Mydriasis
Conditions
Brief summary
This study evaluated pupil dilation after administration of fixed combination tropicamide-phenylephrine (TR/PE) vs. phenylephrine (PE) alone and tropicamide (TR) alone. Participants attended 3 visits. At each visit, after baseline measurements, 1 of the 3 drugs was administered to both eyes, then pupil dilation and safety assessments were performed at specific time intervals.
Detailed description
Volunteer participants were screened for study eligibility during a Screening Visit and enrolled after signing the study-specific informed consent form. Subjects meeting all inclusion/exclusion criteria were scheduled for 3 treatment visits, which were at least 2 days, but no more than 7 days apart. At each treatment visit, baseline measurements were taken, then 1 of the 3 study drugs was administered to both eyes (each participant's drug administration sequence was randomly determined). Afterwards, efficacy and safety assessments were performed at 20, 35, 50, 65, 80, 120, and 180 minutes.
Interventions
DRUGTropicamide 1%-Phenylephrine 2.5% ophthalmic solution (TR/PE)
Fixed combination tropicamide 1%-phenylephrine 2.5% ophthalmic solution administered with the Optejet microdose dispenser
DRUGTropicamide 1% ophthalmic solution (TR)
Tropicamide 1% ophthalmic solution administered with the Optejet microdose dispenser
DRUGPhenylephrine 2.5% ophthalmic solution (PE)
Phenylephrine 2.5% ophthalmic solution administered with the Optejet microdose dispenser
Sponsors
Eyenovia Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DIAGNOSTIC
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
There were no differences in the presentation of drug administered and all study personnel conducting ophthalmic assessments after drug administration were masked to treatment assignment.
Intervention model description
This trial was a double-masked, active-controlled, cross-over superiority study evaluating the efficacy of the fixed combination drug vs. the drug's 2 individual components. All participants in the trial were to receive each of the 3 drugs.
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
Inclusion criteria
* Ability to provide written consent and return for all study visits * Photopic pupil diameter \<= 3.5 mm in each eye
Exclusion criteria
* Allergy to phenylephrine hydrochloride, tropicamide, or benzalkonium chloride * History of benign prostatic hyperplasia * Use of a benzodiazepine, monoamine oxidase inhibitor, tricyclic antidepressant, anticonvulsant, or cholinergic drug * History of closed-angle glaucoma * Anatomically narrow anterior chamber angles * Ocular surgery or laser treatment of any kind * History of chronic or acute uveitis * History of traumatic iritis or hyphema * History of traumatic mydriasis or angle recession * History of heterochromia * Irregularly-shaped pupil secondary to ocular trauma or congenital defect. * History of neurogenic pupil disorder * History of anterior chamber intraocular lens (IOL) or iris-fixated IOL * History of iris surgery, iris atrophy, or iris-cornea apposition/touch * Unwilling or unable to discontinue use of contact lenses at treatment visits. * Current active eye disease for which topical or systemic ophthalmic medication is necessary, except for dry eye disease managed using artificial tears. * Presence of a severe/serious ocular condition, or any other unstable medical condition that, in the Investigator's opinion, may preclude study treatment and/or follow-up * Pregnancy or lactation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pupil Diameter From Baseline | 35 minutes after initial dose | Difference in 35-minute pupil diameter vs. baseline measured using pupillometry in highly photopic conditions. Pupil diameter is reported in millimeters. For the change in pupil diameter, larger measurements indicate a better outcome. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Eyes Achieving Pupil Diameter 6.0 mm or Larger After Receipt of Each Medication | 35 minutes after initial dose | The percent of eyes with pupil diameter 6.0 mm or larger as measured using pupillometry in highly photopic conditions. As this is a cross-over study, each of the 62 participants received each medication. Data is reported separately for the right and left eyes of the 62 participants. A higher percentage indicates a better outcome. |
| Percentage of Eyes Achieving Pupil Diameter 7.0 mm or Larger After Receipt of Each Medication | 35 minutes after initial dose | The percent of eyes with pupil diameter 7.0 mm or larger as measured using pupillometry in highly photopic conditions. As this is a cross-over study, each of the 62 participants received each medication. Data is reported separately for the right and left eyes of the 62 participants. A higher percentage indicates a better outcome. |
Countries
United States
Participant flow
Recruitment details
70 patients signed the study informed consent form and were screened for eligibility between October 31, 2018 and November 16, 2018 at a clinical research center located in Cypress, California.
Pre-assignment details
64 of the 70 participants enrolled initiated treatment. Of those who did not initiate treatment, 4 failed to meet all study eligibility criteria, 1 was exited during screening due to behavioral issues, and 1 was exited after screening (before treatment) because the investigator believed the required number of subjects had initiated treatment.
Participants by arm
| Arm | Count |
|---|---|
| All Participants Participants were administered each of the 3 assigned drugs on 3 separate days in the clinic (drug administration sequence was equally randomized across 6 possible administration sequences). | 64 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 39.4 years STANDARD_DEVIATION 12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 22 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 42 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Iris color category Dark | 54 Participants |
| Iris color category Light | 10 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants |
| Race (NIH/OMB) Black or African American | 19 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 35 Participants |
| Region of Enrollment United States | 64 participants |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 62 | 0 / 64 | 0 / 62 |
| other Total, other adverse events | 2 / 62 | 4 / 64 | 4 / 62 |
| serious Total, serious adverse events | 0 / 62 | 0 / 64 | 0 / 62 |
Outcome results
Primary
Change in Pupil Diameter From Baseline
Difference in 35-minute pupil diameter vs. baseline measured using pupillometry in highly photopic conditions. Pupil diameter is reported in millimeters. For the change in pupil diameter, larger measurements indicate a better outcome.
Time frame: 35 minutes after initial dose
Population: Per-protocol population (participants who completed all planned assessments without a major protocol deviation)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TR/PE - Right Eye | Change in Pupil Diameter From Baseline | 35-minute pupil diameter | 7.301 millimeters | Standard Deviation 0.8943 |
| TR/PE - Right Eye | Change in Pupil Diameter From Baseline | Baseline pupil diameter | 2.672 millimeters | Standard Deviation 0.5673 |
| TR/PE - Right Eye | Change in Pupil Diameter From Baseline | Change in 35-minute pupil diameter | 4.629 millimeters | Standard Deviation 0.8343 |
| TR/PE - Left Eye | Change in Pupil Diameter From Baseline | 35-minute pupil diameter | 7.329 millimeters | Standard Deviation 0.9771 |
| TR/PE - Left Eye | Change in Pupil Diameter From Baseline | Baseline pupil diameter | 2.583 millimeters | Standard Deviation 0.4674 |
| TR/PE - Left Eye | Change in Pupil Diameter From Baseline | Change in 35-minute pupil diameter | 4.746 millimeters | Standard Deviation 0.8173 |
| TR - Right Eye | Change in Pupil Diameter From Baseline | 35-minute pupil diameter | 6.762 millimeters | Standard Deviation 0.8619 |
| TR - Right Eye | Change in Pupil Diameter From Baseline | Baseline pupil diameter | 2.657 millimeters | Standard Deviation 0.6016 |
| TR - Right Eye | Change in Pupil Diameter From Baseline | Change in 35-minute pupil diameter | 4.105 millimeters | Standard Deviation 0.7207 |
| TR - Left Eye | Change in Pupil Diameter From Baseline | 35-minute pupil diameter | 6.690 millimeters | Standard Deviation 0.8682 |
| TR - Left Eye | Change in Pupil Diameter From Baseline | Baseline pupil diameter | 2.569 millimeters | Standard Deviation 0.5211 |
| TR - Left Eye | Change in Pupil Diameter From Baseline | Change in 35-minute pupil diameter | 4.121 millimeters | Standard Deviation 0.6839 |
| PE - Right Eye | Change in Pupil Diameter From Baseline | 35-minute pupil diameter | 3.388 millimeters | Standard Deviation 0.895 |
| PE - Right Eye | Change in Pupil Diameter From Baseline | Baseline pupil diameter | 2.651 millimeters | Standard Deviation 0.5749 |
| PE - Right Eye | Change in Pupil Diameter From Baseline | Change in 35-minute pupil diameter | 0.737 millimeters | Standard Deviation 0.7939 |
| PE - Left Eye | Change in Pupil Diameter From Baseline | Baseline pupil diameter | 2.584 millimeters | Standard Deviation 0.5344 |
| PE - Left Eye | Change in Pupil Diameter From Baseline | Change in 35-minute pupil diameter | 0.969 millimeters | Standard Deviation 0.8943 |
| PE - Left Eye | Change in Pupil Diameter From Baseline | 35-minute pupil diameter | 3.552 millimeters | Standard Deviation 0.934 |
Other Pre-specified
Percentage of Eyes Achieving Pupil Diameter 6.0 mm or Larger After Receipt of Each Medication
The percent of eyes with pupil diameter 6.0 mm or larger as measured using pupillometry in highly photopic conditions. As this is a cross-over study, each of the 62 participants received each medication. Data is reported separately for the right and left eyes of the 62 participants. A higher percentage indicates a better outcome.
Time frame: 35 minutes after initial dose
Population: Per-protocol population (participants who completed all planned assessments without a major protocol deviation)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TR/PE - Right Eye | Percentage of Eyes Achieving Pupil Diameter 6.0 mm or Larger After Receipt of Each Medication | 95.2 percentage of eyes |
| TR/PE - Left Eye | Percentage of Eyes Achieving Pupil Diameter 6.0 mm or Larger After Receipt of Each Medication | 93.5 percentage of eyes |
| TR - Right Eye | Percentage of Eyes Achieving Pupil Diameter 6.0 mm or Larger After Receipt of Each Medication | 79.0 percentage of eyes |
| TR - Left Eye | Percentage of Eyes Achieving Pupil Diameter 6.0 mm or Larger After Receipt of Each Medication | 77.4 percentage of eyes |
| PE - Right Eye | Percentage of Eyes Achieving Pupil Diameter 6.0 mm or Larger After Receipt of Each Medication | 1.6 percentage of eyes |
| PE - Left Eye | Percentage of Eyes Achieving Pupil Diameter 6.0 mm or Larger After Receipt of Each Medication | 1.6 percentage of eyes |
Other Pre-specified
Percentage of Eyes Achieving Pupil Diameter 7.0 mm or Larger After Receipt of Each Medication
The percent of eyes with pupil diameter 7.0 mm or larger as measured using pupillometry in highly photopic conditions. As this is a cross-over study, each of the 62 participants received each medication. Data is reported separately for the right and left eyes of the 62 participants. A higher percentage indicates a better outcome.
Time frame: 35 minutes after initial dose
Population: Per-protocol population (participants who completed all planned assessments without a major protocol deviation)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TR/PE - Right Eye | Percentage of Eyes Achieving Pupil Diameter 7.0 mm or Larger After Receipt of Each Medication | 67.7 percentage of eyes |
| TR/PE - Left Eye | Percentage of Eyes Achieving Pupil Diameter 7.0 mm or Larger After Receipt of Each Medication | 67.7 percentage of eyes |
| TR - Right Eye | Percentage of Eyes Achieving Pupil Diameter 7.0 mm or Larger After Receipt of Each Medication | 43.5 percentage of eyes |
| TR - Left Eye | Percentage of Eyes Achieving Pupil Diameter 7.0 mm or Larger After Receipt of Each Medication | 41.9 percentage of eyes |
| PE - Right Eye | Percentage of Eyes Achieving Pupil Diameter 7.0 mm or Larger After Receipt of Each Medication | 0 percentage of eyes |
| PE - Left Eye | Percentage of Eyes Achieving Pupil Diameter 7.0 mm or Larger After Receipt of Each Medication | 0 percentage of eyes |