replacement (ILR) procedure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OMS302 | Mean Area-under-the-Curve (AUC) Analysis of Change From Baseline in Pupil Diameter (mm) During Surgery | 0.1 mm | Standard Deviation 0.41 |
| Placebo | Mean Area-under-the-Curve (AUC) Analysis of Change From Baseline in Pupil Diameter (mm) During Surgery | -0.5 mm | Standard Deviation 0.58 |
p-value: <0.000195% CI: [0.475, 0.678]Cochran-Mantel-Haenszel
Secondary
Best Corrected Visual Acuity (BVCA) Log Score on Day 1
Best-Corrected Visual Acuity (BCVA) summarized by the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity log score. For subjects without a score due to inability to read the ETDRS chart, the log score was imputed as 1.6 for the purpose of treatment comparisons. Subjects without a score because the manifest refraction was not completed were excluded from the analysis.
Time frame: One day
Population: Subject who could read well enough to obtain visual acuity score.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OMS302 | Best Corrected Visual Acuity (BVCA) Log Score on Day 1 | 0.1 Log score | Standard Deviation 0.18 |
| Placebo | Best Corrected Visual Acuity (BVCA) Log Score on Day 1 | 0.1 Log score | Standard Deviation 0.19 |
p-value: 0.0963Wilcoxon rank-sum test
Secondary
Mean Area-under-the-Curve Analysis of Ocular Pain Visual Analog Scale (VAS) Score Within 12 Hours Postoperatively
The primary analysis of the ocular pain VAS (where 0 = no pain and 100 = worst possible pain) was based on the mean area-under-the-curve (AUC). The AUC of the ocular pain VAS during 12 hours postoperatively was calculated by the trapezoidal rule in which the hour 11 was used to represent the time-point 10-12 hours. The mean AUC was defined as the AUC divided by the number of hours with ocular pain VAS results during the first 12 hours postoperatively.
Time frame: 12 hours
Population: Subjects with scores at time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OMS302 | Mean Area-under-the-Curve Analysis of Ocular Pain Visual Analog Scale (VAS) Score Within 12 Hours Postoperatively | 4.1 units on a scale | Standard Deviation 8.07 |
| Placebo | Mean Area-under-the-Curve Analysis of Ocular Pain Visual Analog Scale (VAS) Score Within 12 Hours Postoperatively | 9.2 units on a scale | Standard Deviation 12.9 |
p-value: <0.000195% CI: [-7.307, -3.091]Cochran-Mantel-Haenszel
Secondary
Ocular Inflammation in Summed Ocular Inflammation Score (SOIS) Grade on Day 1
The mean SOIS summarized by treatment arm and time point on Day 1 postoperatively. Ocular inflammation was evaluated by measuring the anterior chamber cell count and flare using a slit lamp biomicroscope. SOIS was calculated by adding the average of subject's anterior chamber cells and flare grades. The minimum SOIS was 0 (indicating absence of inflammation), whereas the maximum SOIS was 8. Grading was as follows: Anterior Chamber Cells: Grade None = 0/no cells; Grade Mild = +1/1-5 cells; Grade Moderate = +2/6-15 cells; Grade Severe = +3/16-30 cells; Grade Very Severe = +4/\>30 cells. Anterior Chamber Flare: Grade None = 0/no Tyndall effect; Grade Mild = +1/barely discernable Tyndall effect; Grade Moderate = +2/moderately intense Tyndall beam in anterior chamber; Grade Severe = +3/severely intense Tyndall beam; Grade Very Severe = +4/very severely intense Tyndall beam with a white and milky appearance to the aqueous
Time frame: One day
Population: Subjects with score at time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OMS302 | Ocular Inflammation in Summed Ocular Inflammation Score (SOIS) Grade on Day 1 | 2.7 units on a scale | Standard Deviation 1.1 |
| Placebo | Ocular Inflammation in Summed Ocular Inflammation Score (SOIS) Grade on Day 1 | 2.9 units on a scale | Standard Deviation 1.4 |
p-value: 0.0532Cochran-Mantel-Haenszel
Secondary
Ocular Pain VAS Score After Day of Surgery - Day 1
Pain VAS scores (where 0 = no pain and 100 = worst possible pain) after the day of surgery summarized by treatment arm and time-point.
Time frame: One day
Population: Number of subjects with scores at time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OMS302 | Ocular Pain VAS Score After Day of Surgery - Day 1 | 5.9 units on a scale | Standard Deviation 13.3 |
| Placebo | Ocular Pain VAS Score After Day of Surgery - Day 1 | 14.2 units on a scale | Standard Deviation 21.4 |
p-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Photophobia at 6 Hours After Surgery (Ocular Pain and Symptoms Numerical Ordinal Scale [Numerical Rating System - NRS] Scores)
Photophobia outcomes based on Ocular Pain and Symptoms Numerical Ordinal Scale (Numerical Rating System - NRS) at 6 hours postoperatively.
Time frame: Six hours postoperatively
Population: Subjects with scores at time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| OMS302 | Photophobia at 6 Hours After Surgery (Ocular Pain and Symptoms Numerical Ordinal Scale [Numerical Rating System - NRS] Scores) | None | 108 participants |
| OMS302 | Photophobia at 6 Hours After Surgery (Ocular Pain and Symptoms Numerical Ordinal Scale [Numerical Rating System - NRS] Scores) | Mild | 70 participants |
| OMS302 | Photophobia at 6 Hours After Surgery (Ocular Pain and Symptoms Numerical Ordinal Scale [Numerical Rating System - NRS] Scores) | Moderate | 17 participants |
| OMS302 | Photophobia at 6 Hours After Surgery (Ocular Pain and Symptoms Numerical Ordinal Scale [Numerical Rating System - NRS] Scores) | Severe | 3 participants |
| Placebo | Photophobia at 6 Hours After Surgery (Ocular Pain and Symptoms Numerical Ordinal Scale [Numerical Rating System - NRS] Scores) | Severe | 2 participants |
| Placebo | Photophobia at 6 Hours After Surgery (Ocular Pain and Symptoms Numerical Ordinal Scale [Numerical Rating System - NRS] Scores) | None | 133 participants |
| Placebo | Photophobia at 6 Hours After Surgery (Ocular Pain and Symptoms Numerical Ordinal Scale [Numerical Rating System - NRS] Scores) | Moderate | 19 participants |
| Placebo | Photophobia at 6 Hours After Surgery (Ocular Pain and Symptoms Numerical Ordinal Scale [Numerical Rating System - NRS] Scores) | Mild | 46 participants |
p-value: 0.0514Cochran-Mantel-Haenszel
Secondary
Photophobia at Day 1 After Surgery (Ocular Pain and Symptoms Numerical Ordinal Scale [Numerical Rating System - NRS] Scores)
Photophobia outcomes based on Ocular Pain and Symptoms Numerical Ordinal Scale (Numerical Rating System - NRS) at Day 1 postoperatively
Time frame: One day
Population: Subjects with scores at time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| OMS302 | Photophobia at Day 1 After Surgery (Ocular Pain and Symptoms Numerical Ordinal Scale [Numerical Rating System - NRS] Scores) | None | 125 participants |
| OMS302 | Photophobia at Day 1 After Surgery (Ocular Pain and Symptoms Numerical Ordinal Scale [Numerical Rating System - NRS] Scores) | Mild | 48 participants |
| OMS302 | Photophobia at Day 1 After Surgery (Ocular Pain and Symptoms Numerical Ordinal Scale [Numerical Rating System - NRS] Scores) | Moderate | 20 participants |
| OMS302 | Photophobia at Day 1 After Surgery (Ocular Pain and Symptoms Numerical Ordinal Scale [Numerical Rating System - NRS] Scores) | Severe | 7 participants |
| Placebo | Photophobia at Day 1 After Surgery (Ocular Pain and Symptoms Numerical Ordinal Scale [Numerical Rating System - NRS] Scores) | Severe | 9 participants |
| Placebo | Photophobia at Day 1 After Surgery (Ocular Pain and Symptoms Numerical Ordinal Scale [Numerical Rating System - NRS] Scores) | None | 90 participants |
| Placebo | Photophobia at Day 1 After Surgery (Ocular Pain and Symptoms Numerical Ordinal Scale [Numerical Rating System - NRS] Scores) | Moderate | 38 participants |
| Placebo | Photophobia at Day 1 After Surgery (Ocular Pain and Symptoms Numerical Ordinal Scale [Numerical Rating System - NRS] Scores) | Mild | 63 participants |
p-value: 0.0034Cochran-Mantel-Haenszel