NCX 470 for Glaucoma

(Denali Trial)

Recruiting at 76 trial locations

Overseen By Nicox Ophthalmics

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Nicox Ophthalmics, Inc.

Disqualifiers: Narrow angles, Ocular disease, Surgery, 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: Unknown

Duration: 12 months

696 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing NCX 470 eye drops to see if they can safely and effectively lower eye pressure in people with high eye pressure or glaucoma. The goal is to protect their vision by reducing the pressure inside their eyes. NCX 470 is a nitric oxide (NO)-donating bimatoprost with clinically demonstrated pressure-lowering effects.

Do I have to stop taking my current medications for the trial?

The trial requires a washout period for any IOP-lowering medications you are currently taking.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) for those currently using IOP-lowering medications. This means you may need to stop taking your current eye pressure medications before participating.

What data supports the idea that NCX 470 for Glaucoma is an effective drug?

The available research does not provide any data on NCX 470 for Glaucoma. The studies listed focus on other drugs and conditions, such as migraine treatments and nasal sprays, without mentioning NCX 470 or its effectiveness for Glaucoma. ^{1 2 3 4 5}

What safety data is available for NCX 470 in glaucoma treatment?

The safety data for NCX 470, which may be related to treatments like latanoprost and bimatoprost, includes findings from various studies. Bimatoprost, a similar agent, has been shown to effectively lower intraocular pressure in glaucoma patients, with common side effects being mild conjunctival hyperaemia and eyelash growth. Long-term use has not raised safety concerns. Comparisons with latanoprost and timolol indicate that bimatoprost is effective and generally well-tolerated, suggesting a favorable safety profile for related treatments like NCX 470. ^{6 7 8 9 10}

Is NCX 470 safe for humans?

Bimatoprost, a related treatment, has been shown to be generally safe in humans, with common side effects including mild eye redness and eyelash growth. No major safety concerns have been reported in long-term use. ^{6 7 8 9 10}

Is NCX 470 a promising drug for glaucoma?

Yes, NCX 470 is a promising drug for glaucoma. It combines latanoprost, which is effective in lowering eye pressure, with a nitric oxide component that helps relax blood vessels. This dual action makes it potentially more effective in reducing eye pressure, which is crucial for treating glaucoma. ^{11 12 13 14 15}

What makes the drug NCX 470 unique for treating glaucoma?

NCX 470 is unique because it combines latanoprost, a prostaglandin analog that increases fluid outflow from the eye, with a nitric oxide (NO) donating component, which helps relax blood vessels and further reduce intraocular pressure (IOP). This dual mechanism may offer more effective IOP reduction compared to treatments that only use one of these mechanisms. ^{11 12 13 14 15}

Research Team

Nicox Ophthalmics

Principal Investigator

Nicox Ophthalmics, Inc.

Eligibility Criteria

This trial is for people who can consent to participate and have open-angle glaucoma or ocular hypertension in both eyes. They must show qualifying eye pressure at different times of the day and have good corrected vision in each eye. Those with recent serious eye surgery, uncontrolled diseases, significant other eye conditions, narrow chamber angles or unsuitable corneal thickness cannot join.

Inclusion Criteria

Your vision with glasses or contacts must be good in each eye.

Ability to provide informed consent and follow study instructions

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

Exclusion Criteria

I have had complex or specific glaucoma surgery in either eye.

I haven't had eye surgery or severe eye trauma in the last 6 months.

I have a disease that is not currently under control.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive NCX 470 0.1% or Latanoprost 0.005% once daily for up to 12 months

12 months

Daily administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Latanoprost 0.005%
• NCX 470 0.1%

Trial Overview The study tests NCX 470 Ophthalmic Solution against Latanoprost to see which is better at lowering intraocular pressure in patients with high eye pressure or open-angle glaucoma. Participants will be randomly assigned to one of these treatments and use it daily for up to a year.

Participant Groups

Group I: NCX 470 0.1% Experimental Treatment 1 Intervention

NCX 470 Ophthalmic Solution, 0.1% dosed once daily to both eyes

Group II: Latanoprost 0.005% Active Control 1 Intervention

Latanoprost Ophthalmic Solution, 0.005% dosed once daily to both eyes

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

Approved in United States as Xalatan for:

• Open-angle glaucoma
• Ocular hypertension

Approved in Canada as Xalatan for:

• Open-angle glaucoma
• Ocular hypertension
• Angle-closure glaucoma treated with peripheral iridotomy or laser iridoplasty

Approved in European Union as Monoprost for:

• Open-angle glaucoma
• Ocular hypertension

Who Is Running the Clinical Trial?

Nicox Ophthalmics, Inc.

Lead Sponsor

Trials

7

Recruited

2,800+

Findings from Research

In a study involving 24 healthy participants, the pharmacokinetics of butorphanol nasal spray were not affected by the co-administration of sumatriptan, indicating no significant drug interaction between the two treatments.

Both butorphanol nasal spray and sumatriptan were well tolerated, with similar safety profiles, suggesting that they can be safely used together for treating acute migraine attacks without the need for dosage adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of pharmacokinetic interaction between butorphanol tartrate nasal spray and sumatriptan succinate. Srinivas, NR., Shyu, WC., Upmalis, D., et al.[2019]

In a post-hoc analysis of a clinical trial involving 1,315 migraine patients, telcagepant (300 mg) provided better 2-hour pain relief than zolmitriptan for patients who had a poor response to triptans, suggesting it may be a beneficial alternative for those who do not respond well to traditional treatments.

The study indicates that different patients may respond better to either triptans or telcagepant, highlighting the need for personalized treatment approaches in migraine management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antimigraine efficacy of telcagepant based on patient's historical triptan response. Ho, TW., Olesen, J., Dodick, DW., et al.[2022]

Almotriptan 12.5 mg was found to be the most effective oral triptan for treating acute migraines, achieving a sustained pain-free rate of 25.9% and the lowest adverse event rate of 14.2% among the studied triptans.

In terms of cost-effectiveness, almotriptan 12.5 mg was the best option, costing $7120 to achieve 100 sustained pain-free patients, while eletriptan 20 mg was the least cost-effective at $16,104.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using patient-centered endpoints to determine the cost-effectiveness of triptans for acute migraine therapy. Kelman, L., Von Seggern, RL.[2006]

In a study involving 529 patients aged 12 and older, long-term treatment with beclomethasone dipropionate (BDP) nasal aerosol significantly improved nasal symptoms in patients with perennial allergic rhinitis (PAR) over 30 and 52 weeks compared to placebo.

BDP nasal aerosol was well tolerated, with a safety profile similar to placebo, although there was a higher incidence of nosebleeds (epistaxis) in the treatment group; overall, there were no clinically significant systemic safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of once-daily treatment with beclomethasone dipropionate nasal aerosol. Weinstein, SF., Andrews, CP., Shah, SR., et al.[2016]

In a study of 522 patients, rizatriptan (10 mg) was found to be more effective than naratriptan (2.5 mg) for treating migraines, providing faster headache relief as early as 30 minutes after administration.

Rizatriptan not only resulted in a higher percentage of patients being pain-free at 2 hours (44.8% vs. 20.7% for naratriptan) but also offered quicker relief from associated migraine symptoms and better overall functioning, with both treatments being well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of rizatriptan 10 mg vs. naratriptan 2.5 mg in migraine. Bomhof, M., Paz, J., Legg, N., et al.[2017]

In a two-month study involving 1283 patients, bimatoprost significantly lowered intraocular pressure (IOP) by an average of 3.4 mm Hg, with the percentage of patients achieving target pressures of ≤18 mm Hg doubling from 33% to 66%.

Bimatoprost was well-tolerated, with conjunctival hyperemia being the most common side effect (3.7%), indicating it is a safe and effective alternative to latanoprost for managing glaucoma and ocular hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocular hypotensive efficacy of bimatoprost when used as a replacement for latanoprost in the treatment of glaucoma and ocular hypertension. Bournias, TE., Lee, D., Gross, R., et al.[2018]

In a study of 606 patients with primary open-angle glaucoma or ocular hypertension, the fixed combination of bimatoprost 0.03% and timolol 0.5% significantly lowered intraocular pressure (IOP) from a baseline of 20.7 mmHg to 16.1 mmHg after 12 weeks, demonstrating a reduction of 22.2%.

The treatment was well tolerated, with 98.7% of physicians and 96.7% of patients rating its tolerability as excellent or good, and only a few adverse events were reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, tolerability and safety of the fixed combination of bimatoprost 0.03% and timolol 0.5% in a broad patient population: multicenter, open-label observational study. Feuerhake, C., Buchholz, P., Kimmich, F.[2019]

In a study of Japanese patients with normal-tension glaucoma who did not respond adequately to latanoprost, switching to bimatoprost resulted in significant reductions in intraocular pressure (IOP) at 4, 8, and 12 weeks.

Bimatoprost was found to be safe and well tolerated, with no significant differences in side effects compared to latanoprost, indicating it is an effective alternative treatment for patients with insufficient response to latanoprost.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of switching from topical latanoprost to bimatoprost in patients with normal-tension glaucoma. Sato, S., Hirooka, K., Baba, T., et al.[2018]

Bimatoprost effectively lowers intraocular pressure (IOP) in patients with open-angle glaucoma and ocular hypertension, showing approximately 1-2 mmHg greater IOP reduction compared to latanoprost and superior efficacy over timolol in clinical trials.

Long-term use of bimatoprost maintains its effectiveness without significant safety concerns, with common side effects being mild conjunctival hyperaemia and eyelash growth, making it a valuable treatment option for glaucoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on bimatoprost in glaucoma therapy. Cantor, LB.[2019]

In a 6-month study involving 61 patients with open-angle glaucoma, both bimatoprost 0.03% and the combination of latanoprost 0.005% with timolol 0.5% effectively lowered intraocular pressure (IOP) without significant differences in efficacy.

The combination of latanoprost and timolol demonstrated a better safety profile, with fewer side effects compared to bimatoprost, which was associated with conjunctival hyperemia and eyelash growth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 6-month randomized clinical trial of bimatoprost 0.03% versus the association of timolol 0.5% and latanoprost 0.005% in glaucomatous patients. Manni, G., Centofanti, M., Parravano, M., et al.[2018]

The fixed-dose combination of netarsudil 0.02% and latanoprost 0.005% (NET/LAT) was found to be non-inferior to bimatoprost 0.03% and timolol maleate 0.5% (BIM/TIM) in reducing intraocular pressure (IOP) in patients with open-angle glaucoma and ocular hypertension over a 6-month study involving 430 patients.

Both treatments had similar safety profiles, with no serious treatment-related adverse events reported; however, NET/LAT was associated with a higher incidence of conjunctival hyperemia and cornea verticillata compared to BIM/TIM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MERCURY-3: a randomized comparison of netarsudil/latanoprost and bimatoprost/timolol in open-angle glaucoma and ocular hypertension. Stalmans, I., Lim, KS., Oddone, F., et al.[2023]

NCX 139, a new compound combining latanoprost amide and a nitric oxide (NO) donor, significantly lowered intraocular pressure (IOP) in both rabbit and dog models of ocular hypertension, demonstrating its potential as an effective treatment for glaucoma.

In contrast to its des-nitro analog, NCX 139 showed a notable NO-mediated vascular relaxant effect and was more effective in reducing IOP compared to standard treatments like bimatoprost and latanoprost, particularly in hypertensive conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A dual acting compound with latanoprost amide and nitric oxide releasing properties, shows ocular hypotensive effects in rabbits and dogs. Impagnatiello, F., Borghi, V., Gale, DC., et al.[2018]

Bimatoprost effectively lowers intraocular pressure (IOP) by 7-8 mmHg over 24 hours when used as a 0.03% topical preparation once daily, making it more effective than timolol and comparable to other prostaglandin analogs.

While bimatoprost is generally safe, with mild side effects like conjunctival hyperemia and periorbital pigmentation, it is also cost-effective for treating open-angle glaucoma, especially when used in combination with other medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bimatoprost - a review. Patil, AJ., Vajaranant, TS., Edward, DP.[2015]

Prostaglandin analogs like bimatoprost, latanoprost, and travoprost are effective and well-tolerated treatments for reducing intraocular pressure in patients with open-angle glaucoma and ocular hypertension, offering an alternative for those who do not respond to standard treatments.

These medications are at least as effective as the commonly used beta-blocker timolol, and while they can be combined with other treatments, more research is needed to determine the best combinations and to assess any differences in efficacy among the prostaglandin analogs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostaglandin analog treatment of glaucoma and ocular hypertension. Alexander, CL., Miller, SJ., Abel, SR.[2018]

Latanoprost, a prostaglandin analogue introduced in 1996, effectively reduces intraocular pressure (IOP) by approximately 30% in glaucoma patients through increased uveoscleral outflow, and is well tolerated with a favorable safety profile.

The most common side effect of latanoprost is increased iris pigmentation, particularly in individuals with green-brown eyes, which may be permanent, while unoprostone, another prostaglandin analogue, has limited documentation and experience outside Japan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostaglandin analogues in the treatment of glaucoma. Lindén, C., Alm, A.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Lack of pharmacokinetic interaction between butorphanol tartrate nasal spray and sumatriptan succinate. [2019]

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

Antimigraine efficacy of telcagepant based on patient's historical triptan response. [2022]

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

Using patient-centered endpoints to determine the cost-effectiveness of triptans for acute migraine therapy. [2006]

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

Long-term efficacy and safety of once-daily treatment with beclomethasone dipropionate nasal aerosol. [2016]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Comparison of rizatriptan 10 mg vs. naratriptan 2.5 mg in migraine. [2017]

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

Ocular hypotensive efficacy of bimatoprost when used as a replacement for latanoprost in the treatment of glaucoma and ocular hypertension. [2018]

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

Efficacy, tolerability and safety of the fixed combination of bimatoprost 0.03% and timolol 0.5% in a broad patient population: multicenter, open-label observational study. [2019]

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

Efficacy and safety of switching from topical latanoprost to bimatoprost in patients with normal-tension glaucoma. [2018]

9. England pubmed.ncbi.nlm.nih.gov

An update on bimatoprost in glaucoma therapy. [2019]

10. Germany pubmed.ncbi.nlm.nih.gov

A 6-month randomized clinical trial of bimatoprost 0.03% versus the association of timolol 0.5% and latanoprost 0.005% in glaucomatous patients. [2018]

11. Germany pubmed.ncbi.nlm.nih.gov

MERCURY-3: a randomized comparison of netarsudil/latanoprost and bimatoprost/timolol in open-angle glaucoma and ocular hypertension. [2023]

12. England pubmed.ncbi.nlm.nih.gov

A dual acting compound with latanoprost amide and nitric oxide releasing properties, shows ocular hypotensive effects in rabbits and dogs. [2018]

13. England pubmed.ncbi.nlm.nih.gov

Bimatoprost - a review. [2015]

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

Prostaglandin analog treatment of glaucoma and ocular hypertension. [2018]

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

Prostaglandin analogues in the treatment of glaucoma. [2018]