Safety and Efficacy of Difluprednate 0.05% for the Treatment of Anterior Uveitis

Study Overview
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Brief Summary
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The purpose of this study was to demonstrate that difluprednate 0.05% (Durezol) dosed 4 times daily is noninferior to prednisolone 1% (Pred Forte) dosed 8 times daily for the treatment of endogenous anterior uveitis.

Official Title
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A Phase 3 Multicenter, Randomized, Double-Masked Study of the Safety and Efficacy of Difluprednate 0.05% Ophthalmic Emulsion Compared to Prednisolone Acetate 1% Ophthalmic Suspension in the Treatment of Endogenous Anterior Uveitis

Conditions
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Endogenous Anterior Uveitis

Intervention / Treatment
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* Drug: Difluprednate 0.05% ophthalmic emulsion
* Drug: Prednisolone acetate 1.0% ophthalmic suspension


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of endogenous anterior uveitis in at least 1 eye. The presence of > 10 cells in the anterior chamber of at least one eye, and a flare score of > 2 in that same eye. Age 2 years or older on day of consent. Negative urine pregnancy test on Day 0 for females of childbearing potential who are not at least 1 year post-menopausal or surgically sterilized. Other protocol-defined inclusion criteria may apply. Exclusion Criteria: Presence of endogenous anterior uveitis diagnosed for > 2 weeks prior to enrollment in the study. Presence of intermediate uveitis, posterior uveitis or panuveitis in either eye. Instillation of any topical corticosteroid or NSAID in the study eye within 7 days of instillation of study drug. History of glaucoma or clinically significant ocular hypertension in the opinion of the Investigator involving an IOP ≥ 21 millimeters mercury in either eye. History of steroid-induced elevation of intraocular pressure. Any confirmed or suspected active viral, bacterial or fungal keratoconjunctival disease in either eye. History of glaucoma or clinically significant ocular hypertension in the opinion of the Investigator involving an intraocular pressure (IOP) > 21 mmHg in either eye. Corneal abrasion or ulceration in either eye. Pregnancy or lactation. Other protocol-defined exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 2 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Durezol<br>Difluprednate 0.05% ophthalmic emulsion, 1 drop in study eye, 4 times a day for 14 days, followed by a 14-day tapering period | Drug: Difluprednate 0.05% ophthalmic emulsion<br>* 1 drop in study eye, 4 times a day, for 14 days, followed by a 14-day tapering period dependent on the Investigator's determination of adequate response to treatment<br>* Other names: Durezol;|
| Active Comparator: Pred Forte<br>Prednisolone acetate 1.0% ophthalmic suspension, 1 drop in study eye, 8 times a day for 14 days, followed by a 14-day tapering period | Drug: Prednisolone acetate 1.0% ophthalmic suspension<br>* 1 drop in study eye, 8 times a day, for 14 days, followed by a 14-day tapering period dependent on the Investigator's determination of adequate response to treatment<br>* Other names: Pred Forte;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline (Day 0) in Anterior Chamber Cell Grade at Day 14 | Inflammatory cells in the anterior chamber were assessed by the investigator during slit lamp examination and graded on a 5-point scale, with 0 = ≤ 1 cell count; 1 = 2 to 10 cell count; 2 = 11 to 20 cell count; 3 = 21 to 50 cell count; and 4 = > 50 cell count. | Baseline (Day 0), Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline (Day 0) in Anterior Chamber Cell Grade at All Time Points Other Than Day 14 | Inflammatory cells in the anterior chamber were assessed by the investigator during slit lamp examination and graded on a 5-point scale, with 0 = ≤ 1 cell count; 1 = 2 to 10 cell count; 2 = 11 to 20 cell count; 3 = 21 to 50 cell count; and 4 = > 50 cell count. | Baseline (Day 0), Day 3, Day 7, Day 21, Day 28, Day 35, Day 42 | 
| Change From Baseline (Day 0) in Anterior Chamber Flare Grade at All Time Points | Anterior chamber flare (protein escaping from dialated vessels) was assessed by the investigator during slit lamp examination and graded on a 5-point scale, with 0 = none; 1 = mild (trace to clearly noticeable, visible); 2 = moderate; 3 = marked; and 4 = severe. | Baseline (Day 0), Day 3, Day 7, Day 14, Day 21, Day 28, Day 35, Day 42 | 
| Proportion of Subjects With Anterior Chamber Cell Grade of 0 | Inflammatory cells in the anterior chamber were assessed by the investigator during slit lamp examination and graded on a 5-point scale, with 0 = ≤ 1 cell count; 1 = 2 to 10 cell count; 2 = 11 to 20 cell count; 3 = 21 to 50 cell count; and 4 = > 50 cell count. Proportion is reported as percentage of subjects. | Day 3, Day 7, Day 14, Day 21, Day 28, Day 35, Day 42 | 
| Proportion of Subjects With Anterior Chamber Cell Count of 0 | Inflammatory cells in the anterior chamber were assessed by the investigator during slit lamp examination and recorded based on actual cell count. Proportion is reported as a percentage of subjects. | Day 3, Day 7, Day 14, Day 21, Day 28, Day 35, Day 42 | 
| Proportion of Subjects With Anterior Chamber Cell Count ≤5 and Flare Grade of 0 | Inflammatory cells in the anterior chamber were assessed by the investigator during slit lamp examination and recorded based on actual cell count. Anterior chamber flare (protein escaping from dialated vessels) was assessed by the investigator during slit lamp examination and graded on a 5-point scale, with 0 = none; 1 = mild (trace to clearly noticeable, visible); 2 = moderate; 3 = marked; and 4 = severe. Proportion is reported as percentage of subjects. | Day 3, Day 7, Day 14, Day 21, Day 28, Day 35, Day 42 | 
| Proportion of Subjects With Anterior Chamber Cell Grade ≤1 | As assessed by the investigator during slit lamp examination. Anterior chamber cell grade was graded on a 5-point scale, with 0 = no cells; 1 = 1 to 10 cells; 2 = 11 to 20 cells; 3 = 21 to 50 cells; and 4 = more than 50 cells. Proportion is reported as percentage of subjects. | Day 3, Day 7, Day 14, Day 21, Day 28, Day 35, Day 42 | 
| Proportion of Subjects Who Discontinued Due to Lack of Efficacy | Lack of efficacy was defined as those subjects who discontinued study participation either due to treatment failure or an adverse event with a preferred term of iridocyclitis, iritis, uveitis, or vitritis. Proportion is reported as percentage of subjects. | Time to Event | 
| Change From Baseline (Day 0) in Visual Analog Scale (VAS) Total Symptom Score at All Time Points | The following symptoms were each graded by the subject according to a 0-100 visual analog scale (VAS) using a mark on a 100 mm line (0 = absent, 100 = maximal): eye pain, photophobia, blurred vision, and lacrimation. The total symptom score was calculated as the sum of the 4 individual symptom scores. | Baseline (Day 0), Day 3, Day 7, Day 14, Day 21, Day 28, Day 35, Day 42 | 
| Change From Baseline (Day 0) in Slit-Lamp Total Sign Score at All Visits | The following signs were each graded on a 0 - 3 scale (0 = absent; 1 = mild; 2 = moderate; 3 = severe): posterior synechia, hypopyon, limbal injection, and keratic precipitates. Peripheral synechia was graded by the combined number of clock hours affected (0 = absent; 1 = < 3 hrs; 2 = 3-6 hours; 3 = > 6 hours). The total sign score was calculated as the sum of the 5 individual sign scores, the anterior chamber cell grade and the anterior chamber flare grade. The minimum/best total sign score was 0, and the maximum/worst total sign score was 23. | Baseline (Day 0), Day 3, Day 7, Day 14, Day 21, Day 28, Day 35, Day 42 |