Eye Drops for Open-Angle Glaucoma

Recruiting at 11 trial locations

Overseen By Alcon Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Alcon Research

Must not be taking: Ocular hypotensives

Disqualifiers: Other glaucoma, Glaucoma surgery, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

450 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this two-stage clinical trial is to assess the safety and hypotensive efficacy of AR-17043 and PG043 ophthalmic solutions in subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT).

Will I have to stop taking my current medications?

The trial requires that you are not using more than 2 eye pressure-lowering medications within 30 days before joining. If you are on more than 2, you may need to stop some of them.

What evidence supports the effectiveness of the drug for open-angle glaucoma?

The combination of netarsudil and latanoprost has been shown to significantly reduce intraocular pressure (IOP) in patients with open-angle glaucoma, with 59-65% of patients achieving a 30% or greater reduction in IOP, compared to 29-37% with latanoprost alone and 21-29% with netarsudil alone. ^{1 2 3 4 5}

Is the eye drop treatment for open-angle glaucoma safe for humans?

The eye drops containing Netarsudil and Latanoprost have been studied in clinical trials and are generally considered safe for humans. The most common side effect is mild redness in the eyes, and there are minimal serious side effects due to low systemic exposure. ^{1 2 3 6 7}

How does the drug AR-17043 differ from other treatments for open-angle glaucoma?

The drug AR-17043 is unique because it combines netarsudil, a Rho kinase inhibitor that enhances fluid outflow through the eye's drainage system, with latanoprost, a prostaglandin analog that increases fluid outflow through a different pathway. This combination has been shown to significantly reduce eye pressure more effectively than using either component alone, offering a novel approach to treating open-angle glaucoma. ^{3 4 8 9 10}

Research Team

Clinical Trial Lead, Pharma

Principal Investigator

Alcon Research, LLC

Eligibility Criteria

This trial is for individuals with open-angle glaucoma or ocular hypertension. Participants should have a specific level of eye pressure and vision capability, and be able to administer eye drops themselves or with help. Those who've had certain eye treatments or conditions that could affect the study's outcome can't join.

Inclusion Criteria

Other protocol-specified inclusion criteria may apply

I have been diagnosed with open-angle glaucoma or high eye pressure in both eyes.

I have been diagnosed with open-angle glaucoma or high eye pressure in both eyes.

Exclusion Criteria

I am using more than 2 eye pressure-lowering medications.

I don't have any conditions that would prevent accurate medical measurements.

I struggle to put in eyedrops correctly.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Stage 1

Participants receive one of the five treatments for 7 days: 3 concentrations of AR-17043, placebo, or netarsudil 0.02%

1 week

Daily visits for IOP measurement

Treatment Stage 2

Participants receive one of the five treatments for 28 days: low/high concentrations of PG043, AR-17043 high concentration, latanoprost, or Rocklatan

4 weeks

Weekly visits for IOP measurement

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• AR-17043
• Latanoprost
• Netarsudil

Trial Overview The trial is testing the safety and effectiveness of two ophthalmic solutions: AR-17043 and PG043, in lowering eye pressure for patients with open-angle glaucoma or ocular hypertension. It compares these new treatments against other known medications like Netarsudil and Latanoprost.

Participant Groups

Group I: PG043 low concentration (Stage 2) Experimental Treatment 1 Intervention

PG043 Ophthalmic Solution, one drop in each eye in the evening on Days 1-28.

Group II: PG043 high concentration (Stage 2) Experimental Treatment 1 Intervention

PG043 Ophthalmic Solution, one drop in each eye in the evening on Days 1-28.

Group III: AR-17043 medium concentration (Stage 1) Experimental Treatment 1 Intervention

AR-17043 Ophthalmic Solution, one drop in each eye in the morning on Day 1, followed by one drop in each eye in the evening on Days 2-7.

Group IV: AR-17043 low concentration (Stage 1) Experimental Treatment 1 Intervention

AR-17043 Ophthalmic Solution, one drop in each eye in the morning on Day 1, followed by one drop in each eye in the evening on Days 2-7.

Group V: AR-17043 high concentration (Stage 1) Experimental Treatment 1 Intervention

AR-17043 Ophthalmic Solution, one drop in each eye in the morning on Day 1, followed by one drop in each eye in the evening on Days 2-7.

Group VI: Rhopressa (Stage 1) Active Control 1 Intervention

Netarsudil 0.02% Ophthalmic Solution, one drop in each eye in the morning on Day 1, followed by one drop in each eye in the evening on Days 2-7.

Group VII: AR-17043 high concentration (Stage 2) Active Control 1 Intervention

AR-17043 Ophthalmic Solution, one drop in each eye in the evening on Days 1-28.

Group VIII: Latanoprost (Stage 2) Active Control 1 Intervention

Latanoprost 0.005% Ophthalmic Solution, one drop in each eye in the evening on Days 1-28.

Group IX: Rocklatan (Stage 2) Active Control 1 Intervention

Netarsudil 0.02%/Latanoprost 0.005% Ophthalmic Solution, one drop in each eye in the evening on Days 1-28.

Group X: AR-17043 vehicle (Stage 1) Placebo Group 1 Intervention

AR-17043 Vehicle, one drop in each eye in the morning on Day 1, followed by one drop in each eye in the evening on Days 2-7.

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

Netarsudil ophthalmic solution 0.02% effectively lowers intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension, showing significant reductions in IOP comparable to the standard treatment of twice-daily timolol over three months in phase III trials.

The most common side effect was mild conjunctival hyperemia, which did not worsen with continued use, and netarsudil had minimal serious or systemic adverse effects, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Netarsudil ophthalmic solution 0.02% for the treatment of patients with open-angle glaucoma or ocular hypertension. Kopczynski, CC., Heah, T.[2019]

The fixed-dose combination (FDC) of netarsudil 0.02% and latanoprost 0.005% significantly lowered intraocular pressure (IOP) more effectively than either medication alone, with reductions of 2.2 to 3.3 mmHg compared to netarsudil and 1.5 to 2.4 mmHg compared to latanoprost over a 3-month period.

The FDC was well-tolerated, with no serious treatment-related adverse events reported, and the most common side effect, conjunctival hyperemia, was generally mild, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Once-Daily Netarsudil/Latanoprost Fixed-Dose Combination for Elevated Intraocular Pressure in the Randomized Phase 3 MERCURY-2 Study. Walters, TR., Ahmed, IIK., Lewis, RA., et al.[2021]

Netarsudil ophthalmic solution 0.02% effectively lowers intraocular pressure (IOP) in patients with open-angle glaucoma and ocular hypertension, showing a reduction of 16%-21% in IOP in clinical trials compared to other common treatments.

In combination with Latanoprost, Netarsudil led to a significant 64.5% of patients achieving a ≥30% reduction in mean diurnal IOP, while the most common side effect, conjunctival hyperemia, did not significantly impact patient tolerance to the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[ROCK (RHO-KINASE INHIBITORS) FOR THE TREATMENT OF OPEN-ANGLE GLAUCOMA AND OCULAR HYPERTENSION]. Hayat, H., Achiron, A., Masarwa, D., et al.[2023]

The fixed-dose combination of netarsudil 0.02% and latanoprost 0.005% is effective in significantly reducing intraocular pressure (IOP) in patients with open-angle glaucoma and ocular hypertension, with 59-65% of subjects achieving a reduction of 30% or greater in clinical trials.

This combination therapy was well tolerated, showing mostly mild ocular side effects and limited systemic effects, making it a safe option for patients compared to the individual components.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Netarsudil/latanoprost fixed-dose combination for the treatment of open-angle glaucoma or ocular hypertension. Radell, JE., Serle, JB.[2019]

Rhopressa (netarsudil) is an effective treatment for open-angle glaucoma that works by inhibiting norepinephrine transport and Rho-associated protein kinase (ROCK), but it can cause side effects like conjunctival hyperemia.

This case report highlights a unique instance of Rhopressa-induced corneal edema in a 79-year-old woman without prior corneal issues, suggesting that there may be unknown effects of the treatment that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rhopressa-induced corneal edema: a case report. Chu, MJ., Song, M., Palmares, T., et al.[2021]

In a 28-day study involving 224 patients with open-angle glaucoma or ocular hypertension, AR-13324 demonstrated a reduction in intraocular pressure (IOP) but was less effective than latanoprost, with a 5.7 mmHg decrease compared to latanoprost's 6.8 mmHg.

The most common side effect of AR-13324 was ocular hyperemia, occurring in 52% to 57% of patients, which was significantly higher than the 16% incidence seen with latanoprost.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-masked, randomized, dose-response study of AR-13324 versus latanoprost in patients with elevated intraocular pressure. Bacharach, J., Dubiner, HB., Levy, B., et al.[2022]

Netarsudil/latanoprost fixed-dose combination therapy significantly reduces intraocular pressure (IOP) more than latanoprost alone, with a mean difference of -2.41 mmHg after 2 weeks and -1.77 mmHg after 4 to 6 weeks, based on a meta-analysis of four studies.

While the combination therapy is effective, it is associated with a higher risk of conjunctival hyperemia compared to latanoprost alone, although the symptoms are generally mild and lead to few discontinuations among patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Netarsudil/Latanoprost Therapy with Latanoprost Monotherapy for Lowering Intraocular Pressure: A Systematic Review and Meta-analysis. Lee, JW., Ahn, HS., Chang, J., et al.[2022]

A study involving 266 patients with ocular hypertension or primary open-angle glaucoma showed that Bausch & Lomb's latanoprost 0.005% eyedrops effectively reduced intraocular pressure (IOP) similarly to Xalatan, with both treatments achieving comparable IOP reductions over 6 weeks.

The trial confirmed that latanoprost was noninferior to Xalatan, meaning it works just as well, and both medications had similar safety and tolerability profiles, making them equally viable options for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Latanoprost 0.005% test formulation is as effective as Xalatan® in patients with ocular hypertension and primary open-angle glaucoma. Allaire, C., Dietrich, A., Allmeier, H., et al.[2018]

Latanoprost is an effective treatment for lowering intraocular pressure (IOP) in patients with open-angle glaucoma and ocular hypertension, achieving a reduction of up to 35% over at least two years, and is comparable or slightly more effective than timolol.

The drug is applied topically at a low dose of 0.005% once daily, and due to its rapid metabolism outside the eye, it has minimal systemic side effects, although it can cause increased iris pigmentation in some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Latanoprost in the treatment of glaucoma and ocular hypertension. Watson, PG.[2019]

Latanoprost (Xalatan) monotherapy significantly reduces intraocular pressure (IOP) in patients with primary open angle glaucoma (POAG), with an average decrease of 5.1 mmHg after 60 days of treatment.

As a once-daily treatment, latanoprost improves patient compliance compared to other drug combinations, while also offering effective IOP control and fewer side effects, potentially reducing the need for surgical interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of latanoprost (Xalatan) monotherapy in newly discovered and previously medicamentously treated primary open angle glaucoma patients. Pavan, J., Stambuk, N., Curković, T., et al.[2018]

References

1. Spain pubmed.ncbi.nlm.nih.gov

Netarsudil ophthalmic solution 0.02% for the treatment of patients with open-angle glaucoma or ocular hypertension. [2019]

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

Once-Daily Netarsudil/Latanoprost Fixed-Dose Combination for Elevated Intraocular Pressure in the Randomized Phase 3 MERCURY-2 Study. [2021]

3. Israel pubmed.ncbi.nlm.nih.gov

[ROCK (RHO-KINASE INHIBITORS) FOR THE TREATMENT OF OPEN-ANGLE GLAUCOMA AND OCULAR HYPERTENSION]. [2023]

4. Spain pubmed.ncbi.nlm.nih.gov

Netarsudil/latanoprost fixed-dose combination for the treatment of open-angle glaucoma or ocular hypertension. [2019]

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

Rhopressa-induced corneal edema: a case report. [2021]

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

Double-masked, randomized, dose-response study of AR-13324 versus latanoprost in patients with elevated intraocular pressure. [2022]

7. Korea (South) pubmed.ncbi.nlm.nih.gov

Comparison of Netarsudil/Latanoprost Therapy with Latanoprost Monotherapy for Lowering Intraocular Pressure: A Systematic Review and Meta-analysis. [2022]

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

Latanoprost 0.005% test formulation is as effective as Xalatan® in patients with ocular hypertension and primary open-angle glaucoma. [2018]

9. Spain pubmed.ncbi.nlm.nih.gov

Latanoprost in the treatment of glaucoma and ocular hypertension. [2019]

10. Croatia pubmed.ncbi.nlm.nih.gov

Effectiveness of latanoprost (Xalatan) monotherapy in newly discovered and previously medicamentously treated primary open angle glaucoma patients. [2018]