Safety and Efficacy of Ophthalmic Phentolamine Mesylate in Glaucoma

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

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.

Study Overview

• Status: Completed
• Conditions: Ocular Hypertension; Open Angle Glaucoma
• Intervention / Treatment: Other: Phentolamine Mesylate Ophthalmic Solution Vehicle (Placebo); Drug: Phentolamine Mesylate Ophthalmic Solution 1%

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Mission Hills, California, United States, 91345
      • North Valley Eye Medical Group
  • Georgia
    • Morrow, Georgia, United States, 30260
      • Clayton Eye Clinical Research
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • University of Michigan Kellogg Eye Center
  • New York
    • Rochester, New York, United States, 14618
      • Rochester Ophthalmological Group
  • Ohio
    • Cleveland, Ohio, United States, 44115
      • Abrams Eye Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 18 years of age or greater
2. Diagnosis of open angle glaucoma (OAG) or ocular hypertension (OHT). A reported history of untreated OHT with IOP ≥22mmHg and ≤ 30mmHg is preferred.
3. Untreated or treated OAG/OHT with 2 or fewer ocular hypotensive medications.
4. Untreated (post-washout) mean IOP ≥ 22mmHg and ≤30mmHg in the study eye at the Qualification Visit (8AM).
5. 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.
6. Otherwise healthy and well-controlled subjects.
7. Able and willing to give signed informed consent and follow study instructions.
8. Able to self-administer study medication or to have study medication administered by a caregiver throughout the study period.

Exclusion Criteria:

1. Closed or very narrow angles (Grade 0-1, Shaffer)
2. Glaucoma: pseudo-exfoliation or pigment dispersion component
3. Known hypersensitivity to any α-adrenoceptor antagonists
4. Previous laser and/or non-laser glaucoma surgery or procedure in either eye
5. Refractive surgery in either eye
6. 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
7. Recent or current evidence of ocular infection or inflammation in either eye
8. Ocular medication in either eye of any kind within 30 days of Screening
9. Clinically significant ocular disease in either eye
10. History of diabetic retinopathy
11. Contact lens wear within 3 days prior to and for the duration of the study
12. Central corneal thickness in either eye >600 μm at Screening
13. Any abnormality in either eye preventing reliable applanation tonometry
14. Known hypersensitivity or contraindication to α- and/or β-adrenoceptor antagonists
15. Clinically significant systemic disease that might interfere with the study
16. Participation in any investigational study within 30 days prior to Screening
17. Use of any topical or systemic adrenergic or cholinergic drugs up to 30 days prior to Screening, or during the study
18. Changes in systemic medication that could have an effect on IOP within 30 days prior to Screening
19. Women of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control
20. Resting heart rate outside the normal range (50-110 beats per minute) at Screening or Qualification Visit
21. Hypertension with resting diastolic blood pressure (BP) > 105 mmHg or systolic BP > 160 mmHg at the Screening or Qualification Visit

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nyxol Ophthalmic Solution 1%; 1 drop in each eye daily (QD) at or before bedtime (8pm to 10pm) for 14 days	Drug: Phentolamine Mesylate Ophthalmic Solution 1%; Topical Sterile Ophthalmic Solution; Other Names: Nyxol®
Placebo Comparator: Nyxol Ophthalmic Solution Vehicle; 1 drop in each eye daily (QD) at or before bedtime (8pm to 10pm) for 14 days	Other: Phentolamine Mesylate Ophthalmic Solution Vehicle (Placebo); Topical Sterile Ophthalmic Solution

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ocuphire Pharma, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2019
• Primary Completion (Actual): September 11, 2019
• Study Completion (Actual): September 11, 2019

Study Registration Dates

• First Submitted: May 21, 2019
• First Submitted That Met QC Criteria: May 21, 2019
• First Posted (Actual): May 23, 2019

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: August 18, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Ocular Hypertension; Open Angle Glaucoma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Hypertension; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Adrenergic alpha-Antagonists; Ophthalmic Solutions; Pharmaceutical Solutions; Phentolamine
• Other Study ID Numbers: OPI-NYXG-201 (ORION-1)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No