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

Presbyopia Clinical Trial

— VEGA-2  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05646719
• Other study ID #: OPI-NYXP-301 (VEGA-2)
• Status: Completed
• Phase: Phase 3
• Start date: December 22, 2022
• Est. completion date: October 11, 2023

Study information

• Verified date: April 2023
• Source: Ocuphire Pharma, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 333
• Est. completion date: October 11, 2023
• Est. primary completion date: October 11, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 64 Years

Eligibility

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.

Related Conditions & MeSH terms

• Presbyopia

Intervention

Drug:
• Phentolamine Opthalmic Solution 0.75%
phentolamine ophthalmic solution 0.75% (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist

Other:
• Placebo
Vehicle for Phentolamine Ophthalmic Solution

Drug:
• Low dose pilocarpine
Pilocarpine hydrochloride ophthalmic solution 0.4%

Other:
• Low dose pilocarpine vehicle
Vehicle for low dose pilocarpine

Locations

Country	Name	City	State
United States	Athens, OH	Athens	Ohio
United States	Austin, TX	Austin	Texas
United States	Azusa, CA	Azusa	California
United States	Bloomington, MN	Bloomington	Minnesota
United States	Chesterfield, MO	Chesterfield	Missouri
United States	Cranberry Township, PA	Cranberry Township	Pennsylvania
United States	Delray Beach, FL	Delray Beach	Florida
United States	Fargo, ND	Fargo	North Dakota
United States	Garner, NC	Garner	North Carolina
United States	Houston, TX	Houston	Texas
United States	Kansas City, MO	Kansas City	Missouri
United States	Lake Villa, IL	Lake Villa	Illinois
United States	Longwood, FL	Longwood	Florida
United States	Memphis, TN	Memphis	Tennessee
United States	New Freedom, PA	New Freedom	Pennsylvania
United States	Newport Beach, CA	Newport Beach	California
United States	Northridge, CA	Northridge	California
United States	Phoenix, AZ	Phoenix	Arizona
United States	Pittsburg, KS	Pittsburg	Kansas
United States	Rochester, NY	Rochester	New York
United States	Roswell, GA	Roswell	Georgia
United States	Saint Louis, MO	Saint Louis	Missouri
United States	San Antonio, TX	San Antonio	Texas
United States	Shawnee Mission, KS	Shawnee Mission	Kansas
United States	Sioux Falls, SD	Sioux Falls	South Dakota
United States	Smithtown, NY	Smithtown	New York

Sponsors (1)

Lead Sponsor	Collaborator
Ocuphire Pharma, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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 30 min post-LDP/vehicle comparing Nyxol + LDP to Nyxol alone at Visit 5 (Stage 2 Day 8).	At 30 min post-LDP/vehicle comparing Nyxol + LDP to Nyxol alone at Visit 5 (Stage 2 Day 8)
Secondary	Percentage of subjects with = 15 letters of improvement in binocular photopic DCNVA and with < 5 letters of loss in binocular photopic BCDVA from Baseline (excluding primary and key secondary outcome timepoints)	Percentage of subjects with = 15 letters of improvement in binocular photopic DCNVA and with < 5 letters of loss in binocular photopic BCDVA from Baseline (excluding primary and key secondary outcome timepoints)	At various timepoints and visits by treatment arms in Stage 1 and Stage 2
Secondary	Percentage of subjects with = 5, = 10, and = 15 letters of improvement in photopic DCNVA from Baseline (monocular and binocular)	Percentage of subjects with = 5, = 10, and = 15 letters of improvement in photopic DCNVA from Baseline (monocular and binocular)	At various timepoints and visits by treatment arms in Stage 1 and Stage 2
Secondary	Change in photopic DCNVA from Baseline (monocular and binocular)	Change in photopic DCNVA from Baseline (monocular and binocular)	At various timepoints and visits by treatment arms in Stage 1 and Stage 2
Secondary	Percentage of subjects with loss or improvement in photopic and mesopic BCDVA from Baseline (monocular and binocular)	Percentage of subjects with loss or improvement in photopic and mesopic BCDVA from Baseline (monocular and binocular)	At various timepoints and visits by treatment arms in Stage 1 and Stage 2
Secondary	Change in photopic and mesopic BCDVA from Baseline (monocular and binocular)	Change in photopic and mesopic BCDVA from Baseline (monocular and binocular)	At various timepoints and visits by treatment arms in Stage 1 and Stage 2
Secondary	Percentage of subjects with = 5, = 10, and = 15 letters of improvement in mesopic binocular DCNVA from Baseline	Percentage of subjects with = 5, = 10, and = 15 letters of improvement in mesopic binocular DCNVA from Baseline	At various timepoints and visits by treatment arms in Stage 1 and Stage 2
Secondary	Change in mesopic binocular DCNVA from Baseline	Change in mesopic binocular DCNVA from Baseline	At various timepoints and visits by treatment arms in Stage 1 and Stage 2
Secondary	Change and percent change in photopic PD from Baseline	Change and percent change in photopic PD from Baseline	At various timepoints and visits by treatment arms in Stage 1 and Stage 2
Secondary	Percentage of subjects with photopic PD of < 3.5, < 3.0, < 2.5, < 2.0, and < 1.5 mm	Percentage of subjects with photopic PD of < 3.5, < 3.0, < 2.5, < 2.0, and < 1.5 mm	At various timepoints and visits by treatment arms in Stage 1 and Stage 2
Secondary	Percentage of subjects with photopic PD 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	Percentage of subjects with photopic PD 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 various timepoints and visits by treatment arms in Stage 1 and Stage 2
Secondary	Change and percent change in mesopic PD from Baseline	Change and percent change in mesopic PD from Baseline	At various timepoints and visits by treatment arms in Stage 1 and Stage 2
Secondary	Percentage of subjects with mesopic PD of < 3.5, < 3.0, < 2.5, < 2.0, and < 1.5 mm	Percentage of subjects with mesopic PD of < 3.5, < 3.0, < 2.5, < 2.0, and < 1.5 mm	At various timepoints and visits by treatment arms in Stage 1 and Stage 2
Secondary	Percentage of subjects with mesopic PD 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	Percentage of subjects with mesopic PD 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 various timepoints and visits by treatment arms in Stage 1 and Stage 2
Secondary	Percentage of subjects with Baseline photopic DCNVA = 20/63, = 20/80, = 20/100, = 20/125, and = 20/160, with a = 10-letter and = 15-letter improvement in photopic DCNVA	Percentage of subjects with Baseline photopic DCNVA = 20/63, = 20/80, = 20/100, = 20/125, and = 20/160, with a = 10-letter and = 15-letter improvement in photopic DCNVA	At various timepoints and visits by treatment arms in Stage 1 and Stage 2
Secondary	Percentage of subjects with Baseline photopic DCNVA from 20/50 to 20/63, 20/50 to 20/80, 20/50 to 20/100, 20/50 to 20/125, and 20/50 to 20/160, with a = 10-letter and = 15-letter improvement in photopic DCNVA	Percentage of subjects with Baseline photopic DCNVA from 20/50 to 20/63, 20/50 to 20/80, 20/50 to 20/100, 20/50 to 20/125, and 20/50 to 20/160, with a = 10-letter and = 15-letter improvement in photopic DCNVA	At various timepoints and visits by treatment arms in Stage 1 and Stage 2
Secondary	Subject questionnaire responses related to change in near vision and satisfaction with near vision.	Subject questionnaire responses related to change in near vision and satisfaction with near vision.	At various timepoints and visits by treatment arms in Stage 1 and Stage 2