Mydriasis
Conditions
Brief summary
This study evaluated pupil dilation after administration of fixed combination tropicamide-phenylephrine (TR/PH) vs. placebo. Participants attended 3 visits. At each visit, after baseline measurements, either the study drug or placebo 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 either the study drug or placebo was administered to both eyes. Afterwards, efficacy and safety assessments were performed at 20, 35, 50, 65, 80, 120, and 180 minutes. Participants' treatment assignments for each treatment visit were equally randomized using 1 of 2 sequences - ABB or BAA, where A was the study drug and B was the placebo.
Interventions
DRUGTropicamide/Phenylephrine ophthalmic solution (TR/PE)
Tropicamide 1%/phenylephrine 2.5% ophthalmic solution administered with the Optejet microdose dispenser
DRUGPlacebo
Eyewash 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 study treatment administered and all study personnel conducting ophthalmic assessments after study treatment administration were masked to treatment assignment.
Intervention model description
This trial was a double-masked, placebo-controlled, cross-over superiority study evaluating the efficacy of the fixed combination drug vs. placebo. All participants in the trial were to receive each treatment.
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 |
|---|---|---|
| Proportion 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 69 participants received each medication. Data is reported separately for the right and left eyes of the 69 participants. A higher percentage indicates a better outcome. |
| Proportion 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 69 participants received each solution. Data is reported separately for the right and left eyes of the 69 participants. A higher percentage indicates a better outcome. |
Countries
United States
Participant flow
Recruitment details
76 patients signed the study informed consent form and were screened for eligibility between November 19, 2018 and December 14, 2018 at clinical research centers located in San Antonio and Austin, Texas.
Pre-assignment details
70 of the 76 participants enrolled initiated study treatment. Of those who did not initiate treatment, 4 failed to meet all study eligibility criteria and 2 were exited after screening (before treatment) because the required number of subjects had initiated treatment.
Participants by arm
| Arm | Count |
|---|---|
| All Participants Participants were administered the assigned treatments on 3 separate days (treatment administration sequence was randomized). | 70 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 35.4 years STANDARD_DEVIATION 14.55 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 35 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Iris Color Category Dark | 50 Participants |
| Iris Color Category Light | 20 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants |
| Race (NIH/OMB) More than one race | 0 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 | 62 Participants |
| Region of Enrollment United States | 70 participants |
| Sex: Female, Male Female | 33 Participants |
| Sex: Female, Male Male | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 69 | 0 / 70 |
| other Total, other adverse events | 2 / 69 | 0 / 70 |
| serious Total, serious adverse events | 0 / 69 | 0 / 70 |
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 | Change in 35-minute pupil diameter | 4.747 millimeters | Standard Deviation 0.7301 |
| TR/PE - Right Eye | Change in Pupil Diameter From Baseline | 35-minutes pupil diameter | 7.344 millimeters | Standard Deviation 0.7981 |
| TR/PE - Right Eye | Change in Pupil Diameter From Baseline | Baseline pupil diameter | 2.597 millimeters | Standard Deviation 0.4784 |
| TR/PE - Left Eye | Change in Pupil Diameter From Baseline | Change in 35-minute pupil diameter | 4.779 millimeters | Standard Deviation 0.8032 |
| TR/PE - Left Eye | Change in Pupil Diameter From Baseline | 35-minutes pupil diameter | 7.304 millimeters | Standard Deviation 0.8264 |
| TR/PE - Left Eye | Change in Pupil Diameter From Baseline | Baseline pupil diameter | 2.524 millimeters | Standard Deviation 0.4802 |
| Placebo - Right Eye | Change in Pupil Diameter From Baseline | Baseline pupil diameter | 2.632 millimeters | Standard Deviation 0.5202 |
| Placebo - Right Eye | Change in Pupil Diameter From Baseline | Change in 35-minute pupil diameter | 0.134 millimeters | Standard Deviation 0.4972 |
| Placebo - Right Eye | Change in Pupil Diameter From Baseline | 35-minutes pupil diameter | 2.766 millimeters | Standard Deviation 0.6598 |
| Placebo - Left Eye | Change in Pupil Diameter From Baseline | Change in 35-minute pupil diameter | 0.032 millimeters | Standard Deviation 0.4983 |
| Placebo - Left Eye | Change in Pupil Diameter From Baseline | 35-minutes pupil diameter | 2.590 millimeters | Standard Deviation 0.5892 |
| Placebo - Left Eye | Change in Pupil Diameter From Baseline | Baseline pupil diameter | 2.559 millimeters | Standard Deviation 0.4666 |
Other Pre-specified
Proportion 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 69 participants received each medication. Data is reported separately for the right and left eyes of the 69 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 | Proportion of Eyes Achieving Pupil Diameter 6.0 mm or Larger After Receipt of Each Medication | 92.8 percentage of eyes |
| TR/PE - Left Eye | Proportion of Eyes Achieving Pupil Diameter 6.0 mm or Larger After Receipt of Each Medication | 94.2 percentage of eyes |
| Placebo - Right Eye | Proportion of Eyes Achieving Pupil Diameter 6.0 mm or Larger After Receipt of Each Medication | 0 percentage of eyes |
| Placebo - Left Eye | Proportion of Eyes Achieving Pupil Diameter 6.0 mm or Larger After Receipt of Each Medication | 0 percentage of eyes |
Other Pre-specified
Proportion 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 69 participants received each solution. Data is reported separately for the right and left eyes of the 69 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 | Proportion of Eyes Achieving Pupil Diameter 7.0 mm or Larger After Receipt of Each Medication | 69.6 percentage of eyes |
| TR/PE - Left Eye | Proportion of Eyes Achieving Pupil Diameter 7.0 mm or Larger After Receipt of Each Medication | 68.1 percentage of eyes |
| Placebo - Right Eye | Proportion of Eyes Achieving Pupil Diameter 7.0 mm or Larger After Receipt of Each Medication | 0 percentage of eyes |
| Placebo - Left Eye | Proportion of Eyes Achieving Pupil Diameter 7.0 mm or Larger After Receipt of Each Medication | 0 percentage of eyes |