Iontophoretic Delivery of EGP-437 in Patients Who Have Undergone Cataract Surgery

Study Overview
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Brief Summary
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Phase 2b trial evaluating the safety and efficacy of EGP-437, versus placebo using the EyeGate® II Drug Delivery System (EGDS) in patients having undergone cataract surgery with implantation of a monofocal posterior chamber intraocular lens (IOL).

Detailed Description
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This will be a Phase 2b, double-masked, multi-site study, in which a total of up to 100 eyes of up to 100 subject will be enrolled at up to 8 clinical sites in the United States. The study has 2 different treatment arms consisting of the following iontophoresis treatment regimen: Treatment Arm 1, up to 50 subjects will receive the following study treatment: 40 mg/ml dexamethasone phosphate solution delivered by iontophoresis treatment consisting of 4.5 mA-min at 3.0 mA on Day 0 (immediately following cataract surgery), Day 1 (24 hours' post-cataract surgery), Day 4, and a potential Day 7 treatment that will be administered for subjects who have ≥11 AC cells per high-power field on slit lamp examination. Treatment Arm 2, up to 50 subjects will receive the following study treatment: 100 mM sodium citrate buffer solution (placebo) delivered by iontophoresis treatment consisting of 4.5 mA-min at 3.0 mA on Day 0 (immediately following cataract surgery), Day 1 (24 hours' post-cataract surgery), Day 4, and a potential Day 7 treatment that will be administered for subjects who have ≥11 AC cells per high-power field on slit lamp examination. Subjects will come in for 6 visits over 28 days. The primary efficacy endpoint (PEP) will evaluate 1) the proportion of subjects with an AC cell count of zero on Day 7 and 2) the proportion of subjects with a pain score of zero on Day 1.

Official Title
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Multi-Center, Double-Masked, Randomized, Placebo-Controlled Phase 2b Clinical Trial Designed to Evaluate the Safety and Efficacy of Iontophoretic Dexamethasone Phosphate Ophthalmic Solution in Patients Having Undergone Cataract Surgery With Implantation of a Posterior Chamber Intraocular Lens (IOL)

Conditions
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Cataract, Anterior Chamber Inflammation, Pain, Postoperative

Intervention / Treatment
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* Combination Product: Dexamethasone phosphate
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Undergoing unilateral cataract extraction and implantation of a monofocal IOL (at the time of enrollment) Age 18 to 85 years Receive, understand, and sign a copy of the written informed consent form (ICF) Are able to return for all study visits and willing to comply with all study-related instructions Exclusion Criteria: Are undergoing implantation of a multifocal and/or depth enhancing IOL Are undergoing or have just undergone cataract surgery on the study eye that is deemed complex or may require manipulation of the iris The study eye has a small pupil or iris requiring manipulation due to synechiae and/ Tamsulosin (Flomax®, Boehringer Ingelheim) use Have a Seidel positive wound following surgical procedure despite suture and/or ReSure® Sealant placement Have had ocular surgery of any kind in the study eye within 3 months prior to baseline visit (Day 0) Have undergone cataract surgery in the fellow eye within 4 weeks prior to baseline visit (Day 0) and still require post-operative medications in that fellow eye Are scheduled for surgery in the fellow eye within the study period Have anterior chamber inflammation as measured by slit lamp examination in the study eye at the baseline visit (Day 0) [Defined as anterior chamber (AC) cell and/or flare grade > 0] Have history of uveitis or inflammatory disease in the study eye Requires simultaneous supplemental surgery, such as glaucoma procedures or vitrectomy, in the study eye Have used any topical ocular medication in either eye, other than tear substitute for dry eye, within the past 2 weeks prior to baseline visit (Day 0) Have used topical corticosteroid or nonsteroidal anti-inflammatory drug (NSAID) treatment in either eye < 48 hours prior to the baseline visit (Day 0) (excluding the use of topical NSAIDs, pre-operatively on Day 0 and administered at the clinic site under the investigator's oversight) Have IOP ≥ 25 mmHg at baseline, a history of glaucoma, and/or require ocular anti-hypertensive medications Are known corticosteroid IOP responder in study eye Have received systemic administration of corticosteroid and/or immunosuppressants within the past 14 days prior to baseline visit (Day 0) Have received intravitreal, sub-Tenon, or any periocular corticosteroid treatment in either eye within the past 6 months prior to baseline visit (Day 0) Have open wounds/skin disease on the forehead area where the iontophoresis return electrode will be applied Have lesions of the eyelids or the ocular surface impeding the application of the iontophoresis applicator Have blepharospasm, blepharophimosis, or other eyelid anatomic variations precluding placement of the iontophoresis applicator Have known allergy to dexamethasone or dexamethasone phosphate or any medication to be used in this study Have history or diagnosis of ocular herpes, corneal lesion of suspected herpetic origin that could be worsened with steroid use Have optic neuritis of any origin Have clinically suspected or confirmed central nervous system or ocular lymphoma Have active hyphema, pars planitis, choroiditis, toxoplasmosis scar, vitreous hemorrhage, and/or clinically significant macular edema (CSME) that would compromise visual acuity recovery Have severe/serious ocular pathology or medical condition which may preclude study completion Have pacemaker and/or any other electrical sensitive support system Are pregnant or lactating female, or female of childbearing age and using inadequate birth control method Have participated in another investigational device or drug study within 30 days of baseline visit (Day 0) (other clinical trial participation while participating in EGP-437-009 would be prohibited per protocol) Have previously participated in a study with EGP-437

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double-masked, randomized, placebo-controlled, multi-center, Phase 2b clinical trial designed to evaluate the efficacy and safety of transcleral iontophoretic delivery of dexamethasone phosphate ophthalmic solution in patients having undergone cataract surgery with implantation of a monofocal posterior chamber IOL.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EGP-437<br>40 mg/ml dexamethasone phosphate solution delivered by iontophoresis treatment consisting of 4.5 mA-min at 3.0 mA | Combination Product: Dexamethasone phosphate<br>* Ocular iontophoretic delivery of a steroid<br>|
| Placebo Comparator: Placebo<br>100 mM sodium citrate buffer solution (placebo) delivered by iontophoresis treatment consisting of 4.5 mA-min at 3.0 mA | Other: Placebo<br>* Ocular iontophoretic delivery of a placebo<br>* Other names: Sodium Citrate Buffer;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AC cell count = 0 | The proportion of subjects with an AC cell count of zero on Day 7 | 7 days' following first study treatment | 
| Pain score = 0 | The proportion of subjects with a pain score of zero on Day 1 | 1 day post-surgery and following first study treatment |