Trial Outcomes & Findings for Safety and Efficacy of OMS302 in Subjects Undergoing Intraocular Lens Replacement With Phacoemulsification (NCT NCT01454063)

NCT ID: NCT01454063

Last Updated: 2014-08-21

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 405 participants
• Primary outcome timeframe: from surgery baseline (pre-incision) through surgery end (time of cortical clean-up/wound closure)
• Results posted on: 2014-08-21

Participant Flow

Participant milestones

Measure	OMS302 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 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.
Randomized STARTED	202	203
Randomized COMPLETED	201	201
Randomized NOT COMPLETED	1	2
Treated STARTED	201	201
Treated COMPLETED	199	201
Treated NOT COMPLETED	2	0

Reasons for withdrawal

Measure	OMS302 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 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.
Randomized Adverse Event	1	1
Randomized Protocol Violation	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

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 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 n=201 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=402 Participants Total of all reporting groups
Age, Continuous	68.2 years STANDARD_DEVIATION 9.6 • n=5 Participants	68.5 years STANDARD_DEVIATION 9.9 • n=7 Participants	68.4 years STANDARD_DEVIATION 9.7 • n=5 Participants
Sex: Female, Male Female	119 Participants n=5 Participants	111 Participants n=7 Participants	230 Participants n=5 Participants
Sex: Female, Male Male	82 Participants n=5 Participants	90 Participants n=7 Participants	172 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.

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.

Outcome measures

Measure	OMS302 n=184 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=180 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.
Mean Area-under-the-Curve (AUC) Analysis of Change From Baseline in Pupil Diameter (mm) During Surgery	0.1 mm Standard Deviation 0.41	-0.5 mm Standard Deviation 0.58

SECONDARY outcome

Timeframe: 12 hours

Population: Subjects with scores at time points.

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.

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 solution through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.	Placebo n=201 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.
Mean Area-under-the-Curve Analysis of Ocular Pain Visual Analog Scale (VAS) Score Within 12 Hours Postoperatively	4.1 units on a scale Standard Deviation 8.07	9.2 units on a scale Standard Deviation 12.9

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 6 hours postoperatively.

Outcome measures

Measure	OMS302 n=198 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=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 solution through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.
Photophobia at 6 Hours After Surgery (Ocular Pain and Symptoms Numerical Ordinal Scale [Numerical Rating System - NRS] Scores) None	108 participants	133 participants
Photophobia at 6 Hours After Surgery (Ocular Pain and Symptoms Numerical Ordinal Scale [Numerical Rating System - NRS] Scores) Mild	70 participants	46 participants
Photophobia at 6 Hours After Surgery (Ocular Pain and Symptoms Numerical Ordinal Scale [Numerical Rating System - NRS] Scores) Moderate	17 participants	19 participants
Photophobia at 6 Hours After Surgery (Ocular Pain and Symptoms Numerical Ordinal Scale [Numerical Rating System - NRS] Scores) Severe	3 participants	2 participants

SECONDARY outcome

Timeframe: One day

Population: Subjects with scores at time point.

Photophobia outcomes based on Ocular Pain and Symptoms Numerical Ordinal Scale (Numerical Rating System - NRS) at Day 1 postoperatively

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 solution 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 solution through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.
Photophobia at Day 1 After Surgery (Ocular Pain and Symptoms Numerical Ordinal Scale [Numerical Rating System - NRS] Scores) Mild	48 participants	63 participants
Photophobia at Day 1 After Surgery (Ocular Pain and Symptoms Numerical Ordinal Scale [Numerical Rating System - NRS] Scores) None	125 participants	90 participants
Photophobia at Day 1 After Surgery (Ocular Pain and Symptoms Numerical Ordinal Scale [Numerical Rating System - NRS] Scores) Moderate	20 participants	38 participants
Photophobia at Day 1 After Surgery (Ocular Pain and Symptoms Numerical Ordinal Scale [Numerical Rating System - NRS] Scores) Severe	7 participants	9 participants

SECONDARY outcome

Timeframe: One day

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

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.

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 solution through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.	Placebo n=201 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.
Best Corrected Visual Acuity (BVCA) Log Score on Day 1	0.1 Log score Standard Deviation 0.18	0.1 Log score Standard Deviation 0.19

SECONDARY outcome

Timeframe: One day

Population: Subjects with score at time point.

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

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 solution through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.	Placebo n=201 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.
Ocular Inflammation in Summed Ocular Inflammation Score (SOIS) Grade on Day 1	2.7 units on a scale Standard Deviation 1.1	2.9 units on a scale Standard Deviation 1.4

SECONDARY outcome

Timeframe: One day

Population: Number of subjects with scores at time point.

Pain VAS 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=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 solution through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.	Placebo n=201 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.
Ocular Pain VAS Score After Day of Surgery - Day 1	5.9 units on a scale Standard Deviation 13.3	14.2 units on a scale Standard Deviation 21.4

Adverse Events

OMS302

Serious events: 1 serious events

Other events: 156 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 154 other events

Deaths: 0 deaths

Serious adverse events

Measure	OMS302 n=201 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 solution through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.	Placebo n=201 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 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.
General disorders electrocution	0.50% 1/201 • Number of events 1 • 14 days post-surgery.	0.00% 0/201 • 14 days post-surgery.

Other adverse events

Measure	OMS302 n=201 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 solution through a syringe filter, resulting in 4.0 mL of the drug product in the 500-mL bottle.	Placebo n=201 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 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.
Eye disorders eye pain	43.8% 88/201 • 14 days post-surgery.	42.8% 86/201 • 14 days post-surgery.
Eye disorders eye inflammation	29.9% 60/201 • 14 days post-surgery.	28.9% 58/201 • 14 days post-surgery.
Eye disorders anterior chamber inflammation	9.5% 19/201 • 14 days post-surgery.	10.4% 21/201 • 14 days post-surgery.
Nervous system disorders headache	2.5% 5/201 • 14 days post-surgery.	7.0% 14/201 • 14 days post-surgery.
Investigations intraocular pressure increased	3.5% 7/201 • 14 days post-surgery.	5.0% 10/201 • 14 days post-surgery.

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