MIST-2: Safety and Efficacy of Phenylephrine 2.5%-Tropicamide 1% Microdose Ophthalmic Solution for Pupil Dilation

• Sponsor: Eyenovia Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03751098
• Collaborator: (none)
• Enrollment: 76
• Locations: 2
• Arms: 2
• Actual Duration (Months): 1.7
• Patients Per Site: 38
• Patients Per Site Per Month: 22.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Mydriasis	Drug: Tropicamide/Phenylephrine ophthalmic solution (TR/PE); Drug: Placebo	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 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 76 participants
• Allocation: Randomized
• Intervention Model: Crossover 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.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.
• Masking: Double (Participant, 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.
• Primary Purpose: Diagnostic
• Official Title: A Multi-Center, Double-Masked, Placebo-Controlled, Phase 3 Study of the Safety and Efficacy of Fixed Combination Phenylephrine 2.5%-Tropicamide 1% Ophthalmic Solution Administered With a Microdose Dispenser for Dilation of the Pupil
• Actual Study Start Date: Dec 1, 2018
• Actual Primary Completion Date: Jan 21, 2019
• Actual Study Completion Date: Jan 21, 2019

Arms and Interventions

Arm	Intervention/Treatment
Other: 1-TR/PE, 2-Placebo, 3-Placebo Participants were dosed once at 3 separate clinic visits in accordance with this sequence. Each participant received 2 sprays of the designated treatment in each eye.	Drug: Tropicamide/Phenylephrine ophthalmic solution (TR/PE); Tropicamide 1%/phenylephrine 2.5% ophthalmic solution administered with the Optejet microdose dispenser; Other Names: Mydcombi ; Drug: Placebo; Eyewash administered with the Optejet microdose dispenser
Other: 1-Placebo, 2-Placebo, 3-TR/PE Participants were dosed once at 3 separate clinic visits in accordance with this sequence. Each participant received 2 sprays of the designated treatment in each eye.	Drug: Tropicamide/Phenylephrine ophthalmic solution (TR/PE); Tropicamide 1%/phenylephrine 2.5% ophthalmic solution administered with the Optejet microdose dispenser; Other Names: Mydcombi ; Drug: Placebo; Eyewash administered with the Optejet microdose dispenser

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Keystone Research	Austin	Texas	United States	78731
2	R&R Research	San Antonio	Texas	United States	78229

Sponsors and Collaborators

• Eyenovia Inc.

Investigators

• Study Director: Tsontcho Ianchulev, MD, MPH, Eyenovia Inc.

Study Documents (Full-Text)

• Study Protocol - Nov 20, 2018
• Statistical Analysis Plan - Jan 18, 2019
• Informed Consent Form - Nov 30, 2018

More Information

Publications

None provided.

• Responsible Party: Eyenovia Inc.
• ClinicalTrials.gov Identifier: NCT03751098
• Other Study ID Numbers: EYN-MYD-TP-32
• First Posted: Nov 23, 2018
• Last Update Posted: Mar 18, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Mydriasis; Phenylephrine; Oxymetazoline; Ophthalmic Solutions; Tropicamide

Study Results

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 Detail	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.

Arm/Group Title	1-TR/PE, 2-Placebo, 3-Placebo	1-Placebo, 2-Placebo, 3-TR/PE
Arm/Group Description	Participants were administered the assigned treatment in each eye on separate days in the following order: 1st Treatment Day: Tropicamide 1%/Phenylephrine 2.5%, 2nd Treatment Day: Placebo, 3rd Treatment Day: Placebo. Each treatment was administered with the Optejet microdose dispenser.	Participants were administered the assigned treatment in each eye on separate days in the following order: 1st Treatment Day: Placebo, 2nd Treatment Day: Placebo, 3rd Treatment Day: Tropicamide 1%/Placebo 2.5%. Each treatment was administered with the Optejet microdose dispenser.
Period Title: Overall Study
STARTED	37	33
COMPLETED	37	32
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	Participants were administered the assigned treatments on 3 separate days (treatment administration sequence was randomized).
Overall Participants	70
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35.4 (14.55)
Sex: Female, Male (Count of Participants)
Female	33 47.1%
Male	37 52.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	35 50%
Not Hispanic or Latino	35 50%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 1.4%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	7 10%
White	62 88.6%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	70 100%
Iris Color Category (Count of Participants)
Dark	50 71.4%
Light	20 28.6%

Outcome Measures

1. Primary Outcome

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	Placebo - Right Eye	Placebo - 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.	Placebo ophthalmic solution administered to the right eye with the Optejet microdose dispenser	Placebo ophthalmic solution administered to the left eye with the Optejet microdose dispenser
Measure Participants	69	69	69	69
Measure eyes	69	69	69	69
Change in 35-minute pupil diameter	4.747 (0.7301)	4.779 (0.8032)	0.134 (0.4972)	0.032 (0.4983)
Baseline pupil diameter	2.597 (0.4784)	2.524 (0.4802)	2.632 (0.5202)	2.559 (0.4666)
35-minutes pupil diameter	7.344 (0.7981)	7.304 (0.8264)	2.766 (0.6598)	2.590 (0.5892)

2. Other Pre-specified Outcome

Title	Proportion 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 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

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	Placebo - Right Eye	Placebo - 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.	Placebo ophthalmic solution administered to the right eye with the Optejet microdose dispenser	Placebo ophthalmic solution administered to the left eye with the Optejet microdose dispenser
Measure Participants	69	69	69	69
Measure eyes	69	69	69	69
Number [percentage of eyes]	92.8	94.2	0	0

3. Other Pre-specified Outcome

Title	Proportion 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 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

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	Placebo - Right Eye	Placebo - 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.	Placebo ophthalmic solution administered to the right eye with the Optejet microdose dispenser	Placebo ophthalmic solution administered to the left eye with the Optejet microdose dispenser
Measure Participants	69	69	69	69
Measure eyes	69	69	69	69
Number [percentage of eyes]	69.6	68.1	0	0

Adverse Events

Time Frame	Adverse event data was collected over each participant's study participation period, which was a maximum of 14 days.
Arm/Group Title	Tropicamide/Phenylephrine		Placebo
Arm/Group Description	Tropicamide 1%/Phenylephrine 2.5% ophthalmic solution administered with the Optejet microdose dispenser		Placebo ophthalmic solution administered with the Optejet microdose dispenser
All Cause Mortality
	Tropicamide/Phenylephrine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/69 (0%)		0/70 (0%)
Serious Adverse Events
	Tropicamide/Phenylephrine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/69 (0%)		0/70 (0%)
Other (Not Including Serious) Adverse Events
	Tropicamide/Phenylephrine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/69 (2.9%)		0/70 (0%)
Eye disorders
Photophobia	1/69 (1.4%)	1	0/70 (0%)	0
General disorders
Instillation site pain	1/69 (1.4%)	1	0/70 (0%)	0

Limitations/Caveats

[Not Specified]

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.