Safety and Efficacy of 0.75% Phentolamine Ophthalmic Solution in Subjects With Post-refractive Surgery Visual Disturbances

Randomized, placebo-controlled, double-masked study of the safety and efficacy of POS (0.75% Phentolamine Ophthalmic Solution) in subjects who have previously had keratorefractive surgery and have decreased visual acuity (VA) under mesopic conditions

Inclusion criteria

• Males or females ≥ 18 years of age
• Previous history of refractive surgery (eg, PRK, LASIK, SMILE, and RK) and have subject-reported night vision disturbances (eg, glare, halos, and/or starbursts). Symptoms must have been first noted within 2 months following refractive surgery
• Able to independently comply with all protocol-mandated procedures and to attend all scheduled office visits
• Able and willing to give written consent to participate in this study
• Able to self-administer study medication

Inclusion criteria

#6, #7, and #8 must all be met in the same eye:

• PD ≥ 5 mm under mesopic conditions in at least 1 eye. This test may be repeated once, following an additional 5 min of dark adaptation to the mesopic light conditions if the initial results do not meet this criterion
• mLCVA ≤ 30 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (20/63 Snellen or worse) in at least 1 eye using the Precision Vision Illuminator Cabinet with 5% translucent contrast chart and a mesopic filter at 4 m
• ≥ 10 ETDRS letters improvement in mLCVA in at least 1 eye during illumination of the contralateral eye with a Brightness Acuity Tester (BAT) system on the low setting using the Precision Vision Illuminator Cabinet with 5% translucent contrast chart and a mesopic filter at 4 m

Exclusion criteria

Ophthalmic (in either eye):

• Prior unresolved dry eye diagnosis, taking prescription drops for dry eye, or taking artificial tear drops routinely for dry eye
• Prior history of fluctuating vision
• Clinically significant ocular disease as deemed by the Investigator (eg, untreated visually significant cataract, glaucoma, corneal edema, uveitis, severe keratoconjunctivitis sicca, retina degeneration, loss of visual field due to glaucoma or stroke, branch retinal vein occlusion, retina flare) that might interfere with the study
• History or presence of corneal endothelial dystrophy (eg, Fuchs' dystrophy or presence of guttae)
• 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
• Pseudophakic subjects with extended depth-of-focus or multifocal intraocular lenses (IOLs)
• Ocular trauma, ocular surgery (eg, IOLs), or laser procedure (eg, LASIK, PRK, SMILE, and RK) within 6 months prior to Screening
• Use of any topical prescription or over-the-counter (OTC) ophthalmic medications of any kind (including artificial tear drops) within 7 days prior to Screening until study completion, with the exception of lid scrubs with OTC products (eg, OCuSOFT® lid scrub, SteriLid®, baby shampoo, etc.)
• Recent or current evidence of ocular infection or inflammation (such as current evidence of clinically significant blepharitis, conjunctivitis, or a history of herpes simplex or herpes zoster keratitis at Screening). Subjects must be symptom free for at least 7 days prior to Screening
• 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 (eg, irregularly shaped pupil, neurogenic pupil disorder, iris atrophy, iridotomy, iridectomy, etc.)
• Unwilling or unable to discontinue use of contact lenses at least 1 hour prior to Screening for soft contact lenses or at least 8 hours prior to Screening for hard gas-permeable contact lenses, and at least 8 hours (for both types of lenses) prior to all other office visits
• Previously undiagnosed dry eye, at the determination of the Investigator. Dry eye diagnosis should be based on one of the following dry eye test results: tear break-up time < 5 seconds, or corneal fluorescein staining ≥ Grade 2 in the inferior zone or ≥ Grade 1 in the central zone using the National Eye Institute scale

Systemic:

• Known hypersensitivity or contraindication to alpha- and/or beta-adrenoceptor antagonists (eg, chronic obstructive pulmonary disease or bronchial asthma; abnormally low BP or HR; second- or third-degree heart blockage or congestive heart failure; or severe diabetes as defined below)

• Predisposition to severe hypoglycemia (2 or more serious hypoglycemic episodes requiring assistance within 12 months prior to Screening)
• Any hospitalization or emergency room visit due to poor diabetic control within 6 months prior to Screening
• Currently untreated diabetes mellitus or previously untreated subjects who initiated oral anti-diabetic medication or insulin within 3 months prior to Screening
• Any sign of diabetic retinopathy in either eye
• Clinically significant systemic disease (eg, severe diabetes as previously defined, myasthenia gravis, cancer, hepatic, renal, endocrine, or cardiovascular disorders) 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 or during the study
• Females of childbearing potential who are pregnant, nursing, planning a pregnancy during the study, or not using a medically acceptable form of birth control. Acceptable methods include the use of at least one of the following: intrauterine device, hormonal (oral, injection, patch, implant, ring), barrier with spermicide (condom, diaphragm), or abstinence. A female is considered to be of childbearing potential unless she is 1 year postmenopausal or 3 months post-surgical sterilization. All females of childbearing potential including those post-tubal ligation must have a negative urine pregnancy test result at each visit
• Resting HR outside 50 to 110 beats per min at Screening. HR may be repeated only once if outside the specified range, following at least a 5-min rest period in the sitting position
• Hypertension with resting diastolic BP > 105 mmHg or systolic BP > 160 mmHg at Screening. BP may be repeated only once if outside the specified range, following at least a 5-min rest period in the sitting position