Phentolamine Eye Drops for Night Vision Impairment

(LYNX-2 Trial)

Not currently recruiting at 26 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests Phentolamine Ophthalmic Solution eye drops, which might aid those experiencing night vision issues after vision-improving surgeries like LASIK. It evaluates the safety and effectiveness of the drops for enhancing vision in low light. The trial includes two groups: one receives the active eye drops, and the other receives a placebo (inactive treatment). Individuals who have recently undergone vision correction surgery and face night vision problems, such as glare or halos, might be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, allowing participants to contribute to a potentially groundbreaking treatment.

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.

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

Research has shown that Phentolamine Ophthalmic Solution is generally safe for use. In earlier studies, over 94% of side effects were mild, including eye discomfort and redness. Importantly, researchers did not link any serious side effects to the treatment. Tests for issues similar to night vision problems revealed no major safety concerns. This suggests that most people tolerate the treatment well. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for night vision impairment?

Unlike most treatments for night vision impairment, which typically involve lifestyle modifications or surgical options, phentolamine eye drops are unique because they offer a non-invasive, pharmacological approach. Phentolamine works by improving blood flow in the eyes, which could enhance night vision more effectively and conveniently than current methods. Researchers are excited about this treatment because it could provide a daily-use solution that enhances night vision without the need for complex procedures or significant lifestyle changes.

What evidence suggests that Phentolamine Ophthalmic Solution might be an effective treatment for night vision impairment?

Research has shown that Phentolamine Mesylate Eye Drops can enhance vision in dim light by reducing pupil size and sharpening vision. In this trial, participants will receive either the 0.75% phentolamine ophthalmic solution or a placebo comparator. One study found that 13% of patients using these drops improved their low-light vision test scores by at least 15 letters after just eight days. This finding suggests the drops can help with night vision problems. The treatment primarily aims to enhance contrast sensitivity and visual clarity. Overall, early results appear promising for those experiencing night vision issues after eye surgery. ^{2 4 6 7 8}

Who Is on the Research Team?

Jay Pepose, MD

Principal Investigator

Ocuphire Pharma

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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).

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36209072/

A randomized phase 2 clinical trial of phentolamine ... Key efficacy outcomes were change from baseline in pupil diameter, contrast sensitivity, and visual acuity. Safety measures including ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01703559

Study Details | NCT01703559 | The Safety and Efficacy of ... The objectives of this study are: To evaluate the efficacy of phentolamine mesylate 0.5% and 1.0% ophthalmic solution (Nyxol) in the treatment of night vision ...

3. fda.gov fda.gov/media/176278/download

Office of Clinical Pharmacology Review: Ryzumvi The primary efficacy endpoint of the studies was the percentage of subjects' study eyes returning to ≤ 0.2 mm from baseline PD at 90 min after ...

4. empr.com empr.com/home/news/drugs-in-the-pipeline/nyxol-ophthalmic-solution-looks-promising-for-night-vision-disturbances/

Nyxol Ophthalmic Solution Looks Promising for Night ... Results showed that the study met the primary endpoint with 13% of patients in the Nyxol arm gaining at least 15 letters of mLCVA at day 8 ...

5. withpower.com withpower.com/trial/phase-3-night-blindness-3-2024-4a564

Phentolamine Eye Drops 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, ...

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. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/217064s000lbl.pdf

NDA 217064 Page 4 | FDA Ophthalmic solution: clear and colorless solution containing phentolamine 0.75% in a single- patient-use vial. 4. CONTRAINDICATIONS. None. 5. WARNINGS AND ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7802916/

Phentolamine Mesylate Ophthalmic Solution Provides Lasting ... Phentolamine mesylate ophthalmic solution (PMOS), applied to the eye topically, was shown previously to have beneficial effects in patients with dim light ...