Safety and Efficacy of Nyxol (0.75% Phentolamine Ophthalmic Solution) in Subjects With Dim Light Vision Disturbances

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 improve mesopic low contrast visual acuity (mLCVA) in subjects with Dim Light Vision Disturbances (DLD) To evaluate efficacy of Nyxol to improve visual performance To evaluate the safety of Nyxol

Detailed Description
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Placebo-controlled, double-masked, multiple-dose, Phase 3 study in approximately 160 randomized subjects with DLD (approximately 136 that are evaluable for efficacy), evaluating safety and efficacy of Nyxol in subjects with DLD following administration of Nyxol once daily (QD) at or near bedtime (at 8PM to 10PM) in both eyes (OU) for 14 days. Following the successful completion of screening, each subject will be stratified by iris color (light/dark irides) and will then be randomized to treatment (masked) 1:1, Nyxol or placebo (vehicle). Treatment (Nyxol or placebo) will be administered in both eyes (OU) by the subjects at or near bedtime each day. At the first visit subjects will be screened for study eligibility. Treatment visits will occur 2 times: Day 8 (+1 day)/Visit 2 and Day 15 (+1 day)/Visit 3. mLCVA evaluations shall be performed on each of these days. A follow-up visit (Visit 4) phone call will occur 1 to 3 days after Visit 3. At select sites OPD Scan measurements will be made using wavefront abhermettry.

Official Title
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Randomized, Placebo-Controlled, Double-Masked Study of the Safety and Efficacy of Nyxol (0.75% Phentolamine Ophthalmic Solution) in Subjects With Dim Light Vision Disturbances

Conditions
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Dim Light Vision Disturbances

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females ≥ 18 years of age Subject-reported DLD (likely subjects with a history of multifocal IOLs, post-laser-assisted in situ keratomileusis [LASIK], corneal scars, and keratoconus) Ability to comply with all protocol-mandated procedures independently and to attend all Otherwise healthy and well-controlled subjects Able and willing to give written consent to participate in this study Able to self-administer study medication PD ≥ 6 mm under mesopic conditions (prior to illumination) in at least one eye ≤ 20 (20/100 Snellen or worse) ETDRS letters in mLCVA score Exclusion Criteria: Ophthalmic: Prior history of dry eye diagnosis, taking prescription drops for dry eye, or taking artificial tear drops occasionally for dry eye Prior history of fluctuating vision Clinically significant ocular disease as deemed by the Investigator that might interfere with the study Known hypersensitivity to any topical alpha-adrenoceptor antagonists Known allergy or contraindication to any component of the vehicle formulation History of cauterization of the punctum or punctal plug (silicone or collagen) insertion or removal Ocular trauma, ocular surgery (e.g., IOLs) or laser procedure (e.g., LASIK, photorefractive keratectomy [PRK]) within 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. Subjects must be symptom free for at least 7 days. History of diabetic retinopathy, diabetic macular edema, or dry or wet macular degeneration History of any traumatic (surgical or nonsurgical) or nontraumatic condition affecting the pupil or iris Unwilling or unable to discontinue use of contact lenses at screening until study completion, except for keratoconus subjects who may wear contacts up to 24 hours prior to their scheduled visits Systemic: Known hypersensitivity or contraindication to alpha- and/or beta-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 and during the conduct of the study 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 specified 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: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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
Interventional Model Description: All subjects will be randomized into the study in a 1:1 ratio to one of the treatment arms (Nyxol or placebo), with a stratification by light/dark irides.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phentolamine Ophthalmic Solution 0.75%<br>One drop in both eyes at or near bedtime (8PM to 10PM) | 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 in both eyes at or near bedtime (8PM to 10PM) | Drug: 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 With 3 Lines mLCVA Improvement in Study Eye | Percent of subjects with ≥ 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (≥3 lines) of improvement in the study eye compared to baseline in monocular mLCVA at Day 8 | 8 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Subjects With mLCVA Improvement in Study Eye | Percent of subjects with ≥ 5, ≥ 10, and ≥ 15 ETDRS letters (≥ 1, ≥ 2, and ≥ 3 lines, respectively) improvement compared to baseline in mLCVA at Day 8 (excluding the primary endpoint) | up to 15 days | 
| Percent of Subjects With Photopic Low Contrast Visual Acuity (pLCVA) and mHCVA Improvement in Study Eye | Percent of subjects with ≥ 5, ≥ 10, and ≥ 15 ETDRS letters (≥ 1, ≥ 2, and ≥ 3 lines, respectively) improvement compared to baseline in pLCVA and mHCVA at Day 8 and Day 15 | up to 15 days | 
| Change From Baseline in Study Eye Mesopic Pupil Diameter (PD) | Change from baseline in study eye mesopic PD | up to 15 days | 
| Percent Change From Baseline in Study Eye Mesopic Pupil Diameter (PD) | Percent change from baseline in study eye mesopic PD | up to 15 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nyxol, Night Vision Disturbances, Glare, Halos, Starbursts