AR-15512 Eye Drops for Dry Eye Syndrome

Recruiting at 1 trial location

Overseen By Alcon Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alcon Research

Must not be taking: Topical anti-inflammatories

Disqualifiers: Glaucoma, Macular degeneration, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 2

81 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

You need to stop using any topical ocular anti-inflammatory medications, corticosteroids, or non-steroidal anti-inflammatory agents at least 30 days before the study visit. The protocol does not specify other medications, so check with the trial team for more details.

What data supports the idea that AR-15512 Eye Drops for Dry Eye Syndrome is an effective drug?

The available research shows that AR-15512 was evaluated in a study called COMET-1, which was a randomized, vehicle-controlled Phase 2b study. This means that the study compared AR-15512 to a placebo (a substance with no therapeutic effect) to see if it was effective in treating dry eye disease. The study found that AR-15512, which works by targeting a specific receptor in the eye, was a potential therapy for improving symptoms of dry eye disease. This suggests that AR-15512 could be an effective treatment for people suffering from this condition. ^{1 2 3 4 5}

What safety data is available for AR-15512 eye drops for dry eye syndrome?

The provided research does not contain specific safety data for AR-15512 eye drops. It includes studies on other compounds like SA001, AR-12286, and AR-13324, as well as the effects of preservatives like benzalkonium chloride in eye drops. None of these directly address the safety of AR-15512. ^{6 7 8 9 10}

Is the drug AR-15512 a promising treatment for dry eye syndrome?

Yes, AR-15512 is a promising drug for treating dry eye syndrome. It was tested in a study and showed potential as a therapy for improving symptoms of dry eye disease, which can greatly affect a person's quality of life. ^{1 2 3 11 12}

What is the purpose of this trial?

The purpose of this study is to evaluate tear production following acute administration of AR-15512 ophthalmic solution 0.003% (0.003% AR-15512) in subjects with dry eye disease (DED).

Research Team

Clinical Trial Lead, Pharma

Principal Investigator

Alcon Research, LLC

Eligibility Criteria

This trial is for individuals who have used or wanted to use artificial tears for dry eye symptoms in the last 6 months, have a vision score of 20/200 or better, and overall good eye health. They must not have worn contact lenses or used lid hygiene products within the past week, nor any ocular anti-inflammatory medications within the past month.

Inclusion Criteria

I have used or wanted to use artificial tears for dry eyes in the last 6 months.

Have a corrected visual acuity score of 20/200 or better in both eyes

Have good general and ocular health, as determined by the investigator using medical history, ophthalmic examination and history

Exclusion Criteria

Use of contact lenses in either eye within 7 days of the Study Visit

I have used eyelid hygiene or heat masks within the last week.

I haven't used any eye inflammation or steroid drops in the last 30 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

Stage 1 Treatment

Participants receive one drop of 0.003% AR-15512 in each eye, staggered 2-4 hours apart

1 day

1 visit (in-person)

Stage 2 Treatment

Participants receive one drop of 0.003% AR-15512 in each eye, staggered 2-4 hours apart

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Treatment Details

Interventions

• AR-15512

Trial Overview The study tests how well a new ophthalmic solution called AR-15512 (0.003%) increases tear production in people with Dry Eye Disease (DED). Participants will receive an acute dose of this medication to assess its effectiveness.

Participant Groups

Group I: 0.003% AR-15512 Experimental Treatment 1 Intervention

One drop in each eye in a staggered cadence (left eye followed by dosing of the right eye) approximately 2-4 hours apart

Who Is Running the Clinical Trial?

Alcon Research

Lead Sponsor

Trials

739

Recruited

128,000+

Raquel C. Bono

Alcon Research

Chief Medical Officer since 2022

MD from Harvard Medical School

David Endicott

Alcon Research

Chief Executive Officer since 2018

MBA from University of Southern California

Findings from Research

In a Phase 2b study involving patients with dry eye disease, the 0.003% concentration of AR-15512 showed significant improvements in eye symptoms and quality of life measures over 12 weeks, particularly at Days 14, 28, and 84.

While the study did not meet its predefined co-primary endpoints, AR-15512 was associated with early and sustained improvements in eye surface health and symptoms, with the most common side effects being mild burning and stinging upon application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, vehicle-controlled, Phase 2b study of two concentrations of the TRPM8 receptor agonist AR-15512 in the treatment of dry eye disease (COMET-1). Wirta, DL., Senchyna, M., Lewis, AE., et al.[2022]

In a study of 2619 individuals with symptomatic dry eye in Japan, 1876 participants did not use any eye drops, highlighting a significant gap in treatment for this condition.

The most commonly used eye drops were artificial tears (53.4%), but various risk factors, such as age and screen exposure time, were identified that contributed to the lack of eye drop use, suggesting areas for targeted intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heterogeneity of eye drop use among symptomatic dry eye individuals in Japan: large-scale crowdsourced research using DryEyeRhythm application. Eguchi, A., Inomata, T., Nakamura, M., et al.[2021]

In a study of 168 patients with moderate dry eye, the HP-Guar gellable lubricant eye drops significantly reduced corneal staining by an average of 4.1 units (62% improvement) after 28 days, indicating effective relief of dry eye signs.

Patients also reported significant symptomatic relief across all six ocular discomfort measures, demonstrating that the eye drops not only improved objective signs but also enhanced subjective comfort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open-label evaluation of HP-Guar gellable lubricant eye drops for the improvement of dry eye signs and symptoms in a moderate dry eye adult population. Hartstein, I., Khwarg, S., Przydryga, J.[2022]

In a study of 50 participants with moderate ocular dryness, Systane(R) Lubricating Eye Drops significantly improved tear film break-up time (TFBUT) after 28 days of use, indicating better eye lubrication.

Participants reported significant relief from all six ocular discomfort symptoms, demonstrating both objective and subjective efficacy of Systane(R) in treating moderate ocular dryness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

One month use of Systane improves ocular surface parameters in subjects with moderate symptoms of ocular dryness. Versura, P., Profazio, V., Campos, EC.[2021]

Dry eye syndrome is a common but often underdiagnosed condition that can lead to chronic pain and increased risk of ocular surface disease, highlighting the need for greater awareness and appropriate interventions.

Experts recommend using preservative-free artificial tear products as the first-line treatment for all levels of dry eye, as they are safer and more effective for patients, ensuring better ocular surface health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increasing importance of dry eye syndrome and the ideal artificial tear: consensus views from a roundtable discussion. Asbell, PA.[2022]

SA001, a new formulation of rebamipide, showed significantly higher systemic exposure of rebamipide compared to conventional rebamipide, with plasma concentrations up to 11.94 times higher at the highest dose, indicating enhanced efficacy potential for treating dry eye disease.

The study demonstrated that SA001 was rapidly absorbed and well-tolerated, with no significant adverse events reported, supporting its safety for further clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Safety, Tolerability and Pharmacokinetic Characteristics of SA001 and Its Active Metabolite Rebamipide after Single and Multiple Oral Administration. Bae, S., Huh, KY., Oh, J., et al.[2023]

In a study involving 18 normal adult volunteers, both formulations of 0.5% AR-12286 Ophthalmic Solution significantly reduced intraocular pressure (IOP) by 3 to 7 mm Hg, demonstrating its efficacy as a treatment for ocular hypertension.

The formulations showed low systemic absorption, with most participants having no measurable drug levels in their blood, and the ocular side effects reported were mild and short-lived, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocular hypotensive efficacy, safety and systemic absorption of AR-12286 ophthalmic solution in normal volunteers. Kopczynski, C., Novack, GD., Swearingen, D., et al.[2013]

Benzalkonium chloride (BAK), a common preservative in eye drops, significantly inhibits mitochondrial function in human corneal epithelial cells and trabecular meshwork cells, leading to potential ocular toxicity, particularly at concentrations used in eye drops.

The study found that BAK is especially harmful to cells with mitochondrial mutations, such as those associated with Leber hereditary optic neuropathy (LHON), suggesting that patients with mitochondrial deficiencies should avoid BAK-containing eye drops to prevent exacerbating their condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Eye Drop Preservative Benzalkonium Chloride Potently Induces Mitochondrial Dysfunction and Preferentially Affects LHON Mutant Cells. Datta, S., Baudouin, C., Brignole-Baudouin, F., et al.[2018]

In a phase 1 clinical trial involving 18 healthy volunteers, the ophthalmic solution AR-13324 (0.02%) showed no significant systemic absorption, with only one subject showing a minimal level of the metabolite AR-13503, indicating a favorable safety profile.

AR-13324 significantly reduced intraocular pressure by up to 6 mm Hg in normotensive subjects, demonstrating its potential efficacy as an ocular hypotensive treatment, with effects greater than those typically seen with other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocular hypotensive safety and systemic absorption of AR-13324 ophthalmic solution in normal volunteers. Levy, B., Ramirez, N., Novack, GD., et al.[2015]

Chronic use of eye drops containing preservatives, particularly benzalkonium chloride (BAC), can lead to significant damage in ocular tissues, including inflammation, fibrosis, and cell loss.

To reduce these harmful effects, preservative-free eye drop formulations are recommended as a safer alternative for treating eye conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Morphological alterations induced by preservatives in eye drops]. Huber-van der Velden, KK., Thieme, H., Eichhorn, M.[2021]

In a survey of 2048 physical education and sports science graduates, the prevalence of diagnosed dry eye syndrome (DES) was found to be 2.9% in men and 9.3% in women, while subjective symptoms were reported at 14.8% in men and 39.8% in women, indicating a significant gender difference in prevalence.

The study identified that contact lens use and daily screen viewing time of 4 hours or more were strongly associated with higher odds of experiencing DES, suggesting that addressing these factors could improve ocular health and quality of life for graduates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of dry eye syndrome and risk factors in physical education and sports science graduates. Murakami, S., Kohmura, Y., Someya, Y., et al.[2023]

The reclassification of dry eye disease (DED) patients from the 2006 to the 2016 diagnostic criteria resulted in a significant increase in the prevalence of definite DED, from 38.8% to 66.8% among 250 patients studied.

Most patients previously classified as having probable DED (79.8%) were reclassified as having definite DED under the new criteria, indicating a shift in how DED is diagnosed and potentially affecting treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in Distribution of Dry Eye Disease by the New 2016 Diagnostic Criteria from the Asia Dry Eye Society. Inomata, T., Shiang, T., Iwagami, M., et al.[2019]

References

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

A randomized, vehicle-controlled, Phase 2b study of two concentrations of the TRPM8 receptor agonist AR-15512 in the treatment of dry eye disease (COMET-1). [2022]

2. Japan pubmed.ncbi.nlm.nih.gov

Heterogeneity of eye drop use among symptomatic dry eye individuals in Japan: large-scale crowdsourced research using DryEyeRhythm application. [2021]

3. England pubmed.ncbi.nlm.nih.gov

An open-label evaluation of HP-Guar gellable lubricant eye drops for the improvement of dry eye signs and symptoms in a moderate dry eye adult population. [2022]

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

One month use of Systane improves ocular surface parameters in subjects with moderate symptoms of ocular dryness. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Increasing importance of dry eye syndrome and the ideal artificial tear: consensus views from a roundtable discussion. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Evaluation of Safety, Tolerability and Pharmacokinetic Characteristics of SA001 and Its Active Metabolite Rebamipide after Single and Multiple Oral Administration. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Ocular hypotensive efficacy, safety and systemic absorption of AR-12286 ophthalmic solution in normal volunteers. [2013]

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

The Eye Drop Preservative Benzalkonium Chloride Potently Induces Mitochondrial Dysfunction and Preferentially Affects LHON Mutant Cells. [2018]

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

Ocular hypotensive safety and systemic absorption of AR-13324 ophthalmic solution in normal volunteers. [2015]

10. Germany pubmed.ncbi.nlm.nih.gov

[Morphological alterations induced by preservatives in eye drops]. [2021]

11. Japan pubmed.ncbi.nlm.nih.gov

Prevalence of dry eye syndrome and risk factors in physical education and sports science graduates. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Changes in Distribution of Dry Eye Disease by the New 2016 Diagnostic Criteria from the Asia Dry Eye Society. [2019]