Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2 & 3
Recruiting
Sponsor: Nicox Ophthalmics, Inc.
Disqualifiers: Narrow angles, Ocular disease, Uncontrolled disease, others
Prior Safety Data
Trial Summary
What is the purpose of this trial?This trial uses an eye drop solution called NCX 470, a nitric oxide (NO)-donating bimatoprost, to study its effects on eye fluid movement in healthy individuals and those with high eye pressure.
Do I need to stop my current medications to join the trial?
The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
What data supports the effectiveness of the drug NCX 470 for glaucoma?
Research shows that NCX 470, a combination of bimatoprost and nitric oxide, is more effective at lowering eye pressure than bimatoprost alone in animal models of ocular hypertension and glaucoma. This suggests it could be a promising treatment for reducing eye pressure in glaucoma patients.
12345Is NCX 470 safe for human use?
NCX 470, a nitric oxide-donating version of bimatoprost, has been studied in animal models and shown to lower eye pressure effectively. While specific human safety data is not detailed in the provided research, bimatoprost, a component of NCX 470, is already used in humans for eye conditions, suggesting a potential safety profile. However, more specific human safety studies would be needed to confirm this.
23456Eligibility Criteria
This trial is for adults over 18 years old, of any gender, who do not have glaucoma but may have ocular hypertension (OHT) with eye pressure between 16 and 28 mmHg. It's not suitable for people already diagnosed with glaucoma.Inclusion Criteria
I do not have glaucoma.
Your eye pressure is between 16 and 28 mmHg.
My gender does not exclude me from this trial.
+2 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
1-2 weeks
Treatment
Participants receive NCX 470 0.1% or placebo, one drop in the randomized eye once a day for 8 days
8 days
Follow-up
Participants are monitored for safety and effectiveness after treatment
2 weeks
Participant Groups
The study tests NCX 470 ophthalmic solution against a placebo to see how it affects the fluid dynamics in the eyes of healthy volunteers or those with high eye pressure but no glaucoma.
2Treatment groups
Active Control
Placebo Group
Group I: NCX 470 0.1%Active Control1 Intervention
NCX 470 0.1% - one drop in the randomized eye once a day for 8 days
Group II: PlaceboPlacebo Group1 Intervention
Artificial tears - one drop in the randomized eye once a day for 8 days
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Mayo ClinicRochester, MN
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Who Is Running the Clinical Trial?
Nicox Ophthalmics, Inc.Lead Sponsor
References
Prostaglandin analog treatment of glaucoma and ocular hypertension. [2018]To review available data related to the use of prostaglandin analogs (bimatoprost, latanoprost, travoprost, unoprostone) in the management of ocular hypertension and open-angle glaucoma.
Intraocular Pressure-Lowering Activity of NCX 470, a Novel Nitric Oxide-Donating Bimatoprost in Preclinical Models. [2015]The prostaglandin F2alpha (PGF2α) analogue bimatoprost lowers intraocular pressure (IOP) by increasing uveoscleral outflow at doses shown to elicit redness of the eye. With the aim to enhance the IOP-lowering effect of bimatoprost we studied NCX 470 [(S,E)-1-((1R,2R,3S,5R)-2-((Z)-7-(ethylamino)-7-oxohept-2-enyl)-3,5-dihydroxycyclopentyl)-5-phenylpent-1-en-3-yl 6-(nitrooxy)hexanoate], a dual-acting compound combining bimatoprost with nitric oxide (NO) known to mainly act via relaxation of trabecular meshwork and Schlemm's canal.
A dual acting compound with latanoprost amide and nitric oxide releasing properties, shows ocular hypotensive effects in rabbits and dogs. [2018]The IOP lowering effects of NCX 139, a new chemical entity comprising latanoprost amide and a NO-donating moiety, were compared to those of the respective des-nitro analog in in vitro assays and in rabbit and dog models of ocular hypertension. The NO donor, molsidomine as well as the prostamide bimatoprost (Lumigan(®)) and the prostaglandin agonist, latanoprost (Xalatan(®)) were also investigated for comparison. NCX 139 but not its des-nitro analog resulted in NO-mediated vascular relaxant effect in pre-contracted rabbit aortic rings (EC(50)=0.70±0.06 μM; E(max)=80.6±2.9%). Like bimatoprost (IC(50)=3.07±1.3 μM) or latanoprost (IC(50)=0.48±0.15 μM), NCX 139 displaced (3)H-PGF2α binding on recombinant human prostaglandin-F (FP) receptors with an estimated potency of 0.77±0.13 μM. In transient ocular hypertensive rabbits, bimatoprost and latanoprost were not effective while molsidomine elicited a dose-dependent reduction of IOP confirming the responsiveness of rabbits to NO but not to FP receptor agonists. NCX 139 tested at a therapeutically relevant dose, significantly lowered IOP while the des-nitro analog was not effective (0.03% NCX 139, Δ(max)=-12.8±2.0 mmHg). In glaucomatous dogs, 0.03% NCX 139 decreased IOP to a greater extent compared to an equimolar dose of the respective des-nitro derivative (Δ(max)=-4.6±1.0 and -2.7±1.3 mmHg, respectively for NCX 139 and its des-nitro analog). Albeit with low potency, NCX 139 also resulted effective in normotensive dogs while it did not reduce IOP in normotensive rabbits. NCX 139, a compound targeting two different and important mechanisms, is endowed with ocular hypotensive effects more evident in hypertensive conditions which may be of interest in the search of more effective treatments for hypertensive glaucoma.
Prostaglandin analogues and nitric oxide contribution in the treatment of ocular hypertension and glaucoma. [2023]In patients with ocular hypertension or glaucoma, all treatments aim to lower intraocular pressure (IOP) by modulating aqueous humour (AH) production and/or uveoscleral and trabecular meshwork/Schlemm's canal AH drainage. PG analogues are considered to be the 'gold standard' treatment and are the most frequently used IOP-lowering agents. Recent data support an important role for NO in regulating IOP. Thus, novel PG analogues carrying a NO-donating moiety were recently advanced. Latanoprostene bunod (LBN) and NCX 470, NO-donating derivatives of latanoprost and bimatoprost, respectively, are examples of such compounds. LBN ophthalmic solution, 0.024% (Vyzulta™), showed greater IOP-lowering efficacy compared with that of Xalatan® (latanoprost ophthalmic solution, 0.005%) or 0.5% timolol maleate in clinical settings. NCX 470 was found to be more effective than bimatoprost in animal models of ocular hypertension and glaucoma. Selective EP2 receptor agonists (i.e. taprenepag isopropyl, omidenepag isopropyl and aganepag isopropyl) and non-selective prostanoid receptor agonists (i.e. ONO-9054, sepetaprost isopropyl) that concomitantly stimulate FP and EP3 receptors have also been shown to hold promise as effective IOP-lowering agents. LINKED ARTICLES: This article is part of a themed section on Eicosanoids 35 years from the 1982 Nobel: where are we now? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.8/issuetoc.
Comparing bimatoprost and travoprost in black Americans. [2022]To compare the intraocular pressure-lowering efficacy and safety of topical bimatoprost 0.03% with that of travoprost 0.004% for the treatment of black patients with open-angle glaucoma (OAG) and ocular hypertension (OHT).
NCX 470 Restores Ocular Hemodynamics and Retinal Cell Physiology After ET-1-Induced Ischemia/Reperfusion Injury of Optic Nerve and Retina in Rabbits. [2022]Purpose: Determine whether NCX 470, a nitric oxide (NO)-donating bimatoprost with clinically demonstrated intraocular pressure (IOP)-lowering effects, improves ocular hemodynamics and retinal physiology. Methods: Endothelin-1 (ET-1)-induced ischemia/reperfusion model in New Zealand white rabbits was used. ET-1 was injected next to the optic nerve twice/week (Monday and Thursday) for 6 weeks. Starting on week 3, animals received NCX 470 (0.1% bid, 6 days/week Monday-Saturday) or vehicle until the end of ET-1 treatment. IOP, ophthalmic artery resistive index (OA-RI) and retina physiology (electroretinogram, ERG) were determined before dosing and at different times post-dosing. All measurements were taken on Mondays before the AM daily dosing (36 h treatment-free). Finally, oxidative stress markers were determined in dissected retina and iris/ciliary body of treated eyes. Results: Injection of ET-1 progressively increased IOP (20.7 ± 0.6, 24.9 ± 1.2, and 27.0 ± 0.6 mmHg at baseline, week 2 and 6, respectively) and OA-RI (0.30 ± 0.02, 0.39 ± 0.02, and 0.42 ± 0.03 at baseline, week 2 and 6, respectively) and reduced rods and/or cones response as indicated by changes in ERG amplitudes under different stimulating conditions. NCX 470 re-established baseline IOP (21.8 ± 1.0 mmHg), OA-RI (0.33 ± 0.02), and ERG amplitude by week 6 (mostly rod response, 0.01Dark_AVeh_6week = 32.2 ± 3.0 μV and 0.01Dark_ANCX470_6week 44.3 ± 4.5 μV; mostly cone response, 3.0Dark_AVeh_6week = 87.6 ± 10.1 μV and 3.0Dark_ANCX470_6week = 122.8 ± 11.4 μV; combined rod/cone response, 3.0Light_AVeh_6week = 49.8 ± 6.5 μV and 3.0Light_ANCX470_6week = 64.2 ± 6.8 μV). NCX 470 also reversed ET-1-induced changes in glutathione and manganese superoxide dismutase (oxidative stress markers) in retina and iris/ciliary body. Conclusions: Repeated ocular topical dosing with NCX 470 reverses ET-1-induced changes in IOP, OA-RI, and ERG suggesting improved ocular hemodynamics and retinal physiology likely independently from its demonstrated IOP-lowering effect.
NCX 470 Reduces Intraocular Pressure More Effectively Than Lumigan in Dogs and Enhances Conventional and Uveoscleral Outflow in Non-Human Primates and Human Trabecular Meshwork/Schlemm's Canal Constructs. [2023]Purpose: To determine NCX 470 (0.1%) and Lumigan® (bimatoprost ophthalmic solution, 0.01%-LUM) intraocular pressure (IOP)-lowering activity after single or repeated (5 days) dosing along with changes in aqueous humor (AH) dynamics. Methods: Ocular hypotensive activity of NCX 470 and LUM was compared with vehicle (VEH) in Beagle dogs using TonoVet®. Non-human primates (NHP) and bioengineered three-dimensional (3D) human Trabecular Meshwork/Schlemm's Canal (HTM/HSC™) constructs exposed to transforming growth factor-β2 (TGFβ2) were used to monitor NCX 470 and LUM-induced changes in AH dynamics. Results: NCX 470 (30 μL/eye) showed greater IOP reduction compared with LUM (30 μL/eye) following single AM dosing [maximum change from baseline (CFBmax) = -1.39 ± 0.52, -6.33 ± 0.73, and -3.89 ± 0.66 mmHg (mean ± standard error of the mean) for VEH, NCX 470, and LUM, respectively]. Likewise, repeated 5 days daily dosing of NCX 470 resulted in lower IOP than LUM across the duration of the study (average IOP decrease across tests was -0.45 ± 0.22, -6.06 ± 0.15, and -3.60 ± 0.22 mmHg for VEH, NCX 470, and LUM, respectively). NCX 470 increased outflow facility (Cfl) in vivo in NHP (CflVEH = 0.37 ± 0.09 μL/min/mmHg and CflNCX470 = 0.64 ± 0.17 μL/min/mmHg) as well as in vitro (CHTM/HSC) in HTM/HSC constructs (CHTM/HSC_VEH = 0.47 ± 0.02 μL/min/mm2/mmHg and CHTM/HSC_NCX470 = 0.76 ± 0.03 μL/min/mm2/mmHg). In addition, NCX 470 increased uveoscleral outflow (FuVEH = 0.62 ± 0.26 μL/min and FuNCX470 = 1.53 ± 0.39 μL/min with episcleral venous pressure of 15 mmHg) leaving unaltered aqueous flow (AHFVEH = 2.03 ± 0.22 μL/min and AHFNCX470 = 1.93 ± 0.31 μL/min) in NHP. Conclusions: NCX 470 elicits greater IOP reduction than LUM following single or repeated dosing. Data in NHP and 3D-HTM/HSC constructs suggest that changes in Cfl and Fu account for the robust IOP-lowering effect of NCX 470.