Safety and Efficacy of Ophthalmic Phentolamine Mesylate in Glaucoma

Study Overview
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Brief Summary
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The objectives of this study are: To evaluate the efficacy of Phentolamine Mesylate to lower intra-ocular pressure (IOP) in the treatment of Open-Angle Glaucoma (OAG) and Ocular Hypertension (OHT). To evaluate the ocular and systemic safety of Phentolamine Mesylate compared to its vehicle. To evaluate additional efficacy of Phentolamine Mesylate to improve visual performance.

Detailed Description
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Placebo-controlled double-masked, multiple dose Phase 2 study in 40 patients with IOP ≥ 22 and ≤30 mmHg, evaluating ocular and systemic safety and efficacy following administration of Phentolamine mesylate 1.0% QD at 8PM to 10PM in both eyes for 14 days.

Official Title
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Randomized, Placebo-Controlled, Double-Masked Study of the Safety and Efficacy of Phentolamine Mesylate Ophthalmic Solution in Subjects With Open Angle Glaucoma or Ocular Hypertension

Conditions
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Open Angle Glaucoma, Ocular Hypertension

Intervention / Treatment
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* Drug: Phentolamine Mesylate Ophthalmic Solution 1%
* Other: Phentolamine Mesylate Ophthalmic Solution Vehicle (Placebo)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or greater Diagnosis of open angle glaucoma (OAG) or ocular hypertension (OHT). A reported history of untreated OHT with IOP ≥22mmHg and ≤ 30mmHg is preferred. Untreated or treated OAG/OHT with 2 or fewer ocular hypotensive medications. Untreated (post-washout) mean IOP ≥ 22mmHg and ≤30mmHg in the study eye at the Qualification Visit (8AM). Corrected visual acuity in each eye +1.0 logMAR or better by Early Treatment Diabetic Retinopathy Study (ETDRS) in each eye (equivalent to 20/200 or better) at the Screening Visit and Qualification Visit. Otherwise healthy and well-controlled subjects. Able and willing to give signed informed consent and follow study instructions. Able to self-administer study medication or to have study medication administered by a caregiver throughout the study period. Exclusion Criteria: Closed or very narrow angles (Grade 0-1, Shaffer) Glaucoma: pseudo-exfoliation or pigment dispersion component Known hypersensitivity to any α-adrenoceptor antagonists Previous laser and/or non-laser glaucoma surgery or procedure in either eye Refractive surgery in either eye Ocular trauma in either eye within the 6 months prior to Screening, or ocular surgery or non-refractive laser treatment within the 3 months prior to Screening Recent or current evidence of ocular infection or inflammation in either eye Ocular medication in either eye of any kind within 30 days of Screening Clinically significant ocular disease in either eye History of diabetic retinopathy Contact lens wear within 3 days prior to and for the duration of the study Central corneal thickness in either eye >600 μm at Screening Any abnormality in either eye preventing reliable applanation tonometry Known hypersensitivity or contraindication to α- and/or β-adrenoceptor antagonists Clinically significant systemic disease that might interfere with the study Participation in any investigational study within 30 days prior to Screening Use of any topical or systemic adrenergic or cholinergic drugs up to 30 days prior to Screening, or during the study Changes in systemic medication that could have an effect on IOP within 30 days prior to Screening Women of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control Resting heart rate outside the normal range (50-110 beats per minute) at Screening or Qualification Visit Hypertension with resting diastolic blood pressure (BP) > 105 mmHg or systolic BP > 160 mmHg at the Screening or Qualification Visit

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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nyxol Ophthalmic Solution 1%<br>1 drop in each eye daily (QD) at or before bedtime (8pm to 10pm) for 14 days | Drug: Phentolamine Mesylate Ophthalmic Solution 1%<br>* Topical Sterile Ophthalmic Solution<br>* Other names: Nyxol®;|
| Placebo Comparator: Nyxol Ophthalmic Solution Vehicle<br>1 drop in each eye daily (QD) at or before bedtime (8pm to 10pm) for 14 days | Other: Phentolamine Mesylate 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 |
| --- | --- | --- |
| Intraocular Pressure | change from Baseline in mean diurnal IOP in the study eye | 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pupil Diameter | Change from Baseline Pupil Diameter (Photopic Conditions) | 15 days | 
| Distance Visual Acuity | Percentage of Subjects Achieving ≥1 line improvement in Distance Visual Acuity from Baseline measured at 4 meters (photopic conditions) | 15 days | 
| Conjunctival Hyperemia | Conjunctival Hyperemia Category | 15 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Open Angle Glaucoma, Ocular Hypertension