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

Intraocular Lens Replacement Clinical Trial

— OMS302-ILR-004  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01579565
• Other study ID #: OMS302-ILR-004
• Status: Completed
• Phase: Phase 3
• First received: April 13, 2012
• Last updated: August 5, 2014
• Start date: April 2012
• Est. completion date: January 2013

Study information

• Verified date: August 2014
• Source: Omeros Corporation
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review BoardNetherlands: Medical Ethics Review Committee (METC)Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)Austria: EthikkommissionAustria: Federal Office for Safety in Health Care
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 416
• Est. completion date: January 2013
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Intraocular Lens Replacement

Intervention

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
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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Omeros Corporation

Countries where clinical trial is conducted

United States,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Primary	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	No
Secondary	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)	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	Yes
Secondary	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	Yes