NCT02973880

Clinical Study to Evaluate the Efficacy and Tolerability of an Anti-inflammatory/Antibiotic Treatment Following Ocular Cataract Extraction

A Prospective, Multi-center, Controlled, Double-blind Study to Evaluate the Efficacy and Tolerability of a Steroid/Antibiotic Associated Treatment Following Cataract Extraction by Means of Phaco-emulsification

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 180 (actual)
• Sponsor: SIFI SpA · Industry
• Sex: All
• Age: 40 Years
• Healthy volunteers: Not accepted

Summary

Cataract is an ophthalmic disease that usually affects the elderly population. Cataract surgery with phaco-emulsification is now the most frequently performed intraocular surgical procedure in the developed world. However, differences in surgical technique impact the severity of surgical trauma and post-operative recovery. The amount of post-operative ocular pain and inflammation plays a significant role in the Patient's perception of the surgical success. Several ophthalmic products have been studied in the management of post-surgery ocular inflammation and pain following cataract surgery. Corticosteroids are considered the gold standard for the treatment of ocular inflammation, and their most commonly used route of administration is the topical instillation as eye drops formulation. After topical administration of Dexamethasone, the concentration in the anterior chamber increases and declines within hours, necessitating frequent daily instillations of eye drops for several weeks. This might be associated with compliance issues, particularly in elderly Patients or in individuals with disabilities. A pharmaceutical formulation allowing for a less frequent administration could therefore be an attractive alternative. NETILDEX™ eye drops solution, containing Netilmicin Sulfate 4.55 mg (3mg/ml) and Dexamethasone Disodium Phosphate 1.32 mg (1mg/ml), is already available for Patients. A new ophthalmic gel, preservative-free formulation has been developed. This new formulation has been tested in pre-clinical animal studies and in a clinical trial. The new formulation contains Xanthan gum, a high molecular mass polysaccharide approved by the FDA in 1969 for food products. It is used in the product as viscosity enhancer and to give to the product pseudo-plastic characteristics and prolonged ocular retention time. The purpose of this trial is to show that the administration of a reduced dose of NETILDEX ™ gel 2 times a day starting on the day of cataract extraction by means of phaco-emulsification and administered until 14 days after surgery is sufficient to obtain a non-inferior efficacy of the NETILDEX ™ eye drops solution administered 4 times a day for the same period.

Detailed description

Cataract is an ophthalmic disease that usually affects the elderly population. Therapy is surgical and during the past decades, improvements in surgical techniques and instruments have dramatically increased the number of cataract extractions performed. With improvements in surgical techniques, Patients' expectations have risen proportionally; however, differences in surgical technique impact the severity of surgical trauma and post-operative recovery. Cataract surgery with phaco-emulsification is now the most frequently performed intraocular surgical procedure in the developed world. The amount of post-operative ocular pain and inflammation plays a significant role in the Patient's perception of the surgical success. Ocular inflammation, commonly observed after cataract surgery, is associated with a breakdown of the blood-aqueous barrier (BAB) as a result of surgical trauma-induced prostaglandin production. Anterior chamber ocular inflammation, clinically assessed as anterior chamber cell counts and flare, is also common following cataract surgery. However, post-surgery inflammation is frequently viewed as an acceptable risk that is largely outweighed by the numerous benefits of cataract surgery. Advanced surgical techniques including phaco-emulsification, capsulorhexis, small clear corneal incisions, improved visco-elastics and foldable implants have helped to optimize post-surgery results and reduce surgical trauma. However, post-surgery inflammation may still occur and can lead to complications such as corneal edema, intra-ocular pressure (IOP) spikes, posterior capsule opacification and cystoid macular edema (CME). The management of post-surgery inflammation is essential, both to ensure rapid recovery following surgery, and to prevent or decrease the potential for long-term complications, such as cystoid macular edema. Several ophthalmic products have been studied for the management of post-surgery ocular inflammation and pain following cataract surgery. The two main treatments for ocular inflammation are topical corticosteroids or non-steroidal anti-inflammatory (NSAID) drugs. Bromfenac is a potent inhibitor of the COX-2 enzyme and a highly lipophilic molecule that rapidly penetrates to produce early and sustained drug levels in all ocular tissues. Studies have shown that Bromfenac ophthalmic solution has equivalent efficacy to the other topical NSAIDs in reducing post-operative inflammation and controlling pain. In order to decrease both intra-surgical and post-operative inflammation, it is now becoming commonplace to extend ophthalmic NSAID dosing to pre-operative use as well to reduce inflammation and minimize the risk of post-surgery complications in particular to prevent post-surgery cystoid macular edema. Corticosteroids are considered the gold standard for the treatment of ocular inflammation, they are routinely used to control post-surgery ocular inflammation. The most commonly used route of administration of corticosteroid agents is the topical instillation as eye drops formulation. Steroids can be used as an additional prophylactic treatment in high-risk cases. After topical administration of Dexamethasone, the concentration in the anterior chamber increases and declines within hours, necessitating frequent daily instillations of eye drops for several weeks. This might be associated with compliance issues, particularly in elderly Patients or in individuals with disabilities. A pharmaceutical formulation allowing for a less frequent administration could therefore be an attractive alternative. Increase in intra-ocular pressure (IOP) is a concern after the use of corticosteroids, irrespective of the route of administration. Repeated use of topical steroids has been shown to induce reversible elevations in IOP, especially in eyes with glaucoma. Although most of the Patients develop an increase in IOP after 3-6 weeks of treatment with topical steroids, some elevation of IOP can be found as early as the first or second week after initiation of topical instillation of steroids. NETILDEX™ eye drops solution, containing Netilmicin Sulfate 4.55 mg (3mg/ml) and Dexamethasone Disodium Phosphate 1.32 mg (1mg/ml), is already available for Patients. A new ophthalmic gel, preservative-free formulation has been developed. This new formulation has been tested in pre-clinical animal studies and in a clinical trial. The new formulation contains Xanthan gum, a high molecular mass polysaccharide approved by the FDA in 1969 for food products and it is used in the product as viscosity enhancer and to give to the product pseudo-plastic characteristics and prolonged ocular retention time. Its usability in ophthalmic preparations is well known and another products containing Xanthan gum is currently available in the market (Timolol GFS, Falcon Pharmaceuticals, USA). The penetration in the target tissue of Netilmicin and Dexamethasone contained in NETILDEX ™ eye drops and NETILDEX™ ophthalmic gel has been studied in a pre-clinical study in rabbits, which results suggest that the ophthalmic gel formulation increases the tissue bioavailability of both active principles. A clinical study has been conducted in 63 healthy volunteers (21 per group) to establish the safety and ocular tolerability of NETILDEX ™ ophthalmic gel, in comparison with placebo and eye drop solution, administered q.i.d. (1 drop) over a period of 14 days . Both formulations were tolerated as placebo. A statistically significant difference between placebo and Dexamethasone/Netilmicin was observed, as expected, for intra-ocular pressure (IOP) values, however in none of the cases the IOP rising was clinically relevant. The purpose of this trial is to show that the administration of a reduced dose of NETILDEX ™ gel 2 times a day starting on the day of cataract extraction by means of phaco-emulsification and administered until 14 days after surgery is sufficient to obtain a non-inferior efficacy of the NETILDEX ™ eye drops solution administered 4 times a day for the same period.

Conditions

• Cataract Extraction
• Cataract

Interventions

Type	Name	Description
DRUG	NETILDEX™ ophthalmic gel	1 drop of NETILDEX™ (Netilmicin Sulfate 3mg/ml / Dexamethasone Disodium Phosphate 1mg/ml) ophthalmic gel immediately after the surgery then 1 drop twice daily (b.i.d.) from Day 1 until Day 14 after surgery + 1 drop of XANTERGEL™ ophthalmic gel twice daily (b.i.d.) from Day 1 until Day 14 after surgery. Bromfenac 0.9 mg/ml 1 drop twice daily (b.i.d.) for 3 days before cataract surgery.
DRUG	NETILDEX™ eye drops solution	1 drop of NETILDEX™ (Netilmicin Sulfate 3mg/ml / Dexamethasone Disodium Phosphate 1mg/ml) eye drops solution immediately after the surgery then 1 drop four times a day (q.i.d.) from Day 1 until Day 14 after surgery. Bromfenac 0.9 mg/ml 1 drop twice daily (b.i.d.) for 3 days before cataract surgery.

Timeline

• Start date: 2017-10-15
• Primary completion: 2018-12-01
• Completion: 2018-12-30
• First posted: 2016-11-25
• Last updated: 2019-01-14

Locations

7 sites across 3 countries: Germany, Italy, Romania