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

• ClinicalTrials.gov Identifier: NCT03751631
• Recruitment Status: Completed
• First Posted: November 23, 2018
• Results First Posted: March 18, 2022
• Last Update Posted: March 18, 2022
• Sponsor: Eyenovia Inc.
• Information provided by (Responsible Party): Eyenovia Inc.

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
Mydriasis	Drug: Tropicamide 1%-Phenylephrine 2.5% ophthalmic solution (TR/PE); Drug: Tropicamide 1% ophthalmic solution (TR); Drug: Phenylephrine 2.5% ophthalmic solution (PE)	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

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: This trial was a double-masked, active-controlled, cross-over superiority study evaluating the efficacy of the fixed combination drug vs. the drug's 2 individual components. All participants in the trial were to receive each of the 3 drugs.
• Masking: Double (Participant, Outcomes Assessor)
• Masking Description: There were no differences in the presentation of drug administered and all study personnel conducting ophthalmic assessments after drug administration were masked to treatment assignment.
• Primary Purpose: Diagnostic
• Official Title: 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
• Actual Study Start Date: November 15, 2018
• Actual Primary Completion Date: January 11, 2019
• Actual Study Completion Date: January 11, 2019

Arms and Interventions

Arm	Intervention/treatment
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 Name: 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
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 Name: 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
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 Name: 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
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 Name: 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
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 Name: 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
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 Name: 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

Outcome Measures

Primary Outcome Measures :

1. Change in Pupil Diameter From Baseline [ Time Frame: 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. Percentage of Eyes Achieving Pupil Diameter 6.0 mm or Larger After Receipt of Each Medication [ Time Frame: 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.
2. Percentage of Eyes Achieving Pupil Diameter 7.0 mm or Larger After Receipt of Each Medication [ Time Frame: 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

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

United States, California

WCCT

Cypress, California, United States, 90630

Sponsors and Collaborators

Eyenovia Inc.

Investigators

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

  Study Documents (Full-Text)

Documents provided by Eyenovia Inc.:

Study Protocol  [PDF] September 21, 2018

Statistical Analysis Plan  [PDF] January 7, 2019

Informed Consent Form  [PDF] October 31, 2018

More Information

• Responsible Party: Eyenovia Inc.
• ClinicalTrials.gov Identifier: NCT03751631
• Other Study ID Numbers: EYN-MYD-TP-31
• First Posted: November 23, 2018
• Results First Posted: March 18, 2022
• Last Update Posted: March 18, 2022
• Last Verified: January 2022

Individual Participant Data (IPD) Sharing Statement:

• 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; Pupil Disorders; Eye Diseases; Phenylephrine; Oxymetazoline; Pharmaceutical Solutions; Ophthalmic Solutions; Tropicamide; Cardiotonic Agents; Mydriatics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Sympathomimetics; Vasoconstrictor Agents; Nasal Decongestants; Respiratory System Agents; Adrenergic alpha-1 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Protective Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents