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

Phase 3

Completed

Interventions: Drug: Phentolamine Ophthalmic Solution Vehicle (Placebo)
Drug: Phentolamine Ophthalmic Solution 0.75%

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Phentolamine Ophthalmic Solution Vehicle	Phentolamine Ophthalmic Solution Vehicle (Placebo)	One drop in both eyes at or near bedtime (8PM to 10PM)
Phentolamine Ophthalmic Solution 0.75%	Phentolamine Ophthalmic Solution 0.75%	One drop in both eyes at or near bedtime (8PM to 10PM)

Primary Outcome Measures

Name	Time	Method
Percent of Subjects With 3 Lines mLCVA Improvement in Study Eye	8 days	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

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Study Eye Mesopic Pupil Diameter (PD)	up to 15 days	Change from baseline in study eye mesopic PD
Percent of Subjects With mLCVA Improvement in Study Eye	up to 15 days	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)
Percent of Subjects With Photopic Low Contrast Visual Acuity (pLCVA) and mHCVA Improvement in Study Eye	up to 15 days	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
Percent Change From Baseline in Study Eye Mesopic Pupil Diameter (PD)	up to 15 days	Percent change from baseline in study eye mesopic PD

Locations (17): Clinical Site 13
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Pittsburg, Kansas, United States
Clinical Site 1
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Petaluma, California, United States
Clinical Site 19
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Ogden, Utah, United States
Clinical Site 5
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San Antonio, Texas, United States
Clinical Site 4
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Elizabeth City, North Carolina, United States
Clinical Site 2
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Fargo, North Dakota, United States
Clinical Site 6
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Newport Beach, California, United States
Clinical Site 18
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Jacksonville, Florida, United States
Clinical Site 3
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Jacksonville, Florida, United States
Clinical Site 20
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Edgewood, Kentucky, United States
Clinical Site 10
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Palisades Park, New Jersey, United States
Clinical Site 9
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High Point, North Carolina, United States
Clinical Site 14
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Louisville, Kentucky, United States
Clinical Site 8
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Pennington, New Jersey, United States
Clinical Site 22
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High Point, North Carolina, United States
Clinical Test 15
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Warwick, Rhode Island, United States
Clinical Site 11
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Memphis, Tennessee, United States