Evaluate Efficacy and Safety of POS to Improve Distance-corrected Near Visual in Participants With Presbyopia (VEGA-3)

Randomized, Double-masked, Placebo-controlled, Multicenter Study of the Efficacy and Safety of Phentolamine Ophthalmic Solution (POS) 0.75% in Participants With Presbyopia

Safety and efficacy of POS in participants with presbyopia

Study Overview

• Status: Completed
• Conditions: Presbyopia
• Intervention / Treatment: Drug: Placebo; Drug: 0.75% phentolamine ophthalmic solution

Detailed Description

Randomized, Double-Masked, Placebo-Controlled, Multicenter, Phase 3 Study of the Efficacy and Safety of Phentolamine Ophthalmic Solution (POS) 0.75% in Participants with Presbyopia

• Study Type: Interventional
• Enrollment (Actual): 569
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Arizona Eye Center
    • Mesa, Arizona, United States, 85202
      • Carrot Eye Center
    • Phoenix, Arizona, United States, 85028
      • Eye Doctors of Arizona
    • Scottsdale, Arizona, United States, 85260
      • MRB Eye Care Consultants, LLC
  • California
    • Bakersfield, California, United States, 93309
      • Empire Eye & Laser Center
    • Glendale, California, United States, 91204
      • Global Research Management, Inc.
    • La Jolla, California, United States, 92307
      • Gordon Schanzlin New Vision Institute
    • Murrieta, California, United States, 92562
      • LoBue Laser and Eye Medical Center, Inc.
    • Newport Beach, California, United States, 92663
      • Eye Research Foundation
    • Torrance, California, United States, 90505
      • Wolstan and Goldberg Eye Associates
  • Florida
    • Delray Beach, Florida, United States, 33484
      • Segal Drug Trials, Inc.
    • Delray Beach, Florida, United States, 33484
      • South Florida Glaucoma
    • Jacksonville, Florida, United States, 32256
      • Bowden Eye & Associates
    • Jacksonville, Florida, United States, 32204
      • Levenson Eye
    • Largo, Florida, United States, 33773
      • Shettle Eye Research
    • Longwood, Florida, United States, 32779
      • Sabal Eye Care/dba Omega Vision Center
    • Mt. Dora, Florida, United States, 32757
      • Mid Florida Eye Center
  • Illinois
    • Rock Island, Illinois, United States, 61201
      • Virdi Eye Clinic
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Price Vision Group
  • Kansas
    • Overland Park, Kansas, United States, 66210
      • Durrie Vision
    • Pittsburg, Kansas, United States, 66762
      • Kannarr Eye Care
    • Shawnee Mission, Kansas, United States, 66204
      • Heart of America Eye Care, P.A.
  • Kentucky
    • Louisville, Kentucky, United States, 40206
      • The Eye Care Institute
  • Michigan
    • Fraser, Michigan, United States, 48026
      • Fraser Eye Care Center
  • Missouri
    • Kansas City, Missouri, United States, 64154
      • Moyes Eye Center
  • New York
    • Rochester, New York, United States, 14618
      • Rochester Ophthalmological Group
  • North Carolina
    • Garner, North Carolina, United States, 27529
      • Oculus Research , Inc.
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Red River Research Partners
    • Fargo, North Dakota, United States, 58103
      • Bergstrom Eye
  • Ohio
    • Athens, Ohio, United States, 45701
      • Athens Eye Care
  • Rhode Island
    • Warwick, Rhode Island, United States, 02888
      • West Bay Eye Associates
  • Tennessee
    • Goodlettsville, Tennessee, United States, 37072
      • Advancing Vision Research
    • Memphis, Tennessee, United States, 38119
      • Total Eye Care
    • Memphis, Tennessee, United States, 38111
      • Optometry Group
  • Texas
    • Houston, Texas, United States, 77055
      • Whitsett Vision Group
    • Lakeway, Texas, United States, 78738
      • Lake Travis Eye and Laser Center/ Revolution Research
    • Richardson, Texas, United States, 75080
      • Red River Research Partners
    • San Antonio, Texas, United States, 78229
      • Parkhurst NuVision
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Eye Institute of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Participants must meet all of the following criteria:

1. Males or females ≥ 45 and ≤ 64 years of age
2. Able to comply with all protocol-mandated procedures independently and to attend all scheduled office visits
3. Able and willing to give signed informed consent

4. Able to self-administer study medication throughout the study period

   Inclusion criteria #5, #6, and #7 must all be met at both Screening and Baseline Visits:

5. BCDVA of 55 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (20/20 Snellen equivalent) or better in photopic conditions in each eye
6. DCNVA of 50 ETDRS letters (20/50 Snellen equivalent) or worse but not <35 ETDRS letters (20/100 Snellen equivalent) in photopic conditions in each eye and binocularly
7. For participants who depend on reading glasses or bifocals, binocular best-corrected near VA of 65 ETDRS letters (20/25 Snellen equivalent) or better
8. Photopic PD of ≥ 4 mm in the study eye at Screening

Exclusion Criteria:

Excluded from the study will be individuals with any of the following characteristics:

Ophthalmic (in either eye):

1. Use of any topical prescription (including Vuity® or Qlosi™) or over-the-counter (OTC) ophthalmic medications of any kind within 7 days of Screening until study completion, with the exception of lid scrubs with OTC products (eg, OCuSOFT® lid scrub, SteriLid®, baby shampoo, etc.) and artificial tears as specified in Exclusion Criterion #2 below
2. Use of any OTC artificial tears (preserved or unpreserved) during visit days or 15 min before or after instillation of study medication
3. Use of Ryzumvi™ (POS) within 7 days prior to Screening
4. Use of any dry eye product, such as topical ophthalmic therapy for dry eye (eg, generic cyclosporine, Restasis®, Xiidra®, Cequa®, Eysuvis®, and Meibo®) or intranasal dry eye product (eg, Tyrvaya®) or other devices within 12 months prior to Screening
5. Tear break-up time of < 5 seconds or corneal fluorescein staining (CFS) Grade ≥ 2 in the inferior zone or Grade ≥ 1 in the central zone using the National Eye Institute scale
6. Clinically significant ocular disease (eg, cataract, glaucoma, corneal edema, uveitis, retinal degeneration, loss of visual field, or any macular pathology) that, in the judgment of the Investigator, might interfere with study procedures
7. Recent or current evidence of ocular infection or inflammation in either eye (such as current evidence of clinically significant blepharitis, conjunctivitis, keratitis, etc.). Participants must be symptom free for at least 7 days prior to Screening
8. Any history of herpes simplex or herpes zoster keratitis
9. Known allergy, hypersensitivity, or contraindication to any component of the phentolamine or vehicle formulations
10. Prior participation in a study involving the use of POS for the treatment of presbyopia or night vision disturbance
11. History of cauterization of the punctum or punctal plug (silicone or collagen) insertion or removal
12. Ocular trauma within 6 months prior to Screening
13. Ocular surgery or any ocular laser treatment within 6 months prior to Screening. Any history of radial keratotomy is prohibited
14. Participants with surgical monovision, multifocal, or extended depth-of-focus intraocular lenses (IOLs). Monofocal IOLs are acceptable if in place > 6 months prior to Screening
15. Monofocal IOL in place > 6 months prior to Screening with any posterior capsule opacification
16. 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, iritis, etc.)

17. 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

    Systemic:

18. Known hypersensitivity or contraindication to alpha- and/or beta-adrenoceptor antagonists (eg, chronic obstructive pulmonary disease or bronchial asthma; abnormally low blood pressure (BP) or heart rate (HR); second- or third-degree heart blockage or congestive heart failure)
19. Known hypersensitivity or contraindication to any systemic cholinergic parasympathomimetic agent
20. Clinically significant systemic disease (eg, uncontrolled diabetes, myasthenia gravis, cancer, hepatic, renal, endocrine, or cardiovascular disorders) that might interfere with the study as deemed by the judgment of the Investigator
21. 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; however, Flomax® (tamsulosin) is specifically excluded
22. Participation in any investigational study within 30 days prior to Screening
23. Females of childbearing potential who are pregnant, nursing, planning a pregnancy, 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 contraception (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 with post-tubal ligation, must have a negative urine pregnancy test result at Visit 1 (Screening)
24. Resting HR outside the range of 50 to 110 beats per min (bpm) following at least a 5 min rest period in the sitting position at Visit 1 (Screening). HR may be repeated only once if outside the specified range, following another 5 min rest period in the sitting position
25. Hypertension with resting diastolic BP > 105 mmHg or systolic BP > 160 mmHg following at least a 5-min rest period in the sitting position at Visit 1 (Screening). BP may be repeated only once if outside the specified range, following another 5-min rest period in the sitting position

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
Active Comparator: 0.75% phentolamine ophthalmic solution; Drug: phentolamine ophthalmic solution 0.75%, a non-selective alpha-1 and alpha-2 adrenergic antagonist	Drug: 0.75% phentolamine ophthalmic solution; Once daily dosing; Other Names: Nyxol
Placebo Comparator: phentolamine ophthalmic solution vehicle; Drug: Placebo	Drug: Placebo; Once daily dosing; Other Names: phentolamine ophthalmic solution vehicle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With ≥ 15 Letters of Improvement in Binocular DCNVA and With < 5 Letters of Loss in Binocular BCDVA From Baseline Comparing POS-treated Participants to Placebo-treated Participants at 12 Hours Post-dose at Visit 4 (Day 8)	The primary efficacy endpoint is the percentage of participants with ≥ 15 letters of improvement in binocular DCNVA and with < 5 letters of loss in binocular BCDVA from baseline comparing POS-treated participants to placebo-treated participants at 12 hours post-dose at Visit 4 (Day 8).	8 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With ≥ 15 Letters of Improvement in Binocular DCNVA and With < 5 Letters of Loss in Binocular BCDVA From Baseline at Day 1 (1-hour Post-dose), Day 3, and Week 6	This secondary efficacy endpoint is the percentage of participants with ≥ 15 letters of improvement in binocular DCNVA and with < 5 letters of loss in binocular BCDVA from baseline comparing POS-treated participants to placebo-treated participants at 12 hours post-dose at Day 1 (1-hour post-dose), Day 3, and Week 6.	6 Weeks
Percentage of Subjects With ≥ 5, ≥ 10, and ≥ 15 Letters of Improvement in DCNVA From Baseline (Binocular) at Day 1 (0.5 Hours and 1 Hour Post-dose), Day 3, Day 8, and Week 6	The percentage of Subjects With ≥ 5, ≥ 10, and ≥ 15 Letters of Improvement in DCNVA From Baseline (Monocular and Binocular) at Day 1 (0.5 hours and 1 hour post-dose), Day 3, Day 8, and Week 6.	6 Weeks
Percentage of Subjects With ≥ 5, ≥ 10, and ≥ 15 Letters of Improvement in DCNVA From Baseline (Monocular - Study Eye) at Day 1 (0.5 Hours and 1-hour Post-dose), Day 3, Day 8, and Week 6	This outcome measure will investigate the percentage of subjects with ≥ 5, ≥ 10, and ≥ 15 letters of improvement in DCNVA from baseline (monocular - study eye) at Day 1 (0.5 hours and 1-hour post-dose), Day 3, Day 8, and Week 6.	6 Weeks
Change in DCNVA From Baseline (Binocular) at Day 1 (0.5 Hours and 1-hour Post-dose), Day 3, Day 8, and Week 6	This outcome measure will investigate the change in DCNVA from baseline (binocular) at Day 1 (0.5 hours and 1-hour post-dose), Day 3, Day 8, and Week 6.	6 Weeks
Change in DCNVA From Baseline (Monocular - Study Eye) at Day 1 (0.5 Hours and 1-hour Post-dose), Day 3, Day 8, and Week 6	This outcome measure will investigate the Change in DCNVA From Baseline (Monocular - Study Eye) at Day 1 (0.5 hours and 1-hour post-dose), Day 3, Day 8, and Week 6	6 Weeks
Change in Mean Binocular DCNVA From Baseline at Week 6 Compared to the Best Prior Observed Change From Baseline in Mean Binocular DCNVA in Subjects Treated With POS	This outcome measure investigates the change in mean binocular DCNVA from baseline at Week 6 compared to the best prior observed change from baseline in mean binocular DCNVA in subjects treated with POS.	6 Weeks
Percentage of Subjects With DCNVA ≤ 20/15, ≤ 20/20, ≤ 20/25, ≤ 20/32, ≤ 20/40, ≤ 20/50, ≤ 20/63, ≤ 20/80, ≤ 20/100, ≤ 20/125, and ≤ 20/160 at Day 1 (0.5 Hours and 1-hour Post-dose), Day 3, Day 8, and Week 6	This outcome measure will investigate the percentage of subjects with DCNVA ≤ 20/15, ≤ 20/20, ≤ 20/25, ≤ 20/32, ≤ 20/40, ≤ 20/50, ≤ 20/63, ≤ 20/80, ≤ 20/100, ≤ 20/125, and ≤ 20/160 at Day 1 (0.5 hours and 1-hour post-dose), Day 3, Day 8, and Week 6.	6 Weeks
Percentage of Subjects With Baseline DCNVA ≤ 20/63, ≤ 20/80, ≤ 20/100, ≤ 20/125, and ≤ 20/160 With a ≥ 10-Letter and ≥ 15-Letter Improvement in DCNVA at Day 1 (0.5 Hours and 1-hour Post-dose), Day 3, Day 8, and Week 6	This outcome measure will investigate the percentage of subjects with baseline DCNVA ≤ 20/63, ≤ 20/80, ≤ 20/100, ≤ 20/125, and ≤ 20/160 with a ≥ 10-Letter and ≥ 15-Letter Improvement in DCNVA at Day 1 (0.5 hours and 1-hour post-dose), Day 3, Day 8, and Week 6.	6 Weeks
Percentage of Subjects With ≥ 5, ≥ 10, and ≥ 15 Letters of Improvement in Binocular DCIVA From Baseline at Day 1 (1-hour Post-dose), Day 3, Day 8, and Week 6	This outcome measure will investigate the percentage of subjects with ≥ 5, ≥ 10, and ≥ 15 letters of improvement in binocular DCIVA from baseline at Day 1 (1-hour post-dose), Day 3, Day 8, and Week 6.	6 Weeks
Change in Binocular DCIVA From Baseline at Day 1 (1-hour Post-dose), Day 3, Day 8, and Week 6	This outcome measure will investigate the change in binocular DCIVA from baseline at Day 1 (1-hour post-dose), Day 3, Day 8, and Week 6.	6 Weeks
Percentage of Subjects With Loss or Improvement in BCDVA From Baseline (Binocular) at Day 1 (1-hour Post-dose), Day 3, Day 8, and Week 6	This outcome measure will investigate the percentage of subjects with loss or improvement in BCDVA from baseline (Binocular) at Day 1 (1-hour post-dose), Day 3, Day 8, and Week 6.	6 Weeks
Change in BCDVA From Baseline (Binocular) at Day 1 (1-hour Post-dose), Day 3, Day 8, and Week 6	This outcome measure will investigate the change in BCDVA from baseline (Binocular) at Day 1 (1-hour post-dose), Day 3, Day 8, and Week 6.	6 Weeks
Change in BCDVA From Baseline (Monocular - Study Eye) at Day 1 (1-hour Post-dose), Day 3, Day 8, and Week 6	This outcome measure will investigate the Change in BCDVA From Baseline (Monocular - Study Eye) at Day 1 (1-hour post-dose), Day 3, Day 8, and Week 6.	6 Weeks
Change in Pupil Diameter From Baseline at Day 3 and Day 8	This outcome measure will investigate the change in pupil diameter from baseline at Day 3 and Day 8.	8 Days
Percent Change in Pupil Diameter From Baseline at Day 3 & Day 8	This outcome measure will investigate the Percent Change in Pupil Diameter from Baseline at Day 3 & Day 8.	8 Days
Percentage of Subjects With Pupil Diameter of < 3.5, < 3.0, < 2.5, < 2.0, and < 1.5 mm at Day 3 and Day 8	This outcome measure will investigate the percentage of subjects with pupil diameter of < 3.5, < 3.0, < 2.5, < 2.0, and < 1.5 mm at Day 3 and Day 8.	8 Days
Percentage of Subjects With Pupil Diameter of 1.5 to < 2.0 mm, 2.0 to < 2.5 mm, 2.5 to < 3.0 mm, and 3.0 to < 3.5 mm at Day 3 and Day 8	This outcome measure will investigate the percentage of subjects with pupil diameter of 1.5 to < 2.0 mm, 2.0 to < 2.5 mm, 2.5 to < 3.0 mm, and 3.0 to < 3.5 mm at Day 3 and Day 8.	8 Days
Change From Baseline in Overall and Component Subject-Reported Outcomes at Day 3, Day 8, and Week 6	This outcome measure investigates the change from baseline in overall and component subject-reported outcomes at Day 3, Day 8, and Week 6. : Responses to each question used a 1-5 scale with 1=Worst outcome and 5=Best outcome.	6 Weeks

Collaborators and Investigators

• Sponsor: Ocuphire Pharma, Inc.
• Investigators: Study Chair: Jay V Pepose, MD, Ocuphire Pharma

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2024
• Primary Completion (Actual): April 3, 2025
• Study Completion (Actual): January 22, 2026

Study Registration Dates

• First Submitted: August 5, 2024
• First Submitted That Met QC Criteria: August 5, 2024
• First Posted (Actual): August 7, 2024

Study Record Updates

• Last Update Posted (Actual): August 17, 2026
• Last Update Submitted That Met QC Criteria: August 12, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Refractive Errors; Presbyopia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Adrenergic Agents; Antihypertensive Agents; Adrenergic Antagonists; Adrenergic alpha-Antagonists; Pharmaceutical Solutions; Ophthalmic Solutions; Phentolamine
• Other Study ID Numbers: OPI-NYXP-302 (VEGA-3)

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