OMS302-ILR-003: Safety and Efficacy of OMS302 in Subjects Undergoing Intraocular Lens Replacement With Phacoemulsification

• Sponsor: Omeros Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01454063
• Collaborator: (none)
• Enrollment: 405
• Locations: 16
• Arms: 2
• Duration (Months): 6
• Patients Per Site: 25.3
• Patients Per Site Per Month: 4.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Intraocular Lens Replacement	Drug: OMS302; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 405 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Randomized, Double-Masked, Placebo-Controlled Study of the Effect of OMS302 on Intraoperative Pupil Diameter and Early Postoperative Pain in Subjects Undergoing Intraocular Lens Replacement With Phacoemulsification
• Study Start Date: Sep 1, 2011
• Actual Primary Completion Date: Mar 1, 2012
• Actual Study Completion Date: Mar 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: OMS302 OMS302 diluted in Balanced Salt Solution and administered as irrigation solution during Intraocular Lens Replacement surgery.	Drug: 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 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.
Placebo Comparator: Placebo Placebo diluted in Balanced Salt Solution and administered as irrigation solution during Intraocular Lens Replacement surgery.	Drug: 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. This will achieve 4.0 mL of the drug product in a 500 mL bottle of BSS.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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

4. 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.

5. 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

6. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Chandler	Arizona	United States	85224
2		Glendale	Arizona	United States	85308
3		Los Angeles	California	United States	90013
4		Cape Coral	Florida	United States	33904
5		Fort Myers	Florida	United States	33901
6		Stuart	Florida	United States	34994
7		Bloomington	Minnesota	United States	55431
8		Saint Louis	Missouri	United States	63131
9		Washington	Missouri	United States	63090
10		Albuquerque	New Mexico	United States	87113
11		New York	New York	United States	10021
12		Goodlettsville	Tennessee	United States	37072
13		Austin	Texas	United States	78731
14		Houston	Texas	United States	77024
15		San Antonio	Texas	United States	78229
16		Salt Lake City	Utah	United States	84132

Sponsors and Collaborators

• Omeros Corporation

Investigators

• Study Director: Steve Whitaker, MD, Omeros Corporation

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Omeros Corporation
• ClinicalTrials.gov Identifier: NCT01454063
• Other Study ID Numbers: OMS302 ILR 003
• First Posted: Oct 18, 2011
• Last Update Posted: Aug 21, 2014
• Last Verified: Aug 1, 2014

• Keywords provided by Omeros Corporation: cataract; lens replacement

Study Results

Participant Flow

Arm/Group Title	OMS302	Placebo
Arm/Group Description	OMS302 diluted in Balanced Salt Solution (BSS) 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 BSS solution through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.	Placebo diluted in Balanced Salt Solution (BSS) 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.
Period Title: Randomized
STARTED	202	203
COMPLETED	201	201
NOT COMPLETED	1	2
Period Title: Randomized
STARTED	201	201
COMPLETED	199	201
NOT COMPLETED	2	0

Baseline Characteristics

Arm/Group Title	OMS302	Placebo	Total
Arm/Group Description	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.	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 of all reporting groups
Overall Participants	201	201	402
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.2 (9.6)	68.5 (9.9)	68.4 (9.7)
Sex: Female, Male (Count of Participants)
Female	119 59.2%	111 55.2%	230 57.2%
Male	82 40.8%	90 44.8%	172 42.8%

Outcome Measures

1. Primary Outcome

Title	Mean Area-under-the-Curve (AUC) Analysis of Change From Baseline in Pupil Diameter (mm) During Surgery
Description	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)

Outcome Measure Data

Analysis Population Description

Subjects with interpretable video images obtained during intraocular lens replacement (ILR) procedure.

Arm/Group Title	OMS302	Placebo
Arm/Group Description	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 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.
Measure Participants	184	180
Mean (Standard Deviation) [mm]	0.1 (0.41)	-0.5 (0.58)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OMS302, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	p-value based on the generalized Cochran-Mantel-Haenszel (CMH) test stratified by randomization strata.
	Method	Cochran-Mantel-Haenszel
	Comments	CMH-weighted mean difference (OMS - Placebo) adjusted for randomization strata.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.577
	Confidence Interval	() 95%; 0.475 to 0.678
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.052
	Estimation Comments

2. Secondary Outcome

Title	Mean Area-under-the-Curve Analysis of Ocular Pain Visual Analog Scale (VAS) Score Within 12 Hours Postoperatively
Description	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

Outcome Measure Data

Analysis Population Description

Subjects with scores at time points.

Arm/Group Title	OMS302	Placebo
Arm/Group Description	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 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.
Measure Participants	201	201
Mean (Standard Deviation) [units on a scale]	4.1 (8.07)	9.2 (12.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OMS302, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	p-value based on the generalized CMH test stratified by randomization strata.
	Method	Cochran-Mantel-Haenszel
	Comments	CMH-weighted mean difference (OMS302-placebo) adjusted for randomization strata.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-5.199
	Confidence Interval	() 95%; -7.307 to -3.091
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.076
	Estimation Comments

3. Secondary Outcome

Title	Photophobia at 6 Hours After Surgery (Ocular Pain and Symptoms Numerical Ordinal Scale [Numerical Rating System - NRS] Scores)
Description	Photophobia outcomes based on Ocular Pain and Symptoms Numerical Ordinal Scale (Numerical Rating System - NRS) at 6 hours postoperatively.
Time Frame	Six hours postoperatively

Outcome Measure Data

Analysis Population Description

Subjects with scores at time point.

Arm/Group Title	OMS302	Placebo
Arm/Group Description	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 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.
Measure Participants	198	200
None	108 53.7%	133 66.2%
Mild	70 34.8%	46 22.9%
Moderate	17 8.5%	19 9.5%
Severe	3 1.5%	2 1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OMS302, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0514
	Comments	Treatment comparisons based on CMH test adjusting for randomization strata.
	Method	Cochran-Mantel-Haenszel
	Comments

4. Secondary Outcome

Title	Photophobia at Day 1 After Surgery (Ocular Pain and Symptoms Numerical Ordinal Scale [Numerical Rating System - NRS] Scores)
Description	Photophobia outcomes based on Ocular Pain and Symptoms Numerical Ordinal Scale (Numerical Rating System - NRS) at Day 1 postoperatively
Time Frame	One day

Outcome Measure Data

Analysis Population Description

Subjects with scores at time point.

Arm/Group Title	OMS302	Placebo
Arm/Group Description	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 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.
Measure Participants	200	200
None	125 62.2%	90 44.8%
Mild	48 23.9%	63 31.3%
Moderate	20 10%	38 18.9%
Severe	7 3.5%	9 4.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OMS302, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0034
	Comments	Treatment comparisons based on CMH test adjusting for the randomization strata.
	Method	Cochran-Mantel-Haenszel
	Comments

5. Secondary Outcome

Title	Best Corrected Visual Acuity (BVCA) Log Score on Day 1
Description	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

Outcome Measure Data

Analysis Population Description

Subject who could read well enough to obtain visual acuity score.

Arm/Group Title	OMS302	Placebo
Arm/Group Description	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 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.
Measure Participants	200	201
Mean (Standard Deviation) [Log score]	0.1 (0.18)	0.1 (0.19)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OMS302, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0963
	Comments	Treatment comparisons based on Wilcoxon rank-sum test stratified by randomization strata. For subjects without a score due to inability to read the ETDRS chart, the log score will be imputed as 1.6 for the purpose of treatment comparisons.
	Method	Wilcoxon rank-sum test
	Comments

6. Secondary Outcome

Title	Ocular Inflammation in Summed Ocular Inflammation Score (SOIS) Grade on Day 1
Description	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

Outcome Measure Data

Analysis Population Description

Subjects with score at time point.

Arm/Group Title	OMS302	Placebo
Arm/Group Description	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 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.
Measure Participants	201	201
Mean (Standard Deviation) [units on a scale]	2.7 (1.1)	2.9 (1.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OMS302, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0532
	Comments	Treatment comparisons are based on generalized CMH test stratified by randomization strata.
	Method	Cochran-Mantel-Haenszel
	Comments

7. Secondary Outcome

Title	Ocular Pain VAS Score After Day of Surgery - Day 1
Description	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

Outcome Measure Data

Analysis Population Description

Number of subjects with scores at time point.

Arm/Group Title	OMS302	Placebo
Arm/Group Description	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 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.
Measure Participants	201	201
Mean (Standard Deviation) [units on a scale]	5.9 (13.3)	14.2 (21.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OMS302, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Generalized CMH test stratified by randomization strata.
	Method	Cochran-Mantel-Haenszel
	Comments

Adverse Events

Time Frame	14 days post-surgery.
Arm/Group Title	OMS302		Placebo
Arm/Group Description	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 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.
All Cause Mortality
	OMS302		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	OMS302		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/201 (0.5%)		0/201 (0%)
General disorders
electrocution	1/201 (0.5%)	1	0/201 (0%)	0
Other (Not Including Serious) Adverse Events
	OMS302		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	156/201 (77.6%)		154/201 (76.6%)
Eye disorders
eye pain	88/201 (43.8%)		86/201 (42.8%)
eye inflammation	60/201 (29.9%)		58/201 (28.9%)
anterior chamber inflammation	19/201 (9.5%)		21/201 (10.4%)
Investigations
intraocular pressure increased	7/201 (3.5%)		10/201 (5%)
Nervous system disorders
headache	5/201 (2.5%)		14/201 (7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.