Anesthesia, Local
Conditions
Keywords
AG-920, articaine, septocaine, Intravitreal Injection
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.
Interventions
DRUGPlacebo
Placebo Topical Ophthalmic Solution
DRUGAG-920
AG-920 Sterile Topical Ophthalmic Solution
Sponsors
American Genomics, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Masking description
The Investigator(s), Sponsor, and the subject will be masked to treatment assignment throughout the conduct of the study. Exceptions to this are limited to one statistician at the Contract Research Organization (CRO) who will prepare the randomization code, and three people at the Sponsor who will review the batch records and release product. None of these unmasked persons will be involved in the day to day execution of the study. The masking will be broken after database lock.
Intervention 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).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Provide written informed consent prior to any study-related procedures being performed. 2. Is male or a non-pregnant, non-lactating female aged 18 years or older. 3. Willing and able to follow instructions and be present for the required study visits. 4. Have an Early Treatment Diabetic Retinopathy Study (ETDRS) Best Correct Visual Acuity (BCVA) of 20/200 or better in each eye. 5. Have an Intraocular Pressure (IOP) between 7 and 30 mmHg. 6. Certified as healthy by clinical assessment. 7. Verbal communication skills adequate to participate. 8. Able to tolerate bilateral instillation of Over-The-Counter artificial tear product based on investigator judgement.
Exclusion criteria
1. Have participated in an investigational study within the past 30 days. 2. Have a contraindication to local anesthetics. 3. Have known decreased corneal or conjunctival sensitivity. 4. Have had ocular surgery in either eye within the past 90 days. 5. Have had an intravitreal injection in either eye within 14 days. 6. Have ocular disease requiring punctual plugs or ocular inflammation. 7. Are currently using a systemic opioid or opiate analgesic or topical NSAID. 8. Cannot withhold their over the counter (OTC) artificial tear lubricant products for one hour preceding or following study medication. 9. Any condition, including alcohol or drug dependency, that would limit the subject's ability to comply with the procedures of the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Patients Who Experienced Ocular Anesthesia Following Treatment of AG-920 Compared to Placebo at 5 Minutes | 5 minutes post dose | Immediately following EACH pinch test, subjects will be asked Was that painful Yes or NO. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time in Minutes of AG-920 to Anesthetize the Eye | 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. | Mean time to no pain score (onset) |
| To Evaluate How Long One Dose of AG-920 Anesthetizes the Eye | 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. | Mean duration of anesthetic effect |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | from randomization through study completion (up to 4 days following treatment) | 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). |
| Number of Participants With a Change in Biomicroscopy | change from baseline through end of study at Day 5 | Slit lamp biomicroscopy and external eye exam measures will be summarized at each measured time point using discrete summary statistics. Clinician examined the eyelid, conjunctiva, cornea, anterior chamber, iris, pupil and lens of the eye with the aid of a slit lamp. |
| Mean Change in Visual Acuity | change from baseline through end of study at Day 5 | Visual Acuity data will be summarized at each time point using continuous and discrete summaries of Logarithmic Minimum Angle of Resolution (logMAR). Distance visual acuity was assessed using an Early Treatment of Diabetic Retinopathy Study (ETDRS) or equivalent chart. The subject should attempt to read each letter, line by line, left to right, beginning with line 1 at the top of the chart (20/200 line).The number of letters missed is multiplied by 0.02 and added to the baseline value to determine the logMAR visual acuity. Baseline is defined as the last line for which the subject reads at least one letter. logMAR units VA = Baseline value + (n x 0.02). |
Countries
United States
Participant flow
Recruitment details
One hundred and twenty (120) subjects were screened, randomized and treated, all of whom completed the study. No subjects failed to meet inclusion/exclusion criteria and no one was discontinued.
Participants by arm
| Arm | Count |
|---|---|
| AG-920 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.
AG-920: AG-920 Sterile Topical Ophthalmic Solution | 60 |
| Placebo 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.
Placebo: Placebo Topical Ophthalmic Solution | 60 |
| Total | 120 |
Baseline characteristics
| Characteristic | AG-920 | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 60 Participants | 59 Participants | 119 Participants |
| Age, Continuous | 32.6 years STANDARD_DEVIATION 13.72 | 30.02 years STANDARD_DEVIATION 11.26 | 31.31 years STANDARD_DEVIATION 12.57 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 13 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 47 Participants | 47 Participants | 94 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 10 Participants | 10 Participants | 20 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 49 Participants | 49 Participants | 98 Participants |
| Region of Enrollment United States | 60 participants | 60 participants | 120 participants |
| Sex: Female, Male Female | 33 Participants | 34 Participants | 67 Participants |
| Sex: Female, Male Male | 27 Participants | 26 Participants | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 60 | 0 / 60 |
| other Total, other adverse events | 34 / 60 | 13 / 60 |
| serious Total, serious adverse events | 0 / 60 | 0 / 60 |
Outcome results
Primary
The Number 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.
Time frame: 5 minutes post dose
Population: Summary of Proportion of Subjects with No Pain at 5 Minutes
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AG-920 | The Number of Patients Who Experienced Ocular Anesthesia Following Treatment of AG-920 Compared to Placebo at 5 Minutes | 41 Participants |
| Placebo | The Number of Patients Who Experienced Ocular Anesthesia Following Treatment of AG-920 Compared to Placebo at 5 Minutes | 2 Participants |
Secondary
Mean 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). Distance visual acuity was assessed using an Early Treatment of Diabetic Retinopathy Study (ETDRS) or equivalent chart. The subject should attempt to read each letter, line by line, left to right, beginning with line 1 at the top of the chart (20/200 line).The number of letters missed is multiplied by 0.02 and added to the baseline value to determine the logMAR visual acuity. Baseline is defined as the last line for which the subject reads at least one letter. logMAR units VA = Baseline value + (n x 0.02).
Time frame: change from baseline through end of study at Day 5
Population: Summary of Best Corrected Visual Acuity (LogMar)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AG-920 | Mean Change in Visual Acuity | Study Eye | -0.0090 LogMar | Standard Deviation 0.07541 |
| AG-920 | Mean Change in Visual Acuity | Non-Study Eye | -0.0110 LogMar | Standard Deviation 0.05977 |
| Placebo | Mean Change in Visual Acuity | Study Eye | -0.0113 LogMar | Standard Deviation 0.04862 |
| Placebo | Mean Change in Visual Acuity | Non-Study Eye | -0.0110 LogMar | Standard Deviation 0.04821 |
Secondary
Number of Participants With a Change in Biomicroscopy
Slit lamp biomicroscopy and external eye exam measures will be summarized at each measured time point using discrete summary statistics. Clinician examined the eyelid, conjunctiva, cornea, anterior chamber, iris, pupil and lens of the eye with the aid of a slit lamp.
Time frame: change from baseline through end of study at Day 5
Population: Slit Lamp Examination Assessment change from baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AG-920 | Number of Participants With a Change in Biomicroscopy | 0 Participants |
| Placebo | Number of Participants With a Change in Biomicroscopy | 0 Participants |
Secondary
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).
Time frame: from randomization through study completion (up to 4 days following treatment)
Population: Summary of Treatment Emergent Adverse Events
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AG-920 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | All TEAEs | 34 participants |
| AG-920 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Ocular TEAEs | 32 participants |
| AG-920 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Non-ocular TEAEs | 4 participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | All TEAEs | 13 participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Ocular TEAEs | 13 participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Non-ocular TEAEs | 0 participants |
Secondary
Time in Minutes of AG-920 to Anesthetize the Eye
Mean time to no pain score (onset)
Time frame: 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.
Population: Summary of Time to No Pain (Onset of Anesthesia Effect in Minutes)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AG-920 | Time in Minutes of AG-920 to Anesthetize the Eye | 0.442 minutes | Standard Deviation 0.6072 |
| Placebo | Time in Minutes of AG-920 to Anesthetize the Eye | 0.330 minutes | Standard Deviation 0 |
Secondary
To Evaluate How Long One Dose of AG-920 Anesthetizes the Eye
Mean duration of anesthetic effect
Time frame: 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.
Population: Summary of Pinch Test for Duration (in Minutes) of Anesthetic effect
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AG-920 | To Evaluate How Long One Dose of AG-920 Anesthetizes the Eye | 4.833 minutes | Standard Deviation 3.8158 |
| Placebo | To Evaluate How Long One Dose of AG-920 Anesthetizes the Eye | 0.267 minutes | Standard Deviation 1.4325 |