Safety and Efficacy of Nyxol Eye Drops as a Single Agent and With Adjunctive Low-Dose Pilocarpine Eye Drops in Subjects With Presbyopia (VEGA-2)

Randomized, Double-Masked, Placebo-Controlled, Multicenter, Phase 3 Study of the Safety and Efficacy of Nyxol (Phentolamine Ophthalmic Solution 0.75%) as a Single Agent and With Adjunctive Low-Dose Pilocarpine Hydrochloride Ophthalmic Solution 0.4% in Subjects With Presbyopia

The objectives of this study are:

To evaluate the safety and efficacy of Nyxol alone and with adjunctive low dose pilocarpine to improve distance-corrected near visual acuity (DCNVA) in subjects with presbyopia.

Study Overview

• Status: Completed
• Conditions: Presbyopia
• Intervention / Treatment: Drug: Phentolamine Opthalmic Solution 0.75%; Drug: Low dose pilocarpine; Other: Low dose pilocarpine vehicle; Other: Placebo

Detailed Description

This is a Randomized, Double-Masked, Placebo-Controlled, Multicenter, Phase 3 Study of the Safety and Efficacy of Nyxol (Phentolamine Ophthalmic Solution 0.75%) as a Single Agent and With Adjunctive Low-Dose Pilocarpine Hydrochloride Ophthalmic Solution 0.4% in Subjects With Presbyopia

• Study Type: Interventional
• Enrollment (Actual): 333
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85003
      • Phoenix, AZ
  • California
    • Azusa, California, United States, 91702
      • Azusa, CA
    • Newport Beach, California, United States, 92663
      • Newport Beach, CA
    • Northridge, California, United States, 91325
      • Northridge, CA
  • Florida
    • Delray Beach, Florida, United States, 33484
      • Delray Beach, FL
    • Longwood, Florida, United States, 32779
      • Longwood, FL
  • Georgia
    • Roswell, Georgia, United States, 30076
      • Roswell, GA
  • Illinois
    • Lake Villa, Illinois, United States, 60046
      • Lake Villa, IL
  • Kansas
    • Pittsburg, Kansas, United States, 66762
      • Pittsburg, KS
    • Shawnee Mission, Kansas, United States, 66204
      • Shawnee Mission, KS
  • Minnesota
    • Bloomington, Minnesota, United States, 55420
      • Bloomington, MN
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • Chesterfield, MO
    • Kansas City, Missouri, United States, 64133
      • Kansas City, MO
    • St Louis, Missouri, United States, 63128
      • Saint Louis, MO
  • New York
    • Rochester, New York, United States, 14618
      • Rochester, NY
    • Smithtown, New York, United States, 11787
      • Smithtown, NY
  • North Carolina
    • Garner, North Carolina, United States, 27529
      • Garner, NC
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Fargo, ND
  • Ohio
    • Athens, Ohio, United States, 45701
      • Athens, OH
  • Pennsylvania
    • Cranberry Township, Pennsylvania, United States, 16066
      • Cranberry Township, PA
    • New Freedom, Pennsylvania, United States, 17349
      • New Freedom, PA
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57108
      • Sioux Falls, SD
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Memphis, TN
  • Texas
    • Austin, Texas, United States, 73301
      • Austin, TX
    • Houston, Texas, United States, 77055
      • Houston, TX
    • San Antonio, Texas, United States, 78229
      • San Antonio, TX

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 64 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Males or females ≥ 40 and ≤ 64 years of age.
2. BCDVA of 0.1 LogMAR (20/25 Snellen equivalent) or better in each eye in photopic conditions.
3. DCNVA of 0.4 LogMAR (20/50 Snellen equivalent) or worse but not > 0.7 LogMAR (20/100 Snellen equivalent) in photopic conditions in each eye and binocularly.
4. For subjects who depend on reading glasses or bifocals, binocular best-corrected near VA is 0.1 LogMAR (20/25 Snellen equivalent) or better.
5. Photopic PD of ≥ 3 mm in either eye.

Exclusion Criteria:

Ophthalmic (in either eye):

1. Use of any topical prescription 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 and artificial tears as specified in Exclusion # 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. Current use of any topical ophthalmic therapy for dry eye.
4. Tear break-up time of < 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..
5. Clinically significant ocular disease that might interfere with the study as deemed by the Investigator.
6. Recent or current evidence of ocular infection or inflammation in either eye.
7. Any history of herpes simplex or herpes zoster keratitis.
8. Known allergy, hypersensitivity, or contraindication to any component of the phentolamine, pilocarpine, or vehicle formulations.
9. Prior participation in a study involving the use of Nyxol for the treatment of presbyopia.
10. History of cauterization of the punctum or punctal plug (silicone or collagen) insertion or removal.
11. Ocular trauma within 6 months prior to Screening.
12. Ocular surgery or any ocular laser treatment within 6 months prior to Screening.
13. Subjects with surgical monovision, multifocal or extended depth of focus intraocular lenses (IOLs) are excluded.
14. History of any traumatic (surgical or nonsurgical) or nontraumatic condition affecting the pupil or iris.

15. Contact lens wear on the day of any study visit and contact lenses must be removed for home dosing and for at least 10 minutes following dosing.

    Systemic:

16. Known hypersensitivity or contraindication to alpha- and/or beta-adrenoceptor antagonists .
17. Known hypersensitivity or contraindication to any systemic cholinergic parasympathomimetic agent.
18. Clinically significant systemic disease that might interfere with the study as deemed by the judgment of the Investigator.
19. 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.
20. Participation in any investigational study within 30 days prior to Screening.
21. Females of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control.
22. Resting HR outside the range of 50 to 110 beats per min.
23. Hypertension with resting diastolic BP > 105 mmHg or systolic BP > 160 mmHg.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nyxol + low dose pilocarpine; Nyxol (phentolamine ophthalmic solution) 0.75% Pilocarpine (0.4%)	Drug: Phentolamine Opthalmic Solution 0.75%; phentolamine ophthalmic solution 0.75% (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist; Other Names: Nyxol; Drug: Low dose pilocarpine; Pilocarpine hydrochloride ophthalmic solution 0.4%; Other Names: Pilocarpine; LDP
Experimental: Nyxol + low dose pilocarpine vehicle; Nyxol (phentolamine ophthalmic solution) 0.75% Pilocarpine vehicle	Drug: Phentolamine Opthalmic Solution 0.75%; phentolamine ophthalmic solution 0.75% (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist; Other Names: Nyxol; Other: Low dose pilocarpine vehicle; Vehicle for low dose pilocarpine
Experimental: Placebo + low dose pilocarpine; Placebo Pilocarpine (0.4%)	Drug: Low dose pilocarpine; Pilocarpine hydrochloride ophthalmic solution 0.4%; Other Names: Pilocarpine; LDP; Other: Placebo; Vehicle for Phentolamine Ophthalmic Solution; Other Names: Phentolamine Ophthalmic Solution Vehicle
Experimental: Placebo + low dose pilocarpine vehicle; Placebo Pilocarpine vehicle	Other: Low dose pilocarpine vehicle; Vehicle for low dose pilocarpine; Other: Placebo; Vehicle for Phentolamine Ophthalmic Solution; Other Names: Phentolamine Ophthalmic Solution Vehicle
Experimental: Nyxol; Nyxol (phentolamine ophthalmic solution) 0.75%	Drug: Phentolamine Opthalmic Solution 0.75%; phentolamine ophthalmic solution 0.75% (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist; Other Names: Nyxol
Experimental: Nyxol placebo	Other: Placebo; Vehicle for Phentolamine Ophthalmic Solution; Other Names: Phentolamine Ophthalmic Solution Vehicle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Subjects With ≥ 15 Letters of Improvement in Photopic Binocular DCNVA and With < 5 Letters of Loss in Photopic Binocular BCDVA in Nyxol-treated Subjects	The primary efficacy endpoint is the percent of subjects with ≥ 15 letters of improvement in photopic binocular DCNVA and with < 5 letters of loss in photopic binocular BCDVA from Baseline at 30 min post-LDP/vehicle comparing subjects treated with Nyxol + LDP to subjects treated with placebo + LDP vehicle at Visit 5 (Stage 2 Day 8).	Baseline at 30 min post-LDP/vehicle comparing subjects treated with Nyxol + LDP to subjects treated with placebo + LDP vehicle at Visit 5 (Stage 2 Day 8)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of subjects with ≥ 15 letters improvement in photopic binocular DCNVA and with < 5 letters of loss in photopic binocular BCDVA in LDP+Nyxol-treated subjects	The percent of subjects with ≥ 15 letters of improvement in photopic binocular DCNVA and with < 5 letters of loss in photopic binocular BCDVA at 0.5 hours post-LDP/vehicle at Visit 5	Visit 5 at 0.5 hours post-LDP/vehicle
Percent of subjects with ≥ 15 letters improvement in photopic binocular DCNVA and with < 5 letters of loss in photopic binocular BCDVA in Nyxol-treated subjects	The percent of subjects with ≥ 15 letters of improvement in photopic binocular DCNVA and with < 5 letters of loss in photopic binocular BCDVA from Baseline in Nyxol-treated subjects at 0.5, 1, 3, 5 and 8 hours post-Nyxol/placebo at Visit 2	Visit 2 at 0.5, 1, 3, 5 and 8 hours post-Nyxol/placebo
Percent of subjects with ≥ 15 letters improvement in photopic binocular DCNVA and with < 5 letters of loss in in photopic binocular BCDVA in LDP+Nyxol-treated subjects	The percent of subjects with ≥ 15 letters of improvement in photopic binocular DCNVA and with < 5 letters of loss in photopic binocular BCDVA at 1, 3, 5 and 8 hours post-LDP/vehicle in LDP+Nyxol-treated subjects at Visit 5	Visit 5 at 1, 3, 5 and 8 hours post-LDP/vehicle
Percentage of subjects with ≥ 5, ≥ 10, and ≥ 15 letters of improvement in photopic binocular distance-corrected intermediate visual acuity (DCIVA) from Baseline in Nyxol-treated subjects	Percentage of subjects with ≥ 5, ≥ 10, and ≥ 15 letters of improvement in photopic binocular DCIVA from Baseline in Nyxol-treated subjects at 0.5, 1, 3, 5, 8 and 12 hours post-Nyxol/placebo at Visit 2	Visit 2 at 0.5, 1, 3, 5, 8 and 12 hours post-Nyxol/placebo
Percentage of subjects with ≥ 5, ≥ 10, and ≥ 15 letters of improvement in photopic binocular DCIVA from Baseline in LDP+Nyxol-treated subjects	Percentage of subjects with ≥ 5, ≥ 10, and ≥ 15 letters of improvement in photopic binocular DCIVA from Baseline in LDP+Nyxol-treated subjects at 0.5, 1, 3, 5 and 8 hours post-LDP/vehicle on Visit 5	Visit 5 at 0.5, 1, 3, 5 and 8 hours post-LDP/vehicle

Collaborators and Investigators

• Sponsor: Ocuphire Pharma, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2022
• Primary Completion (Actual): October 11, 2023
• Study Completion (Actual): October 11, 2023

Study Registration Dates

• First Submitted: December 2, 2022
• First Submitted That Met QC Criteria: December 2, 2022
• First Posted (Actual): December 12, 2022

Study Record Updates

• Last Update Posted (Actual): March 12, 2026
• Last Update Submitted That Met QC Criteria: March 10, 2026
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Presbyopia; Nyxol; Pilocarpine
• Additional Relevant MeSH Terms: Eye Diseases; Refractive Errors; Presbyopia; Heterocyclic Compounds; Alkaloids; Pilocarpine
• Other Study ID Numbers: OPI-NYXP-301 (VEGA-2)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No