Netarsudil vs Brimonidine for Normal Tension Glaucoma

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

100 Participants Needed

Trial Summary

What is the purpose of this trial?

A randomized, multicenter, investigator-masked prospective study of NTG patients currently on latanoprost 0.005% monotherapy, to study the effect of IOP change with the introduction of netarsudil 0.02% vs brimonidine 0.1%. Subjects will be assessed at a screening visit, and 1 follow-up visit. Clinical evaluations will include visual acuity and IOP .

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 data supports the effectiveness of the drug Netarsudil for treating normal tension glaucoma?

Research shows that Netarsudil is effective in lowering eye pressure in patients with open-angle glaucoma and ocular hypertension, which are conditions similar to normal tension glaucoma. It works by increasing the outflow of fluid in the eye, leading to significant reductions in eye pressure. ^{1 2 3 4 5}

Is Netarsudil safe for use in humans?

Netarsudil has been shown to be generally safe in humans, with the most common side effect being mild redness in the eyes. Serious side effects are rare, likely because the drug does not spread much beyond the eye. ^{1 2 3 5 6}

What makes the drug Netarsudil unique for treating normal tension glaucoma?

Netarsudil is unique because it is a Rho kinase inhibitor that lowers intraocular pressure by increasing the outflow of fluid through the eye's trabecular meshwork, which is different from other treatments that often reduce fluid production or increase outflow through different pathways. It is administered as an eye drop once daily in the evening, and it has a mild side effect profile with minimal systemic exposure. ^{2 4 7 8 9}

Research Team

Zarmeena Vendal, MD

Principal Investigator

Westlake Eye Specialists

Eligibility Criteria

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 am 18 years old or older.

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 an adult without cognitive impairments and not critically ill.

Timeline

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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/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 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 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]

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]

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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

The effectiveness and safety profile of netarsudil 0.02% in glaucoma treatment: real-world 6-month outcomes. [2022]

2. Spain pubmed.ncbi.nlm.nih.gov

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

3. United States 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). [2019]

4. 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]

5. India pubmed.ncbi.nlm.nih.gov

Pragmatic adjunctive usage of netarsudil: A retrospective chart review from a tertiary care center. [2022]

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

The Effects of Netarsudil Ophthalmic Solution on Aqueous Humor Dynamics in a Randomized Study in Humans. [2019]

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

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

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

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

9. Israel pubmed.ncbi.nlm.nih.gov

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