Nyxol (0.75% Phentolamine Ophthalmic Solution) to Reverse Pharmacologically-Induced Mydriasis in Pediatric Subjects (MIRA-4)

• ClinicalTrials.gov Identifier: NCT05223478
• Recruitment Status: Completed
• First Posted: February 4, 2022
• 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 safety of Nyxol in pediatric subjects
• To evaluate the efficacy of Nyxol to expedite the reversal of pharmacologically induced mydriasis in pediatric subjects The Sponsor intends to use this study to evaluate Nyxol in pediatric subjects aged 3 to 11 for the indication "the treatment of pharmacologically induced mydriasis produced by adrenergic (phenylephrine) or parasympatholytic (tropicamide) agents, or a combination thereof."

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

Detailed Description:

This is a randomized, parallel-arm, double-masked, placebo-controlled study in approximately 20 randomized pediatric subjects evaluating the safety and efficacy of Nyxol in pediatric subjects with pharmacologically induced mydriasis with three dilating agents (e.g., phenylephrine, tropicamide, and Paremyd). Pediatric subjects will be recruited for the study into 2 age groups as follows:1) 3 to 5 years of age: 10 subjects 2) 6 to 11 years of age: 10 subjects.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 23 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 Pediatric Subjects
• Actual Study Start Date: December 17, 2021
• Actual Primary Completion Date: April 18, 2022
• Actual Study Completion Date: April 28, 2022

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Phentolamine Ophthalmic Solution 0.75%; One drop of study medication in each eye.	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; One drop of study medication in each eye.	Drug: Phentolamine Ophthalmic Solution Vehicle; Phentolamine Ophthalmic Solution Vehicle

Outcome Measures

Primary Outcome Measures :

1. Safety Measurements [ Time Frame: 0 Minutes ]
   Change from Baseline (-1 Hour) Conjunctival Hyperemia Grading; Cornea and Contact Lens Research Unit (CCLRU scale) Grades range from 0 to 4, with 4 being considered the most severe.
2. Safety Measurements [ Time Frame: 90 Minutes ]
   Change from Baseline (-1 Hour) Conjunctival Hyperemia Grading; Cornea and Contact Lens Research Unit (CCLRU scale) Grades range from 0 to 4, with 4 being considered the most severe.
3. Safety Measurements [ Time Frame: 3 Hours ]
   Change from Baseline (-1 Hour) Conjunctival Hyperemia Grading; Cornea and Contact Lens Research Unit (CCLRU scale) Grades range from 0 to 4, with 4 being considered the most severe.
4. Safety Measurements [ Time Frame: 24 Hours ]
   Change from Baseline (-1 Hour) Conjunctival Hyperemia Grading; Cornea and Contact Lens Research Unit (CCLRU scale) Grades range from 0 to 4, with 4 being considered the most severe.
5. Vital Signs [ Time Frame: 3 Hours ]
   Change from Screening Heart Rate
6. Vital Signs [ Time Frame: 3 Hours ]
   Change from Screening Blood Pressure
7. Vital Signs [ Time Frame: 24 Hours ]
   Change from Screening Heart Rate
8. Vital Signs [ Time Frame: 24 Hours ]
   Change from Screening Blood Pressure
9. Safety Measurement [ Time Frame: 0 Minutes ]
   Change from Baseline (-1 Hour) Best Corrected Distance Visual Acuity
10. Safety Measurement [ Time Frame: 3 Hours ]
    Change from Baseline (-1 Hour) Best Corrected Distance Visual Acuity
11. Safety Measurement [ Time Frame: 24 Hours ]
    Change from Baseline (-1 Hour) Best Corrected Distance Visual Acuity

Secondary Outcome Measures :

1. Efficacy Measurement: Pupil Diameter [ Time Frame: 0 Minutes, 90 Minutes, 3 Hours, and 24 Hours ]
   Percentage of Subjects Returning to ≤ 0.2 mm from Baseline (-1 hour) Pupil Diameter
2. Efficacy Measurement: Pupil Diameter [ Time Frame: 90 Minutes, 3 Hours, and 24 Hours ]
   Change (in mm) in Pupil Diameter from Max Pupil Dilation (0 minutes)
3. Efficacy Measurement: Pupil Diameter [ Time Frame: Up to 24 Hours ]
   Time (Hours) to Return to ≤ 0.2 mm from Baseline (-1 Hour) Pupil Diameter (Time-savings Analysis)

Eligibility Criteria

• Ages Eligible for Study: 3 Years to 11 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Males or premenstrual females 3 to 11 years of age
2. Ability to comply with all protocol-mandated procedures independently and to attend all scheduled office visits
3. Parent/Legal guardian willing to give written informed consent to participate in this study. Children aged 7 to 11 years to provide signed assent form, as well as a separate parental/legal guardian consent.

Exclusion Criteria:

1. Clinically significant ocular disease as deemed by the Investigator(eg, amblyopia, congenital cataract, congenital glaucoma) 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 or ocular surgery 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
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. History of any traumatic (surgical or nonsurgical) or non-traumatic condition affecting the pupil or iris

9. Known allergy, hypersensitivity, or contraindication to any component of the phentolamine ophthalmic solution or to any component of the mydriatic agents or vehicle formulation

   Systemic:

10. Known hypersensitivity or contraindication to α- and/or β-adrenoceptor antagonists
11. Clinically significant systemic disease (eg, uncontrolled diabetes, cancer, hepatic, renal, endocrine, or cardiovascular disorders) that in the opinion of the Investigator could interfere with the study
12. Subjects with learning disabilities that in the opinion of the investigator could interfere with the study
13. Initiation of treatment with or any changes to the current dosage, drug, or regimen of any systemic adrenergic or cholinergic drugs within 7 days prior to screening or during the study(Appendix 4)
14. Participation in any investigational study within 30 days prior to screening

Contacts and Locations

Locations

United States, Florida

Clinical Site 1

Longwood, Florida, United States, 32779

United States, Ohio

Clinical Site 2

Athens, Ohio, United States, 45701

Sponsors and Collaborators

Ocuphire Pharma, Inc.

Investigators

• Study Director: Charles Slonim, MD; Oculos Development Services

More Information

• Responsible Party: Ocuphire Pharma, Inc.
• ClinicalTrials.gov Identifier: NCT05223478
• Other Study ID Numbers: OPI-NYXRMP-303 (MIRA-4)
• First Posted: February 4, 2022
• 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; Pediatrics; Phentolamine; Mydriasis; Phenylephrine; Tropicamide; Paremyd

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