Difluprednate Pediatric Study for the Treatment of Inflammation Post-Cataract Surgery

Study Overview
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Brief Summary
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The primary objective of this study was to compare the safety and efficacy of Durezol™ compared to Pred Forte™ for the treatment of inflammation following cataract surgery in a pediatric population 0 to 3 years of age.

Detailed Description
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Parents or guardians instilled patients' assigned study medications once on the day of surgery (Day 0) and 4 times daily (QID) beginning on the day after surgery (Day 1) for 14 days followed by a tapering period of 14 days (dependent upon the Investigator's determination of adequate response to treatment). Patients were evaluated for safety and efficacy on the following visits: Day 0 (day of surgery), Day 1, Day 8 ± 1 day, Day 15 ± 2 days and Day 29 ± 2 days (end of study drug treatment). Additional safety visits occurred at 1 week after the last dose + 2 days and at 3 Months + 1 week. No inferential statistical analysis was planned for this study. Data was summarized using descriptive statistics.

Official Title
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A Phase IIIB, Multicenter, Randomized, Double-Masked, Parallel-Group, Active-Controlled Study of the Safety and Efficacy of Difluprednate Ophthalmic Emulsion, 0.05% (Durezol™) 4 Times Daily (QID) and Prednisolone Acetate Ophthalmic Suspension, 1.0% (Pred Forte™) QID for the Treatment of Inflammation Following Cataract Surgery in Children 0 to 3 Years of Age

Conditions
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Cataracts, Inflammation

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 0 to 3 years of age. Undergoing uncomplicated cataract extraction in 1 eye with or without intraocular lens. Informed consent signed by a parent or legal guardian. Other protocol-defined inclusion criteria may apply. Exclusion Criteria: Presence of any active or suspected viral, bacterial, or fungal disease in the study eye. Use of any topical medication in the study within 7 days prior to surgery, except for drops that are needed to examine the eye or to prepare for surgery. Patients with posttraumatic cataract. Active uveitis in the study eye. Ocular neoplasm in the study eye. Human immunodeficiency virus (HIV); acquired immunodeficiency syndrome (AIDS). Suspected permanent low vision or blindness in the fellow nonstudy eye. The study eye must not be the patient's only good eye. Patients on systemic steroids or nonsteroidal anti-inflammatory drugs. History of steroid-induced intraocular pressure (IOP) rise. Currently on medication for ocular hypertension or glaucoma in the study eye. Diabetes. Other protocol-defined exclusion criteria may apply.

Ages Eligible for Study
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Maximum Age: 3 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 ophthalmic emulsion, 0.05%, 1 drop in the study eye at the end of surgery (Day 0) and 4 times a day beginning on the day after surgery (Day 1) for 14 days, followed by a tapering period of 14 days, dependent upon the Investigator's determination of adequate response to treatment | Drug: Difluprednate ophthalmic emulsion, 0.05%<br>* Topical ocular administration<br>* Other names: DUREZOL™;|
| Active Comparator: PRED FORTE<br>Prednisolone acetate ophthalmic suspension, 1.0%, 1 drop in the study eye at the end of surgery (Day 0) and 4 times a day beginning on the day after surgery (Day 1) for 14 days, followed by a tapering period of 14 days, dependent upon the Investigator's determination of adequate response to treatment | Drug: Prednisolone acetate ophthalmic suspension, 1.0%<br>* Topical ocular administration<br>* Other names: PRED FORTE™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With an Anterior Cell Grade of 0 (no Cells) at Day 15 ± 2 Days | Anterior cell grade was assessed by the Investigator during slit lamp or ophthalmoscopy/light examination and graded on a 5-point scale: Grade 0=0 cells; Grade 1=1 to 10 cells; Grade 2=11 to 20 cells; Grade 3=21 to 50 cells; Grade 4=>50 cells. The presence of blood cells (red and white) in the anterior chamber of the eye (the fluid-filled space inside the eye between the iris and the cornea's innermost surface) is a sign of intraocular inflammation. A score of 0 indicates an absence of inflammation. | Day 15 ± 2 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global Assessment Score of Postoperative Inflammation by Visit | A Global Assessment Score (GAS) was assigned by the Investigator based on the clinical evidence of postoperative inflammation: 0=clear, 1=improving satisfactorily; 2=not improving or worsening, withdrawal from study indicated to allow appropriate alternative therapy to be instituted. A score of 0 indicates an absence of inflammation. For this outcome measure, percentage of patients by grade and visit is reported. | Day 1, Day 8 ± 1 day, Day 15 ± 2 days, Day 29 ± 2 days, 1 Week after Last Dose + 2 days, 3 Months + 1 week | 
| Global Assessment of Inflammation - Individual Component Scoring by Visit: Anterior Chamber Cell Grade | Anterior chamber cell grade was assessed by the Investigator during slit lamp or ophthalmoscopy/light examination and graded on a 5-point scale: Grade 0=0 cells; Grade 1=1 to 10 cells; Grade 2=11 to 20 cells; Grade 3=21 to 50 cells; Grade 4=>50 cells. The presence of blood cells (red and white) in the anterior chamber of the eye (the fluid-filled space inside the eye between the iris and the cornea's innermost surface) is a sign of intraocular inflammation. A score of 0 indicates an absence of inflammation. For this outcome measure, percentage of patients by grade and visit is reported. | Day 1, Day 8 ± 1 day, Day 15 ± 2 days, Day 29 ± 2 days, 1 Week after Last Dose + 2 days, 3 Months + 1 week | 
| Global Assessment of Inflammation - Individual Component Scoring by Visit: Anterior Chamber Flare Grade | Anterior chamber flare was assessed by the Investigator during slit lamp or ophthalmoscopy/light examination and graded on a 4-point scale: 0=absent; 1=mild; 2=moderate; 3=severe. The presence of flare (increased protein levels) in the anterior chamber of the eye (the fluid-filled space inside the eye between the iris and the cornea's innermost surface) is a sign of intraocular inflammation. A score of 0 indicates an absence of inflammation. For this outcome measure, percentage of patients by grade and visit is reported. | Day 1, Day 8 ± 1 day, Day 15 ± 2 days, Day 29 ± 2 days, 1 Week after Last Dose + 2 days, 3 Months + 1 week | 
| Global Assessment of Inflammation - Individual Component Scoring by Visit: Corneal Clarity | Corneal clarity was assessed by the Investigator during slit lamp or ophthalmoscopy/light examination and graded on a 4-point scale: 0=absent; 1=mild; 2=moderate; 3=severe. Lack of corneal clarity (1-3) is a sign of intraocular inflammation. A score of 0 indicates an absence of inflammation. For this outcome measure, percentage of patients by grade and visit is reported. | Day 1, Day 8 ± 1 day, Day 15 ± 2 days, Day 29 ± 2 days, 1 Week after Last Dose + 2 days, 3 Months + 1 week | 
| Global Assessment of Inflammation - Individual Component Scoring by Visit: Conjunctival Injection | Conjunctival injection was assessed by the Investigator during slit lamp or ophthalmoscopy/light examination and graded on a 4-point scale: 0=absent; 1=mild; 2=moderate; 3=severe. Conjunctival injection (redness of the white sclera of the eye) is a sign of intraocular inflammation. A score of 0 indicates an absence of inflammation. For this outcome measure, percentage of patients by grade and visit is reported. | Day 1, Day 8 ± 1 day, Day 15 ± 2 days, Day 29 ± 2 days, 1 Week after Last Dose + 2 days, 3 Months + 1 week | 
| Global Assessment of Inflammation - Individual Component Scoring by Visit: Ciliary/Limbal Injection | Ciliary/limbal injection was assessed by the Investigator during slit lamp or ophthalmoscopy/light examination and graded on a 4-point scale: 0=absent; 1=mild; 2=moderate; 3=severe. Ciliary/limbal injection (redness of the white sclera of the eye near the limbal ring) is a sign of intraocular inflammation. A score of 0 indicates an absence of inflammation. For this outcome measure, percentage of patients by grade and visit is reported. | Day 1, Day 8 ± 1 day, Day 15 ± 2 days, Day 29 ± 2 days, 1 Week after Last Dose + 2 days, 3 Months + 1 week | 
| Global Assessment of Inflammation - Individual Component Scoring by Visit: Chemosis | Chemosis was assessed by the Investigator during slit lamp or ophthalmoscopy/light examination and graded on a 4-point scale: 0=absent; 1=mild; 2=moderate; 3=severe. Chemosis (swelling of the conjunctiva) is a sign of intraocular inflammation. A score of 0 indicates an absence of inflammation. For this outcome measure, percentage of patients by grade and visit is reported. | Day 1, Day 8 ± 1 day, Day 15 ± 2 days, Day 29 ± 2 days, 1 Week after Last Dose + 2 days, 3 Months + 1 week | 
| Global Assessment of Inflammation - Individual Component Scoring by Visit: Hypopyon | Hypopyon was assessed by the Investigator during slit lamp or ophthalmoscopy/light examination and graded on a 4-point scale: 0=absent; 1=mild; 2=moderate; 3=severe. Hypopyon (pus in the anterior chamber of the eye) is a sign of ocular inflammation. A score of 0 indicates an absence of inflammation. For this outcome measure, percentage of patients by grade and visit is reported. | Day 1, Day 8 ± 1 day, Day 15 ± 2 days, Day 29 ± 2 days, 1 Week after Last Dose + 2 days, 3 Months + 1 week | 
| Global Assessment of Inflammation - Individual Component Scoring by Visit: Vitritis | Vitritis was assessed by the Investigator during slit lamp or ophthalmoscopy/light examination and graded on a 4-point scale: 0=absent; 1=mild; 2=moderate; 3=severe. Vitritis (accumulation of inflammatory cells or exudates in the vitreous humor, the fluid that fills the middle chamber of the eye) is a sign of ocular inflammation. A score of 0 indicates an absence of inflammation. For this outcome measure, percentage of patients by grade and visit is reported. | Day 1, Day 8 ± 1 day, Day 15 ± 2 days, Day 29 ± 2 days, 1 Week after Last Dose + 2 days, 3 Months + 1 week | 
| Global Assessment of Inflammation - Individual Component Scoring by Visit: Wound Integrity | Wound integrity was assessed by the Investigator during slit lamp or ophthalmoscopy/light examination and graded on a 4-point scale: 0=absent; 1=mild; 2=moderate; 3=severe. Lack of wound integrity (healing, 1-3) is a sign of inflammation. A score of 0 indicates an absence of inflammation. For this outcome measure, percentage of patients by grade and visit is reported. | Day 1, Day 8 ± 1 day, Day 15 ± 2 days, Day 29 ± 2 days, 1 Week after Last Dose + 2 days, 3 Months + 1 week | 
| Global Assessment of Inflammation - Individual Component Scoring by Visit: Photophobia | Photophobia was assessed by the Investigator during slit lamp or ophthalmoscopy/light examination and graded on a 4-point scale: 0=absent; 1=mild; 2=moderate; 3=severe. Photophobia (abnormal intolerance to visual perception of light) is a symptom of intraocular inflammation. A score of 0 indicates an absence of inflammation. For this outcome measure, percentage of patients by grade and visit is reported. | Day 1, Day 8 ± 1 day, Day 15 ± 2 days, Day 29 ± 2 days, 1 Week after Last Dose + 2 days, 3 Months + 1 week | 
| Global Assessment of Inflammation - Individual Component Scoring by Visit: Lacrimation | Lacrimation was assessed by the Investigator during slit lamp or ophthalmoscopy/light examination and graded on a 4-point scale: 0=absent; 1=mild; 2=moderate; 3=severe. Excessive lacrimation (tear production and secretion, 1-3) is a symptom of ocular inflammation. A score of 0 indicates an absence of inflammation. For this outcome measure, percentage of patients by grade and visit is reported. | Day 1, Day 8 ± 1 day, Day 15 ± 2 days, Day 29 ± 2 days, 1 Week after Last Dose + 2 days, 3 Months + 1 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pediatric, Cataracts, Inflammation, Durezol, Pred Forte, Difluprednate, Prednisolone