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

Study Overview
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Brief Summary
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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

Detailed Description
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A randomized, parallel arm, double-masked, placebo-controlled Phase 3 study in at least 168 randomized subjects (160 completed), 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 1:1, Nyxol or placebo (vehicle). Stratification by iris color will be 1:1, light or dark irides. The mydriatic agent randomization will be 3:1:1 (2.5% phenylephrine, 1% tropicamide, and Paremyd). That is, approximately 60% of the randomized subjects will receive one drop of 2.5% phenylephrine 1 hour before treatment (96 completed subjects), approximately 20% will receive one drop of 1% tropicamide 1 hour before treatment (32 completed subjects), and approximately 20% will receive Paremyd 1 hour before treatment (32 completed subjects). 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. At the Follow-Up Visit, which is 1 day after Visit 1, measurements will again be recorded 24 hours after treatment dosing.

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 Subjects

Conditions
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Mydriasis, Dilation

Intervention / Treatment
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* Drug: Phentolamine Ophthalmic Solution 0.75%
* Other: Phentolamine Ophthalmic Solution Vehicle (Placebo)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females ≥ 12 years of age Otherwise healthy and well controlled subjects Exclusion Criteria: Ophthalmic (in either eye): Clinically significant ocular disease as deemed by the Investigator 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, ocular surgery or non-refractive laser treatment 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 History of diabetic retinopathy or diabetic macular edema Closed or very narrow angles that in the Investigator's opinion are 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 or contraindication to any component of the mydriatic agents or the vehicle formulation History of cauterization of the punctum or punctal plug (silicone or collagen) insertion or removal Systemic: Known hypersensitivity or contraindication to α- and/or β adrenoceptor antagonists. Clinically significant systemic disease that might 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 Participation in any investigational study within 30 days prior to screening Females of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control Resting HR outside the normal range (50-110 beats per minute) Hypertension with resting diastolic BP > 105 mmHg or systolic BP > 160 mmHg

Ages Eligible for Study
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Minimum Age: 12 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phentolamine Ophthalmic Solution 0.75%<br>2 drops in study eye and 1 drop in non-study eye, 1 hour post pharmacologically-induced mydriasis | 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>2 drops in study eye and 1 drop in non-study eye, 1 hour post pharmacologically-induced mydriasis | Other: Phentolamine Ophthalmic Solution Vehicle (Placebo)<br>* Topical sterile ophthalmic solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Subjects' Study Eyes Pupil Diameter Returning to Baseline | Percentage of subjects' study eyesreturning to less than or equal to 0.2 mm from baseline pupil diameter | up to 24 hours | 
| Pupil Diameter (Change From Max) | Change (mm) from maximum pharmacologically-induced mydriatic pupil diameter (0 minutes) | up to 24 hours | 
| Percent of Subjects With Unchanged Accommodation From Baseline | Percentage of subjects with unchanged accommodation from baseline (-1 hour) | up to 6 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