Trial Outcomes & Findings for Safety, Efficacy and Pharmacokinetics of OMS302 in Subjects Undergoing Intraocular Lens Replacement With Phacoemulsification (NCT NCT01579565)

NCT ID: NCT01579565

Last Updated: 2017-06-14

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 416 participants
• Primary outcome timeframe: From surgery baseline (pre-incision) through surgery end (time of cortical clean-up/wound closure)
• Results posted on: 2017-06-14

Participant Flow

Participant milestones

Measure	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 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 are added to a 500-mL bottle of commercially available balanced saline solution (BSS) through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.	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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.
Randomized STARTED	207	209
Randomized COMPLETED	202	204
Randomized NOT COMPLETED	5	5
Treated STARTED	202	204
Treated COMPLETED	200	201
Treated NOT COMPLETED	2	3

Reasons for withdrawal

Measure	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 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 are added to a 500-mL bottle of commercially available balanced saline solution (BSS) through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.	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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.
Randomized Adverse Event	1	3
Randomized Withdrawal by Subject	3	0
Randomized inadequate preoperative pupil dilation	0	1
Randomized prohibited preoperative eating	1	0
Randomized prohibited preoperative medication	0	1
Treated Physician Decision	0	1
Treated Lost to Follow-up	2	1
Treated declined to return for final visit	0	1

Baseline Characteristics

Safety, Efficacy and Pharmacokinetics of OMS302 in Subjects Undergoing Intraocular Lens Replacement With Phacoemulsification

Baseline characteristics by cohort

Measure	OMS302 n=202 Participants 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.	Placebo n=204 Participants 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.	Total n=406 Participants Total of all reporting groups
Age, Continuous	69.2 years STANDARD_DEVIATION 9.2 • n=5 Participants	67.5 years STANDARD_DEVIATION 10.6 • n=7 Participants	68.3 years STANDARD_DEVIATION 10.0 • n=5 Participants
Sex: Female, Male Female	117 Participants n=5 Participants	126 Participants n=7 Participants	243 Participants n=5 Participants
Sex: Female, Male Male	85 Participants n=5 Participants	78 Participants n=7 Participants	163 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	OMS302 n=195 Participants 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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.	Placebo n=200 Participants 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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.
Mean Area Under the Curve Analysis of Change-from-Baseline in Pupil Diameter (mm) During Surgery	0.1 mm Standard Deviation 0.43	-0.5 mm Standard Deviation 0.57

PRIMARY outcome

Timeframe: 12 hours postoperatively

Population: Subjects with scores at time points.

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.

Outcome measures

Measure	OMS302 n=202 Participants 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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.	Placebo n=202 Participants 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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.
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	8.9 units on a scale Standard Deviation 15.19

SECONDARY outcome

Timeframe: at time of cortical clean-up (i.e., end of surgical procedure)

Population: Subjects with interpretable video images obtained during ILR 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.

Outcome measures

Measure	OMS302 n=195 Participants 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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.	Placebo n=200 Participants 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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.
Pupil Diameter Greater Than or Equal to 6 mm at Completion of Cortical Clean up	187 participants	154 participants

SECONDARY outcome

Timeframe: Intraoperative

Population: Subjects with interpretable video images obtained during ILR procedure.

The number of subjects with pupil diameter less than 6 mm at any time during surgery summarized by treatment arm.

Outcome measures

Measure	OMS302 n=195 Participants 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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.	Placebo n=200 Participants 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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.
Pupil Diameter Less Than 6 mm Anytime During Surgery	18 participants	76 participants

SECONDARY outcome

Timeframe: 12 hours postoperatively

Population: Subjects with VAS scores at time points.

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.

Outcome measures

Measure	OMS302 n=202 Participants 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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.	Placebo n=202 Participants 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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.
Moderate-to-Severe Pain (VAS Greater Than or Equal to 40) at Any Time Point During 12 Hours Postoperatively	16 participants	27 participants

SECONDARY outcome

Timeframe: 12 hours postoperatively

Population: Subjects with scores at time points.

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.

Outcome measures

Measure	OMS302 n=202 Participants 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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.	Placebo n=202 Participants 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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.
Ocular Pain-Free (VAS Equal to 0) at All Time Points During 12 Hours Postoperatively	56 participants	41 participants

SECONDARY outcome

Timeframe: One day postoperatively

Population: Subjects with score at time point.

VAS pain scores (where 0 = no pain and 100 = worst possible pain) after the day of surgery summarized by treatment arm and time point.

Outcome measures

Measure	OMS302 n=202 Participants 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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.	Placebo n=204 Participants 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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.
Ocular Pain VAS Score on Day 1	5.8 units on a scale Standard Deviation 13.1	12.2 units on a scale Standard Deviation 20.1

SECONDARY outcome

Timeframe: Six hours postoperatively

Population: Subjects with scores at time point.

Photophobia outcomes based on Ocular Pain and Symptoms Numerical Ordinal Scale (Numerical Rating System - NRS) at each time point.

Outcome measures

Measure	OMS302 n=200 Participants 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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.	Placebo n=202 Participants 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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.
Ocular Symptoms Using Numerical Rating System (NRS) - Photophobia 6 Hours Post-Surgery None	140 participants	128 participants
Ocular Symptoms Using Numerical Rating System (NRS) - Photophobia 6 Hours Post-Surgery Mild	51 participants	58 participants
Ocular Symptoms Using Numerical Rating System (NRS) - Photophobia 6 Hours Post-Surgery Moderate	8 participants	13 participants
Ocular Symptoms Using Numerical Rating System (NRS) - Photophobia 6 Hours Post-Surgery Severe	1 participants	3 participants

SECONDARY outcome

Timeframe: One day postoperatively

Population: Subjects with scores at time point.

Photophobia outcomes based on Ocular Pain and Symptoms Numerical Ordinal Scale (Numerical Rating System - NRS) at each time point.

Outcome measures

Measure	OMS302 n=202 Participants 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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.	Placebo n=204 Participants 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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.
Ocular Symptoms Using Numerical Rating System (NRS) - Photophobia 1 Day Post-Surgery Moderate	16 participants	37 participants
Ocular Symptoms Using Numerical Rating System (NRS) - Photophobia 1 Day Post-Surgery None	119 participants	95 participants
Ocular Symptoms Using Numerical Rating System (NRS) - Photophobia 1 Day Post-Surgery Mild	63 participants	63 participants
Ocular Symptoms Using Numerical Rating System (NRS) - Photophobia 1 Day Post-Surgery Severe	4 participants	9 participants

SECONDARY outcome

Timeframe: One day postoperatively

Population: Subjects with scores at time point.

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

Outcome measures

Measure	OMS302 n=202 Participants 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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.	Placebo n=204 Participants 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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.
Postoperative Ocular Inflammation - Mean Summed Ocular Inflammation Score (SOIS) on Day 1	2.8 units on a scale Standard Deviation 1.0	2.9 units on a scale Standard Deviation 1.3

SECONDARY outcome

Timeframe: One day postoperatively

Population: Subjects with score at time point.

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.

Outcome measures

Measure	OMS302 n=201 Participants 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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.	Placebo n=203 Participants 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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.
Postoperative Best Corrected Visual Acuity (BVCA) on Day 1	0.1 Log score Standard Deviation 0.20	0.1 Log score Standard Deviation 0.18

SECONDARY outcome

Timeframe: 24 hours

Population: Subset of subjects randomized to OMS302 treatment.

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.

Outcome measures

Measure	OMS302 n=14 Participants 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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.	Placebo n=12 Participants 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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.
Systemic Pharmacokinetics (PK) of OMS302 Subjects with detectable PE	1 participants	0 participants
Systemic Pharmacokinetics (PK) of OMS302 Subjects with detectable KE	10 participants	1 participants

Adverse Events

OMS302

Serious events: 2 serious events

Other events: 118 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 143 other events

Deaths: 0 deaths

Serious adverse events

Measure	OMS302 n=202 participants at risk 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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.	Placebo n=204 participants at risk 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 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, resulting in 4.0 mL of the drug product in the 500-mL bottle.
Cardiac disorders Myocardial infarction	0.50% 1/202 • Number of events 1 • 90 days	0.00% 0/204 • 90 days
Cardiac disorders Pericardial effusion	0.00% 0/202 • 90 days	0.49% 1/204 • Number of events 1 • 90 days
Respiratory, thoracic and mediastinal disorders Respiratory arrest	0.00% 0/202 • 90 days	0.49% 1/204 • Number of events 1 • 90 days
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/202 • 90 days	0.49% 1/204 • Number of events 1 • 90 days
Metabolism and nutrition disorders Dehydration	0.50% 1/202 • Number of events 1 • 90 days	0.00% 0/204 • 90 days

Other adverse events

Measure	OMS302 n=202 participants at risk 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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.	Placebo n=204 participants at risk 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 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, resulting in 4.0 mL of the drug product in the 500-mL bottle.
Eye disorders Eye pain	16.8% 34/202 • 90 days	37.3% 76/204 • 90 days
Nervous system disorders Headache	10.4% 21/202 • 90 days	11.8% 24/204 • 90 days
Eye disorders Posterior capsule opafication	8.4% 17/202 • 90 days	6.9% 14/204 • 90 days
Eye disorders Anterior chamber inflammation	8.4% 17/202 • 90 days	6.4% 13/204 • 90 days
Eye disorders Ocular discomfort	5.0% 10/202 • 90 days	7.4% 15/204 • 90 days
Eye disorders Vision blurred	2.5% 5/202 • 90 days	7.8% 16/204 • 90 days
Eye disorders Conjunctival hyperaemia	5.0% 10/202 • 90 days	4.9% 10/204 • 90 days
Eye disorders Photophobia	2.0% 4/202 • 90 days	6.4% 13/204 • 90 days
Investigations Intraocular pressure increased	5.9% 12/202 • 90 days	2.0% 4/204 • 90 days

Additional Information

Chief Medical Officer

Omeros Corporation

Phone: (206) 676-5000

Email: swhitaker@omeros.com

Results disclosure agreements

• Principal investigator is a sponsor employee The PI agreed not to publish or otherwise to disclose Study data without prior written consent from the sponsor for a period of 24 months following Study completion or until data are published in a combined publication (whichever occurs first). The sponsor can review communications containing results prior to public release and embargo those communications for a period that is no longer than 60 days from the date of receipt of the non-public communication. The sponsor cannot extend the embargo.
• Publication restrictions are in place

Restriction type: OTHER