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

• ClinicalTrials.gov Identifier: NCT05134974
• Recruitment Status: Completed
• First Posted: November 26, 2021
• Last Update Posted: June 22, 2022
• Sponsor: Ocuphire Pharma, Inc.
• Information provided by (Responsible Party): Ocuphire Pharma, Inc.

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Mydriasis; Dilation	Drug: Phentolamine Ophthalmic Solution 0.75%; Drug: Phentolamine Ophthalmic Solution Vehicle	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 368 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: November 18, 2021
• Actual Primary Completion Date: March 18, 2022
• Actual Study Completion Date: March 29, 2022

Arms and Interventions

Arm	Intervention/treatment
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
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

Outcome Measures

Primary Outcome Measures :

1. Percent of Subjects' Study Eyes with Pupil Diameter Returning to Baseline [ Time Frame: 90 minutes ]
   Percentage of subjects' study eyes returning to less than or equal to 0.2 mm from baseline pupil diameter

Secondary Outcome Measures :

1. Percent of Subjects' Study Eyes with Pupil Diameter Returning to Baseline [ Time Frame: 30 minutes to 24 hours ]
   Percentage of subjects' study eyes returning to less than or equal to 0.2 mm from baseline pupil diameter
2. Pupil Diameter (Change from Max) [ Time Frame: 30 minutes to 24 hours ]
   Change (mm) from maximum pharmacologically-induced mydriatic pupil diameter (0 minutes)
3. Percent of Subjects with Unchanged Accommodation from Baseline [ Time Frame: 2 hours ]
   Percentage of subjects with unchanged accommodation from baseline (-1 hour)
4. Change in Best-Corrected Distance Visual Acuity (BCDVA) Under Normal Photopic Lighting Versus Glare [ Time Frame: 6 hours ]
   Change in best-corrected distance visual acuity (BCDVA) under normal photopic lighting versus glare

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, California

Clinical Site 10

Newport Beach, California, United States, 92663

Clinical Site 12

Westminster, California, United States, 92655

United States, Florida

Clinical Site 9

Delray Beach, Florida, United States, 33484

Clinical Site 8

Longwood, Florida, United States, 32779

United States, Georgia

Clinical Site 6

Morrow, Georgia, United States, 30260

Clinical Site 1

Roswell, Georgia, United States, 30009

United States, Illinois

Clinical Site 13

Lake Villa, Illinois, United States, 60046

United States, Kansas

Clinical Site 5

Pittsburg, Kansas, United States, 66762

United States, Minnesota

Clinical Site 2

Bloomington, Minnesota, United States, 55420

United States, North Carolina

Clinical Site 15

Garner, North Carolina, United States, 27529

United States, Ohio

Clinical Site 4

Athens, Ohio, United States, 45701

United States, Pennsylvania

Clinical Site 14

Shrewsbury, Pennsylvania, United States, 17349

United States, Rhode Island

Clinical Site 7

Warwick, Rhode Island, United States, 02888

United States, South Dakota

Clinical Site 11

Sioux Falls, South Dakota, United States, 57101

United States, Tennessee

Clinical Site 3

Memphis, Tennessee, United States, 38119

Sponsors and Collaborators

Ocuphire Pharma, Inc.

More Information

• Responsible Party: Ocuphire Pharma, Inc.
• ClinicalTrials.gov Identifier: NCT05134974
• Other Study ID Numbers: OPI-NYXRM-302 (MIRA-3)
• First Posted: November 26, 2021
• Last Update Posted: June 22, 2022
• Last Verified: June 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

Keywords provided by Ocuphire Pharma, Inc.:

Nyxol; Pharmacologically Induced Mydriasis; Dilation

Additional relevant MeSH terms:

Mydriasis; Dilatation, Pathologic; Pathological Conditions, Anatomical; Pupil Disorders; Eye Diseases; Phentolamine; Pharmaceutical Solutions; Ophthalmic Solutions; Adrenergic alpha-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Antihypertensive Agents