Netarsudil vs Brimonidine for Normal Tension Glaucoma

No longer recruiting at 3 trial locations

Overseen By Zarmeena Vendal, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Westlake Eye Specialists

Must be taking: Latanoprost

Must not be taking: Brimonidine, Netarsudil

Disqualifiers: Angle closure glaucoma, Secondary glaucoma, others

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

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how two different treatments, netarsudil and brimonidine (both eye drop medications), affect eye pressure in people with normal tension glaucoma. The goal is to determine which treatment better assists those already using latanoprost, a common glaucoma medication. Participants must have normal tension glaucoma, characterized by specific eye conditions, and must have used latanoprost for at least six weeks. The study focuses on changes in eye pressure and vision quality for those meeting these criteria. As a Phase 4 trial, this research involves FDA-approved treatments and aims to understand how they can benefit more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does require that you continue using latanoprost 0.005% monotherapy.

What is the safety track record for these treatments?

Research has shown that netarsudil, a drug for glaucoma, is generally safe. The FDA has already approved it for treating glaucoma and high eye pressure. Studies have found that netarsudil effectively lowers eye pressure.

However, some common side effects have been reported. About 20% of patients experience mild eye pain, some bleeding in the eye, or changes on the eye's surface, which are usually harmless. These side effects are typically not serious and tend to resolve over time.

Brimonidine, another treatment compared in the trial, is also commonly used to lower eye pressure. It has been available for a while and is generally well-tolerated.

In summary, both netarsudil and brimonidine are considered safe for people with glaucoma, with some manageable side effects. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for normal tension glaucoma aim to reduce intraocular pressure, typically using medications like beta-blockers or prostaglandin analogs. However, Netarsudil is unique because it works by inhibiting rho kinase, which not only lowers eye pressure by enhancing outflow through the trabecular meshwork but also reduces episcleral venous pressure. Researchers are excited about Netarsudil because this dual mechanism offers a new avenue for managing glaucoma, potentially providing better outcomes for patients who don't respond well to traditional treatments.

What evidence suggests that this trial's treatments could be effective for normal tension glaucoma?

This trial will compare Netarsudil and Brimonidine for treating normal tension glaucoma. Research has shown that Netarsudil, one of the treatments participants may receive, helps lower eye pressure in people with glaucoma. In one study, Netarsudil reduced eye pressure by 5.2 to 6.6 mm Hg. Lowering eye pressure is crucial because it can prevent eye damage. Another study found that Netarsudil successfully reached the desired eye pressure in 58% of cases, which is significant for those who might need additional treatment like laser therapy or surgery. Furthermore, the FDA has approved Netarsudil for treating glaucoma, underscoring its proven effectiveness. ^{1 2 6 7 8}

Who Is on the Research Team?

Zarmeena Vendal, MD

Principal Investigator

Westlake Eye Specialists

Are You a Good Fit for This Trial?

This trial is for patients with Normal Tension Glaucoma (NTG) who are already using latanoprost. Participants should be stable on their current treatment and available for a screening visit and at least one follow-up. Specific inclusion or exclusion criteria were not provided.

Inclusion Criteria

I have normal tension glaucoma and have been on latanoprost for 6 weeks.

Exclusion Criteria

I have a type of glaucoma that is not primary.

I have a specific type of glaucoma not caused by high eye pressure alone.

I am allergic to or have not responded to brimonidine or netarsudil.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Participants receive either netarsudil 0.02% or brimonidine 0.1% in addition to latanoprost 0.005% for 6 weeks

6 weeks

Regular assessments including visual acuity and IOP

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Brimonidine
• Netarsudil

Trial Overview The study compares the effect of adding netarsudil versus brimonidine to NTG patients' existing latanoprost regimen on intraocular pressure (IOP). It's a randomized, multicenter trial where participants won't know which additional medication they're receiving.

How Is the Trial Designed?

Group I: Netarsudil Experimental Treatment 1 Intervention

netarsudil 0.02%

Group II: Brimonidine Active Control 1 Intervention

brimonidine 0.1%

Netarsudil is already approved in United States, European Union for the following indications:

Approved in United States as Rhopressa for:

• Open-angle glaucoma
• Ocular hypertension

Approved in European Union as Rhokiinsa for:

• Open-angle glaucoma
• Ocular hypertension

Who Is Running the Clinical Trial?

Westlake Eye Specialists

Lead Sponsor

Trials

1

Recruited

100+

Sengi

Industry Sponsor

Trials

28

Recruited

2,100+

Published Research Related to This Trial

Netarsudil ophthalmic solution 0.02% is a newly approved treatment for lowering intraocular pressure in patients with open-angle glaucoma or ocular hypertension, working by enhancing aqueous humour outflow through the trabecular meshwork.

The recommended dosage is one drop in the affected eye(s) once daily in the evening, and further clinical development is ongoing in Europe and Japan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Netarsudil Ophthalmic Solution 0.02%: First Global Approval. Hoy, SM.[2019]

In a study of 133 glaucoma patients prescribed netarsudil, the medication led to a modest average reduction in intra-ocular pressure (IOP) of -0.8 mmHg, with 67% of eyes showing a decrease, indicating variable efficacy in this population.

However, netarsudil had a high discontinuation rate of 52%, primarily due to reasons such as the need for surgery, allergies, and cost, highlighting challenges in patient compliance and the need for careful consideration of treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pragmatic adjunctive usage of netarsudil: A retrospective chart review from a tertiary care center. Goergen, NS., Gagrani, M., Gulati, V., et al.[2022]

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]

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]

In a study of 340 eyes from 233 glaucoma patients, netarsudil 0.02% significantly reduced intraocular pressure (IOP) by at least 20% in 48% of eyes after one month, with effects maintained over six months, even in patients already using multiple glaucoma medications.

While netarsudil was generally safe, 27.6% of patients reported conjunctival hyperemia and 31.1% experienced blurred vision, though these did not lead to significant visual acuity loss; 15.6% discontinued due to insufficient IOP-lowering effects or side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effectiveness and safety profile of netarsudil 0.02% in glaucoma treatment: real-world 6-month outcomes. Shiuey, EJ., Mehran, NA., Ustaoglu, M., et al.[2022]

Netarsudil 0.02% ophthalmic solution significantly reduced intraocular pressure in patients with open-angle glaucoma and ocular hypertension, showing noninferiority to timolol, a standard treatment, in two large clinical trials involving 1167 patients.

The most common side effect of netarsudil was conjunctival hyperemia, occurring in 50-59% of patients, which was significantly higher than the incidence seen with timolol, indicating a need for monitoring but suggesting netarsudil is generally well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two Phase 3 Clinical Trials Comparing the Safety and Efficacy of Netarsudil to Timolol in Patients With Elevated Intraocular Pressure: Rho Kinase Elevated IOP Treatment Trial 1 and 2 (ROCKET-1 and ROCKET-2). Serle, JB., Katz, LJ., McLaurin, E., et al.[2019]

Netarsudil 0.02% significantly increased the diurnal outflow facility in healthy volunteers, indicating its effectiveness in lowering intraocular pressure (IOP) through enhanced aqueous humor dynamics.

The treatment also reduced episcleral venous pressure, suggesting that netarsudil works through multiple mechanisms to improve fluid drainage in the eye, which is beneficial for patients with open-angle glaucoma and ocular hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of Netarsudil Ophthalmic Solution on Aqueous Humor Dynamics in a Randomized Study in Humans. Kazemi, A., McLaren, JW., Kopczynski, CC., et al.[2019]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8572117/

Effectiveness of Netarsudil as an Additional Therapy for ... Moreover, it was successful in achieving a pre-specified target IOP in 58% of eyes for which glaucoma laser or surgery would be the only ...

2. fda.gov fda.gov/media/108389/download

Rhopressa™ (netarsudil ophthalmic solu Also in this study of subjects with low baseline IOP (14 to 20 mmHg), netarsudil produced substantial IOP reductions that were statistically ...

3. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK572105/

Netarsudil Ophthalmic Solution - StatPearls - NCBI Bookshelf Netarsudil ophthalmic solution (0.02%) is an FDA-approved medication used to treat glaucoma and ocular hypertension.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0002939419300121

Long-term Safety and Ocular Hypotensive Efficacy ... In this randomized, double-masked trial, once-daily dosing of netarsudil 0.02% was effective, consistently lowering IOP through 12 months, and was tolerated by ...

5. glaucomatoday.com glaucomatoday.com/articles/2016-mar-apr/rho-kinasenorepinephrine-transporter-inhibition-for-the-treatment-of-glaucoma-and-ocular-hypertension

Rho Kinase/Norepinephrine Transporter Inhibition for the ... AR-13324 0.02%, the concentration chosen for Rhopressa, reduced IOP by 5.2 to 6.6 mm Hg across all time points. This decrease was approximately 1 mm Hg less ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7647436/

Pooled Efficacy and Safety Profile of Netarsudil Ophthalmic ... In pooled phase III analyses, once-daily netarsudil 0.02% resulted in intraocular pressure (IOP) reduction that was noninferior to twice-daily timolol 0.5%, ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0002939415000550

Ocular Hypotensive Safety and Systemic Absorption of AR ... AR-13324 dosed once daily in the morning produced substantial reductions in baseline intraocular pressure of up to 6 mm Hg that were statistically significant ( ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2017/208254lbl.pdf

RHOPRESSA (netarsudil ophthalmic solution) Label Other common. (approximately 20%) ocular adverse reactions reported were: corneal verticillata, instillation site pain, and conjunctival hemorrhage.