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

Mydriasis Clinical Trial

— MIRA-3  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05134974
• Other study ID #: OPI-NYXRM-302 (MIRA-3)
• Status: Completed
• Phase: Phase 3
• Start date: November 18, 2021
• Est. completion date: March 29, 2022

Study information

• Verified date: August 2023
• Source: Ocuphire Pharma, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 368
• Est. completion date: March 29, 2022
• Est. primary completion date: March 18, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 12 Years and older

Eligibility

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 a- and/or ß-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.

Related Conditions & MeSH terms

• Dilation
• Mydriasis

Intervention

Drug:
• Phentolamine Ophthalmic Solution 0.75%
0.75% phentolamine ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist
• Phentolamine Ophthalmic Solution Vehicle
Phentolamine Ophthalmic Solution Vehicle

Locations

Country	Name	City	State
United States	Clinical Site 4	Athens	Ohio
United States	Clinical Site 2	Bloomington	Minnesota
United States	Clinical Site 9	Delray Beach	Florida
United States	Clinical Site 15	Garner	North Carolina
United States	Clinical Site 13	Lake Villa	Illinois
United States	Clinical Site 8	Longwood	Florida
United States	Clinical Site 3	Memphis	Tennessee
United States	Clinical Site 6	Morrow	Georgia
United States	Clinical Site 10	Newport Beach	California
United States	Clinical Site 5	Pittsburg	Kansas
United States	Clinical Site 1	Roswell	Georgia
United States	Clinical Site 14	Shrewsbury	Pennsylvania
United States	Clinical Site 11	Sioux Falls	South Dakota
United States	Clinical Site 7	Warwick	Rhode Island
United States	Clinical Site 12	Westminster	California

Sponsors (1)

Lead Sponsor	Collaborator
Ocuphire Pharma, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Pupil Diameter (Change From Max)	Change (mm) from maximum pharmacologically-induced mydriatic pupil diameter (0 minutes)	30 minutes to 24 hours
Secondary	Percent of Subjects With Unchanged Accommodation From Baseline	Percentage of subjects with unchanged accommodation from baseline (-1 hour)	90 minutes to 6 Hours
Secondary	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