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

April 13, 2012
August 5, 2014
April 2012
November 2012   (final data collection date for primary outcome measure)
  • 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.
  • Intraoperative pupil diameter [ Time Frame: Intraoperative ] [ Designated as safety issue: No ]
    Change in pupil diameter over time from surgical baseline to end of the surgical procedure determined by video capture during ILR.
  • Pain during the early postoperative period [ Time Frame: 12 hours ] [ Designated as safety issue: No ]
    Postoperative pain as measured by the Visual Analog Scale at 2, 4, 6, 8 and 10-12 hours after ILR surgery.
Complete list of historical versions of study NCT01579565 on ClinicalTrials.gov Archive Site
  • 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.
  • Intraoperative pupil diameter [ Time Frame: Intraoperative ] [ Designated as safety issue: No ]
    Proportion of subjects having a pupil diameter >= 6mm at cortical clean-up.
  • Intraoperative pupil diameter [ Time Frame: Intraoperative ] [ Designated as safety issue: No ]
    Proportion of subjects having a pupil diameter < 6mm anytime during surgery.
  • Moderate-to-severe pain pain during the early postoperative period [ Time Frame: 12 hours ] [ Designated as safety issue: No ]
    Proportion of subjects reporting moderate-to-severe pain at any timepoints during 12 hours postoperatively.
  • No Pain during the early postoperative period [ Time Frame: 12 hours ] [ Designated as safety issue: No ]
    Proportion of subjects reporting no pain at all timepoints during 12 hours postoperatively.
  • Pain during the late postoperative period [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    Postoperative pain as measured by the Visual Analog Scale at 24 and 48 hours, and Days 3-7 and 14 after ILR surgery.
  • Safety as measured by adverse events [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]
    Safety as assessed by the incidence of adverse events and serious adverse events through day 90.
  • Postoperative photophobia [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    Photophobia as measured by the photophobia scale of the NRS at 2, 6, 24, and 48 hours, and 7 and 14 days after surgery.
  • Postoperative best-corrected visual acuity (BVCA) [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]
    BVCA as measured using the Early Treatment Diabetic Retinopathy Study method at 24 and 48 hours, and 7, 14 and 90 days after surgery.
  • Postoperative inflammation [ Time Frame: 90 days ] [ Designated as safety issue: No ]
    Postoperative inflammation as measured using the Summed Ocular Inflammation Score at 24 and 48 hours, and 7, 14 and 90 days after surgery.
  • Systemic Pharmacokinetics of PE and KE [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
    Pharmacokinetics will be evaluated using plasma concentrations of PE and KE at baseline and at approximately 15 and 30 minutes and 1, 2, 4, 8 and 24 hours following initiation of study drug administration.
Not Provided
Not Provided
 
Safety, Efficacy and Pharmacokinetics of OMS302 in Subjects Undergoing Intraocular Lens Replacement With Phacoemulsification
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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Intraocular Lens Replacement
  • 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.
  • 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.
  • Experimental: OMS302
    OMS302 diluted in Balanced Salt Solution and administered as irrigation solution during Intraocular Lens Replacement surgery.
    Intervention: Drug: OMS302
  • Placebo Comparator: Placebo
    Placebo diluted in Balanced Salt Solution and administered as irrigation solution during Intraocular Lens Replacement surgery.
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
416
January 2013
November 2012   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Netherlands
 
NCT01579565
OMS302-ILR-004
No
Omeros Corporation
Omeros Corporation
Not Provided
Study Director: Steve Whitaker, MD Omeros Corporation
Omeros Corporation
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP