Phentolamine Eye Drops for Presbyopia

(VEGA-3 Trial)

Recruiting at 12 trial locations

Overseen By Drey V Coleman

Age: 18 - 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Ocuphire Pharma, Inc.

Must not be taking: Ophthalmic medications, Dry eye products

Disqualifiers: Ocular disease, Ocular surgery, Systemic disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 1 week

545 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial requires you to stop using any topical prescription or over-the-counter eye medications 7 days before screening and throughout the study, except for certain lid scrubs and artificial tears. You also cannot start or change the dosage of any systemic adrenergic or cholinergic drugs within 7 days before screening or during the study, except for Flomax® (tamsulosin).

Will I have to stop taking my current medications?

The trial requires you to stop using any topical eye medications, including over-the-counter ones, 7 days before screening and during the study. You also cannot start or change any systemic adrenergic or cholinergic drugs within 7 days before screening or during the study, except for Flomax (tamsulosin).

What data supports the idea that Phentolamine Eye Drops for Presbyopia is an effective drug?

The available research shows that Phentolamine Eye Drops can help improve near vision in people with presbyopia. In a study, these eye drops were found to reduce pupil size and improve vision in dim light conditions for patients with both presbyopia and glaucoma. This suggests that the drops can help people see better up close. Compared to another drug, pilocarpine, which also helps with near vision, Phentolamine Eye Drops seem to offer a different approach by focusing on pupil size modulation. While pilocarpine improved near vision in 12 to 22% of early presbyopes, Phentolamine Eye Drops have shown benefits in a specific group of patients, indicating their potential effectiveness. ^{1 2 3 4 5}

What evidence supports the effectiveness of the drug phentolamine eye drops for treating presbyopia?

Phentolamine mesylate eye drops have been shown to improve near visual acuity in presbyopic patients with glaucoma by reducing pupil size, which can help with focusing on close objects. Additionally, these drops have been effective in reversing mydriasis (dilated pupils), which suggests they can help restore functional vision quickly. ^{1 2 3 4 5}

What safety data is available for Phentolamine Eye Drops used for presbyopia?

The ORION-1 trial evaluated the long-term safety and efficacy of Phentolamine Mesylate Ophthalmic Solution (PMOS) in presbyopic glaucoma patients, showing beneficial effects such as decreased pupil diameter and improved visual acuity. However, specific safety data from this trial is not detailed in the provided abstracts. ^{1 6 7 8 9}

Is Phentolamine Eye Drops safe for humans?

Phentolamine mesylate eye drops have been studied for safety in people with glaucoma and presbyopia, showing benefits like improved vision and reduced eye pressure, with no major safety concerns reported in the study. ^{1 6 7 8 9}

Is the drug 0.75% phentolamine eye drops a promising treatment for presbyopia?

Yes, 0.75% phentolamine eye drops are promising for treating presbyopia. They help improve near vision by reducing pupil size, which can enhance focus on close objects. This drug is easy to use and offers a noninvasive option for people with presbyopia. ^{1 3 5 8 10}

How is the drug phentolamine eye drops unique for treating presbyopia?

Phentolamine eye drops are unique for treating presbyopia because they are applied topically to the eye and work by modulating the pupil size, which can improve near visual acuity without affecting distance vision. This approach differs from traditional methods like glasses or surgery, offering a noninvasive and easy-to-use alternative. ^{1 3 5 8 10}

What is the purpose of this trial?

Safety and efficacy of POS in participants with presbyopia

Research Team

Jay V Pepose, MD

Principal Investigator

Ocuphire Pharma

Eligibility Criteria

This trial is for people aged 45-64 with presbyopia, who rely on reading glasses or bifocals. They must have certain levels of visual acuity and pupil diameter, be able to self-administer medication, and attend all visits. Pregnant women, those with significant eye diseases or systemic diseases, contact lens users, and individuals allergic to the study's components cannot participate.

Inclusion Criteria

For participants who depend on reading glasses or bifocals, binocular best-corrected near VA of 65 ETDRS letters (20/25 Snellen equivalent) or better at both Screening and Baseline Visits

I can take my own medication during the study.

BCDVA of 55 ETDRS letters (20/20 Snellen equivalent) or better in photopic conditions in each eye at both Screening and Baseline Visits

Exclusion Criteria

I use over-the-counter artificial tears during study visits.

I do not have any eye conditions that could affect the study.

Prior participation in a study involving the use of POS for presbyopia or night vision disturbance

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Phentolamine Ophthalmic Solution or placebo to assess efficacy and safety

1 week

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• 0.75% phentolamine ophthalmic solution

Trial Overview The trial is testing the safety and effectiveness of a 0.75% phentolamine ophthalmic solution (POS) compared to a placebo in improving near vision for people with presbyopia. Participants will receive either POS or a placebo without knowing which one they are getting.

Participant Groups

Group I: 0.75% phentolamine ophthalmic solution Active Control 1 Intervention

Drug: phentolamine ophthalmic solution 0.75%, a non-selective alpha-1 and alpha-2 adrenergic antagonist

Group II: phentolamine ophthalmic solution vehicle Placebo Group 1 Intervention

Drug: Placebo

0.75% phentolamine ophthalmic solution is already approved in United States for the following indications:

Approved in United States as Ryzumvi for:

• Reversal of pharmacologically-induced mydriasis produced by adrenergic agonists (e.g., phenylephrine) or parasympatholytic (e.g., tropicamide) agents

Who Is Running the Clinical Trial?

Ocuphire Pharma, Inc.

Lead Sponsor

Trials

13

Recruited

2,200+

Findings from Research

In a Phase 2b trial involving 39 patients with elevated intraocular pressure (IOP), phentolamine mesylate ophthalmic solution (PMOS) did not significantly lower IOP compared to placebo, but showed a trend towards greater decreases in patients with lower baseline IOP.

PMOS significantly reduced pupil diameter by 20% and improved distance-corrected near visual acuity in many patients, indicating potential benefits for those with presbyopia and dim light vision disturbances, while being well tolerated with no significant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phentolamine Mesylate Ophthalmic Solution Provides Lasting Pupil Modulation and Improves Near Visual Acuity in Presbyopic Glaucoma Patients in a Randomized Phase 2b Clinical Trial. Pepose, JS., Hartman, PJ., DuBiner, HB., et al.[2022]

In a study involving 31 subjects, phentolamine mesylate ophthalmic solution (PMOS) significantly reduced pupil diameter after pharmacological dilation, showing a greater return to baseline compared to placebo at 2 and 4 hours post-treatment.

PMOS was effective regardless of the mydriatic agent used (phenylephrine or tropicamide) and had a good safety profile, with only mild side effects like conjunctival hyperemia that resolved quickly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phentolamine Eye Drops Reverse Pharmacologically Induced Mydriasis in a Randomized Phase 2b Trial. Karpecki, PM., Foster, SA., Montaquila, SM., et al.[2023]

Ophthalmic pilocarpine (1.25%) can improve near vision in early presbyopes, with 12-22% of patients achieving better visual acuity compared to a placebo, making it a potential treatment option for those with failing accommodation.

The drug is well tolerated, acts quickly within minutes, and its effects last for several hours, although it may cause reduced night vision and minor distance acuity issues due to smaller pupil size.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical Review: Pilocarpine-induced Miosis as Help for Early Presbyopes? Westheimer, G.[2022]

Pharmacological treatments for presbyopia, a common age-related condition affecting near vision, offer a promising noninvasive option, with three main strategies including inducing miosis to improve depth of focus, rehabilitating accommodation for better vision at all distances, and using lipoic acid to restore lens elasticity.

These treatments are delivered as topical eyedrops and have shown no serious adverse effects, highlighting their safety, but require careful patient selection to ensure effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological Treatments for Presbyopia. Orman, B., Benozzi, G.[2023]

Presbyopia affects over a billion people globally, leading to a significant need for effective and noninvasive treatment options beyond traditional methods like glasses and surgery.

Recent investigations into pharmacological treatments, specifically eye drops for presbyopia, show promise as an alternative approach, potentially improving daily visual tasks without interfering with patients' activities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of Pharmacological Presbyopia Treatment. Grzybowski, A., Markeviciute, A., Zemaitiene, R.[2022]

Phenylephrine, commonly used as a mydriatic agent in eye drops, can lead to several adverse effects, particularly cardiovascular issues, as observed in the study.

Other potential side effects include allergic reactions, pigment release in the anterior chamber, and iatrogenic corneal edema, highlighting the need for caution when using this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adverse effects of neosynephrine]. Leroy, MP., Cantineau, D., Brasdefer, D., et al.[2013]

The combination of pilocarpine and oxymetazoline ocular drops showed a significant dose-dependent improvement in uncorrected near visual acuity (UNVA) in individuals with presbyopia, particularly with pilocarpine concentrations between 1.16% and 1.32%.

The most common side effect reported was headache, and while pilocarpine was effective, oxymetazoline did not significantly enhance efficacy or reduce headache severity when added to pilocarpine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combinations of Pilocarpine and Oxymetazoline for the Pharmacological Treatment of Presbyopia: Two Randomized Phase 2 Studies. Price, FW., Hom, M., Moshirfar, M., et al.[2022]

Patients receiving mydriatic eye-drops before cataract surgery experienced significantly higher rates of side effects, including ataxia (9.9% vs. 2%), dizziness (15.1% vs. 1.3%), and dry mouth (19.7% vs. 6.6%) compared to those who did not receive these drops.

Using lidocaine 1% plus epinephrine 1/200,000 as an adjunct to topical anesthesia during phacoemulsification was found to be an effective and safe alternative, reducing the side effects associated with mydriatic eye-drops.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Phacoemulsification without mydriasis before surgery: benefits to the patient]. Benatar-Haserfaty, J., Alvarez de Rementería-Fernández, L., Muriel García, A.[2019]

In a study involving 43 adults with presbyopia, pilocarpine ophthalmic solution (1.25%) was found to be inferior to placebo in overall night-driving performance, indicating caution for patients when driving at night after using this treatment.

While no serious adverse events were reported, common side effects included headache and visual impairment with pilocarpine, suggesting that patients should be aware of potential visual disturbances when using this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of presbyopia treatment pilocarpine hydrochloride 1.25% on night-driving performance. Waring, GO., Brujic, M., McGee, S., et al.[2023]

A proposed treatment for presbyopia in people over 40 involves using a combination of a cholinergic agent and non-steroidal anti-inflammatory drugs (NSAIDs) to improve near vision without impacting distance vision.

The treatment is designed to stimulate the ciliary muscle and iris through muscarinic receptors, and it is formulated to avoid any inflammatory or adverse side effects, making it a potentially safe option for correcting accommodation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Presbyopia: a new potential pharmacological treatment. Benozzi, J., Benozzi, G., Orman, B.[2021]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Phentolamine Mesylate Ophthalmic Solution Provides Lasting Pupil Modulation and Improves Near Visual Acuity in Presbyopic Glaucoma Patients in a Randomized Phase 2b Clinical Trial. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Phentolamine Eye Drops Reverse Pharmacologically Induced Mydriasis in a Randomized Phase 2b Trial. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Topical Review: Pilocarpine-induced Miosis as Help for Early Presbyopes? [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Pharmacological Treatments for Presbyopia. [2023]

5. China pubmed.ncbi.nlm.nih.gov

A Review of Pharmacological Presbyopia Treatment. [2022]

6. France pubmed.ncbi.nlm.nih.gov

[Adverse effects of neosynephrine]. [2013]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Combinations of Pilocarpine and Oxymetazoline for the Pharmacological Treatment of Presbyopia: Two Randomized Phase 2 Studies. [2022]

8. Spain pubmed.ncbi.nlm.nih.gov

[Phacoemulsification without mydriasis before surgery: benefits to the patient]. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Impact of presbyopia treatment pilocarpine hydrochloride 1.25% on night-driving performance. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Presbyopia: a new potential pharmacological treatment. [2021]