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

NCT03751631 — Phase 3, Completed, 70 participants, Eyenovia Inc.

ClinicalTrials Daily · Areas · Conditions · Drugs · Sponsors ·

A Double-Masked, Active-Controlled Study of the Safety and Efficacy of Phenylephrine 2.5%-Tropicamide 1% Ophthalmic Solution Administered With a Microdose Dispenser for Dilation of the Pupil

Registry	NCT03751631, acronym MIST-1
Status	Completed
Phase	Phase 3
Study type	Interventional; randomized, crossover, masking: double, diagnostic
Enrollment	70 (Actual)
Sponsor	Eyenovia Inc. (Industry)
Conditions	Mydriasis
Interventions	Tropicamide 1%-Phenylephrine 2.5% ophthalmic solution (TR/PE), Tropicamide 1% ophthalmic solution (TR), Phenylephrine 2.5% ophthalmic solution (PE) (Drug)
Dates	start 2018-11-15, primary completion 2019-01-11, completion 2019-01-11, first posted 2018-11-23, last updated 2022-03-18
Locations	1 site in United States

-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.

Expand all sections · Collapse all

+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.

+Arms and interventions

Arm	Type	Interventions	Description
1-TR/PE, 2-TR, 3-PE	Other	Drug: Tropicamide 1%-Phenylephrine 2.5% ophthalmic solution (TR/PE); Drug: Tropicamide 1% ophthalmic solution (TR); Drug: Phenylephrine 2.5% ophthalmic solution (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.
1-TR/PE, 2-PE, 3-TR	Other	Drug: Tropicamide 1%-Phenylephrine 2.5% ophthalmic solution (TR/PE); Drug: Tropicamide 1% ophthalmic solution (TR); Drug: Phenylephrine 2.5% ophthalmic solution (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.
1-TR, 2-TR/PE, 3-PE	Other	Drug: Tropicamide 1%-Phenylephrine 2.5% ophthalmic solution (TR/PE); Drug: Tropicamide 1% ophthalmic solution (TR); Drug: Phenylephrine 2.5% ophthalmic solution (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.
1-TR, 2-PE, 3-TR/PE	Other	Drug: Tropicamide 1%-Phenylephrine 2.5% ophthalmic solution (TR/PE); Drug: Tropicamide 1% ophthalmic solution (TR); Drug: Phenylephrine 2.5% ophthalmic solution (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.
1-PE, 2-TR/PE, 3-TR	Other	Drug: Tropicamide 1%-Phenylephrine 2.5% ophthalmic solution (TR/PE); Drug: Tropicamide 1% ophthalmic solution (TR); Drug: Phenylephrine 2.5% ophthalmic solution (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.
1-PE, 2-TR, 3-TR/PE	Other	Drug: Tropicamide 1%-Phenylephrine 2.5% ophthalmic solution (TR/PE); Drug: Tropicamide 1% ophthalmic solution (TR); Drug: Phenylephrine 2.5% ophthalmic solution (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.

Tropicamide 1%-Phenylephrine 2.5% ophthalmic solution (TR/PE) (Drug), also known as Mydcombi: Fixed combination tropicamide 1%-phenylephrine 2.5% ophthalmic solution administered with the Optejet microdose dispenser
Tropicamide 1% ophthalmic solution (TR) (Drug): Tropicamide 1% ophthalmic solution administered with the Optejet microdose dispenser
Phenylephrine 2.5% ophthalmic solution (PE) (Drug): Phenylephrine 2.5% ophthalmic solution administered with the Optejet microdose dispenser

+Outcome measures

Primary outcomes

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 outcomes

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

Sex: All, accepts healthy volunteers

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

+Posted results

Participant flow

Milestone	TR/PE - TR - PE	TR/PE - PE - TR	TR - TR/PE - PE	TR - PE - TR/PE	PE - TR/PE - TR	PE - TR - TR/PE
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

Outcome results

Change in Pupil Diameter From Baseline (Primary), Mean, millimeters: TR/PE - Right Eye 2.672 +/- 0.5673; TR/PE - Left Eye 2.583 +/- 0.4674; TR - Right Eye 2.657 +/- 0.6016; TR - Left Eye 2.569 +/- 0.5211; PE - Right Eye 2.651 +/- 0.5749; PE - Left Eye 2.584 +/- 0.5344
Percentage of Eyes Achieving Pupil Diameter 6.0 mm or Larger After Receipt of Each Medication (Other pre specified), Number, percentage of eyes: TR/PE - Right Eye 95.2; TR/PE - Left Eye 93.5; TR - Right Eye 79.0; TR - Left Eye 77.4; PE - Right Eye 1.6; PE - Left Eye 1.6
Percentage of Eyes Achieving Pupil Diameter 7.0 mm or Larger After Receipt of Each Medication (Other pre specified), Number, percentage of eyes: TR/PE - Right Eye 67.7; TR/PE - Left Eye 67.7; TR - Right Eye 43.5; TR - Left Eye 41.9; PE - Right Eye 0; PE - Left Eye 0

Adverse events

Time frame: Adverse event data was collected over each subject's study participation period, which was a maximum of 14 days

Arm	Deaths	Serious adverse events	Other adverse events
Tropicamide/Phenylephrine	0/62 (0.0%)	0/62 (0.0%)	2/62 (3.2%)
Tropicamide	0/64 (0.0%)	0/64 (0.0%)	4/64 (6.3%)
Phenylephrine	0/62 (0.0%)	0/62 (0.0%)	4/62 (6.5%)

Other adverse events by term

Term	Organ system	Tropicamide/Phenylephrine	Tropicamide	Phenylephrine
Vision blurred	Eye disorders	1/62	3/64	1/62
Visual acuity reduced	Eye disorders	1/62	1/64	1/62
Vital dye staining cornea present	Investigations	0/62	0/64	1/62
Eye pain	Eye disorders	0/62	0/64	1/62

+Locations (1)

Facility	City	Country	Status
WCCT	Cypress, California	United States

+Study documents

Study Protocol (PDF, 2018-09-21)
Statistical Analysis Plan (PDF, 2019-01-07)
Informed Consent Form (PDF, 2018-10-31)

+Investigators

Tsontcho Ianchulev, MD, MPH, Study director, Eyenovia Inc.

My Notes

Public

To Read Reading Read