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

Phase 3

Completed

• Conditions: Mydriasis; Dilation
• Interventions: Drug: Phentolamine Ophthalmic Solution Vehicle; Drug: Phentolamine Ophthalmic Solution 0.75%

• Registration Number: NCT05134974
• Lead Sponsor: Ocuphire Pharma, Inc.

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

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 Timeline

• Study First Submitted: 2021-11-16
• Study Start: 2021-11-18
• Study First Submitted QC: 2021-11-24
• Study First Posted: 2021-11-26
• Primary Completion: 2022-03-18
• Study Completion: 2022-03-29
• Results First Submitted: 2023-06-22
• Results First Submitted QC: 2023-07-13
• Status Verified: 2023-08
• Results First Posted: 2023-08-01
• Last Update Submitted: 2023-08-07
• Last Update Posted: 2023-08-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 368

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phentolamine Ophthalmic Solution Vehicle	Phentolamine Ophthalmic Solution Vehicle	2 drops in study eye and 1 drop in non-study eye, 1 hour post pharmacologically-induced mydriasis
Phentolamine Ophthalmic Solution 0.75%	Phentolamine Ophthalmic Solution 0.75%	2 drops in study eye and 1 drop in non-study eye, 1 hour post pharmacologically-induced mydriasis

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (15)

Clinical Site 5; 🇺🇸 Pittsburg, Kansas, United States

Clinical Site 10; 🇺🇸 Newport Beach, California, United States

Clinical Site 9; 🇺🇸 Delray Beach, Florida, United States

Clinical Site 8; 🇺🇸 Longwood, Florida, United States

Clinical Site 6; 🇺🇸 Morrow, Georgia, United States

Clinical Site 1; 🇺🇸 Roswell, Georgia, United States

Clinical Site 13; 🇺🇸 Lake Villa, Illinois, United States

Clinical Site 14; 🇺🇸 Shrewsbury, Pennsylvania, United States

Clinical Site 2; 🇺🇸 Bloomington, Minnesota, United States

Clinical Site 4; 🇺🇸 Athens, Ohio, United States

Clinical Site 3; 🇺🇸 Memphis, Tennessee, United States

Clinical Site 12; 🇺🇸 Westminster, California, United States

Clinical Site 15; 🇺🇸 Garner, North Carolina, United States

Clinical Site 7; 🇺🇸 Warwick, Rhode Island, United States

Clinical Site 11; 🇺🇸 Sioux Falls, South Dakota, United States