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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Omeros Corporation
ClinicalTrials.gov Identifier:
NCT01579565
First received: April 13, 2012
Last updated: August 5, 2014
Last verified: August 2014
  Purpose

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 Intervention Phase
Intraocular Lens Replacement
Drug: OMS302
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Further study details as provided by Omeros Corporation:

Primary Outcome Measures:
  • Mean Area Under the Curve Analysis of Change-from-Baseline in Pupil Diameter (mm) During Surgery [ Time Frame: From surgery baseline (pre-incision) through surgery end (time of cortical clean-up/wound closure) ] [ Designated as safety issue: No ]
    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.

  • Mean Area Under the Curve Analysis of Ocular Pain VAS Score Within 12 Hours Postoperatively [ Time Frame: 12 hours postoperatively ] [ Designated as safety issue: No ]
    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:
  • Pupil Diameter Greater Than or Equal to 6 mm at Completion of Cortical Clean up [ Time Frame: at time of cortical clean-up (i.e., end of surgical procedure) ] [ Designated as safety issue: No ]
    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.

  • Pupil Diameter Less Than 6 mm Anytime During Surgery [ Time Frame: Intraoperative ] [ Designated as safety issue: No ]
    The number of subjects with pupil diameter less than 6 mm at any time during surgery summarized by treatment arm.

  • Moderate-to-Severe Pain (VAS Greater Than or Equal to 40) at Any Time Point During 12 Hours Postoperatively [ Time Frame: 12 hours postoperatively ] [ Designated as safety issue: No ]
    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.

  • Ocular Pain-Free (VAS Equal to 0) at All Time Points During 12 Hours Postoperatively [ Time Frame: 12 hours postoperatively ] [ Designated as safety issue: No ]
    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.

  • Ocular Pain VAS Score on Day 1 [ Time Frame: One day postoperatively ] [ Designated as safety issue: No ]
    VAS pain scores (where 0 = no pain and 100 = worst possible pain) after the day of surgery summarized by treatment arm and time point.

  • Ocular Symptoms Using Numerical Rating System (NRS) - Photophobia 6 Hours Post-Surgery [ Time Frame: Six hours postoperatively ] [ Designated as safety issue: No ]
    Photophobia outcomes based on Ocular Pain and Symptoms Numerical Ordinal Scale (Numerical Rating System - NRS) at each time point.

  • Ocular Symptoms Using Numerical Rating System (NRS) - Photophobia 1 Day Post-Surgery [ Time Frame: One day postoperatively ] [ Designated as safety issue: No ]
    Photophobia outcomes based on Ocular Pain and Symptoms Numerical Ordinal Scale (Numerical Rating System - NRS) at each time point.

  • Postoperative Ocular Inflammation - Mean Summed Ocular Inflammation Score (SOIS) on Day 1 [ Time Frame: One day postoperatively ] [ Designated as safety issue: No ]

    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


  • Postoperative Best Corrected Visual Acuity (BVCA) on Day 1 [ Time Frame: One day postoperatively ] [ Designated as safety issue: Yes ]
    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.

  • Systemic Pharmacokinetics (PK) of OMS302 [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 416
Study Start Date: April 2012
Study Completion Date: January 2013
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01579565

Locations
United States, Arizona
Chandler, Arizona, United States, 85224
United States, California
Los Angeles, California, United States, 90013
United States, Florida
Fort Myers, Florida, United States, 33901
United States, Massachusetts
Boston, Massachusetts, United States, 02114
United States, Missouri
Saint Louis, Missouri, United States, 63131
Washington, Missouri, United States, 63090
United States, New Mexico
Albequerque, New Mexico, United States, 87113
United States, New York
New York, New York, United States, 10021
United States, Tennessee
Goodlettsville, Tennessee, United States, 37072
United States, Texas
Austin, Texas, United States, 78731
Houston, Texas, United States, 77024
San Antonio, Texas, United States, 78229
United States, Utah
Salt Lake City, Utah, United States, 84132
Netherlands
Zwolle, Netherlands
Sponsors and Collaborators
Omeros Corporation
Investigators
Study Director: Steve Whitaker, MD Omeros Corporation
  More Information

No publications provided

Responsible Party: Omeros Corporation
ClinicalTrials.gov Identifier: NCT01579565     History of Changes
Other Study ID Numbers: OMS302-ILR-004
Study First Received: April 13, 2012
Results First Received: July 2, 2014
Last Updated: August 5, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Netherlands: Medical Ethics Review Committee (METC)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Austria: Ethikkommission
Austria: Federal Office for Safety in Health Care

Keywords provided by Omeros Corporation:
cataract
lens replacement

ClinicalTrials.gov processed this record on October 22, 2014