A Study of the Safety and Anesthetic Effect of AG-920 Topical Ophthalmic Solution

Study Overview
=================
Brief Summary
-----------------
This is a Phase 3, randomized, placebo-controlled, double masked, parallel design study in healthy subjects performed in the US. It is designed to evaluate the safety and anesthetic efficacy of AG-920 Sterile Topical Ophthalmic Solution.

Detailed Description
-----------------
This is a Phase 3, randomized, placebo-controlled, double masked, parallel design study in healthy subjects performed in the US. It is designed to evaluate the safety and anesthetic efficacy of AG-920 Sterile Topical Ophthalmic Solution. In this study, subjects who provide informed consent and fulfill all the inclusion criteria and none of the exclusion criteria will be randomized in a 1:1 ratio to receive a single dose of AG-920 or identical looking placebo into the study eye. Subjects will undergo a conjunctival pinch procedure and the pain associated with the pinch rated.

Official Title
-----------------
A Randomized, Double-Masked, Vehicle-Controlled, Parallel Evaluation of the Local Anesthetic Effect of Articaine Sterile Topical Ophthalmic Solution

Conditions
-----------------
Anesthesia, Local

Intervention / Treatment
-----------------
* Drug: AG-920
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Provide written informed consent prior to any study-related procedures being performed. Is male or a non-pregnant, non-lactating female aged 18 years or older. Willing and able to follow instructions and be present for the required study visits. Have an Early Treatment Diabetic Retinopathy Study (ETDRS) Best Correct Visual Acuity (BCVA) of 20/200 or better in each eye. Have an Intraocular Pressure (IOP) between 7 and 30 mmHg. Certified as healthy by clinical assessment. Verbal communication skills adequate to participate. Able to tolerate bilateral instillation of Over-The-Counter artificial tear product based on investigator judgement. Exclusion Criteria: Have participated in an investigational study within the past 30 days. Have a contraindication to local anesthetics. Have known decreased corneal or conjunctival sensitivity. Have had ocular surgery in either eye within the past 90 days. Have had an intravitreal injection in either eye within 14 days. Have ocular disease requiring punctual plugs or ocular inflammation. Are currently using a systemic opioid or opiate analgesic or topical NSAID. Cannot withhold their over the counter (OTC) artificial tear lubricant products for one hour preceding or following study medication. Any condition, including alcohol or drug dependency, that would limit the subject's ability to comply with the procedures of the protocol.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects who provide informed consent and fulfill all the inclusion criteria and none of the exclusion criteria will be randomized in a 1:1 ratio to receive a single dose of AG-920 or identical looking placebo into one (study) eye (2 drops 30 seconds apart).
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AG-920<br>Articaine Sterile Topical Ophthalmic Solution (AG-920) is a sterile, isotonic, non-preserved aqueous solution containing the active ingredient Articaine HCl 8%, Boric Acid, Mannitol, Sodium Acetate Trihydrate, Glacial Acetic Acid, and Edetate Disodium Dihydrate. The product formulation is adjusted to pH 4.5 to 5.0. Each subject randomized to AG-920 will receive a single dose of 2 drops 30 seconds apart from a single vial into study eye. | Drug: AG-920<br>* AG-920 Sterile Topical Ophthalmic Solution<br>* Other names: articaine;|
| Placebo Comparator: Placebo<br>Placebo ophthalmic solution is identical to the active product, with the exception of the active ingredient. Each subject randomized to placebo will receive a single dose of 2 drops 30 seconds apart from a single vial into study eye. | Drug: Placebo<br>* Placebo Topical Ophthalmic Solution<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients who experienced ocular anesthesia following treatment of AG-920 compared to placebo at 5 minutes | Immediately following EACH pinch test, subjects will be asked Was that painful Yes or NO. | 5 minutes post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate how long it takes one dose of AG-920 to anesthetize the eye | Mean time to no pain score (onset) | 20, 40 and 60 seconds following dosing or until pain stops. 5-minutes post dose. If subject became anesthetized before 5 minutes, every 5 minutes for up to 30 minutes or until pain resumes. | 
| To evaluate how long one dose of AG-920 anesthetizes the eye | Mean duration of anesthetic effect | 20, 40 and 60 seconds following dosing or until pain stops. 5-minutes post dose. If subject became anesthetized before 5 minutes, every 5 minutes for up to 30 minutes or until pain resumes. | 
| Number of Participants with Treatment Emergent Adverse Events (TEAEs) | TEAEs will be summarized by treatment group using frequency and percent for each system organ class and preferred term within each system, organ and class (SOC). Summaries will be presented separately for ocular and non-ocular Adverse Events (AEs). | from randomization through study completion (up to 4 days following treatment) | 
| Change in biomicroscopy | Slit lamp biomicroscopy and external eye exam measures will be summarized at each measured time point using discrete summary statistics. | change from baseline through end of study at Day 5 | 
| Change in visual acuity | Visual Acuity data will be summarized at each time point using continuous and discrete summaries of Logarithmic Minimum Angle of Resolution (logMAR). | change from baseline through end of study at Day 5 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
AG-920, articaine, septocaine, Intravitreal Injection