Inflammation
Conditions
Brief summary
The purpose of this phase III study is to determine the efficacy of difluprednate in the treatment of inflammation following ocular surgery.
Interventions
DRUGDifluprednate
DRUGPlacebo
Sponsors
Sirion Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Inclusion criteria
* Unilateral ocular surgery in the day prior to study enrollment. * Anterior chamber cell grade ≥ 2 on the day after surgery (Day 1). * Aged 2 years or older on the day of consent. * Negative urine pregnancy test on Day 1 for postmenarchal subjects; negative urine pregnancy test for premenarchal subjects at the investigator's discretion. * Provide signed written consent prior to entering the study or signed written consent from parent or legal guardian if subject is a minor and signed assent from minor subject, if appropriate. Presurgical
Exclusion criteria
* Systemic administration of any corticosteroid in the 2 weeks prior to study enrollment. * Periocular injection in the study eye of any corticosteroid solution within 4 weeks prior to instillation of the study drug, or of any corticosteroid depot within 2 months prior to instillation of the study drug. * Instillation of any topical ocular corticosteroid or NSAID within 24 hours prior to instillation of the study drug or during the course of the study, with the exception of presurgical administration of a topical NSAID to prevent miosis. * Any history of glaucoma or ocular hypertension in the study eye. * History or presence of endogenous uveitis. * Any current corneal abrasion or ulceration. * Any confirmed or suspected active viral, bacterial, or fungal keratoconjunctival disease. * Allergy to similar drugs, such as other corticosteroids. * History of steroid-related IOP increase. * Scheduled surgery on the contralateral eye during the treatment period. * Unwilling to discontinue use of contact lenses during the study period. * Pregnancy or lactation. * Participation in any study of an investigational topical or systemic new drug or device within 30 days prior to screening, or at any time during the study. * Prior participation in the study described in this protocol. * Unable or unwilling to give signed informed consent prior to participation in any study related procedures. Postsurgical
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Anterior Chamber Cell Grade of 0 on Day 8 (Difluprednate QID vs Placebo). | Day 8 (QID) | Measured on a 0 to 4 scale: 0 is ≤ 1 cell; 1 is 2-10 cells; 2 is 11-20 cells; 3 is 21-50 cells; 4 is \> 50 cells. |
Countries
United States
Participant flow
Recruitment details
First subject enrolled January 24, 2007 and last subject completed September 20, 2007 at 11 sites in the United States.
Pre-assignment details
Subjects enrolled if, 24 hours after ocular surgery, they had an anterior chamber cell grade of ≥ 2 and met the protocol inclusion and exclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| Difluprednate 0.05% BID Difluprednate 0.05% 1 drop BID for 14 days | 54 |
| Difluprednate 0.05% QID Difluprednate 0.05% 1 drop QID for 14 days | 52 |
| Placebo Placebo for 14 days. Placebo was administered BID for 14 days and QID for 14 days. The outcomes of the 2 placebo groups were examined and were determined to be statistically indistinguishable so the placebo groups were pooled for comparison with the difluprednate groups. | 113 |
| Total | 219 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 |
| Overall Study | Lack of Efficacy | 5 | 2 | 54 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Difluprednate 0.05% BID | Difluprednate 0.05% QID | Placebo | Total |
|---|---|---|---|---|
| Age Continuous | 70.7 years STANDARD_DEVIATION 0 | 68.4 years STANDARD_DEVIATION 0 | 69.9 years STANDARD_DEVIATION 0 | 69.8 years STANDARD_DEVIATION 0 |
| Sex: Female, Male Female | 30 Participants | 29 Participants | 70 Participants | 129.0 Participants |
| Sex: Female, Male Male | 24 Participants | 23 Participants | 43 Participants | 90.0 Participants |
Outcome results
Primary
Anterior Chamber Cell Grade of 0 on Day 8 (Difluprednate QID vs Placebo).
Measured on a 0 to 4 scale: 0 is ≤ 1 cell; 1 is 2-10 cells; 2 is 11-20 cells; 3 is 21-50 cells; 4 is \> 50 cells.
Time frame: Day 8 (QID)
Population: The ITT population was defined as all randomized subjects who received at least 1 administration of the study drug. Analysis of the ITT population, with LOCF for missing data, was conducted for all primary and secondary endpoints at Days 3, 8, 15, and 29.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Difluprednate 0.05% BID | Anterior Chamber Cell Grade of 0 on Day 8 (Difluprednate QID vs Placebo). | Proportion of Subjects w/AC cell grade=0 on Day 8 | 0 participants |
| Difluprednate 0.05% QID | Anterior Chamber Cell Grade of 0 on Day 8 (Difluprednate QID vs Placebo). | Proportion of Subjects w/AC cell grade=0 on Day 8 | 18 participants |
| Placebo | Anterior Chamber Cell Grade of 0 on Day 8 (Difluprednate QID vs Placebo). | Proportion of Subjects w/AC cell grade=0 on Day 8 | 7 participants |
p-value: <0.0001Mantel Haenszel