E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety and efficacy of the 700 µg DEX PS DDS Applicator System (700 µg dexamethasone) and 350 µg DEX PS DDS Applicator System (350 µg dexamethasone) compared with a Sham DEX PS DDS Applicator System (needle-less applicator) in patients with diabetic macular edema. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and efficacy of the 700 µg DEX PS DDS Applicator System (700 µg dexamethasone) compared with the 350 µg DEX PS DDS Applicator System (350 µg dexamethasone) in patients with diabetic macular edema. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female, at least 18 years of age 2. Diagnosis of diabetes mellitus (type 1 or type 2). Any one of the following will be considered to be sufficient evidence that diabetes is present: - Current regular use of insulin for the treatment of diabetes - Current regular use of oral hypoglycemic agent(s)for the treatment of diabetes - Diabetes as defined by American Diabetes Association (ADA) guidelines: • Symptoms of diabetes (polyuria, polydipsia, and unexplained weight loss) plus plasma glucose concentration at any time of the day regardless of time since last meal ≥ 200 mg/dl (11.1 mmol/l) or • Eight-hour fasting plasma glucose ≥ 126 mg/dl (7.0 mmol/l) or • Two-hour postload (75 g) glucose ≥ 200 mg/dl (11.1 mmol/l) during an oral glucose tolerance test 3. Diabetic macular edema in the study eye defined as clinically observable macular edema involving the center of the macula (fovea) associated with diabetic retinopathy, with any of the following characteristics: a) Prior medical therapy for diabetic macular edema b) Prior macular laser(s) for diabetic macular edema with the most recent laser at least 3 months prior to Baseline/ Qualification where, in the opinion of the investigator, the patient will be able to improve 15 or more letters in BCVA from baseline with the resolution of the macular edema despite the presence of macular laser scars c) In the investigator’s opinion the patient would not benefit from macular laser treatment d) The patient refuses laser treatment 4. BCVA score between 34 letters (approximately 20/200 Snellen equivalent) and 68 letters (approximately 20/50 Snellen equivalent) in the study eye measured by the ETDRS method at qualification/baseline 5. Retinal thickness of ≥ 300 μm by OCT in the 1mm central macular subfield of the study eye at qualification/baseline as determined by the investigator 6. Patients who have received intravitreal triamcinolone acetonide must satisfy the following: • The intended dose for each injection was 4 mg or less • The most recent dose was at least 6 months prior to qualification/baseline visit • No treatment-related adverse event was seen that, in the opinion of the investigator, has the potential to worsen or reoccur with study treatment 7. Female patients of childbearing potential must have a negative urine pregnancy test at the randomization (day 0) visit 8. Written informed consent has been obtained 9. Written Authorization for Use and Release of Health and Research Study Information (US sites only) has been obtained 10. Written Data Protection Consent (European sites only) has been obtained 11. Written documentation has been obtained, in accordance with state and country privacy requirements, where applicable |
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E.4 | Principal exclusion criteria |
1. Uncontrolled systemic disease or current immunosuppressive disease (e.g., HIV+, AIDS) 2. Initiation of medical therapy for diabetes or a change from oral hypoglycemic agents to insulin therapy within 4 months prior to the qualification/baseline visit 3. Blood HbA1c level greater than 10% at the qualification/baseline visit 4. Renal failure requiring hemodialysis or peritoneal dialysis within 6 months prior to the qualification/baseline visit 5. Adjusted glomerular filtration rate (GFR) less than 50 mL/min, based on the Modified Diet in Renal Disease (MDRD) formula adjusted for body surface area, at the qualification/baseline visit 6. Any ocular condition in the study eye that in the opinion of the investigator would prevent a 15-letter improvement in visual acuity (e.g., severe macular ischemia, extensive macular laser scarring or atrophy) 7. Presence of branch retinal vein occlusion, central retinal vein occlusion, uveitis, pseudophakic cystoid macular edema or any other condition in the study eye which could be contributing to macular edema 8. Presence of an epiretinal membrane or vitreo-retinal interface changes in the study eye which, in the opinion of the investigator, is the primary cause of macular edema, or is severe enough to prevent improvement in visual acuity despite reduction in macular edema 9. History of IOP elevation in response to steroid treatment in either eye that resulted in any of the following: 1) a ≥ 10 mm Hg increase in IOP from baseline with an absolute IOP ≥ 25 mm Hg 2) required therapy with 3 or more anti-glaucoma medications 10. History of glaucoma or optic nerve head change consistent with glaucoma damage, and/or glaucomatous visual field loss in the study eye. Patients with a history of previous angle-closure or similar conditions that have been successfully treated with either a laser or surgical peripheral iridotomy are allowed as long as the visual fields and optic nerves have been stable for > 1 year prior to study entry and the patient has been and can be safely dilated 11. Ocular hypertension in the study eye at qualification/baseline with any of the following: 1) IOP > 23 mm Hg if taking no anti-glaucoma medications 2) IOP > 21 mm Hg if taking one anti-glaucoma medication 3) use of 2 or more anti-glaucoma medications (combination products should be considered 2 medications) Note: Anti-glaucoma medications or lack thereof must be stable for at least 4 weeks prior to qualification/baseline. 12. Aphakia or presence of anterior chamber intraocular lens in the study eye 13. Active optic disc or retinal neovascularization in the study eye at qualification/baseline 14. Active or history of choroidal neovascularization in the study eye 15. Presence of rubeosis iridis in the study eye at qualification/baseline 16. Any active ocular infection (i.e., bacterial, viral, parasitic, or fungal) in either eye at qualification/baseline 17. History of herpetic infection in the study eye or adnexa 18. Presence of active or inactive toxoplasmosis in either eye at qualification/baseline 19. Presence of visible scleral thinning or ectasia in the study eye 20. Media opacity in the study eye at qualification/baseline that precludes clinical and photographic evaluation (including but not limited to preretinal or vitreous hemorrhage, lens opacity) 21. Intraocular surgery, including cataract surgery, and/or laser of any type in the study eye within 90 days prior to qualification/baseline 22. History of central serous chorioretinopathy in either eye 23. History of pars plana vitrectomy in the study eye 24. Anticipated need for ocular surgery or laser in the study eye within 1 year following the qualification/baseline visit (e.g., panretinal photocoagulation (PRP), cataract surgery) 25. History of use of intravitreal steroids in the study eye other than triamcinolone acetonide 26. History of use of intravitreal bevacizumab, ranibizumab or pegaptanib in the study eye within 3 months prior to qualification/baseline visit 27. History of use of any intravitreal agent in the study eye other than triamcinolone acetonide, bevacizumab, ranibizumab, or pegaptanib, or intravitreal doses of triamcinolone acetonide > 4mg, bevacizumab > 1.25 mg, ranibizumab > 0.5 mg, or pegaptanib > 0.3 mg 28. Periocular depot of steroids to the study eye within 6 months prior to qualification/baseline 29. Use of systemic steroids (e.g., oral, intravenous, intra-articular, epidural, intra-bursal) within 1 month prior to the qualification/baseline visit or anticipated use at any time during the study. Inhaled and intranasal steroids are allowed 30. For patients who participate in therapeutic drug monitoring evaluation only: use of dexamethasone within 1 month prior to qualification/baseline or anticipated use during the first 90 days in any form/route of administration
DUE TO SPACE RESTRICTIONS, ONLY EXCLUSION CRITERIA 1-30 ARE LISTED. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Best Corrected Visual Acuity (BCVA) is the primary efficacy variable and will be measured using the ETDRS method. It will be measured in both eyes (study eye and non-study eye) at the qualification visit and each follow-up visit. BCVA will be performed following manifest refraction, except 1, 7 and 21 days after the study treatment or re-treatment,. At days 1, 7 and 21 after a treatment or re-treatment, visual acuity (VA) evaluations may be performed using refraction obtained at baseline or at the preceding re-treatment visit, respectively. These VA evaluations will be considered as safety measures but not as efficacy measures. All other VA evaluations will be considered as both safety and efficacy measures. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 96 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 96 |