AR-15512 Eye Drops for Dry Eye Syndrome

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests eye drops called AR-15512 to determine if they increase tear production in people with dry eye disease. It targets individuals who have experienced dry eyes in the past year and have used or considered using artificial tears in the past six months. Participants should have good eye health and reasonable vision without significant issues like glaucoma. The trial requires using the eye drops in a specific sequence, with one drop in each eye a few hours apart. As a Phase 3 trial, it represents the final step before FDA approval, allowing participants to contribute to the potential availability of a new treatment.

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.

Is there any evidence suggesting that AR-15512 eye drops are likely to be safe for humans?

Research has shown that AR-15512 eye drops have been well-tolerated in past studies, with no major safety issues identified. One study found no serious eye-related side effects, suggesting that the eye drops are safe for treating dry eye syndrome. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for dry eye syndrome, which often include artificial tears and anti-inflammatory medications, AR-15512 eye drops offer a promising new approach. This treatment uses a unique active ingredient at a concentration of 0.003%, potentially providing relief with a novel mechanism of action. Researchers are particularly excited because AR-15512 is designed to be administered in a staggered cadence, which could enhance its effectiveness and convenience for patients. This innovative delivery method might lead to faster or more sustained relief from symptoms, setting it apart from current options.

What evidence suggests that AR-15512 might be an effective treatment for dry eye disease?

Studies have shown that AR-15512 eye drops hold promise for treating dry eye disease. Earlier research found that the drops significantly increased tear production, a primary concern for those with dry eye. Another study showed that, although not all main goals were achieved, clear improvements in dry eye signs were evident. Participants in this trial will receive this unique treatment, which has been favorably compared to current treatments for its potential to become a new standard of care. Overall, AR-15512 shows great promise in relieving dry eye disease symptoms. ^{1 3 4 6 7}

Who Is on the Research Team?

Clinical Trial Lead, Pharma

Principal Investigator

Alcon Research, LLC

Are You a Good Fit for This Trial?

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

I do not have any serious eye conditions besides dry eye.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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]

Citations

1. alcon.com alcon.com/media-release/alcon-announces-positive-topline-results-phase-3-comet-trials-ar-15512-novel-topical/

Alcon Announces Positive Topline Results From Phase 3 ... AR-15512 demonstrated this important achievement in both pivotal efficacy and safety studies and it represents a first-in-class candidate for chronic dry eye.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05360966

Study Evaluating the Safety and Efficacy of AR-15512 ... 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 90 days ... dry eye symptoms (prior to drop exposure). The 2 scores were multiplied and ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35970431/

A randomized, vehicle-controlled, Phase 2b study of two ... Although predefined co-primary study endpoints were not met, AR-15512 demonstrated statistically significant improvements in DED signs, ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0161642025006050

Acoltremon Ophthalmic Solution 0.003% for Signs and ... In both phase 3 studies, ACO compared with VEH led to consistent, clinically meaningful tear production as well as reductions in other DED signs ...

5. clinicaltrialsarena.com clinicaltrialsarena.com/news/aerie-doses-participant-dry-eye-disease/

Aerie doses first participant in Phase III dry eye disease ... AR-15512 has the potential to be the new standard of care for patients suffering from dry eye disease.”

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2025/217370Orig1s000RiskR.pdf

217370Orig1s000 - accessdata.fda.gov The applicant was informed that based on the currently available data, no significant safety concerns had been identified to date. 3.

7. clinicaltrialsarena.com clinicaltrialsarena.com/news/alcons-dry-eye-drug-achieves-primary-endpoints-in-phase-iii-trials/

Alcon's dry eye drug achieves primary endpoints in Phase ... Alcon noted that AR-15512 was well tolerated, with no serious ocular adverse events being reported during the trials.