Two Randomized, Double-masked, Placebo-controlled Studies of the Local Anesthetic Effect of Articaine Ophthalmic Solution

Abstract

Background

We wanted to develop a new topical ocular anesthetic with good bioavailability in anterior segment tissues. Given concerns about contamination and sterility in multi-dose products, we selected a unit-dose, nonpreserved presentation of AG-920 (articaine ophthalmic solution) in blow-fill-seal containers (similar to currently marketed pharmacological therapies for dry eye disease).

Methods

Consistent with US Food and Drug Administration guidance, two pivotal, Phase 3, randomized, placebo-controlled, double-masked, parallel design studies conducted at two US private practices in 240 healthy subjects. A single dose of AG-920 or identical looking placebo into one (study) eye (2 drops 30 s apart). Subjects underwent a conjunctival pinch procedure and assessment of the pain associated with the pinch. The main outcome measure was the proportion of subjects with rating of “No pain at 5 minutes”.

Results

AG-920 provided a rapid onset of local anesthesia (less than one minute) with clinically and statistically significantly greater effect in AG-920 (68% and 83%) than placebo (3% and 18% for Study 1 and Study 2, respectively, P<0.0001). The most frequent adverse event was instillation site pain (27% vs 3%) followed by conjunctival hyperemia (probably related to the pinch, 9% vs 10%) in the AG-920 and placebo groups, respectively.

Conclusion

AG-920 was found to be have a rapid onset and useful duration of local anesthesia with no major safety issues, and may be useful for the eye-care professional. Registered with clinicaltrials.gov as NCT04513652 and NCT04829344.

Keywords:

• local anesthesia
• articaine
• controlled trial

Data Sharing Statement

The authors are pleased to review responsible requests for data sharing after regulatory clearance. (Martin Uram, MD, MPH, [email protected]).

Acknowledgments

The authors wish to thank Linda Wirta and Yesenia Salinas for their conduct of the studies. Portions of this work were previously presented at the Association for Research in Vision and Ophthalmology, May 2022 (Gonzalez VH, Novack GD, Wirta D, Uram M, Schupp A, Widmann MC. Two Randomized, Double-Masked, Placebo-Controlled, Parallel-Group Studies of the Local Anesthetic Effect of Articaine Sterile Topical Ophthalmic Solution 8% (AG-920). Investigative Ophthalmology & Visual Science. 2022;63(7):334).

Disclosure

Dr Martin Uram reports Inventor on US Pat. No. 11,096,922. Ms Audrey Schupp reports personal fees from American Genomics, during the conduct of the study. Dr Gary D Novack reports consulting fees paid to employer from American Genomics, during the conduct of the study; and he consults with several medical device and pharmaceutical firms. The authors report no other conflicts of interest in this work.

Additional information

Funding

This research was sponsored by American Genomics, LLC.