Timolol + Latanoprost for Glaucoma

Recruiting at 2 trial locations

Overseen By Nadine Helmy

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Ohio State University

Must not be taking: Cannabis, Lumify, Latisse, Steroids

Disqualifiers: Pregnancy, Advanced visual loss, 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

Compensation: Varies

Number of Visits: 7

100 Participants Needed

Trial Summary

What is the purpose of this trial?

Glaucoma is a major cause of blindness. The inability to predict a patient's IOP response to medications is a critical barrier for the clinician to consistently provide highly effective IOP-based treatments. Current trial-and-error approaches to glaucoma management are inefficient and have not addressed this barrier as there are no predictive factors for drug response. Our long-term goal is to improve outcomes by identifying biomarkers and environmental factors that profile a patient at risk for glaucoma by age-of-onset, rate of disease progression, "poor response" to treatment, and large IOP fluctuation. Our purpose of this research project is to address this critical barrier by focusing on physiological factors that predict IOP response to drugs.

Do I need to stop my current medications for the trial?

You may need to stop certain medications for this trial. Participants must be on a stable regimen of medications that affect eye pressure for at least 30 days before starting the trial, and some medications like cannabis products and certain eye drops are not allowed during the study.

What data supports the effectiveness of the drug Timolol + Latanoprost for treating glaucoma?

Research shows that the combination of latanoprost 0.005% and timolol 0.5% is effective in lowering intraocular pressure (the pressure inside the eye) in glaucoma patients, providing an alternative to using each drug alone or in an unfixed combination. ^{1 2 3 4 5}

Is the combination of Timolol and Latanoprost safe for humans?

Studies have shown that the combination of Timolol and Latanoprost is generally safe for humans, particularly for those with open-angle glaucoma or ocular hypertension. These medications have been compared to other treatments and have been found to be well-tolerated, with safety profiles similar to other commonly used eye pressure-lowering treatments. ^{5 6 7 8 9}

How is the drug combination of Timolol and Latanoprost unique for treating glaucoma?

The combination of Timolol and Latanoprost is unique because it combines two different types of medications into one solution, which can be more convenient and effective for lowering eye pressure in glaucoma patients compared to using each drug separately. This fixed combination is typically administered once daily in the evening, offering an effective alternative for patients who need additional pressure reduction. ^{1 5 8 9 10}

Research Team

Sayoko Moroi, MD, PhD

Principal Investigator

Professor and Chair

Eligibility Criteria

This trial is for people with open-angle glaucoma or ocular hypertension, who have not had certain eye surgeries or treatments. Participants should have an untreated eye pressure of at least 21 mmHg and be able to remove contact lenses for tests. They must also be willing to attend multiple on-site visits and cooperate with study procedures.

Inclusion Criteria

I have at least one eye with its natural lens.

I can attend all required study visits in person.

Any self-declared ethnicity-race

Exclusion Criteria

I have had surgery for glaucoma in my eye(s) involved in the study.

I have taken oral steroids in the last 30 days.

I have been on a stable medication for over 30 days that could affect my eye pressure.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Measurement

AHD measurements are performed at baseline without glaucoma medications, including IOP, aqueous humor flow, outflow facility, and episcleral venous pressure.

1 week

1 visit (in-person)

Treatment Phase 1

Participants receive timolol 0.5% (1 drop two times daily) for 7 days, followed by a washout period.

1 week

1 visit (in-person)

Washout

Participants undergo a washout period to clear the effects of the first treatment before starting the second treatment.

1 week

1 visit (in-person)

Treatment Phase 2

Participants receive latanoprost 0.005% (1 drop daily in the evening) for 7 days.

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including IOP fluctuation assessment using the Icare® HOME tonometer.

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• Latanoprost 0.005% Ophthalmic Solution
• Timolol 0.5% ophthalmic solution

Trial Overview The trial is testing the effects of two eye drop medications, Timolol (a beta-blocker) and Latanoprost (a prostaglandin analogue), on intraocular pressure in patients with glaucoma or high eye pressure. It aims to identify factors that predict how well a patient will respond to these drugs.

Participant Groups

Group I: Timolol 0.5% Experimental Treatment 1 Intervention

To compare the variation in response to timolol between individuals

Group II: Latanoprost 0.005% Experimental Treatment 1 Intervention

To compare the variation in response to latanoprost between individuals

Latanoprost 0.005% Ophthalmic Solution is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Xalatan for:

• Glaucoma
• Ocular hypertension

Approved in United States as Xalatan for:

• Glaucoma
• Ocular hypertension

Approved in Canada as Xalatan for:

• Glaucoma
• Ocular hypertension

Approved in Japan as Monoprost for:

• Glaucoma
• Ocular hypertension

Who Is Running the Clinical Trial?

Ohio State University

Lead Sponsor

Trials

891

Recruited

2,659,000+

University of Nebraska

Collaborator

Trials

563

Recruited

1,147,000+

Mayo Clinic

Collaborator

Trials

3,427

Recruited

3,221,000+

National Eye Institute (NEI)

Collaborator

Trials

572

Recruited

1,320,000+

Findings from Research

The fixed combination of 0.005% latanoprost and 0.5% timolol maleate, administered once daily in the evening, effectively lowers intraocular pressure (IOP) in glaucoma patients.

This combination serves as a beneficial alternative for patients who are not achieving optimal IOP control with either drug alone or with an unfixed combination of latanoprost and timolol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect on diurnal intraocular pressure of the fixed combination of latanoprost 0.005% and timolol 0.5% administered in the evening in glaucoma. Polo, V., Larrosa, JM., Ferreras, A., et al.[2018]

In a study involving 34 participants with primary open-angle glaucoma, the fixed combination of timolol and dorzolamide (TDFC) showed a statistically significant lower mean diurnal intraocular pressure compared to latanoprost, particularly at the 10:00 PM measurement.

Patients preferred latanoprost due to its once-daily dosing convenience, and it had fewer adverse effects, with a notable absence of the bitter taste reported with TDFC and only one case of new-onset asthma linked to TDFC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Twenty-four-hour diurnal curve comparison of commercially available latanoprost 0.005% versus the timolol and dorzolamide fixed combination. Konstas, AG., Papapanos, P., Tersis, I., et al.[2018]

In a study of 32 subjects with primary open-angle glaucoma, both the latanoprost/timolol fixed combination (LTFC) and the combination of brimonidine with latanoprost effectively reduced intraocular pressure (IOP) to similar levels, indicating comparable efficacy.

Safety profiles for both treatment regimens were also similar, with no significant differences in side effects, suggesting that both options are safe for managing IOP in glaucoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of the latanoprost/timolol maleate fixed combination vs concomitant brimonidine and latanoprost therapy. Stewart, WC., Stewart, JA., Day, DG., et al.[2018]

In a study of 32 patients with primary open-angle glaucoma or ocular hypertension, the fixed combination of timolol maleate and latanoprost (TLFC) given once daily in the evening significantly reduced intraocular pressure (IOP) more than the twice-daily treatment of brimonidine and timolol, with a mean IOP decrease from 20.9 mmHg to 17.9 mmHg (p = 0.02).

Both treatment regimens had similar side effects, indicating that TLFC is not only more effective in lowering IOP but also maintains a comparable safety profile to the brimonidine and timolol combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of timolol maleate/latanoprost fixed combination versus timolol maleate and brimonidine given twice daily. Stewart, WC., Stewart, JA., Day, D., et al.[2019]

In a study involving 408 patients with open-angle glaucoma or ocular hypertension, the combination of travoprost 0.004% and timolol 0.5% (Trav/Tim) significantly lowered intraocular pressure (IOP) compared to latanoprost 0.005% and timolol 0.5% (Lat/Tim) at multiple time points, indicating its efficacy as a treatment.

Both treatments were well-tolerated, with mild adverse events reported; however, Trav/Tim had a slightly higher incidence of hyperemia, which was not clinically significant, suggesting that it is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 1-year study to compare the efficacy and safety of once-daily travoprost 0.004%/timolol 0.5% to once-daily latanoprost 0.005%/timolol 0.5% in patients with open-angle glaucoma or ocular hypertension. Topouzis, F., Melamed, S., Danesh-Meyer, H., et al.[2019]

In a study involving 30 patients with primary open-angle glaucoma or ocular hypertension, both timolol hemihydrate and timolol maleate gel were found to be equally effective in lowering intraocular pressure when used alongside latanoprost, with no significant differences in pressure reduction (P = .74).

Both treatments were safe, showing no adverse effects or differences in visual acuity, indicating that either form of timolol can be a reliable adjunctive therapy for managing intraocular pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of timolol solution once daily vs timolol gel added to latanoprost. Stewart, WC., Day, DG., Sharpe, ED., et al.[2019]

In a study involving 313 patients with open-angle glaucoma, latanoprostene bunod demonstrated the greatest reduction in intraocular pressure (IOP) after 3 months of treatment compared to latanoprost and timolol maleate.

All three treatments were effective in lowering IOP, but latanoprostene bunod was found to be superior, while common adverse ocular effects were observed across all treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative evaluation of Latanoprostene Bunod, Timolol Maleate, and latanoprost Ophthalmic Solutions to assess their safety and efficacy in lowering intraocular pressure for the management of Open-Angle Glaucoma. Wang, Y., Liao, Y., Nie, X.[2022]

In an 8-week study involving 250 Chinese patients with primary open-angle glaucoma or ocular hypertension, a single evening dose of the fixed-combination latanoprost and timolol (LTFC) was found to be as effective as the unfixed combination of the same medications taken at different times (LTuFC) in lowering intraocular pressure (IOP).

Both treatment options were well tolerated, indicating that LTFC is a safe and effective once-daily alternative for patients whose IOP was not adequately controlled with β-blocker therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy and safety of the fixed versus unfixed combination of latanoprost and timolol in Chinese patients with open-angle glaucoma or ocular hypertension. Zhao, JL., Ge, J., Li, XX., et al.[2021]

In a study involving 37 patients with glaucoma or ocular hypertension, both Timoptol XE and Lizmon TG gel-forming timolol solutions effectively maintained intraocular pressure (IOP) levels similar to the standard timolol solution, indicating their efficacy as treatment options.

Patient preference surveys showed that 78.4% of participants preferred the gel-forming solutions over the traditional twice-daily timolol, and there were no significant differences in tolerability or adverse effects between the two gel formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of efficacy and tolerability between two gel-forming timolol maleate ophthalmic solutions in patients with glaucoma or ocular hypertension. Shibuya, T., Kashiwagi, K., Tsukahara, S.[2017]

A 4-week trial of latanoprost alone or in combination with timolol-gel in 45 patients with normal-tension glaucoma (NTG) can predict intraocular pressure (IOP) outcomes after 6 months of treatment.

Both latanoprost and timolol-gel significantly reduced IOP from baseline during the trial, indicating their efficacy in managing NTG, with the combination showing sustained effects over the longer term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Short and long-term hypotensive effect of timolol-gel and latanoprost instillation in normal-tension glaucoma]. Hashimoto, T., Hara, T., Takahashi, Y., et al.[2022]

References

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

Effect on diurnal intraocular pressure of the fixed combination of latanoprost 0.005% and timolol 0.5% administered in the evening in glaucoma. [2018]

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

Twenty-four-hour diurnal curve comparison of commercially available latanoprost 0.005% versus the timolol and dorzolamide fixed combination. [2018]

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

Efficacy and safety of the latanoprost/timolol maleate fixed combination vs concomitant brimonidine and latanoprost therapy. [2018]

4. Denmark pubmed.ncbi.nlm.nih.gov

Efficacy and safety of timolol maleate/latanoprost fixed combination versus timolol maleate and brimonidine given twice daily. [2019]

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

A 1-year study to compare the efficacy and safety of once-daily travoprost 0.004%/timolol 0.5% to once-daily latanoprost 0.005%/timolol 0.5% in patients with open-angle glaucoma or ocular hypertension. [2019]

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

Efficacy and safety of timolol solution once daily vs timolol gel added to latanoprost. [2019]

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

Comparative evaluation of Latanoprostene Bunod, Timolol Maleate, and latanoprost Ophthalmic Solutions to assess their safety and efficacy in lowering intraocular pressure for the management of Open-Angle Glaucoma. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Comparative efficacy and safety of the fixed versus unfixed combination of latanoprost and timolol in Chinese patients with open-angle glaucoma or ocular hypertension. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Comparison of efficacy and tolerability between two gel-forming timolol maleate ophthalmic solutions in patients with glaucoma or ocular hypertension. [2017]

10. Japan pubmed.ncbi.nlm.nih.gov

[Short and long-term hypotensive effect of timolol-gel and latanoprost instillation in normal-tension glaucoma]. [2022]