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

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

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."

Study Overview

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

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 Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Florida
    • Longwood, Florida, United States, 32779
      • Clinical Site 1
  • Ohio
    • Athens, Ohio, United States, 45701
      • Clinical Site 2

Participation Criteria

Eligibility Criteria

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

Description

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

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
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Measurements	Study Eye Change from Baseline (-1 Hour) Conjunctival Hyperemia Grading; Cornea and Contact Lens Research Unit (CCLRU scale) Grades range from 0 to 3, with 3 being considered the most severe.	0 Minutes, 90 Minutes, 3 Hours, 24 Hours
Vital Signs	Change from Screening Heart Rate	3 Hours, 24 Hours
Vital Signs	Change from Screening Blood Pressure (Systolic)	3 Hours, 24 Hours
Safety Measurement	Study Eye Change from Baseline (-1 Hour) in Best Corrected Distance Visual Acuity	0 Minutes, 3 Hours, 24 Hours
Change From Screening Blood Pressure (Diastolic)		3 Hours, 24 Hours

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Ocuphire Pharma, Inc.
• Investigators: Study Director: Charles Slonim, MD, Oculos Development Services

Study record dates

Study Major Dates

• Study Start (Actual): December 17, 2021
• Primary Completion (Actual): April 18, 2022
• Study Completion (Actual): April 28, 2022

Study Registration Dates

• First Submitted: December 16, 2021
• First Submitted That Met QC Criteria: January 19, 2022
• First Posted (Actual): February 4, 2022

Study Record Updates

• Last Update Posted (Actual): September 5, 2023
• Last Update Submitted That Met QC Criteria: August 8, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Pediatrics; Nyxol; Pharmacologically Induced Mydriasis; Dilation; Mydriasis; Phenylephrine; Tropicamide; Phentolamine; Paremyd
• 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-NYXRMP-303 (MIRA-4)

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