Safety and Efficacy of Nyxol (0.75% Phentolamine Ophthalmic Solution) to Reverse Pharmacologically-Induced Mydriasis (MIRA-3) (MIRA-3)

Randomized, Parallel Arm, Double-Masked, Placebo-Controlled Study of the Safety and Efficacy of Nyxol (0.75% Phentolamine Ophthalmic Solution) to Reverse Pharmacologically-Induced Mydriasis in Healthy Subjects

The objectives of this study are:

• To evaluate the efficacy of Nyxol to expedite the reversal of pharmacologically-induced mydriasis across multiple mydriatic agents with an emphasis on phenylephrine
• To evaluate the efficacy of Nyxol to return subjects to baseline accommodation after worsening (with cycloplegic agents tropicamide and Paremyd)
• To evaluate the safety of Nyxol
• To evaluate any additional benefits of the reversal of pharmacologically-induced mydriasis
• To evaluate the systemic exposure of Nyxol on pharmacokinetic (PK) sampling

Study Overview

• Status: Completed
• Conditions: Mydriasis; Dilation
• Intervention / Treatment: Drug: Phentolamine Ophthalmic Solution 0.75%; Drug: Phentolamine Ophthalmic Solution Vehicle

Detailed Description

A randomized, parallel arm, double-masked, placebo-controlled Phase 3 study in at least 330 randomized subjects, evaluating the safety and efficacy of Nyxol in subjects with pharmacologically-induced mydriasis.

Following the successful completion of screening, each subject will be stratified by eye color and then simultaneously be randomized to mydriatic agent (unmasked) and treatment (masked). Treatment randomization will be 2:1, Nyxol or placebo (vehicle). Stratification by iris color will be 1:1, light or dark rides. The mydriatic agent randomization will be 3:1:1 (2.5% phenylephrine, 1% tropicamide, and Paremyd).

At the treatment visit, subjects who have been randomized and stratified by iris color (1:1 [light/dark]) will receive one of three approved mydriatic agents approximately 1 hour prior to receiving study treatment. Measurements will be measured before (-1 hour /baseline) and 60 minutes after (maximum/0 minutes) the mydriatic agent instillation in each eye (i.e. right before the study treatment is administered), and at 30 minutes, 60 minutes, 90 minutes, 2 hours, 3 hours, 4 hours, and 6 hours after treatment dosing. Measurements will include pupil diameter (PD), distance and near visual acuity (VA), accommodation, and redness in each eye.

Blood sampling for Nyxol PK measurements will be conducted in a subset of approximately 30 adult subjects at approximately two select study sites.

At the Follow-Up Visit, which is 1 day after Visit 1, measurements will again be recorded 24 hours after treatment dosing.

• Study Type: Interventional
• Enrollment (Actual): 368
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Newport Beach, California, United States, 92663
      • Clinical Site 10
    • Westminster, California, United States, 92655
      • Clinical Site 12
  • Florida
    • Delray Beach, Florida, United States, 33484
      • Clinical Site 9
    • Longwood, Florida, United States, 32779
      • Clinical Site 8
  • Georgia
    • Morrow, Georgia, United States, 30260
      • Clinical Site 6
    • Roswell, Georgia, United States, 30009
      • Clinical Site 1
  • Illinois
    • Lake Villa, Illinois, United States, 60046
      • Clinical Site 13
  • Kansas
    • Pittsburg, Kansas, United States, 66762
      • Clinical Site 5
  • Minnesota
    • Bloomington, Minnesota, United States, 55420
      • Clinical Site 2
  • North Carolina
    • Garner, North Carolina, United States, 27529
      • Clinical Site 15
  • Ohio
    • Athens, Ohio, United States, 45701
      • Clinical Site 4
  • Pennsylvania
    • Shrewsbury, Pennsylvania, United States, 17349
      • Clinical Site 14
  • Rhode Island
    • Warwick, Rhode Island, United States, 02888
      • Clinical Site 7
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57101
      • Clinical site 11
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Clinical Site 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Males or females ≥ 12 years of age
2. Ability to comply with all protocol-mandated procedures independently and to attend all scheduled office visits

Exclusion Criteria:

1. Clinically significant ocular disease as deemed by the Investigator (eg, glaucoma, corneal edema, uveitis, severe keratoconjunctivitis sicca) that might interfere with the study
2. Unwilling or unable to discontinue use of contact lenses at screening until study completion
3. Unwilling or unable to suspend use of topical medication at screening until study completion
4. Ocular trauma, ocular surgery, or non-refractive laser treatment within the 6 months prior to screening
5. Use of any topical prescription or over-the-counter (OTC) ophthalmic medications of any kind within 7 days of screening, with the exception of lid scrubs with OTC products (eg, OCuSOFT® lid scrub, SteriLid®, baby shampoo, etc.)
6. Recent or current evidence of ocular infection or inflammation in either eye (such as current evidence of clinically significant blepharitis, conjunctivitis, or keratitis). Subjects must be symptom-free for at least 7 days prior to screening
7. Closed or very narrow-angle that in the Investigator's opinion is potentially occludable if the subject's pupil is dilated
8. Prior participation in a study involving the use of Nyxol for the reversal of mydriasis
9. Known hypersensitivity or contraindication to α- and/or β-adrenoceptor antagonists
10. Clinically significant systemic disease (eg, uncontrolled diabetes, myasthenia gravis, cancer, hepatic, renal, endocrine, or cardiovascular disorders) that might interfere with the study
11. Participation in any investigational study within 30 days prior to screening
12. Resting heart rate (HR) outside the normal range (50-110 beats per minute) at the Screening Visit.
13. Hypertension with resting diastolic blood pressure (BP)>105 mmHg or systolic BP > 160 mmHg at the Screening Visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Phentolamine Ophthalmic Solution Vehicle; 2 drops in study eye and 1 drop in non-study eye, 1 hour post pharmacologically-induced mydriasis	Drug: Phentolamine Ophthalmic Solution Vehicle; Phentolamine Ophthalmic Solution Vehicle
Active Comparator: Phentolamine Ophthalmic Solution 0.75%; 2 drops in study eye and 1 drop in non-study eye, 1 hour post pharmacologically-induced mydriasis	Drug: Phentolamine Ophthalmic Solution 0.75%; 0.75% phentolamine ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist; Other Names: Nyxol®; Nyxol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline	Percentage of subjects' study eyes returning to less than or equal to 0.2 mm from baseline pupil diameter	90 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline	Percentage of subjects' study eyes returning to less than or equal to 0.2 mm from baseline pupil diameter	30 minutes to 24 hours
Pupil Diameter (Change From Max)	Change (mm) from maximum pharmacologically-induced mydriatic pupil diameter (0 minutes)	30 minutes to 24 hours
Percent of Subjects With Unchanged Accommodation From Baseline	Percentage of subjects with unchanged accommodation from baseline (-1 hour)	90 minutes to 6 Hours
Change From Baseline in Best-Corrected Distance Visual Acuity (BCDVA) Under Normal Photopic Lighting Without Glare Conditions	Change from Baseline in best-corrected distance visual acuity (BCDVA) under normal photopic lighting without glare conditions	6 hours

Collaborators and Investigators

• Sponsor: Ocuphire Pharma, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2021
• Primary Completion (Actual): March 18, 2022
• Study Completion (Actual): March 29, 2022

Study Registration Dates

• First Submitted: November 16, 2021
• First Submitted That Met QC Criteria: November 24, 2021
• First Posted (Actual): November 26, 2021

Study Record Updates

• Last Update Posted (Actual): August 29, 2023
• Last Update Submitted That Met QC Criteria: August 7, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Nyxol; Pharmacologically Induced Mydriasis; Dilation
• Additional Relevant MeSH Terms: Eye Diseases; Pathological Conditions, Anatomical; Pupil Disorders; Dilatation, Pathologic; Mydriasis; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Adrenergic alpha-Antagonists; Ophthalmic Solutions; Pharmaceutical Solutions; Phentolamine
• Other Study ID Numbers: OPI-NYXRM-302 (MIRA-3)

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