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

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

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.

Study Overview

• Status: Completed
• Conditions: Intraocular Lens Replacement
• Intervention / Treatment: Drug: Placebo; Drug: OMS302

• Study Type: Interventional
• Enrollment (Actual): 416
• Phase: Phase 3

Contacts and Locations

Study Locations

• Netherlands
  • Zwolle, Netherlands
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
  • California
    • Los Angeles, California, United States, 90013
  • Florida
    • Fort Myers, Florida, United States, 33901
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
  • Missouri
    • Saint Louis, Missouri, United States, 63131
    • Washington, Missouri, United States, 63090
  • New Mexico
    • Albuquerque, New Mexico, United States, 87113
  • New York
    • New York, New York, United States, 10021
  • Tennessee
    • Goodlettsville, Tennessee, United States, 37072
  • Texas
    • Austin, Texas, United States, 78731
    • Houston, Texas, United States, 77024
    • San Antonio, Texas, United States, 78229
  • Utah
    • Salt Lake City, Utah, United States, 84132

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Area Under the Curve Analysis of Change-from-Baseline in Pupil Diameter (mm) During Surgery	The co-primary analysis of the change in pupil diameter based on the mean area under the curve (AUC) pupil diameter change from baseline. First, the AUC of the pupil diameter from surgical baseline to wound closure was calculated using the trapezoidal rule. Second, the mean AUC was obtained by dividing the AUC by the total time of surgery. Third, the mean AUC of change from baseline was calculated by subtracting the baseline pupil diameter from the mean AUC.	From surgery baseline (pre-incision) through surgery end (time of cortical clean-up/wound closure)
Mean Area Under the Curve Analysis of Ocular Pain VAS Score Within 12 Hours Postoperatively	The co-primary analysis of the ocular pain VAS (where 0 = no pain and 100 = worst possible pain) based on the mean area under the curve (AUC). The AUC of the ocular pain VAS during 12 hours postoperatively was calculated by the trapezoidal rule in which the hour 11 was used to represent the time-point 10-12 hour. The mean AUC was defined as the AUC divided by the number of hours with ocular pain VAS results during the first 12 hours postoperatively.	12 hours postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pupil Diameter Greater Than or Equal to 6 mm at Completion of Cortical Clean up	The number of subjects with pupil diameter of at least 6 mm at the completion of cortical clean up summarized by treatment arm. The last pupil diameter was used if not available at completion of cortical clean up.	at time of cortical clean-up (i.e., end of surgical procedure)
Pupil Diameter Less Than 6 mm Anytime During Surgery	The number of subjects with pupil diameter less than 6 mm at any time during surgery summarized by treatment arm.	Intraoperative
Moderate-to-Severe Pain (VAS Greater Than or Equal to 40) at Any Time Point During 12 Hours Postoperatively	The number of subjects with moderate -to-severe pain (VAS greater than or equal to 40) at any time point during 12 hours postoperatively summarized by treatment arm.	12 hours postoperatively
Ocular Pain-Free (VAS Equal to 0) at All Time Points During 12 Hours Postoperatively	The number of subjects who report ocular pain-free status (VAS equal to 0) at all time points during 12 hours postoperatively summarized by treatment arm. Subjects with missing VAS scores during the 12 hours postoperatively were considered as not being pain-free.	12 hours postoperatively
Ocular Pain VAS Score on Day 1	VAS pain scores (where 0 = no pain and 100 = worst possible pain) after the day of surgery summarized by treatment arm and time point.	One day postoperatively
Ocular Symptoms Using Numerical Rating System (NRS) - Photophobia 6 Hours Post-Surgery	Photophobia outcomes based on Ocular Pain and Symptoms Numerical Ordinal Scale (Numerical Rating System - NRS) at each time point.	Six hours postoperatively
Ocular Symptoms Using Numerical Rating System (NRS) - Photophobia 1 Day Post-Surgery	Photophobia outcomes based on Ocular Pain and Symptoms Numerical Ordinal Scale (Numerical Rating System - NRS) at each time point.	One day postoperatively
Postoperative Ocular Inflammation - Mean Summed Ocular Inflammation Score (SOIS) on Day 1	Postoperative inflammation as measured using the Summed Ocular Inflammation Score (SOIS), summarized by treatment arm and time point. Ocular inflammation was evaluated by measuring the anterior chamber cell count and flare using a slit lamp biomicroscope. SOIS was calculated by adding the average of subject's anterior chamber cells and flare grades. The minimum SOIS was 0 (indicating absence of inflammation), whereas the maximum SOIS was 8. Grading was as follows: Anterior Chamber Cells: Grade None = 0/no cells; Grade Mild = +1/1-5 cells; Grade Moderate = +2/6-15 cells; Grade Severe = +3/16-30 cells; Grade Very Severe = +4/>30 cells. Anterior Chamber Flare: Grade None = 0/no Tyndall effect; Grade Mild = +1/barely discernable Tyndall effect; Grade Moderate = +2/moderately intense Tyndall beam in anterior chamber; Grade Severe = +3/severely intense Tyndall beam; Grade Very Severe = +4/very severely intense Tyndall beam with a white and milky appearance to the aqueous	One day postoperatively
Postoperative Best Corrected Visual Acuity (BVCA) on Day 1	Best Corrected Visual Acuity (BCVA) summarized by the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity log score. The reason for missing scores (e.g., subject could not read enough letters to obtain a score or refraction was not completed) was also summarized. For subjects without a score due to inability to read the ETDRS chart, the log score was imputed as 1.6 for the purpose of treatment comparisons. Subjects without a score because the manifest refraction was not completed were excluded from the analysis.	One day postoperatively
Systemic Pharmacokinetics (PK) of OMS302	Systemic pharmacokinetics (PK) of phenylephrine (PE) and ketorolac (KE) were performed in a subset of subjects. Descriptive summary statistics for area-under-the-serum-concentration-time curve (AUC), maximum concentration (Cmax), time to Cmax (Tmax), and terminal phase half-life (t1/2) were to be generated if measured plasma concentrations were adequate for analysis. Descriptive statistics for pharmacokinetics were not performed as detected concentrations were low and insufficient for analysis.	24 hours

Collaborators and Investigators

• Sponsor: Omeros Corporation
• Investigators: Study Director: Steve Whitaker, MD, Omeros Corporation

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: April 13, 2012
• First Submitted That Met QC Criteria: April 16, 2012
• First Posted (Estimate): April 18, 2012

Study Record Updates

• Last Update Posted (Actual): June 14, 2017
• Last Update Submitted That Met QC Criteria: May 19, 2017
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: cataract; lens replacement
• Other Study ID Numbers: OMS302-ILR-004