Safety, Efficacy and Pharmacokinetics of OMS302 in Subjects Undergoing Intraocular Lens Replacement With Phacoemulsification (OMS302-ILR-004)
|ClinicalTrials.gov Identifier: NCT01579565|
Recruitment Status : Completed
First Posted : April 18, 2012
Results First Posted : August 22, 2014
Last Update Posted : June 14, 2017
|Condition or disease||Intervention/treatment||Phase|
|Intraocular Lens Replacement||Drug: OMS302 Drug: Placebo||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||416 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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 :||April 2012|
|Primary Completion Date :||November 2012|
|Study Completion Date :||January 2013|
OMS302 diluted in Balanced Salt Solution and administered as irrigation solution during Intraocular Lens Replacement surgery.
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.
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.
- 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) ]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 ]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.
- 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) ]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 ]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 ]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 ]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 ]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 ]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 ]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 ]
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 ]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 ]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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01579565
|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|
|Albuquerque, 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|
|Study Director:||Steve Whitaker, MD||Omeros Corporation|