Phentolamine Eye Drops for Night Vision Impairment

(LYNX-2 Trial)

Recruiting at 23 trial locations

Overseen By Drey V Coleman

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Ocuphire Pharma, Inc.

Must not be taking: Alpha antagonists, Beta antagonists

Disqualifiers: Dry eye, Fluctuating vision, Diabetes, 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: Unknown

Duration: 2 weeks

200 Participants Needed

Trial Summary

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

Yes, you must stop using any topical prescription or over-the-counter ophthalmic medications, including artificial tear drops, at least 7 days before the trial and until it is completed. Additionally, you cannot change the dosage or start new systemic adrenergic or cholinergic drugs within 7 days before the trial or during the study.

Will I have to stop taking my current medications?

The trial requires that you stop using any topical eye medications, including over-the-counter drops, at least 7 days before the screening and throughout the study. Additionally, you should not start or change any systemic adrenergic or cholinergic medications within 7 days before the screening or during the study.

What data supports the idea that Phentolamine Eye Drops for Night Vision Impairment is an effective treatment?

The available research shows that Phentolamine Eye Drops can help with night vision problems by reducing pupil size and improving vision clarity in dim light. In a study, patients with night vision disturbances experienced better image quality after using the drops. Compared to another treatment, pilocarpine, which helps with close-up vision but can reduce night vision, Phentolamine Eye Drops specifically target night vision issues, making them a more suitable option for this condition. ^{1 2 3 4 5}

What evidence supports the effectiveness of the drug Phentolamine Ophthalmic Solution for night vision impairment?

Research shows that Phentolamine Mesylate Ophthalmic Solution can improve vision in dim light conditions by reducing pupil size and enhancing visual acuity, which may help with night vision issues. ^{1 2 3 4 5}

What safety data is available for Phentolamine Eye Drops?

The ORION-1 trial evaluated the long-term safety and efficacy of Phentolamine Mesylate Ophthalmic Solution (PMOS) in a glaucomatous, presbyopic population, indicating its safety profile in these patients. Additionally, PMOS was shown to reverse pharmacologically induced mydriasis in a Phase 2b trial, suggesting it is well-tolerated for this use. ^{1 2 6 7 8}

Is Phentolamine Eye Drops safe for use in humans?

Phentolamine mesylate ophthalmic solution has been studied in clinical trials and shown to be safe for use in humans, with no major safety concerns reported in patients with dim light vision disturbances and glaucoma. ^{1 2 6 7 8}

Is the drug Phentolamine Ophthalmic Solution a promising treatment for night vision problems?

Yes, Phentolamine Ophthalmic Solution shows promise as it can improve vision in low light by reducing pupil size, enhancing visual clarity, and helping with issues like glare and halos. It also helps reverse eye dilation after exams, making it easier for patients to regain normal vision quickly. ^{1 2 3 7 9}

How is the drug Phentolamine Ophthalmic Solution unique for night vision impairment?

Phentolamine Ophthalmic Solution is unique because it is applied directly to the eyes and works by reducing pupil size, which can improve vision in low light conditions and help with symptoms like glare and halos. Unlike other treatments, it also has the potential to lower eye pressure and reverse pupil dilation caused by other medications. ^{1 2 3 7 9}

What is the purpose of this trial?

Safety and efficacy of 0.75% Phentolamine Ophthalmic Solution to improve mesopic low contrast visual acuity in subjects with post-refractive surgery visual disturbances.

Research Team

Jay Pepose, MD

Principal Investigator

Ocuphire Pharma

Eligibility Criteria

This trial is for individuals experiencing night vision problems after refractive eye surgery. Participants should have stable post-surgery vision and no other ongoing eye conditions that could affect the study results.

Inclusion Criteria

I've had eye surgery like LASIK and now have night vision issues.

mLCVA ≤ 30 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (20/63 Snellen or worse) in at least 1 eye using the Precision Vision Illuminator Cabinet with 5% translucent contrast chart and a mesopic filter at 4 m

Able and willing to give written consent to participate in this study

Exclusion Criteria

I have had changes in my vision over time.

My blood pressure is not higher than 160/105 mmHg.

Known hypersensitivity to any topical alpha-adrenoceptor antagonists

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily dosing of 0.75% Phentolamine Ophthalmic Solution or placebo

2 weeks

Daily dosing

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Phentolamine Ophthalmic Solution

Trial Overview The trial tests if a special eye drop solution, Phentolamine Ophthalmic Solution at 0.75%, can improve low-light visual sharpness in people with night vision issues post-eye surgery, compared to a placebo (a substance with no active drug).

Participant Groups

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

Daily dosing

Group II: phentolamine ophthalmic solution vehicle Placebo Group 1 Intervention

Daily dosing

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

Who Is Running the Clinical Trial?

Ocuphire Pharma, Inc.

Lead Sponsor

Trials

13

Recruited

2,200+

Viatris Inc.

Industry Sponsor

Trials

11

Recruited

5,600+

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]

In a clinical trial involving 24 adults with severe dim light vision disturbances, 1.0% phentolamine mesylate ophthalmic solution (PMOS) significantly reduced pupil size and improved contrast sensitivity and visual acuity compared to placebo.

PMOS was well tolerated, with the only side effect being mild conjunctival hyperemia, suggesting it is a safe option for improving vision quality in patients with dim light vision disturbances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase 2 clinical trial of phentolamine mesylate eye drops in patients with severe night vision disturbances. Pepose, J., Brigell, M., Lazar, E., et al.[2022]

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]

Cholinomimetics, particularly oxotremorine, were found to induce significant miosis (pupil constriction) in a dose-dependent manner, suggesting their potential efficacy in modulating eye responses through muscarinic receptors.

The study identified that M2 (ileal) type muscarinic receptors may play a key role in these effects, with scopolamine being the most potent antagonist, indicating a specific receptor involvement in the eye's response to cholinomimetics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The relative potencies of cholinomimetics and muscarinic antagonists on the rat iris in vivo: effects of pH on potency of pirenzepine and telenzepine. Hagan, JJ., van der Heijden, B., Broekkamp, CL.[2020]

The study aimed to evaluate the effectiveness of 1% hydroxyamphetamine as an alternative to 10% phenylephrine for inducing mydriasis, addressing concerns about systemic side effects associated with higher concentrations of phenylephrine.

Preliminary findings suggest that 1% hydroxyamphetamine may provide similar mydriatic effects without the same level of concern for adverse systemic reactions, making it a potentially safer option for routine pupillary dilation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mydriatic effectiveness of hydroxyamphetamine. Semes, LP., Bartlett, JD.[2013]

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]

In two studies involving volunteers without eye conditions, oxymetazoline (0.025%) was found to have no effect on pupil size or near point recession, indicating its safety in therapeutic doses.

Participants reported that oxymetazoline was well tolerated, with a preference for the formulation in boric acid over phosphate, suggesting it may be a favorable option for ocular treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and toleration of oxymetazoline ophthalmic solution. Samson, CR., Danzig, MR., Sasovetz, D., et al.[2013]

The study involved 80 participants, including 60 adults and 20 children, and found that Tyzine nasal drops effectively treated both uncomplicated and complicated acute mucous membranous rhinitis.

Ciliary transport improved significantly with the use of Tyzine, indicating its efficacy as a local treatment, provided it is used according to medical guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The usage of nasal drops Tyzine in otorhinolaryngology]. Kozłowski, Z., Jankowski, A., Modzelewska-Radwan, B.[2015]

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. England pubmed.ncbi.nlm.nih.gov

A randomized phase 2 clinical trial of phentolamine mesylate eye drops in patients with severe night vision disturbances. [2022]

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

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

5. Germany pubmed.ncbi.nlm.nih.gov

The relative potencies of cholinomimetics and muscarinic antagonists on the rat iris in vivo: effects of pH on potency of pirenzepine and telenzepine. [2020]

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

Mydriatic effectiveness of hydroxyamphetamine. [2013]

7. France pubmed.ncbi.nlm.nih.gov

[Adverse effects of neosynephrine]. [2013]

8. England pubmed.ncbi.nlm.nih.gov

Safety and toleration of oxymetazoline ophthalmic solution. [2013]

9. Poland pubmed.ncbi.nlm.nih.gov

[The usage of nasal drops Tyzine in otorhinolaryngology]. [2015]