Intraocular Lens Replacement
Conditions
Keywords
cataract, lens replacement
Brief summary
The purpose of this study is to determine the safety, efficacy and pharmacokinetics of OMS302 (the study drug) for maintaining intraoperative mydriasis and preventing post operative pain 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 saline salt (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 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) | The co-primary analysis of the change in pupil diameter 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. |
| Mean Area Under the Curve Analysis of Ocular Pain VAS Score Within 12 Hours Postoperatively | 12 hours postoperatively | The co-primary analysis of the ocular pain VAS (where 0 = no pain and 100 = worst possible pain) 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 hour. 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Moderate-to-Severe Pain (VAS Greater Than or Equal to 40) at Any Time Point During 12 Hours Postoperatively | 12 hours postoperatively | The number of subjects with moderate -to-severe pain (VAS greater than or equal to 40) at any time point during 12 hours postoperatively summarized by treatment arm. |
| Ocular Pain-Free (VAS Equal to 0) at All Time Points During 12 Hours Postoperatively | 12 hours postoperatively | The number of subjects who report ocular pain-free status (VAS equal to 0) at all time points during 12 hours postoperatively summarized by treatment arm. Subjects with missing VAS scores during the 12 hours postoperatively were considered as not being pain-free. |
| Ocular Pain VAS Score on Day 1 | One day postoperatively | VAS pain scores (where 0 = no pain and 100 = worst possible pain) after the day of surgery summarized by treatment arm and time point. |
| Ocular Symptoms Using Numerical Rating System (NRS) - Photophobia 6 Hours Post-Surgery | Six hours postoperatively | Photophobia outcomes based on Ocular Pain and Symptoms Numerical Ordinal Scale (Numerical Rating System - NRS) at each time point. |
| Pupil Diameter Greater Than or Equal to 6 mm at Completion of Cortical Clean up | at time of cortical clean-up (i.e., end of surgical procedure) | The number of subjects with pupil diameter of at least 6 mm at the completion of cortical clean up summarized by treatment arm. The last pupil diameter was used if not available at completion of cortical clean up. |
| Postoperative Ocular Inflammation - Mean Summed Ocular Inflammation Score (SOIS) on Day 1 | One day postoperatively | Postoperative inflammation as measured using the Summed Ocular Inflammation Score (SOIS), summarized by treatment arm and time point. 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 |
| Postoperative Best Corrected Visual Acuity (BVCA) on Day 1 | One day postoperatively | Best Corrected Visual Acuity (BCVA) summarized by the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity log score. The reason for missing scores (e.g., subject could not read enough letters to obtain a score or refraction was not completed) was also summarized. 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. |
| Systemic Pharmacokinetics (PK) of OMS302 | 24 hours | Systemic pharmacokinetics (PK) of phenylephrine (PE) and ketorolac (KE) were performed in a subset of subjects. Descriptive summary statistics for area-under-the-serum-concentration-time curve (AUC), maximum concentration (Cmax), time to Cmax (Tmax), and terminal phase half-life (t1/2) were to be generated if measured plasma concentrations were adequate for analysis. Descriptive statistics for pharmacokinetics were not performed as detected concentrations were low and insufficient for analysis. |
| Ocular Symptoms Using Numerical Rating System (NRS) - Photophobia 1 Day Post-Surgery | One day postoperatively | Photophobia outcomes based on Ocular Pain and Symptoms Numerical Ordinal Scale (Numerical Rating System - NRS) at each time point. |
| Pupil Diameter Less Than 6 mm Anytime During Surgery | Intraoperative | The number of subjects with pupil diameter less than 6 mm at any time during surgery summarized by treatment arm. |
Countries
Netherlands, 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 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. | 202 |
| 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. | 204 |
| Total | 406 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Randomized | Adverse Event | 1 | 3 |
| Randomized | inadequate preoperative pupil dilation | 0 | 1 |
| Randomized | prohibited preoperative eating | 1 | 0 |
| Randomized | prohibited preoperative medication | 0 | 1 |
| Randomized | Withdrawal by Subject | 3 | 0 |
| Treated | declined to return for final visit | 0 | 1 |
| Treated | Lost to Follow-up | 2 | 1 |
| Treated | Physician Decision | 0 | 1 |
Baseline characteristics
| Characteristic | OMS302 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 69.2 years STANDARD_DEVIATION 9.2 | 67.5 years STANDARD_DEVIATION 10.6 | 68.3 years STANDARD_DEVIATION 10 |
| Sex: Female, Male Female | 117 Participants | 126 Participants | 243 Participants |
| Sex: Female, Male Male | 85 Participants | 78 Participants | 163 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 118 / 202 | 143 / 204 |
| serious Total, serious adverse events | 2 / 202 | 2 / 204 |
Outcome results
Primary
Mean Area Under the Curve Analysis of Change-from-Baseline in Pupil Diameter (mm) During Surgery
The co-primary analysis of the change in pupil diameter 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 Analysis of Change-from-Baseline in Pupil Diameter (mm) During Surgery | 0.1 mm | Standard Deviation 0.43 |
| Placebo | Mean Area Under the Curve Analysis of Change-from-Baseline in Pupil Diameter (mm) During Surgery | -0.5 mm | Standard Deviation 0.57 |
p-value: 0.000195% CI: [0.494, 0.686]Cochran-Mantel-Haenszel
Primary
Mean Area Under the Curve Analysis of Ocular Pain VAS Score Within 12 Hours Postoperatively
The co-primary analysis of the ocular pain VAS (where 0 = no pain and 100 = worst possible pain) 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 hour. 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 postoperatively
Population: Subjects with scores at time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OMS302 | Mean Area Under the Curve Analysis of Ocular Pain VAS Score Within 12 Hours Postoperatively | 4.3 units on a scale | Standard Deviation 8.75 |
| Placebo | Mean Area Under the Curve Analysis of Ocular Pain VAS Score Within 12 Hours Postoperatively | 8.9 units on a scale | Standard Deviation 15.19 |
p-value: 0.000295% CI: [-6.917, -2.244]Cochran-Mantel-Haenszel
Secondary
Moderate-to-Severe Pain (VAS Greater Than or Equal to 40) at Any Time Point During 12 Hours Postoperatively
The number of subjects with moderate -to-severe pain (VAS greater than or equal to 40) at any time point during 12 hours postoperatively summarized by treatment arm.
Time frame: 12 hours postoperatively
Population: Subjects with VAS scores at time points.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OMS302 | Moderate-to-Severe Pain (VAS Greater Than or Equal to 40) at Any Time Point During 12 Hours Postoperatively | 16 participants |
| Placebo | Moderate-to-Severe Pain (VAS Greater Than or Equal to 40) at Any Time Point During 12 Hours Postoperatively | 27 participants |
p-value: 0.076Chi-squared
Secondary
Ocular Pain-Free (VAS Equal to 0) at All Time Points During 12 Hours Postoperatively
The number of subjects who report ocular pain-free status (VAS equal to 0) at all time points during 12 hours postoperatively summarized by treatment arm. Subjects with missing VAS scores during the 12 hours postoperatively were considered as not being pain-free.
Time frame: 12 hours postoperatively
Population: Subjects with scores at time points.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OMS302 | Ocular Pain-Free (VAS Equal to 0) at All Time Points During 12 Hours Postoperatively | 56 participants |
| Placebo | Ocular Pain-Free (VAS Equal to 0) at All Time Points During 12 Hours Postoperatively | 41 participants |
p-value: 0.0806Chi-squared
Secondary
Ocular Pain VAS Score on Day 1
VAS pain 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 postoperatively
Population: Subjects with score at time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OMS302 | Ocular Pain VAS Score on Day 1 | 5.8 units on a scale | Standard Deviation 13.1 |
| Placebo | Ocular Pain VAS Score on Day 1 | 12.2 units on a scale | Standard Deviation 20.1 |
p-value: 0.0002Cochran-Mantel-Haenszel
Secondary
Ocular Symptoms Using Numerical Rating System (NRS) - Photophobia 1 Day Post-Surgery
Photophobia outcomes based on Ocular Pain and Symptoms Numerical Ordinal Scale (Numerical Rating System - NRS) at each time point.
Time frame: One day postoperatively
Population: Subjects with scores at time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| OMS302 | Ocular Symptoms Using Numerical Rating System (NRS) - Photophobia 1 Day Post-Surgery | None | 119 participants |
| OMS302 | Ocular Symptoms Using Numerical Rating System (NRS) - Photophobia 1 Day Post-Surgery | Moderate | 16 participants |
| OMS302 | Ocular Symptoms Using Numerical Rating System (NRS) - Photophobia 1 Day Post-Surgery | Mild | 63 participants |
| OMS302 | Ocular Symptoms Using Numerical Rating System (NRS) - Photophobia 1 Day Post-Surgery | Severe | 4 participants |
| Placebo | Ocular Symptoms Using Numerical Rating System (NRS) - Photophobia 1 Day Post-Surgery | Mild | 63 participants |
| Placebo | Ocular Symptoms Using Numerical Rating System (NRS) - Photophobia 1 Day Post-Surgery | None | 95 participants |
| Placebo | Ocular Symptoms Using Numerical Rating System (NRS) - Photophobia 1 Day Post-Surgery | Severe | 9 participants |
| Placebo | Ocular Symptoms Using Numerical Rating System (NRS) - Photophobia 1 Day Post-Surgery | Moderate | 37 participants |
p-value: 0.006Cochran-Mantel-Haenszel
Secondary
Ocular Symptoms Using Numerical Rating System (NRS) - Photophobia 6 Hours Post-Surgery
Photophobia outcomes based on Ocular Pain and Symptoms Numerical Ordinal Scale (Numerical Rating System - NRS) at each time point.
Time frame: Six hours postoperatively
Population: Subjects with scores at time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| OMS302 | Ocular Symptoms Using Numerical Rating System (NRS) - Photophobia 6 Hours Post-Surgery | None | 140 participants |
| OMS302 | Ocular Symptoms Using Numerical Rating System (NRS) - Photophobia 6 Hours Post-Surgery | Mild | 51 participants |
| OMS302 | Ocular Symptoms Using Numerical Rating System (NRS) - Photophobia 6 Hours Post-Surgery | Moderate | 8 participants |
| OMS302 | Ocular Symptoms Using Numerical Rating System (NRS) - Photophobia 6 Hours Post-Surgery | Severe | 1 participants |
| Placebo | Ocular Symptoms Using Numerical Rating System (NRS) - Photophobia 6 Hours Post-Surgery | Severe | 3 participants |
| Placebo | Ocular Symptoms Using Numerical Rating System (NRS) - Photophobia 6 Hours Post-Surgery | None | 128 participants |
| Placebo | Ocular Symptoms Using Numerical Rating System (NRS) - Photophobia 6 Hours Post-Surgery | Moderate | 13 participants |
| Placebo | Ocular Symptoms Using Numerical Rating System (NRS) - Photophobia 6 Hours Post-Surgery | Mild | 58 participants |
p-value: 0.3923Cochran-Mantel-Haenszel
Secondary
Postoperative Best Corrected Visual Acuity (BVCA) on Day 1
Best Corrected Visual Acuity (BCVA) summarized by the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity log score. The reason for missing scores (e.g., subject could not read enough letters to obtain a score or refraction was not completed) was also summarized. 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 postoperatively
Population: Subjects with score at time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OMS302 | Postoperative Best Corrected Visual Acuity (BVCA) on Day 1 | 0.1 Log score | Standard Deviation 0.2 |
| Placebo | Postoperative Best Corrected Visual Acuity (BVCA) on Day 1 | 0.1 Log score | Standard Deviation 0.18 |
p-value: 0.2361Wilcoxon rank-sum test
Secondary
Postoperative Ocular Inflammation - Mean Summed Ocular Inflammation Score (SOIS) on Day 1
Postoperative inflammation as measured using the Summed Ocular Inflammation Score (SOIS), summarized by treatment arm and time point. 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 postoperatively
Population: Subjects with scores at time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OMS302 | Postoperative Ocular Inflammation - Mean Summed Ocular Inflammation Score (SOIS) on Day 1 | 2.8 units on a scale | Standard Deviation 1 |
| Placebo | Postoperative Ocular Inflammation - Mean Summed Ocular Inflammation Score (SOIS) on Day 1 | 2.9 units on a scale | Standard Deviation 1.3 |
p-value: 0.3286Cochran-Mantel-Haenszel
Secondary
Pupil Diameter Greater Than or Equal to 6 mm at Completion of Cortical Clean up
The number of subjects with pupil diameter of at least 6 mm at the completion of cortical clean up summarized by treatment arm. The last pupil diameter was used if not available at completion of cortical clean up.
Time frame: at time of cortical clean-up (i.e., end of surgical procedure)
Population: Subjects with interpretable video images obtained during ILR procedure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OMS302 | Pupil Diameter Greater Than or Equal to 6 mm at Completion of Cortical Clean up | 187 participants |
| Placebo | Pupil Diameter Greater Than or Equal to 6 mm at Completion of Cortical Clean up | 154 participants |
p-value: 0.0001Chi-squared
Secondary
Pupil Diameter Less Than 6 mm Anytime During Surgery
The number of subjects with pupil diameter less than 6 mm at any time during surgery summarized by treatment arm.
Time frame: Intraoperative
Population: Subjects with interpretable video images obtained during ILR procedure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OMS302 | Pupil Diameter Less Than 6 mm Anytime During Surgery | 18 participants |
| Placebo | Pupil Diameter Less Than 6 mm Anytime During Surgery | 76 participants |
p-value: 0.0001Chi-squared
Secondary
Systemic Pharmacokinetics (PK) of OMS302
Systemic pharmacokinetics (PK) of phenylephrine (PE) and ketorolac (KE) were performed in a subset of subjects. Descriptive summary statistics for area-under-the-serum-concentration-time curve (AUC), maximum concentration (Cmax), time to Cmax (Tmax), and terminal phase half-life (t1/2) were to be generated if measured plasma concentrations were adequate for analysis. Descriptive statistics for pharmacokinetics were not performed as detected concentrations were low and insufficient for analysis.
Time frame: 24 hours
Population: Subset of subjects randomized to OMS302 treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| OMS302 | Systemic Pharmacokinetics (PK) of OMS302 | Subjects with detectable PE | 1 participants |
| OMS302 | Systemic Pharmacokinetics (PK) of OMS302 | Subjects with detectable KE | 10 participants |
| Placebo | Systemic Pharmacokinetics (PK) of OMS302 | Subjects with detectable PE | 0 participants |
| Placebo | Systemic Pharmacokinetics (PK) of OMS302 | Subjects with detectable KE | 1 participants |