Safety and Efficacy of Nyxol With Pilocarpine Eye Drops in Subjects With Presbyopia

Study Overview
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Brief Summary
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The objectives of this study are: To evaluate the efficacy of Nyxol + Pilocarpine to improve DCNVA in subjects with presbyopia

Official Title
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Safety and Efficacy of Nyxol (0.75% Phentolamine Ophthalmic Solution) With Pilocarpine Eye Drops in Subjects With Presbyopia

Conditions
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Presbyopia

Intervention / Treatment
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* Drug: Phentolamine Ophthalmic Solution 0.75%
* Drug: Pilocarpine
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females ≥ 40 and ≤ 64years of age. BCDVA of 0.0 LogMAR(20/20 Snellen equivalent) or better in each eye under photopic conditions. DCNVA of 0.4 LogMAR (20/50 Snellen equivalent) or worse under photopic conditions in each eye and binocularly. Subjects who depend on reading glasses or bifocals in which their binocular best-corrected near VA is 0.1 LogMAR (20/25 Snellen equivalent) or better. Exclusion Criteria: Ophthalmic (in either eye): Use of any topical prescription or OTC ophthalmic medications of any kind within 7 days of Screening until study completion. Use of any over-the-counter (OTC) artificial tears (preserved or unpreserved) at least once per day within 7 days of Screening until study completion. Current use of any topical ophthalmic therapy for dry eye. Tear break-up time of < 5 seconds or corneal fluorescein staining. Clinically significant ocular disease that might interfere with the study as deemed by the Investigator. Recent or current evidence of ocular infection or inflammation in either eye. Any history of herpes simplex or herpes zoster keratitis. History of diabetic retinopathy or diabetic macular edema. Known allergy, hypersensitivity, or contraindication to any component of the phentolamine, pilocarpine, or vehicle formulations. History of cauterization of the punctum or punctal plug (silicone or collagen) insertion or removal. Ocular trauma, ocular surgery, ocular laser treatment within the 6 months prior to Screening. Any subject with multifocal intraocular lenses are excluded. History of any traumatic (surgical or nonsurgical) or non traumatic condition affecting the pupil or iris. Unwilling or unable to discontinue use of contact lenses. Conjunctival hyperemia ≥ grade 2 on the CCLRU 4-point scale. Systemic: Known hypersensitivity or contraindication to alpha- and/or beta adrenoceptor antagonists. Known hypersensitivity or contraindication to any systemic cholinergic parasympathomimetic agents. Clinically significant systemic disease that might interfere with the study as deemed by the Investigator. 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 specified range of 50 to 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: 40 Years
Maximum Age: 64 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nyxol + Pilocarpine<br>1 drop of Nyxol (Treatment 1) and 1 drop of Pilocarpine (Treatment 2) | 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®;Drug: Pilocarpine<br>* Pilocarpine ophthalmic solution<br>|
| Active Comparator: Nyxol<br>1 drop of Nyxol (Treatment 1) | 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®;|
| Active Comparator: Pilocarpine<br>1 drop of Pilocarpine (Treatment 2) | Drug: Pilocarpine<br>* Pilocarpine ophthalmic solution<br>Other: Placebo<br>* Topical sterile ophthalmic solution<br>* Other names: Phentolamine Ophthalmic Solution Vehicle;|
| Placebo Comparator: Placebo<br>1 drop of Placebo (Treatment 1) | Other: Placebo<br>* Topical sterile ophthalmic solution<br>* Other names: Phentolamine Ophthalmic Solution Vehicle;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Subjects With ≥ 15 Letters of Improvement in Photopic Binocular DCNVA | The primary efficacy endpoint was the percent of subjects with ≥ 15 letters of improvement in photopic binocular DCNVA on Visit 2 at 1 hour with POS + LDP compared to placebo alone. The improvement in binocular DCNVA for each subject was relative to the subject's own baseline value (Visit 1). | Visit 2 at 1 hour | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Improvement of ≥ 5, ≥ 10, and ≥ 15 Letters in DCNVA (Photopic) From Baseline | The percentage of subjects with improvement of ≥ 5, ≥ 10, and ≥ 15 letters in DCNVA (photopic) from Baseline at 0.5 hours, at 2 hours, at 3 hours, at 4 hours, and at 6 hours | Visit 2 at 0.5 hours, at 2 hours, at 3 hours, at 4 hours, and at 6 hours | 
| Percentage of Subjects With Improvement of ≥ 15 Letters in DCNVA (Photopic) at 1 Hour and With < 5 Letters of Loss in Photopic Binocular BCDVA From Baseline | The percentage of subjects with improvement of ≥ 15 letters in DCNVA (photopic) at 1 hour and with < 5 letters of loss in photopic binocular BCDVA from Baseline | Visit 2 at 1 hour | 
| Percentage of Subjects With Improvement in DCIVA (Photopic) From Baseline | The percentage of subjects with improvement in DCIVA (photopic) from Baseline of ≥ 5, ≥ 10, and ≥ 15 letters | Visit 2 at 1 hour, at 3 hours, and at 6 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nyxol, Presbyopia, Pilocarpine