OMS302-ILR-004: Safety, Efficacy and Pharmacokinetics of OMS302 in Subjects Undergoing Intraocular Lens Replacement With Phacoemulsification

• Sponsor: Omeros Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01579565
• Collaborator: (none)
• Enrollment: 416
• Locations: 14
• Arms: 2
• Duration (Months): 9
• Patients Per Site: 29.7
• Patients Per Site Per Month: 3.3

Study Details

Study Description

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.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 416 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 Pharmacokinetics of OMS302 and the Effect of OMS302 on Intraoperative Pupil Diameter and Early Postoperative Pain in Subjects Undergoing Intraocular Lens Replacement With Phacoemulsification
• Study Start Date: Apr 1, 2012
• Actual Primary Completion Date: Nov 1, 2012
• Actual Study Completion Date: Jan 1, 2013

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 saline salt (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 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.

2. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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

9. 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.

10. 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.

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		Los Angeles	California	United States	90013
3		Fort Myers	Florida	United States	33901
4		Boston	Massachusetts	United States	02114
5		Saint Louis	Missouri	United States	63131
6		Washington	Missouri	United States	63090
7		Albuquerque	New Mexico	United States	87113
8		New York	New York	United States	10021
9		Goodlettsville	Tennessee	United States	37072
10		Austin	Texas	United States	78731
11		Houston	Texas	United States	77024
12		San Antonio	Texas	United States	78229
13		Salt Lake City	Utah	United States	84132
14		Zwolle		Netherlands

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: NCT01579565
• Other Study ID Numbers: OMS302-ILR-004
• First Posted: Apr 18, 2012
• Last Update Posted: Jun 14, 2017
• 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 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 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.
Period Title: Randomized
STARTED	207	209
COMPLETED	202	204
NOT COMPLETED	5	5
Period Title: Randomized
STARTED	202	204
COMPLETED	200	201
NOT COMPLETED	2	3

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 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	202	204	406
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69.2 (9.2)	67.5 (10.6)	68.3 (10.0)
Sex: Female, Male (Count of Participants)
Female	117 57.9%	126 61.8%	243 59.9%
Male	85 42.1%	78 38.2%	163 40.1%

Outcome Measures

1. Primary Outcome

Title	Mean Area Under the Curve Analysis of Change-from-Baseline in Pupil Diameter (mm) During Surgery
Description	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)

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 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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.
Measure Participants	195	200
Mean (Standard Deviation) [mm]	0.1 (0.43)	-0.5 (0.57)

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 the randomization strata.
	Method	Cochran-Mantel-Haenszel
	Comments	CMH-weighted mean difference (OMS302 - Placebo) is adjusted for the randomization strata.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.590
	Confidence Interval	() 95%; 0.494 to 0.686
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.049
	Estimation Comments

2. Primary Outcome

Title	Mean Area Under the Curve Analysis of Ocular Pain VAS Score Within 12 Hours Postoperatively
Description	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

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	202	202
Mean (Standard Deviation) [units on a scale]	4.3 (8.75)	8.9 (15.19)

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	0.0002
	Comments	p-value is based on the generalized CMH test stratified by the randomization strata.
	Method	Cochran-Mantel-Haenszel
	Comments	CMH-weighted mean difference (OMS302 - Placebo) is adjusted for the randomization strata.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.580
	Confidence Interval	() 95%; -6.917 to -2.244
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.192
	Estimation Comments

3. Secondary Outcome

Title	Pupil Diameter Greater Than or Equal to 6 mm at Completion of Cortical Clean up
Description	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)

Outcome Measure Data

Analysis Population Description

Subjects with interpretable video images obtained during 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 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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.
Measure Participants	195	200
Number [participants]	187 92.6%	154 75.5%

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	0.0001
	Comments	Chi-square test.
	Method	Chi-squared
	Comments

4. Secondary Outcome

Title	Pupil Diameter Less Than 6 mm Anytime During Surgery
Description	The number of subjects with pupil diameter less than 6 mm at any time during surgery summarized by treatment arm.
Time Frame	Intraoperative

Outcome Measure Data

Analysis Population Description

Subjects with interpretable video images obtained during 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 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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.
Measure Participants	195	200
Number [participants]	18 8.9%	76 37.3%

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	Chi-square test
	Method	Chi-squared
	Comments

5. Secondary Outcome

Title	Moderate-to-Severe Pain (VAS Greater Than or Equal to 40) at Any Time Point During 12 Hours Postoperatively
Description	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

Outcome Measure Data

Analysis Population Description

Subjects with VAS 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 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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.
Measure Participants	202	202
Number [participants]	16 7.9%	27 13.2%

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	0.0760
	Comments	Chi-square test
	Method	Chi-squared
	Comments

6. Secondary Outcome

Title	Ocular Pain-Free (VAS Equal to 0) at All Time Points During 12 Hours Postoperatively
Description	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

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 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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.
Measure Participants	202	202
Number [participants]	56 27.7%	41 20.1%

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	0.0806
	Comments	Chi-square test
	Method	Chi-squared
	Comments

7. Secondary Outcome

Title	Ocular Pain VAS Score on Day 1
Description	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

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 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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.
Measure Participants	202	204
Mean (Standard Deviation) [units on a scale]	5.8 (13.1)	12.2 (20.1)

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	0.0002
	Comments	Generalized CMH test stratified by randomization strata.
	Method	Cochran-Mantel-Haenszel
	Comments

8. Secondary Outcome

Title	Ocular Symptoms Using Numerical Rating System (NRS) - Photophobia 6 Hours Post-Surgery
Description	Photophobia outcomes based on Ocular Pain and Symptoms Numerical Ordinal Scale (Numerical Rating System - NRS) at each time point.
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 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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.
Measure Participants	200	202
None	140 69.3%	128 62.7%
Mild	51 25.2%	58 28.4%
Moderate	8 4%	13 6.4%
Severe	1 0.5%	3 1.5%

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	0.3923
	Comments	Treatment comparisons are based on Cochran-Mantel-Haenszel test adjusting for the randomization strata.
	Method	Cochran-Mantel-Haenszel
	Comments

9. Secondary Outcome

Title	Ocular Symptoms Using Numerical Rating System (NRS) - Photophobia 1 Day Post-Surgery
Description	Photophobia outcomes based on Ocular Pain and Symptoms Numerical Ordinal Scale (Numerical Rating System - NRS) at each time point.
Time Frame	One day 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 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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.
Measure Participants	202	204
None	119 58.9%	95 46.6%
Mild	63 31.2%	63 30.9%
Moderate	16 7.9%	37 18.1%
Severe	4 2%	9 4.4%

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	0.0060
	Comments	Treatment comparisons are based on Cochran-Mantel-Haenszel test adjusting for the randomization strata.
	Method	Cochran-Mantel-Haenszel
	Comments

10. Secondary Outcome

Title	Postoperative Ocular Inflammation - Mean Summed Ocular Inflammation Score (SOIS) on Day 1
Description	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

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 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 through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.
Measure Participants	202	204
Mean (Standard Deviation) [units on a scale]	2.8 (1.0)	2.9 (1.3)

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	0.3286
	Comments	Treatment comparisons are based on generalized CMH test stratified by randomization strata.
	Method	Cochran-Mantel-Haenszel
	Comments

11. Secondary Outcome

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

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	203
Mean (Standard Deviation) [Log score]	0.1 (0.20)	0.1 (0.18)

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	0.2361
	Comments	Treatment comparisons based on Wilcoxon rank-sum test stratified by randomization strata.
	Method	Wilcoxon rank-sum test
	Comments

12. Secondary Outcome

Title	Systemic Pharmacokinetics (PK) of OMS302
Description	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

Outcome Measure Data

Analysis Population Description

Subset of subjects randomized to OMS302 treatment.

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	14	12
Subjects with detectable PE	1 0.5%	0 0%
Subjects with detectable KE	10 5%	1 0.5%

Adverse Events

Time Frame	90 days
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 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 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.
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	2/202 (1%)		2/204 (1%)
Cardiac disorders
Myocardial infarction	1/202 (0.5%)	1	0/204 (0%)	0
Pericardial effusion	0/202 (0%)	0	1/204 (0.5%)	1
Metabolism and nutrition disorders
Dehydration	1/202 (0.5%)	1	0/204 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant	0/202 (0%)	0	1/204 (0.5%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory arrest	0/202 (0%)	0	1/204 (0.5%)	1
Other (Not Including Serious) Adverse Events
	OMS302		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	118/202 (58.4%)		143/204 (70.1%)
Eye disorders
Eye pain	34/202 (16.8%)		76/204 (37.3%)
Posterior capsule opafication	17/202 (8.4%)		14/204 (6.9%)
Anterior chamber inflammation	17/202 (8.4%)		13/204 (6.4%)
Ocular discomfort	10/202 (5%)		15/204 (7.4%)
Vision blurred	5/202 (2.5%)		16/204 (7.8%)
Conjunctival hyperaemia	10/202 (5%)		10/204 (4.9%)
Photophobia	4/202 (2%)		13/204 (6.4%)
Investigations
Intraocular pressure increased	12/202 (5.9%)		4/204 (2%)
Nervous system disorders
Headache	21/202 (10.4%)		24/204 (11.8%)

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.