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

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

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.

Study Overview

• Status: Completed
• Conditions: Mydriasis
• Intervention / Treatment: Drug: Tropicamide 1%-Phenylephrine 2.5% ophthalmic solution (TR/PE); Drug: Tropicamide 1% ophthalmic solution (TR); Drug: Phenylephrine 2.5% ophthalmic solution (PE)

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 Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Cypress, California, United States, 90630
      • WCCT

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / 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: Mydcombi; 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: Mydcombi; 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: Mydcombi; 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: Mydcombi; 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: Mydcombi; 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: Mydcombi; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	35 minutes after initial dose

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	35 minutes after initial dose
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.	35 minutes after initial dose

Collaborators and Investigators

• Sponsor: Eyenovia Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2018
• Primary Completion (Actual): January 11, 2019
• Study Completion (Actual): January 11, 2019

Study Registration Dates

• First Submitted: November 14, 2018
• First Submitted That Met QC Criteria: November 21, 2018
• First Posted (Actual): November 23, 2018

Study Record Updates

• Last Update Posted (Actual): March 18, 2022
• Last Update Submitted That Met QC Criteria: March 16, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Pupil Disorders; Mydriasis; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Protective Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Cardiotonic Agents; Respiratory System Agents; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Nasal Decongestants; Adrenergic alpha-1 Receptor Agonists; Ophthalmic Solutions; Pharmaceutical Solutions; Phenylephrine; Oxymetazoline; Tropicamide
• Other Study ID Numbers: EYN-MYD-TP-31

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No