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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Mydriasis, Dilation

Intervention / Treatment
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* Drug: Phentolamine Ophthalmic Solution 0.75%
* Drug: Phentolamine Ophthalmic Solution Vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or premenstrual females 3 to 11 years of age Ability to comply with all protocol-mandated procedures independently and to attend all scheduled office visits 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: Clinically significant ocular disease as deemed by the Investigator(eg, amblyopia, congenital cataract, congenital glaucoma) that might interfere with the study Unwilling or unable to discontinue use of contact lenses at screening until study completion Unwilling or unable to suspend use of topical medication at screening until study completion Ocular trauma or ocular surgery within the 6 months prior to screening Use of any topical prescription or over-the-counter (OTC)ophthalmic medications of any kind within 7 days of screening 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 Closed or very narrow-angle that in the Investigator's opinion is potentially occludable if the subject's pupil is dilated History of any traumatic (surgical or nonsurgical) or non-traumatic condition affecting the pupil or iris 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: Known hypersensitivity or contraindication to α- and/or β-adrenoceptor antagonists 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 Subjects with learning disabilities that in the opinion of the investigator could interfere with the study 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) Participation in any investigational study within 30 days prior to screening

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 11 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Phentolamine Ophthalmic Solution 0.75%<br>One drop of study medication in each eye. | Drug: Phentolamine Ophthalmic Solution 0.75%<br>* 0.75% phentolamine ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist<br>* Other names: Nyxol;|
| Placebo Comparator: Phentolamine Ophthalmic Solution Vehicle<br>One drop of study medication in each eye. | Drug: Phentolamine Ophthalmic Solution Vehicle<br>* Phentolamine Ophthalmic Solution Vehicle<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nyxol, Pharmacologically Induced Mydriasis, Dilation, Pediatrics, Phentolamine, Mydriasis, Phenylephrine, Tropicamide, Paremyd