MIST-1: Safety and Efficacy of Phenylephrine 2.5%-Tropicamide 1% Microdose Ophthalmic Solution for Pupil Dilation
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 3 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Other: 1-TR/PE, 2-TR, 3-PE Participants were dosed once at 3 separate clinic visits in accordance with this sequence. Each participant received 2 sprays of the study drug in each eye. |
Drug: Tropicamide 1%-Phenylephrine 2.5% ophthalmic solution (TR/PE)
Fixed combination tropicamide 1%-phenylephrine 2.5% ophthalmic solution administered with the Optejet microdose dispenser
Other Names:
Drug: Tropicamide 1% ophthalmic solution (TR)
Tropicamide 1% ophthalmic solution administered with the Optejet microdose dispenser
Drug: Phenylephrine 2.5% ophthalmic solution (PE)
Phenylephrine 2.5% ophthalmic solution administered with the Optejet microdose dispenser
|
Other: 1-TR/PE, 2-PE, 3-TR Participants were dosed once at 3 separate clinic visits in accordance with this sequence. Each participant received 2 sprays of the study drug in each eye. |
Drug: Tropicamide 1%-Phenylephrine 2.5% ophthalmic solution (TR/PE)
Fixed combination tropicamide 1%-phenylephrine 2.5% ophthalmic solution administered with the Optejet microdose dispenser
Other Names:
Drug: Tropicamide 1% ophthalmic solution (TR)
Tropicamide 1% ophthalmic solution administered with the Optejet microdose dispenser
Drug: Phenylephrine 2.5% ophthalmic solution (PE)
Phenylephrine 2.5% ophthalmic solution administered with the Optejet microdose dispenser
|
Other: 1-TR, 2-TR/PE, 3-PE Participants were dosed once at 3 separate clinic visits in accordance with this sequence. Each participant received 2 sprays of the study drug in each eye. |
Drug: Tropicamide 1%-Phenylephrine 2.5% ophthalmic solution (TR/PE)
Fixed combination tropicamide 1%-phenylephrine 2.5% ophthalmic solution administered with the Optejet microdose dispenser
Other Names:
Drug: Tropicamide 1% ophthalmic solution (TR)
Tropicamide 1% ophthalmic solution administered with the Optejet microdose dispenser
Drug: Phenylephrine 2.5% ophthalmic solution (PE)
Phenylephrine 2.5% ophthalmic solution administered with the Optejet microdose dispenser
|
Other: 1-TR, 2-PE, 3-TR/PE Participants were dosed once at 3 separate clinic visits in accordance with this sequence. Each participant received 2 sprays of the study drug in each eye. |
Drug: Tropicamide 1%-Phenylephrine 2.5% ophthalmic solution (TR/PE)
Fixed combination tropicamide 1%-phenylephrine 2.5% ophthalmic solution administered with the Optejet microdose dispenser
Other Names:
Drug: Tropicamide 1% ophthalmic solution (TR)
Tropicamide 1% ophthalmic solution administered with the Optejet microdose dispenser
Drug: Phenylephrine 2.5% ophthalmic solution (PE)
Phenylephrine 2.5% ophthalmic solution administered with the Optejet microdose dispenser
|
Other: 1-PE, 2-TR/PE, 3-TR Participants were dosed once at 3 separate clinic visits in accordance with this sequence. Each participant received 2 sprays of the study drug in each eye. |
Drug: Tropicamide 1%-Phenylephrine 2.5% ophthalmic solution (TR/PE)
Fixed combination tropicamide 1%-phenylephrine 2.5% ophthalmic solution administered with the Optejet microdose dispenser
Other Names:
Drug: Tropicamide 1% ophthalmic solution (TR)
Tropicamide 1% ophthalmic solution administered with the Optejet microdose dispenser
Drug: Phenylephrine 2.5% ophthalmic solution (PE)
Phenylephrine 2.5% ophthalmic solution administered with the Optejet microdose dispenser
|
Other: 1-PE, 2-TR, 3-TR/PE Participants were dosed once at 3 separate clinic visits in accordance with this sequence. Each participant received 2 sprays of the study drug in each eye. |
Drug: Tropicamide 1%-Phenylephrine 2.5% ophthalmic solution (TR/PE)
Fixed combination tropicamide 1%-phenylephrine 2.5% ophthalmic solution administered with the Optejet microdose dispenser
Other Names:
Drug: Tropicamide 1% ophthalmic solution (TR)
Tropicamide 1% ophthalmic solution administered with the Optejet microdose dispenser
Drug: Phenylephrine 2.5% ophthalmic solution (PE)
Phenylephrine 2.5% ophthalmic solution administered with the Optejet microdose dispenser
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | WCCT | Cypress | California | United States | 90630 |
Sponsors and Collaborators
- Eyenovia Inc.
Investigators
- Study Director: Tsontcho Ianchulev, MD, MPH, Eyenovia Inc.
Study Documents (Full-Text)
More Information
Publications
None provided.- EYN-MYD-TP-31
Study Results
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 Detail | 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. |
Arm/Group Title | TR/PE - TR - PE | TR/PE - PE - TR | TR - TR/PE - PE | TR - PE - TR/PE | PE - TR/PE - TR | PE - TR - TR/PE |
---|---|---|---|---|---|---|
Arm/Group Description | Participants were administered the assigned study drug in each eye on separate days in the following order: 1st Treatment Day - Tropicamide 1%-Phenylephrine 2.5%; 2nd Treatment Day - Tropicamide 1%; 3rd Treatment Day - Phenylephrine 2.5%. Each drug was administered with the Optejet microdose dispenser. | Participants were administered the assigned study drug in each eye on separate days in the following order: 1st Treatment Day - Tropicamide 1%-Phenylephrine 2.5%; 2nd Treatment Day - Phenylephrine 2.5%; 3rd Treatment Day - Tropicamide 1%. Each drug was administered with the Optejet microdose dispenser. | Participants were administered the assigned study drug in each eye on separate days in the following order: 1st Treatment Day - Tropicamide 1%; 2nd Treatment Day - Tropicamide 1%-Phenylephrine 2.5%; 3rd Treatment Day - Phenylephrine 2.5%. Each drug was administered with the Optejet microdose dispenser. | Participants were administered the assigned study drug in each eye on separate days in the following order: 1st Treatment Day - Tropicamide 1%; 2nd Treatment Day - Phenylephrine 2.5%; 3rd Treatment Day - Tropicamide 1%-Phenylephrine 2.5%. Each drug was administered with the Optejet microdose dispenser. | Participants were administered the assigned study drug in each eye on separate days in the following order: 1st Treatment Day - Phenylephrine 2.5%; 2nd Treatment Day - Tropicamide 1%-Phenylephrine 2.5%; 3rd Treatment Day - Tropicamide 1%. Each drug was administered with the Optejet microdose dispenser. | Participants were administered the assigned study drug in each eye on separate days in the following order: 1st Treatment Day - Phenylephrine 2.5%; 2nd Treatment Day - Tropicamide 1%; 3rd Treatment Day - Tropicamide 1%-Phenylephrine 2.5%. Each drug was administered with the Optejet microdose dispenser. |
Period Title: Overall Study | ||||||
STARTED | 10 | 11 | 11 | 11 | 10 | 11 |
Received 1st Drug in Sequence | 10 | 11 | 11 | 11 | 10 | 11 |
Received 2nd Drug in Sequence | 10 | 11 | 10 | 10 | 10 | 11 |
Received 3rd Drug in Sequence | 10 | 11 | 10 | 10 | 10 | 11 |
COMPLETED | 10 | 11 | 10 | 10 | 10 | 11 |
NOT COMPLETED | 0 | 0 | 1 | 1 | 0 | 0 |
Baseline Characteristics
Arm/Group Title | All Participants |
---|---|
Arm/Group Description | 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). |
Overall Participants | 64 |
Age (years) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [years] |
39.4
(12.00)
|
Sex: Female, Male (Count of Participants) | |
Female |
27
42.2%
|
Male |
37
57.8%
|
Ethnicity (NIH/OMB) (Count of Participants) | |
Hispanic or Latino |
22
34.4%
|
Not Hispanic or Latino |
42
65.6%
|
Unknown or Not Reported |
0
0%
|
Race (NIH/OMB) (Count of Participants) | |
American Indian or Alaska Native |
0
0%
|
Asian |
8
12.5%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
Black or African American |
19
29.7%
|
White |
35
54.7%
|
More than one race |
2
3.1%
|
Unknown or Not Reported |
0
0%
|
Region of Enrollment (participants) [Number] | |
United States |
64
100%
|
Iris color category (Count of Participants) | |
Dark |
54
84.4%
|
Light |
10
15.6%
|
Outcome Measures
Title | Change in Pupil Diameter From Baseline |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
Per-protocol population (participants who completed all planned assessments without a major protocol deviation) |
Arm/Group Title | TR/PE - Right Eye | TR/PE - Left Eye | TR - Right Eye | TR - Left Eye | PE - Right Eye | PE - Left Eye |
---|---|---|---|---|---|---|
Arm/Group Description | Tropicamide 1%/Phenylephrine 2.5% ophthalmic solution administered to the right eye with the Optejet microdose dispenser | Tropicamide 1%/Phenylephrine 2.5% ophthalmic solution administered to the left eye with the Optejet microdose dispenser | Tropicamide 1% ophthalmic solution administered to the right eye with the Optejet microdose dispenser | Tropicamide 1% ophthalmic solution administered to the left eye with the Optejet microdose dispenser | Phenylephrine 2.5% ophthalmic solution administered to the right eye with the Optejet microdose dispenser | Phenylephrine 2.5% ophthalmic solution administered to the left eye with the Optejet microdose dispenser |
Measure Participants | 62 | 62 | 62 | 62 | 62 | 62 |
Baseline pupil diameter |
2.672
(0.5673)
|
2.583
(0.4674)
|
2.657
(0.6016)
|
2.569
(0.5211)
|
2.651
(0.5749)
|
2.584
(0.5344)
|
35-minute pupil diameter |
7.301
(0.8943)
|
7.329
(0.9771)
|
6.762
(0.8619)
|
6.690
(0.8682)
|
3.388
(0.8950)
|
3.552
(0.9340)
|
Change in 35-minute pupil diameter |
4.629
(0.8343)
|
4.746
(0.8173)
|
4.105
(0.7207)
|
4.121
(0.6839)
|
0.737
(0.7939)
|
0.969
(0.8943)
|
Title | Percentage of Eyes Achieving Pupil Diameter 6.0 mm or Larger After Receipt of Each Medication |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
Per-protocol population (participants who completed all planned assessments without a major protocol deviation) |
Arm/Group Title | TR/PE - Right Eye | TR/PE - Left Eye | TR - Right Eye | TR - Left Eye | PE - Right Eye | PE - Left Eye |
---|---|---|---|---|---|---|
Arm/Group Description | Tropicamide 1%/Phenylephrine 2.5% ophthalmic solution administered to the right eye with the Optejet microdose dispenser | Tropicamide 1%/Phenylephrine 2.5% ophthalmic solution administered to the left eye with the Optejet microdose dispenser | Tropicamide 1% ophthalmic solution administered to the right eye with the Optejet microdose dispenser | Tropicamide 1% ophthalmic solution administered to the left eye with the Optejet microdose dispenser | Phenylephrine 2.5% ophthalmic solution administered to the right eye with the Optejet microdose dispenser | Phenylephrine 2.5% ophthalmic solution administered to the left eye with the Optejet microdose dispenser |
Measure Participants | 62 | 62 | 62 | 62 | 62 | 62 |
Measure Eyes | 62 | 62 | 62 | 62 | 62 | 62 |
Number [percentage of eyes] |
95.2
|
93.5
|
79.0
|
77.4
|
1.6
|
1.6
|
Title | Percentage of Eyes Achieving Pupil Diameter 7.0 mm or Larger After Receipt of Each Medication |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
Per-protocol population (participants who completed all planned assessments without a major protocol deviation) |
Arm/Group Title | TR/PE - Right Eye | TR/PE - Left Eye | TR - Right Eye | TR - Left Eye | PE - Right Eye | PE - Left Eye |
---|---|---|---|---|---|---|
Arm/Group Description | Tropicamide 1%/Phenylephrine 2.5% ophthalmic solution administered to the right eye with the Optejet microdose dispenser | Tropicamide 1%/Phenylephrine 2.5% ophthalmic solution administered to the left eye with the Optejet microdose dispenser | Tropicamide 1% ophthalmic solution administered to the right eye with the Optejet microdose dispenser | Tropicamide 1% ophthalmic solution administered to the left eye with the Optejet microdose dispenser | Phenylephrine 2.5% ophthalmic solution administered to the right eye with the Optejet microdose dispenser | Phenylephrine 2.5% ophthalmic solution administered to the left eye with the Optejet microdose dispenser |
Measure Participants | 62 | 62 | 62 | 62 | 62 | 62 |
Measure Eyes | 62 | 62 | 62 | 62 | 62 | 62 |
Number [percentage of eyes] |
67.7
|
67.7
|
43.5
|
41.9
|
0
|
0
|
Adverse Events
Time Frame | Adverse event data was collected over each subject's study participation period, which was a maximum of 14 days | |||||
---|---|---|---|---|---|---|
Adverse Event Reporting Description | ||||||
Arm/Group Title | Tropicamide/Phenylephrine | Tropicamide | Phenylephrine | |||
Arm/Group Description | Tropicamide 1%/Phenylephrine 2.5% ophthalmic solution administered with the Optejet microdose dispenser | Tropicamide 1% ophthalmic solution administered with the Optejet microdose dispenser | Phenylephrine 2.5% ophthalmic solution administered with the Optejet microdose dispenser | |||
All Cause Mortality |
||||||
Tropicamide/Phenylephrine | Tropicamide | Phenylephrine | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/62 (0%) | 0/64 (0%) | 0/62 (0%) | |||
Serious Adverse Events |
||||||
Tropicamide/Phenylephrine | Tropicamide | Phenylephrine | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/62 (0%) | 0/64 (0%) | 0/62 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
Tropicamide/Phenylephrine | Tropicamide | Phenylephrine | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 2/62 (3.2%) | 4/64 (6.3%) | 4/62 (6.5%) | |||
Eye disorders | ||||||
Vision blurred | 1/62 (1.6%) | 1 | 3/64 (4.7%) | 3 | 1/62 (1.6%) | 1 |
Visual acuity reduced | 1/62 (1.6%) | 1 | 1/64 (1.6%) | 1 | 1/62 (1.6%) | 1 |
Eye pain | 0/62 (0%) | 0 | 0/64 (0%) | 0 | 1/62 (1.6%) | 1 |
Investigations | ||||||
Vital dye staining cornea present | 0/62 (0%) | 0 | 0/64 (0%) | 0 | 1/62 (1.6%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | VP, Development |
---|---|
Organization | Eyenovia, Inc. |
Phone | 714-269-8838 |
gclasby@eyenoviabio.com |
- EYN-MYD-TP-31