Phentolamine Eye Drops for Presbyopia

(VEGA-3 Trial)

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests eye drops containing phentolamine to determine their safety and effectiveness for people with presbyopia, a condition that makes close-up vision difficult, such as when reading. The study compares the treatment to a placebo (a substance with no active drug) to evaluate which works better. It seeks participants who rely on reading glasses or bifocals but still struggle with close-up vision. Those who have experienced presbyopia and meet the criteria might be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to a potentially groundbreaking treatment.

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).

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the 0.75% phentolamine eye solution is generally safe for people. In earlier studies, most side effects were mild, such as eye discomfort and redness. Over 94% of these side effects were mild, and no serious side effects occurred. The FDA has approved this solution for another use, indicating it is usually well-tolerated. This information supports its safety for those considering participation in a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for presbyopia?

Most treatments for presbyopia, like reading glasses or contact lenses, focus on correcting vision externally. But the 0.75% phentolamine ophthalmic solution offers a unique approach by using a non-selective alpha-1 and alpha-2 adrenergic antagonist to improve near vision internally. Researchers are excited because this eye drop targets the eye's internal muscles, potentially reducing the need for corrective lenses. This new delivery method could provide a more convenient and less invasive option for managing presbyopia.

What evidence suggests that this treatment might be an effective treatment for presbyopia?

Research has shown that 0.75% phentolamine eye drops, which participants in this trial may receive, can help individuals with presbyopia, a condition requiring reading glasses as one ages. Studies have found that these eye drops significantly enhance close-up vision for those with presbyopia. The drops work by constricting the pupil, improving the eye's ability to focus on nearby objects. Previous trials reported that users noticed an improvement in their near vision after using the drops. Additionally, these eye drops are generally safe and well-tolerated. ^{2 5 6 7 8}

Who Is on the Research Team?

Jay V Pepose, MD

Principal Investigator

Ocuphire Pharma

Are You a Good Fit for This Trial?

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.

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

I am not pregnant, nursing, planning to become pregnant, and I use effective birth control.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2024/217064Orig1s000MedR.pdf

217064Orig1s000 CLINICAL REVIEW(S) - accessdata.fda.gov Phentolamine Ophthalmic Solution, 0.75% (POS) is a sterile, solution of phentolamine mesylate,. USP (1%) without an antimicrobial preservative ...

2. ophthalmologytimes.com ophthalmologytimes.com/view/opus-genetics-reports-positive-phase-3-results-for-phentolamine-ophthalmic-solution-0-75-

Opus Genetics reports positive phase 3 results for ... VEGA-3 trial showed significant efficacy of phentolamine ophthalmic solution 0.75% in improving near vision in presbyopia patients compared to ...

3. aaojournal.org aaojournal.org/article/S0161-6420(24)00558-X/fulltext

Reversal of Pharmacologically Induced Mydriasis with ... Phentolamine ophthalmic solution 0.75% consistently reduced pupil diameter rapidly, demonstrating statistically significant and clinically ...

4. ir.opusgtx.com ir.opusgtx.com/press-releases/detail/443/ocuphire-pharma-announces-publication-of-full-phase-3-results-of-phentolamine-ophthalmic-solution-0-75for-pharmacologically-induced-mydriasis-in-ophthalmology

Ocuphire Pharma Announces Publication of Full Phase 3 ... A Phase 2 and the first Phase 3 trial for the use of Phentolamine Ophthalmic Solution 0.75% to treat presbyopia met their primary endpoints.

5. optometrytimes.com optometrytimes.com/view/fda-approves-ryzumvi-phentolamine-ophthalmic-solution-for-the-treatment-of-pharmacologically-induced-mydriasis

FDA approves Ryzumvi (phentolamine ophthalmic solution ... Phentolamine ophthalmic solution 0.75% consistently showed a favorable safety and tolerability profile across all trials. In addition, the ...

6. ryzumvi.com ryzumvi.com/efficacy-safety

Rapid eye dilation reversal is possible 1 Most (>94%) side effects were mild, including eye discomfort and redness. No serious side effects related to RYZUMVI were reported in clinical trials.4,5. There ...

7. dailymed.nlm.nih.gov dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=96bb1e53-c2cc-4e60-a21a-db0269c371bf

RYZUMVI- phentolamine mesylate solution/ drops - DailyMed Ryzumvi (phentolamine ophthalmic solution) 0.75% is a sterile, clear and colorless solution for topical ophthalmic use containing 1% phentolamine mesylate ...

8. adisinsight.springer.com adisinsight.springer.com/drugs/800043975

Phentolamine - Opus Genetics - AdisInsight - Springer An ophthalmic solution containing 0.75% phentolamine (or 1% phentolamine mesylate), is being developed by Opus Genetics (previously Ocuphire Pharma), ...